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YANG Genmeng, PENG Yanxia, ZHANG Xinjie, HOU Yuhan, XU Jing, LI Lihua, DU Qi, HONG Shijun
2024,34(12):1-7, DOI: 10.3969/j.issn.1671-7856.2024.12.001
Abstract:
Objective To investigate the regulatory role of nuclear factor erythroid 2-related factor 2 (Nrf2) in the activation and polarization of microglia induced by methamphetamine (METH). Methods BV2 and HMC3 cells were studied in vitro and wild-type mice and Nrf2-knockout mice were studied in vivo. In vivo and in vitro toxicity models induced by METH were established, respectively. The activation and polarization of microglia in each group were examined using immunofluorescence and Western blot, respectively. Results METH treatment significantly increased the fluorescence level of inducible nitric oxide synthase (iNOS) in BV2 and HMC3 cells (P<0.001), and significantly decreased the fluorescence level of Arginase1 (Arg1) (P<0.05, P<0.01). METH exposure activated microglia in the cortex, increased expression levels of ionized calcium binding adaptor molecule-1 (IBA1) and iNOS (P<0.001, P<0.05), and decreased the expression of Arg1 (P<0.01). The number of activated microglia was significantly increased after Nrf2 gene knockout (P<0.01), compared with the WT METH group, while the expression levels of IBA1 and iNOS were also increased (P<0.001, P<0.01) and the expression level of Arg1 was decreased (P<0.01). Conclusions Nrf2 plays an important role in regulating the activation and polarization of microglia induced by METH. Nrf2 may thus be a potential target for the treatment of neuroinflammation induced by METH.
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LIU Gaoyuan, PENG Mengwei, LUO Zilong, KUANG Luoyi, CHEN Yulong, YANG Tiezhu, WU Yaosong, LIU Yan
2024,34(12):8-18, DOI: 10.3969/j.issn.1671-7856.2024.12.002
Abstract:
Objective To observe the influence of Creb protein over-expression and under-expression in the prefrontal cortex on depressive behavior in rats. Methods Adeno-associated virus (AAV) strains that can knock down Creb expression in the prefrontal cortex of rats were injected using the stereotaxic injection method and screened by Western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. Forty rats were divided randomly into Control, chronic restraint stress (CRS), CRS combined with AAV interference (CRS+AAVI), and CRS combined with AAV overexpression (CRS+AAVO) groups. The body weight and food intake of the rats in each group were monitored during establishment of the animal model. After establishment of the model, behavioral changes in the rats were monitored by sucrose preference, elevated plus maze, forced swimming, and open field tests. The 5 hydroxytryptamine (5-HT), norepinephrine (NE), and corticosterone (CORT) contents in the prefrontal cortex of rats in each group were measured by enzyme-linked immunosorbent assay. Results Western blot and immunofluorescence showed that Creb protein expression was significantly reduced in the short hairpin RNA2 (shRNA2) knockdown groups compared with the other groups (P<0.05). RT-qPCR showed that Creb mRNA expression was also significantly reduced compared with the other three groups (P<0.01). The AAV-CREB1-shRNA2 virus strain was therefore selected for subsequent Creb knockdown experiments in this study. After modeling, the food intake of rats in the CRS+AAVI group was significantly reduced compared with the other groups (P<0.01). Rats in this group also showed slow weight gain and decreased desire to explore new environments, significantly increased despair and nervous behavior, and significantly decreased 5-HT and NE levels(P<0.01) and significantly increased CORT levels in the prefrontal cortex (P<0.01). These depressive behaviors and associated neurotransmitter levels were reversed in the CRS+AAVO group. Conclusions Lower expression of Creb in the prefrontal cortex can aggravate the degree of depression in rats, while high expression of Creb can alleviate depression to a certain extent. These result confirm that Creb expression in the prefrontal cortex is an important target in the pathogenesis of depression, thus providing ideas and references for the construction of animal gene models and further studies of the pathogenesis of depression.
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WANG Lu, GUO Xia, MA Shangjia, YONG Wen, YU Wenlong, WU Lie, JIA Jianxin
2024,34(12):19-28, DOI: 10.3969/j.issn.1671-7856.2024.12.003
Abstract:
Objective To investigate the neuroprotective effect and mechanism of glycosides of Cistanche (GCs) on cerebral ischemia reperfusion injury (CIRI) in rats. Methods Forty-eight male Wistar rats were divided randomly into Sham, Model, GCs, and Nim groups. A rat model of focal CIRI was established by middle cerebral artery occlusion. Neurological function was scored using the Zea-Longa scoring method. The sensory and motor abilities of rats in each group were evaluated by sticker removal, balance beam, and open field tests. The area of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC) staining, Nissl staining was used to observe the morphology of nerve cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling was used to detect apoptosis of nerve cells. Expression levels of the apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), and cysteine aspartic protease-3 (Caspase-3) were detected by immunohistochemical staining and Western blot. Results Compared with the Sham group, the neurological deficit score was significantly increased (P<0.05) and the times to remove stickers and passing the balance beam were significantly increased (P<0.05), motor ability was decreased, infarct size was increased, the number of neurons was decreased, and the number of apoptotic cells was increased after CIRI. Bax and Caspase-3 expression were significantly increased (P<0.05) and Bcl-2/Bax was significantly decreased (P<0.05). Compared with the Model group, GCs improved the behavioral performance of CIRI model rats, reduced the infarct size, inhibited cell apoptosis, downregulated the expression of Bax and Caspase-3 (P<0.05), and up-regulated the expression of Bcl-2/Bax (P<0.05). Conclusions GCs have a neuroprotective effect on CIRI, and may play a role in inhibiting cell apoptosis by regulating the expression of the apoptosis-related factors Bax, Bcl-2, and Caspase-3.
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HAN Bingyang, SHEN Tingting, FAN Zhengyuan, LI Gaofeng, LI Ya, LI Suyun
2024,34(12):29-40, DOI: 10.3969/j.issn.1671-7856.2024.12.004
Abstract:
Objective To investigate the mechanism by which Xuanfei Jiedu Formula (XFJDF) ameliorates pulmonary damage in rats with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) pneumonia, by modulating the activity of the inhibitor of nuclear factor (NF)-κB kinase (IKK) IKK/NF-κB signal transduction cascade. Methods Eighty-four rats were divided randomly into seven groups: control, model, XFJDF-low dose, XFJDF-medium dose, XFJDF high dose, imipenem (IPM), and pyrrolidinedithiocarbamate ammonium (PDTC) groups (n=12 rats per group). A MDR-PA pneumonia rat model was established by oral tracheal intubation. After successful model construction, rats in the low-, medium-, and high-dose XFJDF groups were given the corresponding dose of drugs by gavage, rats in the IPM group were given an intraperitoneal injection of IPM, and rats in the control and model groups were given the same volume of normal saline by gavage, twice a day for 7 days. PDTC was injected intraperitoneally 1 h before model establishment, 12 h and 24 h after model establishment in the NF-κB inhibitor group. The behavior status, body weight changes, spleen and thymus indexes, and lung wet weight/dry weight ratio were observed in the different groups. Histological changes in the lung tissue were assessed by hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to detect apoptosis of lung tissue cells, and serum levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and IL-10 were detected by enzyme-linked immunosorbent assay, and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and total antioxidant capacity (T-AOC) were determined by colorimetry and thiobarbituric acid assay. NF-κBp65 in lung tissue was identified by immunohistochemical analysis, IKKβ and NF-κBp65 mRNA were analyzed by reverse transcription quantitative polymerase chain reaction, and expression levels of IKKβ, phosphorylated (p)-IKKβ, NF-κBp65, and p-NF-κBp65 were measured by Western blot. Results Compared with the control group, rats in the model group exhibited decreased appetite, dull fur, sluggish responsiveness, decreased mobility, increased respiratory rate, audible murmurs, and notable weight loss (P<0.01). The spleen and thymus indices were significantly enhanced (P<0.01) and the lung wet/dry weight ratio was significantly increased (P<0.01), concurrent with increased alveolar secretions in lung tissue. Infiltration of abundant inflammatory cells and increased apoptosis in lung tissue were also noted. Serum concentrations of IL-1β, TNF-α, TGF-β, and IL-10 were increased (P<0.01) and the MDA content and MPO activity were also increased (P<0.01). Conversely, GSH levels and T-AOC were significantly decreased (P<0.01). Lung levels of IKKβ and NF-κBp65 mRNA were significantly increased (P<0.01) and the ratios of p-IKKβ/IKKβ and p-NF-κBp65/NF-κBp65 were also significantly increased (P<0.01) compared with the control group. XFJDF, IPM and PDTC improved these parameters to varying degrees, compared with the model group (P<0.05, P<0.01), with particularly significant effects in the high-dose XFJDF and IPM groups. Conclusions XFJDF may improve lung injury in rats with MDR-PA pneumonia by inhibiting the IKK/ NF-κB signaling pathway.
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DU Wenya, DAI Yumei, YUE Linzhi, MA Tao, WU Lixian
2024,34(12):41-49, DOI: 10.3969/j.issn.1671-7856.2024.12.005
Abstract:
Objective miR-207 is differentially expressed in many diseases. We investigated the mechanism by which miR-207 overexpression regulates the survival of Mycobacterium tuberculosis (H37Ra) in macrophages, to provide a theoretical basis for the targeted therapy of tuberculosis. Methods Macrophages were divided into four groups: blank (Ana-1 cells), control (cells infected with H37Ra), mi (infected with H37Ra and transfected with miRNA-207 mimics), and mi-NC (infected with H37Ra and transfected with NC mimics) groups. A model of tuberculosis infection was established using H37Ra-infected Ana-1 cells, and miRNA-207 and NC mimics were transfected into Ana-1 cells using the liposome transfection method. Tuberculosis colony-forming units were counted to assess the effect of miR-207 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria. The total apoptosis rate was detected by flow cytometry. The relative expression levels of miR-207 and apoptosis, pyroptosis, inflammation, and autophagy genes were measured by quantitative real-time polymerase chain reaction (qPCR). Relative expression levels of apoptosis, pyroptosis, and autophagy proteins were detected by Western blot. Fluorescence microscopy and multifunctional enzyme labeling were used to detect the fluorescence intensity of intracellular reactive oxygen species (ROS) and lactate dehydrogenase (LDH). Results Successful establishment of the infection model was observed under the microscope. qPCR showed that miR-207 expression was lower in the control compared with the blank group(P<0.01), indicating differential expression between these two groups. miR-207 expression was significantly higher in the mi compared with the mi-NC group(P<0.0001), indicating successful establishment of the transfection model. The number of colonies and total apoptosis were both higher in the mi group compared with the mi-NC and control groups(P<0.001). qPCR and Western blot showed that the relative expression levels of apoptotic genes and proteins were higher in the control group than in the blank group(P<0.05), and higher in the mi group than in the mi-NC group(P<0.05). The relative expression levels of inflammatory genes were higher in the control than in the blank group(P<0.001). The relative expression levels of inflammatory genes were higher in the mi group than in the mi-NC group(P<0.05), and the relative expression levels of pyroptosis genes and proteins were higher in the control group compared with the blank group(P<0.01) and higher in the mi group compared with the mi-NC group(P<0.05). The relative expression levels of the autophagy positively-regulated genes LC3 and Beclin1 were higher in the control compared with the blank group(P<0.0001), and lower in the mi than in the mi-NC group(P<0.05), while negatively-regulated autophagy genes showed the opposite trend. Autophagy-related proteins showed similar trends to the autophagy genes. ROS fluorescence intensity was higher in the control compared with the blank group(P<0.05), and higher in the mi compared with the mi-NC group(P<0.001). LDH content was higher in the control than in the blank group(P<0.01), but there was no significant difference between the mi and mi-NC groups(P>0.05). Conclusions miR-207 overexpression promotes apoptosis, cellular pyroptosis, and inflammation, inhibits autophagy, and favors H37Ra survival. These result provide a potential new direction for the treatment of tuberculosis.
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ZHOU Haiyi, HE Siyi, HAN Ruifang, GUAN Yongge, DONG Lijuan, SONG Yang
2024,34(12):50-58, DOI: 10.3969/j.issn.1671-7856.2024.12.006
Abstract:
Objective To compare the reparative effects of moxibustion at “Guanyuan” and “Shenshu” points in rats with a thin endometrium. Methods Thirty-two female Sprague-Dawley rats were divided randomly into control(CON), model(MOD), Guanyuan(GY), and Shenshu(SS) groups. A thin endometrium model was established using 95% anhydrous alcohol. The Guanyuan and Shenshu groups underwent moxibustion at the Guanyuan and Shenshu points, respectively, and the other two groups of rats were fixed in the same way. Temperature changes at the acupoint area were measured at different time points. The pathological morphology of the uterus was observed by hematoxylin and eosin (HE) staining, and serum levels of inflammatory factors and hormone levels were detected by enzyme-linked immunosorbent assay (ELISA). Expression levels of proliferation and endometrial receptivity factors were detected by immunohistochemistry (IHC), and angiogenesis factors were detected by Western blot. Results The temperatures immediately after moxibustion and after 5 min were higher at the Shenshu compared with the Guanyuan acupoint (P<0.01). Endometrial thickness and numbers of glands and blood vessels were decreased in the MOD group compared with the CON group (P<0.01), serum interleukin 1β (IL-1β) was increased (P<0.01) and PROG was decreased (P<0.01), and Ki67, proliferating cell nuclear antigen (PCNA), leukemia inhibitory factor (LIF), integrin β3 (ITG-β3),angiopoietin-1 (ANG-1), and CD34 protein in uterine tissue were all decreased (P<0.01). Endometrial thickness and numbers of glands and blood vessels were increased in the GY and SS groups compared with the MOD group (P<0.01), while serum IL-1β was decreased (P<0.05), E2 and PROG were increased (P<0.05), and serum interleukin 10 (IL-10) was increased in the SS group (P<0.05). Ki67, PCNA, LIF, and ITG-β3 were all increased in both treatment groups compared with the MOD group (P<0.01). PCNA was higher in the GY group compared with the SS group (P<0.05), while LIF and ITG-β3 were higher in the SS group compared with the GY group (P<0.01, P<0.05, respectively). CD34 and VEGFA levels were increased in the two treatment groups compared with the model group (P<0.01). ANG-1 was higher in the GY group than that in the SS group (P<0.01), while CD34 was higher in the SS group than that in the GY group (P<0.05). Conclusions Moxibustion at the Guanyuan and Shenshu points could help to repair the pathological thin endometrium in rats. The GY group may be superior to the SS group for reducing the levels of serum IL-1β , increasing E2, and promoting the expression of proliferation factors, while the SS group may be superior to the GY group for increasing the levels of PROG and promoting the expression of endometrium receptor-related factors. Both acupoints can promote the expression of angiogenesis factors, potentially acting via different pathways.
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LI Shuo, LI Nian, ZHOU Xiaofeng, YUAN Xiaolong
2024,34(12):59-69, DOI: 10.3969/j.issn.1671-7856.2024.12.007
Abstract:
Objective We aimed to investigate the effect of roofplate-specific spondin 2 (RSPO2) on oxidative stress and apoptosis in ovarian granulosa cells, using human ovarian granulosa tumor cells as a cellular model. Methods We transiently transfected COV434 human granulosa cells with RSPO2 overexpression plasmid and small interfering RNA (siRNA). The efficiencies of the overexpression and interference were detected by quantitative real-time polymerase chain reaction (qPCR) and Western blot. Intracellular reactive oxygen species (ROS) were detected using a ROS assay kit, and apoptosis was detected by flow cytometry. Expression levels of oxidative stress- and apoptosis-related genes were determined by qPCR and Western blot, and interacting proteins were detected by co-immunoprecipitation. Results RSPO2 overexpression and interference were successfully realized. Overexpression of RSPO2 significantly inhibited ROS levels in COV434 cells (P<0.05) and the early apoptosis of granulosa cells (P<0.01), while RSPO2 interference had the opposite result. Overexpression of RSPO2 significantly upregulated the mRNA and protein levels of superoxide dismutase (SOD) 1, SOD2, and catalase (CAT) (P<0.05), and significantly downregulated the levels of Caspase 3 and Caspase 8 (P<0.05). In contrast, RSPO2 interference significantly downregulated SOD1 and CAT (P<0.05) and significantly upregulated Caspase 3 and Caspase 8 (P<0.05). We found protein interactions between RSPO2, SOD1, CAT, and Caspase 3. Conclusions Interfering with RSPO2 promotes the accumulation of ROS within cells and downregulates the expression of SOD1 and CAT, thereby enhancing oxidative stress. Additionally, interfering with RSPO2 upregulates the expression of Caspase 3 and Caspase 8, promoting cell apoptosis. These findings suggest that RSPO2 plays a crucial role in ovarian granulosa cells.
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WANG Yingnan, WU Jianhua, WU Chensi, ZHANG Fengbin, ZHANG Ruixing, GUO Zhanjun
2024,34(12):70-76, DOI: 10.3969/j.issn.1671-7856.2024.12.008
Abstract:
Objective To prepare human SET8 monoclonal antibody and explore its effects on the proliferation, apoptosis, and cell cycle of hepatoma cells, and to evaluate its anti-tumor effect in mouse models of hepatocellular carcinoma. Methods We immunized mice with human SET8 polypeptide fragment and screened and fused B cells and myeloma cells to establish a hybridoma cell line that stably secreted SET8 monoclonal antibody. Production was expanded by intraperitoneal injection into mice and the collection and purification of ascites. We investigated the effects of SET8 monoclonal antibody on the proliferation, apoptosis, cell cycle, and apoptosis-related protein expression of hepatocellular carcinoma cells by CCK-8, flow cytometry, and Western blot, respectively. Finally, we constructed a mouse model of human hepatocellular carcinoma by cell transplantation to evaluate the inhibitory effect of SET8 monoclonal antibody on tumor growth in vivo. Results Human SET8 monoclonal antibody significantly inhibited the viability of Huh-7 and Mahlavu hepatoma cells at concentrations of 50 and 100 μg/mL, in a concentration-dependent manner (P<0.05). Flow cytometry analysis showed that SET8 monoclonal antibody, paclitaxel, and their combination significantly increased the apoptosis rate of Mahlavu cells compared with the blank control group, with the combination group having the greatest effect (P<0.05). SET8 monoclonal antibody also induced Mahlavu cell cycle arrest in S and G2 phases and reduced G1 phase cells. Western blot analysis showed that the monoclonal antibody increased the expression of the apoptosis-related proteins Bax and Caspase-3 (P<0.05). SET8 monoclonal antibody, alone or in combination with paclitaxel, also effectively inhibited the proliferation of hepatocellular carcinoma cells in nude mice, with the combination therapy having the most significant effect (P<0.05). Conclusions The prepared human SET8 monoclonal antibody effectively inhibited the proliferation and promoted the apoptosis of hepatocellular carcinoma cells, and showed good anti-tumor effects in mice.
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2024,34(12):77-84, DOI: 10.3969/j.issn.1671-7856.2024.12.009
Abstract:
The elective course “Practical Mouse Anatomy & Comparative Medicine” is a comprehensive technical course designed to cultivate fundamental theoretical knowledge and experimental skills in laboratory mouse anatomy for undergraduate students in medical and pharmaceutical-related fields. Given the increasing demand for innovation and entrepreneurship training programs and undergraduate participation in research laboratories, this course systematically provides students with anatomical knowledge of the eight major systems and local anatomy of experimental mice, emphasizing the combination of theory and practice, to provide a comprehensive learning platform. The course continually explores and reforms its practices to ensure that the teaching content keeps pace with the forefront of scientific research, fostering a rigorous and pragmatic scientific attitude in students, thereby laying a solid foundation for their future research work. This paper discusses the effectiveness of the course in enhancing students’ research literacy and practical abilities, aiming to provide a reference for the design and implementation of similar courses.
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ZHAO Zhongmin, LIANG Shuzhi, GAO Xiangye, HOU Suyu, LUO Dandan, ZHANG Yan, WANG Shijun
2024,34(12):85-95, DOI: 10.3969/j.issn.1671-7856.2024.12.010
Abstract:
Insomnia is a prevalent clinical condition that not only diminishes the patient’s quality of life but also has the potential to give rise to further health complications. Traditional Chinese medicine (TCM) has been used to treat insomnia for thousands of years, with distinct advantages. TCM uses syndrome differentiation and therapy to achieve its therapeutic effects, by regulating the internal balance of the human body. To gain a deeper understanding of how TCM treats insomnia, it is crucial to create animal models that exhibit insomnia symptoms closely resembling those found in humans. This review summarizes the current disease-syndrome combination models, which can be classified into four categories: liver depression and Qi stagnation, heart-spleen deficiency, heart-kidney incompatibility, and Yin and blood deficiency. This paper focuses on specific modelling method ologies, assessment indicators, and model performances, with the aim of enhancing our understanding of the pathophysiology of insomnia in the context of TCM, and providing technical assistance for clinical efficacy evaluation and the creation of novel drugs.
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LI Hongyu, LAN Rui, TANG Chen, LIU Shuang, ZHANG Yong, SHEN Xiaoming
2024,34(12):96-101, DOI: 10.3969/j.issn.1671-7856.2024.12.011
Abstract:
Parkinson’s disease(PD) is a neurodegenerative disease that primarily affects middle-aged and older adults. Its main clinical manifestations include resting tremor, bradykinesia, myotonia, and balance disorders. Berberine is a naturally occurring isoquinoline alkaloid. Several studies over the previous decade have reported that berberine plays a crucial role in the pathophysiologic processes of a range of diseases, including playing an active role in the development of PD via different pathways. This paper systematically reviews the mechanism of action of berberine in the prevention and treatment of PD and the current status of research, to provide references for the future clinical application of berberine for the treatment of PD.
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LI Chao, LI Jian, TIAN Zhaoyang, PU Jingjing, LI Jiayu, HAN Rujie, ZHANG Biwei, WANG Meng
2024,34(12):102-110, DOI: 10.3969/j.issn.1671-7856.2024.12.012
Abstract:
The pathogenesis of depression is complex and treatment method are currently limited, and it is therefore important to clarify its pathogenesis and develop new therapeutic drugs. Hormones and hormone-modifying compounds have been used to treat depression, and their therapeutic effects are attributed to regulation of the peripheral endocrine system and their effects on non-endocrine circuits in the central nervous system. The hypothalamic-pituitary adrenal (HPA)/hypothalamic-pituitary-thyroid (HPT)/hypothalamic-pituitary-gonadal (HPG) axes are closely related to the pathogenesis of depression. The mechanism of action of traditional Chinese medicines in the treatment of depression is extensive, and the three axes are regulated in a variety of ways. Based on new evidence of hormones and hormone operon compounds involved in the pathology and treatment of depression, this review summarizes the relevant mechanisms of current traditional Chinese medicine in the treatment of depression, to provide new ideas and references for traditional Chinese medicine research.
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LI Ruixue, XIE Yabin, SHAO Guo
2024,34(12):111-116, DOI: 10.3969/j.issn.1671-7856.2024.12.013
Abstract:
Hypoxic/ischemic preconditioning(H/IPC) can induce endogenous protective mechanisms that increase the tolerance of nerve cells to hypoxia/ischemia. This protective mechanism involves changes in gene expression during the critical decision-making period between cell survival and death. DNA methylation, as a crucial mechanism for gene expression regulation, plays an essential role in hypoxia/ischemia tolerance. DNA methyltransferases (DNMTs) contribute to neuroprotection by influencing gene expression via regulating DNA methylation levels. DNMTs thus have important functions in the neuroprotection induced by hypoxic/ischemic preconditioning. This paper reviews the role of DNMTs in this process, providing insights into neuroprotection targeting DNMTs.
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ZHOU Ying, SUN Wei, YANG Genmeng, DONG Wenjuan, DAI Rui, HONG Shijun, LI Lihua
2024,34(12):117-126, DOI: 10.3969/j.issn.1671-7856.2024.12.014
Abstract:
Methamphetamine(METH) is a new type of abused drug with a strong central stimulant effect. Its excitatory pathway involves a series of central higher-level functions, including drug-related rewards and motivation, learning and memory, decision-making, and execution. METH not only causes neurotoxicity, but its long-term use may also cause cognitive dysfunction, loss of personality, and may lead to serious social violence in addicts. Exosomes, as a novel cell-to-cell carrier, are involved in the occurrence and development of drug addiction, and exosome microRNAs are important biomarkers for METH addiction and are also involved in various aspects of METH-induced neurotoxicity. Eoxosmes may thus be useful therapeutic carriers providing a new approach for the diagnosis and treatment of METH abuse.
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HE Changhui, PAN Haidi, DOU Xin, MEI Xiao, DENG Hualiang, WANG Wei
2024,34(12):127-135, DOI: 10.3969/j.issn.1671-7856.2024.12.015
Abstract:
The incidence of diarrhea-predominant irritable bowel syndrome (IBS-D) remains high, with microRNA (miRNA)-mediated intestinal barrier dysfunction, visceral hypersensitivity, low-grade inflammation, and dysbiosis playing significant roles in its pathogenesis. Traditional Chinese medicines can treat IBS-D by directly or indirectly targeting miRNAs to regulate multiple pathways and targets in a coordinated manner. This article systematically reviews the involvement of miRNAs in the pathogenesis of IBS-D and the progress of traditional Chinese medicine interventions. It explores the relationship between traditional genetics, epigenetics, and the Chinese medicine concepts of ‘kidney’ and ‘spleen’ in terms of congenital and acquired interactions from a molecular biology perspective. This review thus provides a reference for exploring the micro-material basis of the ‘Zang-Xiang’ theory of traditional Chinese medicine, and offers new ideas and method for the effective treatment of IaBS-D using traditional Chinese medicine.
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Research progress in nuclear factor E2-related factor 2 in oxidative stress after spinal cord injury
XI Huilin, WU Jiajun, WANG Qingyan, BAI Xinyue, HE Mengze, YANG Yanling
2024,34(12):136-142, DOI: 10.3969/j.issn.1671-7856.2024.12.016
Abstract:
Spinal cord injury (SCI) is a central nervous system disease with high morbidity, disability, and mortality. A series of pathological and physiological changes after SCI, including oxidative stress, can promote further deterioration of the microenvironment at the injury site, resulting in impaired neurological function. Nuclear factor E2related factor 2 (Nrf2) is highly correlated with oxidative stress, suggesting that targeting the regulation of Nrf2 and alleviating oxidative stress may be an effective treatment for SCI. We consider the application of Nrf2 in post-SCI oxidative stress, based on the occurrence of oxidative stress after SCI and the relationship between oxidative stress and Nrf2. We also summarize the strategies for targeting and regulating Nrf2, including genes, non-coding RNAs, and drugs, with the aim of providing new ideas for targeted therapy of SCI.
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DU Weifei, XU Xuemin, LIU Xiaoming
2024,34(12):143-150, DOI: 10.3969/j.issn.1671-7856.2024.12.017
Abstract:
Autophagy is a crucial physiological process in cells and an important mechanism in the maintenance of cell homeostasis and regulation of cell survival. Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease of unknown etiology with a poor prognosis, characterized by alveolar epithelial cell damage and abnormal proliferation and activation of fibroblasts. IPF is accompanied by the excessive deposition of extracellular matrix(ECM), and its pathogenesis involves a complex interaction between cell types and signaling pathways. Defects in autophagy function have been shown to play a key role in the occurrence and development of IPF. This review aims to investigate the mechanism of autophagy in IPF and reveal its complexity and related signaling pathways.
Volume 34,2024 Issue 12
Volume 34,2024 Issue 12
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Study of the effect of CB1R modulation of synaptic plasticity on ASD-like behavior in mice
Yilin Zhang, Du Caiyao, Guo Peiwen, Cheng Zeyu, Gao Ya, Zou Mingyang, Sun Caihong
Abstract:
【】? Objective? To investigate the regulation of synaptic plasticity by CB1R and its effects on ASD-like behavior. ?Methods ?CB1R knockout (knockout,KO) mice and valproic acid (VPA)-induced ASD model mice (VPA mice) were used as study subjects. Behavioral experiments assessed the effects of CB1R on ASD-like behavior in mice; neuronal structural integrity and dendritic density were detected by passaging MAP2 staining experiments, and Western Blot experiments detected the expression of synapse-associated proteins to assess the effects of CB1R on synaptic plasticity. Results ?Behavioral results showed that VPA mice had significant ASD-like behavior; CB1R-/- mice had a significantly lower ratio of residence time in the central region of the open field, a significant increase in the number of buried beads and self-combing time, a significant decrease in the time spent socialising with unfamiliar mice2 and exploring unfamiliar objects, and a significant increase in the time spent exploring old objects (P <0.05); CB1R+/- mice had a significantly lower ratio of The ratio of dwell time was significantly reduced, and the number of buried beads and self-combing time were significantly increased (P <0.05). The results of synaptic plasticity assay showed that there was significant synaptic plasticity impairment in VPA mice; the hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/- and CB1R+/- mice, and the expression levels of SYN1 were significantly increased (P <0.05).? Conclusion ?CB1R knockdown causes mice to exhibit significant ASD-like behavior such as anxiety and repetitive stereotyped behavior, social and cognitive impairments, as well as neuronal damage, dendritic dysplasia and disrupted synaptic protein expression, suggesting that CB1R is involved in regulating abnormal synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.
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Erianin alleviates atopic dermatitis by regulating the HMGB 1 / RAGE-RhoA / ROCK 1 signaling pathway
Xu Kexin, Wang Dandan, Jin Hongyu, Du Yue, Li Li, Song Yilan, Yan Guanghai, Li Liangchang
Abstract:
Objective: To explore the role of Erianin in specific dermatitis (AD) and its regulatory mechanism in HMGB 1 / RAGE-RHOA / ROCK 1-signaling pathway. Methods: DNCB induced BALB/c mice serve as a model for AD. Measure the skin thickness, spleen, and lymph node weight of mice. Methylamine blue and H&E staining were used to detect pathological changes in the back skin and ears of mice. ELISA detects levels of inflammatory factors. Establishment of an in vitro model of Alzheimer"s disease using HaCaT cells stimulated by TNF - α. Use flow cytometry to detect cellular ROS. Immunofluorescence assay was used to detect mtROS. TUNEL method was used to detect cell apoptosis. Use immunoblotting to detect the expression of HMGB1, RAGE, RhoA, and ROCK1 proteins.Results: It inhibited the increase of skin thickness, reduced the weight of spleen and lymph nodes, improved the infiltration of inflammatory cells, and the degranulation of mast cells, and reduced the level of inflammatory factors. In vitro, Erianin reduced the production of cellular ROS, mtROS induced by TNF- α. The protein expression of HMGB 1, RAGE, RhoA and ROCK 1 decreased. Treatment of r-HMGB1-stimulated HaCaT cells with RAGE-specific blocker (TFA) showed no change in HMGB1 expression, and the expression of RAGE, RhoA, and ROCK1 decreased. In the Rho kinase inhibitor (Y-27632) + TNF- α group, except for RAGE, the results were similar to the TFA + TNF- α group. Conclusion: Erianin relieves atopic dermatitis by regulating the HMGB 1 / RAGE-RhoA / ROCK 1 signaling pathway.
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Study on renal injury in rats after entering a low-pressure and low-oxygen environment from the plain into the plateau
Jia Meng, qu zhen ji mu, suo lang de ji, guo yi dan, guo shi kun, wei hua ying, zhou xiao ling, wang rui ji
Abstract:
【Abstract】Objective To explore the changes in renal function, renal injury biomarkers, and renal pathology in rats over time after entering a simulating low-pressure and low-oxygen environment from the plains to the plateau. Methods 30 male Sprague-Dawley rats were divided into 5 groups randomly, with 6 rats in each group. The control group was placed outside the chamber under normal pressure and oxygen conditions. The experimental groups were placed in a low-pressure and low-oxygen(LPLO) chamber to simulate a plateau environment at 5000m above sea level, living in the chamber for 3 days, 7 days, 14 days, and 28 days respectively. Observe the renal injury biomarkers of each group: serum creatinine (CRE), serum cystatin C (CysC), serum neutrophil gelatinase-associated lipocalin (NGAL), serum kidney injury molecule-1(KIM-1) and serum interleukin-18 (IL-18) levels. HE staining and PAS staining is used to observe the pathological changes of kidney injury. Results Compared with the control group, the levels of NGAL, KIM-1, CysC, and CRE in the experimental group were significantly increased (all P<0.05). The average diameter of glomeruli was significantly reduced in the LPLO 3day group, significantly increased in the LPLO 14day group (both P<0.05). The PTC/tubule was significant decreased. The renal tubular injury score and OM congestion score were significant increased (both P<0.05). Regression analysis showed that PTC/tubule was linearly negatively correlated with the duration of low-pressure and low-oxygen, while CRE, CysC, and pathological indicators (mean glomerular diameter, OM congestion score, and renal tubular injury score) were curvilinearly correlated with the duration of low-pressure and low-oxygen (all P<0.05). For the variables that showed curvilinear correlation, restricted cubic splines (RCS) analysis was used: each curve exhibited an "inverted L" shape, with inflection points occurring on the 7th day, indicating that the rate of increase for all indicators was highest within the first 7 days of low-pressure and low-oxygen, and the rate of increase slowed from 7 days to 28 days. Conclusions After simulating entering the plateau environment from the plain, there were significant damage in the kidney in terms of structure and function, and the kidney had a self-adaptive adjustment process toward the plateau environment.
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Study on mechanism of Liangxue Tuizi Formula in the treatment of Henoch-Sch?nlein purpura rats through ROS-mediated activation of NLRP3 inflammasome
SONG Jin-wan, REN Xin-qing, XING Qiong-qiong, LI Yi-fan, YANG Man-xiang
Abstract:
Objective To study the effect of Liangxue Tuizi Formula(LXTZF) on reactive oxygen species(ROS)-mediated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation in Henoch-Sch?nlein purpura rats, and to explore the possible mechanism of Liangxue Tuizi Formula in the treatment of HSP. Methods 24 rats were randomly divided into 4 groups: blank group, model group, LXTZF group and Compound Glycyrrhizin (CG) group. Except the blank group, the rat model of a Henoch-Sch?nlein purpura was established by heat drug combined with egg albumin (OVA). After successful modeling, LXTZF group was given LXTZF solution 7.47 g·kg-1, CG group was given CG solution 13.5 mg·kg-1 by gavage, blank group and model group were given normal saline solution gavage once a day for 4 weeks. Samples were collected 8 hours after the last gavage. Hematoxylin-eosin staining (HE) was used to observe the skin histopathologic changes. Serum Interleukin-18 (IL-18) and Interleukin-1β (IL-1β) levels were detected by enzyme-linked immunosorbent assay (ELISA). The changes of ROS levels in the skin of rats were detected by immunofluorescence. Real-time quantitative PCR (RT-qPCR), immunohistochemical and western blot methods were used to detect Apoptosis-associated speckle-like protein (ASC), NLRP3, Cysteinyl Aspartate-Specific Protease-1 (Caspase-1) gene mRNA and protein expression in rat skin. Results Compared with the blank group, the skin pathology of the model group showed obvious inflammatory cell infiltration. Serum IL-18 and IL-1β levels were significantly increased (P<0.05), skin ROS levels were significantly increased (P<0.05), and skin ASC, NLRP3, Caspase-1 mRNA and protein expression levels were significantly increased (P<0.05). Compared with the model group, the infiltration of inflammatory cells in the skin tissues of rats in the LXTZF group and the CG group was alleviated, the levels of serum IL-18 and IL-1β in the CG group and LXTZF group were significantly decreased (P<0.05). The level of ROS in the skin was significantly decreased (P<0.05), and the mRNA and protein expression levels of ASC, NLRP3 and Caspase-1 in the skin were significantly decreased (P<0.05). Conclusion The mechanism of Liangxue Tuizi Formula in the treatment of Henoch-Sch?nlein purpura may be related to the inhibition of ROS-mediated NLRP3 inflammasome activation.
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Progress in the cryopreservation protocols of adipose-derived stem cells
LIU Qin, ZHU Yiliang, CHEN Fang, YU Jing, YANG Lijun, ZHANG Yi
Abstract:
Adipose derived stem cells(ASCs) become one of the hot seed cells in tissue engineering because of their unique advantages. An ideal method of cryopreservation of ASCs is the goal that researchers have been working on. So far, a lot of researches on cryopreservation protocols of ASCs have been done. In this review, the basical cryobiology and cryopreservation protocols of ASCs were summarized. We also looked forward to the future research interest of cryopreservation protocols of ASCs.
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Exploring the Molecular Mechanisms of Moxibustion Treatment for Osteoporosis Model Rats Using MicroRNA Sequencing Technology
Cui Lu, Li Xiao, Li Xing, Chen Xiaoli, Hu Xiaoshen, Zhou Haiyan, Li Xiang
Abstract:
Objective: Based on high-throughput sequencing technology for micro-RNA (miRNA), this study explores the molecular mechanisms of moxibustion in improving osteoporosis in rats. Methods: A total of 18 female SD rats were randomly divided into a sham operation group (6 rats) and an operation group (12 rats). The operation group was subjected to ovariectomy to induce osteoporosis (OP), and the 12 rats with successful modeling were randomly divided into a model group and an moxibustion group, with 6 rats in each group. The moxibustion group rats were treated with moxibustion at the “Shenshu” (BL23) and “Guanyuan” (CV4), once a day, for 20 minutes each time, for 12 weeks. Micro-CT scan the rat femur and image it, analyze the trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and bone volume fraction (BV/TV) of the trabecular bone, and HE staining was used to observe the morphology of tibia tissue. Serum alkaline phosphatase (ALP) and osteocalcin (OCN) levels were measured using ELISA. Three randomly selected rats from each group were used for miRNA high-throughput sequencing, and differentially expressed miRNAs were screened. The functional enrichment analysis and target gene prediction were performed for the differentially expressed miRNAs. Results: The Micro-CT images showed that the bone density of the moxibustion group was superior to that of the model group, and compared to the model group, the moxibustion group showed a significant increase in the thickness of the trabecular bone (Tb.Th), a significant rise in the bone volume/tissue volume (BV/TV) score, and a significant decrease in the trabecular separation (Tb.Sp) (P < 0.05). The ELISA results indicated that compared to the model group, the moxibustion group showed a significant decrease in serum ALP activity and a significant increase in serum OCN content (P < 0.05). The miRNA sequencing results showed that 34 miRNAs were commonly expressed between the model group and the intervention group, and 15 miRNAs were commonly expressed between the model group and the intervention group. The KEGG pathway enrichment analysis showed that the expression of different genes was mainly enriched in signaling pathways such as MAPK, Ras, FoxO, TNF, and cancer-related microRNAs. For the top 5 differentially expressed microRNAs with the highest significance, namely miR-153-5p, miR-201-5p, miR-449c-5p, miR-451-3p, and miR-153-3p, target gene predictions yielded 10 major targets: Ebf2, Rtn4, Fbxl3, Naa15, Vamp2, Daam1, Akap6, Camta1, Ptprz1, and Lamp1. Conclusion: Acupuncture can slow down the progression of OP, improve bone microstructure, and balance bone metabolism. This therapeutic effect may be achieved by regulating the expression of microRNAs and their target genes, and a more detailed mechanism awaits further exploration.
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The effect of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis
Wang Jingya, yan kang, Li Ji-an, Wang Meng, Yang Yuyang, Yu Yueyue
Abstract:
Objective: To investigate the effects of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in knee osteoarthritis (KOA) rats. Method: Anterior cruciate ligament dissection (ACLT) was used to create a KOA model in SD rats. The successfully modeled rats were randomly divided into a model group, a celecoxib group, and a traditional Chinese medicine group. Each group received medication intervention on the second day of modeling, for a total of 8 weeks. HE and safranin O staining were used to observe the pathological changes of articular cartilage; ELISA detection of serum IL-1β, IL-18; Micro CT analysis of bone microstructure. RT-PCR detection of MMP13, NLRP3, ASC, Caspase-1, GSDMD, IL-1β, IL-18, ACSL-4, FTH-1, GPX-4, and COX-2. immunohistochemical detection of NLRP3, Caspase-1and COX-2. Result: Compared with the sham surgery group, the expression levels of NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 in the cartilage tissue of the model group were increased, the expression levels of ACSL-4 and COX-2 of model group rats were significantly increased, while the expression levels of FTH-1 and GPX-4 were significantly decreased. Compared with the model group, the NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 expression levels of rats in the traditional Chinese medicine group were decreased, the expression levels of ACSL-4 and COX-2 of rats in the traditional Chinese medicine group were decreased, while the expression levels of FTH-1 and GPX-4 were increased. Conclusion: Yishen Zhuyu Tongluo Decoction could treat KOA by inhibiting chondrocyte pyroptosis and ferroptosis in KOA rats, reducing the level of serum inflammatory factors, and improving bone microstructure.
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The Latest Research Progress On The Effects Of Mitochondrial Damage On Cardiomyocytes
Abstract:
Cardiovascular disease is still an important cause of death and morbidity worldwide. Mitochondria are considered key organelles in cardiac physiology, accounting for 1/3 of the volume of cardiomyocytes. They are not only the power plant of cardiomyocytes, but also the center of signal transmission, which determines the survival and death of cells, and are potential targets for improving cardiac function. Recent studies have shown that mitochondria are closely related to cell activities such as apoptosis, reactive oxygen species (ROS) production and lipid metabolism, so mitochondrial damage plays an important role in the pathogenesis of cardiovascular diseases (CVD). The purpose of this review is to elucidate the effects of mitochondrial damage (such as mitochondrial autophagy, mitochondrial dynamics) on cardiomyocytes.
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Exploration of Batch Identification Methods for Model Mice
Jin You, Ni Lan, Wei Qi, Zhao Huan, He Jingang
Abstract:
Objective To establish a simple，fast and economic total DNA extraction method to serve the rapid identification of model mouse genotype in large number of mice. Methods Four methods，i.e.alkali boiling routine method, alkali boiling simplified method, protease K lysis and DNA extraction kit methods were used to extract the total DNA from transgenic mice tails．The purity and concentrationof DNA obtained by the four methods were measured, the advantages and disadvantages of gel electrophoresis were evaluated, and the time-consuming and experimental costs of the four methods were compared．Results The DNA concentration extracted by protease K cleavage method is the highest, followed by alkaline boiling simplified method and conventional method; The DNA purity obtained from the reagent kit treatment is relatively high, followed by the alkaline boiling simplification method. The DNA templates obtained by four methods can be amplified by PCR and Gel electrophoresis to obtain clear DNA target bands, and can also be used for gene identification after being stored at -20 ℃ for one month. In addition, the simplified alkaline boiling method has the lowest cost and the least time consumption. Conclusion The alkaline boiling simplification method is currently the fastest and most economical DNA template extraction method for batch genotyping of model mice.
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5-aza-2 "-deoxycytosine reverses PMT by inhibiting Epo gene promoter hypermethylation in rat primary renal myoblasts______________________________________________________________
yuan ling, wang lei, CHENG Peng, JIANG Qian, CUI Xiao-xue
Abstract:
Objective To observe the effect of demethylating agent 5-aza-2 "-deoxycytidine (5-Aza-CdR) on pericyte-myofibroblast transition(PMT)of primary rat renal myofibroblast. Methods Rat primary renal myofibroblast were treated with 5-Aza-CdR 250 ng/ml for 72h, and the methylation degree of Epo promoter was detected by pyrosequencing. The protein expression levels of α-SMA, PDGFRβ and DNA methyltransferase (DNMT3a) were detected by immunofluorescence and Western blot, and EPO levels in the supernatant were detected. Results Compared with control group, 5-Aza-CdR treatment significantly decreased the expression of Dnmt3a and the hypermethylation level of Epo promoter, and subsequently decreased the expression of α-SMA and the expression ratio of α-SMA to PDGFRβ in myofibroblast. Meanwhile, 5-Aza-CdR treatment increased the level of EPO in the cell supernatant. Conclusions 5-Aza-CdR can reverse PMT by inhibiting Epo promoter hypermethylation in primary renal myofibroblast.
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Exploration of a behavioral model of motivation deficiency in rats and the role of dopamine receptors in the nucleus accumbensZHANG Jianjun1,3, WU Shuang2, XUE Bing3, ZHANG Lulu1, YU Ping2
zhangjianjun, wushuang, xuebing, ZHANG LULU, yuping
Abstract:
In recent years, “lie flat” is a buzz word which describes a special psychological state of some people, but its animal behavioral models are lacking, and its psychological meaning and mechanisms remain unclear. Lack of motivation under certain conditions may be one of the key psychological characteristics for “lie flat”. In this study, a novel rat behavioral model of “lie flat” was designed and was used to explore the possible effects of dopamine receptor in the nucleus accumbens on motivation deficiency in “lie flat”.
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Lentinan inhibits TNFα-ferritinophagy and antagonizes hepatic ferroptosis in Sodium arsenite exposed mice
Yuan Yang, Bao Jiacheng, Deng Yekang, Chen Yang, He Qin
Abstract:
Objective: To explore the intervention effect and mechanism of Lentinan (LNT) on liver ferroptosis in mice exposed to sodium arsenite (SA). Methods: C57BL/6 male mice as experimental subjects, The experiment was divided into control group, SA low-dose group, SA high-dose group, and LNT intervention+SA high-dose group. Biochemical methods and Hematoxylin eosin (HE) staining of liver tissue were applied to evaluate hepatic pathological damage; Enzyme linked immunosorbent assay (Elisa) was used to detect the levels of tumor necrosis factorα (TNFα), microtubule associated protein 1 light chain 3B (MAP1LC3B), Interleukin-6 (IL-6), glutathione peroxidase 4 (GPX4), and iron ions (Fe); Immunoblotting (WB) or immunoprecipitation (IP) methods were used to detect the levels of ferritin heavy chain (FTH1), ratio of LC3B to LC3A, or the co-expressions of FTH1 and LC3, or FTH1 and ubiquitin (Ub); Molecular docking software was applied to analyze the interactions between mitochondrial ferritin (FTMT) and LC3A, LC3B, or Ub. Results: Compared with control group, SA exposure group exhibited hepatic pathological damage and the elevated levels of AST, ALT, TNFα, and IL-6, and the elevated ferritinophagy markers LC3B, FTH1, and Fe, while the levels of ferroptosis biomarkers GPX4 decreased (P<0.05); Compared with SA exposure group, LNT intervention showed a significant reduction in hepatic pathological damage, and showed the downregulations of AST, ALT, TNFα, IL-6, LC3B, FTH1, and Fe, while the level of GPX4 upregulated (P<0.05); WB or IP experiment showed that SA exposure induced the upregulated levels of FTH1 and LC3B/A, and the higher co-expressions of FTH1 and LC3B or Ub protein compared to control group, while LNT intervention showed the downregulated levels of FTH1 and LC3B/A, and the decreased co-expressions of FTH1 and LC3B or Ub protein compared to SA exposure group (P<0.05). Molecular docking simulations showed that FTMT binds stably to LC3A, LC3B or Ub by hydrogen bond. Conclusion: Lentinan antagonizes against sodium arsenite exposure mice hepatic injury and ferroptosis, which may be associated with the inhibition or TNFα-ferritinophagy signaling.
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Coinfection of Coxsackievirus A6 and B1 Experimental Study on Syrian Hamsters Animal Model
houjinghan, duansuqin, xuhongjie, sunwenting, limingxue, liyanyan, jinweihua, chenlixiong, liuquan, zhaoyuan, yangfengmei, hezhanlong
Abstract:
Objective To establish an animal model of hand, foot and mouth disease (HFMD) in Syrian hamsters coinfected with Coxsackievirus A6 (CVA6） and Coxsackievirus B1 (CVB1）. Methods Twenty-four Syrian hamsters were divided into CVA6 infection group, CVB1 infection group, CVA6 and CVB1 coinfection group and control group. The model was established by nasal instillation of virus solution and PBS. Clinical indicators, physiological indicators, and detoxification status were monitored and recorded for 15 days, and animals were selected on D7 after infection for histopathology and viral antigen and nucleic acid testing. Results Hamsters in the single and coinfection groups showed clinical symptoms similar to human HFMD. The results of WBC, NEUT and LYMPH indicated the blood characteristics of viral infection. Both viral nucleic acids were detected in throat swabs, feces, blood and tissues. Both viruses were isolated in fecal samples. Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues. Conclusion The nasal instillation of CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters, replicate herpes similar to human hand, foot and mouth disease, and cause viral myocarditis and encephalitis pathological damage. The results showed that the coinfection group was more serious than the single infection group, with worse clinical symptoms, increased viral replication and obvious tissue pathological damage. This study provides a certain reference for the basic and clinical research of human enterovirus coinfection.
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Study on the establishment of rat model of pelvic inflammatory disease by non-surgical uterine injection
Abstract:
【Abstract】 Objective To establish an efficient and stable model of pelvic inflammatory disease in rats by non-surgical method and evaluate its application in pharmacodynamic test. Methods Female SD rats were randomly divided into control group, model group treated with phenol for 7 days, model group treated with phenol for 10 days, Chinese medicine treatment group with phenol modeling, model group with low concentration of bacterials, model group with high concentration of bacterias and Chinese medicine treatment group with bacterial modeling. SD rats in model group or treatment group were injected with 25% phenol gel, 2×107 or 2×108 Escherichia coli and Staphylostreptococcus aureus mixture by non-surgical method to construct the rat model of pelvic inflammatory disease. The rats in the treatment group were gavaged with Qingpen Huoxue decoction, and the rats in the control group were given the same volume of solvent solution at the same time. The health status, weight change and uterine appearance of rats were observed. The uterine coefficient was calculated. HE staining was used to detect pathological changes of uterus and fallopian tube, endometrial thickness and number of glands. Serum levels of IL-1β, IL-6 and TNF-α were detected by ELISA. Macrophage marker CD68 protein expression was detected by immunofluorescence staining. The expression of TLR4/NF-KB pathway-related proteins in the uterus of rats was detected by western blotting. Results The mortality rate in the model group was only 5%. Compared with the control group, the body weight of rats decreased, uterine coefficient increased, pathological changes of uterus and fallopian tube appeared in different degrees, endometrium thinned, the number of glands decreased, serum levels of IL-1β, IL-6, TNF-α and the number of macrophages in uterine tissue increased significantly, and TLR4/NF-kB signaling pathway was activated. The 7-day phenol model and low-concentration bacterial solution model were judged to be mild pelvic inflammatory disease model, and the 10-day phenol model and high-concentration bacterial solution model were judged to be severe pelvic inflammatory disease model. After the treatment of Chinese patent medicine--Jingangteng, the pathological symptoms of uterus and fallopian tube were obviously relieved, which was in line with the efficacy evaluation of clinical pelvic inflammatory disease. Conclusion The rat model of pelvic inflammatory disease established by using phenol and mixed bacterial solution in non-surgical method can better simulate the different pathological states of pelvic inflammatory disease caused by different causes, which is suitable for drug efficacy evaluation and elucidating the pathological mechanism of pelvic inflammatory disease.
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Regulatory role of KHSRP in lung adenocarcinoma: Key role of JAK1/STAT3 pathway
Ma Chaonan, Wang Mengyao, Liu Yangyang, lili, Wei Haitao
Abstract:
Objective To investigate the effect of KHSRP on the malignant biological behavior of lung adenocarcinoma by targeting JAK1/STAT3 signaling axis. Methods The clinical data of 64 cases of LUAD tissues and adjacent tissues diagnosed in Huaihe Hospital from January 2017 to December 2018 were collected. The expression level of KHSRP in LUAD tissues and adjacent tissues was observed by immunohistochemical staining. qRT-PCR was used to detect the expression of KHSRP in lung adenocarcinoma cell lines (SPC-A1, H1975, CL1-5, PC-9, Calu-3, H446) and normal human bronchial epithelial cell line (NHBE). Lentivirus transfection changed the expression of KHSRP in lung adenocarcinoma cell lines SPC-A1, H1975, PC-9 and Calu-3. Cell counting kit-8 (CCK-8) and Transwell assay were used to determine the effect of KHSRP on the proliferation, migration and invasion of lung adenocarcinoma cells. Detection to knock down and xenograft tumor model expression KHSRP in living animals. WB experiment KHSRP targeted JAK/STAT signaling pathway. Rescue experiment was conducted to verify whether KHSRP promotes malignant progression of LUAD cells by regulating JAK1/STAT3 signaling pathway. Results Compared with adjacent normal tissues, KHSRP expression in LUAD organizations significantly higher (P<0.05). Overexpression of KHSRP significantly promoted the proliferation, migration and invasion of LUAD cells in vitro (P<0.05). The results of in vivo animal experiments showed that KHSRP can promote LUAD cell xenograft tumor growth and lung nodule metastasis in nude mice (P<0.01). After KHSRP knockdown, the levels of JAK1, p-JAK1 and STAT3 in JAK/STAT signaling pathway were significantly decreased, while the situation was opposite after KHSRP overexpression (P<0.05). Rescue experiment showed that KHSRP can reverse the inhibitory effect of knockdown (P<0.05). Conclusion KHSRP targets JAK1/STAT3 signaling pathway and acts as an oncogene in lung adenocarcinoma.
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Comparative experimental study of sodium benzoate and corticosterone in a mouse model of asthenozoospermia with high SDF
Lu zong lin, Zhao hai yang, Wang hui, Wang xin, Sun zi xue
Abstract:
【】? Objective? The preparation of an animal model of asthenozoospermia with hypersperm DNA fragmentation was explored by inducing the construction of a mouse model of asthenozoospermia (AZS) with hypersperm DNA fragmentation (SDF) by the hormone corticosterone (CORT) and the compound sodium benzoate (NaB).? Methods? Fifty 3-week-old male ICR mice were randomly divided into 30 CORT-treated groups and 20 NaB-treated groups. The CORT treatment group was divided into 6 groups, with 5 animals in each group, of which 3 groups were high (500 μg/ml), medium (200 μg/ml) and low (10 μg/ml) dose groups of CORT drinking water modeling, 1 group was drinking water control group, 1 group was CORT injection molding group (40 mg/kg), and 1 group was injection control group (normal saline), and the model was continuously modeled for 50 days. The NaB treatment group was divided into 4 groups, with 5 animals in each group, of which 3 groups were high (500 mg/kg), medium (300 mg/kg) and low (100 mg/kg) NaB gavage groups, and 1 group was control group (normal saline), and the model was continuously modeled for 50 days. The physiological state of the mice in each group was observed and the weight changes were continuously recorded, and the sperm motility capacity and DNA fragmentation index (DFI) of the sperm were observed from the tail of the epididymis of the mice after the end of the modeling. Results? The rate of weight change in the CORT injection group showed a downward trend, There was no significant difference (P>0.05) in the high-dose NaB gavage group, and the change rate of body weight in the high-dose NaB gavage group decreased significantly compared with the control group (P<0.05), the percentage of forward motility sperm in the CORT injection group decreased compared with the control group (P>0.05), the percentage of forward motility sperm in the high-dose NaB gavage group decreased significantly compared with the control group (P<0.05), the DFI in the CORT injection group increased with no significant difference compared with the control group (P>0.05), and the DFI in the high-dose NaB gavage group increased significantly compared with the control group (P>0.05).? Conclusion? Intragastric gavage at NaB 500mg/(kg·d) for 50 days is an ideal method to construct an animal model of AZS with high SDF.
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Research on the Potential Mechanism of Pepper Extract Regulating Ferroptosis and Alleviating Depression
GUAN Dongyan, ZHANG Mijia, HOU Zhiying, WANG Jiayin, YU Jiawei, FAN Bei, XIE Hui, DUAN Zhouwei, BAI Yajuan, WU Honghong, WANG Fengzhong, WANG Qiog
Abstract:
Abstract: Objective Using network pharmacology and molecular docking techniques to predict the potential mechanism by which active components in Piper (Piper nigrum L., PN) regulate ferroptosis to alleviate depression. Methods Firstly, the chemical composition of Piper was obtained from the Traditional Chinese Medicine System Pharmacology Database (TCMSP), and disease-related genes were obtained using the Online Mendelian Inheritance Database for Humans (OMIM), Genecards, and FerrDB databases. The active ingredient-target-disease network was mapped using Cytoscape software, the protein interaction network (PPI) was mapped using the STRING database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the open-source bioinformatics software Bioconductor. Next, molecular docking was conducted to validate the binding capacity between the core targets and their corresponding active components. Finally, we established a chronic restraint stress (CRS) mouse model, treated with different concentrations of PN (75, 150, and 300 mg/kg) for four weeks, followed by behavioral assessments and qPCR to verify the expression of core genes. Results We identified nine active components from PN, corresponding to 27 targets. There are 8,377 targets related to depression and 547 targets related to ferroptosis, resulting in an intersection of 25 target genes. KEGG enrichment analysis revealed that these core targets are primarily enriched in signaling pathways such as cholinergic synapses, serotonergic synapses, and neuroactive ligand-receptor interactions. Molecular docking results indicate that the main active components of PN exhibit strong binding affinity with the targets CHRM2, SLC6A4, PTGS2, and SLC6A2. Behavioral assessments demonstrated that PN significantly increased the saccharin preference index in treated mice, reduced immobility time in the tail suspension and forced swimming tests, and enhanced exploratory behavior in the open field test. Neurotransmitter analysis revealed that PN significantly elevated serotonin and acetylcholine levels in the hippocampus of mice. qPCR results showed that PN can downregulate the mRNA expression of SLC6A4 and PTGS2. Conclusion PN may regulate ferroptosis and improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels, participating in immune regulation, and exerting neuroprotective effects.
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Research advances on Iron overload and related Animal models
TANG Huian, AO Guangyu, CHEN Min, ZHANG Yujiao, CHEN Zejun
Abstract:
Iron is an essential trace element for the human body, critical for vital cellular processes such as DNA synthesis, respiration, and oxygen transport. The body meticulously maintains iron homeostasis through a coordinated balance of absorption, utilization, storage, and distribution. Both iron deficiency and excess can lead to pathologies; the latter can trigger lipid peroxidation and DNA mutations through the Fenton reaction, potentially causing iron-induced cell death in severe cases. Iron overload is recognized to inflict significant damage on multiple organs, including the brain, liver, spleen, heart, ovaries, and kidneys. Despite this, the mechanisms that regulate iron homeostasis in response to overload are not fully understood.To elucidate these mechanisms, various animal models have been developed, each reflecting different aspects of iron overload (IOL) relevant to human diseases. Accurately simulating the pathological and physiological states associated with human IOL-related diseases necessitates the selection of the most appropriate animal models. This review synthesizes recent literature on animal models pertinent to iron overload, aiming to offer insights for the development and analysis of models for diseases related to iron overload.
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Research progress on the role of common vitamins and elements in the treatment of Alzheimer's disease
Abstract:
Alzheimer"s disease (AD) is a neurodegenerative disease caused by a variety of risk factors, which is the main cause of dementia in the old people. At present, the pathogenesis of AD has not been studied clearly, and the treatment of AD is very limited. Clinical drugs can only alleviate the symptoms of AD to a certain extent, but can not delay the course of AD. At present, the pathogenesis of AD has not been studied clearly, and the treatment of AD is very limited. Clinical drugs can only alleviate the symptoms of AD to a certain extent, but can not delay the course of AD. A large number of studies have shown that a variety of micronutrients play a positive role in the treatment of AD. Vitamins, trace metal elements, unsaturated fatty acids and polyphenols have many functions such as anti-inflammation, anti-oxidation and protection of mitochondria. Micronutrients can effectively reduce Aβ protein plaque deposition and Tau protein hyperphosphorylation to improve brain energy metabolism, thereby achieving the prevention and treatment of AD. The purpose of this article is to explore the mechanism of micronutrients in the treatment of AD, and to review its application and effect in the treatment of AD, and to provide theoretical basis and new strategies for micronutrient intervention in the treatment of AD.
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Proton Pump Inhibitor Pantoprazole Promotes Colonization of Helicobacter pylori SS1 in Mouse Stomachs
Shuo Yan, Xue Li, Chao Wang, Jiali Xu, Yu Cheng, Liping Zhang, Lei Su, Jianan Gong
Abstract:
Objective To explore methods for improving the colonization efficiency of Helicobacter pylori (Hp) in the mouse stomach and to determine whether the proton pump inhibitor (PPI) pantoprazole can act as a colonization adjuvant to enhance Hp colonization. This study aims to provide an effective tool for establishing an Hp infection mouse model. Methods The Hp Sydney strain (SS1) was introduced, and solid plate and liquid culture systems were established and identified. The effects of different doses of pantoprazole on gastric acid secretion in mice were compared. The impact of Hp inoculation alone or combined with pantoprazole pretreatment on Hp colonization efficiency was analyzed using rapid urease tests, bacterial plate cultures, and TaqMan qPCR. Results Proton pump inhibitor pretreatment inhibited gastric acid secretion and, to some extent, promoted Hp colonization in the mouse stomach. Conclusion Proton pump inhibitors can serve as colonization adjuvants to enhance the efficiency of constructing Hp infection mouse models.
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Effects of circadian rhythm on mood and cognitive behavior in male and female mice under chronic restraint stress
qiangmeng, jiangning, huanghong, zhangyiwen, chenfang, lizhaohui, liuxinmin, lvguanghua
Abstract:
Objective To investigate the effects of chronic restraint stress for 28 days during the day and night on the mood and cognitive-like behavior of male and female ICR mice, so as to provide a basis for the selection of sex and restraint period in experimental animals in the chronic restraint stress model. Methods ?A total of 72 male and half ICR mice were divided into 6 groups: male blank control group, male daytime restraint group, male nighttime restraint group, female blank control group, female daytime restraint group, and female nighttime restraint group. Except for the blank control group, the other groups were bound for 10 h every day and continuously restrained for 28 days to establish a chronic restraint stress model. The emotional and cognitive behaviors induced by restraint in male and female ICR mice at different times were observed by empty field experiment, Y maze experiment, novel inhibition feeding experiment, elevated cross maze experiment, tail suspension experiment, forced swimming experiment, and dark avoidance experiment. Results In the tail suspension experiment, the immobility time of the male mouse in the daytime restraint group was significantly increased compared with that in the blank group (P<0.05). In the forced swimming experiment, the immobility time of the daytime and nocturnal restraint groups of male mice was significantly increased compared with that of the blank group (P<0.05). In the novelty inhibition feeding experiment, there was no significant difference between the daytime binding group and the blank group, and the feeding latency of the nighttime binding group was significantly longer than that of the blank group (P<0.05) and significantly longer than that of the daytime binding group (P<0.05), and the feeding latency of female mice was significantly longer than that of males during nocturnal binding (P<0.05). In the empty field experiment, the central zone time and central zone time compared with the male blank group were significantly decreased compared with the blank group (P<0.05), the central zone time and central zone time compared with the blank zone were significantly decreased compared with the blank group in the female mice (P<0.05), and the central zone time and central zone compared with the margin zone of the female mouse blank group were significantly increased compared with the male blank group (P<0.05). There was no significant difference between the groups in the elevated cross maze experiment and the Y maze experiment. In the dark avoidance experiment, there was no significant difference between the dark latency of the daytime restraint group and that of the blank group, and the darkness latency of the nighttime restraint group was significantly shortened compared with that of the blank group (P<0.05). Conclusions Male mice exhibit depression after 28 days of chronic restraint stress during the daytime. After 28 days of chronic restraint stress, female mice were prone to anxiety. Learning and memory impairment occurred in male mice after 28 days of chronic restraint stress during the night period.
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Exploring the Mechanism of Modified Jisheng Shenqi Decoction in Improving Hypoxia Microenvironment and Preventing Cirrhosis Based on HIF-1 α/Notch Signaling Pathway
moyiling, zhouxiaoling, liulin, sundongqi, wuteng, luoyi, ruanbowen, wangyueming, jiayao
Abstract:
Objective: To explore the mechanism of Jiawei Jisheng Shenqi Decoction in improving the hypoxic microenvironment and antagonizing liver cirrhosis. Method: In vivo experiments were conducted on a rat model of liver cirrhosis induced by carbon tetrachloride. Normal group, model group, colchicine group, and low, medium, and high dose groups of Jiawei Jisheng Shenqi Decoction were set up. HE staining and Masson staining were used to observe the pathological changes in liver tissue of rats in each group;Test kit was used to to detect changes in serum liver function in each group of rats; Elisa was used to detect the levels of hyaluronic acid (HA), laminin (LN), procollagen III (PCIII)and collagen type IV(COL4) in each group of rats; Western blot was used to detect the expression of hypoxia inducible factor-1α(HIF-1α), Notch1, Jagged1, and α-smooth muscle actin(α-SMA) proteins in rats. In vitro experiments were conducted on HSC-T6 cells, and the CCK-8 method was used to screen for the most suitable (100 μM, 200 μM, 400 μM, 600 μM, 800 μM) concentrations of CoCl2 cultured cells and the optimal intervention concentrations of drug containing serum (5%, 10%, 15%, 20%); Scratch test was used to detect the migration ability of cells in each group; Flow cytometry was used to detect changes in apoptosis rate of cells in each group; Western blot was used to detect the expression of HIF-1α, Notch1, Jagged1, a-SMA, Matrix Metallopeptidase 9(MMP9), and Tissue Inhibitor of Metalloproteinases 1(TIMP-1) proteins in each group of cells. Results：In vivo experiment: Compared with the control group, the model group rats showed significantly increased liver swelling, inflammatory cell infiltration, and collagen deposition, as well as the appearance of pseudolobules. The levels of serum ALT, AST, HA, LN, PCIII, COL4 were significantly increased, while ALB was significantly decreased. The expression of HIF-1α, Notch1, Jagged1, and α-SMA proteins in liver tissue was significantly increased (P<0.01). Compared with the model group, the liver swelling, inflammatory cell infiltration, and collagen deposition in each treatment group rats were significantly reduced, and the degree of fibrosis was reduced. The levels of serum ALT, AST, HA, LN, PCIII, COL4 were significantly decreased, while ALB was significantly increased. The expression of HIF-1α, Notch1, Jagged1, and α-SMA proteins in liver tissue was also significantly increased. Decreased to varying degrees (P<0.05). In vitro experiments: Hypoxia can promote HSC-T6 migration, reduce HSC-T6 apoptosis, and increase the expression of HIF-1α, Notch1, Jagged1, a-SMA, and TIMP-1 proteins, while reducing the expression of MMP9 protein (P<0.01). The serum containing Jiawei Jisheng Shenqi Decoction can inhibit HSC-T6 migration, promote HSC-T6 apoptosis, and lower the expression of HIF-1α, Notch1, Jagged1, a-SMA, and TIMP-1 proteins, while enhance the expression of MMP9 protein (P<0.01). However, its inhibitory effect on HSC-T6 cell activation can be reversed by the HIF-1 α agonist DMOG. Conclusion: Jiawei Jisheng Shenqi Decoction can improve the hypoxic microenvironment through the HIF-1α/Notch pathway, thereby exerting an anti liver cirrhosis effect.
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Application and research progress of electroencephalographic resting microstates in generalized anxiety disorder
LI Chenrui, WU Yiming, CHEN Xinwang, HE Yayong, NAN Shanzhu
Abstract:
In recent years, the incidence of generalized anxiety disorder (GAD) is at an increasing stage year by year in a complex social environment. Currently, the diagnosis of GAD often relies on DSM-5 and ICD-10 criteria, which have certain subjectivity and limitations. Understanding the intrinsic activity of brain network function and structural connectivity has proven to be an important goal of contemporary neuroscience research. EEG microstates are capable of observing broad frequency components and capturing dynamic changes in brain activity as a way to provide a new way of thinking about the accuracy of GAD diagnosis. This paper delves into the EEG microstate features and explores the abnormalities in the functional brain network of GAD patients, aiming to further provide a clear diagnosis, optimize the therapeutic efficacy and improve the quality of medical care for GAD patients.
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Research Progress on the Role and Mechanisms of Epigenetics in Delirium Diseases
Abstract:
Delirium has a high incidence and is prone to lead to poor prognosis of patients. The pathogenesis is still not completely clear, and antipsychotic drugs are mainly used to intervene in clinical practice, and there is no drug that can definitively improve the long-term health-related quality of life of patients with delirium. In this study, we review the research on the association between epigenetic modifications such as non-coding RNA, DNA methylation, histone acetylation and the development of delirium, with the aim of providing clinical decisions on the early identification and diagnosis of delirium, its treatment and prognosis, and the development of relevant targeted drugs.
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Research Progress on The Biomarkers of Drug Addiction
HUANG Wenxin, ZHANG Qianyao, LI Xiaodong, TIAN Yunqing, HUANG Jian, ZHANG Rui-lin
Abstract:
Drug addiction is a chronic disease that not only causes serious physical and psychological harm to the individual, but more importantly, it also causes serious damage to society. Biomarkers are indicators that differ significantly between healthy people and patients, and are important for both diagnosis and treatment of diseases. Due to the increasing number of drug-addicted patients in recent years and the increasing variety and number of new drugs, the study of biomarkers of drug addiction has been increasing, and biomarkers are present in different biological samples. This paper reviews the biomarkers in hair, blood, urine and faeces, which can help to explore the biosignature markers of drug addiction and facilitate the clinical diagnosis and treatment of drug addiction.
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Effects of five-element music on depressive behaviors and intestinal flora of stress-phobic offspring during pregnancy
lixiaolin, yangliping, houjunlin, wangyaohui, yuchenyang, lilingling
Abstract:
Objective Exploring the effects of five-element music on depressive behavior and gut flora of stress-phobic offspring during pregnancy. Methods Thirty-six 0.5-day pregnant Wistar female rats were randomly divided into the blank group, the stress-phobic group and the five-element music group, and the litters were continued in the maternal group. Pregnant rats in the 1-19 day gestation stress-phobic group and the five-element music group were modeled by the side-by-side electroshock method, while the five-element music group was given the five-element music feathering intervention. The effect of modeling was evaluated by using the absent field experiment, enzyme-linked immunosorbent assay (ELISA) to detect the fearful behavior and serum glucocorticoid (GC) content of the pregnant rats on the 20th day of gestation; the depressed mood of the rats was evaluated by using the absent field experiment, the tail-hanging experiment and the sugar-water preference experiment at the age of 3 weeks; and the changing pattern of the intestinal flora of the rats was analyzed by using 16S rRNA sequencing. Results Compared with the blank group, pregnant rats in the stress-phobic group stayed longer in the peripheral area of the absent field, had fewer entries into the central area (p < 0.05), and had higher serum GC levels (p < 0.001), whereas the five-element music group reversed the behavioral changes in the stress-phobic group (p < 0.05) and the serum GC levels (p < 0.001). Compared with the blank group, the stress-phobic group showed a decrease in the number of absentee grids worn (p < 0.01), a decrease in the glycemic index, and a prolongation of the time of tail suspension (p < 0.05), while the five-element music group showed an increase in the number of absentee grids worn, the glycemic index, and a shortening of the time of tail suspension (p < 0.05), and the total distance traveled by the rats in each group did not show any significant difference. The intestinal flora species diversity of the rats in the stress-phobic group decreased (p < 0.01) and the structure of the flora was significantly changed compared with that of the blank group, in which the abundance of Proteobacteria, Enterobacteriaceae, Enterococcus and Escherichia were up-regulated, and the abundance of Spirochaetes and Spirochaetaceae, Lachnospiraceae, Ruminococcaceae,Treponema, Prevotella,Coprococcus, Allobaculum, Ruminococcaceae_Ruminococcus, Dorea was down-regulated, and five-element music group of littermates showed an increase in species diversity of the intestinal flora compared to the stress-phobic group (p < 0.01) and reversed the changes in the abundance of the above flora. Conclusion A five-element music intervention during pregnancy is effective in ameliorating fearful stress-induced depression behavior and gut flora disruption in offspring during pregnancy.
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Neuroprotective effect of Dendrobium nobile Lindl extract on Caenorhabditis elegans model of Parkinson"s disease
FAN Xinyue, HE Wenlu, DONG Li, HOU Zhiyin, ZHENG Hanwen, Alberto Carlos Pires Dias, WANG Qiong
Abstract:
Objective To investigate the effect of Dendrobium nobile Lindl (DNL) on Caenorhabditis elegans (C. elegans) model of Parkinson"s disease, 6-OHDA was used to induce C. elegans model of Parkinson"s disease(PD), and Dendrobium nobile was used to interfere with C. elegans. Methods C. elegans NL5901 and 6-OHDA-induced N2, BZ555, PD4521 and BC7272 were treated with DNL of 7.5, 15 and 30mg/L. The survival rate, basal slowing response rate, α-synuclein aggregation(α-syn), dopaminergic neurons(DNs), mitochondrial distribution density of body wall muscle cells and protein levels in the membrane were observed. In addition, the activity of SOD and GSH in 6-OHDA-induced N2 was detected to explore the effect of DNL on the anti-oxidative stress ability of Parkinson disease C. elegans models. Results Compared with the PD model group, the DNs fluorescence intensity of the nematodes treated with DNL and L-DOPA was significantly increased (P<0.001), α-syn aggregation was significantly decreased (P<0.05 or P<0.001), the basal slowing rate was increased (P<0.05 or P<0.001), mitochondrial density was increased (P<0.001), mitochondrial intima protein content was increased (P<0.05 or P<0.001), SOD(P<0.05) and GSH content are also increased. The lifespans of N2 wild type C. elegans and PD C. elegans models were prolonged after DNL treatment (P<0.05 or P<0.001). Conclusions A certain concentration of DNL can effectively improve the paralysis of C. elegans model of Parkinson"s disease, improve the degeneration of dopaminergic neurons, reduce the accumulation of α-syn and suppressed the loss of DNs. Overall, DNL treatment increase the ability of anti-oxidative stress, and slow down the aging process of C. elegans. These results provide reference for the screening of effective drugs for Parkinson"s disease.
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Exploring the mechanism of action of Gegen QinLian Decoction in improving Non-alcoholic Fatty Liver Disease by inhibiting iron death based on the Nrf2/SCLC7A11/GPX4 pathway
LUO Qian, LUO Tao, SONG Zhenzhen, LIANG Fang, LI Junsen, PENG Shuhong, CAO Lan, ZHAO Haiping, ZHANG Changhua
Abstract:
Objective To investigate the mechanism of the action of nuclear factor erythroid 2-related factor 2Nrf2/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway in NAFLD by in vivo and in vitro experiments. The mechanism of Gegen QinLian Decoction in the treatment of non-alcoholic fatty liver disease (NAFLD) was investigated in vivo and in vitro. Methods Animal experiments: Rats were fed with high-fat chow for 24 weeks to complete the induction modeling of NAFLD, and were randomly divided into normal, model, Gegen QinLian Decoction high-dose, medium-dose, low-dose, and metformin (Met) groups. From the 25th week onwards, the corresponding drugs were gavaged for two weeks according to the grouping until sampling. Biochemical kits were used to measure the levels of oxidative stress: malondialdehyde (MDA) and glutathione (GSH) in the liver tissues of rats in each group. A ferrous ion kit was used to detect ferrous iron (Fe2+) in rat liver tissues. qRT-PCR was used to detect Nrf2, heme oxygenase-1 (HO-1), SLC7A11, glutathione synthetase (GSS), GPX4 and acyl coenzyme A synthetase 4 in rat liver tissues. Glutathione Synthetase (GSS), GPX4 and Acyl Coenzyme A synthase (ACSL4) mRNA expression levels. Cellular experiments: 1 mmol/L free fatty acid (FFA) was used to induce lipid accumulation in hepatocellular carcinoma HepG2 cells mimicking the NAFLD in vitro model, and different concentrations of Gegen QinLian Decoction and metformin-containing serum were added for treatment. Oil red O staining was used to detect the lipid accumulation of cells in each group. Kits were used to determine the MDA and GSH content of HepG2 cells in different groups. Cell-specific ferrous kit was used to detect the ferrous content of cells in each group. qRT-PCR was used to detect the expression levels of Nrf2, HO-1, SLC7A11 , GSS, GPX4 and ACSL4 mRNA in cells of each group. Results Animal experiments: MDA and Fe2+ contents in liver tissues of rats in the model group were significantly higher than those in the blank group, and GSH contents were significantly lower (P<0.01); the Gegen QinLian Decoction high and medium dose groups and the metformin group could substantially reduce MDA and Fe2+ contents and elevate GSH contents, compared with the model group (P<0.01, 0.05). Compared with the model group, the Gegen QinLian Decoction high- and medium-dose groups and the metformin group increased the expression levels of Nrf2, HO-1, GSS, and GPX4 mRNA, and decreased the level of ACSL4 mRNA (P<0.01, 0.05). Cellular assay:Red lipid droplets were significantly increased in the HepG2 cell model group compared with the blank group, and the use of Gegen QinLian Decoction and metformin led to a significant decrease in lipid droplets. The kit assay revealed that MDA and Fe2+ content increased significantly in the HepG2 cell model group, and GSH content decreased significantly compared with the normal group (P<0.01),while all dose groups of Gegen QinLian Decoction and metformin group significantly decreased MDA and Fe2+ content compared with the model group (P<0.01), and the high and middle dose groups of Gegen QinLian Decoction, the low dose group, and the metformin group increased GSH content (P<0.01, 0.05). qRT-PCR experiments showed that the mRNAs of Nrf2, GSS, GPX4, and SLC7A11 in the high dose group of Gegen QinLian Decoction, Nrf2, HO-1, and SLC7A11 in the middle dose group, HO-1, SLC7A11, and GSS in the low dose group, as well as GSS, Nrf2, HO-1 in the metformin group, mRNA expression levels of GPX4 and SLC7A11 were significantly increased compared with the model group (P<0.01, P<0.05). The mRNA expression of ACSL4 was significantly decreased in the middle and low dose groups of Gegen QinLian Decoction and the metformin group (P<0.01, 0.05). Conclusion Gegen QinLian Decoction can improve NAFLD by inhibiting iron death, and its mechanism of action may be related to the regulation of Nrf2/SLC7A11/GPX4 signaling pathway.
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Mechanism of Vagus Nerve Stimulation in the Neuro-regulation of Attention
zhijincao, jiaxueyan, changqing, xuhe, jiweiwei, wangyan
Abstract:
Attention refers to the body’s capacity to maintain an alert awareness of the internal and external stimuli. Attention deficit can significantly impairs the learning capacity and working proficiency with a heavy burden to the family and society. Vagus nerve stimulation (VNS), as an emerging neuroregulatory technique that can achieve reciprocal interaction between the central and peripheral nervous system, has been found to have great potential in the treatment of neurological and psychiatric diseases. However, it has not been used in the clinic for treating the attention-deficient developmental disorders in children and neurodegenerative diseases in aged population. In this paper, the anatomical and physiological basis of VNS, the application status of VNS, and potential use of VNS in treating attention deficit diseases are briefly reviewed. The potential mechanism of VNS participating in attention nervous regulation is proposed in order to lay a theoretical foundation for the application of VNS in the field of attention nervous regulation.
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Breeding and biological risk control of laboratory monkeys for Animal Biosafety Level 2 Laboratories
Lu Shuangshuang, Li Xiaoyan, Lu Ziwei, Bi Xiang, Lu Xuancheng
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Animal biosafety laboratories generally use negative-pressure cages to raise animals to guarantee biosafety. The monkeys are much larger when compared with the rodents. The monkeys are mostly housed in negative-pressure rearing cages within animal biosafety laboratories in a semi-open form. With practical work experience in an animal Biosafety Level 2 (ABSL-2) laboratory, the author discussed how to control biological risk at various stages of monkey breeding and infectious experiments within the ABSL-2 laboratory. This exploration provides valuable insights and references for controlling biological risks with monkey infectious experiments in ABSL-2 and ABSL-3 laboratories in the future.
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Analysis of Vascular Restenosis Animal Model Based on Data Mining
xiebeili, liumingwang, wenwei, yanyuxin, gaomengjie, jianglulian, jinzhidie, zhaofuhai
Abstract:
Objective: To analyze the modeling methods and evaluation methods of vascular restenosis animal model in recent 10 years, and provide reference for improving vascular restenosis animal model. Methods: Literature related to vascular restenosis was retrieved from Chinese and English mainstream databases from 2013 to 2023. Data of experimental animal strain, modeling method, modeling cycle and detection method were extracted from the included literature, and a database was established by Excel for summary analysis. Results: Among the 122 articles, the experimental animal strains were mainly rats, rabbits and pigs, and the sex was mainly male. The most commonly used modeling method was balloon injury, and the modeling cycle was mainly within 4W-8W. The detection indexes were mainly histopathology, accounting for 37.18%, including routine hematoxylin-eosin staining, Masson staining and EVG staining. Conclusion: At present, the translatability of porcine vascular restenosis model is more in line with expectations, but the cost is high and it is difficult to popularize. Rats and rabbits are still the mainstream. Balloon injury is the main mode of modeling. Different vascular restenosis animal models and modeling methods have advantages and disadvantages, and should be selected according to the experimental purpose.Animal models of vascular restenosis still have some limitations, and it is inevitable to seek more ideal animal models in the future.
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Overview of the Mechanisms by Which Traditional Chinese Medicine Modulates the NF-κB Signaling Pathway to Alleviate Diabetic Kidney Disease
Abstract:
Diabetic kidney disease (DKD) is a common complication of diabetes mellitus (DM) and a leading cause of end-stage renal disease (ESRD). Increasing evidence indicates that the nuclear factor-kappa B (NF-κB) signaling pathway plays a pivotal role in the onset and progression of DKD. Numerous experimental studies have demonstrated that traditional Chinese medicine (TCM) can attenuate inflammatory responses by modulating the NF-κB signaling pathway, thereby delaying the progression of DKD. This review summarizes the relationship between the NF-κB signaling pathway and DKD, and discusses the advances in research on how TCM interventions targeting the NF-κB signaling pathway can alleviate DKD. The aim is to provide new references for targeted therapy of DKD.
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To compare the changes of depressive behavior in mice induced by different doses of corticosterone injection
Abstract:
【Abstract】Objective To observe the changes of depressive behavior and neuronal damage induced by different doses of corticosterone (CORT) in mice, and to explore the best dose of corticosterone-induced depression model in mice. Methods Forty male C57BL/6J mice were randomly divided into four groups: normal control group and corticosterone group (low, medium and high, 20, 40 and 60 mg/kg), and the corresponding drug intervention lasted for 4 weeks. The behavioral changes of mice after subcutaneous injection of corticosterone for 3 and 4 weeks were detected by sugar water preference test, forced swimming test, tail suspension test and open field test. Hematoxylin-eosin staining (HE) and Nissl staining were used to observe the morphological changes of neurons in hippocampal CA1 area and forebrain cortex area of mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of 5- hydroxytryptamine (5-HT) in serum. To compare the behavioral changes of depression in mice induced by different doses of corticosterone. Results Compared with the control group, the weight of mice in corticosterone dosage groups (20 mg/kg, 40 mg/kg and 60 mg/kg) decreased (P < 0.05) and the preference of sucrose solution decreased (P < 0.01). The immobility time of forced swimming mice in corticosterone 20 mg/kg and 40 mg/kg groups was prolonged (P < 0.01). The immobility time of mice in the 40 mg/kg corticosterone group was prolonged (P < 0.05). The total distance, the average speed and the times of entering the central area of the open-field experimental mice in the corticosterone 40 mg/kg and 60 mg/kg groups decreased (P < 0.05), and the stay time in the peripheral area of the mice was prolonged (P < 0.05). In addition, corticosterone injection resulted in incomplete neuronal cell morphology, cell deformation and nuclear condensation in hippocampal CA1 area and forebrain cortex area of mice in different degrees. The level of 5-HT in serum of 40 mg/kg and 60 mg/kg corticosterone decreased (P < 0.05). Conclusion Corticosterone at 20 mg/kg, 40 mg/kg and 60 mg/kg can induce depression-like behavioral changes and neuronal damage in mice to varying degrees, and the effect of corticosterone at 40 mg/kg is more obvious. Under the experimental conditions, it is preliminarily considered that 40 mg/kg is the best dose to replicate the depression model induced by corticosterone in mice.
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Research progress of LncRNA in cerebral ischemia/reperfusion injury
huazhipeng, lv xue, li hao, yang zhan jun, jia jian xin, yang zhi fu
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Cerebral ischemia/reperfusion injury (CIRI) is a significant pathophysiological process affecting the prognosis of patients with ischemic stroke. Its mechanism is complicated and has not been completely clarified. Long non-coding RNA (LncRNA) is a class of non-coding RNA (ncRNA). Early studies focused on its relationship with tumor-related diseases. Recent studies have found that, It is also closely related to the pathological process of ischemia/reperfusion injury. Therefore, in this paper, the relevant mechanisms of LncRNA in cerebral ischemia-reperfusion injury were reviewed.
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Preparation of human SET8 monoclonal antibody and its effect on hepatocellular carcinoma cell proliferation, apoptosis and cell cycle
Wang Yingnan, Wu Jianhua, Wu Chensi, Zhang Fengbin, Zhang Ruixing, Guo Zhanjun
Abstract:
Objective To prepare human SET8 monoclonal antibody and explore its effects on the proliferation, apoptosis and cell cycle of hepatoma cells, and evaluate its anti-tumor effect in mouse models of hepatocellular carcinoma. Methods By immunizing mice with human SET8 polypeptide fragment, B cells and myeloma cells were screened and fused to establish hybridoma cell line that secreted SET8 monoclonal antibody stably. The production was expanded by intraperitoneal injection of mice and collection and purification of ascites. The CCK-8, flow cytometry and Western blot were used to analyze the effects of SET8 monoclonal antibody on the proliferation, apoptosis, cell cycle and apoptosis-related protein expression of hepatocellular carcinoma cells. Finally, a mouse model of human hepatocellular carcinoma cell transplantation was constructed to evaluate the inhibitory effect of SET8 monoclonal antibody on tumor growth in vivo. Results Human SET8 monoclonal antibody significantly inhibited the viability of Huh-7 and Mahlavu hepatoma cells at the concentration of 50ug/ml and 100ug/ml, and the higher the concentration, the stronger the inhibitory effect. Flow cytometry analysis showed that compared with the control group, SET8 monoclonal antibody, paclitaxel and their combination treatment significantly increased the apoptosis rate of Mahlavu cells, and the combination group had the best effect. Meanwhile, SET8 monoclonal antibody induced Mahlavu cell cycle arrest in S and G2 phases and reduced G1 phase cells. Western blot analysis showed that the monoclonal antibody increased the expression of apoptosis-related proteins Bax and caspase-3. Further animal experiments showed that SET8 monoclonal antibody alone or in combination with paclitaxel effectively inhibited the proliferation of hepatocellular carcinoma cells in nude mice, and the combination therapy had the most significant effect. Conclusion The prepared human SET8 monoclonal antibody effectively inhibited the proliferation of hepatocellular carcinoma cells, promoted the apoptosis of hepatocellular carcinoma cells, and showed a good anti-tumor effect in animals.
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Research progress of haptoglobin in digestive system tumors
He Chao, Yang Chun Bai Xue, Zhang Hao, Diao Qingfei, Jia Juming, wuxueliang, Fan Jianchun
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Gastrointestinal tumors pose a serious threat to human health, with their incidence and mortality rates accounting for more than half of all malignant tumors. Haptoglobin (Hp), an acute-phase glycoprotein, has been found to be elevated in both plasma and tumor tissues in various clinical conditions, particularly in different types of cancers such as liver cancer, gastric cancer, colorectal cancer, pancreatic cancer, and gallbladder cancer. Numerous studies suggest that Hp plays a significant role in the prognosis of cancer patients, highlighting its potential as a prognostic marker for gastrointestinal tumors with important clinical applications. Although research indicates that Hp is crucial in the development of various tumors, its specific mechanisms of action in gastrointestinal tumors remain controversial. Therefore, this paper reviews the differential expression and clinical significance of Hp in the five major types of gastrointestinal tumors, exploring its role in different stages of cancer progression and clinical prognosis. This aims to provide reliable and accurate serum biomarkers for the screening, early diagnosis, treatment, and prognosis monitoring of gastrointestinal tumors, which is of great significance for predicting the survival and prognosis of cancer patients.
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Role of Cancer-Associated Fibroblasts in the Formation of the Pre-Metastatic Niche
Ziting Wang1, Guantong Yang1, Jianchun Fan2, Siqi Gao1, Rui Guo1, Lina Jiang1, Yaxiong Guo1
Abstract:
As the global incidence of cancer continues to rise, tumor metastasis has emerged as the leading cause of death among cancer patients. The formation of the pre-metastatic niche creates a favorable microenvironment for tumor cell colonization and metastasis, significantly driving the spread of cancer. In this context, cancer-associated fibroblasts (CAFs) have garnered significant attention for their multifaceted roles in tumor progression. CAFs contribute to the establishment of the pre-metastatic niche and enhance the invasive behavior of tumor cells by remodeling the extracellular matrix, inducing epithelial-mesenchymal transition, stimulating angiogenesis, and modulating the tumor immune microenvironment. These actions not only accelerate the metastatic process but also facilitate immune evasion by the tumor. This review delves into the pivotal mechanisms and functions of CAFs in tumor metastasis, exploring their potential applications in cancer research and therapy, and offering new perspectives for the development of anti-metastatic strategies.
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Research progress of SHP2 in colitis associated colon cancer and colorectal cancer
Abstract:
【】Colorectal cancer (CRC), as one of the most common malignant tumors that threaten human life, seriously affects the quality of life of patients. In recent years, SHP2 has become a hot topic in the field of cancer and has been proven to have a close relationship with colorectal cancer. SHP2, Encoded by the PTPN11 gene, it is a non receptor tyrosine kinase commonly present in various tissues and cells of the human body. Existing research shows that, SHP2 plays a crucial role in regulating CRC and colitis associated colon cancer (CAC). And with the emergence of SHP2 allosteric inhibitors, SHP2 has become a new potential therapeutic target for CRC patients. This article mainly reviews the structure of SHP2 and its impact in CRC and CAC.
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Research Progress on Animal Models of Lung "Inflammation-Cancer" Transformation
chen yajuan, chen lanying, duan wenbin, huang yuqing, jin xuhui
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[Abstract] Lung cancer is a serious pulmonary tumor disease, and the exacerbation of its chronic inflammatory state is a precursor to lung cancer formation. To gain a deeper understanding of the pathogenesis of lung cancer and to develop preventive treatment strategies, relevant animal models are widely used in experimental research. In particular, induced lung cancer animal models are considered an important entry point for understanding the transition from chronic lung inflammation to lung cancer. Early intervention is of great significance for the prevention and treatment of lung cancer. Based on this, this paper reviews recent literature on various inducing factors of lung cancer, including many carcinogens (such as Nicotine-derived nitrosamine ketone(NNK), B[a]P, Benzopyrene(DEN), Atmospheric fine particulate matter(PM2.5), coal smoke, heavy metal ions, radiation, biological infections, etc.). It summarizes the animal models of lung inflammation and cancer transformation induced by these factors, discusses the mechanisms by which relevant carcinogens induce lung cancer, analyzes the advantages and limitations of animal models, and looks forward to future development directions. The aim is to provide a valuable reference for the establishment of related models in the future.
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Progress in the animal model of pollen-induced allergic rhinitis
XuDan, GaoFeihong, LiLin, LiShanshan, WangYili
Abstract:
【Abstract】Pollen allergen-induced allergic rhinitis (AR), also known as seasonal allergic rhinitis (SAR), typically manifests during the pollen dissemination period of anemophilous plants. Over the past three decades, the prevalence of SAR has more than doubled. The etiology of SAR is multifaceted, encompassing various elements such as pollen allergens, environmental and climatic conditions, genetic predispositions, and the immunological status of individuals.Animal models serve as a critical tool in elucidating the mechanisms underlying AR and in advancing the development of efficacious preventive and therapeutic strategies. This review synthesizes the pertinent literature on pollen-sensitized AR animal experiments conducted both domestically and internationally over recent years. It systematically delineates the factors influencing the efficacy of these models, including the selection of animal strains, the production and associated challenges of sensitizing agents, specifically pollen antigens, the utilization and limitations of adjuvants, the procedural steps involved in model creation, and the methodologies for evaluating model effectiveness.The insights provided herein are intended to offer guidance and support for the development of appropriate animal models of pollen-induced AR, thereby facilitating both fundamental and applied research in this area.
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Research progress of berberine in neuroprotection of Parkinson"s disease
lihongyu, lanrui, tangchen, liushuang, zhangyong, shenxiaoming
Abstract:
Parkinson"s disease (PD) is a neurodegenerative disease commonly found in middle-aged and elderly people. A type of disease characterized by static tremors, bradykinesia, muscle rigidity, and postural balance disorders in clinical practice. Berberine (BBR) is a natural quinoline alkaloid. In recent years, studies have found that berberine has hypoglycemic, lipid-lowering, antioxidant, and anti-inflammatory effects, and can effectively improve the misfolding and aggregation of alpha synuclein. Its mechanism of action may include reducing inflammation, alleviating oxidative stress, improving mitochondrial autophagy, regulating intestinal microbiota, and clearing function. This article systematically reviews the mechanism of action and research status of berberine in the neuroprotective field of Parkinson"s disease, providing some reference for the future clinical application and treatment of berberine in Parkinson"s disease.
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Study on the Role of DNA Methyltransferases in Neuroprotection During Hypoxia/Ischemia Preconditioning DNALI Ruixue1,XIE Yabin1,SHAO Guo1,2.
li rui xue, Xie Yabin, Shao Guo
Abstract:
Hypoxic preconditioning can induce endogenous protective mechanisms that increase the tolerance of nerve cells to hypoxia/ischemia. This protective mechanism involves changes in gene expression during the critical decision-making period between cell survival and death. DNA methylation, as a crucial mechanism for gene expression regulation, plays an essential role in hypoxia/ischemia tolerance. DNA methyltransferases (DNMTs) contribute to neuroprotection by influencing gene expression through the regulation of DNA methylation levels. Therefore, DNMTs have significant functions in the neuroprotection induced by hypoxic/ischemic preconditioning. This paper reviews the role of DNMTs in this process, providing insights into neuroprotection targeting DNMTs.
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Research Progress on the Mechanism of MicroRNA Regulation in IBS-D and Intervention with Traditional Chinese Medicine
hechanghui, panhaidi, douxin, meixiao, wangwei
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The incidence of diarrhea-predominant irritable bowel syndrome (IBS-D) remains high, with microRNA-mediated intestinal barrier dysfunction, visceral hypersensitivity, low-grade inflammation, and dysbiosis playing significant roles in its pathogenesis. Studies found that traditional Chinese medicine can treat IBS-D by directly or indirectly targeting miRNA to regulate multiple pathways and targets in a coordinated manner. This article systematically reviews the involvement of miRNA in the pathogenesis of IBS-D and the progress of traditional Chinese medicine interventions. It explores the relationship between traditional genetics, epigenetics, and the Chinese medicine concepts of "kidney" and "spleen" in terms of congenital and acquired interactions from a molecular biology perspective. This provides a reference for exploring the micro-material basis of traditional Chinese medicine's Zang-Xiang theory and offers new ideas and methods for the effective treatment of IBS-D with traditional Chinese medicine.
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Exploration and practice of the elective course “Practical Mouse Anatomy & Comparative Medicine” in undergraduate stage under the perspective of teaching and research integration
Abstract:
The elective course “Practical Mouse Anatomy & Comparative Medicine” is a comprehensive technical course designed to cultivate the foundational theoretical knowledge and experimental skills in laboratory mouse anatomy for undergraduate students in medical and pharmaceutical-related fields. With the increasing demand for innovation and entrepreneurship training programs and undergraduate participation in research laboratories, this course systematically teaches the anatomical knowledge of the eight major systems and local anatomy of experimental mice, emphasizing the combination of theory and practice to provide a comprehensive learning platform. The course continually explores and reforms its practices to ensure that the teaching content keeps pace with the forefront of scientific research, fostering a rigorous and pragmatic scientific attitude in students, thereby laying a solid foundation for their future research work. This paper discusses the effectiveness of the course in enhancing students’ research literacy and practical abilities, aiming to provide a reference for the design and implementation of similar courses.
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Mechanistic study of miR-207 regulates Mycobacterium tuberculosis survival in macrophages
DU Wenya, DAI Yumei, YUE Linzhi, MA Tao, WU Lixian
Abstract:
【Abstract】Objective miR-207 is differentially expressed in many diseases. It investigate the mechanism study of miR-207 overexpression on regulating the survival of Mycobacterium tuberculosis (H37Ra) in macrophages to provide a theoretical basis for targeted therapy of tuberculosis. Methods The experiment was divided into four groups: blank group (Ana-1 cells only), control group (cells infected with H37Ra), mi group (infected with H37Ra and transfected with miRNA-207 mimics), and mi-NC group (infected with H37Ra and transfected with mimics NC). A model of TB infection was established using H37Ra infected Ana-1 cells, and miRNA-207 mimics and mimics NC were transfected into Ana-1 cells using the liposome transfection method. Tuberculosis colony-forming unit counting to assess the effect of miR-207 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria. Flow cytometry was used to detect the total apoptosis rate. The relative expression of miR-207, apoptosis genes, pyroptosis genes, inflammation genes and autophagy genes were measured by qRT-PCR. western blot was used to detect the relative expression of apoptosis proteins, pyroptosis proteins and autophagy proteins. Fluorescence microscope and multifunctional enzyme labeling instrument were used to detect the fluorescence intensity of intracellular ROS, as well as to detect the content of intracellular LDH. Results Successful establishment of infection model was observed under the microscope. qRT-PCR detection found that miR-207 expression in control group was lower than that in blank group, indicating that miR-207 was differentially expressed in blank and control groups. miR-207 expression in mi group was significantly higher than that in mi-NC group, indicating successful establishment of transfection model. Colony forming unit counting found that the number of colonies in the mi group was higher than that in the mi-NC and control groups. The total apoptosis in mi group was higher than that in mi-NC and control groups by flow cytometry. qRT-PCR and western blot showed that the relative expression of apoptotic genes and apoptotic proteins was higher than that in blank group in control group, and that in mi group was higher than that in mi-NC group. the relative expression of inflammatory genes was higher than that in blank group in control group, and the relative expression of inflammatory genes was higher than that in mi-NC group, and the relative expression of inflammatory genes was higher than that in mi-NC group. The relative expression of inflammatory genes in control group was higher than that in blank group, and that in mi group was higher than that in mi-NC group, and the relative expression of pyroptosis genes and pyroptosis proteins in control group was higher than that in blank group and that in mi group was higher than that in mi-NC group. The relative expression of autophagy positively regulated genes LC3 and Beclin1 as detected by qRT-PCR was higher in the control group than in the blank group, and lower in the mi group than in the mi-NC group. The relative expression of negatively regulated autophagy genes had the opposite trend to that of autophagy positively regulated genes. The relative expression of autophagy-related proteins was consistent with the trend of autophagy genes. ROS fluorescence intensity was found to be higher in control group than in blank group, and higher in mi group than in mi-NC group. LDH content was found to be higher in control group than in blank group, and there was no statistically significant difference between the content in mi group and that in mi-NC group.The relative expression of negatively regulated autophagy genes LC3 and Beclin1 was higher than that in blank group, and lower than that in mi-NC group. Conclusions The miR-207 overexpression promotes apoptosis, cellular pyroptosis and inflammation, inhibits autophagy, favors H37Ra survival and provides a new direction for the treatment of tuberculosis.
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Xuanfei Jiedu Formula improves lung injury in rats with multidrug-resistant Pseudomonas aeruginosa pneumonia by inhibiting IKK/NF-κB signaling pathway
HAN Bing Yang, Shen Tingting, Fan Zhengyuan, Li Gaofeng, Li Ya, Li Suyun
Abstract:
[ Abstract ] Objective To investigate the operational dynamics through which the Xuanfei Jiedu Formula ameliorates pulmonary damage in rats afflicted with Multidrug Resistant Pseudomonas Aeruginosa (MDR-PA) pneumonia, by modulating the activity of the IKK/NF-κB signal transduction cascade. Methods Eighty-four rats were randomly divided into 7 groups : Control group, Model group, XFJDF-low dose group, XFJDF-medium dose group, XFJDF-high dose group, Imipenem ( IPM ) group and Pyrrolidinedithiocarbamate ammonium ( PDTC ) group. 12 in each group. The MDR-PA pneumonia rat model was established by oral tracheal intubation. After the model was successfully constructed, the rats in the low, medium and high dose Xuanfei Jiedu Decoction groups were given the corresponding dose of drugs by gavage, the rats in the imipenem cilastatin group were given intraperitoneal injection of IPM, while the rats in the control group and the model group were given the same volume of normal saline by gavage, twice a day for 7 days. PDTC was intraperitoneally injected at 1 h before model establishment, 12 h and 24 h after model establishment in NF-κB inhibitor group. The behavior status, body weight change, spleen and thymus index, lung wet weight / lung dry weight ratio of rats were observed. The pathological changes of lung tissue were evaluated by HE staining. TUNEL staining was used to detect the apoptosis of lung tissue cells. The levels of IL-1β, TNF-α, TGF-β and IL-10 in serum were detected by ELISA. The contents of GSH and MDA, MPO activity and total antioxidant capacity ( T-AOC ) in serum of rats were determined by colorimetry and TBA method. The expression of NF-κBp65 in lung tissue was detected by immunohistochemistry. The expression of IKKβ and NF-κBp65 mRNA in lung tissue was analyzed by PCR. The expression levels of IKKβ, p-IKKβ, NF-κBp65 and p-NF-κBp65 in lung tissue were measured by Western Blot. Results Compared with the Control group, the rats in the Model group had reduced diet, lack of luster in hair, slow response, reduced activity, accelerated respiratory rate, accompanied by murmurs, and significantly reduced body weight ( P < 0.01 ). Marked enhancements were observed in both the spleen and thymus indices (P < 0.01). The lung wet weight / lung dry weight ratio exhibited a substantial rise (P < 0.01), concurrently with an augmentation of alveolar secretions in lung tissue. Infiltration of abundant inflammatory cells was noted, alongside a notable escalation in lung tissue apoptosis. Serum concentrations of IL-1β, TNF-α, TGF-β, and IL-10 demonstrated a substantial upsurge (P < 0.01), alongside an augmented MDA content and heightened MPO activity (P < 0.01). Conversely, GSH levels and T-AOC capabilities displayed a notable decline (P < 0.01). In the lung tissue, there was a remarkable elevation in the expression of IKKβ and NF-κB p65 mRNA (P < 0.01). Furthermore, the ratios of p-IKKβ/IKKβ and p-NF-κBp65/NF-κBp65 in the lung tissue also showed a significant rise (P < 0.01).Compared with the Model group, the treatment group could improve the above indicators to varying degrees ( P < 0.05, P < 0.01 ), among which the Xuanfei Jiedu Formula high-dose group and the IPM group were more significant. Conclusion Xuanfei Jiedu Formula may improve lung injury in rats with MDR-PA pneumonia by inhibiting IKK / NF-κB signaling pathway.
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Protective effect and mechanism of Glycosides of cistanche on rats in cerebral ischemia reperfusion injury model
WANG Lu, GUO Xia, MA Shangjia, YONG Wen, YU Wenlong, WU Lie, JIA Jianxin
Abstract:
Objective To investigate the neuroprotective effect of Glycosides of cistanche (GCs) on cerebral ischemia reperfusion injury in rats and its mechanism. Methods Forty-eight male Wistar rats were randomly divided into Sham group, Model group, GCs group and Nim group. A rat model of focal cerebral ischemia reperfusion injury (CIRI) was established by middle cerebral artery occlusion (MCAO). Sticker removal test, balance beam test, and open field test were used to evaluate the sensory and motor abilities of rats in each group. TTC staining was used to detect the area of cerebral infarction, Nissl staining was used to observe the morphology of nerve cells, and TUNEL staining was used to detect the apoptosis of nerve cells. The expressions of apoptosis-related proteins Bax, Bcl-2 and Caspase-3 were detected by immunohistochemical staining and Western blot. Results Compared with the Sham group, the neurological deficit score was significantly increased (P < 0.05), the time of removing stickers and passing balance beam was significantly increased (P < 0.01), the motor ability was decreased, the infarct size was increased, the number of neurons was decreased, and the number of apoptotic cells was increased after cerebral ischemia reperfusion. The expressions of Bax and Caspase-3 were significantly increased (P < 0.05), and the expression of Bcl-2/Bax was significantly decreased (P < 0.05). Compared with the Model group, GCs could improve the behavioral performance of cerebral ischemia reperfusion model rats, reduce the infarct size, inhibit cell apoptosis, down-regulate the expression of Bax and Caspase-3 (P < 0.05), and up-regulate the expression of Bcl-2/Bax (P < 0.05). Conclusion GCs has a neuroprotective effect on cerebral ischemia-reperfusion injury, which may play a role in inhibiting cell apoptosis by regulating the expression of apoptosis-related factors Bax, Bcl-2 and Caspase-3.
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Regulation of Nrf2 on activation and polarization of microglia induced by Methamphetamine
YANG Genmeng, PENG Yanxia, ZHANG Xinjie, HOU Yuhan, XU Jing, LI Lihua, DU Qi, HONG Shijun
Abstract:
Objective To investigate the regulation of Nrf2 on activation and polarization of microglia induced by METH. Methods BV2 cells and HMC3 cells were studied in vitro. Wild-type mice and Nrf2 knockout mice were studied in vivo.TheStoxicity models induced by METH inSvivoSand inSvitro were established respectively. And the IF and WesternBlot were used to detect the activation and polarization of microglia in each group, respectively. Results After treatment with METH, the fluorescence level of iNOS(Marker protein of polarized M1 phenotype in microglia) increased significantly in BV2 and HMC3 cells, while the fluorescence level of Arg1 (Marker protein of polarized M2 phenotype in microglia) decreased significantly. The results showed that METH could induce microglia polarization, and enhance the pro-inflammatory effect, and reduce the anti-inflammatory effect of microglia. The Nrf2 gene knockout mice were used to further explore the regulation of Nrf2 on the activation and polarization of microglia induced by METH. The results showed that after exposure to METH, microglia in the cortex of mice were obviously activated, and the expression levels of IBA1 and iNOS were obviously increased, while the expression level of Arg1 was decreased. Compared with wild-type METH group, the number of microglia activated after Nrf2 gene knockout was significantly increased, while the expression levels of IBA1 and iNOS were increased and the expression level of Arg1 was decreased. The above results indicated that METH could enhance the pro-inflammatory effect of microglia and reduce its anti-inflammatory effect while inducing the activation and polarization of microglia. However, after Nrf2 gene was knocked out, the effect of METH activated microglia and its pro-inflammatory and anti-inflammatory effects were stronger. Conclusions Nrf2 plays an important role in regulating the activation and polarization of microglia induced by METH, and Nrf2 was expected to be a potential target for the treatment of neuroinflammation induced by METH.
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Research progress of exosomal miRNAs in methamphetamine-induced neurotoxicity and drug development
ZHOU Ying, SUN Wei, YANG Genmeng, DONG Wenjuan, HONG Shijun, LI Lihua
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As a new type of abused drug, methamphetamine (METH) has a strong central stimulant effect, and the excitatory pathway involved a series of central higher-level functions, including drug-related rewards and motivation, learning and memory, decision-making and execution, etc. Methamphetamine not only causes neurotoxicity in the body, but long-term use could cause cognitive dysfunction, loss of personality, and serious social violence in addictions. Exosomes, as a new carrier of cell-to-cell communication, were involved in the occurrence and development of drug addiction, and exosome miRNAs were not only important biomarkers for methamphetamine addiction, but also involved in various aspects of methamphetamine induced neurotoxicity, which could be used as a therapeutic carrier to provide new ideas for the diagnosis and treatment of methamphetamine abuse.
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Application of gene-editing technique in experimental animals
LIU Chaonan, YAN Lihong, WANG Jing, SHEN Yanhua, PAN Mingming, ZHOU Zhengyu
Abstract:
Recently , with the rapidly developing of molecular biological technique, gene-editing, as a means of genome modification, has been used in the establishment of experimental animal models due to its high efficiency, accuracy and flexibility. This article mainly summarizes the construction and application of the latest gene-editing technique in animal models such as experimental animal pigs, non-human primate, and experimental animal dogs, it provides a theoretical reference for the applied widely and in-depth study of gene-editing technique in experimental large animals, so as to better simulating human diseases and study the potential pathogenesis of biomedical and human complex diseases.
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Research progress of autophagy in pathogenesis of idiopathic pulmonary fibrosis
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Autophagy, as a crucial physiological process of cells, is an important mechanism to maintain cell homeostasis and regulate cell survival. idiopathic pulmonary fibrosis (IPF), as an interstitial lung disease with unknown etiology and poor prognosis, is characterized by alveolar epithelial cell damage, abnormal proliferation and activation of fibroblasts. It is accompanied by the excessive deposition of extracellular matrix (ECM). Its pathogenesis involves a complex interaction between cell types and signaling pathways. Studies have shown that defects in autophagy function play a key role in the occurrence and development of pulmonary fibrosis. This review aims to investigate the mechanism of autophagy in IPF and reveal its complexity and related signaling pathways.
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Relationship Between Color Doppler Ultrasound Parameters and Insulin Sensitivity Index and Clinical Efficacy in Rats with Polycystic Ovary Syndrome Complicated with Hyperinsulinemia
Sun Xizhen, Geng Linlin, Zhang wei, Chen juan, Sun Deming, Li Nan
Abstract:
Objective To analyze the relationship between color doppler ultrasound parameters and insulin sensitivity index (ISI) and clinical efficacy in rats with polycystic ovary syndrome (PCOS) combined with hyperinsulinemia (HI). Methods 140 3-week-old female SD rats of SPF grade were selected and randomly divided into two groups. The PCOS combined with hi rat model (Study Group) and PCOS without hi rat model (control group) was prepared respectively. After successful modeling, the rats were examined by color doppler ultrasound, and the total area (TA), ovarian volume (OV), interstitial area (SA), vascularization index (VI), blood flow index (FI), vascularized blood flow index (VFI), peak systolic blood flow velocity (PSV), peak diastolic blood flow velocity (PDV), resistance index (RI), and ovarian interstitial artery pulsation index (PI) were compared between the two groups. Fasting insulin (fins) and fasting blood glucose (FPG) were measured in rats" fasting venous blood at the same time, and ISI was calculated. Pearson correlation analysis was used to analyze the correlation between color doppler ultrasound parameters and ISI in the study group. The rats in the study group were treated with metformin by intragastric administration. According to the therapeutic effect, the rats in the study group were divided into the good effect group and the poor effect group. The color doppler ultrasound parameters of the two groups were compared, and the receiver operating characteristic curve (ROC) was drawn to analyze the value of color doppler ultrasound parameters in evaluating the curative effect of PCOS combined with hi rats. Results: 65 rats with PCOS and hi were successfully established in the study group, and 60 rats without PCOS and hi were successfully established in the control group. The body weight, body mass index, systolic blood pressure, diastolic blood pressure, Ta, OV, SA, VI, fi, VFI, PSV, PDV, fins and FPG of the study group were higher than those of the control group, while RI, PI and ISI of the study group were lower than those of the control group, and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that color doppler ultrasound parameters TA and SA were negatively correlated with ISI (r=-0.501, -0.492, P<0.05), and ovarian RI and PI were positively correlated with ISI (r=0.504, 0.485, P<0.05). In the group with good curative effect, Ta、OV、SA、VI、FI、VFI、PSV、PDV、 Low density lipoprotein cholesterol, FPG, fins, LH, FSH were lower than those in the poor efficacy group, RI, PI were higher than those in the poor efficacy group, the difference was statistically significant (P<0.05). ROC curve analysis showed that the sensitivity and specificity of color doppler ultrasound parameters combined with clinical efficacy were 90.9% and 90.2%, respectively, and the area under the curve (AUC) was 0.901. Conclusion Color doppler ultrasound parameters are closely related to ISI and clinical efficacy of PCOS combined with hi rats, which can predict the clinical efficacy of such patients to a certain extent.
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Research advances in the regulation of HPA/HPT/HPG axis in the treatment of depression in traditional Chinese medicine
Abstract:
The pathogenesis of depression is complex and the treatment methods are limited, and it is of great significance to clarify its pathogenesis and develop new therapeutic drugs. Currently, hormones and hormone-modifying compounds have been used to treat depression, and their therapeutic effects are attributed not only to the regulation of the peripheral endocrine system, but also to the effects of hormones on the central nervous system of non-endocrine brain circuits. HPA/HPT/HPG is closely related to the pathogenesis of depression. The mechanism of action of traditional Chinese medicine in the treatment of depression is extensive, and the regulation of the three axes also presents a variety of ways. Based on the new evidence of hormones and hormone operon compounds involved in the pathology and treatment of depression, this paper summarizes the relevant mechanisms of current traditional Chinese medicine in the treatment of depression, in order to provide ideas and references for the research of traditional Chinese medicine.
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The effect of Creb expression in the prefrontal cortex on depressive behavior in rats
Liugaoyuan, Pengmengwei, Luozilong, Kuoluoyi, Chenyulong, Yangtiezhu, Wuyaosong, Liuyan
Abstract:
Objective To observe the influence of Creb protein over-expression and under-expression in the prefrontal cortex on depressive behavior in rats. Methods Adeno-associated virus (AAV) strains that can knock down Creb expression in the prefrontal cortex of rats were injected by using stereotaxic injection method and screened by using Western blot, qRT-PCR and immunofluorescence methods. 40 Rats were randomly divided into control group（Control）,chronic restraint stress group（CRS）,chronic restraint stress combined with adeno-associated virus interference group（CRS＋AAVI）and chronic restraint stress combined with adeno-associated virus overexpression group（CRS＋AAVO）. During the establishment of animal model, the body weight and food intake of each group of rats were monitored. After the establishment of the animal model, the behavioral changes of rats were monitored by using sucrose preference test, elevated plus maze test, forced swimming test and open field test. The contents of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and corticosterone (CORT) in the prefrontal cortex of rats in each group were measured by using Elisa method. Results The results of Western blot and immunofluorescence detection showed that the expression of Creb protein of rats in shRNA2 group was significantly lower than that of the other groups (P< 0.05). The results of qRT-PCR experiment showed that the expression of Creb mRNA in the shRNA2 group was significantly lower than that of the other three groups. Therefore, the AAV-Creb1-shRNA2 virus strain was selected for modelling of subsequent Creb knock-down experiments in this study. After knock down and high expression Creb AAVs were injected into the brains of rats, compared with other groups, the food intake of rats in the CRS＋AAVI group was significantly reduced compared with other groups (P< 0.05). At the same time, the rats in this group showed slow weight gain, decreased desire and pleasure to explore new environment, significantly increased despair and nervous behavior, significantly decreased 5-HT and NE levels in the prefrontal cortex, and significantly increased CORT levels. While these depressive behaviors and associated neurotransmitter levels were reversed by injection of the overexpressing AAV-Creb1 virus strain. Conclusion Lower expression of Creb in the prefrontal cortex can aggravate the degree of depression in rats, while the high expression of Creb can alleviate the degree of depression of rats to a certain extent. These results further confirm that Creb expression in the prefrontal cortex is one of the important targets involved in the pathogenesis of depression, and can provide ideas and references for the construction of animal gene models and pathogenesis of depression in future.
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Evaluation study on zebrafish insomnia model by illumination method and combined illumination and caffeine method
Abstract:
【】 Objective: to establish different sleep deprivation models using zebrafish to provide more reproducible and practical modeling reference solutions for basic research on insomnia. Methods: Zebrafish insomnia model was induced by two interventions: continuous light (150 lux) and light plus caffeine, and the zebrafish were randomly divided into control, light, combined and caffeine (100 μmol/l) groups. The difference in locomotor ability of zebrafish in each group was observed by using open field experiment and circadian rhythm behavioral experiment; the expression and secretion of related sleep genes and 5-HT neurotransmitter were detected by using Qpcr technology and Elisa technology. Results: 1. The sleep time of zebrafish in the light group was significantly reduced compared with that of the blank control group (P=0.01), and there was no statistically significant difference between the sleep time of zebrafish in the combined group and the caffeine group (see Table 1); the resting time of zebrafish during the daytime in the light group was significantly reduced compared with that of the blank control group (P<0.01), and the resting time during the daytime of zebrafish in the combined group and the caffeine group was increased (P<0.01) (Table 3). There was no statistically significant difference in the black light resting time of zebrafish in all groups (Table 3); the daytime moving distance of zebrafish in the light group was significantly increased compared with that of blank control group (P < 0.01), and the 10-h activity distance of zebrafish in the light group in the dark day was significantly increased compared with that of blank control group (P < 0.01), and there was no statistically significant difference in the dark day activity distance of zebrafish in the combined and caffeine groups (Table 4); and the sleep rounds of zebrafish in the light group was blank control group was significantly reduced (P < 0.01), and the sleep rounds of zebrafish in the combined and caffeine groups were significantly increased (P < 0.01) compared to the blank control group (Table 2).2. The percentage of swimming distance in the central region of the light group was reduced (P < 0.05) compared to the blank group, while the percentage of swimming distance in the central region of the caffeine group was significantly reduced (P < 0.01) compared to the light group (see Figure 6); the light group The percentage of swimming time in the central region was lower than that in the blank group (P < 0.05), while the percentage of swimming time in the central region was significantly lower in the caffeine group than that in the light group (P < 0.01) (Fig. 7).3. The expression of HTR1aa mRNA level in zebrafish in the light group was higher than that in the blank group at 6:00 a.m. and 12:00 p.m. (P < 0.05) (Figs. 10 and 11), and the expression of There was no statistically significant difference in the expression of HTR1ab mRNA levels between the light group and the combined group (P > 0.05) (Figs. 12 and 13); compared with the blank group, the amount of 5-HT secretion in the light group was reduced in both groups at 6:00 a.m. (P < 0.01), and at 12:00 p.m. the amount of 5-HT was reduced in both the light and combined groups (P < 0.01), and the amount in both groups remained lower than that in the blank group at 6:00 p.m. (P<0.01).
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The effects of combined exposure to PM2.5 and high-salt diet on liver inflammatory cytokines and lymphangiogenesis in mice
ding shibin, JIANG Jinjin, LI Yang
Abstract:
Objective The effects of combined exposure to PM2.5 and high-salt diet on hepatic inflammation and lymphangiogenesis in mice. Methods Thirty-two C57BL/6J mice were randomly assigned to: control group, PM2.5 group, high-salt group and PM2.5+high-salt group. Mice in the high-salt group and PM2.5+high-salt group were fed with 8% high-salt diet for 8 weeks, mice in the other groups were fed with control diet containing 0.4% salt. Mice in the PM2.5 group and PM2.5+high-salt group were treated with PM2.5 by tracheal instillation (twice per week); and mice in the mice in the other groups were instilled with equal volume of saline at the same time (twice per week). All mice were sacrificed after the last PM2.5 exposure. TNF-α and IL-6 in liver tissues of mice were determined. Moreover, the LYVE1 expression of liver tissues were?visualized using immunofluorescence staining. The protein expression levels of lymphangiogenesis markers PROX1 and LYVE1, lymphangiogenesis regulatory proteins VEGFR-3 and VEGF-C in liver tissue were measured using Western blot. Results Compared to the control group, the levels of TNF-α and IL-6, as well as the protein expressions of PROX1，LYVE1, VEGFR-3 and VEGF-C in liver tissues of mice in the high-salt group (HSD) were obviously increased (P<0.05). Compared to the HSD, the levels of TNF-α and IL-6 and the protein expressions of PROX1，LYVE1, VEGFR-3 and VEGF-C in liver tissues of mice in the PM2.5+HSD were obviously increased (P<0.05). Moreover, there were significant interaction effects between PM2.5 and high-salt diet on these above indicators. Conclusions Combined exposure of PM2.5 and high-salt diet obviously aggravated hepatic inflammation, and may increase hepatic lymphangiogenesis through upregulating VEGFR-3 and VEGF-C in the liver of mice.
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The application value of dual energy CT imaging in the evaluation of bone repair
sudanyang, mayuanbo, liujinlong, zhanghaoran, yangshenyu, miaoqiuju, baizhen, yangxiaopeng
Abstract:
Bone defect repair is an urgent problem to be solved in the field of orthopedics, and numerous researchers are working to develop more effective treatment plans. However, accurate evaluation of bone repair after surgery is an crucial step. With the development of computed tomography (CT) imaging, dual energy CT imaging has shown significant advantages in analyzing bone composition and reducing metal artifacts. This article reviews the application value of dual energy CT imaging in the evaluation of bone repair in animals.
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MiRNA investigation of the regulatory effects of Allium guajava and Allium cepa sempervirens soup on the Epsin1-FGFR1 pathway in atherosclerotic mice
wang zhao bo, pan yi, lin qian
Abstract:
: This study aimed to evaluate the therapeutic effects of Gualou Xiebai Banxia Decoction (GXBD) on atherosclerosis (AS) in a mouse model and to explore its underlying mechanisms. Male APOE-/- mice were used to induce the AS model through a 16-week high-fat diet. The mice were randomly divided into a model group, a control group, different dosage groups of GXBD, and a lipid-lowering drug group. Histological analysis using HE and Oil Red O staining was performed to observe changes in arterial walls and plaque formation. The results demonstrated that GXBD significantly reduced plaque formation. Further miRNA sequencing analysis revealed that GXBD regulated multiple AS-related miRNA genes, influencing the expression of key proteins such as Epsin1 and FGFR1, thereby exerting potential therapeutic effects on AS lesions. Western blot and immunofluorescence experiments further validated these regulatory effects. The findings suggest that GXBD exhibits significant efficacy in the treatment of atherosclerosis, potentially through miRNA regulation and protein expression modulation.
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Effects of RSPO2 on oxidative stress and apoptosis of ovarian granulosa cells
LI Shuo, LI Nian, ZHOU Xiaofeng, YUAN Xiaolong
Abstract:
Objective Utilizing human ovarian granulosa tumor cells as the cellular model, we tried to investigate the effect of roofplate-specific spondin 2 (RSPO2) on the oxidative stress and apoptosis level of ovarian granulosa cells. Methods We performed transient transfection of RSPO2 overexpression plasmid and small interfering RNA (siRNA) in COV434 cells. Real-time Quantitative PCR (RT-PCR) and Western blot were used to detect efficiency of overexpression and interference. The reactive oxygen species assay kit was used to determine the amount of intracellular reactive oxygen species. The apoptosis level was detected by flow cytometry. RT-PCR and Western blot were used to determine the expression levels of oxidative stress and apoptosis-related genes. Co-immunoprecipitation was used to detect interacting proteins. Results The overexpression and interference of RSPO2 were successfully realized. Overexpression of RSPO2 significantly inhibited the level of reactive oxygen species in COV434 cells (P < 0.05) and extremely significant inhibited the early apoptosis of granulosa cells (P < 0.01), interference of RSPO2 obtained the opposite results. Overexpression of RSPO2 significantly upregulated the mRNA and protein levels of SOD1, SOD2, CAT (P < 0.05), and significant downregulated the levels of caspase 3 and caspase 8 (P < 0.05). On the contrary, interference of RSPO2 significantly downregulated the levels of SOD1 and CAT (P < 0.05), and significantly upregulated the level of caspase 3 and caspase 8 (P < 0.05). We found the protein interactions between RSPO2, SOD1, CAT and caspase 3. Conclusion Interfering with RSPO2 promotes the accumulation of reactive oxygen species within cells, downregulates the expression of SOD1 and CAT, thereby enhancing oxidative stress. Additionally, interfering with RSPO2 upregulates the expression of caspase 3 and caspase 8, promoting cell apoptosis. These findings suggest that RSPO2 plays a crucial role in ovarian granulosa cells.
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Current research status of ferroptosis in endometriosis
pengjiahua, song xin, liangruining, sun yu, jian hui, luoxiaoquan
Abstract:
Endometriosis (EMs)? is a common challenge in global women"s health. In recent years, ferroptosis, as an emerging form of regulated cell death, has attracted attention in EMs research. In terms of disease mechanisms, ferroptosis drives ovarian EMs fibrosis through iron overload induction, and promotes disease progression by regulating multiple signaling pathways such as p38MAPK/STAT6, enhancing angiogenesis, autophagy, etc. In terms of infertility, ferroptosis affects embryo development and ovarian function, significantly reducing fertility. In terms of diagnosis, the high expression of ferroptosis-related genes provides potential biomarkers for early diagnosis of EMs, effectively distinguishing patients from healthy individuals, and has important clinical application value. In terms of treatment strategies, non-natural compounds like Erastin, as well as natural compounds like resveratrol, ursolic acid, baicalein, etc., show potential therapeutic effects, relieving the pathological process and related symptoms of EMs. Therefore, this article
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Research progress of the ketogenic diet in the field of Parkinson"s disease
LI Boyang, LAN Rui, YANG Huijie, LI Hongyu, LI Chiyang, SHEN Xiaoming
Abstract:
A ketogenic diet refers to an eating pattern designed to promote individuals to achieve a low-calorie content, minimum carbohydrate intake, high-fat consumption, and standard protein levels. The ketogenic diet is used in clinical practice to treat applications including heart dis-ease, diabetes, obesity, autism, glioblastoma, and other cancers. However, the ketogenic diet has not been recommended for any neurological disorder except epilepsy. With the intensive research on the ketogenic diet in recent years, more and more evidence has proved that the ketogenic diet has a neuroprotective effect on Parkinson's disease, and it is a new dietary ther-apy for the treatment of Parkinson's disease. In this review, we discuss in detail the neuropro-tective effects of the ketogenic diet in Parkinson's disease by different mechanisms, aiming to provide some references for clinical and experimental studies in this field.
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Study on repairing effect of moxibustion at different acupoints
zhouhaiyi, hesiyi, hanruifang, guanyongge, donglijuan, Song Yang
Abstract:
Objective: To compare the repair effects of moxibustion "Guanyuan" and "Shenshu" on thin endometrium rats. Methods: 32 SD rats were randomly divided into normal group, model group, Guan Yuan group and Shenshu group with 8 rats in each group. Thin endometrium model was established using 95% anhydrous alcohol. After two estrus cycles, the Guanyuan group and Shenshu group moxibusted "Guanyuan" and "Shenshu" points, once a day, and rested for 1 day every 6 days for a total of 21 days. The other two groups were fixed in the same way. The temperature changes in the acupoint area at different time were measured by infrared thermometer, the pathological morphology of uterus was observed by HE staining, and serum levels of IL-1β, IL-10, E2 and PROG were detected by ELISA. The expressions of Ki67, PCNA, LIF and ITG-β3 in uterus were detected by immunohistochemistry. The expression levels of ANG-1、CD34和VEGFA in uterus were detected by Western blot. Results: Immediately after moxibustion and 5min after moxibustion, the body surface temperature at Shenshu point was higher than that at Guanyuan point (P<0.001, P<0.01). Compared with normal group, endometrial thickness, number of glands and blood vessels in model group were decreased (P<0.0001, P< 0.01, P<0.001), The endometrial thickness, number of glands and blood vessels increased in Guanyuan group (P<0.0001, P<0.01, P<0.01) and Shenshu group (P < 0.0001, P<0.01, P<0.05),and the endometrial thickness, number of glands and blood vessels in Guanyuan group were better than those in Shenshu group, but the difference was not statistically significant. Compared with normal group, the serum IL-1β level in model group was increased (P<0.01), and the PROG level was decreased (P<0.001). Compared with model group, the serum IL-1β in Guanyuan group were decreased (P<0.01), E2 level and PROG level increased (P<0.01, P<0.05),and the serum IL-1β were decreased (P<0.05), IL-10,E2 and PROG levels (P<0.05, P<0.05, P<0.01) were increased in Shenshu group. Compared with normal group, the expressions of Ki67, PCNA, LIF and ITG-β3 of model group were decreased (P< 0.0001). Compared with model group, the expressions of Ki67, PCNA, LIF and ITG-β3 in Guanyuan group (P<0.0001) and Shenshu group (P<0.001, P<0.001, P<0.0001, P<0.001) were increased, and PCNA expression in Guanyuan group was higher than that in Shenshu group (P<0.05). The expressions of LIF and ITG-β3 in Shenshu group were stronger than those in Guanyuan group (P<0.01, P<0.05). Compared with normal group, the expression of ANG-1 and CD34 protein in uterine tissue of model group was decreased (P<0.0001). Compared with model group, the expressions of ANG-1, CD34 and VEGFA in Guanyuan group were increased (P<0.0001), and the expressions of CD34 and VEGFA in Shenyu group were increased (P<0.0001). The expression of ANG-1 in Guanyuan group was higher than that in Shenyu group (P<0.0001), while the expression of CD34 in Shenyu group was higher than that in Guanyuan group (P<0.05). Conclusion: Moxibustion "Guanyuan" point and "Shenshu" point could repair thin endometrium, Guanyuan point is superior to Shenshu point in reducing the level of inflammatory factors, increasing the level of E2, promoting the expression of proliferation factors, while Shenshu point is superior to Guanyuan point in increasing the level of anti-inflammatory factors and PROG, and promoting the expression of endometrium receptor related factors. The two points may play a role in promoting angiogenesis through different ways.
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Preliminary Study on the Application of Three-Dimensional Time-of-Flight Magnetic Resonance Angiography (3D-TOF-MRA) to Observe the Cerebral Arteries in Mongolian Gerbils
JIAO Kun, ZHANG Jing, MENG Xia, WANG Zhanjing, LEI Jianfeng, CHEN Baian, LU Jing
Abstract:
Objective Establishment of a three dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) technique for observing cerebral arteries in live Mongolian gerbils. Method 1. Employ a 7.0T MRI scanner to image the cerebral arteries of Mongolian gerbils, with data subsequently processed using the RadiAnt DICOM Viewer software；2. Validate and compare imaging results via the latex perfusion method；Attempt to perform 3D reconstruction of the posterior communicating branch and surrounding cerebral blood vessels of the Mongolian gerbil and rats through analysis software; 4. Attempt to use this method to screen individuals with abnormal vascular development in Mongolian gerbils to verify the effectiveness of this method. Result 1.The 3D-TOF-MRA technology can effectively observe the cerebral arteries of living Mongolian gerbils; 2.The 3D-TOF-MRA technology has high accuracy in observing the main cerebral arteries of Mongolian gerbils, but its observation effect on finer vascular branches is not as good as latex perfusion method; 3.The data obtained from 3D-TOF-MRA technology can be used for three-dimensional reconstruction of blood vessels; 4. The application of this technology has a good effect on screening for abnormal development of arterial structure in Mongolian gerbils. Conclusion The 3D-TOF-MRA technology can be applied to the structural observation and related research of the cerebral arteries in live Mongolian gerbils.
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Macrophage polarization in the research development of renal ischemia-reperfusion injury
SUN Haojie, LIU Xianqin, WANG Suogang ?
Abstract:
Macrophages are important immune cells in innate immunity, with significant heterogeneity and polarization. It can polarize into various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus exerting different roles and functions. It plays an important role in the pathophysiological mechanism of renal ischemia-reperfusion injury (RIRI). Excessive immune response will inevitably lead to tissue damage. M1 macrophages are pro-inflammatory cells, which are involved in the clearance of pathogens. M2-type macrophages have anti-inflammatory effects and participate in the repair and remodeling of renal tissue after RIRI. The balance between macrophage phenotypes is important for the outcome and treatment of RIRI. Reason from the macrophage polarization Angle, the macrophages in RIRI pathophysiologic mechanism and the latest treatments, designed to further study the function of macrophage polarization in RIRI for reference, to adjust the macrophage polarization to improve RIRI treatment strategies.
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Research progress of TAM in tumorigenesis, development and drug resistance of gastric carcinoma
Cai Qiuling, Yang Jing, Shen Huiling, xuwenlin
Abstract:
Tumor-associated macrophages(TAM) are a current focus in the study of the tumor microenvironment. To achieve their functionally distinct roles, macrophages undergo phenotypic polarizations resulting in two major subgroups: M1 macrophages with pro-inflammatory and anti-tumor effects, and M2 macrophages with anti-inflammatory and pro-tumor effects. Among them, M2 polarization, which is the main manifestation of TAM, has been associated with poor prognosis in various cancers and has shown supportive properties for malignancies. Gastric carcinoma patients have a low early diagnosis rate, late disease stage, and poor prognosis, with biological behavior characteristics of easy recurrence and metastasis. Currently, drug resistance and toxic side effects significantly limit the application and effectiveness of gastric carcinoma treatment. Therefore, it is urgent to explore new therapeutic drugs or targets. We summarize in this review the recent progress in the studies of TAM in the occurrence, development and drug resistance of gastric carcinoma, providing new ideas for clinical treatment and prognosis analysis of patients with gastric carcinoma.
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Construction of Lep gene knockout mouse model based on CRISPR/Cas9 system
CAO YUAN, YANG YUANSONG, GU WENDA, ZHAO HAOYANG, ZHAI SHIJIE, SUN XIAOWEI, FAN CHANGFA
Abstract:
Objective The ob mice (C57BL/6-Lepem1/Nifdc) with the Lep gene knocked out mice (ob/ob) were generated by CRISPR/Cas9 system, establishing an animal model suitable for preclinical drug evaluation in clinical diseases such as diabetes. Methods According to the principle of CRISPR/Cas9 target design, sgRNA targeted mouse Lep gene was designed for transcription in vitro, and micoinjected with Cas9 mRNA into mouse zygotes. Mice tails DNA was extracted and detected by PCR and sequencing, followed by mating positive mice and wild-type mice. Blood biochemistry and liver pathology were assessed in homozygous ob mice. Results 8 positive mice were identified and a stable mouse strain was selected for further breeding. The serum triglycerides (TG), total cholesterol (CHO) and alanine aminotransferase (ALT) levels in homozygous ob mice were significantly higher than wild-type mice. Liver pathology result showed significant inflammatory infiltration and lipid vacuolar transformations. Conclusion The successful establishment of Lep gene knockout mice has enriched the national rodent experimental animal database and provided an animal model for preclinical drug evaluation.
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The role of astrocytes in traumatic brain injury and therapeutic strategies
Huang Yizhen, Cheng hao, Wang Hao-wei, Zhang Qian-yao, Luo Cheng-liang, Zeng Xiao-feng
Abstract:
Traumatic brain injury (TBI) is an injury caused by the direct or indirect effects of external factors that result in structural or functional loss of brain tissue. Astrocytes, as homeostatic cells of the central nervous system, proliferate and activate rapidly in the early stages of TBI, and participate in a series of pathological processes such as neuroinflammation, blood-brain barrier disruption, glial scarring, and excitotoxicity after injury, and play a crucial role in the secondary neurological injury of TBI. This paper reviews the role of astrocytes in the repair of TBI damage with the aim of providing new strategies for the prevention and treatment of TBI.Traumatic brain injury (TBI) is a kind of craniocerebral injurious disease caused by external force that results in structural destruction of brain tissue and physiological dysfunction, with high morbidity, high disability, high mortality and high treatment burden, for which there has not yet been an effective therapeutic measure. Astrocytes, as homeostatic cells of the central nervous system, are rapidly proliferated and activated in the early stages of TBI to participate in a series of pathological processes such as neuroinflammation, blood-brain barrier disruption, glial scarring, excitotoxicity and other pathological processes after injury, and play a crucial role in the secondary neurological injury of TBI. The article focuses on the role of astrocytes in the pathological damage of TBI and reviews the research progress of astrocyte-targeted drugs, aiming to provide new strategies for the prevention and treatment of TBI.
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Research progress on anti-tumor effects of LRRC8A/VRAC ion channels
yangrunze, huyaohua, qinjing, wangyongfeng, shichanghong
Abstract:
Volume adjusting anion channel (VRAC) in vertebrate cells and each type of general expression in tumor cells. Leucine-rich repeat containing 8A(LRRC8A) and its four homologous family members (LRRC8B-E), of which LRRC8A is an essential subunit. It has been confirmed that LRRC8A/VRAC is involved in the proliferation, migration, invasion and multi-drug resistance of tumor cells through various signaling pathways. This ion transporter has shown good potential in killing tumor cells and preventing the development of tumor, and can be used as a new target for tumor therapy. Therefore, this paper reviews the latest research on the involvement of LRRC8A/VRAC in tumorigenesis and development, including the molecular structure, function and regulation of LRRC8A/VRAC in tumor and immune cells, with emphasis on the application of LRRC8A/VRAC in tumor diagnosis and immunotherapy, in order to provide reference for exploring LRRC8A/VRAC as a new target of tumor therapy.
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The role of PI3K/AKT signal pathway in peripheral nerve injury and the research progress of traditional Chinese medicine intervention
guo xiaojing, ZHANG bo, Wang Yan, ZHANG Li
Abstract:
Peripheral nerve injury (PNI), caused by contusions, fractures, and other traumas, leads to abnormal sensory functions, limited motor capabilities, neuropathic pain, and muscle atrophy, severely impacting patients' quality of life. Post-PNI, Wallerian degeneration occurs, involving axonal degeneration and myelin sheath collapse. Notably, the dorsal root ganglia (DRG), as the primary sensory neurons in pain signal transmission, are crucial targets in neuropathic pain (NP) induced by PNI. Therefore, changes in these targets trigger a series of complex signaling pathway alterations. Among them, the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling pathway, a vital regulator of cell survival and death, promotes Schwann cells (SCs) proliferation and migration, thereby enhancing axonal growth and myelination to facilitate nerve regeneration, and supports the survival of DRG neurons to alleviate NP. Current treatment methods include stem cell transplantation and neurotrophic medications, but all have certain limitations. Studies have shown that traditional Chinese medicine (TCM) has gained increasing attention and has been applied to some extent in the treatment of PNI due to its advantages of low cost and fewer side effects. This article discusses the relationship between oxidative stress, apoptosis, autophagy, inflammation, angiogenesis, the cell cycle, and other pathophysiological mechanisms in PNI and the PI3K/AKT signaling pathway, as well as its associated molecular targets. It also delves into the potential mechanisms of action of TCM monomers, compound formulas, and acupuncture based on the PI3K/AKT signaling pathway in the treatment of PNI, aiming to provide systematic and standardized theoretical guidance for the healing of PNI with TCM and a useful reference for the development of related medications.
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Research progress in the mechanism of PPARγ gene in osteoarthritis
Zhang Jian, Wang Dong, Qi Tiantian, Wu Liangbin, Yang Qi, Yu Fei
Abstract:
Osteoarthritis (OA) is a chronic degenerative disease with a high incidence rate among middle-aged and elderly people. In the early stage, OA can be treated by conservative methods. In the late stage, most patients choose joint replacement and other surgical methods to treat OA, causing pain to patients and their families. Peroxisome proliferator activated receptor γ (PPAR γ) is a gene discovered in recent years that plays an important role in the degeneration or inflammation of OA cartilage, synovium, adipose, and other tissues. Signaling pathways such as AMPK, Wnt, and SIRT1 may be involved in this process. This review focuses on the role and mechanism of PPARγ gene’s function on OA via joint related tissues and signaling pathways.
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Biogenesis of exosomes and their role in neurodegenerative diseases
Abstract:
The incidence of neurodegenerative diseases (NDs) is increasing with the years, and current drugs targeting NDs are basically symptom-based, not therapeutic, so they can’t prevent disease progress. Exosomes are a subset of extracellular vesicles that can be produced by all cells in the human body and exert biological effects in a variety of ways after they are released into the extracellular environment. Many studies have shown that although exosomes have two sides in the central nervous system, they can still be used as a tool for the prevention, remission, treatment and diagnosis of NDs due to their unique biological characteristics. This article reviews the biogenesis of exosomes and their roles in neurodegenerative diseases, so as to provide new ideas for clinical treatment of NDs.
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Research progress on hypoxic cell models
LI Jing, XU Dongyang, LI Changqing, SU Mengyao, WANG Zhijuan, ZHAO Mingjun, ZHAO Jialong, YANG Junyi, YANG Qiaodie, Kang Longli
Abstract:
Hypoxia is associated with the occurrence and development of many diseases in clinical settings. Cell hypoxia not only serves as a vital marker for disease advancement but also plays a pivotal role in exacerbating the disease process. Therefore, improving tissue hypoxia may provide new strategies for the treatment of related diseases.. To investigate these diseases at the cellular and molecular levels, it is paramount to establish a cellular hypoxia model. At present, the extensively employed hypoxic cell models can be primarily categorized into three types: chemical hypoxia model, physical hypoxia model, and glucose deprivation hypoxia model.This article will overview the various types of hypoxic cell models and scrutinize their application and limitations in disease research.
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Vascular smooth muscle cell phenotype switch and Cell pyroptosis in the role and research progress of Abdominal aortic aneurysm
Liu Xin, Tang hongyue, Guo chang, Ma dong, Zhang mingming
Abstract:
Abdominal aortic aneurysm (AAA) is a hidden and fatal disease, but its underlying developmental mechanism remains unclear. It has been found that phenotypic switching of vascular smooth muscle cells and pyroptosis are two biological processes closely related to the appearance and progress of AAA, which may become an important theory to reveal the mechanism of AAA and provide a new direction for the diagnosis and treatment of AAA. In this review, we will discuss the phenotypic switch of VSMCs and the regulatory relationship between cell pyroptosis and AAA.
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Recent progress of research into the role of lncRNA in the molecular mechanism of pulmonary hypertension
WU Daoxiong, LI Yanjin, HU Ying, WANG Yuming, HU Wei, MA Run
Abstract:
Pulmonary hypertension (PH) is a fatal disease characterized by pulmonary vascular remodeling that ultimately leads to right heart failure and death. Current PH treatment is suboptimal, with no substantial improvement in the overall survival of patients with advanced PH. Despite the current partial progress has been made in the pathogenesis of PH, more exploration at the molecular level is needed to develop more effective treatments for PH. Recent researches have shown that long non-coding RNA (lncRNA) plays an important regulatory function in the pathophysiological process of PH, and has become a potential disease biomarker and therapeutic target. In this paper, we review the molecular mechanisms of lncRNA in PH in recent years.
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Research Progress of microRNA in the Field of Deep Vein Thrombosis
LILei, YUAN Qidong, PENG Xitao, ZHU Jin, PENG Juncai, HE Changhai, FU Liqing
Abstract:
Micro-ribonucleic acid (miRNA) is a class of endogenous RNA molecules with a length typically ranging from 19 to 25 nucleotides.They regulate gene expression levels by identifying homologous sequences and intervening in transcription, translation,or epigenetic processes.miRNAs exhibit potential application value in the pathogenesis, progression,and treatment of deep vein thrombosis (DVT).DVT refers to the abnormal coagulation of blood within the lumen of the deep veins,blocking the venous lumen and leading to venous return obstruction, which is more common in the lower limbs.The detachment of thrombus into the lungs can lead to death.This article comprehensively reviews the diverse mechanisms of action of miRNAs in DVT in recent years.Given that the regulation of miRNA expression through targeted therapeutic approaches may promote the recovery of DVT,this article also discusses in detail the potential applications of miRNAs in the clinical diagnosis and treatment of DVT.This article aims to provide valuable references and insights for clinical and basic research in the field of DVT.
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Research progress of Wnt/β-catenin signaling pathway in programmed cell death after ischemic stroke
Panrui, Zhangming, Zhengxinyue, Wangchunxiao, Renqiongdi
Abstract:
【】 Ischemic stroke (IS) is a neurological disease that damages brain tissue from insufficient blood supply to the brain due to blockage or stenosis of the brain vessels. In recent years, there has been increasing evidence that the Wnt/β-catenin signaling pathway plays an important role in the pathophysiological response to the occurrence and development of IS. Programmed cell death includes many forms such as apoptosis, necrotic apoptosis, pyrodeath, autophagy, panapoptosis and iron death. In this review, we will elucidate the characteristics of these different cell death modes and their cross-talk relationships with each other, and systematically outline the role of Wnt/β-catenin signaling pathways in the intervention of different cell death modes in IS, aiming to provide reference for future clinical and basic research.
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Comparison of stabilizing effect of different dose-bleomycin-induced pulmonary fibrosis in rats
songqinghua, tanghuimeng, sunxin, liuyang, xieyunyun, tianyange
Abstract:
Objective: To compare the success rate and stability of rat pulmonary fibrosis (PF) models induced by intratracheal instillation of different doses of bleomycin (BLM). Methods: 150 SD rats were randomly divided into control group, low-dose BLM 3 mg/kg group (BL-L group), and high-dose BLM 5 mg/kg group (BL-H group). The general status, mortality, and weight changes of the rats were observed, the inspiratory capacity (IC), vital capacity (VC), chord compliance (Cchord) and dynamic compliance (Cdyn) of the lungs were detected on the 28th, 42nd, 56th and 84th days. Lung coefficients were recorded, pathological changes in lung tissue were observed by HE and MASSON staining, and collagen type III (COL III) expression in lung tissue was detected by immunohistochemistry. Results: (1) Mortality rate: The mortality rates of BL-L group and BL-H group were 20% and 28%. (2) Weight: The weight of the BL-L group was lower than that of the control group on days 0-56, and the weight loss was most significant on day 14 (P < 0.01), with weight recovery after day 56. From day 0 to day 56, the weight of the BL-H group was significantly lower than that of the control group and BL-L group (P < 0.01), and the weight gain remained relatively slow after day 56. (3) Lung function: compared with the control group, on day 28, the lung function of IC, VC, Cchord, and Cdyn were significantly lower in the BL-L group (P < 0.01, P < 0.05), and IC and Cdyn were significantly lower in the BL-H group (P < 0.01). On day 42, IC, VC, and Cchord decreased significantly in the BL-L group (P < 0.01, P < 0.05), while IC, VC, Cchord, and Cdyn significantly decreased in the BL-H group (P < 0.01, P < 0.05), and IC, VC, and Cchord were significantly lower compared with those in the BL-L group (P < 0.01). On day 56, Cchord was significantly lower in the BL-H group than in the control and BL-L groups (P < 0.01), and on day 84, there was no significant difference in lung function between the groups. (4) Lung coefficient: on day 28, the lung coefficients of the BL-L and BL-H groups were significantly higher than those of the control group (P < 0.01), and from day 42 to 56, the lung coefficients of the BL-H group were significantly higher than those of the BL-L group and the control group (P < 0.01), and on day 84, the lung coefficients of the groups did not differ significantly from those of the control group. (5) Lung histopathology and immunohistochemistry: inflammatory infiltration, fibrotic streaks and COL III expression were observed in the BL-L group from day 28 to 56, with the severity of the lesions decreasing over time, and the fibrotic lesions had almost disappeared on day 84, while in the BL-H group, significant fibrotic lesions could be observed from day 28 to 84, and the degree of COL III expression was significantly higher than that in the control group (P < 0.01). Conclusions: Both 3 mg/kg and 5 mg/kg BLM can successfully induce PF rat models. The PF model prepared with 3 mg/kg BLM developed fibrosis on day 28, which lasted until day 42 and gradually recovered. The PF model prepared with 5 mg/kg BLM showed fibrosis formation on day 28, and the degree of fibrosis was more severe than in the lower dose, with fibrotic lesions persisting stably up to day 56, and moderate-to-severe fibrosis still present in half of the cases until day 84.
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Research progress on the evaluation and intervention of social interaction behavior in animal models of autism
KONG Minghui, LU Liming, XIANG Leiying, CHEN Xiaoyi, ZHU Zhiru
Abstract:
Autism Spectrum Disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic structure. However, preclinical trials currently under investigation for ASD mainly rely on rodent models to test the effects of non–pharmacological and pharmacological interventions on the core and related symptoms of ASD. This article elaborates on the brain regions that affect social interaction behaviors from the perspective of cognitive neural mechanisms; reviews behavioral testing experiments such as the three–chamber social interaction test, the visible burrow system, and the ecological HAB system; summarizes effective non–pharmacological interventions and pharmacological interventions such as baclofen, oxytocin, and metformin in the core and related symptom areas of ASD. This review aims to provide reference directions for promoting the development of preclinical trials using rodent models in the future.
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Study on the Pathology of Gouty Arthritis Based on Purinergic Receptor P2X7R
Wang Yinfeng, Liu Zeyu, Yin Xiaoyang, Lu Chengjin, Lin Zhijian, Zhang Bing
Abstract:
Abstract: Objective: To observe the effects of Ice-Water Swimming on pathological changes in gouty rat model and investigate the regulatory mechanism of P2X7R therein. Methods: Male SD rats were divided into Normal group and Experimental groups, which included Gouty Control group, Ice-Water Swimming group and BBG group. Experimental groups were modeled to hyperuricemia and gouty arthritis by inhibiting uric acid metabolism combined with Coderre method. Ice-Water Swimming group were treated with 5 min of endurance swimming in an ice-water mixture at a depth of about 0.5 m for 0 h and 12 h after modeling by Coderre method, while the BBG group were injected intraperitoneally with BBG solution for 1 time immediately after modeling. Formula to calculate ankle swelling index. The serum uric acid level of rats was detected by uricase assay. The expression level of serum inflammatory factors IL-1β, IL-6 and TNF-α was detected by ELISA. HE staining was used to observe the pathological state of the subject ankle joints. Western Blot and Immunohistochemistry for P2X7R and NLRP3 Protein Expression in Synovial Tissue respectively. Results: Compared with Normal group, the serum uric acid level and ankle joint swelling index of Experimental groups were significantly higher (P < 0.05 or P < 0.01), and the synovial tissues all had different degrees of inflammatory infiltration. Compared with Gouty control group, the ankle swelling index of Ice-Water Swimming group was significantly higher at 12h (P < 0.05). The serum IL-1β, IL-6, TNF-α levels (P < 0.01) and the protein expression of P2X7R, NLRP3 in the synovial tissues were all significantly elevated (P < 0.05). Pathology results showed that the cartilage surface was broken. In addition, the synovial tissue showed severe hyperplasia and erosion, accompanied by a large number of inflammatory cell aggregates. There were no significant changes in P2X7R, NLRP3 protein expression and pathological damage in synovial tissues of BBG group compared with Gouty control group (P > 0.05), whereas the expression of serum IL-1β, IL-6, and TNF-α were all significantly suppressed (P < 0.01). Conclusion: Cold stimulation and strenuous exercise simulated by Ice-Water Swimming can exacerbate pathological damage in gouty arthritis by a mechanism that may be related to high localized P2X7R expression in the joints.
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Research progress on animal models of insomnia based on combination of disease and syndrome
ZHAO Zhongmin, LIANG Shuzhi, GAO Xiangye, HOU Suyu, LUO Dandan, WANG SHIjun, ZHANG Yan
Abstract:
Insomnia, a prevalent clinical condition, not only diminishes patients" quality of life but also has the potential to give rise to further health complications. Traditional Chinese medicine has amassed and passed down knowledge about treating insomnia for thousands of years, resulting[1] in distinct advantages. It utilises syndrome differentiation and therapy to accomplish therapeutic effects by regulating the internal balance of the human body. To get a deeper understanding of how Traditional Chinese Medicine (TCM) treats insomnia, it is crucial to create animal models that exhibit symptoms closely resembling those found in humans with insomnia. This article provides a concise overview of the current disease-syndrome combination models, which may be classified into four categories: liver-depression, liver-depression for fire or liver-depression for spleen deficiency, heart-spleen deficiency, heart-kidney incompatibility, Yin and blood deficiency, This discussion will focus on particular modelling methodologies, assessment indicators, and model performance. The aim is to enhance the understanding of the pathophysiology of this disease in the context of traditional Chinese medicine. Additionally, this discussion aims to provide technical assistance for clinical efficacy evaluation and the creation of novel drugs.
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Current situation and countermeasures of laboratory animal license management in Hubei Province
liuconglin, qiaochuhua, liyanmei, chenxiaoli, zhangjinming, liudan, chenrui
Abstract:
This paper introduces the daily management service of experimental animal license in Hubei Province and the supervision matters during and after the event. It expounds the current situation of experimental animal license management, achievements, problems and countermeasures in Hubei Province.The focus was on analyzing the legislative situation of experimental animals in Hubei Province, the issuance and distribution of permits, the scale of facilities, and the composition of employees. In recent years, the number of experimental animal licenses issued in Hubei Province has been increasing year by year, and the number of animal production and use by licensed units has continued to rise. While the related industries are flourishing, there are also some regulatory deficiencies. this paper from the perspective of biosafety, combined with the problems encountered in the license management service work, put forward the relevant safety supervision countermeasures and suggestions, so as to better promote the development of experimental animal industry in Hubei Province.
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Application research progress of single-cell sequencing technology in Multiple Sclerosis
MA Zhihong, ZHANG Lihong, CAO Yuan, CHENG Ming
Abstract:
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by neuroinflammation and neurodegeneration. The pathogenesis of these diseases is complex, and a variety of central nervous system and peripheral cells are involved. In recent years, single-cell sequencing has gradually been applied in neurological disorder, which is of great significance for understanding intercellular heterogeneity, disease development mechanisms, and treatment strategies. This review will summarize the single-cell sequencing and its applications in MS.
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Mechanism study of mechanical stress mediated KOA synovial fibrosis through Piezo1/ERK1/2 axis
YuLikai, TianDi, SuZishan, JieLishi, GuoShaobo, WangPeimin, ZhangNongshan
Abstract:
Objective To investigate the effect of Piezo1 activated by mechanical stress on KOA synovial fibrosis via ERK1/2 signaling pathway. Methods (1) Animal experiments: 25 SD rats were divided into blank group, exercise group, exercise +GsMTx4 group, exercise +PD98059 group, exercise +GsMTx4+PD98059 group, 5 in each group. After the modeling was completed, the serum and synovial tissue of rats were extracted and the collagen deposition was evaluated by Sirius scarlet staining and Masson staining. Western Blot and RT-qPCR were used to detect the expressions of Piezo1, ERK1/2, p-ERK1/2, α-SMA, TGF-β, Collagen I and TIMP-1, and the contents of IL-1β, IL-6 and TNF-α were detected by ELISA. (2) Cell experiment: the synovial cells were divided into five groups: blank group, pull group, pull +GsMTx4 group, pull +PD98059 group, pull +GsMTx4+PD98059 group. WB, RT-qPCR and other techniques were used to detect the above indexes in the molded cells. Results (1) Animal experiments: Mechanical stress increased Collagen deposition in synovial tissue of rats, and increased the protein and mRNA expressions of Piezo1, P-ERK /Erk, α-SMA, TGF-β, Collagen I and TIMP-1 of pathway-related and fibrosis-specific indicators (P< 0.05). The expression of Piezo1 was significantly down-regulated with both inhibitors (P< 0.05), but the ERK inhibitor (PD98059) had no significant effect on PIEZO1 expression. The content of serum inflammatory factors in exercise group was significantly higher than that in blank group (P < 0.05), and the improvement was obvious after the use of inhibitors (P< 0.05). (2) Cell experiment: WB and RT-qPCR results showed the same trend as animal experiments. Conclusion The Piezo1 ion channel can sense mechanical stress and activate the ERK1/2 pathway to mediate knee synovial fibrosis.
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Design and Application of Energy Monitoring System for Laboratory Animal Facilities
XU Xiao, XIONG Wenjing, MA Xixiang, MU Dandan, ZHOU Shunchang
Abstract:
Objective The energy consumption of experimental animal facilities accounts for a significant proportion of the energy consumption in scientific research institutions, and its energy consumption characteristics are significantly different from those of ordinary buildings, thus requiring specialized monitoring and management. Method A set of energy consumption monitoring systems was designed for experimental animal facilities, and was deployed in the SPF-level experimental animal facility of Huazhong University of Science and Technology. Results After the system went online, it achieved real-time collection and recording of the facility"s electricity consumption data, and proposed energy-saving measures for three application scenarios. Conclusion The energy consumption monitoring system for experimental animal facilities has the characteristics of being reliable, efficient, and user-friendly, and has guiding significance and promotion value for the energy management work of experimental animal facilities.
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To study the effect of Houpu Sanwu decoction on exosomes of colorectal cancer model mice based on Rab27a
CHEN shu, RONG kang, ZHANG nan
Abstract:
Objective: TO investigate THE effect and mechanism of Houpu Sanwu Decoction on subcutaneous tumor in C57BL/6J mice. Methods: Mouse colorectal cancer MC-38 cells were subcutaneously injected into C57BL/6J mice to establish a subcutaneous tumor model of colorectal cancer. The mice with successful model were randomly divided into model control group, Houpu Sanwu decoction low-dose group, Houpu Sanwu decoction medium-dose group, Houpu Sanwu decoction high-dose group, 5-fluorouracil group (5-FU group), and combination group (5-fluorouracil + Houpu Sanwu decoction medium-dose group), with 6 mice in each group. The mice were treated with normal saline and Houpu Sanwu decoction by gavage or normal saline and 5-FU by intraperitoneal injection once a day for 24 consecutive days. During the intervention period, the mental state, diet and other general conditions of mice were regularly detected, and the changes in tumor volume of mice were regularly detected. After sampling, the subcutaneous tumors of each group were weighed and the pathological changes of subcutaneous tumors were observed by HE staining Transmission electron microscopy, Western blot and NTA were used to identify the exosomes derived from colorectal cancer tissues. RT-qPCR and WB were used to detect the mRNA and protein expression levels of Rab27a and exosome markers CD63, TSG101, and ALIX in tumor tissues.Results: Houpu Sanwu decoction could inhibit the growth of tumor in mice. The tumor growth was slow in all dose groups of Houpu Sanwu decoction and its combination group, and the tumor growth was inhibited to varying degrees. The anticancer effect of middle dose of traditional Chinese medicine was the best, and the combination group showed synergistic effect with 5-FU. Houpu Sanwu decoction could induce tumor necrosis, showing the same anticancer effect as 5-FU group, and the higher the dose, the more serious the necrosis was. Moreover, Houpu Sanwu decoction combined with 5-FU showed synergistic effect. Houpusanwu decoction can inhibit the protein and mRNA expression of Rab27a and exosome specific markers CD63, ALIX and TSG101 in mice.Conclusion: Houpu Sanwu Decoction inhibits the secretion of exosomes regulated by Rab27a possibly by inhibiting the secretion of exosomes.
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Analysis of an animal model of hepatic encephalopathy based on the characteristics of clinical diseases in Chinese and Western medicine
liyaqing, wangcan, miaomingsan
Abstract:
Objective To classify and analyze the existing animal models of hepatic encephalopathy based on the characteristics of Chinese and Western medicine clinical conditions, with a view to providing ideas for improving and perfecting the existing animal models of hepatic encephalopathy, so as to prepare animal models of hepatic encephalopathy that better meet the characteristics of the clinical conditions of Chinese and Western medicine combined with the conditions of hepatic encephalopathy. Methods In China Knowledge Network and Wanfang database, the Keywords "hepatic encephalopathy", "hepatic coma", "animal", "animal model" were used as Keywords, and in Pubmed database, "hepatic encephalopathy", "hepatic coma", " animal model", "animal" as the Keywords to search, collate effective literature with specific animal model preparation methods, collate and classify according to different modeling factors and methods, summarize the modeling methods and characteristics, and assess the clinical match of the animal model based on the characteristics of clinical diseases of hepatic encephalopathy in Chinese and western medicine. The clinical match of the animal model was assigned and analyzed according to the clinical symptoms of hepatic encephalopathy in Chinese and western medicine. Results There were 128 valid literature articles with 11 animal models, including 15 different modeling methods, among which, the CCl4 oil solution model had a high degree of agreement, and the highest degree of agreement in Western medicine was the CCl4 oil solution intraperitoneal injection+gavage+ammonium chloride intraperitoneal injection model (92%), and the highest degree of agreement in traditional Chinese medicine was the CCl4 oil solution intraperitoneal injection+ethanol aqueous solution self-drinking model (65%), but there was a lack of Chinese and Western medicine clinical disease characteristics.Conclusion The existing animal models of hepatic encephalopathy are all in accordance with the characteristics of the disease, but generally lack the manifestation of Chinese medicine, and lack of animal models combining the characteristics of Chinese and Western medicine. Combining the clinical characteristics of Chinese and Western medicine in the preparation of animal models is expected to provide a model basis for clinical diagnosis and treatment of hepatic encephalopathy, and point out the direction for the combination of Chinese and Western medicine in the treatment of hepatic encephalopathy.
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Establishment and optimization of a method for transferring golden hamster embryos using true pregnancy receptors
Abstract:
Objective By optimizing the technical parameters of golden hamster embryo transfer, explore the optimal number and developmental period of transplanted embryos for golden hamster true pregnancy recipients. Methods By establishing a population of true pregnant albino golden hamsters as embryo transfer recipients, the effects of different embryonic development stages, recipient embryo reduction, and secondary transfer recipients on litter yield, donor embryo yield, and offspring survival rate were compared. Results Compared to wild-type golden hamsters as transplant recipients, true pregnancy albino receptors can quickly determine the origin of offspring and are suitable for various reproductive experimental programs based on embryo transfer. Fertilized eggs or two cell embryos have no significant impact on the transfer effect (P>0.05); The rate of donor embryos in the recipient embryo reduction group was significantly increased (22%, P<0.05), and the lower total number of births resulted in a significant decrease in cage survival rate (56%, P<0.01). The second transfer recipient"s non pregnancy rate was significantly increased (42%, P<0.01); The highest embryo yield rate (27%, P<0.01) and normal survival rate (89%) were observed in the transfer of 6-10 embryos. Conclusion The transfer of 6-10 donor embryos can help improve the yield and survival rate of donor embryos, We have successfully established an embryo transfer method using albino pregnant golden hamsters as recipients, providing technical support for the application and development of gene modification models in golden hamsters.
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Progress in the study of the regulation of rheumatoid arthritis-related pathways by external treatment of traditional Chinese medicine
Abstract:
Rheumatoid arthritis (RA) is an autoimmune disease with symmetric small joints pain as an early clinical manifestation, which gradually worsens and often involves multiple joints, ultimately resulting in arthritic deformities and loss of labor capacity. Molecular signaling pathways have always been the focus of research on the prevention and treatment of RA. Studies have found that the progression of RA disease is closely related to a variety of signaling pathways which include the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, mitogen-activated protein kinases (MAPKs) signaling pathway, the NOD-like receptor protein 3 (NLRP3) signaling pathway, the toll-like receptors (TLRs) signaling pathway, the Wnt signaling pathway, Notch signaling pathway, hypoxia-inducible factor 1-alpha and vascular endothelial growth factor (HIF-1alpha/VEGF) signaling pathway, programmed death factor 1 and ligand 1 (PD-1/PD-L1) signaling pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. In recent years, the studies on the treatment of RA with external treatment of traditional Chinese medicine based on the above signaling pathways have gradually increased and deepened. In this paper, we reviewed the relevant data and reports to explain the relationship between the above pathways and the pathogenesis and prevention of RA and summarized the research results on the modulation of the above signaling pathways by external treatment of traditional Chinese medicine to prevent and treat rheumatoid joints with a view to providing a scientific basis for the clinical selection of this treatment.
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Study on optimization of preparation method of frozen section of skeletal muscle tissue
Abstract:
Objective To explore the optimal frozen section method for fresh and fixed skeletal muscle tissue, and to lay an experimental foundation for the rapid diagnosis of skeletal muscle diseases and the study of the pathogenesis of skeletal muscle diseases.Methods The tibialis anterior muscle of C57BL/6J mice was extracted, and the fresh tissue was treated by liquid nitrogen direct quick freezing, embedding agent combined with liquid nitrogen quick freezing, and foreign body alkane combined with liquid nitrogen quick freezing. The fixed tissues were pre-treated by direct embedding, embedding agent combined with liquid nitrogen quick freezing. After making frozen sections, HE staining was performed, and TISSUEFAX200 was used for scanning. The cross-sectional area of ice crystals and muscle fibers was calculated to evaluate the effect of different pre-treatment methods. Results The morphology of muscle fiber bundles disappeared and a large number of ice crystal vacuoles were observed in fresh tissues after liquid nitrogen direct freezing and foreign body alkane combined with liquid nitrogen freezing. The embedding agent combined with liquid nitrogen quick freezing ( the surface of the tissue is not in direct contact with liquid nitrogen ) shows that the muscle fiber bundle is complete and dense, and there is no ice crystal. It is a pre-treatment method suitable for fresh tissue. Fixed tissue directly embedded is not easy to slice ; after embedding agent combined with liquid nitrogen quick freezing treatment, the muscle fiber bundle was complete and there was no ice crystal.Conclusions The muscle fiber bundles of fresh and fixed tissues treated with embedding agent combined with liquid nitrogen quick freezing are complete and free of ice crystals, which is convenient for further experiments such as immunohistochemistry and immunofluorescence, and is conducive to the accurate and rapid diagnosis of skeletal muscle diseases and the exploration of the pathogenesis of skeletal muscle diseases.
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WEffect of Fuling Xingren Gancao granule on Polarization Phenotype Transformation of Atherosclerotic Macrophages
Abstract:
Objective To explore the regulatory effect of Fuling Xingren Gancao granule (FXG) on macrophage polarization in atherosclerosis (AS) mice. Methods ApoE -/- mice were used to construct an AS model, while RAW264.7 macrophages were used to construct a polarized model. Oil red O and hematoxylin eosin staining (HE) were used to observe the total area of aortic plaques and the degree of aortic stenosis. PCR and Western blot were used to detect the expression levels, signal transduction, and transcription of M1 polarization factor inducible nitric oxide synthase (iNOS), monocyte chemotactic protein 1 (CCL2), M2 polarization factor arginase-1 (Arg-1), chitinase like protein 3 (YM1), and mannose receptor 1 (Mrcl or CD206) in vitro and in vivo. The phosphorylation level of signal transducer and activator of transcription (STAT3). Result: FXG significantly reduced the total area of aortic plaques in ApoE -/- mice, decreased the expression levels of M1 macrophage polarization factors iNOS and CCL2, and increased the expression levels of M2 macrophage polarization factors Arg-1 and YM1 (P<0.05). The phosphorylation levels of STAT3 in the model group mice and M1 macrophages decreased, but were upregulated after FXG intervention (P<0.05). The P-STAT3 inhibitor Stattic partially eliminated the regulatory effect of FXG on iNOS and Arg-1 (P<0.05).Result FXG significantly reduced the total area of aortic plaques in ApoE -/- mice, decreased the expression levels of M1 macrophage polarization factors iNOS and CCL2, and increased the expression levels of M2 macrophage polarization factors Arg-1 and YM1 (P<0.05). The phosphorylation levels of STAT3 in the model group mice and M1 macrophages decreased, but were upregulated after FXG intervention (P<0.05). The P-STAT3 inhibitor Stattic partially eliminated the regulatory effect of FXG on iNOS and Arg-1 (P<0.05).Conclusion FXG has an inhibitory effect on the progression of AS, which is related to the targeted regulation of macrophage polarization by STAT3.
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Research progress of nuclear factor E2-related factor 2 in oxidative stress after spinal cord injury
xihuilin, wujiajun, wangqingyan, baixinyue, hemengze, yangyanling
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Spinal cord injury (SCI) is a central nervous system disease with high morbidity, high disability and high mortality. A series of pathological and physiological changes after SCI, such as oxidative stress, will promote the further deterioration of the microenvironment at the site of injury, resulting in impaired neurological function. Nuclear factor E2-related factor (Nrf2) is a factor highly correlated with oxidative stress, so targeting the regulation of Nrf2 and alleviating oxidative stress may be one of the treatments for SCI. This article discusses the application of Nrf2 in post-SCI oxidative stress based on the occurrence of oxidative stress after SCI and the relationship between oxidative stress and Nrf2, and summarizes the strategies for targeting and regulating Nrf2, such as genes, non-coding RNAs and drugs, in the hope of providing new ideas for targeted therapy of SCI.
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Advances in the pathogenesis of abnormal copper metabolism disorder in Parkinson's disease
YANG Huijie, LAN Rui, WANG Manman, Wang Weiwei, LI Hongyu, TANG Chen, LIU Shuang, YANG Jieli, SHEN Xiaoming
Abstract:
Parkinson's disease is a neurodegenerative disease associated with abnormal copper metabolism in the brain,which leads to misfolding and aggregation of α-synuclein-copper complexes, which is an important pathological sign of Parkinson's disease. Copper metabolism refers to the cellular metabolic process involving copper ions, which is closely related to the pathogenesis of α-synuclein aggregation, dopamine metabolism, mitochondrial dysfunction, oxidative stress and iron death in Parkinson's disease. In this review, we describe the molecular metabolic mechanism of copper toxicity by studying the pathological role of copper metabolism in Parkinson's disease，in order to provide evidence and help for further improvement of the mechanism of action and drug development.
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Study on the changes of intestinal permeability secondary to pig’s firearm penetrating wound of abdominal intestine in cold environment at high altitudes
QU Jinquan, LI Jiajia, LU Hongnan, YANG Xingyue, SUN Jiu, LIANG Feixing, WANG Yan, LIU Jiangwei
Abstract:
Objective To observe the changes and possible mechanism of intestinal permeability in pigs without direct injury after abdominal intestinal firearm penetrating injury in plateau cold environment. Methods 55 experimental pigs were divided into two groups: plateau cold group (HC) and plain normal temperature group (LN). According to the observation time, each group was divided into five experimental subgroups: 0h, 2h, 4h, 8h and 24h. There were 6 pigs in each subgroup in HC group and 5 pigs in each subgroup in LN experimental group. According to the time point of euthanasia, intestinal tissues were taken and the levels of inflammatory factors TNF- α, IL6 and IL-10 in intestinal homogenate and the concentrations of intestinal permeability related proteins DAO and D-lactic acid in blood were detected by ELISA method. The intestinal tissues of experimental pigs were taken at LN-0h, LN-8h and HC-8h time points, and the intestinal pathological changes were observed and scored after HE staining. The contents of Occludin, ZO-1, Claudin-3 proteins related to intestinal permeability and TLR4, NF- κ B and MLCK proteins related to intestinal permeability were detected by WB method to explore the effect of cold environment at high altitude on secondary intestinal permeability changes after injury and its possible mechanism.
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Strain and gender differences in the behavioral models of chronic fatigue syndrome induced by Polyinosinic-polycytidylic acid and swimming in mice
TIAN Jiao, SU rui, WANG tingting, PEI Hailuan, WANG Jing
Abstract:
Objective To compare the strain and gender differences between the ICR and C57BL/6J mice in the chronic fatigue syndrome model, and provide experimental evidence for the selection of model animals for chronic fatigue syndrome. Methods Mice were injected intraperitoneally with polyinosinic-polycytidylic acid (poly I:C) every three days and swam daily. The modeling was performed for 15 consecutive days, during which the weight and food intake of the mice were measured, and fatigue scores were assessed. After the modeling was completed, behavioral tests were carried out, including exhaustive swimming, tail suspension, mechanical pain threshold, and elevated plus maze. Results Compared with the control group, the exhaustion time of both strains of model mice in exhaustive swimming significantly decreased, the immobility time in tail suspension significantly increased, the mechanical pain threshold significantly decreased, the open arm entry time and frequency of the elevated plus maze in model male mice significantly decreased. The weight of model male C57BL/6J mice significantly decreased. The weight of model female ICR mice increased after the significant reduction. The exhaustion time of control C57BL/6J mice was significantly lower than that of control ICR mice. The immobility time of model C57BL/6J mice was significantly higher than that of model ICR mice. Conclusion There are differences between the two strains of mice in weight, fatigue level, and depression. Among the same strain of mice, there are differences between males and females, and the anxiety level of males is higher than that of females.
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The study of the mechanism by which EFHD2 regulates the NOX4/ROS pathway to initiate glycometabolism reprogramming and promote breast cancer progression
Xu ming fei, Zhang Yi, Kang ru yi, Liu chao yue
Abstract:
Objective To investigate the mechanism of EFHD2 affecting the occurrence and progression of breast cancer based on NOX4/ROS signaling pathway. Methods The cells were divided into NC-shRNA group and EFHD2-shRNA group. The lentiviral vector silencing EFHD2 expression and its control vector were constructed and transfected MDA-MB-23 and MCF-7 breast cancer cells. The transfection efficiency was verified by qRT-PCR.CCK8 assay was used to detect cell proliferation activity. Plate cloning assay was used to detect cell colony formation ability. Scratch test was used to detect cell migration. Transwell assay was used to detect cell invasion. Flow cytometry was used to detect apoptosis and ROS levels. qRT-PCR was used to detect the mRNA expression of GLUT1, PDK1, PFK1, PKM2, PDH, and LDH. Western blot was used to detect the expression of Cleaved caspase-3, MMP-2 and NOX4 proteins. Results Compared with NC-shRNA group, EFHD2 expression was significantly decreased in EFHD2-SHRNA group, and cell survival and colony formation ability were weakened. The apoptosis rate and the expression of pro-apoptotic protein Cleaved caspase-3 increased. The cell migration distance was shortened, the number of cell invasion and the expression of MMP-2, which promotes migration and invasion, were decreased. The levels of lactic acid and GLUT1, PDK1, PFK1, PKM2 and LDH decreased, while the levels of ATP and PDH increased. Streaming results showed that ROS levels were reduced and NOX4 protein was down-regulated after silencing EFHD2. Conclusion EFHD2 can inhibit ROS production by regulating NOX4/ROS signaling pathway, cause lactic acid and glucose accumulation, promote apoptosis of breast cancer cells, and inhibit cell proliferation, migration and invasion.
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The Current Situation and Suggestions of Research on Laboratory Animal Welfare and Ethics in China
lihuiping, DENG Shaochang, YANG Jingchun, WEN Jingyin, ZHAO Weibo
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Objective? Exploring the current research status, research context, evolution process, and future research directions of laboratory animal welfare and ethics in China. Methods? Using literature related to laboratory animal welfare and ethics collected from source journals in the China National Knowledge Infrastructure (CNKI) database from 2001 to 2023 as the data source, a combination of qualitative description through literature review and CiteSpace visual bibliometric analysis was used to summarize the achievements, hot topics, and directions of laboratory animal welfare and ethics research. Results? Research shows that the overall popularity of research on the laboratory animal welfare and ethics in China is on the rise. The main research institutions include the systematic units of the Chinese Academy of Medical Sciences, the Nanjing General Hospital of the Nanjing Military Region, and the National Institutes for Food and Drug Control. The hot research topics in this field include the basic theories of laboratory animal welfare and ethics, legislation on laboratory animal welfare and ethics, technologies for laboratory animal welfare and ethics, censorship of laboratory animal welfare and ethics, and teaching research on laboratory animal welfare and ethics. In response to ethical issues arising from emerging interdisciplinary fields, continuous innovation is being made in research content. Conclusions? Suggestions have been put forward from the perspectives of legal system, censorship mechanism, education and training, and innovative research of laboratory animals welfare and ethics, with the purpose to provide reference and guidance for welfare and ethics work of laboratory animals.
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Evaluation of a nude mouse model of endometriosis fibrosis by the human xenograft subcutaneous transplantation method
zhouxue, wanguiping, zhangzhenzhen
Abstract:
Objective To assess the feasibility of establishing a nude mouse model of endometriosis fibrosis of human origin and to determine whether endometrial mesenchymal stem cells are involved in inducing endometriosis fibrosis. Methods Four endometrial tissue specimens were collected and transplanted 1∶3 into 12 BABL/c nude mice by subcutaneous injection. The morphology and volume of the lesions were recorded, and the nude mice were executed on the 15th day after transplantation to observe the morphology of the lesions and their adhesion to the periphery of the abdominal wall, and HE staining was used to judge the results of modelling, Masson staining was used to assess the extent of fibrosis, and immunofluorescence was used to track the role of endometrial mesenchymal stem cells in the fibrotic process of endometriosis. Results The volume of ectopic lesions in nude mice increased over time, showing restricted, vesicular-like changes, with tight adhesion to the abdominal wall, endometrioid glands and collagen fiber deposition were seen microscopically, the success rate of modelling was 83.4%, and the collagen fiber volume fraction of the lesions was significantly higher after modelling (P<0.01), confocal imaging suggested that endometrial mesenchymal stem cells (SUSD2+) could differentiate into myofibroblasts (α-SMA+) in vivo. Conclusion The nude mice model established by the method of human allogeneic subcutaneous injection transplantation is consistent with the lesion characteristics of endometriosis fibrosis, which is simple and feasible, in addition to the in vivo observation that endometrial mesenchymal stem cells are involved in inducing the formation of endometriosis fibrosis, and it provides a better model reference for the further investigation of its pathogenesis.
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Research progress of the mechanism of medial prefrontal cortex layered structure in general anesthesia
lijia, yushouyang, luotianyuan, yutian
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The medial prefrontal cortex engages in various higher brain functions, including attention, transition of consciousness, and information integration, and becomes the central structure of action of general anesthetics. In addition, it is considered both the end point of the bottom-up model of layer-by-layer transmission of information and the starting point of the top-down modulation and integration of information. Classically, the medial prefrontal cortex can be divided into six layers in the vertical direction, with rich neural connections and different functions between layers. In this review, it describes laminar flow structures in the medial prefrontal cortex. Then, the review discusses that the general anesthetics change consciousness via cortical laminar flow structures. To this aim, the article reviews the available evidence in current studies from rodents, primates, and human studies that highlight the role of the medial prefrontal cortex in anesthesia.
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Transcriptome analysis of ethanol extract of Akebia trifoliate (Thunb.) Koidz on cell proliferation inhibitory functions and promote apoptosis in human liver cells
Abstract:
Objective To investigate the effects and molecular mechanism of EEATK on proliferation, apoptosis of human hepatocellular carcinoma Hep3B cells and Huh-7 cells and to explore its underlying mechanism . Methods Human hepatoma cells Hep3B cells and Huh-7 cells cultured in vitro, blank control group, Sorafenib group (5uM), EEATK groups (0.10 mg/mL、0.15 mg/mL、0.20 mg/mL、0.3 mg/mL)were set and given corresponding drug intervention, respectively. CCK-8 assay was used to measure the viability of different interventions on the proliferation of Hep3B cells and Huh-7 cells, to screen the optimal action concentration for subsequent experiments. Hep3B cells and Huh-7 cells were divided into the blank control group and EEATK group(0.15mg/mL) treated with for 24 hours,EdU staining assay, colony formation assay were used to explore the effect of EEATK on the proliferation , the apoptosis rate,were detected by Annexin V-FITC/PI double staining assay.The transcriptome sequencing(RNA-seq)technology was used to analyze differentially expressed genes (DEGs) related to cell proliferation, apoptosis on Hep3B cells in blank control group and EEATK group(0.15mg/mL)of Hep3B cells, DEGs were analyzed for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. CTD (Comparative Toxicogenomics Database) was used to validate the expression of key proteins related to cell proliferation, apoptosis. Results Compared with the blank control group, different concentration of EEATK could significantly inhibit the activity of Hep3B and Huh-7 cells (P <0. 01) ; After treated with 0.15 mg/mL EEATK, the EdU positive cell rate and cell clone formation rate were significantly decreased (all P <0. 01), at the same time ,the apoptotic rates of EEATK group were significantly increased(P < 0.01). Compared with the blank control group, The transcriptome sequencing of Hep3B cells showed that EEATK induced significant changes in the expression of 1577 DEGs (P <0. 01) , of which 942 were up-regulated and 635 were down-regulated. GO functional enrichment analysis revealed that DEGs were mainly enriched in cholesterol synthesis, inflammation, and extracellular matrix. KEGG pathway analysis showed that EEATK may mainly pass through TFG- β Signal pathways and NF-κB signaling pathway plays an anti-tumor role.DEGs enrichment analysis showed that EEATK can significantly downregulate the expression of apoptosis related genes such as BIRC5 and CDK1 (P<0.01), the expression of CDKN1A and EGLN3 were significantly upregulated (P<0.01), At the same time, EEATK can cause significantly downregulation of cell proliferation related genes such as FAM83D and Ki-67 (P<0.01), mean while, the expression of MYC and FoxC1 were significantly upregulated (P<0. 01).
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Research progress on the improvement effect of Morinda officinalis oligosaccharides on depression
HE Mengjie, DAI Xueling, HUO Qing, LI Xin
Abstract:
Depression is a psychosomatic disorder. In recent years, the rising incidence of depression around the world, bringing a heavy economic burden on society. The active substances extracted from the Chinese herb Morinda officinalis can soothe depression and calm the mind, tonify the kidney and benefit the intellect, and can also regulate monoamine neurotransmitter levels, enhance neuroplasticity, regulate the HPA axis, and regulate cytokine levels in antidepressant, as well as improve cognitive disorders in patients to a certain extent. Based on the hypothesis of the pathogenesis of depression, this paper summarises the role of Morinda officinalis oligosaccharides in antidepressant, and provides theoretical basis for the research and development of Morinda officinalis oligosaccharides antidepressant drugs.
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Research on potential dominant diseases of Traditional Chinese Medicine in the treatment of geriatric diseases based on bibliometrics
ZUO Yiming, SHI Guohua, LV Shichao, LIU Xuezheng
Abstract:
Objective In order to effectively use the characteristics and benefits of traditional Chinese medicine in clinical therapy, bibliometric approaches are being used to investigate the Dominant diseases of traditional Chinese medicine in the treatment of Geriatric diseases. Methods The clinical research literature of traditional Chinese medicine in the treatment of Geriatric diseases in the past 10 years was retrieved from CNKI, Wanfang, VIP and CBM. The research trend and clinical efficiency of each disease were statistically analyzed to determine the potential dominant diseases of TCM treatment. Results A total of 22,859 articles were collected, with 3768 being included in the research. According to the International Statistical Classification of Diseases and Related Health Problems (ICD-11) of the World Health Organization, the diseases were classified into 17 categories and 149 diseases, primarily affecting the circulatory system, the skeletal musculoskeletal system or connective tissue system, and the digestive system. Conclusion Traditional Chinese medicine clinical trials on the treatment of geriatric illnesses cover a diverse spectrum of diseases, although the distribution is unequal. Potential dominant illnesses are eventually identified to include osteoporosis, constipation, and hypertension, with heart failure, stroke, coronary heart disease, diabetes and its complications, and insomnia being potential sub-dominant diseases.
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Exploring the effect and mechanism of action of secukinumab on calcific aortic valve disease based on IL-23/Th17 inflammatory pathway
lixinxin, zhangning, fengguangling, lanzhenzhen, guojiao, liuxincan
Abstract:
Objective To observe whether the IL-23/Th17 inflammatory pathway is involved in the development of calcific aortic valve disease, and whether secukinumab can delay the progression of calcific aortic valve disease by inhibiting the IL-23/Th17 inflammatory pathway. Methods Forty-seven mice were divided into a blank control group, a model group, and a secukinumab group according to the random number table method. The blank control group was fed with normal chow, the model group and the secukinumab group were fed with pro-calcification chow for 16 weeks to establish a calcific aortic valve disease model, and the peak flow velocity changes of the aortic valves were detected under Doppler ultrasonography in all the mice after 4 weeks of intervention by secukinumab on the secukinumab group; relevant indexes were determined by HE staining, Von kossa staining, immunohistochemical staining, ELISA, and PCR. PCR were used to determine the relevant indexes. Results Compared with the model group, 4 weeks of drug intervention in the secukinumab group significantly reduced peak flow velocity ( P<0.05) and serum IL-6 levels ( P<0.05) in the aortic valve; compared with the secukinumab group, the leaflet thickness in the model group was significantly increased and there were more calcium deposits; Immunohistochemical results showed that macrophages ( P<0.05), IL-17A ( P<0.05), and IL-23 ( P>0.05) infiltration in the valve leaflets were reduced in the secukinumab group compared with the model group.PCR results suggested that the expression of STAT3, BMP-2 and α-SMA mRNA were significantly reduced in the secukinumab group compared with the model group ( P<0.05).Conclusion The IL-23/Th17 inflammatory pathway is involved in the pathogenesis of calcific aortic valve disease, and the inflammation, fibrosis, osteogenic differentiation, and calcification of mouse valves were alleviated after the intervention of secukinumab, which may delay the disease progression by inhibiting the IL-23/Th17 inflammatory pathway.
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Research development on the interaction between neuroimmunity and inflammation in the treatment of depressive disorder by traditional Chinese medicine
GUO Dong-jing, PAN Wen-chao, WANG Si-jia, MAO Qian-cheng, ZHAGN Hong-xiu, MA Ke
Abstract:
As a common mood disorder, depression has a complex pathogenesis. In recent years, with the accelerated pace of people’s lives, the prevalence rate has increased year by year, attracting people extensive attention. External stress and inflammation jointly damage blood vessel and brain functions, induce immune disorders, cause microglia activation and increase the expression of pro-inflammatory cytokines and their receptors, inflammatory reaction continues to occur, which affects the normal metabolism and metabolism of the neurotransmitter system. Abnormal functioning of molecular pathways leads to mutations in brain cells and nerves, and the further formation of the immune-inflammation-neuron cycle path becomes an important mechanism in the occurrence and development of depression. a large number of studies have shown that Traditional Chinese medicine treatment can improve depression symptoms by restoring neuroimmune inflammation homeostasis. From the perspective of neuroimmune inflammation, this article explains its close connection with depression and its pathogenesis, and reviews the role of various traditional Chinese medicine antidepressant therapies in improving and treating depression by participating in the regulation of neuroimmune inflammation to provide a new angle of view for the precise treatment of depression and the development of immune-targeted drugs.
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Research progress on the mechanism of D-galactose-induced brain aging model: A review
ZHU Ziyue, JIN Meiling, XU Xiangyue, LIU Qing, ZHU Jiaxue, FU Mingjun, LEI Xia, ZHANG Ning
Abstract:
As a normal physiological substance, D-galactose (D-gal) can induce a process similar to natural brain aging in vivo and in vitro under excessive intake, so it is widely used to induce brain aging model in China. The model of brain failure induced by D-galactose has the advantages of short time, low cost and significant effect, but its inducting mechanism is complex and diverse, and the relationships between the mechanisms are not clear, which leads to the limitation of the practical application of the model. This article reviews the in vivo metabolism of D-galactose and the various mechanisms of inducting brain aging, as well as the links between the mechanisms, in order to provide reference for the application and development of this model and the in-depth study of brain aging.
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Role of NLRP3-pyroptosis in experimental sepsis-induced lung injury
LI Yuting, NIU Chunyu, ZHAO Zigang
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Nod-like receptor pyrin domain-associated protein 3 (NLRP3) -mediated pyroptosis of pulmonary parenchymal and immune cells plays a key role in the pathogenesis of acute lung injury (ALI) during sepsis, and NF-?B, JAK2/STAT3, MAPK signaling pathways are involved in NLRP3-mediated pyroptosis. Targeting NLRP3-pyroptosis and its related signaling pathway, the pharmacological intervention of Physalin B, Schisandrin, 4-hydroxynonenal, Baicalin, GYY4137, and Erythropoietin, the physiatrics of acupuncture at Zusanli and Feishu, and the NLRP3 specific inhibitors such as Ergolide, play a good anti-septic effect on ALI. This article reviews the role and mechanism of NLRP3-pyroptosis in sepsis-induced ALI, as well as the experimental progress of targeting NLRP3-pyroptosis in the prevention and treatment of sepsis-induced ALI, hoping to take NLRP3-pyroptosis as the entry point to provide thinking for the formation of a new prevention and treatment strategy for sepsis-induced ALI.
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Effect of folic acid on the expression of Flotillin-1 and Aβ in the brain of mice with AD inflammation
Zewei MA, Li HUANG, Yunqin ZHENG, Meilin ZHANG, Huan LIU
Abstract:
【Objective】To observe the effects of folic acid (FA) supplementation on the expression of Flotillin-1 and β-amyloid protein (Aβ) metabolism-related proteins in the brains of inflammation-stimulated AD mice.【Methods】Twenty-seven 6-month-old male APP/PS1 mice were randomly divided into AD, AD+LPS, and AD+LPS+FA groups, with 9 mice in each group. 9 same-month-old C57BL/6J male mice were used as the wild control group (Control). The AD+LPS+FA group was given folic acid supplemented feed (8 mg/kg) for three months of intervention, while the other three groups were fed normal feed. Lipopolysaccharide solution (LPS, 250 μg/kg/day) was injected intraperitoneally into mice in the AD+LPS group and AD+LPS+FA group one week before the end of the experiment, and saline was injected into the remaining two groups. The serum inflammatory factors TNF-α and IL-6 levels and brain tissue Aβ1-40 and Aβ1-42 levels of mice in each group were detected by ELISA, Flotillin-1 protein expression in brain tissue was detected by Western blot, and immunofluorescence double-labeling was used to detect the co-expression of Flotillin-1 in the cortical region of the brain and Aβ1-42/APP/PS1/ BACE1 co-expression. 【Results】 After ANOVA analysis, compared with the Control group, mice in the AD group had elevated serum TNF-α and IL-6 levels (P < 0.05), elevated levels of Aβ1-40 and Aβ1-42 (P < 0.05), increased expression of Flotillin-1 protein (P < 0.05), and increased co-expression of Flotillin-1 and Aβ1-42/APP/PS1/BACE1 in the cortical region of brain tissue (P < 0.05); Compared with the AD group, mice in the AD+LPS group had further increases in serum inflammatory factors and Aβ levels in the brain (P < 0.05), and increased expression of double-labeled positive proteins in the cortical region of brain tissue for Flotillin-1 and Aβ1-42/APP/BACE1 (P < 0.05) ; Compared with the AD+LPS group, mice in the AD+LPS+FA group had lower in vivo inflammation levels and Aβ content in the brain (P < 0.05), lower brain tissue Flotillin-1 protein expression (P < 0.05), and lower co-expression of Flotillin-1 with Aβ1-42/APP/PS1/BACE1 proteins in the cortical region of brain tissue (P < 0.05). 【Conclusion】 Folic acid supplementation may reduce Flotillin-1 protein expression and Aβ deposition in the brain of AD inflammatory mice.
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Practice and reflection on combining teaching and training to promote the standardization of animal experiments for medical postgraduates
CHEN Qin, LI Jianmin, GAO Yun, QIU Chen
Abstract:
Standardized animal experiments are the basic prerequisite and important guarantee for eliminating potential biosafety risk factors and obtaining accurate medical research results. Professional training for graduate students who conduct animal experiments and strengthening publicity and education on animal experiment management regulations can help establish a sense of responsibility for standardizing animal experiments among medical graduate students. The innovative teaching-training model will fundamentally help to ensure the smooth implementation of animal experiments, and truly promote the healthy development of laboratory animal work in universities.
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The effect of Angelica sinensis polysaccharides on Th17/Treg cell balance and expression of related inflammatory factor proteins in bone marrow of mice with aplastic anemia
chenxiubao, xufei, yinxi, chenweida, cuixing, liuxiujuan, chenzetao
Abstract:
Objective：To investigate the effect of Angelica sinensis polysaccharides on the balance of Th17/Treg cells and the expression of related inflammatory factor proteins in bone marrow of mice with aplastic anemia.Methods 50 male BALB/c mice were randomly divided into normal group,model group,cyclosporineA group,APS low and high dose groups.A mouse model of aplastic anemia was prepared by combining radiation irradiation with allogeneic lymphocyte infusion.After modeling,the mice were orally administered for 28 days.The general condition,weight changes,and spleen index of the mice were observed.Blood samples were taken to test the changes in basic hematological parameters of peripheral blood,and HE staining was used to evaluate the pathological changes in mouse bone marrow tissue;ELSIA method for detecting bone marrow TGF-β1.The expression levels of proteins such as IL-10,IL-17A,and IL-6;FCM detection of bone marrow Th17,Treg cell ratio,and Th17/Treg cell balance changes.Results Compared with the normal group,the model group mice showed clumsiness in activity,lethargy,pale eyelids,lips,and ears,and reduced food and water intake;Both body weight and spleen index significantly decreased;The peripheral blood red blood cell,white blood cell,platelet count,and hemoglobin concentration were significantly reduced;Disordered bone marrow tissue structure and significantly reduced proliferation of hematopoietic tissue;The expression of IL-17A and IL-6 proteins is significantly upregulated,and TGF-β1.The expression of IL-10 protein was significantly downregulated;The proportion of Th17 cells in bone marrow significantly increased,the proportion of Treg cells significantly decreased,and the ratio of Th17/Treg cells significantly increased(P<0.01).Compared with the model group,the general condition of the low and high dose APS groups improved,with an increase in food and water intake,a significant increase in body weight and spleen index,a significant increase in peripheral blood red blood cell,white blood cell,platelet count,and hemoglobin concentration(P<0.05),an improvement in bone marrow tissue structure,and an increase in hematopoietic tissue proliferation (P<0.05);The expression of IL-17A and IL-6 proteins is significantly downregulated,and TGF-β1. The expression of IL-10 protein was significantly upregulated(P<0.05 or P<0.01);The proportion of Th17 cells in bone marrow significantly decreased,the proportion of Treg cells significantly increased,and the ratio of Th17/Treg cells significantly decreased (P<0.01).Conclusion Angelica sinensis polysaccharides can improve bone marrow hematopoietic function in AA mice,and its mechanism may be achieved by regulating Th17/Treg cell balance.
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Analysis of ankylosing spondylitis’ animal model based on clinical characteristics of traditional Chinese and western medicine
Zhang Fangzhi, Miao Furui, Fan Yushan, He Yujun
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Ankylosing spondylitis is an autoimmune disease with sacroiliac arthritis and spinal arthritis as the main manifestations. The disease mainly occurs in young men, with a high disability rate and a serious threat to the life and health of patients. Biological agents are expensive, and there are many adverse reactions of hormones, non-steroidal anti-inflammatory drugs and anti-rheumatic drugs. Traditional Chinese medicine can regulate immunity and anti-inflammatory, and has a good clinical effect. In order to further study the pathogenesis of ankylosing spondylitis and the development and screening of therapeutic drugs, this paper summarizes the modeling method and mechanism of the existing animal model of ankylosing spondylitis, and analyse advantages and disadvantages of the model. To evaluate the coincidence of Clinical Characteristics of Chinese Medicine and Western Medicine,the paper compares the characteristics of Chinese and Western medical syndromes of the animal model. To build an animal model of ankylosing spondylitis with a higher degree of coincidence between traditional Chinese and western medicine is the key to innovative research of traditional Chinese medicine for treating ankylosing spondylitis. In order to lay a foundation for the research of traditional Chinese medicine for ankylosing spondylitis，this paper analyzes the degree of coincidence between Clinical Characteristics of Chinese Medicine and Western Medicine of animal model.
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Advances in bee venom research: novel drug candidate library for the treatment of inflammatory skin diseases
WU Qiang, Yang Yue, LI Peng, GU Jiajie, DONG Degang, YI Jun
Abstract:
Inflammatory skin diseases (ISD) are characterized by persistent inflammatory infiltration and lingering and intractable skin lesions. At present, corticosteroids are the main drugs used in the treatment of ISD. However, due to the characteristics of recurrent and intractable ISD, long-term use of these hormone drugs may cause serious side effects to patients. In recent years, more and more studies have confirmed that bee venom (BV) has significant anti-inflammatory, anti-apoptosis, anti-fibrosis, antibacterial and other effects, so as to effectively treat ISD. In this paper, the main active components of BV are reviewed and its anti-inflammatory mechanism, and the latest status of BV in acne, atopic dermatitis, psoriasis, urticaria and systemic lupus erythematosus is discussed, which provides reference for the basic research and clinical treatment of ISD.
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Effect and Mechanism of Qishishenshu Capsule on Renal Fibrosis in Mouse Early Diabetic Nephropathy
LAO Xiao-qing, CHEN Chen, ZHANG Hong-min, YANG Xiu, SHI Jiang-shan, SU Hong-wei, SHEN Hong-ping, WANG Li, YOU Man-rui, LI Xiao-bin, ZHAO Chang-ying
Abstract:
【Abstract】Objective To investigate the therapeutic effect and underlying mechanism of Qishishenshu capsule on renal fibrosis in mice with early diabetic nephropathy (DN). Methods DN mouse model was established by multiple injection of streptozotocin (STZ). The mice were randomly divided into the normal group (NC), model group (DN) and Qishi group (QS)(0.9 g/kg/d), 8 mice in each group, gavaged continuously for 4 weeks, and fasting blood glucose (FBG) was measured weekly. 4 weeks later, urinary microalbumin creatinine ratio (UACR), serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin staining (HE staining), periodic acid-Schiff staining (PAS staining) and Sirius red staining were used to analyze renal pathological changes. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the Message RNA (mRNA) levels of fibronectin (FN), collagen type I alpha 1 (Col1a1), and α-smooth muscle actin (α-SMA). Immunohistochemistry (IHC) and Western blot (WB) were performed to detect FN, collagen type I (Collagen I), collagen type III (Collagen III), α-SMA, Podocin, Nephrin and transforming growth factor-β1/SMAD family member2/3 (TGF-β1/Smad2/3) pathway-related proteins. Results Compared with the NC group, mice in the DN group showed significantly higher levels of FBG and UACR (P<0.001). Mesangial hyperplasia, basement membrane thickening and collagen deposition occurred in renal tissue. The mRNA levels of FN, Col1a1 and α-SMA were increased (P<0.05). Protein levels of Podocin and Nephrin were decreased (P<0.05). The levels of FN, Collagen I, Collagen III, α-SMA and TGF-β1/Smad2/3 pathway protein were increased (P<0.05). Compared with the DN group, the level of UACR in QS group was decreased (P<0.05), and renal pathological injury was alleviated. The mRNA levels of FN, Collagen1 and α-SMA were attenuated (P<0.05). The protein levels of Podocin and Nephrin were elevated (P<0.05). Protein levels of FN, Collagen I, Collagen III, α-SMA and TGF-β1/Smad2/3 pathway protein were also decreased (P<0.05). Conclusions Qishishenshu Capsules improved renal fibrosis in DN mice probably through the inhibition of TGF-β1/Smad2/3 signaling pathway.
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Research progress of diarrhea animal model and its drug therapy
Shi Yucun, Dong Xiaoli, Hou Xiaoying, Yin Kai, Gao Fan, Wu Guotai
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Diarrhea is a common and frequently occurring disease in clinic, and there are many factors causing diarrhea. At present, there are many methods to study the animal model of diarrhea, but there are limited kinds of drugs to treat diarrhea in clinic, some of the drugs available also apply to single-factor diarrhea. Therefore, the establishment and selection of diarrhea animal model is not only an important basis for further study of the pathogenesis of diarrhea, but also an effective means for clinical screening and evaluation of all-round anti-diarrhea drugs. This article reviews the establishment and evaluation of animal models of diarrhea and the progress in the research of therapeutic drugs, in order to provide reference for the animal experimental research and drug prevention and treatment of diarrhea.
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Overexpression of TFB1M inhibits hepatocellular carcinoma cell migration and invasion
Tao Jia, He linli, wang li, ge pengsheng, sai shunhai
Abstract:
Objective To explore the effect of transcription factor B1,mitochondrial,(TFB1M) on cell survival and migration of hepatocellular carcinoma cells and related molecular mechanisms. Methods TFB1M gene was overexpressed by transfection of eukaryotic recombinant plasmid. Cell survival and cell cycle distribution were detected by CCK-8 and flow cytometry. Cell migration and invasion were assessed by scratch healing and transwell chamber assays. Results The expression of TFB1M was significantly decreased in HCC, and the expression of TFB1M was more lower in female HCC patients than that tin male HCC patients. The mRNA expression of TFB1M was significantly increased after transfection of recombinant plasmid. Moreover, our results showed that overexpression of TFB1M had no effect on the growth and cell cycle distribution of HepG2 and Huh7 cells. However, overexpession of TFB1M remarkably attenuated the migration and invasion activity of HCC cells(all P<0.05). The results from the bioinformatics presented that the low expression of TFB1M might be related to the extracellular matrix assembly gene set in HCC. Conclusions TFB1M regulates the cell metastasis and invasion through influencing extracellular matrix assembly in HCC.
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Research progress on the mechanism of STAT3 in diabetic kidney disease
liuruidi, xujiangyan, xiezhishen, zhangxiaowei, chenjie, zhangzhenqiang
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Signal transducer and activator of transcription 3 (STAT3) is known to modulate expression related to cell transformation, proliferation and survival making it a significant target for cancer therapy. Recent research has also highlighted the crucial involvement of aberrant STAT3 activation in the pathogenesis of diabetic kidney disease (DKD). This paper aims to explore the therapeutic implications of targeting STAT3 in DKD, encompassing its structural characteristics, regulatory mechanisms of activity, pathological activation in DKD, and an overview of current research progress, with the objective of advancing understanding of DKD pathogenesis.
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Research Progress on Macrophage Metabolism and Immune Function in Coronary Heart Disease (CHD) with Phlegm and Blood Stasis Syndrome
CAO Panxia, PENG Zining, LI Jian, WU Hong
Abstract:
In traditional Chinese medicine, coronary heart disease falls under the categories of "chest impediment and heart pain" and "true heart pain", with lipid metabolism disorder and inflammatory response acting as biochemical manifestations of "phlegm and stasis" throughout the disease. The energy metabolism of macrophages is closely related to their immune function and is an important factor in regulating the metabolic disorder and inflammatory response in coronary heart disease. This article reviews the role of macrophages in the pathophysiology of coronary heart disease, discusses how these metabolic pathways affect the immune response of macrophages, and how they influence the disease through energy metabolism pathways. It delves into the different modes of macrophage energy metabolism, especially the metabolic characteristics and immune regulatory functions of pro-inflammatory M1 and anti-inflammatory M2 macrophages in the syndrome of phlegm and blood stasis in coronary heart disease. This provides theoretical guidance for understanding the pathogenic mechanism of the syndrome of phlegm and blood stasis in coronary heart disease and developing new treatment strategies.
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Research progress on pharmacological mechanism of traditional Chinese medicine in the treatment of cerebral ischemia-reperfusion injury based on regulating AMPK signaling pathway
hechenfei, machiyuan, ranchunlong, chenghaoge, liuxiangzhe
Abstract:
Cerebral ischemia-reperfusion injury(CIRI)refers to the recovery of blood supply after cerebral ischemia, leading to further damage and dysfunction of brain tissue. At present, modern medicine has made some progress in the prevention and treatment of CIRI, but it still faces some challenges and limitations. Therefore, it is of great clinical value to find effective interventions to prevent and treat CIRI. AMP-activated protein kinase(AMPK)and its downstream proteins are important targets for the treatment of CIRI and play a key role in the regulation of cellular energy homeostasis. Traditional Chinese medicine has the characteristics of multi-target, multi-pathway and multi-effect. It can activate the cascade reaction of AMPK signaling pathway, and treat CIRI by regulating autophagy, oxidative stress, inflammatory response and apoptosis, and has achieved certain results. Therefore, this paper summarizes the structure and mechanism of AMPK-related signaling pathway, elaborates its relationship with CIRI, and systematically summarizes the research status of traditional Chinese medicine regulating AMPK signaling pathway in the prevention and treatment of CIRI, in order to provide new ideas for the prevention and treatment of CIRI in traditional Chinese medicine and the development of new drugs.
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Effects of hypoxic preconditioning on NR2B in mouse hippocampal cell and HT22 cell
Wang Zhigang, Liu Xiaolei, yanlei, Wang Zhiguang, zhang Zhiyong, JIANG shuyuan, yang jing, Shao Guo
Abstract:
objective: N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B) and its phosphorylation are involved in cerebral ischemia/hypoxic neural injury. Hypoxic preconditioning (HPC) serves as an endogenous protective intervention to protect the brain from ischemic/hypoxic injury. This study intends to explore the effect of HPC on NR2B and its two tyrosine sites phosphorylation (1252 and 1336) in hippocampal cells through in vivo and in vitro experiments, and explore its role in HPC neuroprotection.
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Research progress on the mechanism of epigenetics in improving Parkinson"s disease through exercise
Liu Bo, Chen XiangHe, LuPengcheng, YangKang
Abstract:
PD is a highly complex neurodegenerative disease, and its pathogenesis is influenced by DNA methylation, histone modification, and non-coding RNA. In research on Parkinson"s brain tissue and blood, it has been shown that changes in DNA methylation/histone modification levels, variations in ncRNA and its target genes may trigger or exacerbate the pathogenesis of neurodegeneration, and serve as potential non-invasive biomarkers for Parkinson"s disease. Exercise can improve neurodegenerative diseases caused by aging and PD by reversing epigenetics. This article reviews the pathogenesis of epigenetics in Parkinson"s disease, explores the role of exercise in it, and provides theoretical reference for improving Parkinson"s disease by regulating epigenetics through exercise.
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Inhibition of Boschniakia rossica Boschnaloside on Epithelial-Mesenchymal Transition of Hepatoma SMMC-7721 Cells
JIN Aihua, ZHU Jiebo, QUAN jishu
Abstract:
Objective To investigate the inhibitory effect of Boschniakia rossica boschnaloside (BRBN) on epithelial-mesenchymal transition (EMT), invasion and migration of human hepatoma SMMC-7721 cells. Methods Transforming growth factor β1 (TGFβ1) was used to induce EMT model of SMMC-7721 cells. The cells were divided into the control group, model group and BRBN group. The cell migration was detected with wound healing test, the cell invasion was observed by transwell chamber assay, and the expressions of E-cadherin, N-cadherin, vimentin, Slug, Twist1, ZEB1 and signal transducers and activators of transcription 3 (STAT3) were determined with the western blot method. Results TGFβ1 resulted in the spindle-shaped changes in SMMC-7721 cells, down-regulated the expression of E-cadherin, and up-regulated the expression of N-cadherin and vimentin, suggesting that SMMC-7721 cells have obtained the mesenchymal phenotype. Compared with the model group, the expression of E-cadherin was significantly increased, expressions of N-cadherin and vimentin were reduced, expressions of Slug, Twist1, ZEB1 as well as STAT3 phosphorylation were also down-regulated in SMMC-7721 cells of BRBN group. Conclusions BRBN could inhibit the invasion and migration of human hepatoma SMMC-7721 cells, possibly by reversing EMT through STAT3 pathway.
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The Relationship Between Insulin Resistance, Hyperandrogenism, and Mitochondrial Oxidative Stress in PCOS
zhaoqi, yangliping, chenping, sunjianhua, mazibo
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Polycystic ovarian syndrome (PCOS) stands as a prevalent reproductive endocrine metabolic disorder within obstetrics and gynaecology. Two pivotal features of PCOS are insulin resistance (IR) and hyperandrogenemia (HA), both instrumental in its pathogenesis. There exists a discernible correlation between PCOS patients and mitochondrial oxidative stress, a relationship heavily influenced by various factors, notably insulin resistance and hyperandrogenemia. This article endeavors to elucidate the interplay between insulin resistance, hyperandrogenemia, and mitochondrial oxidative stress, while also exploring the impacts of insulin resistance and hyperandrogenemia on mitochondrial oxidative stress among PCOS patients.
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Research Progress on the Role of Microglia Efferocytosis in Alzheimer's Disease
Machiyuan, Wangxinzhi, Liuxiangzhe, Hanzhenzhen, Guoming, Lixiao
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Microglia efferocytosis is the process by which microglia phagocytose damaged and dead cells, with anti-inflammatory and pro-damage repair effects. Recent studies have shown that microglia efferocytosis plays a crucial role in the pathogenesis of Alzheimer"s disease (AD) and may be a novel therapeutic target for AD. This paper reviews the relationship between microglia efferocytosis and AD pathogenesis and the potential of efferocytosis-related molecules as therapeutic targets for AD. The aim is to provide new ideas and approaches for the treatment of AD.
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Research Progress on the Intervention of Tryptophan Metabolism in Alzheimer"s Disease
WU Cui, LI Canwei, ZHAO Hairong, YANG Zizhong, GAO Pengfei, ZHAO Yu, ZHANG Chenggui
Abstract:
Alzheimer"s Disease (AD) is a degenerative neurological disorder that can lead to cognitive decline, mental behavior abnormalities, and reduced ability to daily lives. Tryptophan is an essential amino acid for the human body and is produced by three main metabolic pathways, namely kynuridine, 5-hydroxytryptamine (5-HT) and indole derivatives. Influencing the metabolites of tryptophan can lead to ameliorated neuroinflammation in the brain and significantly improvdcognitive ability, while the occurrence and development of AD.is affected and intervened. In this paper, we reviewed the research literature on tryptophan metabolism intervention in AD in recent 3 years from CNKI, PubMed and other databases.
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Role and mechanism of DNMT1 regulating LSM4 in HCY-induced hepatocyte apoptosis in mice
Xia Tongtong, Ma Fang, Liu Honglin, Zhang Zhenghao, Ding Hanshuang, Hao Yinju, Zhang Huiping, Wu Kai, Jiao Yun, Jiang Yideng, Li Guizhong
Abstract:
Objective To study the effect of DNA methyltransferase 1 (DNMT1) on sm-like protein-4 (LSM4) in the hepatocytes apoptosis of mice induced by Hcy. Methods 12 ApoE-/- mice were divided into two groups: normal diet (ND, n = 6), high methionine diet (HMD, n = 6). Normal hepatocytes of NCTC1469 were divided into normal group (control, 0 μL/L Hcy), Hcy intervented group (Hcy, 100 μL/L Hcy), transfected NC siRNA control group (si-NC group, 0 μmol/L Hcy), transfected LSM4 siRNA group (si-LSM4 group, 0 μmol/L Hcy), transfected DNMT1 siRNA group (si-DNMT1 group, 0 μmol/L Hcy), transfected NC siRNA in the Hcy intervened group (Hcy＋si-NC group, 100 μmol/L Hcy), transfected LSM4 siRNA in the Hcy intervened group (Hcy＋si-LSM4 group, 100 μmol/L Hcy) and transfected siRNA DNMT1 in the Hcy intervened group (Hcy＋si-DNMT1 group, 100 μmol/L Hcy); Analysis of the expression of LSM4 in various tissues by NCBI database; quantitative real-time PCR (qRT-PCR) and Western blot (WB) were used to detect the difference of LSM4 protein expression in mice tissues (HMD and ND) and hepatocytes (control and Hcy). Western blot was used to detect the protein expression of Bcl2-associated X (Bax) and B-cell lymphoma-2 (Bcl-2). The cell apoptosis rate of control, Hcy, Hcy＋si-NC and Hcy＋si-LSM4 were detected by flow cytometry. MethPrimer online software was used to analyze the CpG islands of LSM4 promoter region. The expression of LSM4 in si-DNMT1 group was detected by qRT-PCR and Western blot. Results The expression of LSM4 in HMD/Hcy group was higher than that in the control group (P＜0.05). Bax protein expression in Hcy＋si-LSM4 was significantly higher than that in the control group (P＜0.05), but Bcl-2 was significantly lower (P＜0.05). The expression of Bax in Hcy＋si-LSM4 was significantly lower than that in Hcy＋si-NC group (P＜0.05), and the level of Bcl-2 was significantly increased. The cell apoptosis rate in Hcy group was higher than that in the control group (P＜0.05). The cell apoptosis rate in Hcy＋si-LSM4 group was lower than that in the Hcy＋si-NC group (P＜0.05). MethPrimer database analysis showed that the promoter region of LSM4 was GC rich and there was one CpG island. Compared with the Hcy+si-NC group, the expression of LSM4 protein in the Hcy+si-DNMT1 group was increased (P＜0.05). Conclusions DNMT1 regulates LSM4 hypomethylation to increase its expression, thereby promoting Hcy-induced apoptosis of mouse hepatocytes.
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Establishment of a multi factor induced hyperuricemic nephropathy rat model and study on the intervention effect of Qiling granules
Zhang Qian, Tu Hai Ye, Zhu Ke Yan, Yu Chen, Cai Yue Qin, Rong Yi Li, Zhang Li Zong, Chen Min Li, Fang Ming Sun
Abstract:
Objective To establish a rat model of hyperuricemic nephropathy (HN) using a multifactorial induction method of potassium oxazinate combined with adenine and yeast feed, and to observe the intervention effect of Qiling granules (QLG). Methods Fifty-eight SPF grade male SD rats were selected, and ten rats were randomly selected as the normal control group. The remaining rats were induced by multiple factors to establish HN rat models. After 2 weeks of modeling, submandibular blood samples were taken to detect serum UA, CREA, BUN, TG, and TC. Forty HN rats with bleeding clearance UA and body weight close to the mean were selected. They were randomly divided into model control group, QLG low and high dose groups, and positive control group using a stratified randomization method, with ten rats in each group. Each group was given corresponding drugs by gavage daily, and after continuous administration for 4 weeks, submandibular blood samples were taken to detect serum UA, CREA, BUN, TG, and TC. After euthanasia of rats, and liver tissue was taken to detect XOD and ADA activity. Renal tissue was taken for HE and Gomori hexamine silver staining, and the protein expression of GLUT9, OAT1, VCAM-1, and TGF-β in the kidneys was observed using immunohistochemistry and WB methods. Results Compared with the normal control group, the serum levels of UA, CREA, BUN, TC, and TG, as well as liver XOD and ADA activities, were significantly increased in model control Group (P<0.01). The renal tissue of rats shows significant pathological changes. The positive area of urate in renal tubules and the expression of GLUT9, VCAM-1, and TGF-β proteins in the kidneys were significantly increased (P<0.01, P<0.05), while the expression of OAT1 was significantly reduced (P<0.01). Compared with model control group, the serum UA levels, liver XOD, ADA activity, and renal VCAM-1 protein expression of rats in each treatment group were significantly reduced (P<0.01, P<0.05). The serum CREA, BUN levels, and renal TGF-β protein expression of rats in the low-dose QLG group were also significantly reduced (P<0.05, P<0.01). The serum CREA, BUN levels, and renal GLUT9 protein expression of rats in the high-dose QLG group were also significantly reduced (P<0.01, P<0.05), and the urate deposition and renal injury caused by them in each treatment group were reduced to varying degrees, but there was no significant difference (P>0.05). Conclusion A stable HN rat model can be induced by gavage of potassium oxyzinate and adenine in combination with yeast feed to rats; QLG can effectively treat HN by improving UA metabolic disorders, reducing renal inflammation and urate deposition, as well as causing renal damage in HN model rats. Its mechanism of action is related to reducing serum UA, CREA, BUN, TG levels, liver XOD and ADA activities, as well as the expression of GLUT9, OAT1, VCAM-1, and TGF-β proteins in the kidneys.
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Ferroptosis and its role during experimental acute lung injury
guohuanrong, wang jing, zhao zi gang, niu chun yu
Abstract:
Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent lipid peroxides accumulation-induced membrane lipid peroxidation and mitochondrial atrophy, and differed from other programmed cell deaths in morphological and biochemical properties. Ferroptosis is regulated by a variety of metabolic pathways, involved in acute lung injury induced by hemorrhagic shock, ischemia-reperfusion, sepsis, and radiation. This article reviews the main regulatory mechanisms of ferroptosis and its role in the pathogenesis of acute lung injury in various animal models, with the aim of providing new strategies for the prevention and treatment of acute lung injury.
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Study of the mechanism of Honokiol protecting pulmonary microvascular endothelial barrier in LPS induced acute lung injury
Abstract:
Objective: To study the effect of Honokiol (HKL) on pulmonary microvascular endothelial cells in lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) and its potential mechanism.Methods: Mouse lung microvascular endothelial cells (PMVEC) were cultured with DMEM+10%FBS in a six-well plate and divided into control group (Con group), Honokiol group (HKL group), Lipopolysaccharide treatment group (LPS group) and LPS+HKL treatment group (HKL+LPS group). The levels of Malondialdehyde and Reactive Oxygen Species in cell lysates were determined by TBARS assay kit and H2DCF-DA, respectively. TUNEL/DAPI double staining was used to detect apoptosis. The cell junction was detected by VE-cadherin/DAPI and Claudin-5/DAPI double staining. Western blotting was used to detect caspase-3, cleaved caspase-3, Sirt3, SOD2, and acetylated SOD2 (Ac-SOD2). 32 mice were randomly divided into control group (Con group), Honokiol group (HKL group), Lipopolysaccharide treatment group (LPS group) and LPS+HKL treatment group (HKL+LPS group). HE staining was used to observe the pathological changes of lung tissue.Results: Honokiol pretreatment could significantly reduce LPS-induced increase of ROS and MDA levels, and decrease LPS-induced increase of SOD2 acetylation and SIRT3 down-regulation. TUNEL and Caspase analysis showed that Honokiol could protect apoptosis of PMECs induced by LPS. VE-cadherin fluorescence staining demonstrate thag Honokiol pretreatment could prevent LPS from damaging cell adhesion. Claudin-5 fluorescence staining show that Honokiol pretreatment could prevent LPS from disrupting tight connections of cells. In animal experiments, HE staining showed that Honokiol significantly inhibited the typical pathological changes of ARDS in the lung tissue of mice in LPS group.Conclusion: HKL can significantly inhibit LPS-induced oxidative stress, apoptosis and cell connection breakdown of pulmonary microvascular endothelial cells, thereby alleviating ARDS symptoms.
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Preliminary studies on the mode of CdCl2 in combination with nicotine on spermatogonial cells
han xue, jiang li, zhang yuan, wu de sheng, huang hai yan, liu jian jun
Abstract:
Objective：To investigate the combined effect of CdCl2 and nicotine on the cell cycle and apoptosis of mouse spermatogonium(GC-1).Methods：CCK-8 assay was used to detect the inhibition of GC-1 cell proliferation in the CdCl2 groups, the nicotine groups, and the combined groups at 24 hours. Flow cytometry was used to detect the effects of the CdCl2 groups, the nicotine groups, and the combined groups at 24 hours on the cell cycle and apoptosis of GC-1 cells. Results：The inhibitory effect on the proliferation of GC-1 cells was increased with the rise of CdCl2 and nicotine concentrations , the IC50 values of CdCl2 and nicotine alone was 5.409μmol/L, 2814μmol/L. When CdCl2 and nicotine were used in combination, the IC50 value of GC-1 cells was 4.422 μmol/L for 0.175 mmol/L nicotine, 4.532 μmol/L for 0.35 mmol/L nicotine, 3.309 μmol/L for 0.7 mmol/L nicotine, and 2.532 μmol/L for 1.4 mmol/L nicotine ,all of which were lower than that of the groups in which CdCl2 was used alone. The combination of CdCl2 and nicotine had a synergistic effect. At a CdCl2 concentration of 2.5 μmol/L, the IC50 concentration of the combination group was lower than that of nicotine alone. The results showed that percentage of G0/G1 phase cells was decreased in the 2.5 μmol/L CdCl2 group and 1.4 mmol/L nicotine group; compared with the CdCl2 groups and the nicotine groups, percentage of G0/G1 phase cells was decreased in the CdCl2 and nicotine combination groups; percentage of G2/M phase cells was increased in the 2.5 μmol/L CdCl2 group, and compared with the CdCl2 groups and nicotine groups, the cells were blocked in G2/M phase in the combined groups. Combined effects of CdCl2 and nicotine on the cell cycle had a synergistic effect , and the effect of CdCl2 on the synergistic effect was stronger. Proportion of cell apoptosis was increased in 2.5μmol/L CdCl2 group. Compared with the CdCl2 groups and the nicotine groups, percentage of cell apoptosis in the CdCl2 and nicotine combined groups were increased significantly, and the effect of CdCl2 was stronger for the synergistic effect. Conclusion：Combination of CdCl2 and nicotine had a synergistic effect on mouse spermatogonium(GC-1) which could lead to enhanced cytotoxicity, G2/M cell cycle arrests, and cell apoptosis. And CdCl2 was the main effect factor of synergistic effect.
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Molecular mechanism of autophagy mediated by AKT/mTOR pathway involved in exercise rehabilitation of rotator cuff tear-related muscle atrophy
Abstract:
objective: To explore the molecular mechanism of autophagy mediated by protein kinase B(AKT)/ mammalian target protein of rapamycin (mTOR) pathway in the rehabilitation of muscle atrophy associated with rotator cuff tears (RCTs). Methods: Forty male C57 mice were randomly assigned to the following four groups: sham group, RCTs group, RCTs+ exercise group and RCTs+ exercise+rapamycin group, with 10 mice in each group. At the eighth week after grouping, the healing of bone-tendon interface and muscle cell atrophy were analyzed by histology. The mRNA expression levels of muscle atrophy related genes (Atrogin-1, Bnip 3, MuRF-1) in supraspinatus muscle tissue were measured by real-time quantitative reverse transcription polymerase chain reaction. The expression of LC3 and AKT/mTOR signal pathway in supraspinatus muscle tissue of different groups was detected by western blot, and the production of autophagy in each group was analyzed by transmission electron microscope. Results: Compared with sham operation group, the maturity score of bone-tendon interface at supraspinatus tendon anchorage and the cross-sectional area of supraspinatus muscle fibers in RCTs group decreased significantly (P<0.001), and the muscle loss and the expression of Atrogin-1, Bnip 3 and MuRF-1 genes increased significantly (P<0.001). Compared with RCTs group, RCTs+ exercise group significantly increased the bone-tendon interface maturity score and the cross-sectional area of supraspinatus muscle fibers (P<0.01), and decreased the muscle loss and the expression of Atrogin-1, Bnip 3 and MuRF-1 genes (P<0.01). Compared with the sham group, the LC3Ⅰ/LC3Ⅱ and number of autophagy in supraspinatus muscle of RCTs group increased significantly (P<0.001), while the p-Akt/Akt, p-mTOR/mTOR decreased significantly (P<0.01). Compared with RCTs group, the LC3Ⅰ/LC3Ⅱ and number of autophagy in RCTs+ exercise group decreased significantly (P<0.01), and the number of p-Akt/Akt and p-mTOR/mTOR increased significantly (P<0.001). The addition of rapamycin significantly inhibited the improvement of exercise on bone-tendon interface healing, muscle atrophy and loss, AKT/mTOR signaling pathway and autophagy number induced by RCTs. Conclusion: This study confirme the anti-atrophy effect of exercise rehabilitation in RCTs diseases, and its mechanism is related to activating AKT/mTOR signal to inhibit autophagy.
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The overview of traditional Chinese medicine in regulating the mechanism of regulatory cell death in vascular dementia
Abstract:
Vascular dementia (VD) is a neurodegenerative disease caused by brain injury, the research on the process of its occurrence is not yet in-depth. The regulatory all death (RCD) mechanism is related to the pathological mechanisms of VD, including apoptosis, pyroptosis, autophagy, ferroptosis, and copper mediated cell death proposed in recent years. Therefore, explain the role between the mechanisms of regulatory death and the pathological mechanisms of VD, is of beneficial for the study of VD. The article provides a review of the roles of five mechanisms of RCD in VD, and summarizes the recent research progress in the treatment of VD with traditional Chinese medicine, in order to development of new traditional Chinese medicine drugs.
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Research progress on animal models of malignant mesothelioma
YONG Sheng, JIN Dacheng, dong xin chun, GOU Yunjiu
Abstract:
Malignant mesothelioma cases are rare and have a long incubation period, making it difficult to conduct clinical research.? Animal models of malignant mesothelioma are crucial for experimental research and elucidating the pathogenesis for malignant mesothelioma. Common animal models include spontaneous, inducible, transplantable, and genetically engineered models, but the applicability of different animal models varies. This article reviews studies related to the establishment of animal models of malignant mesothelioma in the past 10 years and summarizes the recent progress in the establishment of four animal models of malignant mesothelioma from three aspects: modeling methods, modeling results, and model advantages and disadvantages. This review summarizes and analyzes the current progress in the establishment of inducing animal models of malignant mesothelioma, this provides a reference for malignant mesothelioma basic research using animal models.
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The effect of ovariectomy on cognitive function and hippocampal estrogen receptor expression in APP/PS1 mice
congchao, Gu zuxi, Wu panqing, Chen siru, Lin guangyao, Xu lianwei
Abstract:
Abstract: Objective: The present study aims to observe the changes in Aβ deposition and estrogen receptor levels in the hippocampal tissue of female APP/PS1 mice with Alzheimer's disease (AD) after ovariectomy (ovx) at different ages. Method: 3-month-old APP/PS1 female mice were divided into 3 groups, with 20 mice in each group. 10 mice in each group were treated with bilateral ovarian resection via abdominal surgery as the model group. 10 mice in the control group (sham group) were treated with only equivalent volume fat removed from the corresponding area during surgery as the control group (sham group). Feed APP/PS1 mice at different ages for 3 months, 4 months, and 5 months as the 6-month, 7-month, and 8-month age groups. Evaluate the cognitive function of APP/PS1 mice at different ages using Morris water maze. Observe the morphological changes of intracellular organelles in the CA1 area of the hippocampus of the two groups of mice using transmission electron microscopy. Immunofluorescence staining is used to detect the deposition of Aβ in the CA1 area of the hippocampus of the two groups of mice. ELISA is used to detect the levels and contents of serum estrogen, ROS, SOD, and MDA, and Western blot is used to determine the expression levels of ERα and ERβ. Result: As the age increased, the escape latency of the ovx group mice in the water maze test gradually prolonged, the deposition of Aβ in the hippocampal CA1 area increased, the mitochondrial swelling of hippocampal neurons increased, and a large amount of lipofuscin and amyloid deposition were observed in the cytoplasm. The serum estradiol level and SOD activity decrease, while the ROS level and MDA content increase. The expression of ERα and ERβ in hippocampal tissue decreases. Conclusion: Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβ deposition and age-dependent cognitive decline.
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The Effect of Western Dietary Feed on the Model of Atherosclerosis in APOE Mice
Abstract:
Objective To study the rapid modeling of Western dietary feed and its impact on biological indicators and histopathology in APOE-/- mice.Methods Using 48 female、48 male APOE-/- mice, 48 female、48 male C57BL/6J mice was tested and divided into 8 groups, namely the APOE-/- ordinary breeding feed group (24 female and 24 male each）、 APOE-/- Western Dietary Feed Group (24 female and 24 male each）、 C57BL/6J ordinary breeding feed group (24 female and 24 male each）、C57BL/6J Western Dietary Feed Group. Feed from 3w until the end of the experiment at 20w. After the experiment, serum was collected for biochemical indicators, and the aorta was separated for gross oil red staining and analysis. The root of the aorta was paraffin sectioned and HE stained. Results Western diet did not significantly increase APOE- / -body weight, western diet could significantly improve the blood lipid index of APOE- / -mice, total cholesterol, low density lipoprotein, high density lipoprotein, promote the formation of atherosclerotic plaque, male mice are suitable for the modeling of gross aortic plaque, and female mice are suitable for plaque modeling of aortic arch root. Conclusion Western dietary diet can promote APOE- / -mice, increase the aortic plaque area ratio, shorten modeling time, and improve modeling uniformity.
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Screening of antidiarrhea active parts and study on the “spectrum-effect” relationship of salt-processed Alpiniae oxyphyllae Fructus -Foeniculi Fructus medicines
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Objective To screen the antidiarrheal active components of salt-processed Alpiniae oxyphyllae Fructus -Foeniculi Fructus medicines (YZYH), and speculate on its pharmacological substance basis and quality markers through the study of the “spectrum-effect” relationship. Methods A model of diarrhea due to spleen and kidney yang deficiency was established in rats, and the pharmacodynamic indexes of YZYH on petroleum ether, ethyl acetate, and water fractions were measured, including behavioral indicators such as body weight, anal temperature, diarrhea incubation period, diarrhea index, and biochemical indicators such as NOS, cGMP, and CPK; Establish HPLC chromatograms of different parts of YZYH, and use grey correlation method to analyze the “spectrum-effect” relationship between the chemical components of each part of YZYH and the antidiarrheal efficacy indicators. Results In the aspect of pharmacodynamics, the ethyl acetate fraction had a better regulatory effect on the activities of DIP, DI, and serum NOS, cGMP, CPK in model rats compared to other treatment groups; In terms of the study of the “spectrum-effect” relationship, the correlation between components such as anisaldehyde and chromatographic peak 4 with the five efficacy indicators of DIP, DI, NOS, cGMP, and CPK was strong. Conclusion The ethyl acetate fraction was the active anti diarrhea fraction of salt-processed Alpiniae oxyphyllae Fructus -Foeniculi Fructus medicines. Its mechanism may be realized by regulating gastrointestinal peptide hormones such as MTL and GAS, inhibiting gastrointestinal hyperfunction, regulating energy metabolism and immunity, and cytoprotection; The ingredients such as anisaldehyde and peak 4 served as the material basis for its antidiarrheal effect, and anisaldehyde and peak 4 could be used as quality indicators for the medicines.
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Exploring the analgesic initiation mechanism of tuina on the dorsal root ganglion of minor CCI model rats via the TRPV1/TRPA1 -cGMP signaling pathway
Abstract:
Objective: To explore the analgesic initiation mechanism of the three-manipulation and three-acupoint of tuina on rats with minor CCI model. Methods: 56 SD rats were randomly divided into 8 groups: normal group, sham group, model 1 group, model 2 group, tuina 1 group, tuina 2 group, tuina 1 + TRPA1 antagonist group, and tuina 2 + TRPV1 antagonist group. The model group, tuina group, and tuina + antagonist group were established with minor CCI models. The tuina group and tuina + antagonist group received the three-method three-point intervention (point method, dial method, kneading method, Yinmen point, Chengshan point, Yanglingquan point) 7 days after modeling. The model group and sham group were subjected to grasping restraint, and the normal group was not intervened. After the intervention, each group was tested for changes in thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) to detect different types of pain. The nitrate reductase method was used to observe the NO content in the DRG of each group on the modeling side, and ELISA, Western blot, qPCR, and other methods were used to observe the changes in the protein and gene expression of the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway in the DRG of each group on the modeling side. Results: Compared with the model group, behavioral testing showed that the MWT and TWL were prolonged to varying degrees in the tuina 1 group and tuina 2 group. The expression of TRPV1, TRPA1, NO, sGCβ, cGMP, and PKG1 in the DRG of the tuina 1 group, tuina 2 group, tuina 1 + TRPA1 antagonist group, and tuina 2 + TRPV1 antagonist group were significantly decreased. Conclusion: Tuina intervention can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one intervention. Tuina can exert immediate analgesic effects through the TRPV1/ TRPA1-NO-cGMP-PKG signaling pathway.
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Establishment of intestinal polyps animal model with Apc-KRAS-Cre genetic mutation
TAN WEI SHAN, WANG SHU YUN, WANG HAO YUE, SUN KE XIANG, GAO JIA MIN, DENG WAN LI
Abstract:
Abstract: Objective To create the mice model of colorectal polyps with Apc-KRAS-Cre gene mutation with the best tamoxifen induction method. Methods C57CL/6J mice were used as healthy control group. Genetically mutated mice were grouped and intraperitoneally injected with tamoxifen of different concentration and dosage for different durations. The survival rate and change in weight of mice were observed. 4 weeks post-tamoxifen induction, mice were euthanized and the length of colons, amount and size of intestinal polyps were observed. Through H&E staining, the histopathological changes of the intestinal tissue and polyps were observed. Results The survival rate of male mice is higher than that of female mice(P<0.05), while the survival rate between the 4 groups shows statistical significance(P<0.05). When compared to the healthy control group, the changed in weight and the length of the colons of each group of mice showed statistical significance（P<0.001）, (P<0.05), the difference in weight change between group 1 and group 2, group 2 and group 3, group 1 and group 4; the difference in length of colons between group 1 and group 3 showed statistical significance (P<0.05). Each group of mice induced by tamoxifen injection showed intestinal polyps of varying sizes, mostly occuring on the distal end of the colon, while those in group 3 and group 4 have a higher amount and larger polyps. Comparing to healthy control group, histopathology of tamoxifen-induced mice showed growth of intestinal polyps, with uneven and misaligned glandular and epithelial arrangements, loosely-packed intestinal mucosal barrier and irregularly-distributed crypts, group 3 and group 4 mice showed signs of inflammation, while regions of group 4 showed necrosis of cells. Conclusion Tamoxifen-induced Apc-KRAS-Cre mice models have been successfully established, with group 3 induction method being the most suitable.
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The method and improvement of implantable osmotic pump for intraventricular drug administration in rats
SUN Heyong, ZHANG Gangli, WU Jiliang, CAO Peili, LI Shuo, SUN Haoqin
Abstract:
Objective To introduce and enhance the experimental technique for intraventricular drug delivery via an implantable osmotic pump. Methods Eight-week-old male SD rats were selected, and the requisite equipment and reagents were prepared. Initially, the osmotic pump was assembled and brought to operational status before conducting the implantation surgery. Following anesthesia, the animals underwent skin preparation, and the skull's upper surface was surgically exposed. Utilizing a brain stereotaxic apparatus, a point directly above the ventricle was located, and a small hole was drilled at that location with a high-speed cranial drill. Subsequently, the pump body was implanted subcutaneously in the neck, the needle was inserted into the drilled hole, and secured with dental cement. Once solidified, the needle base was removed, the subcutaneous soft tissue and scalp were sutured in layers, and the animal was returned to its cage for isolated rearing. Results The osmotic pump was successfully implanted subcutaneously in the rat's neck, the needle was securely affixed to the skull, and the catheter interface remained intact. Upon examination of the extracted brain tissue, no significant hematoma was observed around the puncture site or needle tract, and the presence of blue dye in the ventricular and adjacent tissues indicated successful drug delivery to the ventricle. Conclusion The introduction of a brain stereotaxic apparatus for localization assistance, coupled with enhancements to the operational procedure, has rendered the implantation process more accurate and safe, achieving a high success rate in intraventricular drug administration.
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The positive effect of the good operation of the CNAS-CL06 system on the scientific nature of animal experimental
maliying, wanghong, guomeng, liangchunnan, yuebingfei, gongwei
Abstract:
The animal laboratory of pharmaceutical and biological product inspection and testing institutions undertakes important basic support tasks for testing and scientific research work. This article summarizes the management experience accumulated in the operation of our institution's CNAS-CL06 quality management system, providing reference for similar institutions in operation to ensure the scientific nature of animal experimental data. In order to ensure the scientific nature of animal experimental data, the experimental animal institution has successfully passed the CNAS accreditation of the experimental animal institution, and has completed rectification on time during on-site supervision and evaluation. At the same time, regular self inspections of the system have been carried out in accordance with the "Quality and Capability Accreditation Guidelines for Experimental Animal Breeding and Use Institutions" (CNAS-CL06). During the self inspection process, we examined issues while improving the content of the system. Starting from animal procurement, occupational health and safety, animal disease treatment and care, and facility operation emergency drills, we enriched the content of the quality management system, ensured the continuous and effective operation of the system, and ensured the effectiveness and standardization of animal experiment data. At the same time, we contributed to the management ideas of our institution in sharing animal experiment platforms, Provide hardware and software support for the construction of cloud platforms for animal experiments. This article aims to explore and form a quality management model for the experimental animal industry based on practical work, Being focused in the standardization strategy， continue to deepen the reform of standardization work, and give full play to the basic and strategic role of standardization in the modernization of the animal experiments system.
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Management and experience exchange of three-level laboratory of animal biosafety in University
Abstract:
Animal Biosafety Level 3 laboratory (Absl-3) is the basic supporting platform of the national biosafety system for new and recurrent infectious diseases, it provides an important hardware basis for the study of biological characteristics, prevention and treatment of highly pathogenic microorganisms. ABSL -3 laboratory also provides an important support for the combination of production, teaching and research. The normal operation of ABSL -3 laboratory and the smooth development of scientific research work can not be separated from the careful planning and effective implementation of emergency planning work. In addition, the reasonable design and layout of the laboratory is also a key factor to avoid and reduce accidents. Based on the practice of construction and management of animal biosafety level III Laboratory in Yangzhou University, starting with the preparation of emergency plan, this paper introduces the points for attention in the layout of laboratory construction, daily operation and emergency treatment, it is expected to provide useful reference for biosafety laboratories operating various pathogenic microorganisms in the future.
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Research progress on the mechanism of miR-138-5p in osteoarthritis
Wu Liangbin, Weng Jian, Li Aikang, Qi Tiantian, Zhang Geng, Zeng Hui, Yu Fei
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MiR-138-5p, as a microRNA, plays an important regulatory role in the pathogenesis of osteoarthritis. It regulates various biological processes such as inflammation, cell apoptosis and proliferation, and matrix degradation in osteoarthritis by modulating signaling pathways including NF-κB, Wnt/β-catenin, and PI3K/AKT. This review summarizes the research progress on the mechanism of miR-138-5p on osteoarthritis.
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Preliminary Discussion on the Existing Issues of Ethical Review of Laboratory Animals Welfare in Medical Research
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Laboratory animals have played an important role in maintaining human health. Advocating ethics and welfare of laboratory animals is a dual manifestation of technological progress and human civilization, and establishing ethical review of laboratory animals welfare is an effective guarantee for achieving the welfare of laboratory animals. Although the construction of animal welfare ethics in China has developed rapidly in recent years, there are still many problems that need to be continuously improved at this stage. This article is based on the understanding and recognition of the ethical concepts related to the welfare of laboratory animals. It summarizes and discusses some issues discovered during the ethical review of laboratory animals welfare in medical research, and puts forward personal suggestions for exchange and mutual refrence.
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Research progress of the role of ferroptosis in infectious diseases
YUE Linzhi, MA Tao, DAI Yumei, DU Wenya, WANG Guofu, WU Lixian
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Ferroptosis is a newly discovered mode of programmed cell death characterized by the accumulation of intracellular iron-dependent lipid peroxidation. At present, the research on ferroptosis mainly focuses on the field of cancer, but more and more evidence shows that ferroptosis is related to the occurrence of infectious diseases, and ferroptosis has been found in Corona Virus Disease 2019, tuberculosis and cryptococcal meningitis and other diseases. This article reviews the role of ferroptosis in infectious diseases, in order to provide new ideas for the prevention and treatment of ferroptosis related infectious diseases.
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Oxidative stress-based exploration of the zebrafish in cardiovascular disease and research progress
Fei Tiantian, Liang Tengyun, Wu Hong
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Cardiovascular disease has been a serious threat to human life, and oxidative stress is an important factor in the occurrence and development of cardiovascular disease. The construction of reliable animal models of oxidative stress is helpful for in-depth study of the pathogenesis of cardiovascular diseases and the development of therapeutic drugs. Zebrafish, with the advantages of easy reproduction, short developmental cycle, transparent embryos for easy observation, and highly homologous cardiovascular gene background with humans, has often been used in recent years for research related to the field of cardiovascular diseases. In this paper, we focus on the application of zebrafish oxidative stress model in cardiovascular disease and the related research progress, which provides reference for its further application in cardiovascular disease related research.
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Effects of ezrin protein on Helicobacter pylori-induced nodular gastritis
Wang Peng, Zhu Hong-wei, Jiang Shuy-uan, Liu Xiao-lei, Gao Bin, Shao Guo
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The ERM protein family (ezrin, radixin, and moesin) plays a pivotal role in cell morphology, migration, and signal transduction. Ezrin, a prominent member of this family, is highly involved in these processes. Particularly, the phosphorylation of ezrin is crucial, as it regulates the interaction between ezrin and the actin cytoskeleton. This interaction is a key mediator of cytotoxicity in host cells infected with Helicobacter pylori, significantly impacting cell morphology. This review comprehensively summarizes the multifaceted role of ezrin protein in Helicobacter pylori-induced nodular gastritis. It delves into the relationship between ezrin"s structure, function, phosphorylation, and signaling pathways in the context of nodular gastritis. Moreover, this paper highlights ezrin protein as a potential therapeutic target, offering novel insights for the prevention and treatment of nodular gastritis.
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Research progress on mitochondrial-associated membranes (MAMs) in the pathogenesis of Alzheimer's disease
liushiyu, xuyumin, xuhongcai, lufangmei
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Mitochondrial-associated membranes (MAMs) is a special domain for communication and material exchange between mitochondrial outer membrane and endoplasmic reticulum membrane, which performs various biological processes of cell life activities under different conditions. MAMs dysfunction-mediated calcium homeostasis imbalance, endoplasmic reticulum stress, mitophagy defects, mitochondrial fission/fusion dynamics imbalance, lipid metabolism disorders, and inflammatory responses are the key pathogenesis of Alzheimer’s disease (AD). This article reviews the structure and function of MAMs, their involvement in AD pathology and drug intervention targets, and discusses the role of MAMs in the pathogenesis of AD and the latest mechanism research progress, in order to provide new ideas for the prevention and treatment of AD.
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Research progress on Mitochondrial Damage in Inflammatory Bowel Disease
WU Xiaoting, XUAN Ang, SHEN Juan
Abstract:
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract that poses a significant threat to human health. The pathogenesis of IBD remains unclear and is believed to involve various factors such as genetics, immune dysregulation, and environmental triggers. In recent years, increasing evidence has highlighted the role of mitochondrial damage and dysfunction in the development of IBD. This review provides a comprehensive review and overview of studies related to mitochondrial damage in inflammatory bowel disease, focusing on the effects of mitochondrial oxidative stress damage, autophagy dysfunction, kinetic disturbances, and respiratory defects on IBD. The aim is to identify potential therapeutic targets and provide new insights for the scientific prevention and treatment of IBD.
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miR-22-3P targets GSDMD to inhibit homocysteine induced pyroptosis of vascular smooth muscle cells
ZHONG Yingyi, Ding Ning, Wang Yicheng, Liu Chao, Ma Shengchao, Xiong Jiantuan, Hao Yinju, Bai Zhigang, Jiang Yideng
Abstract:
Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells induced by homocysteine. Method Human vascular smooth muscle cells (VSMC) were cultured in vitro and divided into the Control group (0 μmol/L Hcy) and the Hcy group (100 μmol/L Hcy). After intervention, Western Blot was performed to detect the expression of Pro Caspase-1, GSDMD, N-GSDMD and NLRP3. The qRT-PCR was used to measure the expression of miR-22-3p. ELISA was utilized to survey the concentration of IL-1β and IL-18 in the supernatant. After transfection with control of miR-22-3p (miR-22-3p-NC) ，mimic of miR-22-3p (miR-22-3p-mimic) , and inhibition of miR-22-3p (miR-22-3p-inhibitor) ， to observe the change of VSMC pyroptosis induced by homocysteine. Result Compared with Control group, the expression levels of Pro Caspase-1, GSDMD, N-GSDMD, NLRP3 in VSMC of Hcy Group were increased (P<0.05) , the concentration of Il-1β,IL-18 were higher (P<0.01) , and the relative expression level of miR-22-3p was lower (P<0.01) . After transfection with miR-22-3p-mimic, the expression levels of Pro Caspase-1, GSDMD, N-GSDMD and NLRP3 in VSMC decreased significantly (P<0.01) , and the concentrations of il-1β and IL-18 decreased significantly (P<0.01) . After transfection with miR-22-3p-inhibitor, the expression levels of Pro Caspase-1, GSDMD, N-GSDMD and NLRP3 in VSMC increased significantly (P<0.01) , and the concentrations of il-1β and IL-18 were higher (P<0.05) . Conclusion miR-22-3p delayed Hcy induced VSMC pyroptosis.
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Dioscin promotes apoptosis of HepG2 cell through inhibiting Wnt/β-catenin signaling pathway
Abstract:
Objective ?To detect the effects of apoptosis on HepG2 cell induce by Dioscin and its possible mechanism of anti-hepatocellular carcinoma. Methods The HepG2 human hepatocellular carcinoma cells were exposed with 0.25,0.5,1,2,4,6,8 μmol/L dioscin, and then the cell proliferation ability was measured with
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Evaluation of pulmonary arteriolar lesions in rats induced by cigarette smoke exposure combined with Klebsiella infection
REN Zhouxin, ZHAO Peng, LI Jiansheng
Abstract:
Objective To analyze the morphological and structural changes of pulmonary arterioles in rats induced by smoke exposure combined with Klebsiella infection, and to evaluate the severity of pulmonary arteriolar lesions. Methods Pulmonary arteriolar images of lung sections of control rats and model rats induced by smoke exposure combined with Klebsiella infection were analyzed by qualitative and quantitative methods. Victorian blue stained sections were used for the detection of pulmonary arteriolar muscularization, vascular wall thickness, vascular occlusion score, intima thickness and media thickness of muscular arterioles, and neointima proliferation. HE stained sections were used for the observation and detection of inflammatory cell infiltration and plexiform lesions around arterioles. VG stained sections were used for the observation of collagen fibers in the intima and detection of the percentage of collagen fibers area in arteriolar wall area. Based on the above results, the degree of pulmonary arteriolar lesions was rated according to the Heath-Edwards criteria. Results For diameter ≤ 50 μm arterioles, compared with the control group, the percentage of non-muscular vessels was significantly decreased, the percentage of muscular vessels was increased, the percentage of partial muscular vessels was not significantly different, the wall thickness of non-muscular vessels and the wall thickness of muscular vessels were significantly increased, and the occlusion scores of both non-muscular and muscular pulmonary arterioles were significantly increased in the model group. For 50 < diameter ≤ 100 μm arterioles, compared with the control group, the percentage of non-muscular vessels was significantly decreased, the percentage of muscular vessels and the percentage of partial muscular vessels were not significantly different, the wall thickness and occlusion score of muscular vessels were significantly increased, the wall thickness and occlusion score of non-muscular vessels were not significantly different in the model group. Compared with the control group, the intimal thickness and media thickness were significantly increased and the perivascular inflammatory infiltration score was significantly increased in muscular arterioles with both diameter of ≤ 50 μm and 50 < diameter ≤ 100 μm of the model group. In the control group (n=9), only one section with neointimal lesion was found with 1.61 % of proliferation degree of neointima. In the model group (n=10), five sections had neointima lesion from 1.04 % to 17.14 % of proliferation degree of neointima, respectively. No plexiform lesions were found in a11 sections. For pulmonary arterioles with diameter of ≤ 100 μm, there was no change in the expression of intimal collagen fibers in the model group compared with the control group, and there was no significant difference in the percentage of collagen fiber area in the vessel wall area. According to the Heath-Edwards criteria, the pulmonary arteriole lesions in the model rats did not reach grade III. Conclusions The model rats show pathological manifestations such as pulmonary arteriolar muscularization, thicking intima and media, and mild to moderate inflammatory reactions around arterioles. The low degree of neointimal proliferation and collagen fiber in the vascular wall and no plexiform lesions suggest that the model is up to grade II lesion according to the Heath-Edwards criteria.
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Progress of animal experimental research on the treatment of Henoch-Schonlein Purpura with TCM
Su Hang, Zhang Shuzi, REN Xianqing
Abstract:
Henoch-Schonlein purpura (HSP) is the most common systemic vasculitis in childhood, which is called "spot toxin", "purpura wind" and "grape plague" in TCM. Modern medical research suggests that the disease is related to factors such as imbalance of cellular and humoral immunity, abnormal secretion of cytokines, disturbance of coagulation and fibrinolysis mechanism, but the exact pathogenesis is still unclear. The incidence of this disease increasing year by year, with a high recurrence rate and a high proportion of kidney damage, which seriously affects the physical and mental health of the[[基金项目] 国家自然科学基金（82374519,U2004107）；河南省青年科学基金项目（232300421309）；河南省中医药科学研究专项（20-21ZY2161） [作者简介] 苏杭（1988-），男，副主任医师，硕士研究生，研究方向：中医药防治小儿肾病及风湿免疫性疾病 Email：362504467@qq.com [通信作者] 任献青（1973-），男，教授，主任医师，博士研究生，研究方向：中医药防治小儿肾病及风湿免疫性疾病 Email：renxq723@163.com ] affected children and poses a great social risk. Numerous studies have shown the clinical efficacy of TCM in treating HSP, but its mechanism of action is not yet completely clear. In recent years, a large number of animal experiments have been carried out to study the efficacy mechanism of TCM with the establishment of animal models of HSP, but there is a lack of a more systematic and detailed reviews. Therefore, the animal experimental literature related to the treatment of HSP with TCM in the past decade were reviewed, and the effects of TCM in alleviating abnormal glycosylation of IgA1, regulating the immune imbalance of Th1/Th2 and Treg/Th17 cell, reducing circulating immune complex, and inhibiting inflammatory responses were compiled and summarized, In order to providing a reference for the further research on TCM for the treatment of HSP and inspiring new research ideas.
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Progress of miRNA in the pathogenesis of pulmonary hypertension
LI Yanjin, XIAO Liying, WU Daoxiong, GUAN Rong, YAN Chunlang, LEI Wen
Abstract:
Pulmonary hypertension(PH) is a progressive disease characterized by pulmonary vascular remodeling. Current treatments for PH remain suboptimal, and there is an urgent need to better decipher the underlying pathomechanisms in order to find new therapeutic targets. miRNA(microRNA) are key components in the post-transcriptional machinery that mediate cellular functions mainly by regulating the expression of downstream target genes. Numerous in vivo and in vitro studies have demonstrated the involvement of miRNA and their regulators in PH development. However, there is no unified conclusion about the mechanism of miRNA regulation of pulmonary vascular remodeling. Therefore, this article provides a review on the mechanisms of miRNA in PH in recent years.
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[ ]Establishment of sterile golden hamster model
GUO ya-xi, duxiaopeng, liukaihui, wangzhaohua, zhuhua
Abstract:
Abstract：【Objective】 A sterile golden hamster model was established by cesarean section purification method.【Methods】The donor female golden hamsterrats selected SPF grade golden hamster, male and female were mated 1:1, and were separated from male rats after meeting the peg. The cage time of the surrogate mothers rats should be one week earlier than that of the donor mothers. The pregnant parturient golden hamsters underwent hysterectomy in a super-clean workbench. at the time of delivery, andThe uterus were transferred into isolation kits for purification. The uterus wasand stripped to obtain the milk mice to be purifiedfor purification, . and sterile Sterile ICR mice and sterile SD rats were respectively used for milk replacement, and transferred to isolation kits for feeding after successful milk separation. The sterility status of feeding isolation kits is tested monthly. 【Results】Three caesarean sections were performed, but the first and second lactation failed. The third milk replacement was successful, and 18 young rats hamsters were obtained with survival rate of 88% and survival rate of 66% after milk release. All of them hamsters were qualified according totested by GB /T 14926.41-2001.【Conclusion】By cesarean section purification technique, sterile ICR mice and sterile SD rats were used for milk replacement to achieve the purpose of microbial purification, and the sterile golden hamster model was obtained.
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Inhibitory effect of 17-DMAG on PD-1 humanized mouse liver cancer transplantation tumor
LI Xiaojuan#, XIU Ye#, LI Xingjie, SUN Yanfeng, LI Ruisheng
Abstract:
Objective Explore the inhibitory effect of 17-DMAG on the growth and angiogenesis of PD-1 humanized mouse liver cancer transplantation tumor. Methods 30 PD-1 humanized mice were selected and human HepG2 cell suspension was injected into the subcutaneous tissue of the right inguinal region of the mice to construct a human liver cancer transplant tumor model. Tumor bearing humanized mice were randomly divided into three groups (10 mice per group): ① model group (injected with 10 mg/kg of physiological saline); ② 17-DMAG group (intraperitoneal injection of 17-DMAG at 25 mg/kg, 3 times/week); ③ The cisplatin group (intraperitoneal injection of 20 mg/kg, 2 times per week), the experiment lasted for 4 week. After injection, the length and short diameter of the humanized mouse transplanted tumor were measured to calculate the volume, and the tumor mass were measured to calculate to calculate the tumor inhibition rate. At the same time, immunohistochemical methods were used to detect the expression of CD31 (tumor microvessel density, MVD) and vascular endothelial growth factor (VEGF) in tumor tissue. Results The tumor volume and mass of the 17-DMAG group and the cisplatin group were significantly reduced compared to the model group (P<0.05), and the tumor inhibition rate of the 17-DMAG group was slightly higher than that of the cisplatin group. However, there was no significant difference in tumor mass, volume, and tumor inhibition rate between the 17-DMAG group and the cisplatin group. The number of MVD labeled microvessels and VEGF expression in the 17-DMAG group and cisplatin group were lower than those in the model group (P<0.05), and the 17-DMAG group was also lower than those in the cisplatin group (P<0.05). Conclusions 17-DMAG can inhibit the growth of humanized mouse liver cancer xenografts by reducing the expression of vascular endothelial growth factor in liver cancer xenograft tissue, thereby inhibiting the generation of tumor neovascularization.
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Research progress of liver fibrosis based on Notch signal pathway
jishaoxiu, zhanghengyao, zhangyuan, wenli
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Liver fibrosis is a necessary pathological process from chronic liver disease to cirrhosis and even liver cancer. The occurrence of liver fibrosis is a highly integrated and dynamic pathological process resulting from the interaction of many cells and cytokines. Notch signaling pathway is an evolutionarily conserved intercellular signal transduction mechanism, which plays an important role in regulating the development and tissue renewal of multicellular animals. More and more studies have shown that Notch signal transduction participates in the formation of liver fibrosis through a variety of ways. Therefore, this paper reviews the role of Notch signaling on cells involved in the formation of liver fibrosis to explain the function of Notch signaling pathway in liver fibrosis.
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Construction and evaluation of an immunosuppression-mediated model of invasive Aspergillus niger lung disease in rats
TANG Zining, CHEN Xiangchi, LIU Xuewu, ZHOU Zhimin, LI Qiao, XIAO Sa, JIANG Dejian, PENG Dongdong
Abstract:
Abstract: Objective This study establishes a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies. Methods Sixty SD rats were randomly divided into a normal control group, a cyclophosphamide control group, and a cyclophosphamide + fungal infection low, medium, and high dose group, with 12 animals in each group. General clinical observations were performed daily, and the serum levels of immunoglobulin G (IgG), immunoglobulin M (IgM) and serum galactomannan (GM) were detected by ELISA on the 3rd and 7th days of modeling, respectively, as well as the ratio of CD4+ and CD8+ cells and the content of white blood cells (WBCs) and neutrophils (Neu) in peripheral blood, and the load of Aspergillus niger in alveolar lavage were observed simultaneously and morphological changes of rat lung tissue. Results The rats in the cyclophosphamide control group and the cyclophosphamide+fungal infection group showed reduced voluntary activity and erect hair after modeling, and the rats in the cyclophosphamide+fungal infection group were accompanied by shortness of breath and audible wet rhonchi in the lungs; compared with the normal control group, the rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+, WBC, Neu, IgG and IgM in the blood, and the proportion of CD8+ was significantly higher (P<0.05, P<0.01); compared with the cyclophosphamide control group, rats in the cyclophosphamide+fungal infection group showed significant decreases in blood levels of CD4+, WBC, Neu, IgG, IgM, and significant increases in levels of CD8+, GM, and the alveolar lavage load of Aspergillus niger (P<0.05, P<0.01); and the lung tissues of the cyclophosphamide+fungal infection rats in the low-, medium-, and high-dose groups showed mycelial distribution and destruction of alveolar epithelium, increase of bronchial epithelial cup cells in the alveoli, and infiltration of inflammatory cells, and the degree of lesions was positively correlated with the modeling dose. Conclusion In this study, we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease, and the duration of the disease was positively correlated with the concentration of the bacterial fluid and the modeling time, which confirms that the cellular immunity plays an important role in the pathogenesis of the disease, and at the same time the immunoglobulin can also affect the development of the disease process of invasive pulmonary aspergillosis, and it is speculated that the pathogenesis of invasive pulmonary aspergillosis may be related to the level of immunoglobulin in the humoral immunity.
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Educational reform of animal experiment course for medical graduate students: cultivating students" ability of active learning and innovative thinking
Abstract:
Animal experiment course is an important practice teaching link in medical and life science. It is of great significance to the cultivation of students' experimental skills, scientific thinking and innovative ability. However, the traditional teaching method of animal experiment course has the problems of single content and low participation of students. In order to promote students' active learning and innovative thinking, this paper aims to discuss the teaching reform of animal experiment course. Firstly, the paper introduces the background and significance of the teaching reform of animal experiment course and emphasizes its importance to the cultivation of students' ability. Secondly, it puts forward the principles of teaching reform of animal experiment course, including student-centered, paying attention to problem solving and practice exploration, and promoting interdisciplinary integration. Then, from the aspects of course design, teaching methods and evaluation methods, this paper expounds the concrete measures of teaching reform of animal experiment course in detail. In the course design, attention should be paid to the selection of challenging and exploratory experimental projects, and students' interests and professional needs should be fully considered. On teaching methods, students should be encouraged to actively participate in, exploration and cooperation, and guide them to problem solving and the cultivation of innovative thinking. In terms of evaluation methods, diversified evaluation methods, such as experimental report, group discussion and project presentation, should be used to comprehensively evaluate students' comprehensive ability and innovative thinking. Finally, through practical verification and effect evaluation, the experience and results of the teaching reform of animal experiment course were summarized, and suggestions for further improvement were put forward.
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Progress of mitochondrial mass control system in the pathogenesis of septic cardiomyopathy
xie you cheng, xiao shu fang, lin xue mei, chen shun, yu xiaohui
Abstract:
Septic cardiomyopathy (SIC) is a frequently observed organ dysfunction in sepsis, characterized by high mortality and poor prognosis. Understanding the complex pathogenesis of SIC and developing effective therapeutic tools are critical issues that require attention. Previous studies have demonstrated the significant role of mitochondrial dysfunction in the development of SIC. In the presence of SIC and resulting mitochondrial dysfunction, aberrant regulation of the mitochondrial quality control system (MQC) can exacerbate cardiomyocyte injury. Recent studies have demonstrated that the mitochondrial quality control system (MQC) maintains mitochondrial dynamic homeostasis through its regulation of mitochondrial biogenesis, fusion/fission, and autophagy. Consequently, this article provides an overview of the role of MQC in SIC pathogenesis, reviews the latest studies, and analyzes its potential as a therapeutic target.
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Animal Model Analysis of Atherosclerosis Based on Clinical Symptoms in Traditional Chinese Medicine and Western Medicine
Abstract:
Objectives Based on the clinical characteristics of atherosclerosis in? traditional Chinese medicine (TCM) and Western medicine, this paper analyzes the common animal models of atherosclerosis(AS), and the coincidence of the models with clinical characteristics was scored, in the hope of providing new ideas and reference for studying animal models of AS. Methods This paper reviewed the varieties, modeling methods, modeling principles and characteristics of common animal models of AS. Moreover, according to the clinical diagnostic criteria and symptom characteristics, the similarity of the common animal models was analyzed. Results High-fat feeding type, mechanical injury combined with high-fat feeding type, genetic engineering combined with high-fat feeding type, chemical induction combined with high-fat feeding type and the models of AS combining Chinese clinical syndrome and western disease are widely established in animal models of AS. Comparative analysis result showed that balloon injury combined with high fat feeding type, ApoE receptor knockout mouse combined with high-fat diet type and phlegm and blood stasis type in models of disease and symptom combination showed a comparatively high level of clinical agreement between Chinese and western medicine. Conclusions Presently, most of the animal models of AS had the high degree of coincidence with western medicine, evaluation criterion is dominated by the western medicine as well, which lack of the combination between disease and syndrome, so as to hinder development of concept of Wholism and treatment by differentiation of syndromes in TCM. Therefore, establishing the exact and high coincidence degree animal model, which combines the disease and its TCM symptoms, is the top priority of studying the prevention and treatment of atherosclerosis.
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The role of UBC9 mediated SUMO modification in homocysteine-induced pyrodeath of macrophages
Ma Lingju, Chi Hongyang, Wu xinxue, Ma Fujun, Tian Yancheng, Zhao Caiqi, He Tianyu, Peng hongjian, JiangYideng, Yang Li, Huang Hui, Ma Shengchao
Abstract:
Objective To study the role of ubiquitin Conjugating Enzyme 9 (UBC9) in the pyrodeath of homocysteine-induced macrophages mediated by SUMO modification. Methods Firstly, The effects of homocysteine at different concentrations (0μmol/L, 50μmol/L, 100μmol/L, 150μmol/L, 200μmol/L) on the viability and pyrodeath of mouse macrophages (RAW264.7) were detected by CCK-8 and Western blot ;Western blot was used to detect the expression levels of UBC9, SUMO-modified protein SUMO-1 and inflammatory cytokine IL-1β in different groups of cells. qRT-PCR was used to detect the mRNA expression of UBC9 before and after interference, and to detect the expression of UBC9, pyrogen-related protein and SUCO-1 after interference.Results After stimulation with 100μmol/L Hcy, the activity of macrophages was not affected, and the expressions of NLRP3 and caspase-1 were the most obvious (P < 0.05).Compared with Control group, the expression levels of and IL-1β were increased in Hcy group (P < 0.01), and the expression of SUMO-1 was increased (P < 0.01). Compared with Control group, UBC9 protein level and mRNA level in Hcy group were increased (P < 0.05). After transfection with si-UBC9, the expressions of NLRP3, caspase-1, IL-1β, UBC9 and SUMO-1 in si-UBC9+Hcy group were decreased compared with si-NC+Hcy group (P < 0.01). Conclusion Hyperhomocysteamine (Hcy) induces pyrodeath in macrophages, and its mechanism is related to the up-regulation of ubiquitin binding enzyme 9 to SUMO modification.
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Visualization Analysis of Research Progress on Neutrophils in Diabetes Based on Citespace
WANG Jin-xi, YU Rong, HUANG Juan, Liu Yangyang, ZHANG Tian-tian, LI Wei, YANG Hui, LEI Shi-hui
Abstract:
Objective This article aims to clarify the development of neutrophils and diabetes fields, as well as the evolving characteristics, potential trends, and research hotspots of neutrophils in the diabetes field. Methods 2998 relevant literatures on neutrophils in the diabetes field indexed in Web of Science from 2010 to 2023 were retrieved, and visual analysis of the relevant literatures on neutrophils in the diabetes field was conducted using Citespace6.1.R6. Results Since 2012, publications on this topic have grown rapidly. Bayat Mohammad, Liu Tong, Amini Abdollah, Zhang Rui are high-yield authors, with 7 related articles published. China and Shanghai Jiao Tong Univ are the countries and institutions with the most published papers. The most influential journal in this field is "PLOS ONE", cited 1380 times. Literature co-citation analysis shows that the highest focus in topics related to diabetes currently are "extracellular trap" and "covid-19 patient". Co-occurrence analysis, clustering analysis, and keyword burst analysis indicate that "lymphocyte ratio" (13.08) and "neutrophil extracellular trap" (7.2) are the most researched topics in the field of neutrophils and diabetes. Literature in this field mainly focuses on "myocardial infarction", "endothelial", "oxidative stress", and "apoptosis". Conclusion This article analyzes the evolving trends of neutrophils in the diabetes field using Citespace, providing new insights for researchers to conduct future research in the diabetes field.
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Observation on the progress of the murine models of chronic ulcerative colitis induced by dextran sodium sulfate
KONG Weijiao, YAN Yiyue, ZHAO Peikai, MAO Xiaojian, WANG Ting
Abstract:
Objective To investigate the progress of chronic Ulcerative Colitis (UC) model induced by dextran sulfate (DSS) in mice. Methods 2.5% DSS solution were provided ad libitum for 5 days, and tap water for were supplied for another 5 days in one induction cycle. Male C57BL/6 mice were undergone continuous three cycles of induction to establish the chronic UC model. The weight, disease activity index (DAI), organ index, colon length of mice and pathological changes of colon tissue were determined. The level of myeloperoxidase (MPO) in colon tissue, cytokines such as IL-1β in serum and colon were detected. Results During the three cycles, all mice had diarrhea, bloody stool, weight loss, colon length shortening and pathological injury, which were aggravated after DSS administration and relieved after drinking water administration. The content of MPO in colon gradually increased. The spleen index and the levels of IL-1β, IL-6, IL-17A, TGF-β and TNF-α in serum increased continuously or fluctuating. The contents of IL-1β, IL-6 and IL-17A in colon increased significantly in the first or second cycle, and then decreased slowly. There was no significant change in TNF-α in colon. The concentrations of IL-10 in serum and colon fluctuated up and down, and decreased to a level lower than or remained the same as that in normal group at the end of the experiment. Conclusion Chronic UC model can be successfully induced by 2.5%DSS solution, which is characterized by alternating symptoms of "attack-remission". The persistent systemic inflammatory reaction and overactivation of colonic neutrophils reflect the characteristics of recurrent UC to some extent. It can be used as a tool for analying the pathological changes and interrention opportunities of UC, as well as for discovering and evaluating UC therapeutic drugs.
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Research progress of ferroptosis in sepsis-associated acute lung injury
SHI Yanglin, YANG Jianya, CHANG Qingqing, WANG Qianqian, WANG Minghang, LI Suyun
Abstract:
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with an extremely high mortality rate. It is the main risk factor for acute lung injury (ALI). However, the pathophysiology and pathogenesis of sepsis-associated ALI are not fully understood, and effective drugs are extremely limited. Therefore, the urgent task is to explore the pathogenesis of sepsis associated ALI and attempt to discover effective intervention measures to improve the prognosis of sepsis associated ALI patients. In recent years, ferroptosis has been considered closely related to the pathological and physiological processes of sepsis associated ALI, and inhibiting related cell ferroptosis can effectively slow down the occurrence and development of the disease. In this paper, the therapeutic strategies targeting ferroptosis of related cells were reviewed, in order to provide reference for the research on ferroptosis of sepsis associated ALI and provide a new perspective for the treatment of sepsis associated ALI.
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Effect and mechanism of ICAM5 on alcohol dependence behavior of mice
Hu Jiajia, Yang Zhuanfang, Sun Xizhe, Yuan Juanjuan, Cheng Yan, Zhang Yu, Yin LITIAN
Abstract:
【Abstract】 Objective We investigated the effects of ICAM5 in hippocampus of mice alcohol drinking preference, and potential mechanisms. Methods A alcohol two-bottle choice model was developed by 8-week-old male C57BL/6J mice, randomly divided to two groups, the control group and alcohol group. The protein expression of ICAM5 in the hippocampus, amygdala, and medial prefrontal cortex was detected. ICAM5 overexpressed adeno-associated virus was constructed and injected into the hippocampus by stereotaxic method. The expression level of ICAM5 protein in hippocampus was detected by immunofluorescence and Western blot. Then detected the alcohol preference and locomotor activity of mice with the open field test, conditioned place preference experiment, and loss of righting reflex test. Western blot analysis was used to identify neuron F-actin/G-actin ratio. Using Golgi staining, the morphology of dendritic spines was identified. Results In the alcohol two-bottle choice model, the expression of ICAM5 in the hippocampus of mice in the alcohol group was considerably lower than the control group. The specific expression of ICAM5 in the hippocampus of mice was observed by fluorescence microscopy. In the open field experiment, the staying time and moving distance of AAV-ICAM5 group were significantly increased compared with the control group (P < 0.01). In the CPP experiment, the residence time of AAV-ICAM5 mice in the alcohol-paired compartment was significantly lower than that of control mice (P < 0.001). In the lose the righting reflex experiment, overexpression of ICAM5 significantly reduced the sedation latency (P < 0.01), but significantly shortened the duration of sedation (P < 0.001). Compared with the control group, the ratio of F-actin/G-actin in hippocampus was significantly increased after drinking (P < 0.01). But after ICAM5 overexpression, the F-actin/G-actin ratio was significantly decreased (P < 0.001). Compared with the control group, the density of dendritic spines in hippocampal CA1 region was increased after drinking alcohol (P < 0.001), but the density of dendritic spines in AAV-ICAM5+EtOH group was significantly decreased (P < 0.01). Conclusions ICAM5 may modulated the expression of cytoskeleton protein to change structural plasticity of dendritic spines, which contribute to alcohol drinking and locomotor behaviors change of mice.
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Combined with systematic pharmacology and metabonomics to explore the mechanism of baicalein in the treatment of hyperuricemia
liangjingzhen, gaoyingjie, yewenqian, weibingyan, cheenzhaoyang, yangfan
Abstract:
Objective to explore the effect and mechanism of baicalein in the treatment of hyperuricemia. Methods the mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate. The effect and potential mechanism of baicalein in the treatment of hyperuricemia were studied by biochemical indexes, pathological changes, non-target metabonomics and network pharmacology. Results baicalein could reduce the contents of uric acid, creatinine and blood urea nitrogen, reduce the inflammatory injury of renal tissue, up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein. Nine disease-related targets such as BCL2, SIRT1 and XDH were screened by network pharmacology. Six key metabolic pathways including nicotinic acid and nicotinamide metabolism, caffeine metabolism and purine metabolism were screened by metabonomics analysis. Conclusion baicalein can treat hyperuricemia and reduce renal injury, and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.
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Progress in the use of gene editing technologies in the research of immunodeficiency animal models
mayunhui, wangxiaotang, gaojiping, songguohua
Abstract:
Immunodeficiency animal models play an important role in preclinical research and are important experimental tools in modern biomedical research, widely used in immunology, genetics, oncology and microbiology, and other research fields. Gene editing is a technology of targeted modification of biological genomes, from emergence to application, it has greatly promoted the development of biomedical research. Gene editing technology mainly includes homing endonucleases (HEs), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 systems. At present, researchers has used these technology to establish a variety type of immune deficiency animal models, each with its own advantages and limitation. In recent years, a large number of studies have confirmed that the human immunodeficiency animal model can accurately simulate the function of cancer cells, drugs and immune system in human body, and can better simulate human diseases, and is widely used in the study of human immunobiology and the potential mechanism of human complex diseases. In this paper, we reviewed the progress in the research and application of gene editing technology in the construction of immune deficiency animal models, discussed the problems and optimization strategies of gene editing technology in the preparation of immune deficiency animal models in depth, and prospected its future development prospects, in order to provide references for researchers to select and build immune deficiency animal models.
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Extreme animal protectionism and experimental animal welfare ethics
Tian Xuemei, Sachiko Kubo, Wu Yingjie, Su Tao
Abstract:
Experimental animals, as "living reagents", promote the development of life science and medicine, and also make the public pay more attention to the welfare ethics of experimental animals. Experimental animal welfare ethics is not only an important part of animal protection, but also plays an important role in protecting the rights and interests of experimental animals and promoting the rationality and morality of scientific research. However, in the evolution of animal protectionism, some extreme theory such as extreme animal protectionism had also emerged. This article summarized the main theories of animal protectionism and the development of animal welfare ethics and analyzed the main problems of extreme animal protectionism. This article expounds the present situation and problems of experimental animal welfare ethics and puts forward some suggestions to promote the practice of experimental animal welfare ethics, in order to provide references for our country's experimental animal welfare ethics practice and system construction.
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Comparative studies of transcriptomics in two murine liver fibrosis models induced by hepatotoxic chemicals
YAN Ruanyu, WU Hongyu, HUANG Kai, SUN Xin, XUE Jingbo, TAO Yanyan, LIU Chenghai, PENG Yuan
Abstract:
Objective To compare the transcriptomic differences between carbon tetrachloride (CCl4)-induced and Diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) diet-induced mouse models of liver fibrosis in order to provide a framework for future research utilizing mouse liver fibrosis models. Methods Mouse models of liver fibrosis were induced by 10%CCl4 (2ml/kg) injection and 0.1%DDC diet, respectively. After the 4 -week induction, the serum levels of ALT, AST, and TBil were detected. HE and Sirius red staining were observed to analyze the hepatic inflammation and collagen deposition. Jamall's method was used to evaluate the hydroxyproline (Hyp) content in the liver tissues. Hepatic tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured by the elisa kits. Total RNA was extracted from murine liver tissues for RNA sequencing (RNA-Seq). The differentially expressed genes of the two models were analyzed by R software and then GO and KEGG enrichment were analyzed. Then, cwas used to verify the significantly different genes. Results Compared with normal mice, the serum levels of ALT, AST, TBil and the expressions of hepatic TNF-α, IL-6 and IL-1β were significantly increased in mice received CCl4-induction and DDC diet mice respectively, while the serum level of Alb was decreased. Pathological staining showed that the structures of liver tissues were destroyed and a large number of hepatocytes around the central vein were hyalinized and necrotic in CCl4-treated mice. In DDC diet mice, a lot of porphyrins were deposited in the liver and a large number of inflammatory cells were infiltrated in the portal area and the bile duct. Different degrees of collagen deposition were observed in the liver tissues of the two model mice. Different genes(DEGs) of CCl4-treated and DDC-diet mice were screened according to a filter (|logFC|> 2 times and P < 0.05). 1820 and 2373 DEGs in CCl4-treated and DDC-diet were analyzed, including 1302 and 1978 up-regulated genes , 518 and 395 down-regulated genes, respectively. GO annotation showed that the two models had important functions in molecular function (MF), biological process (BP) and cell component (CC). KEGG analysis showed that 22 and 29 signaling pathways were activated in CCl4-induction and DDC diet model, respectively. Among these, 16 signaling pathways such as extracellular matrix receptor interaction, cell cycle, protein digestion and absorption, focal adhesion, and PI3K-Akt were significantly enriched in the two models (P < 0.05). Cluster analysis showed that Mup11, Mup15, Mup17, Mup1 were significantly down-regulated in both models, which were identified by RT-qPCR (P < 0.05). Conclusions This study reported and compared the RNA-Seq transcriptomic characteristics of liver fibrosis models induced by CCl4-induction and DDC-diet, respectively. By observing the locations of gene expression and the pathways regulated by the genes, an example was established for the subsequent selection of animal models to study the pathogenesis and treatment of liver fibrosis.
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Mechanism of Juanxiao decoction regulating type 3 innate lymphoid cells in treating obese asthmatic mice
TIAN Min ping, ZHANG Qing yuan, XIANG Shuang di, CHENG Ling ling, SUN Peng, XUE Han-rong
Abstract:
Objective: Explore the mechanism of Juanxiao Decoction in regulating the type 3 innate lymphoid cells (ILC3s) in the treatment of obese asthma. Method: Sixty male BALB/C mice were randomly divided into a normal group, a model group (High Fat Diet+OVA), and Juanxiao Decoction groups (low-, middle-, and high doses of 8.5, 17, and 34 g?kg-1), dexamethasone group (1 mg?kg-1), with10 in each group. Except for the normal group, other groups were fed high-fat diet for 12 weeks, and OVA sensitization and atomization inhalation were used to establish an obesity asthma model. From the first atomization, the low-, medium-, and high dose groups of Juanxiao decoction and the dexamethasone group were given corresponding drugs by gavage, while the normal group and model group were given equal amounts of saline by gavage for 7 days. Observing the state of each group of mice and changes in typical symptoms of obesity asthma. Within 24 hours after the last challenge, a fully automated biochemical analyzer was used to detect the four items of blood lipids and the classified count of inflammatory cells in alveolar lavage fluid (BALF). Hematoxylin- eosin (HE) staining was used to observe the morphological changes of lung tissue and abdominal fat in mice. Enzyme linked immunosorbent assay (ELISA) for detecting levels of immunoglobulin E (IgE) in BALF and serum of mice, as well as the levels of interleukin-1β(IL-1β)、Interleukin-13(IL-13)and mouse thymus activation regulating chemokine (CCL17) in lung tissue. The levels of IL-17A+ILC3 and IL-22+ILC3 cells in lung tissue and peripheral blood of mice were analyzed by flow cytometry. Western blot was used to detect the expression of P-STAT3 protein in lung tissue. Results: Compared with the model group, the general state and typical obese asthma symptoms in the middle and high dose groups of Juanxiao decoction were obviously improved. Pathological staining showed that the airway inflammatory cells infiltrated and the airway wall thickened in the model group. However, compared with the model group, the lung inflammation in dexamethasone group and Juanxiao decoction group was improved, especially in the middle and high dose groups. The levels of IL-1β, IL-17A+ILC3, IL-13 and CCL17 in lung tissue of mice in model group were higher than those in normal group (p＜0.05), while the proportion of IL-22＋ILC3 and the expression of P-STAT3 were significantly lower than those in normal group(p <0.01,p＜0.05). After the intervention of middle and high dose of Juanxiao decoction, the levels of IL-1β, 17A+ILC3, IL-13 and CCL17 decreased significantly(p＜0.05,p＜0.01,p＜0.001)and the the proportion of IL-22＋ILC3 and the expression of P-STAT3 increased significantly(p＜0.05,p＜0.01,p＜0.001).Conclusion: Juanxiao decoction can alleviate lung inflammation and allergic reaction in obese asthmatic mice, and improve the inflammatory environment of the body, and its mechanism may be related to regulating the secretion of cytokines by ILC3.
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Adra1a regulates LPS-induced inflammation in primary hepatocytes of Lbp-/-mice
MI Chuanliang, FU Bin, LI Sidi, CHEN Zhida, GUO Zhongkun, WANG Kezhou
Abstract:
Objective To Explore the Adra1a regulation of inflammatory response in primary hepatocytes of LBP knockout mice (Lbp-/-) induced by LPS. Method Using two-step perfusion method to extract primary hepatocytes and constracting an primary hepatocyte inflammation model from WT group and Lbp-/- group. Inhibition of Adra1a expression in Lbp-/- mouse primary hepatocytes by adding inhibitor prazosin and transfecting siRNA .The inhibitor method divided the cells into control group (blank control), LPS group (LPS stimulation), and inhibitor piperazine group (LPS stimulation added after 1 hour of prazosin intervention). The method of siRNA transfection divided primary hepatocytes into four groups: control group (blank control), LPS group (LPS stimulation for 12 hours), negative control group (si-NC interference for 12 hours followed by LPS stimulation for 12 hours), and interference group (si-adra1a interference for 12 hours followed by LPS stimulation for 12 hours). The primary hepatocytes of WT mice were divided into two groups: the control group (blank control) and the LPS group (LPS stimulation for 12 hours). This study used WT type and Lbp-/- type mouse primary liver cells as the research subjects to verify the changes of Adra1a under LPS stimulation using Western blot method. Experimental methods such as CCK8, qPCR, and Western blot were used to verify the improvement of inflammation and survival rate of primary liver cells in Lbp-/- mice treated with prazosin and si-adra1a. Results under LPS stimulation, the expression of Adra1a protein in primary hepatocytes of Lbp-/- mice was significantly increased (P < 0.01), while the wild-type did not change; The cell survival rate of the inhibitor prazosin group and the interference group was significantly increased (P < 0.01; P < 0.05); In the inhibitor prazosin group and interference group, the expression of inflammatory factors TNF-α、IL-1β significantly decreased (P < 0.01). The expression levels of proteins p-p38, p-ERK, and p-JNK related to cell damage and inflammation were also significantly reduced (P < 0.01). Conclusion upregulation of Adra1a expression in Lbp -/- mouse primary liver cells induced by LPS compensates for the role of lipopolysaccharide binding protein (LBP) in conducting injury and inflammatory signals, inhibiting the expression of Adra1a gene can significantly reduce the occurrence of inflammation and cell damage in primary liver cells.
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Study on the effect of radiation on mouse salivary gland tissue damage based on NLRP3
wuyuqi, huangguilin, xiaolijun, zhangmin, zhangnini
Abstract:
Objective: To study the effects of radiation on the morphology, function, and NLRP3 expression of mouse salivary gland tissue, and provide new ideas for repairing radiation-induced damage to salivary gland tissue. Methods: To establish a mouse model of radiation-induced submandibular gland injury and record the weight of drinking water. Salivary flow rate was detected, HE staining was used to observe the submandibular gland injury and Immunohistochemistry and real-time PCR were used to detect the expression of NLRP3 and Caspase-1 in the radiation-induced submandibular gland injury of mice at 1, 3, 7 and 14 days after radiation. Results: With the accumulation of time, the amount of water consumed by the radiation group mice gradually increased, the salivary flow rate decreased, and inflammatory cells in the submandibular gland continued to increase. acinar cells gradually showed lesions such as nuclear pyknosis and vacuolization. At 7 and 14 days after radiation, the expression levels of NLRP3 and Caspase-1 protein and gene in the radiation group were significantly higher than those in the normal group (P < 0.05). Conclusion: Radiation can induce damage to mouse submandibular gland tissue and activate NLRP3 inflammasome to increase its expression level.
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Study on the efficacy of 1470 nm semiconductor laser therapy instrument for canine prostatectomy
HUANG Heng, PAN Yongming, HUANG Junjie, ZHANG Hui, YU Chen, CHEN Minli, XU Qingfeng, ZHENG Guo
Abstract:
Objective To evaluate the effectiveness of 1470 nm semiconductor laser therapeutic instrument (referred to as curestar therapeutic instrument) for prostatectomy in Beagle dogs. Method 28 adult male Beagle dogs were randomly divided into 3 groups: sham group (n=3), experimental group (n=15), and control group (n=10). The experimental group was further divided into 3 subgroups: 120 W/50 W, 150 W/50 W, and 160 W/50 W for vaporization cutting/coagulation hemostasis, while the control group was divided into 2 subgroups: 120 W/50 W and 150 W/50 W. 5 in each subgroup. Both the experimental group and the control group underwent canine prostatectomy through the entrance of the bladder neck under electrocision. The operational suitability and effectiveness of the product during surgery were observed. After the operation, the general condition of the dogs was observed, and blood biochemical and hematological indicators were measured at before, immediately, 3 days, 7 days, and 28 days after operation. At 1h and 4 weeks after surgery, B-ultrasound and electric resection were performed under anesthesia to observe the condition of the urethra and prostate, and the prostatic tissue was subjected to H&E staining for pathological observation. The thickness of the coagulation layer at 1h after the operation and the repair of the urethelial epithelium at 4 weeks were analyzed. Results During the operation, the experimental and control groups had good operability and showed good vaporization cutting and coagulation hemostasis performance. After the operation, there were no significant effects on the general condition, blood biochemical, and hematological indicators of the dogs. Ultrasound showed that the urethral expansion was visible immediately after the operation, and the echo of the urethral epithelium was slightly enhanced. At 4 weeks, the prostate tissue was slightly low-echo with uniformly distributed small point-like echoes inside, and the capsule was linearly high-echo, consistent with the sham group. The measurement and analysis showed that the weight of the vaporized prostate tissue in the experimental and control groups was about 0.91-1.33 g, with a resection rate of 17.11-20.27 %. And as the power of vaporization cutting increases, the laser emission time gradually decreases, while the vaporization cutting speed and efficiency both increase.However, there was no significant difference between the experimental and control groups (P>0.05). Under the electrocision microscope, a burn-like change was observed in the surgical wounds of the prostate urethra in the experimental group and the control group at 1 h after surgery, and the boundary between the wound and the normal urothelium was clearly visible. At 4 weeks, the urothelium of the prostate had been repaired and flattened, and the boundary with the surrounding normal urothelium was blurred. Similarly, pathological observations also showed that at 1 h after surgery, both the experimental and control groups showed significant damage to the prostate urethral orifice, with a small amount of carbonization and coagulative necrosis on the surface of the wound, a small amount of inflammatory cell infiltration, and a coagulation layer thickness of about 0.4 mm. At 4 weeks, the prostate urethral morphology of the sham group was normal, while the experimental group and the control group both showed new epithelial growth covering the wound, with uniform thickness and no coagulative necrosis tissue attached to the wound. Mild inflammatory reaction was still present in the surrounding area, fibroblast proliferation was obvious, and stromal and epithelial cell proliferation was visible in the surrounding prostate, some of which showed squamous metaplasia. The prostate capsule was intact and the morphology of the surrounding nerves and blood vessels was normal. Conclusion The curestar therapy instrument is effective for prostatectomy in Beagle dogs, with good vaporization cutting and coagulation hemostasis performance, and there was no significant difference in postoperative physiological indicators compared to the sham group.
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Characteristics燼nd營nnovations爄n燛ducation爋f爈aboratory animal science 爄n燭raditional燙hinese燤edicine燙olleges燼nd燯niversities
ZHANG Min, LIU Yanyun, GU Xin, TIAN Daizhi, YANG Yang
Abstract:
Laboratory animal science plays燼燾rucial爎ole爄n爐he爀ducation燼nd爐raining爋f爉edical爏tudents.燭o爀nsure爐he爀ffective爐eaching爋f爈aboratory animal science爄n燙hinese爉edicine爄nstitutions,爄t爄s爄mperative爐o爄ncorporate爐he爌rinciples爋f燙hinese爉edicine燾haracteristics燼nd爄nnovation.燭his爌edagogical燼pproach燼ims爐o爀nrich爐raditional燾ultural爈iteracy爓ithin燙hinese爉edicine燼nd爁oster爏tudents'燾apacities爁or爄nnovation燼nd燾ritical爐hinking.燭he燿aily爐eaching爋f爈aboratory animal science爏hould爀ncompass爒arious爀ducational燼spects,爄ncluding爄nheritance爀ducation,爀thical爀ducation,爉igration爀ducation,爀xploration爀ducation,爄nspiration爀ducation,燼nd爀xtension爀ducation.燘y爄ntegrating爐hese燾omponents燼nd爀mphasizing爐he爄ntersections爋f燙hinese爉edicine爓ith爈aboratory animal science,爄mportant燼reas爏uch燼s燼nimal爓elfare爄n燙hinese爉edicine爎esearch,爐he燼pplication爋f燙hinese爉edicine爐heories爄n燼nimal爀xperiments,燾onsiderations爁or燼nimal爉odels爄n燙hinese爉edicine,燼nd爐he爏election爋f爀xperimental燼nimal爏pecies,燾an燽e燼ddressed.燗dditionally,爐his燼pproach爌rovides爂uidance爁or爊ew燿evelopment燿irections燼nd燾ultivates爏tudents'爏cientific爎esearch,爄nnovation,燼nd爌ractical燼bilities爀ffectively.燭he爌rimary爋bjective爋f爐his爌rogram爄s爐o爊urture爏cientific爄nnovation燼nd爌ractical燾ompetence燼mong爏tudents爓hile爌rioritizing爐he爏uperior爍uality爋f爄nnovative爀ducation爓ithin爐he燾ontext爋f燙hinese爉edicine.燬uch爀fforts爋ffer燼爏olid爁oundation爁or燼dvancing爄ndigenous爉edical爌ractices燼nd爊urturing燼爊ew爂eneration爋f爌rofessionals燿edicated爐o爌reserving爐raditional爉edicine.
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Effects of acute sleep deprivation on behavior and synaptic biomarker expression in rats at different times
zhangshibin, wang lu, wang chu, guo pengcheng, yan xusheng, huo dongsheng, yang zhanjun, wang yanguo, jia jianxin
Abstract:
Objective: To investigate the effects of acute sleep deprivation on the behavior and synaptic protein expression in rats at different times. Methods: Seventy healthy male Wistar rats were randomly divided into 7 groups, control group, different time sleep deprivation groups (24 hour, 48 hour, 72 hour, 96 hour, 120 hour and 144 hour). The sleep deprivation rat model was established by modified multi-platform water environment sleep deprivation method. Spatial learning and memory was detected by Morris water maze, anxiety was detected by open field test, and the morphology and quantity of hippocampal neurons were observed by Nissl staining. Western blotting and Real-time PCR determined the expressions of synaptophysin (SYN), post-synaptic density protein-95 (PSD-95) and brain-derived neurotrophic factor (BDNF) in rats. Results: Compared with the control group, the numbers of standing and modification all significantly increased accompanied by the prolongation of sleep deprivation time (P<0.05). The escape latency and path length significantly increased in rats in the 120 h and 144 h groups (P<0.05), while the number of crossing platforms and the percentage of target quadrant time all significantly decreased (P<0.01), and were negatively correlated with sleep deprivation time. The expression levels of BDNF, SYN and PSD-95 all significantly decreased accompanied by the prolongation of sleep deprivation time (P<0.01), and was negatively correlated with sleep deprivation time. Conclusion: With the increase of sleep deprivation time, cognitive dysfunction and anxiety gradually deteriorated, which may be related to decrease in expression level of synaptic biomarkers.
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Exploring the mechanism of Inonotus obliquus extract in treating Crohn?s disease based on proteomics
han lihua, Zhao Xiaoru, Peng Lili, Hao Miao, Yuan Hongxia
Abstract:
Objectives To investigate the effect of Inonotus obliquus extract on Crohn's disease and its mechanism by proteomics technology. Methods Crohn's disease (CD) model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). A total of 48 SD male rats were randomized into control, model, mesalazine (225 mg/kg), and low-dose (200 mg/kg), medium-dose (400 mg/kg), high-dose (800 mg/kg) Inonotus obliquus groups. The disease activity index (DAI) score and the colonic mucosal injury index (CMDI) score were assessed after one week of drug intervention. HE staining was used to observe the histopathological changes in the colon, and ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the blood. Proteins were extracted from the colonic tissues of the control group, model group, and Inonotus obliquus extract high-dose group, and bioinformatics analysis was performed for the proteins identified by quantitative proteomics. Finally, WB and RT-PCR were employed to verify the key proteins. Results The Inonotus obliquus extract improved the symptoms of colitis induced by TNBS in rat, and decrease the levels of IL-1β, IL-6, and TNF-α in the blood. Proteomic tests showed that there were 199 differentially expressed proteins (DEPs) between the Inonotus obliquus extract high-dose group and the model group, of which 63 DEPs were related to CD. Bioinformatics analysis showed that these 63 DEPs were mainly involved in NOD-like receptor signaling pathway, calcium signaling pathway, necroptosis, and other pathways. Consistent with proteomic results, expressions of Vdac1 and Trpv2 were confirmed by WB and RT-PCR in colon tissue. Conclusion Inonotus obliquus extract may regulate NOD-like receptor signaling pathway, calcium signaling pathway, and necroptosis by interfering with the expression of Vdac1 and Trpv2, so as to achieve the effect of treating CD.
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The research progress of traditional Chinese medicine treatment of breast cancer depression and co -disease
PENG Mengwei, WU Yaosong, LIU Gaoyuan, KUANG Luoyi, LUO Zilong, CHEN Yulong, LIU Yan
Abstract:
Pathological mood changes, mainly depression, occurring during the diagnosis and treatment of breast cancer are clinically called breast cancer related depression(BCRD). A large number of epidemiology and clinical studies have confirmed that BCRD is complex， difficult to treat,and has a poor prognosis. Most of the existing clinical treatments are postoperative chemotherapy for breast cancer and antidepressant drugs, which treats breast cancer and depression as two independent diseases,with many defects such as low efficiency and strong adverse reactions. Traditional Chinese medicine（TCM）has a unique value in the prevention and treatment of breast cancer-related depression by virtue of its significant advantage of regulating multiple pathways and targets with its multiple components at the same time.In this paper,we review the mechanism of BRCD and the therapeutic mechanism of TCM from the aspects of neurological disorders, inflammatory immune response, and intestinal flora disorders, with a view to providing certain references for the clinical application and research of TCM in the treatment of BCRD.
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Study on the therapeutic effect of Qingre Jiedu formula on gout mice based on immune inflammation and intestinal microecology
hexianshun, linkun, weiyurou, tianjiaqing, jiangyulai, weitengfei, lintianye, hemincong, weiqiushi
Abstract:
Objective: To explore the anti-inflammatory effect of Qingre Jiedu（QRJD） Formula on gout mice and its effect on gut microbiota.Method: Forty 20-22 g C57BL/6 were divided into Control group（CON）, model group（MOD）, allopurinol group（Allo）, QRJD Formula group（QRJD）, and ig 10 g/ 0.1ml carboxymethyl cellulose in blank group every morning from 1 to 28 days. Hyperuricemia mouse model was prepared by potassium oxyazinic acid (500 mg/kg) + yeast extract (10 g/kg) suspension intragaically. On the 29th day, 80ul sterile carboxymethyl cellulose was injected into the left ankle of mice in the CON group under isoflurane anesthesia, and gouty arthritis model was prepared by injecting the same amount of sodium urate solution into the left ankle of mice in the other groups. At the same time, each group was treated with corresponding drugs every day. On the 35th day, samples were taken from mice who had been fasting for 6 hours without water. Blood indexes such as uric acid, creatinine and urea nitrogen were detected. Hematoxylin-eosin staining was performed on ankle joints. The cecum contents of mice were collected and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing method. Results: ① After 7 days of treatment, compared with MOD group, QRJD formula can effectively reduce the concentrations of blood uric acid (P < 0.001), creatinine (P < 0.001) and urea nitrogen (P < 0.05), and effectively protect renal function; ② The pathological results indicated that compared with the MOD group, HE staining showed that the synovial hyperplasia and inflammatory cell infiltration were reduced in the QRJD formula group after treatment. It was found that the cartilage arrangement of the compound was more orderly than before, the cartilage destruction was less than that of the MOD group, and no matrix loss was observed.③ The immunohistochemical results of ankle joint indicated that IL-10 and TGF-β1 were not significantly increased in CON group and MOD group; Compared with MOD group, the expressions of IL-10 and TGF-β1 of QRJD recipe were increased (P < 0.05).④ In terms of biodiversity, there was no significant difference in α diversity among the four groups (P < 0.05), while β-diversity was found to be more similar to the CON group (P=0.001).⑤Compared to the CON group, the MOD group exhibited increased abundances (P < 0.05) of Ruminococcaceae spp., Dubosiella sp., Tyzzerella sp., Ileibacterium sp.and Bacteroidales spp.In contrast to the MOD group, the QRJD group showed elevated abundances (P < 0.05) of Lactobacillus sp., Ligilactobacillus sp., and Bacteroides sp. Furthermore, the interaction network of the gut microbiota indicated mutual interactions among these microorganisms.⑥In the correlation analysis between gut microbiota and renal function, as well as anti-inflammatory factors, it was observed that the relative abundance of Dubosiella sp., Tyzzerella sp.and Bacteroidales spp. was significantly positively correlated with SUA and SCR (P < 0.05). On the other hand, Lactobacillus sp., Ligilactobacillus sp., and Mitochondria spp. exhibited a positive correlation with anti-inflammatory factors IL-10 and TGF-β1, with a more significant association observed with TGF-β1 (P < 0.05).⑦COG function prediction suggested that the functions of QRJD formula group were concentrated on inorganic ion transport and metabolism, carbohydrate transport and metabolism, etc. Conclusions: QRJD effectively modulates immune inflammation and gut microbiota dysbiosis, thereby treating gout. It is hypothesized that its mechanism of gout prevention and treatment involves the regulation of gut microbiota diversity and abundance, as well as the control of the abundance of differential bacterial species such as Ruminococcaceae spp., Dubosiella sp.and Lactobacillus sp. to achieve the goal of gout therapy.
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Research progress on the involvement of macrophages in myocardial ischemia reperfusion injury mediated by NF-κB signaling pathway
Abstract:
Myocardial ischemia reperfusion injury（MIRI）has become one of the most serious complications affecting the clinical outcome of patients with cardiovascular diseases. The immune inflammatory response of macrophages is closely related to the occurrence and development of MIRI.Many studies have shown that the NF-κB signaling pathway can participate in MIRI regulation by influencing the polarization and inflammatory state of macrophages, pyrodeath, infiltration and other functions, and is a potential target for MIRI therapy.Therefore, this article will review the research progress of NF-κB signaling pathway between macrophage function and MIRI regulation.
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Comparison of liver and adrenal orthotopic transplantation models of neuroblastoma
chen Hongxia, Tan Zhigang, Lin Huiran, Feng Luping, Zheng Chuya, Liao Wenfeng, Zeng Rufeng, Liu Jinxin, Zhuo Zhenjian
Abstract:
【Abstract】Objective The Neuroblastoma (NB) liver transplantation model was established and compared with the adrenal orthotopic transplantation model to explore the characteristics of the model.. Methods 5×105 (SK-N-SH) cells was implanted into the left lobe of mouse liver along the long axis of liver lobe with a micro-injection needle. The growth, metastasis, expression of related genes and histopathological changes of tumor were detected after the modeling. Results The tumor formation rate of mice inoculated with tumor cells reached 100% after 21 days, and the tumor growth, metastasis, related gene expression and pathological characteristics were obvious. Conclusion In this paper, neuroblastoma liver transplantation model was successfully constructed by a relatively simple surgical modeling method, which provides more ideal model choices for future scientific experiments of NB researchers.
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A comparative study of two methods for the clearance of macrophages from the rat endometrium
XIA Liangjun, CUI Chuting, LI Junwei, CHENG Jie, XIA Youbing
Abstract:
Objectives A comparison of different administration routes of clodronate disodium liposomes to determine which is the most effective method of rat endometrial macrophage clearance. Methods Female 8-week-old SD rats were randomly divided into the unilateral control group (injected 100μL PBS liposomes into the left uterine cavity), unilateral clearance group (injected 100μL clodronate liposomes into the right uterine cavity), bilateral control group (injected 100 μL PBS liposomes into the bilateral intrauterine), bilateral clearance group (injected 100 μL clodronate liposomes into the bilateral intrauterine), and whole-body control group (injected 500 μL PBS liposomes into the caudal vein ) and whole-body clearance group (injected 500 μL clodronate liposomes into the caudal vein). Haematoxylin and eosin (H&E) staining was used to observe the morphology and structure of uterine and ovarian tissues, immunohistochemistry was used to observe the positive presence of macrophages in uterine and ovarian tissues, and flow cytometry was used to detect changes of the macrophages cell counts in uterine and ovarian tissues. Results There was no significant difference in the structure and morphology of the uterus and ovary among all groups. Immunohistochemical staining showed that compared to the control group, the positive expression of uterine macrophages in unilateral and bilateral clearance groups was significantly decreased (P<0.001), and had no effect on the accumulation of macrophages in the ovary (P>0.05). The numbers of macrophages in both uterine and ovarian tissues decreased of whole-body clearance group (P<0.01, P<0.01). Compared with unilateral and bilateral clearance groups, whole-body clearance group had a greater effect on the positive expression of macrophages in ovarian tissues (P<0.05). Flow cytometry showed that compared with the control group, the percentage of macrophages in the uterine tissue was significantly reduced in each clearance group (P<0.001, P<0.001, P<0.05). Compared to the whole-body clearance group, the clearance effect of endometrial macrophages was better in the unilateral and bilateral clearance groups (P<0.05，P<0.05). In addition, the number of macrophages in ovarian tissue decreased in all clearance groups compared to the control group. The decrease in macrophage number was most pronounced in the whole-body clearance group (P<0.05), and there was no statistically significant difference between the unilateral and bilateral clearance groups compared with the control group (P>0.05).
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Effect of Alzheimer"s disease on auditory function in APP/PS1 transgenic mice
GUI Fei, SONG Dan-dan, WANG Hai-yan, SUN Xiao-pin, Yang Lei
Abstract:
Objective To explore the hearing and cochlear himorphological changes in APP/PS1 transgenic mice during the process of AD, and to determine whether the occurrence and development of AD will affect their hearing function. Methods APP/PS1 transgenic mice and littermates wild type mice were selected at the age of 4, 8 and 12 months. The changes of auditory function in APP/PS1 transgenic mice at different months were detected by immunofluorescence staining and auditory brainstem response (ABR). Results Compared with the control group, the number of Aβ plaques in the hippocampus of 4-month-old APP/PS1 transgenic mice was significantly increased, indicating that AD symptoms were already present at this time. At the age of 4, 8 and 12 months, there was no significant difference in the hearing threshold between APP/PS1 transgenic mice and wild type mice. The histomorphological examination of the cochlea showed that there was no significant difference in the key cells of the inner ear such as cochlear hair cells and spiral ganglion between the two groups of mice. ABR test results of APP/PS1 transgenic mice and littermate wild-type mice showed that the hearing threshold of both mice increased significantly with age, both of them showed age-related hearing loss. Conclusion There is age-related hearing loss in APP/PS1 transgenic mice, but the occurrence and development of AD has little effect on the hearing function of APP/PS1 transgenic mice.
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Improvement of Depressive-like Behavior in Hemerocallis citrina Baroni Using a Zebrafish Model
Zheng Hanwen, Wang ZiHang, Liu Xinyue, Yu Jiawei, Alberto Carlos Pires Dias, Wang Qiong
Abstract:
Abstract OBJECTIVE: This study aimed to investigate the potential positive effects of the alcoholic extract of Hemerocallis citrina Baroni on depressive behaviors in zebrafish larvae (Danio rerio) induced by reserpine. METHODS: Zebrafish larvae were divided into various groups, which included a control group, a model group, a model group with fluoxetine (a positive drug), a model group with a low dose of HCE (1.5 mg/L), a model group with a medium dose of HCE (3 mg/L), and a model group with a high dose of HCE (4.5 mg/L). Depression-like behaviors were analyzed using sound and light stimulation. RT-qPCR was utilized to investigate the effects of the alcoholic extracts of HCE on depression-related astrocyte markers (GFAP, C3, C4B, EMP-1, S100α-10) as well as the neurotrophic factor (BDNF) and its receptor genes (P75, TrkB). RESULTS: In comparison to the control group, the model group demonstrated significantly shorter movement distance and reduced movement time under sound and light stimulation (P<0.05, P<0.0001). Following the administration of the alcoholic extract of HCE, zebrafish larvae exhibited significantly heightened sensitivity to light and sound stimulation when compared to the model group (P<0.05, P<0.01). Astrocyte marker genes were up-regulated in the zebrafish brain in the model group compared to the control group (P<0.01). However, when the model group was administered with the alcoholic extract, the expression of astrocyte markers was significantly down-regulated compared to the model group (P<0.01). Neurotrophic factor and its receptor genes (BDNF, P75, TrkB) were down-regulated in the zebrafish brain in the model group compared to the control group (P<0.01). However, in the group administered with Brassica campestris alcoholic extract, the expression of BDNF, P75, and TrkB was significantly up-regulated compared to the model group (P<0.001). These findings suggest that the alcoholic extract of HCE suppresses the inflammatory response caused by astrocyte activation and promotes the production of neurotrophic factors and their receptor genes, thereby exerting an ameliorative effect on depression. CONCLUSION: Alcoholic extracts of HCE can improve depression-like behavioral changes induced by reserpine in zebrafish larvae . They reduce the expression of astrocyte markers in the zebrafish brain and promote the production of neurotrophic factors and their receptor genes, playing an antidepressant role.
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Establishment and validation of a liver injury model in mice induced by chronic low-dose exposure to atrazine
ZHU Yu, SU Ying-shi, HE Bao-guo, LIU Xi, QIN Lei
Abstract:
Objective To establish a model of long-term atrazine (ATR)-induced liver injury in mice and to evaluate the hepatotoxic effects induced by ATR. Methods C57BL/6-N male mice were randomly divided into drinking control group, 1.5mg/L and 150mg/L ATR dose groups. Serum liver function biochemical indexes and inflammatory factors were detected after 35 and 63 d, hepatosomatic ratio was calculated, and histopathology and ultrastructure of the liver were observed. The levels of lipid peroxidation and antioxidant capacity, the activities of major phase I metabolic enzymes and phase II detoxification enzymes, the expression of related proteins in liver tissues were detected. Results Compared with control group, AST/ALT ratio, pro-inflammatory factors CCL2, TNF-α and IL-6, H2O2 content and the activities of metabolic enzymes NCR, CYPb5 and UDPGT in ATR groups had significant changes (P < 0.05). In 150mg/L ATR group, GGT content, MDA level of peroxide and CYP1A2 expression were significantly increased (P < 0.01), while GSH content was significantly decreased (P < 0.05). Moreover, hepatocyte injury and mitochondrial vacuolation were more serious. Conclusions In a mouse model of low-dose ATR- liver injury, both 1.5 mg/L and 150 mg/L atrazine exposure induced liver injury in mice, with 150 mg/L ATR inducing greater metabolic toxicity in the liver after 63 d.
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Research progress on roles of ferroptosis in chemotherapy resistance of leukemia
Abstract:
Chemotherapy resistance in leukemia is an urgent clinical therapeutic challenge. Ferroptosis is a unique mode of cell death driven by iron-dependent phospholipid peroxidation. Since leukemia is characterised by increased oxidative stress and iron overload, it can be hypothesised that leukemia cells are susceptible to ferroptosis, suggesting therapeutic potential. In recent years, ferroptosis has been extensively studied and used in the treatment of various types of leukemia. Several studies have demonstrated the association between the regulatory pathways of ferroptosis and the mechanisms of leukemia drug resistance. The induction of ferroptosis through different pathways can effectively reduce the resistance of various types of leukemia cells to chemotherapeutic drugs, and thus improve the clinical efficacy. This article summarizes the regulatory mechanisms of ferroptosis, analyzes in detail the association between oxidative stress pathways and iron metabolism pathways of ferroptosis and the mechanism of leukemia drug resistance, and compiles the experimental studies and clinical applications of ferroptosis in the treatment of various types of drug-resistant leukemias, with the aim of providing new ideas and directions for the study of ferroptosis and a new strategy to reverse chemotherapy resistance for leukemia patients in the future.
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Analysis on the Construction and Practice of Animal Biosafety Level-3(ABSL-3)Simulated Laboratory
Li Xiaoyan, Lu Xuancheng, Lu Shuangshuang, Wang Jiaqi, Kalibixiati Aimulajiang, Liu Mei, Liu Keliang, Zainawudong·Yushan
Abstract:
ABSL-3 laboratory is Animal Biosafety Level-3 laboratory where highly pathogenic microorganisms can be done. In recent years, with the continuous emergence of emerging and re-emerging infectious diseases, high-level biosafety laboratories have played an increasingly important role in the hardware support of pathogenic mechanism, drug and vaccine research and development. The demand for ABSL-3 laboratories is increasing year by year. At the same time, there is also an increasing demand for personnel competence of working in ABSL-3 laboratories. The standardization of pre-service training has become an important guarantee to reduce the risk of personnel working in the ABSL-3 laboratory. The systematized, normalized and standardized training work needs to be carried out in a specific place. Simulated laboratory is the best place. Therefore, it is necessary to establish animal biosafety level-3 simulated laboratory and establish scientific and effective operating standards and mechanisms. This paper introduces the design, construction, operation and function of ABSL-3 simulated laboratory.
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Measurement and Comparative Analysis of Blood Physiological and Biochemical Indexes of Spontaneous Type 2 Diabetes Chinese Hamster in the SHANXI MU Colony
yangyuting, yangyichun, weibingyan, wujianqin, zhangruihu, chenzhaoyang
Abstract:
Objective: Investigate the blood physiological and biochemical changes in the spontaneously developed type 2 diabetes mellitus (T2DM) animal model of the SHANXI MU colony inbred strain established by the research team in the preliminary stage. Methods: A cohort of spontaneously developed T2DM Chinese hamsters and normal hamsters, each comprising 10 individuals at 12 months of age, were selected for the study. Fasting blood samples were collected and analyzed using the Sysmex XT automated hematology analyzer and the Hitachi fully automatic biochemical analyzer to measure and statistically analyze 15 physiological parameters and 16 biochemical indicators in the blood. Results: Compared with the control group, WBC, RBC, PLT, HGB, ALT, AST, GLU, TC, TG and UA in diabetic group were significantly different(P < 0.05). Conclusion: The blood physiological and biochemical indexes of the Chinese hamster spontaneous T2DM model established by the research group in the early stage were detected, and the changes were in line with the trend of human T2DM incidence, which provided basic data for the application and application of the model.
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Progress in the optimization of CRISPR/Cas9 technology for the construction of genetically modified mouse models
wangyu, wuyong, liangchunnan, fanchangfa
Abstract:
The rise of CRISPR/Cas9 technology has driven the development of various fields of life science. With the continuous deepening of its understanding, people have made multiple improvements and optimizations to adapt to different application scenarios. The optimization of CRISPR/Cas9 technology has also brought many breakthroughs in the production of genetically modified mouse models. This article briefly reviews the development process of CRISPR/Cas9 technology, and summarizes optimization strategies at the level of CRISPR/Cas9 element optimization, construction of conditional knockout/knockin gene modified mouse models, and delivery systems for CRISPR/Cas9 elements and HDR templates. It looks forward to the future development of this technology.
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The correlation of periodontitis and central nervous system inflammation in hypobaric hypoxia environment at plateau
chen lu, jiang xiao xia, zhu ling ling
Abstract:
In recent years, with the increasing number of people active in the plateau and mountainous areas, high altitude exposure has become increasingly common, and many patients with underlying diseases are affected by the hypobaric hypoxia of the plateau environment, which further aggravates the disease process and even leads to cognitive disorders. Periodontitis is a common inflammatory disease that induces periodontal local inflammatory responses and even causes central nervous system inflammation. At high altitudes, the body suffers from decreased immunity and tissue hypoxia, which can promote the occurrence and development of periodontitis and may even increase the risk of periodontitis leading to central nervous system inflammation. With the deepening of plateau medicine research, the relationship between periodontitis and central nervous system inflammation in the hypobaric hypoxia of plateau environment has attracted more and more attention. This work reviews the research progress of periodontitis and central nervous system inflammation and discusses the correlation between periodontitis and central nervous system inflammation in the hypobaric hypoxia environment at plateau.
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Research progress of exercise on muscular atrophy based on mitochondrial quality Control
Abstract:
Skeletal muscle wasting refers to the loss of skeletal muscle mass and function. Mitochondrial quality control (MQC) is the basis for maintaining normal physiological mitochondrial function, which mainly involves the regulation of mitochondrial biogenesis, mitochondrial dynamics (fission/fusion) and mitophagy. It maintains muscle homeostasis by regulating the relative stability of mitochondrial shape, quantity and quality. As an economical and effective treatment for muscular atrophy, exercise intervention has been widely used, but the relationship between exercise intervention and MQC is not clear. This paper discusses the role of mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in skeletal muscle atrophy and related molecular targets, and thoroughly analyzes the mechanism of MQC-mediated exercise in improving skeletal muscle atrophy caused by aging, disuse, and cancer cachexia, in order to provide theoretical guidance for exercise intervention in skeletal muscle atrophy.
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A comparative study of enzymatic digestion methods for the preparation of single cell suspensions from the lamina propria of the mouse intestine
zengqin, liangying, wangxinhui, yanlei, wangxiangpeng, yangjiayi, yurenhuan
Abstract:
Objective To investigate the best digestion method for the preparation of single cell suspensions from mouse small intestinal lamina propria. Methods Ten mouse small intestines of uniform length were collected and randomly divided into two groups. Each group prepared the lamina propria single cell suspensions by enzymatic digestion with collagenase A or collagenase VIII, and compared the effects of these two enzymatic digestion methods on the cell yield, cell activity and cell surface antigen of the single cell suspensions, and then the single cell suspensions prepared by the superior enzymatic digestion method were subjected to flow assay. Results Compared to collagenase VIII-based enzymatic digestion, collagenase A-based enzymatic digestion resulted in higher cell yields (9.48 ?1.10) ?109 vs. (4.18 ?1.02) ?109, live cell proportions (86.36 ?3.32) % vs. (61.62 ?10.93) % and active CD45 cells (57.19 ?5.11) ) % vs (26.01?1.44) %, active CD3 cells (8.73?.89) % vs (4.52?.49) %, active CD4 cells (6.19?.09) % vs (3.22?.91) % and active B220 cells (15.06?.27) % vs (5.07?.20) %, providing high quality cells for subsequent flow assays. Conclusion The collagenase A-based enzymatic digestion method is more suitable for the preparation of single cell suspensions from the lamina propria of the mouse small intestine.
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Establishment of chimeric rabbits with FOXN1 gene knockout
liu tian ping, li gui ling, liu ke, chen bang zhu, wang gang, gu wei wang
Abstract:
Objective The aim of this study was to establish F0 generation chimeric rabbits with FOXN1 gene knockout to explore methods for in vivo conservation of immunodeficient rabbits in a conventional housing environment. Methods Initially, the CRISPR/Cas9 technology was employed to inject the constructed sgRNA and Cas9 protein into a single cell of rabbit two-cell stage embryos to obtain chimeric embryos with FOXN1 gene editing. Subsequently, the embryos were transferred into surrogate does. Finally, the F0 generation offspring were genotyped using PCR and Sanger sequencing, and their growth and development in a conventional housing environment were observed. Results The PCR and Sanger sequencing results confirmed the successful establishment of chimeric rabbits with FOXN1 gene knockout. Observation revealed that the chimeras exhibited normal growth and development in a conventional environment without any immunodeficient phenotypes. Conclusion This study has initially established a chimeric rabbit model with FOXN1 gene knockout, which can grow and develop normally in ordinary environments. This lays the foundation for further breeding of FOXN1 immunodeficient rabbits in the future.
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Characterisation of the immune microenvironment and immunotherapy for cholangiocarcinoma: mechanisms, challenges and prospects
Abstract:
Cholangiocarcinoma is a malignant tumour with biliary epithelial features. Currently, early diagnosis of cholangiocarcinoma is difficult and the outcome of treatment is poor. Its microenvironment includes abundant fibrotic mesenchyme and a variety of cell types, and these components promote the development and metastasis of cholangiocarcinoma by interacting with tumour cells through mechanisms such as facilitating migration, suppressing immune response and inducing angiogenesis and lymphangiogenesis. Immunotherapy is one of the important means of current tumour treatment, and immunotherapy for cholangiocarcinoma has made some progress. This article reviews the characteristics of the immune microenvironment of cholangiocarcinoma, its relationship with immunotherapy and cutting-edge therapeutic strategies.
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RANBP9 targeted the expression of TGF-β1 induced the cell apoptosis in colorectal cancer Colo320 Cell
Abstract:
objective: To investigate Ran binding protein in microtubule-organization center (RANBP9) targeted the expression of transforming growth factor β1 (TGF-β1) and its effect on colorectal cancer Colo320 cell apoptosis. Methods: The expression data of RANBP9 (gene)? in 625 cases of colon cancer tissues and 20 cases of normal colon tissues in the TCGA database (TCGA) were analyzed. KMPLOT was used to analyze the relationship between the expression of RANBP9 and the survival time of colon cancer patients. The human protein immunohistochemistry database was used to analyze the expression of TGF-β1 in normal colon tissues and colon cancer tissues. The UALCAN database was used to analyze the relationship between the expression of TGF-β1 and the survival of colon cancer patients.The dual luciferase experiment analyzes the relationship between RANBP9 and TGF-β1.The pcDNA3.1-GFP-RANBP9 and pcDNA3.1-GFP-RANBP9-NC were transfected into the cells in the experimental group and the control group,respectively. And the normal group of cells will be established without transfection operation and routinely cultured.MTT method was used to detect the growth viability of each group of cells, flow cytometry was used to detect the apoptotic rate of each group of cells, JC-1 staining was used to detect the mitochondrial membrane potential of each group of cells, and Western blot was used to detect the expression of RANBP9 and TGF-β1 in each group of cells. Results: The expression of RANBP9 in colon cancer tissue was significantly reduced. Compared with patients with low RANBP9 expression, colon cancer patients with high RANBP9 expression had a higher survival curve, and the expression of TGF-β1 in colon cancer tissue was significantly increased. Compared with patients with high TGF-β1 expression, patients with low TGF-β1 expression had a higher survival curve, and the differences were statistically significant (all P<0.05).In colon cancer, RANBP9 can target the expression of TGF-β1. Compared with the normal group, the growth viability of the experimental group, the mitochondrial membrane potential, and the expression of TGF-β1 were significantly down-regulated, and the apoptosis rate and the expression of RANBP9 were significantly increased. The differences were statistically significant (all P<0.05).Conclusion: RANBP9 can target the expression of TGF-β1, promote the growth of colon cancer cell Colo320 and decrease the mitochondrial membrane potential, and induce its apoptosis.
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Hypoglycemic effect of Chinese Yam polysaccharide on DEX-induced IR-3T3-L1 fat cell
LIU Xinyue, WANG Fengzhong, ZHENG Hanwen, Alberto Carlos Pires Dias, FAN Bei, Wang Qiong
Abstract:
Objective To examine the hypoglycemic effect of Chinese yam polysaccharide on 3T3-L1 insulin resistance cell model. Methods After the creation of the IR-3T3-L1 cell model stimulated by DEX (1 μmol/L). Followed the Chinese yam polysaccharide treatment, the glucose intake and the levels of TC, TG, LDL-C, HDL-C, GSH-Px, MDA, HK and PK were measured. Additionally, the AMPK-PI3K/Akt signaling pathway"s associated genes were identified using qRT-PCR. Results The glucose consumption of IR-3T3-L1 cells was considerably decreased after 48 hours of treatment with 1 μmol/L DEX compared to the control group (P < 0.01), and the reduction persisted for 60 hours. When CYPS at 0.05, 0.15, and 0.45 mg/mL was applied to IR-3T3-L1 cells, the following outcomes were observed: the significantly increased glucose consumption (P < 0.01), HK, PK, GSH-Px enzyme activities (P < 0.01), and HDL-C content (P < 0.01). There was a reduction in the MDA activity (P < 0.01) and the concentrations of TG, LDL-C, and T-CHO (P < 0.01). Additionally, CYPS administration dramatically decreased the levels of PI3K, Akt, GLUT-4, AMPK, IRS-2, PPARa, and Adiponectin mRNA expression (P < 0.05), and reduced the IRS-1, GSK-3β, ACC, and FAS mRNA expression levels (P < 0.01). Conclusions In IR-3T3-L1 cells, CYPS can reduce oxidative stress, control lipid metabolism disorders, and enhance DEX-induced glucose intake. The AMPK-PI3K/Akt signaling pathway"s associated genes may be connected to the process.
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Progress in the study of the mechanism of acupuncture in regulating ferroptosis after ischemic stroke
Abstract:
Ischemic Stroke(IS)presents a complex pathogenesis,posing numerous challenges in treatment and rehabilitation.Acupuncture, as a traditional Chinese medicine treatment, has garnered widespread attention for its effectiveness in treating IS, particularly in regulating ferroptosis. Ferroptosis is a type of cell death dependent on iron and lipid peroxidation, closely linked to neurological impairment following IS. This article reviews the primary mechanisms of ferroptosis post-IS, emphasizing the interconnections between iron metabolism, lipid peroxidation, mitochondrial damage, and ferroptosis. It further explores the regulatory mechanisms of acupuncture on ferroptosis after IS, including its roles in enhancing mitochondrial function, modulating iron metabolism, alleviating oxidative stress, suppressing inflammatory responses, and influencing various ferroptosis signaling pathways. This aims to provide more scientific evidence and theoretical support for comprehensive therapeutic strategies for IS.
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Effects and comparison of ginsenosides Rg1 and Rb1 depression and anxieti-like behavior induced by chronic unpredictable stress in rats by regulating inflammation
Bei Xueyi, Jiang Ning, Yao Caihong, Zhang Yiwen, Sun Xinran, Luo Yanqin, Li Liang, Xie Mengzhou, Liu Xinmin
Abstract:
Objective: To study the effect and comparison of ginsenosides Rg1 and Rb1 on depression-like and anxiety-like behavior in chronic unpredictable stress-induced rats by regulating inflammation. Methods: Seventy SPF grade SD male rats were tested for sugar and water preference after 5 days of adaptation. The animals were divided into 7 groups according to the sugar and water preference index, namely blank control group, model group, positive drug group, ginsenoside Rg1 30 μmol/kg dose group, ginsenoside Rg1 60 μmol/kg dose group, ginsenoside Rb1 30 μmol/kg dose group, ginsenoside Rb1 60 μmol/kg dose group. Except for the blank control group, the other rats were randomly subjected to 1-2 different stimulating factors every day for a total of 35 days. On the 36th day, behavioral experiments such as sugar and water preference, open field experiment, novel environment feeding inhibition experiment, elevated cross maze experiment and forced swimming were conducted to investigate its anti-depression and anti-anxiety effects. The serum and hippocampal levels of IL-1β, IL-6, TNF-α and serum corticosterone (CORT) were measured by Elisa. Result: Compared with model group, ginsenoside Rg1 and Rb1treatments significantly increased the sucrose consumption in the sucrose preference test and decrease in immobility in the forced swimming test., the latency to eat in novelty-suppressed feeding test of ginsenoside Rg1 (60 μmol/kg) group was significantly reduced, and percentage of open arm entries and time in elevated plus maze test of ginsenoside Rg1 (30 and 60 μmol/kg) groups was significantly increased. The content of serum corticosterone in ginsenoside Rg1 and Rb1 dose groups was significantly decreased. The levels of serum IL-1β and IL-6 in ginsenoside Rg1 (30 μmol/kg) dose group were significantly decreased, The levels of TNF-α and IL-6 in serum of ginsenoside Rb1 (30 μmol/kg) group were significantly decreased. And the contents of IL-1β, IL-6 and TNF-α in hippocampus of ginsenoside Rg1 and Rb high dose group were significantly decreased. Conclusion: Both ginsenosides can regulate the HPA axis and inhibit neuroinflammation, improving depression and anxieti-like behavior in rats induced by chronic unpredictable stress. In addition, ginsenoside Rg1 has a significantly better anti-anxiety effect than Rb1.
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Gualou Xiebai Baijiu Decoction regulating intestinal microflora and its metabolites to improve atherosclerosis in mice
chenzhifan, chenyulin, niesha, sunwenhao, lichang, mazishan, hukai, heyingying, liuying, tangyaoping
Abstract:
Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction in improving atherosclerosis (AS) in mice by regulating gut microbiota (GM) and its metabolites. Methous Thirty two male Apoe-/- mice were randomly divided into blank group, model group, atorvastatin(Ato) group and Gualou Xiebai Baijiu Decoction (GXB) group, with 8 mice in each group. Except for the Blank group, three groups of mice were established with AS models and administered by gavage according to their respective groups. Oil red O staining was used to detect the area of aortic plaques. HE staining was used to observe pathological changes in aortic tissue. Using 16S rRNA gene sequencing technology to analyze mouse GM. Detection of mouse GM metabolites trimethylamine oxide (TMAO), short chain fatty acids (SCFA), and serum levels of TG, TC, LDL-C, HDL-C, and NO. Results Compared with the Blank group, both the Model group and Ato group showed an increase in AS plaque area (P<0.05); The serum levels of TG, TC, and LDL-C in the Model group increased (P<0.001), while the levels of HDL-C and NO decreased (P<0.01, P<0.001). Compared with the Model group, the Ato group and GXB group showed a decrease in plaque area (P<0.05); The levels of serum TG, TC, and LDL-C decreased (P<0.001) and the levels of NO were increased (P<0.01) in the Ato and GXB groups; The HDL-C level in the GXB group was increased (P<0.05). Compared with the Ato group, the plaque area in the GXB group was decreased (P<0.05) and the NO level increased (P<0.01).There are 6345 characteristic sequences obtained from 16srRNA. α Diversity analysis suggests that GXB can reduce the richness of GM in AS mice (P<0.001) and improve its uniformity (P<0.05). β Diversity analysis suggests that the microbial community structure of the GXB group is similar to that of the Blank group. There are differences in the abundance of microbial communities among different groups at the phylum and genus levels. At the phylum level, the abundance of Proteobacteria was increased (P<0.01) in mouse AS modeling, while GXB intervention reduced its abundance (P<0.01) and increased the abundance of Verrucomimicrobiota (P<0.05).. At the genus level, GXB intervention can effectively increase the abundance level of Akkermansia (P<0.05). Compared with the Model group, the SCFA level in the GXB group significantly increased (P<0.01), while the TMAO level significantly decreased (P<0.01). Conclusions Gualou Xiebai Baijiu Decoction can regulate intestinal flora and intestinal flora metabolites SCFA, TMAO to improve AS.Akkermansia may be a key bacterial genus for GXB to improve AS through gut microbiota.
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Chronic myocardial ischaemia mouse model of coronary artery disease and evaluation methods
wang zhao bo, panyi, linqian, zhongjuying
Abstract:
Objective To establish a stable mouse model of chronic myocardial ischemia, and to preliminarily elaborate the electrophysiological principle of T-wave flattening under ischemic state. Methods 1. C57BL/6 J mice were used as control group with normal diet for 3 months. APOE-/- mice were randomly divided into a model group and a Lipid-lowering Drug (LLD) group, and were fed a high-fat diet for 3 months; 2. Plaque condition was assessed by Hematoxylin-eosin staining (HE) and oil red staining; 3. Electrocardiograms of the mice before and after modelling; and 4. Recordings of the ventricular myocytes' action potentials. Results 1. Cholesterol (CHO) and low-density lipoprotein (LDL-C) were significantly elevated in the model group, and lipid plaques appeared in the aorta of the model mice after modelling, while the lesions in the LLD group were significantly reduced, and no plaques were found in the control group; 2. There was no significant change in the T/QRS wave (T/QRS) in the ECG after modelling in the control group, whereas a significant reduction in T/QRS was observed in the model and LLD groups. 3. There was a significant positive correlation between the degree of T/QRS depression and the levels of lipids and the degree of atherosclerosis (AS) pathology. 4. The inner layer of the cardiomyocyte action potential repetitions more slowly than the outer layer of cardiomyocytes, whereas the repetitive rate was accelerated by the ischemic inner layer of cardiomyocytes. cardiomyocytes accelerated the repolarisation rate. Conclusions APOE-/- mice can be used as a mouse model of chronic myocardial ischemia, and the increased repolarisation rate of the inner myocardium in ischemia may be the main reason for the depression of the electrocardiographic "T wave" in ischemia.
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Analysis and reflection on the quarantine and supervision policy of imported experimental animals in Japan
DING Ning, LIANG Jiaqi, FU Hongkun, WANG Ying, ZHU Daozhong, WANG Chunxia, REN Jiao, LIN Zhixiong, TAO Yufeng, MA Lidan, GAO Zhiqiang, WU Xiaowei, Yu haiqiong
Abstract:
Japan is an important trading partner of China's import and export of experimental animals, and its quarantine supervision policy of experimental animals is meticulous and strict. In this paper, experimental dogs, cats and monkeys are taken as examples to make an in-depth analysis of the regulatory policies of major experimental animals for export to Japan. Through the current experimental animal related laws and regulations, inbound and outbound management measures, experimental animal breeding production and management situation and import and export business trend thinking, from the perfect experimental animal laws and regulations and inbound and outbound management measures, safeguard security, improve the management level of experimental animal breeding and promote experimental animal import and export trade. In order to provide reference for comprehensively improving the level of production, use and management of laboratory animals in China and strengthening the work exchange of laboratory animals between China and Japan.
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Inhibition of gallic acid on lipopolysaccharide-induced inflammatory response in human THP1 macrophages
DIAO Jiawen, XU Hui, MA Xinyue, QUAN Jishu
Abstract:
Objective To investigate the inhibitory effect of gallic acid (GA) on lipopolysaccharide (LPS)-induced inflammatory responses in human THP1 macrophages. Methods THP1 monocytes were differentiated into macrophages with phorbol myristate acetate (PMA) and then the macrophage inflammation model was established with LPS induction，and GA was given in different concentrations. The safe concentrations of LPS and GA on THP1 cells were screened by CCK-8 method，and the normal group, model group (100 μg/L LPS ) and GA group（100 μg/L LPS + different concentrations of GA）were set up. ELISA was used to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in the cell culture fluid of each group. Microplate method was used to detect LDH activity and NO content in cell cultures of each group, and fluorescence staining was used to detect ROS levels, cell damage and changes in mitochondrial transmembrane potential in each group.Western blotting assay was performed to detect the levels of cyclooxygenase-2 (COX-2), HMGB1,c-Jun amino-terminal kinase (JNK), extracellular-regulated protein kinase (ERK), P38 mitogen-activated protein kinase (P38), nuclear transcription factor-κB (NF-κB), NOD-like receptor protein 3(NLRP3), Caspase-1,IL-1β、Gasdermin D(GSDMD). Results Compared with the normal group, the secretion of IL-6, TNF-α, IL-1β and NO in cell cultures was increased in the model group (P<0.05), and the secretion of COX-2, HMGB1, p-ERK, p-JNK, and p-P38 and p-NF-κB, NLRP3, Caspase-1, IL-1? protein expression was elevated (P<0.05), the expression level of GSDMD protein activation fragment was reduced (P<0.05), ROS generation and cellular damage were significantly increased, mitochondrial transmembrane potential was significantly lower than that of the normal group, and the activity of LDH was elevated (P<0.05); in comparison with the model group, the cell culture fluid of the GA group IL-6, TNF-α, IL-1β and NO secretion were decreased (P<0.05), COX-2, HMGB1, p-ERK, p-JNK and p-P38 and p-NF-κB, NLRP3, Caspase-1, IL-1β protein expression was decreased (P<0.05), GSDMD protein activation fragment expression level was increased (P<0.05), ROS generation and cellular damage were decreased, mitochondrial transmembrane potential was gradually increased, and LDH activity was decreased (P<0.05).Conclusion GAhas an inhibitory effect on LPS-induced inflammatory response in THP1 macrophages, and its anti-inflammatory mechanism may involve MAPK and NF-κB signalingpathways.
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Sanguisorbae Radix alleviates damage in Ulcerative Colitis Mice Based on PPARG and SCL7A11/GPX4
Xiaoxi Yin, Zixuan Chen, Yi Yuan, Jingnan Ma, Jing Wang, Tianyi Lv, Miaomiao Tong, Li Li
Abstract:
Objective: To investigate the mechanism of Sanguisorbae Radix (SR) in the treatment of Ulcerative Colitis (UC). Methods: The study analyzed GSE92415 from the Gene Expression Omnibus (GEO) database using differentially expressed genes analysis, weighted gene correlation network analysis (WGCNA) and FerrDb. Core genes were identified through protein-protein interaction (PPI) network and correlation analysis. The efficacy of SR in UC was evaluated in a dextran sodium sulphate (DSS)-induced colonic inflammatory mouse model by analyzing DAI, histopathology and colon length. ELISA was used to examine levels of inflammatory cytokines and lipid peroxidation. The expression levels of ZO-1 tight junction protein, PPARG, SLC7A11 and GPX4 protein were examined through Western blotting or immunofluorescence labeling. Results:S Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene. The experimental animal results showed that SR significantly prevented colon shortening and ameliorated histological injuries of colons in DSS-treated mice. SR inhibited cytokine levels of IL-6 and TNF-α, improved the reduction of ZO-1 and levels of MDA and GSH in colon tissues of DSS mice. Meanwhile, it enhanced the activation of PPARG, SLC7A11 and GPX4, which reversed the therapeutic effect of DSS in mice with colitis. Conclusion: Iron death is closely related to UC. SR can inhibit iron death by regulating the PPARG and SCL7A11/GPX4 expression, thereby improving colon epithelial injury and dysfunction in UC mice. This provides ideas and direction for UC treatment strategies.
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Lipidomics driven biomarker discovery in chronic lung disease
Zhang Ang, Liu Xinguang, Du Yan, Xie Yang
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Chronic lung diseases (CLD) include chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, etc. Studies have shown that CLD is closely related to the disorder of lipid metabolism. Therefore, lipids, as biomarkers of CLD, may be of great value in the diagnosis, prevention and monitoring of disease treatment.This review mainly discusses four aspects of lipidomics, selection of clinical samples for lipidomics, discovery of biomarkers for CLD, and differentiation of TCM syndromes for CLD.
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Establishment of WHBE rabbit knee osteoarthritis model and intervention study of platelet-rich fibrin releasates
Huang Jun-jie, Chen Min-li, Zhu Ke-yan, Jiang Jing-ao, Zhang Jing-hui, Jiang Chao, Pan Yong-ming
Abstract:
Objective WHBE rabbit KOA model was established by excision of medial collateral and partial patellar ligaments and intervention with platelet-rich fibrin release solution (PRFr). To investigate the mechanism of cartilage injury and inflammation in WHBE rabbit KOA model and the effect of PRFr intervention on KOA process. Methods Twenty-four WHBE rabbits were randomly divided into three groups: normal control (NC) group (n=6), KOA group (n=12) and PRFr group (n=6). The KOA group and PRFr group injected 0.5 mL of saline and PRFr into both joint cavities on the 7th and 14th postoperative days, respectively. At 4 and 8 weeks of modeling, knee joint grade score, X-ray imaging observation and gross score were performed. Serum levels of IL-1β, TNF-α and MMP-13 were detected by ELISA. Pathological sections were made after decalcification, and then HE staining, toluidine blue staining, safranin o-fast green staining and immunohistochemical expression of TGF-β, BMP3 and NF-κB were detected. Results Lequesne MG behavioral score, Mankin's score and Pelletier score of WHBE rabbits after the operation were significantly increased vs NC group (P<0.01); Pathological observation shows surface defects of cartilage and partial loss of chondrocytes; These results above indicated that the KOA model was established successfully. In KOA rabbits, knee joint swelling, joint pain stimulation and movement limitation were obvious, and X-ray showed high-density soft tissue shadow, indicating more joint effusion, and rough articular surface in general. After PRFr treatment, the levels of serum inflammatory factors (IL-1β, TNF-α, MMP-13) in KOA model rabbits were significantly reversed (P<0.05, P<0.01), and the surface of cartilage became smooth, and most of the chondrocytes were neatly distributed. At the same time, the expression levels of TGF-β, BMP3 and NF-κB induced by KOA were significantly decreased(P<0.01). Conclusion This study successfully established the KOA model of WHBE rabbits, and PRFr can improve the cartilage injury and inflammation of WHBE rabbits KOA model through TGF-β/BMP and NF-κB pathways.
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Potential risks of biosafety and prevention strategies in medical and pharmaceutical research laboratories
Chen Mo, Tao Jiayi, Wang Hongxu, Zhang Qingjian
Abstract:
Medical and pharmaceutical research laboratory usually involves wide range of study aspects. The materials used in the laboratory are various, including animals, microorganisms and nano-particles and other kinds. Meanwhile, with the production of more and more waste, more biosafety risks would be created. Here, we outlined the potential safety risks related with gene amplification, gene recombination, pathogenic microorganism research, nanotechnology, animal experiments, genetically altered animals, and experimental waste, etc. It also proposed preventive measures for laboratory biosafety risks, which mainly associate with developing strict legal frameworks, bettering hardware infrastructure, strengthening safety awareness, and enhancing education and training programs.
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Research progress on related complications after snake bite
LI Yumei, YANG Yue, YI Jun, YAN Zhangren, WANG Wanchun, DONG Degang
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Snake bite is a common clinical emergency, which has the characteristics of acute onset, rapid changes in condition, high disability and mortality rates. In addition to the common systemic and local tissue damage, snake envenomation can also cause significant complications, including immediate and delayed effects. These complications are also the main causes of disability and even death caused by snake bite, which seriously affect the long-term prognosis and quality of patients’ life. This paper summarizes the symptoms, diagnosis and treatment of snakebite complications from the aspects of blood system, nervous system, motor system, endocrine system, reproductive system and other aspects, in order to provide references for effective and precise treatment of snake bite in clinical practice.
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Research progress of ferroptosis in the mechanism of cerebral ischemia reperfusion injury
jianghuan, BAI Wenya, SHAO Jianlin
Abstract:
Ferroptosis is a newly cell death mode discovered in recent years, involving in a variety of pathophysiological processes, such as ischemia reperfusion injury, neurodegenerative diseases and tumors, etc. At present, there is a lack of effective methods to prevent and treat ischemic stroke worldwide, and ferroptosis which is involved in cerebral ischemia reperfusion injury. 50 articles were included in this paper after searching the related literature, which published in databases such as PebMed, Wanfang, CNKI and VIP in recent years. Discussing theIorn metabolism and the concept, mechanism and regulation of ferroptosis, the role of ferroptosis in the mechanism of cerebral ischemia reperfusion injury, and the methods of inhibiting ferroptosis, this paper attempts to provide reference for finding a new potential treatment for ischemic stroke from the direction of inhibiting ferroptosis.
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Research progress on MHC function and transgenic mouse models
CAO Xiangwen, LI Min, YIN Qi, HAN Xueliang, WANG Yuan, ZHAO Guangyu
Abstract:
The major histocompatibility complex (MHC) is closely related to immune regulation, and not only has genetic polymorphisms, but also has species differences in MHC restriction. The construction of humanized MHC transgenic mouse models is an important strategy to break through the differences of MHC species and simulate the characteristics of human immune response. MHC transgenic mice are mainly divided into MHC I or MHC II. single transgenic mouse models and MHC I and MHC II double transgenic mouse models. At present, the strategy of knocking out H-2Kb and H-2Db or knocking out murine β2m is adopted to eliminate the competitive inhibition of HLA I molecules by endogenous H-2 class I molecules, and the construction of HLA II transgenic mouse model is to knock out the β strand of murine origin and transfer it to HLA II. class genes.With the optimization of construction strategies, MHC transgenic mouse models have been applied to epitope vaccine development, tumor treatment, and disease genetic association studies, becoming a powerful tool for preclinical trials. In this paper, we summarize the relevant data of MHC transgenic mouse models, and summarize the construction strategies of MHC transgenic mouse models and their application progress in vaccine development and disease treatment.
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Advances in the study of glucose metabolic reprogramming in the pathogenesis of Alzheimer's disease
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by widespread dementia. Despite extensive research on the pathogenesis of AD over the past fifty years, the underlying mechanisms responsible for AD-related cellular damage and cognitive impairment remain elusive. Currently, multiple studies have confirmed alterations in glucose metabolism patterns within nerve cells in individuals with AD. This metabolic transition plays a crucial role in cell survival and disease progression, even occurring decades before pathological changes and cognitive dysfunction manifest. This article provides an overview of potential mechanisms through which glucose metabolism reprogramming contributes to AD development in various types of nerve cells and brain regions, as well as their interplay, aiming to establish a foundation for further investigation into AD while offering insights and ideas for the development of novel preventive and therapeutic approaches.
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Analysis of animal model of psoriatic arthritis based on the characteristics of Chinese medicine and Western medicine
Shi Yajin, LI Hanbing, LI Genlin, WU Suhui
Abstract:
Purpose: In recent years, with the incidence of psoriatic arthritis gradually increasing and incurable in China, it has become a major problem in the medical career. Therefore, In this study, we actively explored the pathogenesis of psoriatic arthritis based on the characteristics of Chinese and Western medicine clinical evidence, summarized the currently available animal models and analyzed and evaluated them. Methods: Literature detected in line with this topic was collated and summarized, and the existing models were given an agreement score through the study of the etiology and pathogenesis of psoriatic arthritis in Chinese and Western medicine, the diagnostic criteria of Chinese and Western medicine, and the analysis of the characteristics of the animal models and their degree of agreement with the clinic. Results: This thesis found that the human leukocyte antigen transgenic mouse model, the multiple hybridization transgenic mouse model, and the mannan-induced mouse model had the highest fit scores. Conclusion: Since psoriatic arthritis is mostly seen in Europe, the preparation methods of animal models are mostly imported from abroad, and there are very few animal models prepared with the characteristics of Chinese medicine, therefore, the model agreement scores of western diagnosis are higher than those of Chinese medicine diagnosis as a whole. It is hoped that in the future, we can combine the unique diagnosis and treatment methods of Chinese medicine to further improve the types of animal models of psoriatic arthritis, so as to provide a basis for the construction of more ideal animal models for the treatment of psoriatic arthritis by combining traditional Chinese medicine and Western medicine.
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Research progress of mitochondrial quality control in respiratory diseases
Abstract:
Respiratory diseases (lung inflammation, pulmonary fibrosis) are a serious threat to human health. As organelles unique to eukaryotic cells, mitochondria not only have important functions in energy production, biosynthesis and maintenance of intracellular homeostasis, but also act as diverse signaling organelles involved in inflammation, proliferation, differentiation, cell repair and other processes. The mitochondrial quality control system includes mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy. It has been found that certain pathological mechanisms of respiratory diseases such as oxidative stress and inflammation are closely related to dysregulation of mitochondrial quality control. Therefore, this paper summarizes the research progress of mitochondrial quality control dysregulation in respiratory diseases (chronic obstructive pulmonary disease, pulmonary fibrosis, acute lung injury, asthma and bacterial pneumonia), in order to seek new ideas for the prevention and treatment of respiratory diseases from the perspective of mitochondria.
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Neuro-pathological study of the intrathalamic neurovirulence test of poliomyelitis vaccine in rhesus macaques
YU Pin, XU Yan-feng, HAN Yun-lin, ZHAO Wen-jie, QIN Chuan
Abstract:
Objective To study the effect and pathological mechanisms of the neuro-immune response of viral encephalomyelitis caused by the virulence reversion of the intrathalamic neurovirulence test of poliomyelitis vaccine in rhesus macaques. Methods The stock solution (not less than 7000 lgCCID50?L-1) of the inactivated polio vaccine (Vero cells) of type I, type II and type III Sabin strains and 10-1 dilution of each type of polio vaccine were carried out using intrathalamic neurovirulence test. We observed the pathological changes of polio. Via immunohistochemical method, the distribution of receptor CD155 and CD4+ T lymphocytes, CD20+ B lymphocytes and CD68+ microglia were detected. Results Lesions were observed on the virulence reverted polio case. Inflammatory cells infiltrating, neuronal degeneration and necrosis, satellite phenomenon, perivascular cuffing and glial cell proliferation were observed in the spinal cord. The inflammatory cells were mainly CD4+ T lymphocytes, CD20+ B lymphocytes, and CD68+ microglia in perivascular cuffing and proliferative glial nodules. There is no significant difference on distribution of poliovirus receptor CD155 in neurons and glial cells of monkeys with and without polio, while no expression was observed in vascular endothelial cells. Conclusion Polio caused by virulence reversion of the intrathalamic neurovirulence test is viral encephalomyelitis.
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Effects and mechanism of Five-elements music on the social behavior of offspring from Stress-Injured pregnant rats
WU Yongye, YANG Liping, ZHAO Jiajia, SONG Qi, HOU Junlin, WANG Yaohui, LI Xiaolin
Abstract:
Objective To investigate the effects and mechanism of Five-element music on the social behavior of Pregnant Children with Allergic Stress during Pregnancy, in order to provide a basis for the early prevention and treatment of clinical fetogenic affective disorders. Methods Forty-five pregnant mice were randomly divided into three groups: a blank group, a model group, and a Five Element Music group. In the model and Five Element Music groups, the model was induced using the bystander electric shock method. Additionally, the Five Element Music group was exposed to Palace Tune Five Element Music daily from 17:00 to 19:00 during pregnancy. On the 19th day of pregnancy, ELISA was employed to assess the levels of adrenocorticotropin (ACTH) and cortisol (CORT) in the serum of pregnant mice in each group for modeling evaluation. The offspring were subsequently grouped with their mother mice and underwent an 8-week-old three-box social experiment to observe social behavior. We utilized the immunofluorescence double-labeling method to detect glutamatergic neuron activity in the mPFC region of the offspring mice. Furthermore, high-performance liquid chromatography was employed to measure the total glutamate (Glu) content in the mPFC region of the offspring mice, while Gorky staining was used to observe changes in dendritic spines of mPFC neurons in the offspring mice.Results Compared to the blank group, the model group exhibited a significant increase in the levels of ACTH and CORT in the serum of pregnant mice, alongside a significant decrease in the social interaction time and social novelty preference index of the offspring mice. Additionally, there was a significant decrease in the activity of glutamate neurons, glutamate content, and neuronal dendritic spines.In contrast, when compared to the model group, the Wuxing Music group demonstrated a reduction in the levels of ACTH and CORT in the serum of pregnant mice, as well as improvements in the social behavior, glutamate neuron activity, glutamate content, and the condition of neuronal dendritic spines in the offspring. Conclusions The intervention of Five-element music effectively ameliorates offspring"s social behavior disorder resulting from prenatal fear stress, with its mechanism potentially linked to enhancing glutamate neuron activity in the mPFC region.
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Immune cell composition analysis of CAST/EiJ mice
LIUQI, HOU Yongzhi, LI Na, ZHANG Jingjing, LU Jiahan, CONG Zhe, ZHU Lin, XUE Jing
Abstract:
Objective To explore the possible causes of susceptibility to multiple pathogens in CAST/EiJ mice, immune cell phenotypes in the peripheral blood and spleen of CAST/EiJ mice were analyzed to clarify the immune cell composition of CAST/EiJ mice. Methods Classical dendritic cells (cDCs), natural killer (NK) cells, B lymphocytes, T lymphocytes and their subsets in peripheral blood and spleen of CAST/EiJ mice and C57BL/6J mice were detected by flow cytometry using the cell surface markers CD3, CD4, CD8, CD11b, CD11c, CD19, CD27, CD49b and TCRβ. Results There was no significant difference in the proportion of cDCs between CAST/EiJ and C57BL/6J mice, but the cDC1 cell subset was low. The proportion of NK cells (mainly mature NK cell subsets) and T lymphocytes (mainly CD8+ T cells) were both lower in CAST/EiJ mice than in C57BL/6J mice, while the proportion of B cells in CAST/EiJ mice were higher than those in C57BL/6J mice. Conclusion The proportion of NK and T lymphocytes in CAST/EiJ mice was lower than those in C57BL/6J mice.
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Evaluation of an animal model of chronic fatigue syndrome based on data mining
Li Ya-qing, Wang Can, miaomingsan
Abstract:
Objective To study the application of the animal model of chronic fatigue syndrome, and to provide reference for its animal experimental methods and model improvement. Methods Using "chronic fatigue syndrome, animal model" and "chronic fatigue syndrom, animal model" as search terms, we searched in China Knowledge, Wanfang and PubMed databases. Literature on animal models of chronic fatigue syndrome was compiled from July 2000 to July 2023, and experimental animals, modeling methods, positive drugs, and detection indexes were sorted out, and a database was established for statistics and analysis. Results A total of 155 articles were included; the most experimental animals were male SD rats of SPF grade and 6-8 weeks of age, with weights of 180-220g; the most used mice were male KM mice of 18-22g and 6-8 weeks of age; the most used positive drug was ginseng saponin tablets; the most used modeling method was the method of "forced cold water swimming + chronic restraint"; the most used modeling method was the method of "forced cold water swimming + chronic restraint"; the most used modeling method was the method of "forced cold water swimming + chronic restraint". +The most widely used modeling method is the "forced cold water swimming" method, and the modeling cycle is mostly concentrated in 14 days, and most of them adopt the method of intervention while modeling; the testing indexes are mainly behavioral, which mainly include the exhaustion swimming experiment, the open field experiment, the rat-tail suspension experiment, the Morris water maze experiment, and the observation of the general state of the animals, and the second is the serum biochemical indexes, and the most frequently detected indexes are serum MDA, SOD, TNF-alpha, IOD, and IBP, TNF-α, IL-1β, CORT, IL-2, IFN-γ, ACTH, GSH-Px, IgG, IgA, IL-6, etc. The rest of the indicators were selected according to the research purpose, including the indexes of spleen, thymus, etc., the morphological indicators detected by HE staining and ultrastructural electron microscopy, the immunohistochemistry-related indicators, the CRH and Smilax detected by fluorescence PCR, the CRH, the Smilax, the Smilax, and the Smilax. The mRNA expression indexes of CRH, Smad4, BDNF, CREB, IFN-γ, NRF-1, TFAM, Tlr4, etc., and the protein expression indexes of BDNF, CREB, ERK, Bmal1, Clock, NGF, PGC-1α, SIRT1, Smad4, Caspsae-3, etc., were determined by Western blot method. and other related protein expression indicators. Conclusion At present, the pathogenesis of chronic fatigue syndrome is still unclear, and the animal model is mainly based on the stress modeling method of "forced cold water swimming + chronic restraint", which simulates the physical and mental fatigue state of human beings; there is no uniform regulation on the criteria for the formation of animal models, and the evaluation of the model is based on the application of a variety of behavioral experiments individually or in combination, and the objective evaluation indexes are mostly used to argue the etiology of the disease and evaluate the effectiveness of interventions. The objective evaluation indexes are mostly used to prove the conjecture of etiology and evaluate the effectiveness of interventions; the results of the application of various test indexes show that chronic fatigue syndrome may be related to inflammatory response, neurological dysfunction, and mitochondrial dysfunction, and there may be abnormalities in the pathogenesis of immune function, energy metabolism, cell proliferation, and cell death, which is expected to provide reference for the application of the model, and to provide ideas for the model"s refinement. The excavated content is expected to provide reference for the application of the model and provide ideas for the improvement of the model.
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Application and prospect in experimental animal model of chronic stress
YUE Xiaoqi, Li Yuting, JIANG Miao, ZHAO Zigang, NIU Chunyu
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The effect and mechanism of chronic stress on psychosomatic diseases is a hot topic in the field of stress research. The establishment of animal models to simulate human chronic stress state is of great significance in the principle of stress response, the pathogenesis of related diseases, clinical treatment and drug development. In this paper, the commonly used animal models of chronic stress at home and abroad were reviewed, the classification of stressors, animal selection, model construction, pathological manifestations and evaluation indexes were summarized, and the advantages and disadvantages and application progress of various models were discussed, hoping to provide references for the study of model selection of chronic stress response.
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Technological advances in the study of post-stroke neural loop
Chenyanxi, Xuzhidong, Liutingting, Maliansu, Sunfangling, Wangwen
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Neural loops are formed by interconnections between neurons through synaptic structures, Which are the basic units of information transmission and processing in the brain and play an important role in the regulation of neural functions. After Stroke, the neural connections between the infarcted area and the peri-infarct region and the remote area are damaged, resulting in patients at risk for neurological dysfunction or even disability. However, with advances in detection technology, more and more studies have demonstrated that patients with stroke can produce some functional recovery during the chronic phase, possibly related to the re-establishment of synaptic connections and neural circuits. Therefore, the development of specific technology to identify and manipulate neuronal activity patterns, as well as the use of high temporal and spatial resolution imaging strategies to decipher these neurological processes allows us to understand the whole-brain network dynamics of stroke recovery and the mechanisms by which neural loop reestablishment occurs. Furthermore, we could neurobiologically comprehend the closed-loop relationships that underlie the development of stroke pathology to behavioral outcomes. Current technology for studying neural circuits focus on optogenetics, chemical genetics, in vivo calcium imaging, and functional magnetic resonance imaging technology. This article will introduce the working principles of these four major technologies, focus on summarizing the results of their respective applications in resolving neural remodeling after stroke, and briefly analyze the application scenarios, advantages and disadvantages, and future development trends of each technique. This paper will help clinical and basic researchers to to utilize these technologies in discovering new therapeutic strategies as well as evaluating the effectiveness of rehabilitation strategies.
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Analysis of the Role of Brain Plasticity in Improving Depression by Exercise
Chen Xianghe, LU Pengcheng, SHEN Ziming, LIU Chi, ZENG Xinyu, YIN Rongbin
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The research on the mechanism of depression is currently a focus in the field of neuroscience, degeneration of brain plasticity (decrease in volume, structural degradation, and functional disorder of the hippocampus, PFC, CG, etc.) leads to depression. Exercise is an important means of improving depression. Current research has confirmed the important mechanism of improving the volume, structure, and function of the hippocampus, PFC, CG, etc. in this process, but related research results only focus solely on changes in a certain brain volume or connectivity function, lacking a comprehensive understanding Systematic analysis of the mechanism of improving brain plasticity in exercise antidepressant effects. Therefore, this study aims to explore the role of brain plasticity in the occurrence of depression and the improvement of depression through exercise. This helps to comprehensively understand the role of brain plasticity in the occurrence of depression, and will also provide new ideas for exercise intervention in depression.
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Construction and application of patient-derived pancreatic tumor organoid model
LI Peng, HUANG Minli, TAN Dengxu, ZHANG Caiqin, ZHANG Yongbin, SHI Changhong
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Objective To construct a patient-derived pancreatic tumor organoid (PDO) and evaluate its effectiveness. Methods Collect fresh surgical specimens from pancreatic cancer patients for PDO culture; Compared the pathological and genetic characteristics of the PDO model with the primary tumors; Using the PDO model to evaluate the efficacy of clinical chemotherapy drugs and evaluate the effectiveness of the model. Results A PDO model of pancreatic cancer was successfully established. Histomorphological analysis displayed that the PDO model basically maintained the pathological characteristics of the primary tumor. Whole-exon sequencing showed that both organoids and original tumor tissue remained consistent in the gene mutation type and characteristics. Drug screening tests have exhibited that the PDO model had good sensitivity to gemcitabine and irinotecan. Conclusion A case of pancreatic cancer PDO was successfully constructed, which can reflect the histological and genetic characteristics of the original tumor, and can be used for drug sensitivity experiments in vitro, which proves the effectiveness of PDO model and is expected to imply precision medicine.
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Advances in the study of epigenetic regulatory mechanisms of astrocytes
xu liuqing, zhaopeiyuan, liuxihong, duxiaodan, fangmengyang, yuchenyang, houjunlin
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Astrocytes (AS) are the most abundant glial cells in the central nervous system and are involved in many physiology and pathology processes in the nervous system. Alterations in their phenotype are particularly important for the health of the CNS. Epigenetic mechanisms, including DNA methylation, histone modification, non-coding RNA regulation and chromatin remodeling, are closely linked to alterations in AS proliferation, differentiation, inflammation and other phenotypic features, but how these mechanisms function still needs to be explored and summarized. By reviewing the recent advances in the role of epigenetic mechanisms in AS under different physiological and pathological states, aim to provide new ideas for the understanding and treatment of related diseases.
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Experimental study of ursolic acid to ameliorate pancreatic β-cell injury in type 1 diabetic rats based on the TLR4/NF-κB pathway and Th17/Treg cell balance
songyu, zhangxiaoli, chenhuanhuan, tangcong
Abstract:
[abstracts] Objective To investigate the effects of ursolic acid (UA) on TLR4/NF-κB signaling pathway and Th17/Treg cells in type 1 diabetes (T1DM) rats. Mmthods The T1DM rat model was prepared by intraperitoneal injection of streptozotocin, and randomly divided into blank (Control group) group, model group (Model group), metformin group (MET group) and UA group. General conditions such as body weight and blood glucose were recorded, and peripheral blood and pancreatic tissues were collected after six weeks of gavage to assess insulin intervention. Immunohistochemistry was used to observe the pathological changes in pancreatic tissues; horseshoe crab reagent was used to detect the changes in serum LPS content; qRT-PCR was used to detect the expression of pancreatic TLR4, MyD88, IκBα, and NF-κB p65 mRNAs, as well as the expression of the transcription factors RORγt and Foxp3 mRNAs; and Western blot was used to detect the expression of pancreatic TLR4, MyD88, IκBα , NF-κB p65 protein expression, and transcription factors RORγt, Foxp3 protein expression; flow cytometry to detect changes in the ratio of peripheral blood Th17, Treg cells; ELISA to detect changes in serum TNF-α, IL-6, IL-1β levels. Results After STZ-induced diabetic rats were treated by gavage for 6 weeks, compared with the Model group, fasting blood glucose (FBG) decreased significantly in both the MET and UA groups, and body weights increased; inflammatory infiltration of pancreatic β-cells was reduced; and the expression of TLR4, MyD88, IκBα, NF-κB p65, RORγt mRNA and protein expression was significantly decreased; LPS content was significantly decreased; IκBα, Foxp3 mRNA and protein expression was significantly increased; Th17/Treg ratio was significantly decreased; and TNF-α, IL-6, and IL-1β content was significantly decreased. Conclusion UA can improve the symptoms of rats by reducing LPS shift, inhibiting TLR4/NF-κB pathway, down-regulating RORγt and up-regulating Foxp3 expression to correct the imbalance of Th17/Treg cell ratio in T1DM rats.
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Effects of Shaoyao Gancao granule on hair growth, behavior and hypothalamic pituitary adrenal axis in mice with alopecia areata
QU Baoquan, LYU Shuying, LIN Wenjun, YANG Dingquan
Abstract:
Objective To explore the effects of Shaoyao Gancao granule on hair growth, behavior and hypothalamic pituitary adrenal (HPA) axis in mice with alopecia areata (AA). Methods Forty-two C3H/HeJ mice were randomly divided into control, model, Shaoyao Gancao granule, corticotropin-releasing hormone receptor 1 (CRHR1) antagonist, and compound glycyrrhizin tablet (CGT) group. Photography, dermoscopy photography, weight weighing, behavioral measurement were taken, as well as corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, glucocorticoid receptor (GR), and brain derived neurotrophic factor (BDNF) were assessed. Results Compared with the model group, high-dose Shaoyao Gancao granules could improve hair regeneration and weight gain (P<0.05), increase the percentage of total exercise distance and central area exercise distance in the open field experiment (P<0.05), reduce the immobility time in the forced swimming experiment and tail suspension experiment (P<0.05), reduce peripheral blood CRH, ACTH, Cortisol levels (P<0.05), and increase the expression of GR and BDNF in the hippocampus (P<0.05). Conclusions Shaoyao Gancao granule can promote hair growth and improve behavioral performance in mice with AA. The effects may be related to downregulating the levels of CRH, ACTH, and Cortisol, upregulating the expression of GR and BDNF, and inhibiting excessive activation of the HPA axis.
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Advances in the study of CAV1 in digestive tract tumors
Wu Zhihang, Pan Haibang, Tang mingzheng, lixiaofeng, rong yao, cuiyan
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[Abstract] Digestive tract tumour is currently one of the most common types of cancer in the world, including esophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer, etc. Their prognosis is not good and the treatment still needs further improvement. Caveolin-1（CAV1）has a dual regulatory effect in digestive tract tumors, which is both a tumor suppressor and a carcinogen. CAV1 plays an important role in cell proliferation, invasion, metastasis, angiogenesis and drug tolerance of digestive tract tumors, the regulation of CAV1 protein and its related signaling pathways may become one of the strategies for the treatment of digestive tract tumors. Therefore, the review analyzes the relationship between CAV1 and digestive tract tumors in terms of structure, function, expression regulation, regulation of epithelial-mesenchymal transition（EMT）and drug resistance in digestive tract tumors in order to provide new ideas for the diagnosis and treatment of clinical digestive tract tumors.
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Advances of Programmed Cell Death in Post-stroke Cognitive Impairment
sunkexin, xiaoyuqian, wanjun, chenshuying, chenlimin, wangyan, baiyanjie
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Post-stroke cognitive impairment (PSCI) is one of the common complications after stroke, which has a significant impact on the quality of life of stroke patients. However, the pathogenesis has not been fully explained. More and more evidence shows that the mechanism of programmed cell death (PCD) is related to PSCI, including apoptosis, necrotic apoptosis, pyroptosis, generalized apoptosis, PARP-1 dependent cell death and iron death. Therefore, it is crucial to have a clear understanding of various mechanisms of PCD and their relationship with PSCI, and to elucidate the role of PCD in the pathogenesis of diseases. The article reviews six PCD pathways related to PSCI, summarizes their mechanisms of action in PSCI, and elucidates the possible crosstalk between different pathways, in order to provide data basis for clinical targeting of regulatory factors in the PCD pathway for the treatment of PSCI.
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Experimental study on the health hazards of brake pad particles and their main component antimony sulfide respiratory exposure in mice
LI Yanhong, XIU Jinghui, ZHOU Li, GUO Jianguo
Abstract:
Objective To study the potential harmful effects of brake source particles. Methods Grind the brake pad particles or antimony sulfide particles. Subsequently, the mice were exposed through tracheal perfusion for 1 month to observe pathological changes in in the lungs, heart, and liver, and flow cytometry was used to analyze the changes in peripheral blood macrophages and regulatory T cells (Treg). Results After exposure, there was deposition of foreign substances in the alveolar wall of mice, with obvious infiltration of inflammatory cells around blood vessels, which worsened with increasing exposure concentration. In addition, pathological changes such as vascular inflammation and microthrombosis in the heart, and hepatocyte swelling in the liver were observed. Treg cells in peripheral blood decreased and macrophages increased in the antimony sulfide group and low-dose brake pad particles group, while the proportion of M2-type macrophages decreased. Conclusions Exposure to brake pad particles and their component antimony sulfide particles has varying degrees of toxic effects on the lung, heart, and liver of mice, and has a impact on the immune system, indicating the potential health hazards of brake-derived air pollution.
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Effect of Sanjie Quban Recipe on the Keloid Model of BALB/C Nude Mice and Influence on Transforming Growth Factor-β1
Huang ChuHan, Yang DingQuan, Zhong ShiYi, Wu RuiYing, Yang ZhiShan, Fang HuiJuan, Liu QingWu
Abstract:
Objective This study aimed to investigate the therapeutic efficacy of the Sanjie Quban Recipe on a keloid nude mice model and its impact on Transforming Growth Factor-β1 (TGF-β1). Methods Keloid tissue after surgical resection was transplanted into the subcutaneous back of healthy SPF BALB/C female nude mice aged 6-8 weeks, and the keloid nude mice model was established. The mice were randomly divided into 3 groups, 5 in each group. They were respectively treated with Sanjie Quban Recipe, Asiaticoside tablet and sterile pure water. After 28 days of continuous gavage, keloid tissue was exfoliated and weighed, HE staining, Masson staining, and immunohistochemical staining (TGF-β1). The difference of keloid weight between the three groups before and after treatment was compared, and the difference of collagen fiber, fibroblast number and TGF-β1 expression between the three groups after treatment was also compared. Results The weight difference of keloid in the Asiaticoside tablet group was greater than that in the control group, and the weight difference before and after keloid treatment was the largest in the Sanjie Quban Fang group compared with the Asiaticoside tablet group and the control group (P < 0.01). Compared with the control group, the collagen fibers in Sanjie Quban Fang group were loose and the number decreased. The number of fibroblasts decreased. The expression of TGF-β1 in Sanjie Quban Formula group was decreased compared with control group (P < 0.01). Conclusion Sanjie Quban Recipe has certain therapeutic effect on keloid, the mechanism may be through reducing the expression of TGF-β1 in keloid tissue, thereby reducing the proliferation of fibroblasts and the synthesis of extracellular matrix. This study provides experimental basis and theoretical basis for the clinical treatment of keloid with Chinese medicine.
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MiR-379-5p inhibits proliferation, invasion and migration of mouse breast cancer 4T1 cells
Song Yanmei, Sun Ningxin, Liu Chen, Song Yifen, Li Hongli, Yin Chonggao
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By investigating the effects of miR-379-5p on the proliferation, invasion and metastasis of mouse breast cancer 4T1 cells, we provide new therapeutic targets for clinical inhibition of breast cancer proliferation, invasion and metastasis. Methods After plasmid transfection, 4T1 cells were utilized to detect the expression of miR-379-5p using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); 5-ethynyl-2' doxyuridine (5-ethynyl-2'-deoxyuridine, EdU) cell proliferation assay and Transwell assay to detect changes in proliferation and invasion ability of 4T1 cells in each group; Migration ability of 4T1 cells after overexpression and knockdown of miR-379-5p was examined by scratch healing assay; BABL/c mice were used to establish the transplanted tumor model of breast cancer mice, and the tumor growth in vivo after miR-379-5p overexpression was observed.The transplanted tumor model of breast cancer was established in BABL/c mice, and the effects of overexpression of miR-379-5p on tumor growth and the number and size of lung metastases were observed . Results EdU results showed that knockdown of miR-379-5p enhanced the proliferation ability of cells compared with the control group, and miR-379-5p overexpression reduced the capacity of breast cancer cells to proliferate (p<0.05). Transwell and wound healing assays showed that knockdown of miR-379-5p enhanced the invasion and migration ability of breast cancer cells, and overexpression of miR-379-5p significantly inhibited the invasive and migratory ability of cells (p<0.01). In vivo tumorigenesis experiment of BABL/c mice showed that overexpression of miR-379-5p could significantly slow down the growth rate of tumor (p<0.05) and inhibit lung metastasis (p<0.01 ).In vivo experiments demonstrated that overexpression of miR-379-5p significantly slowed tumor growth (p<0.05). Conclusions miR-379-5p plays the role of tumor suppressor gene in breast cancer and inhibits the proliferation, invasion and migration of mouse breast cancer 4T1 cells.
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Study on pathogenesis and animal model building mechanism of ovarian dysfunction
yangzhihui, Hu Yang, Zong Zheng, Sun Xiangming, Song Hui, Chen Yingxiang, Xu Beilei, Zhang Wenjun, Chen Luning, Li Wenlan
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Premature ovarian insufficiency (POI), also known as "ovarian insufficiency", has a high incidence of 1%-5%, and has been on the rise in recent years, which has seriously affected women's physical and mental health and quality of life. At present, the cause and mechanism of POI are still unclear, and the methods and applications of model construction are also confusing, and most models have some shortcomings in pertinence and stability. This also greatly limits the related research and clinical diagnosis and treatment of POI. Therefore, this paper summarizes and discusses the etiology and pathogenesis of POI and the construction of POI animal models, in order to provide more reference for the study of POI etiology and pathogenesis and the selection and construction of models.
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The effect of AIM in inflammatory reaction and lipid metabolism diseases
Zhang Fan, Tian Chun yu, Wang Jingcun, La Xiaojin
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Apoptosis inhibitor of macrophage (AIM), belongs to the group B of scavenger receptor cysteine rich-super family (SRCR-SF). AIM is a soluble protein secreted by macrophages. The expression of this protein is controlled by the liver X receptor (LXR), and it plays an important role in the immune response of the body. AIM, as a secreted protein of macrophages, plays a broad role. It not only inhibits the apoptosis of macrophages, but also participates in the regulation of macrophage polarization. In addition, relevant studies have revealed that AIM is involved in various physiological and pathological processes such as inflammation, obesity, atherosclerosis and cancer; It was used as a biological diagnosis marker for diseases such as tuberculosis, liver cirrhosis and the like; Besides, it can promote lipolysis of adipose cells by inhibiting the activity of fatty acid synthase (FAS), playing an important role in the regulation of lipid homeostasis, lipid metabolism and autoimmune diseases. In this paper, we reviewed the molecular characteristics of AIM and its effects on inflammation, lipid metabolism and other related diseases, showing multiple functional characteristics of AIM to provide the basis for relevant medical research.
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Autophagy and Neurological Diseases
Liang YuYing, Huang Yong, Liu JunSheng, Ou YiLin, Li YiWen, Zhang Rui, Li Zheng, Zhang Zhi Nan
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Autophagy is the main degradation and recycling pathway of abnormal aggregates and damaged organelles in cells, which maintain the normal metabolic balance and material renewal of cells. Autophagy has neuroprotective effects and can affect the functional state of the nervous system by regulating the homeostasis, development, apoptosis and other physiological processes of neurons and glial cells. In recent years, a large number of studies have shown that nervous system diseases are closely related to abnormal autophagy, and inhibition or overactivation of autophagy affects the occurrence and development of depression, neurodegenerative diseases and schizophrenia. Understanding the mechanism of autophagy in nervous system diseases is of great significance for the prevention and treatment of related diseases. This review mainly reviews the current research progress of autophagy and the above diseases of nervous system, in order to provide reference for further research of these diseases.
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Research progress in the effects of Δ9-tetrahydrocannabinol on the blood-brain barrier
Zhang Qianyao, CHENG Hao, HUANG Yi-zhen, TENG Han-xin, ZHANG Yue, ZAHNG Rui-lin
Abstract:
The psychoactive properties of cannabinoids are well known, and there has been controversy about whether cannabinoids can be used for therapeutic purposes worldwide.Δ9-tetrahydrocannabinol(tetrahidrocannabinol, THC), the main psychoactive substance in cannabis, its neurological mechanism has not been discovered until recently, and its neurological mechanism of action is still not fully understood. The blood-brain barrier(blood-brain barrier, BBB) is a very important barrier structure to protect the brain and is the first line of defense against foreign substances entering the brain. THC's lipophilic nature and its interaction with the endocannabinoid system make it more likely to act on the BBB. In this paper, we review the neurotoxic effects of THC, focusing on the effect and mechanism of THC on the BBB, and provide a theoretical basis for elucidating the neural mechanism of THC.
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Establishment and evaluation of animal model of Varicocele and Erectile dysfunction
lujie, liqunsheng, zhoulei, lidongrun, shenzhennan, lininghua, zhufanyu, chendong, tangwenping, yangwentao
Abstract:
Objective By surgery inducing Varicocele(VC) in SD rats and Apomorphine Test(APO Test),we screened the rats with Erectile dysfunction(ED) after VC,and explored the method of establishing VC and ED model.Methods Randomly divide 60 rats into control group,sham group,and model group,with 20 rats in each group.Referring to the Turner method,partially ligate the left renal vein to induce left VC.And conduct three APO Tests to screen rats with ED after inducing VC,observe and record the number of erection,genital grooming,and yawning.Measuring the diameter of spermatic vein.Weighing both testises and kidneys.HE staining and observing the pathological changes in the penis and left testis.The success rate of modeling was calculated in the model group.Results 15 out of 20 rats in the model group were successfully established VC and ED model,with a success rate of 75%.After modeling,the diameter of the left spermatic vein in the model group increased significantly and were significantly higher than before-modeling,and the diameter of the right spermatic vein in the model group increased and were higher than before-modeling.The weight of the left testises in the model group significantly decreased compared to the right testises.There was no significant difference between or within groups in the comparison of bilateral kidney weight. In the model group,the number of erections,yawning and genital grooming decreased significantly,and decreased with the time of modeling.The pathological changes of the left testis and penis were significant in the model group.Conclusions Turner method can induce the increase of the diameter of spermatic vein in rats,causing testis injury and weight loss,and APO Test can screen the rats with ED after VC induction.The combination of the two methods is suitable for establishing an animal model with VC and ED status similar to human.
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Establishment and evaluation of hyperuricemia mouse model based on triple method
ni jianyu, bai ningning, liu xianli, gong lihong, shou qiyang
Abstract:
Objective: To investigate whether a stable and reliable hyperuricemia model can be established in mice with ICR background by triple modeling method (combined with potassium oxazine, hypoxanthine and 30% yeast paste), and to evaluate the modeling method with positive drug febuxoesta. Methods: The hyperuricemia model of ICR mice was established by using potassium oxazine, hypoxanthine and 30% yeast paste diet, respectively, and the serum uric acid, creatinine, xanthine oxidase (XOD), uric acid oxidase (UOX) and other indicators were detected to evaluate the success of hyperuricemia model.Results: The serum uric acid level of ICR mice was not significantly changed by potassium oxazinate alone, which showed an increasing trend but no significant difference with that of 30% yeast paste diet and hypoxanthine combined groups, while the serum uric acid level in triple administration group was significantly increased at 7 days (P<0.01). After 14 days of dynamic monitoring, blood uric acid level of triple dose induced ICR mice peaked at 7 days. Meanwhile, the activity of XOD enzyme was increased, while that of UOX enzyme was decreased (P<0.001). In addition, triple-dose induced hyperuricemia in ICR mice was sensitive to the positive drug febuxoat, with a significant decrease in blood uric acid levels (P<0.001). Conclusion: The hyperuricemia model of ICR mice can be stably induced by triple administration at 7 days.
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Optimization and evaluation of an acute obstructive suppurative cholangitis model in rats
yukui, Liangxiaoqiang, hanmian, zhangjingzhe
Abstract:
Objective A stable model of acute obstructive suppurative cholangitis in rats was established to detect its pathophysiological indexes and provide a stable and reliable standardized animal model for the study of acute cholangitis and cholestasis.Methods SPF grade male SD rats were selected and the model was constructed by injection of toxoid into the lower bile duct and ligation of the common bile duct, and the changes in body weight, mortality, major indexes of liver function and histopathological changes in the liver were evaluated before and after modeling.Results After modeling, the body weight of rats in the model group decreased significantly; the number of rats died was less; the main indexes of liver function and liver pathology showed obvious changes of cholestasis and liver function damage.Conclusion In this study, a rat acute obstructive suppurative cholangitis model was successfully established, which has the advantages of easy operation, low damage, low mortality and high successful modeling rate, and can provide a standardized experimental animal model for the study of the mechanism of many common diseases and drug development.
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Research progress of pyroptosis in renal ischemia-reperfusion injury
sunhaojie, zhujunlei, liwei, wangsuogang
Abstract:
Pyroptosis is a programmed cell death mediated by cysteine proteases, which is characterized by mitochondrial participation, inflammasome assembly, plasma membrane perforation, and inflammatory release. As an important mechanism mediating the body's inflammatory response, pyroptosis plays a key role in renal ischemia-reperfusion injury (RIRI). This article reviews the molecular mechanism of pyroptosis, the mechanism of pyroptosis in RIRI and the research progress of therapeutic drugs in recent years, aiming to provide theoretical reference for the early treatment of RIRI.
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Research progress of mitochondria function regulation by TRP channels and its relationship with cardivascular diseases
Abstract:
TRP channel is a non-selective cation channe. In recent years, a large number of studies have found that TRP channels take participate in variety of cardiovascular diseases, and the study on mitochondrial function regulation by TRP channel and its relationship with cardiovascular diseases has become a research hotspot. Up to date, the relative references are mainly focused on TRPV, TRPM and TRPC channels. This review focuses on above TRP channels in the regulation of mitochondrial function and their relationship with cardiovascular diseases.
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Exploration of mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress
liu yan, pengmengwei, Liu gaoyuan, Yang Tiezhu, Zhang wenxian, Wuyaosong, Chen Yulong
Abstract:
【Abstract】Objective To study the core behavioral symptoms, biological indicators and pathological changes of the mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress (CRS). Methods BABL/c mice were randomly divided into control group, stress group, tumor group and stress combined with tumor group (S T). 4T1 cell lines were inoculated into the underarm of mice in tumor and S T groups. After tumor formation, mice in the stress and S T groups were subjected to CRS for 21 days. Body weight and food intake of each group were monitored during modeling. After the experiment, depression-like behavior of mice in each group was evaluated by sucrose preference test, open field test, elevated plus-maze test, and forced swimming test. After the mice were decapitated, the weight and volume of mouse tumor were measured. Serum tumor markers including carbohydrate antigen (CA199), carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF) and related neurotransmitters including 5-hydroxytryptamine (5-HT), norepinephrine (NE) and corticosterone (CORT) were determined by using Elisa method. HE staining was used to observe the histopathological changes of hippocampus and tumor of mice. Results In mice of S T group, the body weight and food intake were significantly decreased, tumor weight and volume were significantly increased, serum tumor markers (CA199, CEA, VEGF) levels were significantly increased, pleasure and desire to explore the new environment were weakened, stress and despair behaviors were significantly increased, serum neurotransmitters 5-HT and NE levels were significantly decreased, and CORT levels were significantly increased. In addition, the cell arrangement of tumor tissue was loose, the interstitial was reduced, the pathological nuclear classification phase was increased, the arrangement and morphology of neurons in the CA3 region of hippocampus were disordered, and the nuclear vacuolation-like changes were obvious. Conclusion The mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell line inoculation combined with chronic restraint stress showed the dual typical symptoms and biological indicators of breast cancer and depression, which can provide a good model reference for the experimental study of breast cancer complicated with depression.
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Study on the effect of Buyang Huanwu Decoction in reducing oxidative stress and protecting cerebral ischemia-reperfusion injury in rats' blood-brain barrier
Abstract:
Objective To explore the mechanism of Buyang Huanwu Decoction (BYHWD) in reducing oxidative stress levels to protect the blood-brain barrier (BBB) in cerebral ischemia/reperfusion injury (CIRI) rats. Methods: Middle cerebral artery occlusion / reperfusion （MCAO/R）model was established by wire embolization method in rats, and PeriCam PSI laser speckle flow imaging system was applied to detect whether the model establishment was successful. The neurological deficits of rats were evaluated by Zea longa score; The histopathological changes in the rat brain were observed by HE staining; The degree of brain edema was detected by dry and wet weight method; The BBB permeability was detected by Evansblue (EB) staining; Ultrastructural changes of BBB were observed by transmission electron microscopy; The levels of ROS, MDA, and SOD activities, which are related to oxidative stress, were detected by kits; The expression levels of MMP-9 were detected by immunohistochemical staining and Western blot; The protein expression levels of Occludin, ZO-1, and Claudin-5 in TJP were determined by double staining of immunofluorescence and Western blot. Results:BYHWD can reduce neurological deficit scores, alleviate the brain histopathological damage, alleviate the disruption of blood-brain barrier structure, prolonged the dense region of tight junction structure, attenuated the edema of the brain in the ischemic side, and reduce the BBB permeability in MCAO / R rats. BYHWD can decrease the levels of ROS and MDA, increase the activity of SOD, decrease the expression levels of matrix metalloproteinase-9 （MMP-9）, and increase the protein expression levels of Occludin, Claudin-5, and ZO-1. Conclusions: BYHWD can increase BBB tight junction protein expression levels, reduce the permeability of the BBB, protect the ultrastructure of the BBB, and reduce brain edema, and its mechanism may be related to the antioxidant stress of BYHWD and inhibition of MMP-9 activation.
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Effects of decoction of Euphorbia fischeriana Steud. and jujuba against breast cancer of different molecular phenotypes via PI3k/Akt pathway
maliwei, YAO Hongyu, CHEN Zhe, NI Shiyu, CHEN Song, LI Jing, LIU Jicheng
Abstract:
Objective To explore the effect of decoction of Euphorbia fischeriana Steud. and jujuba (DEFSJ) against estrogen receptor (ER) negative (-) and ER positive (+) of breast cancer via PI3k/Akt pathway, and to provide reference for targeted treatment of breast cancer. Methods DEFSJ extract was prepared and analysed by using UHPLC-Triple Quad. DEFSJ containing serum (CS) was prepared by a method of serumal pharmacology. Different concentrations of DEFSJ-CS were applied to (ER-) MDA-MB-453 cells and (ER ) MCF-7 of breast cancer in vitro for 48 h. Flow cytometry was used to detect the distribution of cellular cycle，DNA ladder assay was used to assess the degree of apoptosis，and Western blot was used to detect the expression of PI3k/Akt pathway-related proteins. The expressions of FoxO3a, FoxO1a and Bim mRNA were detected by a real-time quantitative polymerase chain reaction (qrt-PCR) method. Nuclear translocation of FoxO3a protein was detected by a confocal laser microscopy. Results Five batches of the DEFSJ extract were analysed by using UPLC, and the results showed that the preparation technology was feasible and the quality was controllable, ensuring the accuracy of pharmacological experiments results. DEFSJ-CS can block cells in G2/M phase (P<0.05，P<0.01). The cells treated with DEFSJ-CS emerged the typical apoptotic ladder in DNA ladder experiment. Compared with negative control group, DEFSJ-CS can decrease the proteins expression of p-PI3k，p-Akt，p-FoxO3a and p-FoxO1a (P<0.05, P<0.01) and can increase the proteins expression of Bim (P<0.05, P<0.01), and can decrease the mRNAs expression of FoxO3a and FoxO1a (P<0.05, P<0.01) and can increase the mRNA expression of Bim (P<0.05, P<0.01), and can enhance nuclear translocation of FoxO3a protein in the cells. Besides, these datas all showed that DEFSJ-CS had better effect on (ER-) MDA-MB-453 cells than (ER ) MCF-7 cells. Conclusion The regulatory effect of the DEFSJ extract on anti-breast cancer is involves the PI3k/Akt pathway, and the effect is varies with phenotypic differences.
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To explore the effect of Bufei Jianpi Formula on mitochondrial damage of skeletal muscle in COPD rats based on IRS-1/PI3K signaling axis
shentingting, lisuyun, liya, xuanyinshuang, lijingmei, Ligaofeng, hanbingyang
Abstract:
Objective To explore the effects of Bufei Jianpi Formula (BJF) on mitochondrial damage of skeletal muscle in COPD rats by regulating IRS-1/PI3K signaling axis. Methods 60 SPF SD rats were randomly divided into blank group, model group (COPD stable stage group), BJF group, pioglitazone group (PIO group), BJF PIO group and aminophylline group, with 10 rats per group. The stable COPD rat model was established by the method of smoking and nasal drip (Klebsiella pneumoniae). The samples were taken from the 9th week to the end of the 20th week, and the weight of the rats was measured every week. Routine sections and HE staining were performed on lung tissue and skeletal muscle tissue respectively, and the corresponding pathological changes were observed under light microscope. Lung function of rats was observed by whole body plethysmography (WBP) at week 0, 8 and 20, including tidal volume (VT) and peak expiratory flow, respectively. PEF), 50% tidal volume expiratory flow (EF50). The mRNA expression of IRS-1, Leptin, PGC1-α and PI3K in rat skeletal muscle was detected by qPCR. The expression of PGC-1α, TFAM, IRS-1, PI3K, AKT, p-AKT and Leptin in rat skeletal muscle tissue was detected by WB technique. Results Compared with the Control group, there were a large number of inflammatory cells infiltrated in the alveolar interstitium and bronchus in the Model group, some alveolar walls were broken and fused to form air cavities, and the fibrous network was destroyed. Compared with Model group, the rupture of alveolar wall and destruction of fibroid network were improved in all groups after medication treatment, and the inflammatory cell infiltration in bronchus was reduced, especially in BJF group and Am group. Compared with the Model group, the skeletal muscle pathology of each group after medication treatment could improve the arrangement space, atrophy and fracture of muscle fibers in different degrees, and the cytoplasmic staining of muscle cells was uneven, among which the BJF group had a more significant effect. Compared with Control group, PEF, VT and EF50 in Model group were significantly decreased from week 8 (P<0.01), while PEF and EF50 in BJF, BJF PIO and Am groups were significantly increased (P<0.01). Compared with Control group, mRNA expression levels of IRS-1, PGC1α and PI3K in Model group were significantly decreased(P<0.01), while Leptin mRNA expression level was significantly increased (P<0.01). Compared with Model group, Leptin mRNA expression levels in four medication groups were significantly decreased (P<0.01), while IRS-1 mRNA expression levels in BJF, PIO and BJF PIO groups were significantly increased (P<0.01). The mRNA expression level of PGC-1α in BJF and BJF PIO groups was significantly higher than that in Model group (P<0.01). Compared with Model group, the expression level of PI3K mRNA in BJF, BJF PIO and Am groups was significantly increased (P < 0.01). Compared with Control group, the protein expression levels of PGC-1α, IRS-1 and PI3K in Model group were significantly decreased (P<0.01), while the protein expression level of Leptin was significantly increased (P<0.01). Compared with Model group, the expression level of PGC-1α protein in BJF group was significantly increased (P<0.05), and the expression level of IRS-1 protein in BJF PIO and BJF groups was significantly increased compared with Model group (P<0.05, P<0.01). The expression level of PI3K protein in Am, BJF and BJF PIO groups was significantly higher than that in Model group (P<0.01), especially in BJF PIO group. Compared with Control group, the protein expressions of TFAM and P-Akt in quadriceps femoris tissue of Model group were significantly decreased, while the protein expressions of TFAM and P-Akt were increased in all treatment groups, but there was no statistically significant difference (P>0.05).Conclusion By regulating IRS-1/PI3K signaling axis, Bufei Jiempi can improve the mitochondrial damage of skeletal muscle, increase the expression of mitochondrial coactivator PGC-1α and mitochondrial transcription factor TFAM, enhance mitochondrial biosynthesis, and reduce the pathological damage of lung and skeletal muscle tissue.
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LIMK1 promotes the progression of cervical cancer by up-regulating the ROS/Src pathway
Jia Yajing, Du Naiyi, Zhao Wei, Li Yongping, Liu Yakun
Abstract:
Abstract: Objective To explore the effect of LIMK1 on the progression of cervical cancer (CC). Methods LIMK1-overexpressed human cervical cancer HeLa cells were constructed and inoculated subcutaneously in nude mice. The tumor volume was observed and the expressions of NOX2, NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 proteins in the tumor cells were detected by Western blot assay. LIMK1-overexpressed HeLa cells were cultured under 5%O2 and added with antioxidants. The protein expressions of LIMK1, NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 in the cells were detected by Western blot assay. The cell migration ability was detected by scratch assay. Transwell assay was used to detect cell migration and invasion ability. Monoclonal proliferation assay was used to detect cell proliferation ability. Results The tumor volume of nude mice inoculated with LIMK1-overexpressed HeLa cells increased significantly, and NOX2, NOX4, p-Src, p-RUNX3, and MMP-9 proteins increased, while RUNX3 protein expression decreased. In LIMK1-overexpressed HeLa cells, the protein expressions of LIMK1, NOX4, p-Src, p-RUNX3, and MMP-9 were increased, RUNX3 protein expression was decreased, while the cell migration, invasion, and proliferation ability were increased. However, after adding antioxidants, the expression levels of NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 proteins, and the ability of cell migration, invasion, and proliferation were not different from those of HeLa cells with normal expression of LIMK1. Conclusion LIMK1 promotes the progression of cervical cancer by promoting the ROS/Src pathway, thereby promoting the migration, invasion, and proliferation ability of cervical cancer cells.
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Research progress of SHP2 in digestive system tumors
WANG Peng, FAN Jianchun, JIA Juming, DIAO Qingfei, WU Xueliang, Xue Jun
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【Abstract】 Currently malignant tumors have become one of the major diseases threatening human health,with disability and mortality rates increasing year by year.Protein tyrosine phosphatase 2 (SHP2) of Src homology 2, an important member of the PTP family, is a tyrosine phosphatase with a wide range of functions,whose expression is elevated in a wide range of solid tumors,and plays a important regulatory role in invasion,metastasis,proliferation,apoptosis and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but there is no systematic report on the role of SHP2 in digestive system tumors.Based on this paper,we reviewed the biological functions and clinical significance of SHP2 in seven different tumors of the digestive system,explored its roles and mechanisms in different cancer development stages,and summarized and looked forward to the development of SHP2 inhibitors,to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance for the improvement of cancer patients' survival rate.
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Research progress on the relationship between regulatory cell death and Dilated cardiomyopathy
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Dilated cardiomyopathy (DCM) is one of the common primary diseases of heart failure and arrhythmias. With the continuous deepening of research in recent years, the intrinsic molecular mechanism of regulatory cell death (RCD) has gradually become clear. Researchers have found that RCD plays a very important role in the occurrence and development of DCM. RCD mainly includes apoptosis, necrotic apoptosis, Pyroptosis, Ferroptosis, autophagy, etc. They have certain correlation and can interact and regulate each other. This article provides an overview of the current research status on the mechanisms of the five RCD modes involved in DCM, in order to provide reference for future related experiments and clinical studies.
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Research progress on the interaction between gut microbiota and microRNA in inflammatory bowel disease
KONG Binghui, BAI Longzhou, YANG Li
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Inflammatory bowel disease (IBD) is a chronic intestinal disorder characterized by an immune response to factors in the intestinal environment. Dysregulation of the intestinal flora may lead to the development of inflammation. Studies suggest that fecal transplants, probiotics, prebiotics, and dietary interventions may play a potential role in reshaping the intestinal flora and treating the disease. MicroRNAs (miRNAs) participate in physiological processes, including cell development, proliferation, and apoptosis. In addition, miRNAs are important in inflammatory processes and play a role in regulating pro- and anti-inflammatory pathways. MiRNA profiles may serve as a diagnostic tool for IBD and prognostic markers for the disease. The relationship between miRNAs and intestinal flora has not been fully elucidated, and recent studies have demonstrated their roles in regulating the intestinal flora and inducing ecological dysbiosis. In turn, the flora can regulate miRNA expression and improve intestinal homeostasis. It is important to continue exploring this relationship. Therefore, the purpose of this review is to analyze the relationship between gut microbiota and miRNAs in IBD and identify possible precision-targeted therapies for IBD.
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Study on the effects of various herbs and different proportions of herbs in Huidu Yinhua Powder on methicillin-resistant Staphylococcus aureus
LI Yufen, JIANG Shuang, SONG Wu, JIANG Tao, LIU Chang, ZHOU Haofang, TANG Yating, SU Xin
Abstract:
Objective: To study the inhibitory ability of Huidu Yinhua Powder, from “Orthodox Manual of External Medicine”, on methicillin?resistant staphylococcus aureus (MRSA) as well as the inhibitory effect of virulence factor α-hemolysin (Hla) activity and biofilm formation, and at the same time, to explore the optimal ratios of Huidu Yinhua Powder, to provide experimental support for the new use of the ancient formula. Methods: The inhibitory effects of Huidu Yinhua Powder and the herbs in the formula on USA300 were analyzed by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and disk diffusion assay (K-B method). Hemolysis assay, neutralization assay, Oligomerization assay, Western Blot (WB) to verify in which form the drug inhibits the activity of the virulence factor alpha-hemolysin (Hla). The biofilm assay was performed to evaluate the inhibitory effect of Huidu Yinhua Powder on biofilm, while finally orthogonal experiments were performed to explore the optimal ratios of Huidu Yinhua Powder. Results: Huidu Yinhua Powder inhibited the MRSA strain with a MIC90 of 64 mg/mL and an MBC of 256 mg/mL, with antibacterial circle diameter of 7.50±0.50 mm. Huidu Yinhua Powder inhibits Hla activity by inhibiting Hla secretion and the minimum effective concentration (MEC) was 16 mg/mL, while the MEC of biofilm was 8 mg/mL. In Huidu Yinhua Powder, Honeysuckle and Astragalus only affected the hemolytic activity of MRSA and the formation of biofilm without inhibiting the growth of bacteria, the hemolytic activity MEC and the biofilm MEC of both of them were 32 mg/mL. Glycyrrhiza had a strong bacterial inhibitory capacity, with a MIC90 of 8 mg/mL and a biofilm MEC of 1 mg/mL, without showing inhibitory hemolytic activity at subinhibitory concentrations. The final orthogonal experiment showed that when the ratio of honeysuckle: astragalus: glycyrrhiza in Huidu yinhua Powder was 1:2:4, the MIC90 was 16 mg/mL, the hemolytic activity MEC was 8 mg/mL, and the biofilm MEC was 4 mg/mL, all of which were the lowest among the nine groups. Conclusion: Huidu Yinhua Powder affects the hemolytic activity and biofilm formation of MRSA at sub inhibitory concentrations, with the optimal ratio of honeysuckle, astragalus, and glycyrrhiza being 1:2:4.
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Effect of vitamin D on the structure and diversity of intestinal flora in spontaneously diabetic rats
chen lin, tan hong xing, hao li ping, li yan yan
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[Abstract] Objective To investigate the effect of vitamin D (VD) on intestinal flora in spontaneously diabetic rats. Methods Zucker diabetic fatty rats (ZDF rats) were randomly divided into control group (Con), VD control group (VD), model group (T2DM) and VD intervention group (VD+T2DM). Fasting blood glucose profile and oral glucose tolerance level were detected in rats in each group. The 16S rDNA sequencing technology was used to detect the changes in rat intestinal flora, and OTU analysis (Venn diagram), Alpha diversity analysis (chao1, observed species, PD whole tree, shannon and simpson), Beta diversity analysis [principal coordinate analysis (PCoA)], flora structure and colony species variability analysis [linear discriminant analysis and influence factor (LEfSe) analysis]. Results VD intervention significantly improved fasting blood glucose levels and insulin resistance in T2DM rats (P<0.05).Alpha diversity results showed no significant differences in chao1, observed species, PD whole tree, shannon and simpson indices between T2DM and VD+T2DM groups (P>0.05) ; Beta diversity analysis showed that the VD+T2DM group had more species similarity with the Con group compared with the T2DM group. The dominant bacteria of rat intestinal flora in each group were significantly different; compared with the T2DM group, the VD+T2DM group showed decreased abundance of Bacteroidetes and increased abundance of Firmicutes and Clostridium XIVa. Conclusion VD improved fasting glucose elevation and insulin resistance in T2DM rats; VD improved the structure of intestinal flora, decreased Bacteroidetes, and elevated Firmicutes and Clostridium XIVa abundance in T2DM rats.
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Overview of in vitro skin models of transdermal drug delivery system
LiuYan, HuXiaolei, XuKeHong, ZhaoHaiRong, WuXiuMei, YangZiZhong, ZhangChengGui, ZhaoYu, GaoPengFei
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Skin modeling of transdermal drug delivery systems refers to the experimental models which can mimic the structure and function of human skin to explore and evaluate the absorption, penetration and efficacy of medicines in transdermal drug delivery. It provides alternative to traditional human skin experiments and reducing the utility of human skin in medicines research, which is convenient, controllable, and cost-effective . For the skin models of transdermal drug delivery systems, this paper introduces commonly used animal skin models, artificial skin models, and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines, and analyzes its advantages and disadvantages as well as its applications, so as to provide references for the research and development of transdermal formulations and topical therapies and so on.
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AMPK: Diverse Regulatory Mechanisms and New Perspectives for Disease Treatment
Ning Jinghua, zhang xin, zhang Yuzhe
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The AMP-activated protein kinase (AMPK) is a conserved cellular energy Adenosine monophosphate, plays an important role in regulating cell growth, proliferation, differentiation, autophagy, phosphorylation, crosstalk, and glucose and lipid metabolism. AMPK is activated when the body is low in energy or under certain extreme conditions, and it's suppressed when there's an excess of nutrients to maintain the energy balance. In addition, the regulatory mechanism of AMPK signaling pathway mediating ferroptosis also reflects its unique role. AMPK plays a special regulatory function in different organelles, which provides a new direction for disease therapy. It is also a therapeutic target for the prevention of diseases such as reproductive system diseases, aging, cancer, inflammation and cardiac dysfunction. This article reviews the damage of cellular energy imbalance to the body's microenvironment. AMPK stimulates its potential therapeutic potential in diseases and drugs through diverse signal regulatory mechanisms, it provides a new way of treatment for different system diseases. This review summarizes the diverse regulatory mechanisms of AMPK signaling pathway, and provides theoretical reference for cancer therapy and other diseases therapy targeting AMPK.
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Discussion on the Mechanism of "Brain-Spleen Inflammation Coupling" in Rat Model of Acute Ischemic Stroke Stasis Toxin Syndrome
dongyilei, Liu Yue, Li Junyuan, Fu Jianhua, Zhang Yunling, Yao Mingjiang
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【Abstract】Objective: To investigate the correlation between brain injury and spleen damage in rat models of acute ischemic stroke and stasis interaction, and its effect on the signal axis of MCP-1/CCR2 chemokine, and to provide experimental basis for the mechanism of "brain-spleen inflammatory coupling" in spleen lesions caused by acute ischemic stroke. Methods: Forty male SD rats were randomly divided into sham group, carrageenan/yeast stasis syndrome group (Carrageenan/Yeast, CA/Y), middle cerebral artery occlusion group (MCAO), middle cerebral artery occlusion (MCAO), middle cerebral artery stasis syndrome group (MCAO CA/Y), 10 rats in each group. The CA/Y group and the MCAO CA/Y group were injected with 10 mg穔g-1 carrageenan, 10 mg穔g-1 intraperitoneally on the first day of molding, and 2 mg穔g-1 of dry yeast suspension were injected subcutaneously on the second day, and the MCAO group and MCAO CA/Y group were established by wire embolism on the second day. 24 h after cerebral infarction model, the neurological deficit score was performed on each group of rats, the percentage of cerebral infarction area was observed by TTC staining, the spleen weight was determined, and the correlation between the percentage of cerebral infarction area and spleen weight was further analyzed by Spearman correlation coefficient, the pathological morphology of brain tissue and spleen tissue was observed by hematoxylin-eosin (HE) staining, and monocyte-1 (monocyte) was detected in rat plasma by enzyme-linked immunosorbent assay (ELISA). chemotactic protein 1, MCP-1), interferon-γ γ (IFN-γ) content, western blot method to detect ischemic side brain tissue chemokine C-C-motif receptor 2 (CCR2) protein expression. Results: Compared with the ham group, the neurological deficit score, cerebral infarction area, MCP-1 and IFN-γ content in plasma were significantly increased (P<0.01), spleen weight decreased significantly (P<0.01), and the expression of CCR2 protein in brain tissue was also significantly up-regulated (P<0.05) in the MCAO group and the MCAO CA/Y group. The area of cerebral infarction increased significantly (P<0.01), the weight of the spleen decreased significantly (P<0.01), and the expression of CCR2 protein in brain tissue and spleen tissue was also significantly up-regulated (P<0.05), compared with the MCAO group, the area of cerebral infarction in the MCAO CA/Y group was significantly increased (P<0.01) and the weight of the spleen decreased significantly (P<0.05). Spearman correlation analysis showed that spleen weight was negatively correlated with the percentage of cerebral infarction area (P<0.01, r=-0.9711). The pathological morphological observation results showed that the pathological changes in the MCAO CA/Y group were the most serious, cerebral liquefaction necrosis foci could be seen in the brain tissue cortex, the arrangement of neuronal cells in the lesions was sparse, disordered, volume atrophy, a small number of vacuoles and nuclear solidification, most of the neuronal cells were red degeneration and necrosis, microglia hyperplasia was obvious, small blood vessels were significantly increased, and interstitial lipid degeneration was superb; The density of periarterial lymph sheath cells in part of the spleen tissue is reduced, and the marginal area is widened. Conclusion: A correlation between brain and spleen injury could be found after acute ischemic stroke with stasis and toxins syndrome, and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of "brain-spleen inflammation coupling".
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Effect of lidocaine regulating Hippo-YAP signal pathway on ischemia-reperfusion injury in orthotopic liver transplantation rats
Liu Yue, Akbar Nurmaimaiti, Ye Jian-rong
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Objective: To explore the effect of lidocaine (LID) on ischemia-reperfusion injury in orthotopic liver transplantation (OLT) rats and to analyze its mechanism of action. Methods: 60 rats were randomly divided into control group, model group, low-dose LID group, medium-dose LID group, high-dose LID group, and Verteporfin group, with 10 rats in each group, except for the control group, and other rats were used to construct OLT models. The pathological changes in liver tissue was observed by hematoxylin-eosin (HE) staining, the serum aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL) and lactate dehydrogenase (LDH) activities were detected by automatic biochemical analyzer, the liver tissue inflammatory factor tumor necrosis factor-α (TNF-α), interleukin (IL) -6, IL-1β and IL-10 levels were detected by enzyme-linked immunosorbent assay (ELISA), the reactive oxygen species (ROS) was detected by fluorescence probe method, the malondialdehyde (MDA) was detected by thiobarbituric acid colorimetric method, the superoxide dismutase (SOD) was detected by nitrogen blue tetrazole colorimetry, the glutathione peroxidase (GSH-Px) was detected by spectrophotometer method, the apoptosis of liver histiocyte was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) , and the expression of mammalian STE20 like protein kinase (MST1), phosphorylation (p) - MST1, large tumor suppressor factor 1 (LATS1), p-LATS1, Yes associated protein (YAP), p-YAP, as well as apoptosis related proteins B-cell lymphoma 2 (Bcl-2) and Bcl-2 related X protein (Bax) were detected by western blotting (WB). Results: Compared with control group, the liver tissue in model group rats showed injury, liver cells necrosis and a large number of inflammatory cells infiltration, the cell apoptosis rate, serum AST, ALT, TBIL, LDH activity, liver tissue TNF-α, IL-6, IL-1β, MDA, ROS, and Bax levels significantly increased, the liver tissue IL-10, SOD, GSH-Px, Bcl-2, p-MST1/MST1, p-LATS1/LATS1 and p-YAP/YAP proteins expression levels were significantly reduced (P<0.05). Compared with model group, the liver tissue injury was reduced in low-dose LID group, medium-dose LID group, and high-dose LID group, the cell apoptosis rate, serum AST, ALT, TBIL, LDH activity, liver tissue TNF-α, IL-6, IL-1β, MDA, ROS and Bax levels were significantly reduced, the liver tissue IL-10, SOD, GSH-Px, Bcl-2, p-MST1/MST1, p-LATS1/LATS1, and p-YAP/YAP proteins expression levels were significantly increased (P<0.05). Hippo-YAP signaling pathway inhibitor Verteporfin reversed the improvement effect of LID on ischemia-reperfusion injury in OLT rats (P<0.05). Conclusion: LID may activate the Hippo-YAP pathway, which reduce inflammatory response, oxidative stress, and liver cell apoptosis, and improve liver ischemia-reperfusion injury in OLT rats.
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Overview of the research of Q fever in animal models
Abstract:
Q fever is a zoonotic disease caused by Coxiella burnetii infection, which is widely spread in nature. Animal models are important tools to study the etiology and pathogenesis of infectious diseases and evaluate the effectiveness of vaccines. In recent years, a variety of animal models such as invertebrates, rodents and non-human primates have been used to study Q fever. This paper summarizes the research status of different Q fever animal models, discusses the advantages and disadvantages of these models, and summarizes the requirements and standards of future modeling work.
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Advances in the application of laser speckle contrast imaging in animal models of chronic cerebral hypoperfusion
Abstract:
Laser speckle contrast imaging technology can be used to dynamically measure microcirculation blood flow in tissues or organs in a visual and quantifiable way. Because of its advantages of in vivo detection, real-time imaging and simple operation, it has been applied in many fields of microcirculation detection.The animal model of chronic cerebral hypoperfusion is mainly constructed by reducing the bilateral common carotid artery blood flow to the brain, which can cause long-term insufficient cerebral blood supply. Laser speckle contrast imaging technology can observe and analyze the cortical cerebral blood flow, collateral circulation opening, neurovascular coupling response, etc., in the animal model of chronic cerebral hypoperfusion , so as to judge the success of animal model modeling and the therapeutic effect of intervention methods. In this paper, the application and advantages and disadvantages of laser speckle contrast imaging technology in the animal model of chronic cerebral hypoperfusion were summarized in order to provide new ideas for clinical treatment and scientific research.
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Research progress of berberine in the field of neuroprotection in ischemic stroke
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Berberine is a natural Isoquinoline alkaloid, which can be initially used as a broad-spectrum antibacterial agent in clinical treatment of enteritis, peptic ulcer, chronic gastritis, pneumonia and other diseases. In recent years, with the in-depth study of the pharmacological effects of Berberine, more and more evidence shows that Berberine has neuroprotective effects on ischemic stroke. In this review, we introduced the intervention of Berberine on risk factors of ischemic stroke, and discussed the neuroprotective effects of Berberine in different mechanisms of ischemic stroke in detail, aiming to provide some reference for clinical and basic research in this field.
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Advances in Research on Mechanisms Related to Myocardial Regeneration in Neonatal Rats
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Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death. It was previously thought that myocardial cells of adult mammalian heart possess a limited ability to proliferate and renew themselves, and that after ischemic injury, a large number of myocardial cells are lost and eventually replaced by non-contractile scar tissue. In contrast, it has been widely reported that mammals have the ability to regenerate myocardium which is restricted to early postnatal life, and that it is strong enough to repair damaged heart tissue. The discovery of myocardial regeneration in neonatal heart has provided an ideal animal model to investigate the mechanisms that affect myocardial cell proliferation, and subsequently many mechanisms that can reverse myocardial cell cycle arrest and promote myocardial cell proliferation have been revealed. In this paper, we review the factors affecting myocardial regeneration gene expression (ncRNAs, transcription factors, etc.), myocardial regeneration-related signaling pathways, and the regulation of myocardial regeneration by non-myocardial cells (extracellular matrix, immune response, epicardium, etc.), so as to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.
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Establishment of genetic monitoring methods for experimental quail
heyang, zhangxiulin, zhangqiuyu, zhangxiaolu, fubo, wangwendong, duxiaoyan, chenzhenwen, lichanglong
Abstract:
Objective To establish a genetic monitoring method for laboratory quails. Methods Quail microsatellite loci were screened through literature search, and microsatellite DNA loci suitable for quail were screened by interspecific transfer method in quail closely related species, chickens and ducks. Quail liver tissue DNA was extracted as a template, and the corresponding loci were screened by PCR amplification and agarose gel electrophoresis. Finally, based on the amplification of the selected microsatellite loci, the number of alleles, and polymorphism, microsatellite loci combinations for quail genetic quality detection were selected and detection methods were established. Results We preliminary determined 23 microsatellite loci for genetic monitoring of closed-colony laboratory quails. Conclusion A genetic monitoring method for laboratory quails is preliminary established.
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Innovation and exploration of Medical Laboratory Animal Science teaching based on smart teaching environment
Abstract:
Objective In the traditional laboratory zoology lecture environment, there is less teacher-student interaction, less student interest and less engagement in learning.In order to further improve the teaching quality of laboratory zoology, Methods this teaching and research department based on the different teaching environment of multimedia classroom and intelligent classroom, the theoretical course teaching of Medical Laboratory Zoology as the research ,object, the course lecture format, teaching mode, teaching methods and other aspects of innovation and exploration. The study used questionnaires to understand changes in student engagement in learning and preferences for smart classroom use, and NVivo qualitative analysis software to code student classroom behaviour. Results The smart teaching environment resulted in higher student interest and more frequent teacher-student interaction in the classroom. At the same time, students are significantly more engaged in learning than in traditional teaching, with higher correct rates on in-class and post-lesson exercises and a better grasp of concepts related to laboratory zoology. Conclusions In summary, the smart teaching environment can bring students a better feeling and experience, improve their interest in laboratory zoology, increase classroom learning engagement and achieve good teaching results.
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Progression of tripterygium wilfordii polyglycoside in mice with premature ovarian insuffici-ency model at different time points
马林纳, makun, fanxiaodi, luojie, lijiani, zhanghan
Abstract:
Objective The changes of relevant indexes in the mice model of early-onset ovarian insufficiency caused by tripterygium wilfordii polyglycoside were discussed, and the best time point for intervention was determined. Methods Forty female ICR mice were randomly divided into blank group, A, B, C, and D model groups, with 8 mice in each group. The blank group was given gavage purified water for 14d (0.01ml/10g), and the remaining groups were given tripterygium wilfordii polyglycoside suspension (80mg/kg, 0.01ml/10g) for 1d (A model group), 3d (B model group), 7d (C model group), 14d (D model group), and the materials were taken in batches. Weigh the body weight, wet weight uterus and bilateral ovaries of mice in each group; Serum FSH, LH, E2, P, AMH, INH-B and T contents were detected by enzyme-linked immunoassay. HE staining observed the number and development status of follicles and corpus luteum at all levels of mice in each group. TUNEL fluorescence staining method detected the apoptosis area in the ovaries of mice in each group. The IHC method detected the positive expression of VEGFA, CD34 and EPO proteins in the ovaries of mice in each group. The mRNA expression of HIF-1α, SDF-1 and CXCR4 in each group of mice was detected by PCR. Results Compared with the blank group, the changes of indicators in model A did not meet the POI modeling standard. The ovarian index, uterine index and body weight of mice in the B model group decreased significantly (P<0.01), the weight of the C model group decreased significantly (P<0.01), and the ovarian index of the D model group decreased significantly (P<0.05). The serum indexes of the B, C and D model groups increased the contents of FSH and LH (P<0.01 or P<0.05), and the contents of E2, PROG, AMH, INH-B and T decreased (P<0.01). The number of basal follicles, presinus follicles, sinusoidal follicles, antral follicles, preovulatory follicles and corpus luteum decreased significantly (P<0.01 or P<0.05) and the number of atresia follicles increased significantly (P<0.01) in the B, C and D model groups. The apoptosis area of TUNEL fluorescent staining in A, B, C, and D model groups increased significantly (P<0.01 or P<0.05). The positive expression of CD34, VEGFA and EPO in the B, C and D model groups decreased significantly (P<0.01 or P<0.05). The expression of mRNA in the A and B model groups of HIF-1α, SDF-1 and CXCR4 was significantly increased (P<0.01 or P<0.05). Compared with the B model group, the relevant indexes of the C and D model groups changed significantly, indicating that the C and D models were more serious and tended to develop POF. Conclusion The B model group is the turning point of ovarian function from impaired POI to irreversible POF, suggesting that 3d administration of tripterygium wilfordii polyglycoside is the best time to induce POI disease model and effective drug intervention.
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Research progress of noncoding RNA in methamphetamine-induced addiction and neurotoxicity
zhang shu wei, cheng hao, wang hao wei, miao lin, li yi, guan li na, zeng xiao feng
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Methamphetamine (METH) is highly addictive and neurotoxic, which can cause cognitive and memory dysfunction in abusers. The harm of METH lies not only in its own toxicity, but also in the high physical and mental dependence of drug addicts, often causing mental disorders and causing violent behavior, bringing great safety risks to society. Non-coding RNA (ncRNA) does not code for proteins and is an important factor in regulating gene expression at the post-transcriptional level. Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity, but the specific mechanism is unclear. This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity, in order to provide a reference for ncRNA as a forensic identification index and potential drug intervention target for METH abusers.
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Advances in the mechanism of action of cyclic RNA in Parkinson's disease
liujuan, Li Yanjie, Qin hewei, Ma luyao, Zhao nannan, Xu zhenhua
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Parkinson's disease (PD) is a neurodegenerative disease characterized by the degenerative death of dopaminergic neurons in the substantia nigra, exhibiting a range of motor and non-motor symptoms that have a serious impact on the quality of life of patients. Circular RNA (circRNA, CircRNA) is a covalent closed-loop noncoding RNA that plays an important role in the progression of PD disease. This article reviews the involvement of circRNA in oxidative stress, regulation of transcriptional levels, neuroinflammation, autophagy, and α-synuclein.
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Analysis of application characteristics of acute liver injury animal model based on data mining
huyilong, zhangshuangli, qiuguangnan, fengyifan, miaomingsan, miaojinxin
Abstract:
Objective To investigate the modeling elements of various types of animal models for acute liver injury, and to provide references and suggestions for the establishment and evaluation of animal models for ALI. Methods The animal experimental literature of acute liver injury from 2002 to 2022 was searched in the databases of China Knowledge Network, WanFang, Chongqing Vip, Chinese Medical Journal Full Text Data, PubMed, etc. The animal species, positive control drugs, modeling methods, modeling drugs and drug administration of the animal models of acute liver injury involved in the literature were summarized and summarized. The results were analyzed using Excel, SPSS Modeler18.0 and Cytoscape3.8.2. Results A total of 896 papers were included in the database. The most used animal models for acute liver injury were male KM mice; the modeling methods were mainly chemical liver injury, alcoholic liver injury, drug-related liver injury and immune liver injury, and the corresponding main modeling methods were : ① intraperitoneal injection of 10.0 mL 0.1% CCl4 vegetable oil, 24 h before the experiment; ② gavage of 12.0 mL 50.0%-56.0% ethanol, 16 h before the experiment; ③intraperitoneal injection of APAP 300 mg/kg, 24 h before the experiment; ④ tail vein injection of Con A 20 mg/kg, 8 h before the experiment. The evaluation of the model was based on liver pathological indexes as the gold index, combined with biochemical indexes Serum ALT, AST, liver tissue homogenate SOD, MDA content and activity were used as direct indicators. Conclusions Since the causes of acute liver injury vary in clinical practice, the preparation of animal models of acute liver injury should be based on the specific study content and characteristics of the study, and the corresponding modeling methods should be selected.
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The mechanism of Yantiao fang regulating Rho/ROCK signaling pathway on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis
Chen Qian, Wang D, Zhang DY, Jia SL, Wang LH, Cao YJ, Li YH
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Objective To investigate the effect of Yantiao Formula on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating Rho/ROCK signaling pathway. Methods 70 BALB/c mice were randomly divided into blank group (10 mice), sham operation group (10 mice) and model group (50 mice).Mice in blank group were fed normally without treatment.Sham operation group mice only open free cecum without perforation ligation;A mouse model of acute gastrointestinal injury caused by sepsis was established by cecal ligation and perforation (CLP). The mice were randomly divided into model group, Yantiao formula low-dose, medium-dose and high-dose groups, and ROCK inhibitor group.Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of mice ileum.Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were determined by ELISA.The expression of PCNA and Ki-67 in mouse ileal cells was detected by immunohistochemistry.The expressions of Caspase 3 and Bax were detected by western blotting.The expression of ROCK mRNA and MLC mRNA in the Rho/ROCK pathway of mouse ileum were detected by RT-qPCR. Results The intestinal mucosa of the ileum tissue of mice with acute gastrointestinal injury caused by sepsis was atrophied obviously, villi were disordered, rupture and shedding were observed, epithelial cells were necrotic and shedding, inflammatory cell infiltration was obvious, and Chiu's pathological score was increased.Compared with blank group and sham group, the serum levels of pro-inflammatory mediators (IL-1β, IL-6, TNF-α) and mRNA levels of Caspase 3, Bax, ROCK and MLC in peripheral blood of mice in model group were increased, while the levels of anti-inflammatory mediators (IL-10) and expressions of PCNA and Ki-67 in ileum were decreased.Compared with model group, the histopathological changes of ileum in all Yantiao fang groups were improved to varying degrees with the increase of dose: the pathological score of Chiu's was decreased, the levels of IL-1β, IL-6 and TNF-α in serum were decreased, and the levels of IL-10 were increased.In addition, the expressions of PCNA and Ki-67 were increased, while the expressions of Caspase 3, Bax, ROCK mRNA and MLC mRNA were decreased. Conclusion Yantiao fang can inhibit the apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating Rho/ROCK signaling pathway, so as to reduce the inflammatory reaction of intestinal tissue and ultimately prevent the damage of intestinal mucosal tissue.
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Research status and trend of animal models of depression: a bibliometric analysis based on CiteSpace
YANG JIAHUI, LIN MENG, LUO XIAOQUAN, LUO TAO, GONG MEIFU
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【Abstract】Objective With the help of literature metrology, the scientific literature in the field of animal models of depression was analyzed, so as to better understand the development trends and hot spots in this field.Methods We obtained publications on depression and animal models from 2013 to 2022 from the Web of Science core set (WOSCC) database. Citespace 6.1R 1(64-bit) Basic was used to analyze the annual publications, countries, institutions, authors and keywords related to this field.Results A total of 1000 articles were included in this study. From 2013 to 2022, the number of papers published gradually increased and stabilized. In terms of the number of articles, the United States has the most published articles (256) and the most Polish Academy of Sciences (50) . Wegener Gregers is considered the most influential author in the field, with 23 published articles. When analyzing keywords, “Animal Model” was the most frequent, followed by“Major depression”. Conclusions This study highlights the important research trends and hot spots in the field of animal models of depression. The US, China and Japan are leading the way in terms of publication, indicating their significant contribution to the development of animal models of depression. However, international cooperation is limited and there is more cooperation within institutions and groups. The field focuses on signaling pathways and therapeutic approaches to determine the pathogenesis of depression and better treatments. The study provides a visual analysis of trends in depression research to help researchers keep abreast of the latest developments.
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Effect of gender difference on the model of rheumatoid arthritis induced by bovine type II collagen
Sun Wenting, Wan Yingying, Yang Jiaxi, Wang Wenqian, Wang Haonan, Ye Wanting, Kou Qiuai
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Objective To construct female and male bovine collagen-induced arthritis (CIA) models and compare the effects of gender differences on the joint and extra-articular manifestations of CIA models. Methods The CIA model was induced by injection of bovine type II collagen and Freund's complete adjuvant into female and male SD rats. The general condition, arthritis index, foot swelling, serum inflammatory factors and plasminogen activator inhibitor levels, spleen index, knee and ankle joint pathology, right rear paw bone destruction, and pulmonary interstitial lesions of rats in each group were evaluated. Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on the 21st day after initial immunization (P<0.05), but there was no significant difference in the degree of foot swelling between the two groups at any time point of observation (P>0.05); Serum tumor necrosis factor α, interleukin1β and spleen index of female CIA rats were significantly higher than those of male CIA rats (P<0.001; P<0.001; P<0.05), there was no significant difference in plasminogen activator inhibitor levels (P>0.05); The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathology of female CIA rats were significantly higher than those of male CIA rats (P<0.05), and the cartilage damage of knee joint and the bone damage of right rear paw of female CIA rats were significantly higher than that of male rats (P<0.05); Both male and female CIA rats showed pulmonary interstitial inflammatory cell infiltration and mild fibrosis, but the pulmonary interstitial lesions in females were more severe than those in males. Conclusion Both female and male CIA models constructed with SD rats can have both arthritis and pulmonary interstitial lesions, but the lesion degree of female CIA rats is more serious. When using CIA models for RA related research, attention should be paid to the impact of gender differences.
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Effects and mechanism of NCTD on proliferation and apoptosis of human leukemia cells by targeting PPP5C
zhangxin, cuibingjie, yuguoxing, wangfei, zhaoliang, gaona, dujing
Abstract:
Objective To study the effects and mechanism of norcantharidin (NCTD) on proliferation and apoptosis of human leukemia NB4 and K562 cells by targeting phosphoprotein phosphatase 5 catalytic (PPP5C). Methods NB4 and K562 cells were cultured in vitro, and the pcDNA3.1 and PPP5C-pcDNA3.1 plasmids were electroporated into NB4 and K562 cells. NB4 and K562 stable cell lines were screened with geneticin (G418). The protein and mRNA expression levels of PPP5C were identified by Western blot and qRT-PCR. The proliferation ability, migration ability and apoptosis rate of NB4、K562 cells were determined by CCK-8 assay, transwell assay and the Live DeadTM animal cell viability/toxicity detection kit. NB4 and K562 cells were divided into control group and different doses of NCTD group, and cultured in 1640 medium containing 0, 8, 16, 32 μg/ml NCTD. The Live DeadTM animal cell viability/toxicity detection kit detected the number of dead and live cells and cell morphology was recorded by microscope. Western blot was used to detect the protein expression levels of caspase 3, Cleaved caspase 3, JNK, p-JNK, p38, p-p38 and α-tubulin in cells of each group. Results? the proliferation ability of cells, the migration ability and apoptosis rate of NB4、K562 cells are enhanced after overexpression of PPP5C in human leukemia NB4 and K562 cells; Compared with the control group, each concentration group of NCTD promoted apoptosis in a dose-dependent manner; PPP5C overexpression antagonizes the killing effect of NCTD on leukemia cells. Conclusions NCTD can promote the apoptosis of NB4 and K562 cells and inhibit the proliferation of cells by inhibiting PPP5C.
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Research on the Mechanism of LSC Immune Escape with Intervention by TCM
ZHANG Meiling, 章, CuiYaru, ChengShupeng, LingZhiming
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Leukaemia is a critical disease with a high incidence in clinic at present, with an extremely high fatality rate. Among them, immune escape from leukaemia stemcells(LSC) is the main factor for recurrence and progression after leukaemia-induced remission. The clinical diagnosis and treatment of TCM has distinct advantages of syndrome differentiation and treatment. Based on the purpose of diagnosis and treatment, the treatment of leukaemia by TCM emphasises the "harmony of yin and yang" to estore human function, which is conducive to improving the body's autoimmunity and conforms to the mechanism of intervention for tumour cell immunity escape. This article discusses the echanism and research progress of TCM intervention in Lsc immune escape from literature research and TCM theory.
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Effects of polysaccharide content and anti-inflammatory, hemostatic and antioxidant activity before and after preparation of Mosla chinensis-jiangxiangru
Maqiuting, Xulei, Zhuyuchen, Xumengting, Zhangwenkai, Liuzhiyong
Abstract:
Abstract：Objective:Exploring the changes in polysaccharides in Jiangxiangyu before and after giner juice, and evaluation of polysaccharide anti -inflammatory and antioxidant antioxidant activity before and after the processing. Methods: The content of polysaccharides beforeand after processing was determined by phenol-sulfuric acid method（Elsholtzia chinensis polysaccharide-JXRPs, Ginger Elsholtzia chinensis polysaccharide-JZJXRPs); The body internal uses the swelling model of rats and the body fat polysaccharide (LPS) to induce mousemacrophages RAW264.7 inflammation model.The best administration concentration is selected by using cell proliferation (MTT) method, Elisa method measures the expression of IL-6, IL-12, NO, IL-4, and IL-10 in the cells;Observe the bleeding time of mice to evaluate its hemostatic effect by observing the tail -cutting method; finally, use the ability to remove DPPH and ABTS to evaluate its in vitro antioxidant activity.Results: The contents of JXRPs and JZJXRPs were 13% and 22%,As a result of the swelling of rats, after 4h in injection, compared with the model group, JXRPs ppear significant difference in dosage doses of 200 mg/kg (P <0.05), and JZJXRPs When the dose is 100 mg/kg, you can significantly reduce the swelling of rats (P <0.05);The in vitro anti-inflammatory results show that the polysaccharides before and after the processing can significantly inhibit cell secretion of IL-6, IL-12 and NO (P <0.01), promote cell secretion of IL-4 and IL-10 (P <0.01), and the processing of the processing The post -effects are stronger.The results of the mouse break the hemostatic experiment show that: compared with the control group, the JXRPs group can speed up the hemostatic effect but there is no significant difference, and there is asignificant difference in the dosage of the JZJXRPs (P <0.05) in the medium dose (P <0.05), and the High doses have accelerated trend but there is no significant difference; The results of antioxidant activity in vitro showed that JXRPs and JZJXRPs had different degrees of scavenging ability for DPPH and ABTS, with IC50 values of JXRPs of 0.2215 mg/ml and 0.2110 mg/ml of JZXRPs, respectively, and IC50 values of 0.1651 mg/ml and 0.1884 mg/ml of JZJXRPs, respectively.Conclusion:After the Jiangxiangyu is produced by ginger juice, it can promote the dissolution of polysaccharides and increase the polysaccharide content. JZJXRPS anti -inflammatory hemostasis and antioxidant capacity are stronger than JXRPS, which can lay the foundation for the follow -up research and clinical application of JXRPS.
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Research progress of SHP-2 in tumor-associated macrophages
Abstract:
Abstract: Tumor-associated macrophages (TAMs) are the dominant cell group in the tumor microenvironment (TME) and are the most important regulatory cells of immune system suppression and tumor cell proliferation in Tmes. Src homologous 2 protein tyrosine phosphatase 2 (SHP-2) is a non-receptor protein tyrosine phosphatase that plays an important role in signaling from the cell surface to the nucleus and is a key intracellular regulatory factor mediating cell proliferation and differentiation, involved in a variety of growth factor and cytokine signaling pathways. Recent studies have shown that SHP-2 is a key enzyme that determines the function of tumor-associated macrophages, but because of its variable function, it plays different or even opposite roles in different solid tumor microenvironments. Based on this, this paper reviews the function of SHP-2 in TAMs and the role of ShP-2 in related solid tumors, providing a solid scientific basis for tumor immunity and targeted therapy.
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Antitumor mechanism of Ardisia Crenata
Abstract:
Ardisia Crenata Radix is a traditional Chinese medicine, which belongs to Myrsinaceae, and its main components are coumarins, saponins, flavonoids and volatile oil. Bergenin, ardisicrenoside A, ardisicrenoside B,ardisiacripin A,ardisiacripin B and embelin are active anticancer compounds with the in-depth study of the anti-tumor effect of Ardisia Crenata Radix. They show high potential in oral cancer, nasopharyngeal carcinoma, liver cancer, colon cancer, bladder cancer, cervical cancer and leukemia mainly through inducing tumor cell apoptosis, increasing tumor cytotoxicity, inhibiting cell proliferation, inhibiting tumor cell metastasis and migration, and inducing cell regulatory enzyme cascade reaction. However, the preclinical experimental data of cinnabar root anti-tumor mechanism are lack of high-quality, multi-sample and multi-repeated randomized controlled trials, and the clinical research data are lack of tumor prognosis, pharmacodynamics and pharmacokinetic data. Accurate research experiments and clinical trials should be designed to further explore the pharmacological effects of mining cinnabar root.
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Research progress in immunoregulation mechanism of exosomes on bacterial infection
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Exosomes are small endosomal derived extracellular vesicles with lipid bilayer structure, which contain substances such as protein, lipids, DNA, RNA, miRNA and lncRNA. Exosomes participate in pathogen recognition, antigen presentation, autophagy regulation, immune activation and immunosuppression in bacterial infection. Studies have shown that miRNA, lncRNA and protein in exosomes play important roles in regulating antibacterial reaction of organism. We reviewed the immunomodulatory effects of exosomes on several intracellular and extracellular bacterial infections to provide evidence for studying the interaction between exosomes and bacterial infections.
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Application and challenges for NHP laboratory animals in neuroscience
HuLingfeng, FanShengtao, LiuJie
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【Abstract】: Currently, non-human primates (NHPs) are becoming increasingly important in laboratory animals, especially in the field of neuroscience, where many significant breakthroughs have been made, including research on brain development, neurodegenerative diseases and psychiatric disorders, but as their breeding and use grows, biosafety and animal ethics issues should be taken into account. This review summarizes the application and challenges of NHP laboratory animal in the neuroscience field from the aspects of NHP overview, feeding and operation, biosafety, and animal ethics.
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Research progress on evaluation of type 2 diabetic peripheral neuropathy animal model
Abstract:
Diabetic peripheral neuropathy is a common diabetic complication. At the moment, our understanding of its pathogenesis is incomplete, and there are no effective treatment options. In-depth research requires the use of animal experiments. The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments on type 2 diabetic peripheral neuropathy, but there is a lack of sorting out and analyzing the evaluation methods for type 2 diabetic peripheral neuropathy models. As a result, the author reviewed recent data, summarized and analyzed the evaluation methods of animal models of type 2 diabetic peripheral neuropathy from small and large nerve fibers, and proposed future development directions in order to provide a reference for related research.
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A review and promising future directions of machine learning in laboratory animal facility management
Abstract:
As the intelligence level gradual improving in domestic laboratory animal facilities，a large amount of valuable data has been accumulated. The data has not been fully exploited due to lacking of analytical means. In the context of Big data, Machine learning algorithms have achieved remarkable results in biomedical, building science and other fields, and also provide a reference for their application in laboratory animal facility management. In this paper, the contents, methods and models of machine learning methods applied to various systems of laboratory animal facilities at home and abroad are reviewed and prospected.
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Optimization of the preparation method of lung tissue cryosections for multiplex immunofluorescence staining
Ye Qianchen, Xu Dan, Wen Fuqiang, Chen Jun, WANG TAO
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Objective Optimizing the preparation method of mouse lung cryosections to improve the quality of lung cryosections helps to enhance the specificity of immunofluorescence staining and obtain more accurate and reliable experimental results. Methods C57BL/6 mice were used to make cryosections by the traditional post-freezing fixation method, the pre-freezing fixation method, and a modified perfusion pre-freezing fixation method, respectively. A laser scanning confocal fluorescence microscope was used to observe lung tissue immunofluorescence staining. The whole areas of mouse lung slices were scanned by fluorescence microscope, and then the numbers of intact airways per unit area of lung tissue were calculated. Results For the lung cryosections made by the traditional post-freezing fixation method, the alveoli structure was damaged, and the airway wall was seriously broken with non-specific staining. The lung cryosections made by the pre-freezing fixation method showed relatively intact alveolar and airway structures but collapsed alveoli and several destroyed airways. The structure and morphology of the alveoli and airways were intact and clear in the lung cryosections prepared by the modified perfusion pre-freezing fixation method. In addition, the locations of target genes were accurate with multiple immunofluorescence staining. The number of intact airways (diameter ≥100 μm) per unit area in the lung cryosections from the modified perfusion pre-freezing fixation method was higher than from the pre-freezing fixation method (0.66±0.15 /mm2 vs. 0.33±0.14 /mm2, P<0.05), and was also significantly higher than that from the traditional post-freezing fixation method (0.66±0.15 /mm2 vs. 0.02±0.04 /mm2, P<0.01). Conclusions The modified perfusion pre-freezing fixation method is beneficial to maintain mouse lung tissue's morphological integrity and obtain high-quality multiplex immunofluorescence staining results.
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To explore the effects of different types of drinking water on the growth and fecal flora of mice
Abstract:
【Abstract】 Objective to explore the effects of different types of drinking water on growth and fecal flora of mice. Methods SPF NIH mice were selected and divided into 5 groups with 32 males and females in each group. they were fed with pure water (control group), acidified water, alkalized water, weak acid water and solid water, respectively. diet and body weight were monitored continuously for 20 days. after the experiment, animal feces samples were collected, and the V3-V4 region was amplified with bacterial16S rDNA universal primers. Illumina Miseq high-throughput sequencing platform was used for high-throughput sequencing, and microbial community, alpha diversity and beta diversity were analyzed by bioinformatics method. Results in terms of body weight, the water of weak acid in female mice was higher than that in the control group at different pH values, while the other groups were lower than that in the control group(P﹥0.05). in male mice, the body weight of acidified water group was higher than that of control group, while that of other groups was lower than that of control group, but there was no statistical difference between groups(P﹥0.05). the body weight of female and male mice with solid water was lower than that of control group(P < 0.05). in terms of food intake and water intake, the water intake and water intake of female mice in the alkalized water group were lower than that of other groups, and the water intake of female and male mice in the solid water group was lower than that of other groups. through OTU cluster analysis, the dilution curve showed that the data volume of this sequencing was reasonable. the fecal flora of NIH mice was divided into five phyla, among which bacteroidetes and firmicutes were the main phyla. at the genus level, pseudopurpuromonas, lactobacillus and mycobacterium were the main genera. there were differences in fecal flora abundance and diversity among the five drinking water types. alpha analysis showed that the acidified water group had the highest flora abundance and diversity, while the solid water group had the lowest flora diversity. beta analysis showed that the fecal flora of the solid water group and the control group were the most similar, followed by alkalized water group, acidified water group and weak acid water group, respectively. Conclusions through the exploration of different types of drinking water, it is revealed that the solid form of drinking water has a great effect on the body weight, feed intake, water intake and fecal flora of mice, and the abundance and diversity of fecal flora of mice are affected by different pH values of drinking water, especially acidified water has a greater effect on the fecal flora of mice.
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The therapeutic effect of licorice zinc on chloasma mice was explored based on nrF-2 /HO-1 pathway
Du Xiaoshuang, Liu Ping, Deng Ying, Yang Hongqiu, Du Yu
Abstract:
[Abstract] Objective To investigate the therapeutic effect of licorice zinc on melasma. Methods Melasma was induced by 100 mJ/cm2 UVB irradiation combined with 15 mg/kg progesterone injection. Tranexamic acid (0.065 g/kg) and low (0.65 g/kg)/medium (1.3 g/kg)/high (2.6 g/kg) zinc licorice were treated for 14 days. Skin was taken for HE and Masson-Fontana staining; and SOD, MDA, GSP-Px, TNF-α, IL-1β and IL-6 contents; plasma protein Nrf-2, nuclear protein Nrf-2, and HO-1 expression levels were measured. Results High dose of zinc licorice significantly reduced melanocyte formation, collagen cell necrosis and inflammatory infiltration, significantly up-regulated the expression of GSP-Px and SOD, decreased the expression of MDA, IL-6, IL-1β and TNF-α, up-regulated the expression of nuclear proteins Nrf-2 and HO-1, and down-regulated the expression of plasma protein Nrf-2. Conclusion Zinc licorice activates Nrf-2/HO-1 pathway to initiate high expression of HO-1, SOD and GSP-Px against oxidative stress, thereby reducing melanogenesis.
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Study on the mechanism of oral microflora involved in areca nut extract induced oral ulcer in rats
pengdongdong, chenxiangchi, tangzining, liuxuewu, yuanxiangzhong, limeng, liqiao, zhangzeheng
Abstract:
Objective The model of oral ulcer in rats was constructed by areca nuts extract, and the structural changes and diversity characteristics of oral flora were observed, so as to explore the pathogenesis of oral flora involved in oral ulcer in rats induced by areca nuts extract, providing theoretical support for clinical prevention and treatment of oral ulcer. Methods Thirty SD rats were randomly divided into normal group, model group, drug treatment group, 10 rats/group. The rat oral mucosa was injected with 10g/mL areca nuts extract subcutaneously to replicate the rat oral ulcer model. Ulceration area, ulceration score, and levels of TNF-α, IL-2, and IL-8 in local tissues were observed, and HE staining was performed on oral mucosal tissues to observe the morphological changes of oral mucosal tissues. High-throughput sequencing method was used to analyze the structure distribution of oral microbial flora and microbial community diversity. Results Compared with normal group, the ulcer area of rats in model group was significantly increased (P<0.01), the ulcer score was significantly increased (P<0.01), the levels of IL-2, IL-8 and TNF-α in oral mucosal tissue were significantly increased (P<0.01), and the shannon index of oral saliva of rats was significantly increased (P<0.05).simpson index was significantly decreased (P<0.01), Strep-tococcus and Veillonella were significantly decreased (P<0.05,0.01), oral mucosal epithelial cell proliferation or focal necrosis, mucosal lamina propria edema and hemorrhage were observed in model group. It was accompanied by abundant infiltration of neutrophils and monocytes. Compared with model group, the ulcer area and ulcer score of model group were significantly decreased (P<0.05), the levels of IL-2, IL-8 and TNF-α in oral mucosal tissue were significantly decreased (P<0.05,0.01), and the shannon index of oral saliva of rats was significantly decreased (P<0.05). Simpson index was significantly increased (P<0.01), Strep-tococcus was significantly increased (P<0.001), Staphylococcus was significantly decreased (P<0.01), and the pathological degree of oral mucosa was significantly improved. Conclusion Areca nuts extract can successfully reproduce the rat model of oral ulcer, and it is speculated that the development of oral ulcer disease induced by areca nuts extract may be related to the imbalance of oral flora and local tissue inflammatory mediators.
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Effects of 5-Aza-CdR on hippocampal neurogenesis in mice via the Notch1 pathway
wangbaojie, suliqing, yanlei, zhangzhiyong, 王志广, baosuya, shaoguo
Abstract:
【 Abstract】 Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration, and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavioral experiments on mice. Methods Sixty 6- to 8-week-old ICR male SPF-grade mice were divided into two groups, and 5-Aza-CdR was administered to one group of mice via lateral ventricular injection (i.c.v.), while the other group was injected with BSA as a control group. 5-Aza-CdR was administered to mice by lateral ventricular injection (i.c.v). mRNA and protein expression levels of Notch1 and HES1 were detected by real-time PCR and Western blot 24 hours after injection; 5-bromo-2'-deoxyuridine (BrdU)-positive cells were observed by laser confocal microscopy and Notch1 expression in hippocampal DG by laser confocal microscopy; Notch1 methylation changes were detected by MS-PCR; and learning and memory behaviours of mice were assessed by measuring passive avoidance tests and shuttle avoidance assays. RESULTS Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity and promoted neuronal regeneration in the DG region, decreased methylation levels in the Notch1 promoter region, and enhanced the ability of mice to perform active avoidance behaviour. Conclusion The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch1 pathway.
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Effects of emodin on autophagy and cycle arrest in fibroblast-like synoviocytes in rheumatoid arthritis
Tao Bonan, WANG Yonglan, HONG Lan, YUAN Lin
Abstract:
Objective: Based on the cGAS/STING signaling pathway to investigate the potential effect of emodin (EMD) on autophagy of human rheumatoid arthritis fibroblast synovial cells (MH7A). Methods: CCK-8 method was used to detect the results of MH7A cell proliferation, and the concentration of drug was screened according to cell survival rate. Then, autophagy inhibitor 3-MA was added to further verify the effect of emodin on autophagy. Autophagy of MH7A cells was detected by MDC method. The protein expression levels of cGAS, STING, p-STING, LC3-I, LC3-II, p62 and Beclin-1 were detected by Western blot. Results: MDC staining indicated that emodin could enhance autophagy of MH7A cells. Western Blot results indicated that emodin could decrease the expressions of autophagy related proteins cGAS, STING, p-STING and P62, and increase the expressions of LC3-II and Beclin-1 in MH7A cells. After addition of autophagy inhibitor 3-MA, the expression of P62 protein in MH7A cells increased, while the expression of LC3-II and Beclin-1 protein decreased. Conclusion: Emodin may accelerate autophagy and inhibit MH7A cell proliferation by down-regulating cGAS/STING signaling pathway.
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Progression of the Relationship between Pyrozosis and Atherosclerosis
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Pyroptosis is a programmed mode of death, and activated aspartase-1 (caspase-1) can induce the occurrence of pyroptosis, promoting the release of inflammatory factors. In recent years, studies have found that pyroptosis may be closely related to the occurrence, development and outcome of atherosclerosis. This article reviews the relevant studies of endothelial cells pyroptosis, vascular smooth muscle cells pyroptosis and macrophages pyroptosis in the development of atherosclerosis, aiming to provide new ideas for the pathogenesis and diagnosis and treatment of atherosclerosis.
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Gli2 regulates the activation of Hedgehog pathway on proliferation, metastasis and epithelial mesenchymal transformation of Tca8113 cells
Liu Maolin, Wang Xiaotang, Song Xiaona, Ma Yunfei, Chang Xiaoqi, Song Guohua
Abstract:
Objective: To investigate the effects of Gli2 on the proliferation, growth, migration and invasion of oral cancer cells (Tca8113) at the cellular level, and to clarify the molecular mechanism of Gli2 regulation on the migration and invasion of oral cancer cells. Methods: siRNA was used to inhibit Gli2 expression in Tca8113 cells. The effects of Gli2 on the proliferation, growth, migration and invasion of Tca8113 cells were examined by CCK-8, plate cloning and transwell chamber assay. Further, qRT-PCR and Western blot were used to explore the mechanism of Gli2 regulation of malignant proliferation and metastasis of Tca8113 cells. Results: The mRNA and protein expression of Gli2 in oral cancer cells (Tca8113) were increased. Interference with Gli2 expression inhibited the proliferation, growth, migration and invasion of Tca8113 cells. Further studies showed that interfering with Gli2 expression inhibited mRNA and protein expression of key factors in Hedgehog (Hh) pathway. In addition, interference with Gli2 expression can significantly affect mRNA and protein expression of key factors in Epithelial mesenchymal transformation (EMT) pathway. Conclusion: Gli2 is abnormally activated during oral cancer, and interference with Gli2 expression significantly inhibits the proliferation, growth, migration and invasion of oral cancer cells. Gli2 influences the migration and invasion of oral cancer cells by regulating Hh pathway and EMT pathway. This study provides a new way to elucidate the pathogenesis of oral cancer and a new perspective for clinical treatment of oral cancer.
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A model study of blood in urine (bladder cancer) under scorching humid fever under MNU-induced SD rats
changtuo, wangjie, linan, wangtianqi
Abstract:
Objective: To investigate the modeling process and mold formation rate of N-methyl-N-nitrosourea (MNU)-induced lower jiao dampness-heat syndrome uremia bladder cancer (BC) model. Methods: Batch samples were collected by bladder perfusion (MNU) and H&E staining and pathological observation of pathological tissues were carried out at a total of 6 time points before, during and after molding, so as to understand the formation and development of carcinoma in situ of the bladder. Results: The experimental process was smooth, and no obvious urinary tract bleeding in rats occurred during the operation. By this modeling technique, considerable bladder tumors can be obtained after the eighth week, and there are obvious epithelial hyperplasia, damage and large-scale tumor formation in the bladder of rats in the model group. Conclusion: MNU can induce SD rat bladder cancer model with obvious model formation and low mortality, and the experimental data can provide a certain reference for the establishment, improvement and application of bladder cancer model.
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Protective effects of HIF-1α pathway in cold storage of isolated organs
wangzhiyang, zhengsiyang, zhuliang
Abstract:
Organ transplantation is the main treatment for organ failure. The functional protection of donor organs during ex vivo transportation is the key to the success of organ transplantation. How to protect the functions of donor organs during in vitro transportation is one of the key issues in the field of organ transplantation research. In a hypoxic environment, the transcriptional activity of a series of genes in cells is activated. These genes are mainly involved in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. In aerobic organisms, hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of the expression of various genes to maintain the homeostasis of tissues and cells under hypoxic conditions, thereby adapting to the hypoxia. Many studies have shown that the HIF-1α pathway plays an important role in protecting isolated organs from cold ischemia injury during cold storage. HIF-1α has been a hot spot in the research on the protective mechanism of cold ischemia injury of isolated organs. The intervention of the HIF-1α-related signal pathway is expected to become a new strategy for maintaining organ function during cold storage of isolated organs.
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Advances in animal models of diet-induced nonalcoholic fatty liver disease
Wang Jialin, Wang Chongyang, Li Yang, Chen Xianwei, Yuan Zhongnan, Zou Chaoxia, Zou Chendan
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The establishment of scientific and effective animal models is a key step to complete disease research. Diet induction is a common method to establish animal models of nonalcoholic fatty liver disease (NAFLD). The common animal models of diet-induced NAFLD mainly include high-fat and high-sugar diet-induced model, high-fat and high-cholesterol diet-induced model, and choline-deficient diet-induced model. Due to the different nutrients ingested by different modeling methods, the pathological characteristics such as fatty deformation, inflammation and fibrosis of the liver are different. In addition, different animal models vary in disease progression, disease severity, and applicable studies. This article analyzes and compares the common animal models of NAFLD induced by different diets in modeling methods, modeling time, pathological characteristics, applicable research, and related advantages and disadvantages, so as to provide reference for NAFLD researchers to select animal models.
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Isolation and extraction of Kupffer cells and hepatic stellate cells in mouse liver
mawenmeng, wuhao, yanyutong, sunxun, zhengqianqian
Abstract:
【】Objective It is to explore the extraction and purification methods of Kupffer cells and hepatic stellate cells from mouse liver, and provide reference and suggestions for the separation and extraction methodology of primary non parenchymal cells from mouse liver.Methods Based on in vivo collagenase perfusion digestion, different reagents and methods such as Percoll and OptiPrep were used to extract C57BL/6 mice Kupffer cells and hepatic stellate cells and evaluate the purity through flow cytometry and immunofluorescence methods. Results The two-layer Percoll method for extracting Kupffer cells and the two-layer OptiPrep method for extracting hepatic stellate cells are feasible,and the purity can reach more than 90%.The cell yield was 1~2×107/liver, the cell survival rate was more than 90%.After 48 hours of primary cell culture, the number of Kupffer cells F4/80-positive cells and hepatic stellate cells α-SMA-positive cells reached more than 75%. Conclusions The separation and extraction method of Kupffer cells and hepatic stellate cells from mouse liver is perfect, reliable, cost-effective and reproducible.
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Application Research Progress of Single-cell RNA-sequencing Technology in Neurodegenerative Diseases
Abstract:
Neurodegenerative diseases (NDs) are the mental diseases closely related to the central nervous system, characterized by morphological abnormalities and slowly progressive loss of function in specific neuron groups. The main diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS) and Huntington's disease (HD). However, the directly therapies for NDs are not founded. In recent years, single-cell RNA-sequencing (scRNA-seq) technology has been widely used in various neurodegenerative diseases. It has been found that the pathogenesis of NDs are involved in conditions of immune cells and biological processes such as mitochondrial function, angiogenesis, inflammation and synaptic transmission. The antilepsis of induced pluripotent stem cells (iPSC) is a potential treatment for NDs. Ultimately, the application of scRNA-seq technology in various NDs was reviewed in this paper ,and provided reference for the future prevention and treatment of NDs.
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Research progress on modeling methods and evaluation indexes of kidney injury in zebrafish
lanailin, Huangchunhua, Xiaming, Limaojuan, Wangsiqi, Loudidong
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Renal function is to filter blood , regulate fluid and electrolyte balance, which is crucial for health of the body, moreover, the kidney is susceptible to toxicity of various compounds in and out of the body, resulting in renal function damage, hence the prevention and treatment of renal function injury caused by various factors is also a hot research topic. Zebrafish is an ideal animal model as it is closely related to humans in terms of morphology, physiology and function of kidney and its response to compounds. In this paper, we will review the methods and evaluation indexes of zebrafish kidney injury modeling.
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Microvascular morphometric analysis of cerebral cortical functional areas in C57BL/6 mice of different months of age
Abstract:
Abstract: Objective To observe and analyze the different functional areas of cerebral cortex in C57BL/6 mice of different months. Methods Improved alkaline phosphatase staining was used to reveal the microvascular morphology of the cerebral cortex of C57BL/6 mice, including motor cortex (primary motor cortex, secondary motor cortex), sensory cortex (primary somatosensory cortex, secondary somatosensory cortex), visual cortex (primary visual cortex, secondary visual cortex), auditory cortex (primary auditory cortex, secondary auditory cortex), olfactory cortex (extrorhinal cortex, entorhinal cortex). Images were captured by OLMPUS BX51 microscope combined with Image-Pro Plus 5.1 software. The microvascular length density (Lv), microvascular surface area density (Sv) and microvascular volume density (Vv) were analyzed by Image-Pro Plus 5.1 software. Results The levels of alkaline phosphatase in microvessels of different functional areas of cerebral cortex increased with age and reached the peak in adults. There were four patterns for pia vessels to enter the cortex including T shape, Y shape, large arc, small arc. The Lv, Sv and Vv in different functional areas of the same aged mice showed a downtrend trend in the motor cortex, sensory cortex, visual cortex, auditory cortex and olfactory cortex. Moreover, the microvascular density of Lv, Sv and Vv in the motor cortex and sensory cortex was statistically significant compared with those in the olfactory cortex (P<0.05). The vascular densities of different functional areas in the aged mice were lower than those in the adult ones, but there was no statistical significance (P>0.05). Conclusion The improved alkaline phosphatase staining may clearly reveal the microvascular architecture in cerebral cortex of C57BL/6 mice and it provides morphological reference for the research of cerebrovascular diseases and the preparation of animal models.
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Research progress of traditional Chinese medicine for stroke based on epigenetic regulation
Abstract:
Epigenetics is a branch of molecular biology, and is a research hotspot in the post-gene era in the field of life sciences. The application of epigenetic modification research methods is the frontier field of the pathogenesis of ischemic stroke, and it is the interpretation of traditional Chinese medicine in the treatment of ischemia. Targets of stroke and effective approaches to their mechanisms of action. At present, the etiology and pathogenesis of ischemic stroke has not been fully clarified, and modern medical treatment is still insufficient. The treatment of ischemic stroke with traditional Chinese medicine has unique advantages and broad prospects. The latest research has found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modification in the treatment of stroke. This article mainly starts from the epigenetic basis of traditional Chinese medicine theory of stroke and the application of DNA methylation, non-coding RNA and histone modification in stroke treatment and traditional Chinese medicine research, and explains the appearance of traditional Chinese medicine in the treatment of stroke. The role of heredity in order to provide new ideas and scientific basis for traditional Chinese medicine treatment of the disease
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Geniposide promotes skin ulcer wound healing in diabetic rats through PI3K/Akt pathway
Abstract:
Objective To investigate the protective effect of geniposide on diabetic skin ulcer and its mechanism. Methods Rats were divided into normal group, model group and geniposide subgroup (Gen-L: 200 mg/kg; Gen-H: 500 mg/kg). The diabetic rats were given normal saline or geniposide by intragastric administration (n = 6). Treatment was administered once a day, and the wound healing and inflammation of each group were recorded every day. After 7 days of treatment for diabetic skin ulcers, the wound area, tissue sections, TUNEL staining and Western blot were used to quantitatively analyze the changes of wound healing, apoptosis and related regulatory protein expression. Results Compared with the model group, geniposide (200 mg/kg and 500 mg/kg) orally could significantly promote the wound healing and increase the contraction of the injured area in diabetic rats. In the study of skin wound apoptosis in diabetic rats, TUNEL staining positive cells in geniposide subgroup were significantly reduced (P<0.05). Geniposide can significantly inhibit skin inflammation and promote wound repair, which may be related to the promotion of PI3K and Akt phosphorylation. Conclusion Geniposide can promote skin wound repair in diabetic rats by inhibiting inflammatory response and apoptosis.
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Effect of Dingkun Pill on PI3K/AKT/mTOR signal pathway in rats with endometriosis
Abstract:
[Abstract] Objective: To explore the effect of Dingkun Pill on PI3K/Akt/mTOR signaling pathway in rats with endometriosis (EMs). Methods: The EMs rat model was constructed by heterotopic transplantation of endometrial tissue and randomly divided into five groups: model group (M group), Dingkun Pill low (1.13g/kg) dose group (DKP-L group), Dingkun Pill medium (2.26g/kg) dose group (DKP-M group), Dingkun Pill high (4.52g/ kg) dose group (DKP-H group), gestrinone (60mg/kg) group (GES group), with 12 rats in each group. Another 12 normal SD rats were opened the abdomen without transplantation ectopic endometrial tissue, and set as sham operation group (sham group). The rats were killed after intervention with drugs, the volume of ectopic endometrium and the weight of ectopic lesions of rats in each group were measured, the microvessel density (CD31 positive rate) and the expression of VEGF and MMP-9 in rat ectopic endometrial tissue were detected by immunohistochemical staining; the rat serum VEGF, MMP-9, iNOS and TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA); the expression of PI3K/Akt/mTOR pathway related proteins in rat ectopic endometrial tissue was detected by western blotting. Results: Compared with the sham group, the microvessel density, VEGF and MMP-9 expression, serum VEGF, MMP-9, iNOS and TNF-α levels, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in the ectopic endometrial tissue were significantly increased in the M group (P<0.05); compared with the M group, the ectopic endometrial volume, the weight of the ectopic lesion, the microvessel density of the ectopic endometrial tissue, VEGF and MMP-9 expression, the serum VEGF, MMP-9, iNOS and TNF- α levels, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR in ectopic endometrial tissue were all decreased in the drug intervention group, and DKP-L, DKP-M and DKP-H groups were dose-dependent (P<0.05); compared with the DKP-H group and the GES group, there was no significant difference in the indicators of rats (P>0.05). Conclusion: Dingkun Dan can reduce inflammation and inhibit ectopic endometrial growth in EMs rats, which may be achieved by blocking PI3K/Akt/mTOR signal pathway.
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Experimental Study on Mongolian Drugs Hatagaqi-7 Promoting Ulcer Wound Healing of diabetes Rats via HIF-1α
DongChenghai, Cheliger, ChaoRiya, manzhu, Bao Yonglin, GongLimin
Abstract:
Objective: To study the effect of mongolian drugs Hatagaqi-7 promoting ulcer wound healing of diabetes rats via hypoxia inducible factor-1α(HIF-1α). Methods: Adult male SD rats were randomly divided into control group, diabetes group, mongolian drug group and cytokine group. Besides the control group, the other three groups were treated with intraperitoneal injection of streptozotocin to establish the diabetes model. The ulcer wounds were prepared in the back of the four groups. One week later, the mongolian drug group was treated with hattagelge-7, and the cytokine group was treated with recombinant bovine basic fibroblast growth factor for two consecutive weeks. Then fasting blood glucose (FBG), wound area, wound pathology, the expression level of advanced glycation end products (AGEs), receptor of AGE (RAGE), HIF-1α, vascular endothelial growth factor (VEGF) and the levels of interleukin-1β(IL-1β), interferon-γ(IFN-γ), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were detected. Results: The FBG of diabetes group, mongolian drug group and cytokine group were higher than those of the the control group(P<0.05), and there was no significant difference among the three groups (P>0.05). Compared with the control group, the area of ulcer wound, the scope of unrepaired tissue under microscope, the expression level of AGEs, RAGE and the levels of IL-1β, IFN-γ, MDA in the wound tissue of the diabetes group increased, the level of T-AOC and expression levels of HIF-1α, VEGF of the diabetes group decreased (P<0.05). Compared with the diabetes group, the area of ulcer wound, the scope of unrepaired tissue under microscope, the expression level of AGEs, RAGE and the levels of IL-1β, IFN-γ, MDA in the wound tissue of the mongolian drug group and cytokine group decreased, the level of T-AOC and expression levels of HIF-1α, VEGF of the mongolian drug group and cytokine group increased (P<0.05) and the indexes of mongolian drug group were better than those of cytokine group. Conclusion: Mongolian drugs Hatagaqi-7 promotes ulcer wound healing of diabetes rats, and the inhibiton of AGEs and RAGE expression and the activaton of HIF-1 α is a possible molecular mechanism.
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Effect of Osteoking on lowering blood sugar and improving intestinal flora in db/db mice
dengshaoyou, zhaoyulan, wangpeijin, lirong, zhaohongbin, jiaojianlin, zhenghong
Abstract:
Objective:To investigate the effects of Osteoking on hyperglycemia and regulating gut microbiota in db/db mice. Methods:The wild mice were used as the cntrol group and db/db mice were randomly into model group and Osteoking group. After intragastric administration for 12 weeks, Fasting blood glucose, serum glycosylated hemoglobin and insulin levels were measured , the changes of intestinal microflora were determined and functional pathways related to intestinal microflora in mice were predicted by 16S rDNA sequencing technology. Results:Compared with model group, Osteoking decreased fasting blood glucose (P < 0.01), serum glycosylated hemoglobin (P < 0.01), insulin resistance index (P < 0.01), and increased insulin content (P < 0.01) in db/db mice. Osteoking increased the abundance of beneficial bacteria of intestinal microflora, while decreased the abundance of harmful bacteria; the abundance of Marvinbryantia was increased. Osteoking alleviated the decrease of metabolism of D-arginine and D-ornithine, sphingolipid and galactose metabolism( P < 0.05), while inhibited lysine degradation, sulfur relay system and propanoate metabolism( P < 0.05). Conclusion:Osteoking has the effects of hypoglycemic properties and improving the intestinal microflora imbalance in db/db mice.
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Research progress on the role of autophagy in the pathogenesis of systemic sclerosis
lixin, sun xiaolin, wang yongfu
Abstract:
【Abstract】 Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular lesions and skin fibrosis, which can cause structural and functional damage to multiple organs. The pathogenesis of SSc is complex, which may be related to genetic, environmental factors and abnormal immune mechanisms. Autophagy is an evolutionarily conservative process of self degradation in the body, which can participate in the pathogenesis of body immunity and autoimmune diseases through a variety of pathways. This article mainly reviews the research progress on the role of autophagy in the angiopathy and fibrosis of SSc through regulating immune cells and mediating signal pathways.
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The role and mechanism of miRNAs in alcoholic liver injury in rats
Abstract:
Objective To investigate the role and mechanism of miRNAs in alcoholic liver injury in rats. Methods Randomly divided 30 male SD rats into model group and control group. The model group was gavaged with 56% liquor and the control group with distilled water for 8 weeks. The liver tissue was dissected. The miRNAs in the liver tissue were detected, analyzed and the target genes of differential miRNAs were predicted by rat miRNA chip. Gene Ontology (GO) and KEGG Pathway enrichment analysis were used to understand the function of differential miRNA target genes. Differential miRNA-mRNA-Pathway regulatory network was constructed using Cytoscape to further screen regulatory key miRNAs versus key pathways, qRT-PCR was performed on selected miRNAs for expression quantity validation analysis. Results: A total of 12 differentially expressed miRNAs (P < 0.05, fold change ≥ 2) were screened out, including 2 upregulated and 10 downregulated miRNAs by comparative analysis of microarray data between the model and control groups. GO classification annotation of differential miRNA target genes showed that there were close associations between differential miRNAs and biological functions such as antioxidant activity, metabolic process, biological regulation, cell killing, signal transduction, and enzyme regulatory activity. Differential miRNA target genes KEGG pathway analysis revealed that AMPK signaling pathway, PI3K Akt signaling pathway, Hippo signaling pathway, Wnt signaling pathway, cancer, autophagy, insulin resistance, Ras signaling pathway and other signaling pathways may play important regulatory roles in alcoholic liver injury lesions. The hub miRNAs and pathways screened by constructing the differential miRNA-mRNA-pathway regulatory network were mir-145-5p, mir-107-3p, mir-297, Hippo signaling pathway, cancer, PI3K Akt signaling pathway, AMPK signaling pathway, etc. The results of qRT-PCR showed that picking validation gene expression trend and gene chip results were consistent. Conclusion: In this study, we established a miRNA profile in alcoholic liver injury in rats, which suggests that mir-145-5p, mir-107-3p and mir-297 may play an important role in the process of liver alcoholic pathology.
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Osteopontin (OPN) activates the PI3K/AKT pathway via upregulating LGALS3BP in promotion of hepatoma cell migration
denglinlin, anriwen, zhaofangxin, linting, liucuihua, hongmei, wujianqiang, zhangxuan
Abstract:
Abstract: Objective To investigate the effect and mechanism of osteopontin (OPN) on hepatoma cell migration through galectin 3 binding protein (LGALS3BP). Methods Human hepatoma cell lines SMMC-7721, SMMC-P (stably transfected with empty eukaryotic expression vectors) and SMMC-OPN (stably transfected with OPN gene) were cultured. The mRNA expression levels of OPN and LGALS3BP were detected by qRT-PCR. Western blot assay was used to analyze the relative expressions of OPN and LGALS3BP. The protein expression level of PI3K/AKT pathway, including p-PI3K, PI3K, p-AKT and AKT were detected by western blot. Wound healing assay was performed to explore the cell migration ability. After transfection with LGALS3BP-targeting small interfering RNA (si-LGALS3BP) and negative control small RNA (si-NC) into SMMC-OPN cells respectively, cell migration ability and the relative expression of PI3K/AKT pathway related proteins were detected. Results Compared with SMMC-7721 and SMMC-P, the migration ability of SMMC-OPN cells was significantly reinforced, and the expression of LGALS3BP was obviously up-regulated at both mRNA and protein. Meanwhile, the relative expression quantity of p-PI3K/PI3K and p-AKT/AKT proteins were significantly increased. Wound healing assay showed that the si-LGALS3BP could obviously suppress the migration ability of SMMC-OPN cells. Furthermore, the relative expression of p-AKT/AKT and p-PI3K/PI3K proteins in SMMC-OPN cells were significantly decreased after transfection with si-LGALS3BP. Conclusion OPN could activate PI3K/AKT pathway through up-regulating LGALS3BP expression in promoting hepatoma cells migration.
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Establishment method and effect evaluation of two common pressure uler rat models
liuyi, lixiaolei, liangxinpei, wangna, mashan, zhangxinping, jiarufu, zhangsu, lixian
Abstract:
Objective : By comparing two different methods of establishing rat models of pressure uler, to explore a more suitable method for preparing animal models of pressure uler. Methods : 18 male SD rats were randomly divided into control group ( n = 6 ), model group A ( n = 6 ) and model group B ( n = 6 ). Control group : iodophor treatment was performed after hair removal at the simulated modeling site. Model A group : longitudinal compression was performed by simple deep tissue foreign body implantation ; model group B : transverse compression was performed by magnet compression method. The whole process time and each stage time of pressure uler model in each group were recorded. The general condition of rats was observed, and the molding rate, mortality rate and infection rate were compared. Results : The naked eye observed that the model A group and the model B group gradually appeared redness and swelling, ulceration, bleeding, exudation and necrosis. Comparison of the whole time of pressure uler in model group A and model group B : the difference between the two groups was statistically significant ( P0.05 ) ; the difference between the two groups was statistically significant ( P < 0.05 ). The difference between the two groups was statistically significant ( P < 0.05 ). There was significant difference between the two groups in stage IV ( P < 0.05 ). The mental and motor scores of the rats in the control group were significantly different from those in the model group A and the model group B ( P < 0.05 ). The general state of rats in model group A and model group B was significantly different, and the coat color was dim and the activity decreased. The model rate of rats in model A and model B was 100 %. The mortality and infection rate of model A group were higher than those of model B group, which were 33.34 % and 16.70 % respectively. Conclusion : Both methods can successfully prepare a four-stage model of pressure uler. The two methods have both commonalities and their own characteristics. The magnet compression method takes a short time, the rats are generally in good condition, and the mortality and infection rate are low. It is suitable for short-term intervention research ; the simple deep tissue foreign body implantation method takes a long time, requires rats to have a certain tolerance, has a high infection rate and a high mortality rate, and can be used in long-term observation of pressure uler rats.
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Research progress in the regulation of glutamate in traditional Chinese medicine in the treatment of depression
Abstract:
Glutamate is a major excitatory neurotransmitter in the central nervous system and a potential neurotoxin. During the development of depression, there is an increase in glutamate concentration in the hippocampus, and when glutamate accumulates, it will cause serious damage to neurons and brain tissue, aggravating the depressive state. Therefore, glutamate accumulation may be an important mechanism for depression. Astrocytes, glutamate transporters and glutamate receptors play important regulatory roles in the concentration of glutamate. This article reviews the mechanism of action of traditional Chinese medicine therapy on the treatment of depression by regulating astrocytes, glutamate transporters, and glutamate receptors, and provides new ideas for exploring the treatment of depression by traditional Chinese medicine.
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To explore cognitive differences among dogs with different sociability
song meng yu, guo yi jun, zhao xue rong, bai jing, zhou zi juan, wang jing yu
Abstract:
Objective:Exploring whether there are differences in the cognitive abilities of socially different Labradors. Methods:The Dog Mentality Assessment (DMA) test created by the Swedish Working Dog Association was modified to use 12 behavioral variables from five subtests of the DMA test: Social contact, Play I, Distance-play, Ghosts and Play II to assess the sociability of the dogs. According to the scoring criteria,49 Labradors provided by The China Guide Dog Training Centre In Da Lian was scored on the social behavioral variables, which were classified into high (n=15) and low (n=34) sociability groups using cluster analysis. A new system for testing canine cognitive ability was developed based on Bray et al.'s Dog Cognitive Development Battery (DCDB), which tests different domains of cognitive ability such as social cue use, unsolvable task, inhibitory control, cognitive flexibility, working memory and multi-step problem solving task, and the dogs' behavioral performance and duration of the test were recorded. Statistical analysis was performed to determine whether there were differences in the cognitive abilities of socially diverse dogs. Results:Dogs in the high and low social subgroups differed significantly on behavioral variables in the unsolvable task, the inhibitory control test and the multi-step problem solving task. In the unsolvable task, dogs in the high social grouping average looked at people time for significantly longer than dogs in the low social grouping (P=0.008) and average looked at people for significantly less latency time than dogs in the low social grouping (P=0.0001). In the inhibitory control, dogs in the high social group chose correctly significantly more than dogs in the low social group (P=0.034) and chose for significantly less time than dogs in the low social group (P=0.039). In the multi-step problem solving task, dogs in the high social group successful completion number of stakes significantly higher than dogs in the low social group (P=0.044); the percentage of operation pale time was significantly lower than dogs in the low social group (P=0.05); the average latency time to solve bone task was significantly higher than dogs in the low social group (P=0.037); and the percentage of operation bone time was significantly lower than dogs in the low social group ( P=0.038). On tests involving manipulable apparatus, dogs in the high social group spent more time looking at people than dogs in the low social group and less time manipulating the apparatus than dogs in the low subgroup, but there were no statistically significant differences (P>0.05). Conclusions:High sociability labradors showed greater cognitive ability,they were more able to suppress impulses during the test, were more able to complete multi-step problem solving task and were more inclined to change strategies to seek new cues from people rather than obsessing over manipulating the apparatus when they were unable to solve a problem.
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Construction of a prognostic risk marker of colon adenocarcinoma based on weighted gene co-expression network and its clinical significance
Abstract:
Objective Due to the poor prognosis of colon adenocarcinoma (COAD) patients, it is necessary to screen prognosis-related genes in COAD and establish a new prognostic risk assessment model. Methods COAD-related data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used as the training set and the validation set, respectively. Weighted gene co-expression network analysis (WGCNA)， Cox regression model and Least Absolute Selection and Shrinkage Operator (LASSO) regression analysis were used to screen prognosis-related genes of COAD and construct a prognostic model. Receiver Operating Characteristic (ROC) curve was combined with survival curve to verify the accuracy of the model, and a nomogram was established. The patients were divided into two groups according to the median value of risk score. The immune cell proportion score (IPS) was used to evaluate the immunotherapy response of the two groups. Results A total of 15 feature genes were screened. The area under the ROC curve (AUC) in the predictive model of COAD patients was >0.6, and the survival rate of high-risk group was significantly lower than that of low-risk group (P<0.05, suggesting good distinguishing ability for high- and low-risk COAD patients. Patients in the low-risk group had a higher IPS (P=0.026), indicating a better response to immunotherapy. Conclusions The model developed for COAD in this study has a good ability to predict the survival of people at high and low risk of COAD.
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Quality Evaluation for Animal Studies on Acupuncture for Glaucoma
lijiaxian, lianglina, 李亚敏, xukai, huangziyang, lixiaoyu, jinyu, zhouwei
Abstract:
Objective To evaluate the quality of animal studies on acupuncture for glaucoma by the SYRCLE’s risk of bias tool, ARRIVE 2.0 guidelines and GSPC checklist. Methods Databases of CNKI, VIP, Wanfang, Sinomed, PubMed, Web of Science, Embase, and Cochrane Library were conducted to find animal research articles on acupuncture for glaucoma. Risk of bias was assessed for included studies using the SYRCLE’s tool, and the reporting quality was evaluated using the ARRIVE 2.0 guidelines and GSPC checklist, statistical analysis was performed by Excel and SPSS software. Results Thirty articles met the inclusion/exclusion criteria and were included in the final analysis. 6 of the 10 items of the SYRCLE’s tool had a low-risk rate of <50%, and the non-low-risk items focused on selectivity bias, implementation bias, and measurement bias. 12 of the 22 essential sub-items of the ARRIVE 2.0 guidelines had a low-risk rate of <50%; 9 of the 16 recommended sub-items had a low-risk rate of <50%; 12 of the 19 subentries of the GSPC list had a low-risk rate of <50%, and randomization, blinding, thical statement, housing and husbandry, animal care and monitoring, protocol registration were non-low-risk items in the ARRIVE 2.0 guidelines and GSPC list. Conclusion The quality of methodology and experimental reportings in animal studies on acupuncture for glaucoma are generally low, and the descriptions of several items are not yet complete, which affects the readers' judgment on whether the animal studies can be further translated into clinical studies. It is advised to further promote the SYRCLE’s tool and reporting guidelines for animal experiments, to enhance the design, performance, and reporting of animal experiments, ensure the reproducibility of experiments and results, and provide reliable evidence for the translation of results to the clinic.
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miR-181a-5p overexpression in the small intestine in a mouse model of subcutaneous transplantation of oral cancer
Abstract:
[Abstarct] Objective By detecting changes in metabolites and metabolic pathways in the small intestine of mice with subcutaneous transplantation of oral cancer, the effects of overexpression of miR-181a-5p on metabolites and metabolites in the small intestine of mice with subcutaneous transplantation of oral cancer were analyzed. Methodes Three groups existed in the experiment: the Control group, the Negative control group, and the Over expression of miR-181a-5p group in the experimental group. To construct a subcutaneous transplantation tumor mouse model of oral cancer, different groups of treated cell suspensions were subcutaneously injected into the right point and upper location of the groin of M-NSG severely immunodeficient female mice. The pathogenic changes in each group were identified while additionally following the changes in the mice's body weight and small intestinal tissues using HE staining. By using tandem Orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry, the metabolites in the small intestine of mice in the NC group, OE group, and Control group have been detected. By pre-analyzing the original data and quality rating sample data, XCMS was able to assess which metabolites were different between the Control group and NC group and between NC group and OE group. To establish the unique metabolic pathways, KEGG enrichment analysis was used. Results A total of 170 distinct metabolites were found in the small intestinal tissues of the Control and NC groups. Choline metabolism, alanine, aspartate, and glutamate metabolism, GABA synaptic metabolism, glycerophospholipid metabolism, cAMP signaling route, cancer center carbon metabolism, and niacin and niacin amine metabolic pathways are important signaling pathways for metabolite enrichment. In the NC group, 16 distinct metabolites with VIP values larger than 2 were found in the small intestine of mice compared to the OE group that overexpressed miR-181a-5p. Glycerin phosphoylcholine, palmitic acid, 3-hydroxybutyryl carnitine, -hydroxybutyric acid, etc. are example of the metabolites which significantly vary. The primary raised metabolism path is the one for choline. Conclusions Mice's small intestine suffered slight changes as a result of subcutaneous transplantation of oral cancer, with the greatest effect in the metabolites critical in energy metabolism. The choline metabolic path was the pathway that selected absolutely metabolites in the small intestine of mice with the subcutaneous grafts of oral cancer.
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The effect of cobalt dichloride regulating inflammatory response and insulin resistance in 3T3-L1 adipocytes based on HIF-1α/ autophagy pathway
yuexinxin, Fu Yang, Li Yi Rang, Yin xiao yan, Yu Fei, Fu quan wei
Abstract:
Objective: To investigate the effect of hypoxia inducer cobalt chloride (CoCl2) on autophagy in 3T3-L1 adipocytes. Methods: 3T3-L1 adipocytes were cultured and induced to become mature adipocytes. CoCl2 was used as an inducer of hypoxia in vitro. Mature adipocytes were divided into control group, CoCl2 intervention group with different concentrations and different time. According to the above results, 150μmol/L cobalt chloride was selected to intervene adipocytes for 0h,12h,24h and 48h, respectively. Then the cells were collected for related tests. MTT assay was used to detect cell survival in each group. The expressions of HIF-1α, autophagy-related protein LC3Ⅱ, Beclin 1 and glucose transporter Glut-1 were analyzed by Western blot. The level of autophagy activity was detected by immunofluorescence.The levels of TNF-α and IL-6 in the supernatants of adipocytes were measured by ELISA. Results: The survival rate of adipocytes was decreased after treatment with 150μmol/L CoCl2 for 24 hours. The expression levels of HIF-1α, LC3-Ⅱ, Beclin 1 and Glut-1 proteins were significantly increased in 24h. Autophagy activity level was significantly increased in 24h. The secretion levels of inflammatory cytokines TNF-α and IL-6 were not significantly increased in 24h. Conclusion: Autophagy can be moderately activated by 150μmol/L CoCl2 intervention in adipocytes for 24 hours. The activation of autophagy can be activated in a HIF-1α-dependent manner, which plays a role in protecting adipocytes from inflammatory damage and improving insulin resistance.
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Progress in microglia-astrocyte interactions and their mediated neuroinflammation in Alzheimer's disease
HU Xin, WANG Qian, ZHANG Chen-xi, ZHENG Hui-hui, LI Peng-yang, ZHAO Hong-ye, DENG Feng-chun
Abstract:
Alzheimer's disease (AD) is an aggressive neurodegenerative disease whose pathogenesis is hitherto unknown. Neuroinflammation is a chronic inflammatory response in the central nervous system (CNS) activated by microglia and astrocytes that is difficult to subside autonomously and is associated with multiple inflammatory factors and the blood-brain barrier (BBB). Recent studies have shown that neuroinflammation has become the third major pathological feature in AD after β-amyloid (Aβ) deposition and neurogenic fiber tangles (NFTs). In this paper, we summarize and analyze microglia and astrocytes and their interaction, and organize and discuss the role of microglia-astrocyte interaction in neuroinflammation and AD. In order to provide a reference for the involvement of microglia and astrocytes in the pathological alterations of neuroinflammation in AD.
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Research progress of miRNA in neuroprotection of ischemic stroke
Abstract:
Ischemic stroke is a cerebrovascular disease with high disability and mortality, and can be life-threatening in severe cases, which has a heavy social and economic burden worldwide. The etiology and pathological process of ischemic stroke are mediated by a variety of molecular processes, and some of these molecular mechanisms are dynamically regulated after transcription. Increasing evidence has shown that Micro-ribonucleic-acid (miRNA), as an important mediator of post-transcriptional gene silencing, plays a crucial role in gene expression and the pathological process of ischemic stroke. In this review, we present the neuroprotective effects of mirnas in different mechanisms of ischemic stroke. Since the promotion or inhibition of miRNA expression through specific drug and non-drug therapy may be beneficial to the recovery of ischemic stroke, the clinical diagnosis and treatment of miRNA in ischemic stroke are also discussed in detail in this paper, aiming to provide a certain reference for clinical and basic research in this field.
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Research progress on the effect of miRNAs on liver metastasis of digestive system tumors
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Liver is the most common organ that tumors spread to, and expression of miRNA is very important in the process of liver metastasis. In this study, research progress of related miRNAs in regulating liver metastases from digestive system malignant tumors was collated and analyzed. Through searching related literature, this paper provides an introduction to the role of miRNAs in liver metastasis of colorectal cancer, gastric cancer, pancreatic cancer and gallbladder cancer, which helps with the diagnosis, treatment and research of tumor liver metastasis.
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Establishment of chronic alcoholic brain injury model in mice
Abstract:
【Abstract】 Objective To establish an effective and reliable chronic alcoholic brain injury model in mice. Methods C57BL/6J mice were randomly assigned into the control group and the model group. Mice in the model group were given free access to 5% (v/v) alcohol in drinking water, and were intragastrically administered with 28% (v/v) alcohol. The gavage dosage increased gradually over the first two weeks (from 0 to 6 g/kg body weight), and remained at 6 g/kg body weight for the subsequent four weeks. Mice in the control group were provided with normal water and given same amount of saline via gavage. At the end of the experiment, the cognitive function and motor ability of mice were evaluated through behavioral tests. The morphological changes of brain tissue of mice were examined by histopathological staining. Results Compared to the control group, mice in the model group showed cognitive impairments and motor dysfunction in the behavioral tests. The pathological examination of the brain tissue from the model group mice showed morphological damage and cell necrosis in the hippocampus. Conclusions The mouse model of chronic alcoholic brain injury was successfully and effectively established in this study, providing a valuable tool for investigating the underlying mechanisms and potential therapeutic interventions for chronic alcoholic encephalopathy.
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Molecular mechanism and prognosis of patients with HBV infection with DLBCL
Abstract:
In recent years, hepatitis B virus (HBV) infection patients with diffuse large B cell lymphoma (DLBCL) have shown an upward trend, and its etiology is complex and treatment is difficult, so it has received extensive attention from scholars at home and abroad. Based on the review and analysis of the research of domestic and foreign scholars, this paper further discusses the mechanism of the occurrence and development of DLBCL caused by HBV infection and the clinical prognosis of related patients, and finally finds that at the genomic and transcriptome levels, HBV may mainly induce the changes of BCL6, FOXO1, ZFP36L1 and other genes, and activate various regulatory genes through HBV's X protein, thereby inducing clonal proliferation of lymphocytes and eventually forming lymphoma. For the clinical prognosis assessment, the clinical prognosis assessment mainly analyzes and compares the patient's age of onset, sex, organ involvement, international prognostic index (IPI), lactate dehydrogenase (LDH) level, proliferation index (Ki-67), bcl-2, bcl-6, inflammatory index and other factors, aiming to put forward a theoretical basis for the clinical diagnosis and treatment of DLBCL and basic research.
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Study on the mechanism of lncRNA SNHG16 regulating the resistance of hepatoma cells to sorafenib by miR-570
Abstract:
Objective: To explore the mechanism of long non-coding RNA SNHG16 (Long non-coding RNA small nucleolar RNA host gene16, lncRNA SNHG16) to anti-liver cancer cell resistance by regulating minimal RNA-570 (miR-570). Methods: The expression of lncRNA SNHG16 and miR-570 of HepG 2 and HepG 2-R cells in human normal liver and hepatoma cells was measured by real-time fluorescence RT-PCR, cell proliferation, apoptosis and invasion were measured by MTT assay, FACS and Transwell test, and cell expression changes of CyclinD1, P21MMP-9 and MMP-2 were determined by Western Blot assay. Results: Compared with normal hepatocytes, lncRNA SNHG16 expression was increased and miR-570 expression was decreased in hepatoma cells (P<0.05). Compared with HepG2-P group, LncRNA SNHG16 and IC50 values were increased in HepG2-R group, and the inhibition rates of miR-570 and HepG2-R cells were decreased at Sorafenib concentrations of 1, 2, 4, 8, 16μmol/L (P<0.05). HepG2-R pcDNA SNHG16 as overexpression group, lncRNA SNHG16 expression was significantly increased (P<0.05), and compared with HepG2-R pcDNA group, In HepG2-R pcDNA SNHG16 group, the number of migrated cells, the expressions of CyclinD1, P21, MMP-9 and MMP-2 were decreased, while the expression of inhibition rate, apoptosis rate and P21 were increased (P<0.05). Compared with HepG2-R anti-miR-NC group, miR-570 level in HepG2-R anti-miR-570 group was decreased (P<0.05), and compared with HepG2-R anti-miR-NC group, HepG2-R anti-miR-570 group decreased the levels of CyclinD1, MMP-9 and MMP-2, and increased the levels of inhibition rate, apoptosis rate and P21 (P<0.05). Dual luciferase reporting experiment showed that compared with miR-NC group, miR-570 reduced the luciferase activity of WT-SNHG16 (P<0.05), but had little effect on the luciferase activity of T-SnHG16 (P>0.05). Overexpression of lncRNA SNHG16 decreased the expression of miR-570 in HepG2-R cells (P<0.05). Compared with HepG2-R pcDNA SNHG16 miR-NC group, In HepG2-R pcDNA SNHG16 miR-570 group, the number of migrated cells, the levels of CyclinD1, MMP-9 and MMP-2 were increased, while the levels of inhibition rate, apoptosis rate and P21 were decreased (P<0.05). Conclusion: By regulating the drug resistance of HepG2-R hepatoma cells, the mechanism is related to the regulation of miR-570 by lncRNA SNHG16, and it can be used as a new target for drug-resistant HCC cell therapy.
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Study on the Mechanism of Hyperuricemia combined with Nonalcoholic Fatty Liver based on PI3K/Akt/NF-kB
Abstract:
Abstract: Objective: To study the pathogenesis of hyperuricemia combined with nonalcoholic fatty liver disease (HUA-NAFLD) based on PI3K/Akt/NF-kB signaling pathway. Methods: 64 SD rats were randomly divided into blank group, HUA group, NAFLD group, and HUA-NAFLD group, 16 rats in each group. The samples were collected at the end of the 8th and 12th week, respectively. The serum biochemical indexes of the rats were detected; The pathological changes and lipid deposition in liver tissue were observed by hematoxylin-eosin staining (HE) and Oil Red O staining; the expression levels of PI3K/Akt/NF-kB signaling pathway-related proteins in liver tissue were detected by Western blot. Results: Compared with the other three groups, the liver index of the rats in the HUA-NAFLD group was significantly increased (P<0.05). Compared with the blank group, the levels of UA and LDL in the HUA group were increased, the levels of HDL in the NAFLD group were decreased, the levels of UA, CHOL, TG and LDL in the HUA-NAFLD group were increased, and the levels of HDL were decreased (P＜0.05); Compared with the HUA-NAFLD group, the levels of CHOL, TG and LDL were decreased in the HUA group, and the levels of UA, TG and LDL in the NAFLD group were decreased (P＜0.05). The results of HE and oil red O staining showed that compared with the other three groups, rat liver cells in the HUA-NAFLD group had a large number of fat vacuoles, blurred liver cord structure and more severe lesions. The WB results showed that compared with the blank group, the phosphorylation levels of AKT and p65 in the NAFLD group were significantly increased, and the phosphorylation levels of AKT, PI3K, p65 and IKKβ in the HUA-NAFLD group were significantly increased, and compared with the HUA-NAFLD group, the phosphorylation levels of AKT and p65 in the HUA-NAFLD group decreased significantly(P<0.05). The phosphorylation level of IKKβ decreased significantly in the HUA group, and compared with the HUA group, the phosphorylation level of p65 in the NAFLD group increased significantly (P<0.05). Conclusion: Compared with the single disease group, the HUA-NAFLD group has more abnormal biochemical indexes and more severe liver lesions. The PI3K/Akt/NF-KB signaling pathway may play an important role in the pathogenesis of HUA, NAFLD and HUA-NAFLD.
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Study on Allicin improves human peritoneal mesenchymal cell-mesenchymal transformation induced by high glucose through the JAK2/STAT3 signaling pathway
Gan Linwang, Li Qiancheng, Gao Lichao, Liu Qi, Li Ying, Wang Yujie, Ou Santao
Abstract:
Objective To investigate the mechanism of allicin in improving human peritoneal mesenchymal cell-mesenchymal transformation induced by high glucose. Methods human peritoneal mesothelial cells (HPMCs) were cultured and divided into two groups. Group 1: ①Control group; ②8.5 mM D-glucose induced group (8.5 mM DG group); ③17 mM D-glucose induced group (17 mM DG group); ④34 mM D-glucose induced group (34 mM DG group); ⑤68 mM D-glucose induced group (68 mM DG group). Except the control group, the other groups were induced with D-glucose of 8.5 mM, 17 mM, 34 mM and 68 mM, respectively, for 48 h. Group 2: ① control group; ②34 mM D-glucose induced group (HG group); ③34 mM D-glucose + low dose allicin induction group (AL-L group); ④34 mM D-glucose + medium dose allicin induction group (AL-M group); ⑤34 mm-glucose + high-dose allicin induction group (AL-H group); ⑥34 mM D-glucose + JAK2 inhibitor induction group (JAK2 group). HG group was induced with 34 mM D-glucose for 48 h, AL-L group, AL-M group and AL-H group were pretreated with 34 mM D-glucose for 6h, and then induced with 10 ng/mL, 20 ng/mL and 40 ng/mL allicin for 48 h, respectively. JAK2 group was pretreated with 1 μmol/L AG490 for 6 h and induced with 34 mM D-glucose for 48 h. The contents of IL-6, TNF-α and IL-1β in HPMCs supernatant were determined by Elisa. CCK-8 was used to detect cell proliferation and morphology. The expressions of JAK2, p-JAK2, STAT3, p-STAT3, N-cadherin, E-cadherin, Vimentin, α-SMA, MCP-1, p65 and p-p65 proteins were detected by Western blot. Results Compared with the control group, the relative survival rate of HPMCs in the high glucose induced group was significantly reduced (P<0.01), and cell morphology was abnormal, the expressions of α-SMA, N-cadherin and Vimentin that promote epithele-mesenchymal transdifferentiation were significantly up-regulated, and the expression of E-cadherin, which inhibits EMT, was significantly down-regulated. JAK2/STAT3 signaling pathway was activated, leading to the occurrence of EMT (P<0.01). Allicin can significantly promote the proliferation of HPMCs induced by high glucose, restore abnormal cell morphology, regulate the level of EMT-related proteins, and improve the epithelial-mesenchymal transdifferentiation of HPMCs. Compared with the high glucose induction group, the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α of HPMCs in allicin treatment group were significantly decreased, and the expressions of pro-inflammatory proteins p-p50 and MCP1 were significantly down-regulated, indicating that allicin could improve the inflammation caused by EMT. Conclution Allicin can improve EMT and inflammation induced by high glucose by inhibiting JAK2/STAT3 signaling pathway to regulate the levels of markers of EMT, inflammatory signaling proteins and inflammatory factors.
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Influence of hyperoside on autophagy in rats with nephrotic syndrome by regulating AMPK/mTOR/ULK1 signaling pathway
kongloujiao, wangxin, liujing, guoxiaoyang, xuemingwei
Abstract:
Objective To investigate the influences of hypericin (Hyp) on renal autophagy and AMPK/mTOR/ULK1 pathway in nephrotic syndrome (NS) rats. Methods Thirty-two 6-week-old SD rats were grouped into normal group (N group), NS group, Hyp group (60 mg/kg Hyp), Hyp AMPK inhibitor group (Hyp CC group) (60 mg/kg Hyp group) 0.2 mg/kg CC), 8 per group. After administration, an automatic analyzer was applied to detect the levels of 24-h urine total protein (UTP), blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB); HE staining and TEM observation were applied to observe renal pathological morphology and ultrastructure; Western blot was applied to detect the expression of autophagy, podocyte and AMPK/mTOR/ULK1 pathway proteins in kidney; immunofluorescence staining was applied to visualize the localization of autophagosomes and podocytes. Results Compared with the N group, the glomerular volume of the NS group increased, the renal tubules atrophied or partially disappeared, and the basement membrane thickened; UTP, BUN, Scr, basement membrane thickness, foot process width and the ratio of p-AMPK/AMPK were obviously increased (P<0.05), the protein levels of ALB, LC3-II/I, Beclin-1, Atg5, Atg7, NPHS2, the relative fluorescence intensity of NPHS2 and Beclin-1, and the ratios of p-AMPK/AMPK and p-ULK1/ULK1 were obviously decreased (P<0.05). Compared with NS group, Hyp treatment was able to improve glomerular morphology, decrease UTP, BUN, Scr, basement membrane thickness, foot process width and ratio of p-AMPK/AMPK (P<0.05), increase protein levels of ALB, LC3-II/I, Beclin-1, Atg5, Atg7, NPHS2, the relative fluorescence intensity of NPHS2 and Beclin-1 and the ratios of p-AMPK/AMPK and p-ULK1/ULK1 (P<0.05). AMPK inhibitor group CC could attenuate the autophagy-promoting and kidney-protecting effects of Hyp. Conclusion Hyp may enhance the autophagy activity of renal cells and attenuate renal pathology such as podocyte injury in NS rats by activating the AMPK/mTOR/ULK1 pathway.
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Study of core symptom impact on baicalein in an animal model of attention deficit hyperactivity disorder SHR rat
zhang yongting, Zhou Rongyi, Ma Bingxiang, Wu Chenlei, Xie Xinyue, Ding Xueying
Abstract:
Objective To explore the efficacy and potential mechanism of baicalin in regulating the core clinical symptoms of ADHD through the Morris water maze test and The open field test. Methods Thirty SHR rats were randomly divided into model group, methylphenidate hydrochloride(MPH) group, baicalin group, baicalin + tetrabenazine group and MPH + tetrabenazine group, with 6 rats in each group. Another 6 WKY rats were used as normal control group. The rats in the MPH group (1.5 mg/kg) and the baicalin group(150 mg/kg) were given the corresponding drugs (1 mL/100 g) by gavage, and those in the normal control group and the model group were given an equal volume of normal saline by gavage . In addition to the corresponding drug gavage,the rats in the MPH+tetrabenazine group and the baicalin+tetrabenazine group were given intraperitoneal injection of tetrabenazine(3 mg/kg) according to body weight (0.5 ml/100 g).The course of treatment was 4 weeks for all groups. Open field and Morris water maze experiments were carried out at the specified time, and the experimental results were recorded and analyzed Results In the open field experiment, the total distance and average speed in the MPH group and baicalin group were significantly lower than those in the model group (P < 0.05), and there was no significant difference between the two groups (P > 0.05);In the open field experiment, the total distance and average speed in the baicalin + bubenazine group were significantly lower than those in the model group (P < 0.05), and obviously higher than those in the baicalin group. In the water maze test, the latency of baicalin + bubenazine group was significantly shorter than that in the model group (P < 0.05), and significantly longer than that in the baicalin group (P < 0.05). The percentage of movement distance and stay time in the target quadrant in the baicalin + bubenazine group were obviously higher than those in the model group. It was significantly lower than that in baicalin group (P < 0.05).Conclusion Baicalin can control the core symptoms of hyperactivity, impulse and inattention in SHR rats, and its curative effect may be related to the regulation of dopamine vesicle transport.
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Study on the mechanism of ethyl acetate extract of Liujunzi Decoction on the energy metabolism of EC9706 cells in CAFs conditioned medium
Chen Xing, Lou Xiangyu, Shang Yiwan, Zhou Zhexu, Liu Yang, Liu Yaru, Hu Xiaobo, Chen Yulong
Abstract:
Objective: To explore the molecular mechanism of ethyl acetate extract of Liujunzi Decoction(EAELD) on energy metabolism of esophageal cancer EC9706 cells in conditioned medium of cancer-associated fibroblasts (CAFs). Methods: Methyl thiazol tetrazolium (MTT) assay was used to detect the effect of EAELD on the proliferation activity of EC9706. The effects of EAELD on lactate and glucose in the supernatant of EC9706 cells in CAFs conditioned medium were detected by colorimetry. seahorse system energy metabolism analysis system was used to detect the effect of EAELD on energy metabolism of EC9706 cells in CAFs conditioned medium. Real-time fluorescent quantitative PCR (q-PCR) and western blotting were used to detect the mRNA and protein expression of energy metabolism-related molecules.. Results: Compared with DMEM, except for the 10μg/mL group,EAELD had a significant inhibitory effect on the proliferation of EC9706 cells (P < 0.05). The inhibitory concentration (IC30) of 25μg/mL and half inhibitory concentration (IC50) of 40μg/mL were selected as the low and high dose groups for subsequent experiments. Among EC9706 cells cultured by CAFM, both low-dose and high-dose EAELD groups could significantly reduce Non-mitochondrial oxygen consumption, Basal respiration value, Maximum respiration value, Oxygen consumption of ATP synthesis, Spare respiration capacity, Basal glycolysis, Compensative glycolysis and glycolysis potential (P <0.01). Decreased the lactate content of EC9706 cells (P <0.01), down-regulated the mRNA expression of GLUT1 (P <0.05, P <0.01), down-regulated the protein expression of p-PKM2, HK2, PKM2 and MCT1 (P <0.01); The high-dose EAELD group could down-regulate the Mitochondrial oxygen consumption and basal use The glycolytic ratio of EC9706 cells (P <0.05), reduce glucose uptake of EC9706 cells (P <0.05), down-regulate the protein expression of p-PKM2 and GLUT1 (P <0.01, P <0.05); The low dose group of EAELD could down-regulate the mRNA expression of MCT1 (P <0.05). Conclusions:EAELD can interfere with the energy metabolism of EC9706 cells in CAFs conditioned medium, and its mechanism may be related to the regulation of HK2, PKM2, GLUT1, MCT1 and MCT4 mRNA and protein expression.
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Application characteristics of animal model of osteosarcoma based on data mining
yushuaike, luomaoli, wanglianrui, zhoutianbao, baili, miaomingsan
Abstract:
Objective To summarize the key points of animal modeling of osteosarcoma, and to provide reference and suggestions for improving the modeling methods and evaluation indexes.Methods The database was established by searching the relevant literature on the animal model of osteosarcoma in CNKI, Wanfang database and PubMed. The species of experimental animals, gender, modeling methods, types of cancer cell lines and detection indicators were summarized, and the database was established for statistical analysis. Results A total of 284 literatures were included. Statistical analysis found that BALB / c-nu / nu nude mice were preferred in osteosarcoma model animals(227 cases，75.17%), followed by SD rats (20 cases, 6.62%). Subcutaneous cell fluid transplantation in the back (66 cases, 21.85%), subcutaneous cell fluid transplantation in the axils (55 cases, 18.21%) or in situ cell fluid transplantation (51 cases, 16.89%) were used as modeling methods. Human MG-63 cells (100 cases, 33.11%) and mouse UMR-106 cells (39 cases, 12.91%) were selected as the cancer cell lines.The most detected indexes were tumor tissue apparent index (238 cases, 83.80%), tumor tissue HE staining (129 cases, 45.42%), Animal apparent indicator (94 cases, 33.10%)，tumor tissue immunohistochemistry (89 cases, 31.34%), etc. Conclusions At present, osteosarcoma BALB / c-nu / nu nude mice aged 4 to 6 weeks are used as experimental animals, and human MG-63 cell heterotopic transplantation (back and axillary transplantation) is used to establish the animal model, and the detection indexes of osteosarcoma are comprehensively evaluated by animal apparent index, tumor apparent index and tumor histopathology. It is suggested to select serum biochemical index, apparent index of tumor tissue as well, HE staining of tumor tissue and immunohistochemistry of tumor tissue to evaluate the model. However, there is still a lack of animal model preparation and evaluation criteria with high clinical consistency. In this paper, the advantages and disadvantages are summarized through literature mining and data analysis, in order to provide reference for the establishment of a good OS model and better application to OS mechanism research and new drug development.
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Effects of moderate intensity and high intensity intermittent exercise on myocardial mitochondria autophagy in mice with nonalcoholic fatty liver disease
he miao, li jia hang, liu xin, yang wei, wu liang wen, fan jing jing
Abstract:
Objective To investigate the effects of moderate aerobic exercise and high intensity intermittent exercise on myocardial mitochondria autophagy in mice with non-alcoholic fatty liver disease and its possible mechanism. Methods Forty 3-week-old male C57BL/6J mice were randomly divided into normal feeding group (Chow group, n=10) and high fat feeding group (HFD group, n=30). At week 18, those whose body weight in HFD group exceeded 20%~30% (including 20%) of the ordinary diet group were judged as obese mice (n=26). Two mice were randomly selected for liver oil red O staining to confirm the successful establishment of NAFLD mouse model. Sixteen NAFLD mice were randomly selected and divided into moderate intensity aerobic exercise group (MICT group) and high intensity intermittent aerobic exercise group (HIIT group), with 8 mice in each group. The two groups were given exercise training for 8 weeks, respectively, and the samples were weighed after intervention. Masson staining was used to observe myocardial fibrosis. The ultrastructure of myocardial cells was observed by transmission electron microscopy. Mitochondrial autophagy and mitochondrial biogenesis were detected by Western Blot. Results ⑴ Compared with Chow group, body weight and heart index in HFD group were significantly increased and decreased. Compared with HFD group, the body weight of MICT and HIIT group increased significantly, and the heart index of MICT group increased. (2) Masson results showed that compared with Chow group, the content of collagen fibers in myocardium in HFD group was significantly increased, and the myocardial fibers were disorganized and broken under electron microscope. The morphology of myocardium was disorganized, mitochondria were swollen, crists were broken and blurred, and lipid droplets were included. Compared with HFD group, the myocardial collagen fiber content in MICT and HIIT groups was significantly reduced, the myocardial fiber arrangement was slightly recovered under transmission electron microscopy, the Z-line was clearly visible, the degree of mitochondrial degeneration was slightly improved, and the lipid droplets were also slightly reduced. Among them, the improvement effect of MICT group on the cardiac tissue structure was better than that of HIIT group. (3) Western Blot results showed that compared with Chow group, the expression levels of PINK1 and Beclin1 in myocardial tissue of HFD group had no significant changes, while the expressions of Parkin, LAMP1 and PGC-1α were significantly decreased (p<0.01). p62 protein expression and LC3-II/LC3-I ratio were significantly increased (p<0.05, p<0.01); Compared with HFD group, the expression levels of PINK1 and Beclin1 in MICT and HIIT groups were not significantly changed, while the expression of PGC-1α was up-regulated, and the expressions of Parkin and LAMP1 in MICT group were significantly increased (p<0.05). p62 protein expression and LC3-II/LC3-I ratio were significantly decreased (p<0.05, p<0.01), Parkin and LAMP1 expression levels were up-regulated, LC3-II/LC3-I ratio and p62 protein expression were significantly decreased in HIIT group (p<0.05, p<0.01). Conclusion Different forms of aerobic exercise can effectively ameliorate myocardial structural and functional injury in NAFLD mice, which may be through stimulating the autophagy flux of mitochondria in cardiomyocytes, activating autophagy and restoring the normal autophagy function of cells, so as to ameliorate myocardial cell damage, and moderate continuous aerobic exercise has better improvement effect.
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Exploring the Management Innovation Mechanism of Emergency Science and Technology Research Projects in the Medical Field
CHEN Yujun, SU Meiyangyi, WANG Qingxuan, GAO Ran
Abstract:
Objective The emergency technology research project highlights the two key aspects of "emergency" and "research", which are how to effectively achieve the goal results.Organizations that undertake such projects need to develop reasonable project management mechanisms to ensure the successful implementation of emergency technology research projects.This article aims to investigate the current problems in the management of emergency technology research projects in the medical field through research, analyze possible improvement measures, and improve the efficiency and quality of scientific research management.Methods This article combines the author's practical experience, investigates the current status of scientific research management in relevant units, and conducts questionnaire surveys on the management aspects that are most concerned by scientific management and researchers.Based on the problems reflected in the survey, experts are organized to discuss and demonstrate.Results Through the research, it is found that: 1. At present, there are few management norms for emergency technology research projects;2. The most concerned issue for scientific researchers is administrative approval and project funding;3. The most concerned issue for scientific management personnel is how to meet the management requirements of higher-level units and the needs of scientific researchers under the premise of legal compliance.Conclusion Emergency technology research projects have their own unique characteristics compared to conventional technology projects. Management optimization can be carried out in terms of project approval, fund use, resource allocation, and safety. This study provides innovative solutions for the management of emergency technology research projects, and provides useful experience and reference for various scientific research units in managing such projects.
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Effects of compound active tea of Lithocarpus litseifolius on uric acid and renal function in mice with hyperuricemia nephropathy
陈, zengyanan, DUXIAOLANG, MUZEJING, liaochengdong, zhangchanghua, caolan
Abstract:
Abstract：Objective To explore the effect of compound active tea of Lithocarpus litseifolius on uric acid and kidney function on mice with hyperuricemia nephropathy , and to provide experimental basis for the development of hyperuricemia nephropathy drugs and functional food. Methods The mouse model of hyperuricemia nephropathy was established by potassium oxyoxide with adenine. Mice were randomly divided into normal group, model group, benbromarone positive drug group (10 mg?kg-1?d-1), and Compound active tea of Lithocarpus litseifolius high,middle, low-dose groups (10g?kg-1?d-1,3.33g?kg-1?d-1,1.11g?kg-1?d-1).1h after the last dose, urine protein (UP) was measured by CBB method,urea nitrogen (UUN) was measured by the urease method;Blood was collected for uric acid (UA) by enzyme ratio method and urea nitrogen (BUN) by urease method;the serum content of interleukin cells 6 (IL-6) and tumor necrosis factor(TNF-α) was measured byeuzymelinked immunosorbent assay;uate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mouse kidneys were measured by quantitative fluorescence analysis.Kidney tissues were harvested and histopathological changes were observed by HE staining.Results Compared with the normal group,the UP, UUN, UA, BUN, IL,URAT1 and ULUT9 of model group mice were significant increased (P<0.01),TNF-α was increased (P<0.05),the renal tissue structure was normal.Compared with the model group,the UP,UUN,UA,BUN of benbromarone positive drug group were significant decreased(P<0.01),IL-6 and TNF-α were decreased(P<0.05),URAT1 was increased(P<0.05),little glomerular atrophy and deformation in the kidney,kidney tubular dilatation was occasionally seen,and no inflammatory cell infiltration.Compared with the model group,the UP,UUN,UA,BUN,IL-6 and URAT1 of high-dose group of compound active tea of Lithocarpus litseifolius were significant decreased(P<0.01),TNF-α and GLUT9 levels were decreased(P <0.05);the UP, UA, UUN content , the levels of IL-6, URAT 1and GLUT9 of middle-dose group of compound active tea of Lithocarpus litseifolius were significant decreased(P<0.01),BUN together with reduced levels of TNF-α(P <0.05);the UP,UUN,UA,IL-6 and URAT1 of low-dose group of compound active tea of Lithocarpus litseifoliuswere significant decreased(P<0.01),BUN content and reduction of TNF-α and GLUT9 levels (P<0.05),the kidney condition of the mice in compound active tea of Lithocarpus litseifolius group was improved.Conclusion: the compound active tea of Lithocarpus litseifolius can reduce uric acid in mice with hyperuricemia nephropathy, and it has a certain protective effect on the kidney,the mechanism may be related to the inhibition of uric acid reabsorption, and the specific mechanism should be further investigated.
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HDAC6 inhibitors improve diabetic nephropathy by protecting glomerular endothelial cell mitochondria
Abstract:
objective: To investigate the protective effect and mechanism of histone deacetylase 6 (HDAC6) specific small molecule inhibitor Tubastatin A on renal injury in diabetic nephropathy (DN) mice. Methods: C57BL/6 mice were randomly divided into 3 groups: control group, DN group and Tubastatin A group. Mice in the DN group and Tubastatin A group were intraperitoneally injected with燬TZ?80爉g/kg) daily for 3 days after the removal of one kidney. Tubastatin A group received Tubastatin A treatment every 3 days for 8 weeks. RNA sequencing analysis of differentially expressed genes in kidney tissue of DN group and Tubastatin A group. Mitochondrial damage was assessed by transmission electron microscopy, and ROS levels in kidney tissue were estimated by DHE staining. Mouse glomerular endothelial cells (mGEC) were exposed to high glucose medium (HG) or 40 mM mannitol (control) with or without Tubastatin A treatment. Western blot analysis was used to analyze the expression of HDAC6, kidney injury markers KIM1 and EMT markers, and flow cytometry was used to detect mitochondrial ROS and apoptosis in cells. Results: HDAC6 expression was up-regulated in DN mouse kidney tissue and mGEC cells exposed to HG, consistent with increased levels of KIM1. Histological analysis showed significant morphological changes in DN mice, including glomerular hypertrophy, mesangial matrix accumulation, glomerular basement membrane thickening, tubular basement membrane thickening and the presence of glomerular, intertubular fibrosis; Tubastatin A treatment alleviated these changes. Compared with control DMSO, Tubastatin A significantly decreased the expression of KIM1, HDAC6, α-SMA, N-cadherin, vimentin (P<0.05) and up-regulated the expression of E-cadherin (P<0.05) in mGEC cells under HG treatment. RNA-sequencing revealed the enrichment of genes related to ECM-receptor interaction and tricarboxylic acid (TCA) cycle in the kidney tissue of Tubastatin A mice compared with DN mice. Transmission electron microscopy showed that the proportion of damaged mitochondria in glomerular endothelial cells in Tubastatin A group was significantly lower than that in DN group (P<0.01). DHE staining showed that the level of ROS in the kidney tissue of Tubastatin A group was lower than that of DN group (P<0.01). In mGEC cells, Tubastatin A treatment down-regulated HG-induced mitochondrial ROS levels in mGEC cells (P<0.01), and reduced apoptosis (P<0.05). Conclusion: Tubastatin A ameliorates HG-induced glomerular endothelial cell injury and DN progression, and its mechanism is related to the protection of mitochondrial homeostasis and inhibition of EMT.
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Effects of human amniotic epithelial cells transplantation on the improvement of endometrium and MMP-8, VEGF in rat model of uterine scar
Abstract:
Objective: To investigate the effect of human amniotic epithelial cells (hAECs) transplantation on endometrium improvement and matrix metalloproteinase-8 (MMP-8) and vascular endothelial growth factor (VEGF) in a rat model of uterine scar. Methods: The uterine scar model of rats was established and randomly divided into model group and transplantation group, with 18 rats in each group. The other 18 rats were selected as sham operation group. The rats in the transplantation group were injected with hAECs in the scar of the uterus, and the rats in the model group and the sham operation group were only given the same amount of PBS. After 4 weeks, the uterine tissues of 8 rats in each group were collected and HE staining was used to observe the histomorphological changes, and the endometrial thickness and the number of glands were measured. Masson staining was used to observe endometrial fibrosis. Endometrial growth and receptivity were evaluated by immunohistochemical staining for cytokeratin and integrin β3, respectively. The mRNA expression levels of MMP-8 and VEGFA in endometrial tissues were detected by RT-qPCR. Western blotting was used to detect the protein expression levels of MMP-8 and VEGFA. After 8 weeks, the remaining 10 rats in each group were selected for gestational ability determination. Results: Compared with the sham-operation group, the endometrial thickness, the number of glands, the IOD value of keratin and integrin β3, the mRNA and protein relative expression levels of MMP-8 and VEGFA, the pregnancy rate and the number of uterine embryos in the model group and the transplantation group were significantly decreased (P<0.05). Compared with the model group, the endometrial thickness, the number of glands, the IOD value of keratin and integrin β3, the mRNA and protein relative expression levels of MMP-8 and VEGFA, the pregnancy rate and the number of uterine embryos were significantly increased in the transplantation group (P<0.05). In addition, hAECs transplantation could improve the pathological morphology of endometrial tissue in rats with uterine scar. Reduce the degree of endometrial fibrosis. Conclusion: hAECs transplantation could improve endometrial injury, reduce scar formation, improve endometrial receptivity, and enhance pregnancy function in model rats, which may be related to the promotion of MMP-8 and VEGFA expression.
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Effect of inhibition of the mitochondrial inner membrane protein OMA1 on apoptosis in a Rot-induced Parkinson's disease cell model
shijin, Lihaining, Luyue, Xuting
Abstract:
Objective To investigate the effect of inhibition the mitochondrial inner membrane protein OMA1 on rotenone-induced apoptosis in Parkinson's disease (PD) cell model. Methods SH-SY5Y cells were cultured in vitro, treated with Rot (final concentrations of 0.05, 0.1, 0.2, 0.3, 0.4 μmol/L) for 24 h, and the best Rot (0.2 μmol/L) was selected for subsequent experiments. The experiment was divided into control group (cells without special treatment), PD model group (0.2 μmol/L Rot treated cells for 24 h), Negative control group (negative control sequence of OMA1 siRNA transfected on the basis of normal control group), OMA1 siRNA group (0.2 μmol/L Rot treated cells for 24 h and transfected with OMA1 siRNA). CCK-8 was used to detect cell survival rate, inverted phase contrast microscope was used to observe cell morphology in each group, Western blot was used to detect changes in the expression of OMA1 and apoptosis-related proteins Caspase-3, Bax, and Bcl-2, and TUNEL apoptosis kit was used to detect cell apoptosis. Results Compared with the control group, the survival rate of SH-SY5Y cells decreased in a concentration-dependent manner with increasing Rot concentration (P<0.05). Compared with the control group, the expression of OMA1 and apoptotic protein Caspase-3 expression were increased and Bax/Bcl-2 values were increased in the PD model group (P<0.01). Compared with the PD model group, the cells in the OMA1 siRNA group, the OMA1 siRNA group gradually restored morphological changes, decreased apoptotic protein Caspase-3 expression and Bax/Bcl-2 values, and TUNEL apoptosis staining suggested reduced apoptosis (P<0.01). Conclusions Inhibition of the mitochondrial inner membrane protein OMA1 ameliorates apoptosis induced by the Rot-induced PD cell model, which in turn may have a protective effect on neurons.
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The effect of CeO2NPs on organ structures and redox indicators in male mice
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Objective To investigate the effects of CeO2NPs sub-acute exposure on body weight, organ structures and redox indicators in male mice. Methods 35 male ICR mice were randomly divided into five groups with seven mice in each group. Normal control group and CeO2NPs (100, 500, 1000, 5000 ug/kg) test groups were set up. Mice were injected CeO2NPs intraperitoneally every other day for 28 days. Results Compared with the control group, there was no significant difference in weight gain (P>0.05) , but there was significant difference in liver coefficient, epididymal coefficient and sperm survival rate (P<0.01). In the 5000 ug/kg group, CeO2NPs were deposited in the liver and spleen, and granuloma was found. The activities of SOD and GSH-Px in serum of 100 ug/kg group were increased, while the content of MDA was decreased, which showed the antioxidant effect of CeO2NPs. With the increase of dose, the oxidative stress induced by CeO2NPs was enhanced. Conclusion The low dose of CeO2NPs is safe and has antioxidant effect. With the increase of dose, the toxicity of CeO2NPs to the body also increases gradually.
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Research progress on gut microbiota and obesity-related metabolic diseases
Su Hei Yan Pa Er Ha Ti, ZHANG Jiaojiao, MA Zhuang, WANG Junren, LI Yanhong
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Obesity centered metabolic diseases such as diabetes, hypertension, and cancer are increasing at an alarming rate worldwide and have become global public health concerns. The treatment of obesity and related metabolic diseases has gradually become a research hotspot. Currently, an increasing number of studies have proved that gut microbiota can regulate energy balance and glycolipid metabolism, and regulate the occurrence and development of obesity and related metabolic diseases. It is very likely that the gut microbiota is a potential new target for the treatment and prevention of metabolic diseases. In this paper, we summarize the progress of gut microbiota in the development and progression of obesity associated metabolic diseases and analyze the role of gut microbiota in metabolic diseases.
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Research progress of exosomal microRNA in early screening and treatment of Alzheimer's disease
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Exosomes, as small molecule extracellular vesicles secreted by a variety of cells, play an important role in the pathological process of Alzheimer's disease by transporting a variety of bioactive substances such as microRNA. Studies have shown that the expression of exosomal microRNA changes in the early stages of AD patients, and exogenous injection of mesenchymal stem cell-derived exosomal microRNA can improve the learning and memory ability of AD animal models. This paper reviews the research progross of exosomes in early screening and treatment of Alzheimer's disease.
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Research progress of disease-syndrome combination models of chronic obstructive pulmonary disease
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Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality, which has become an important health problem in today's society. Traditionray Chinese Medicine has accumulated rich historical experience in the treatment of COPD and has unique clinical advantages. In order to further explore the therapeutic effect of traditional Chinese medicine on this disease, the preparation of COPD animal model combining disease and syndrome is the key premise of studying the occurrence and development of the disease. The combined models of disease and syndrome summarized in this paper include five types: the animal model of lung qi deficiency, the animal model of lung and spleen deficiency, the animal model of phlegm-heat stagnation of lung, the animal model of phlegm-stasis obstructing lung, and the animal model of cold drink. Now the common disease and syndrome in recent years combined with the method of class modeling are simply described and combed, in order to provide new ideas for researchers, and promote the research process of traditional Chinese medicine treatment of this disease.
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Research Progresses on the Effects of the Plateau on Mitochondrial Function and Energy Metabolism
LIBOSHEN, ZHANGYUXUAN, FANRONGHUI, LIMAOXING
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The plateau is a unique environment with low pressure, low oxygen and high cold. The plateau environment will reduce the metabolism of energy substances and mitochondrial work, thus affecting the plateau operation. In recent years, mitochondrial damage has attracted wide attention. As the energy factory of cells, mitochondria are closely linked to the movement of the body. We focused our attention on mitochondrial damage at high altitude, and summarized the effects of high altitude on the metabolism of basic energy substances and the changes of key enzyme activities and mitochondrial structure and function in mitochondrial biochemical energy supply response. It was found that protein, carbohydrate and lipid metabolism was negatively affected at high altitude, resulting in fatigue, hyperlipidemia and body repair. The activities of enzymes related to pyruvate metabolism, tricarboxylic acid cycle, β-oxidation and oxidative phosphorylation are inhibited, and the morphology and number of mitochondria are changed, which will lead to impaired mitochondrial function and affect exercise energy supply. In the future, the exploration of the mechanism of plateau cell injury will vigorously promote the research of plateau injury prevention and treatment drugs.
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A review of animal models of vascular dementia
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Abstract: Vascular Dementia (VD) is caused by cerebrovascular diseases, either hemorrhage or ischemic damage in the brain, with ischemia being the most common. In recent years, much more efforts have been made to study the etiology, pathogenesis and prevention of VD. The establishment of appropriate animal models for studying the mechanism of VD and exploring efficacy of VD treatment has become one of key issues in the research field. On the basis of the conventional methods such as the bilateral occlusion of the common carotid arteries (2VO) and the four-vessel occlusion, the researchers had modified these methods to improve the stability with better reflection of the clinical manifestations of VD. This paper mainly summaries these modified methods, and discuss possible cellular and molecular mechanisms and their advantages and disadvantages.
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Keratin 17 knockout aggravates wound healing in diabetic mice
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Objective To explore the effects of keratin 17 (Krt17) knockout on wound healing in diabetic mice. Methods To establish the diabetic models, 60% high-fat diet was fed and streptozotocin was administered intraperitoneally at 40mg/kg once per day for 5 consecutive days in wild-type (WT) and Krt17 knockout (Krt17-/-) mice at six weeks of age. The mice were anesthetized with isoflurane, the back was shaved, and a 6 mm circular skin lesion was made in vivo at one week after successful modeling. Western blotting and immunofluorescence staining were used to detect the expression and localization of KRT17 and histopathological examination was analyzed in wound healing on the 8th day. Photos were taken at 0, 2, 4, 6 and 8 days after wound manufacturing, and wound healing rate was calculated. Results KRT17 was mainly expressed in mouse hair follicles in physiological conditions. When the skin was injured, the expression of KRT17 in keratinocytes in the proximal wound was significantly increased. However, the expression of KRT17 in wounds of diabetic mice was significantly down-regulated compared with that of control mice. The wound healing rate of Krt17-/- mice was significantly reduced and the local inflammatory reaction was more persistent compared with WT mice. Conclusions Krt17 knockout aggravates wound healing in diabetic mice. Krt17 may be an important modifier gene of diabetic wound healing.
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Effects of baicalin on proliferation and apoptosis of laryngeal cancer cells via miR-125b-5p/IRF4 axis
WANGJIAN, SUNYONGDONG, ZHOUXINGWEI, LIULEI, TONGXINGKE, CHENLONG, HEXIAN
Abstract:
Objective: To explore the mechanism of baicalein inhibiting the proliferation and migration of laryngeal cancer cells. Methods: Hep-2 cells were used as the research object. The cell proliferation activity of each group was detected by MTT method, cell migration was detected by scratch assay, cell apoptosis was detected by flow cytometry, western blot was used to detect the expression levels of Beclin-1, LC3II/I, p62 and HDAC1 in laryngeal cancer cells in each group, RT-PCR detection of the expression levels of miR-449a in each group of cells. The targeted binding sites of miR-449a and HDAC1 were analyzed by bioinformatics software and identified by dual luciferase reporter gene experiments. The number of autophagosomes was observed by projection microscopy. Results: Baicalein significantly inhibited the proliferation and migration of laryngeal cancer cells, and significantly induced apoptosis. Baicalein increased the protein expression levels of intracellular autophagy-related genes Beclin1 and LC3II, but decreased the protein expression levels of p62 and LC3I. Baicalein significantly increased the expression level of miR-449a in laryngeal cancer cells and decreased the protein expression of HDAC1. There is a binding effect between HDAC1 and miR-449a. Baicalein combined with miR-449a mimic to treat laryngeal cancer cells can more significantly inhibit cell proliferation and HDAC1 protein expression, as well as more effectively up-regulate the relative expression of miR-449a and induce autophagy. Conclusion: Baicalein can mediate autophagy and inhibit the proliferation and migration of laryngeal cancer cells via the miR449a/HDAC1 axis.
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Effects of low-dose BPA and DEHP on the expression of AKR1C3 in prostate of adult rats
Huangdongyan, Wushuangshuang, Shaocongcong, Suxin, Yangrongfu, Wangkaiyue, Zhouping, Wujianhui
Abstract:
Objective To investigate the effects of of low dose of bisphenol A (BPA) and di (2-ethyl) hexyl phthalate (DEHP) on Aldo-keto reductase 1C3 (AKR1C3) in adult SD rats. Method 56 adult male SD rats were randomly divided into 7groups (8 rats in each group) and they were given BPA (10.0µg/kg,30.0µg/kg,90µg/kg, i.g.), DEHP (30.0µg/kg ,90.0µg/kg ,270 µg/kg, i.g.) and vehicle respectively once a day for 4 weeks. The animals were sacrificed on the day subsequent to last treatment and the blood was collected, the prostate tissues were dissected and categorized into different lobes. The levels of AKR1C3 in serum and prostate were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of AKR1C3 in each lobe of prostate was analyzed by immunohistochemistry. Result After the administration of BPA, the expression of AKR1C3 in 90µg/kg and 270µg/kg group increased, and there was significant difference in the high-dose group (P<0.05); The level and protein expression of AKR1C3 in dorsal prostate increased, and there was significant difference in 10µg/kg group (P<0.01, P<0.001). After administration of DEHP, the level of serum AKR1C3 in 270µg/kg group was significantly higher than that in the control group (P<0.001), the level of AKR1C3 in the ventral prostate was significantly higher than that in the control group (P<0.05, P<0.01), and the expression of AKR1C3 protein increased, there was significant difference in 270µg/kg group (P<0.05); The level of AKR1C3 in 90µg/kg and 270µg/kg dose group of dorsal prostate was higher than that in the control group, and there was significant difference in 30µg/kg group (P<0.05). The expression of AKR1C3 protein in each group increased, and there was significant difference in 30µg/kg and 90µg/kg dose group (P<0.001, P<0.05). Conclusion Low-dose BPA and DEHP can promote the expression of AKR1C3 in the prostate of adult SD rats, but the sensitivity of ventral and dorsal lobes of prostate to BPA and DEHP is different.
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Bone marrow mesenchymal stem cells isolated from rats by bone marrow and slice adherent culture in vitro and PKH26 labeling
Abstract:
Objective To establish an efficient method for isolation and culture of rat bone marrow mesenchymal stem cells (BMSCs), and apply PKH26 to label them in vitro to explore the effect of PKH26 labeling on the biological characteristics of BMSCs, as well as the in vitro tracing. Methods The bone of both hind limbs of 5d suckling rats were separated, the surrounding muscle and fascia were removed, and cut into small pieces for culture. BMSCs were purified by fluid exchange and passage, and the third generation cell surface antigen was determined by flow cytometry. Under the same culture conditions, the third generation BMSCs were labeled with PKH26. Cell morphology and proliferation status were observed under fluorescence microscope in the labeled group and the unlabeled group, and the adipogenic induction characteristics and identification of the labeled group and the unlabeled group were compared. Results The bone marrow slice method was used to separate the hind limb bones of suckling mice. The BMSCs were slender spindle shaped and uniform in shape. A large number of BMSCs could be rapidly obtained in a short time; The results of flow cytometry showed that the expression of CD29 was (91.18 ± 1.29)%, the expression of CD90 was (91.18 ± 1.29)%, and the expression of CD45 was (1.74 ± 0.36)%; PHK26 labeling had no significant effect on the morphology and proliferation of BMSCs cells (P>0.05), and had no effect on the induction of osteogenesis and adipogenesis. Conclusions A large number of high-purity BMSCs can be rapidly cultured by the method of 5-day rat bone marrow slices, which can be used as seed cells for bone tissue engineering; PKH26 can label rat BMSCs in vitro.
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Regulation of ADAM10 gene osteogenic differentiation of bone marrow mesenchymal stem cells and tibial fracture union through Notch1 pathway
TangXiaoxu, Liu wanting, Douyinxia, Li Fuqin, Wang Nan
Abstract:
Objective To study the regulation of a disintegrin and metalloproteinase 10 (ADAM10) gene on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and tibial fracture union. Methods BMSCs of SD rats were cultured, BMSCs stably transfected with negative control (NC) shRNA or ADAM10 shRNA pGFP-V-RS vector were established, the osteogenesis was induced for 14 days. During the induction process, DMSO or 10 μmol/L Notch1 agonist valproic acid (VPA) were added. absorbance at 405nm of alizarin red staining, ALP activity and the expression levels of ADAM10, OCN, Runx2, CoL-I, NICD and Hes1 were detected. The tibial fracture model of SD rats was established and NC shRNA or ADAM10 shRNA pCMV5.0 vector was injected locally. The fracture healing and gene expression were observed for 4 weeks later. Results The expression level of ADAM10 in BMSCs in sh-ADAM10 group was lower than that in sh-NC group. After osteogenesis induction, the absorbance value of alizarin red staining at 405nm, ALP activity and the expression levels of OCN, Runx2, CoL-I, NICD and Hes1 of sh-ADAM10 group were higher than those in sh-NC group (P<0.05). the absorbance value of alizarin red staining at 405nm, ALP activity and the expression levels of OCN, Runx2, CoL-I of sh-ADAM10 VPA group after osteogenesis induction were lower than those in sh-ADAM DMSO group (P < 0.05). The fracture healing of tibial fracture rats in sh-ADAM10 group was better than that in sh-NC group, and the expression levels of OCN, Runx2, CoL-I, NICD and Hes1 were higher than those in sh-NC group (P<0.05). Conclusion Knockdown of ADAM10 can promote the osteogenic differentiation of BMSCs and the healing of tibial fractures by inhibiting Notch1 pathway.
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The improvement effect and mechanism of modified Chaihu Guizhi Decoction on osteoporosis rats by regulating Wnt/β-catenin signaling pathway
Abstract:
Objective: To investigate the improvement effect of modified Chaihu Guizhi Decoction (CGD) on osteoporosis rats by regulating the Wnt/β-catenin signaling pathway. Methods: SD rats were separated into CK group, Model group, low-dose CGD group (CGD-L group, 5 g/kg), high-dose CGD group (CGD-H group, 20 g/kg), and estradiol valerate group (EV group, 9 mg/kg), DKK-1 (Wnt/β-catenin pathway inhibitor) group (100 mg/kg), and CGD-H DKK-1 group (20 g/kg 100 mg/kg), 12 per group. Except for the CK group, the rats in other groups were given 70 mg/kg retinoic acid to build the OP rat model, and the rats in the CK group were given the same amount of normal saline. From the 4th week of modeling, the corresponding drug intervention was given for 4 weeks. ELISA was applied to detect the levels of collagen type I C-terminal peptide (CTX-Ⅰ) and osteocalcin (BGP) in serum of rats; the changes of bone volume fraction, bone trabecular thickness, bone mineral density and bone trabecular number were observed; HE staining was applied to detect the pathological changes of rat femur; Alkaline phosphatase (ALP) calcium-cobalt staining was applied to detect osteoblast activity in rat femur; the activity of osteoclasts in rat femur tissue was detected by tartrate-resistant acid phosphatase (TRAP) staining; Western blot was applied to detect Wnt and β-catenin proteins in femoral tissue of rats in each group. Results: Compared with the CK group, the femoral tissue of the Model group had severe pathological damage, CTX-I level and osteoclast activity increased, BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression decreased (P<0.05); compared with the Model group, the pathological damage of the femur in the CGD-L group, the CGD-H group and the EV group was alleviated, CTX-I level and osteoclast activity decreased, BGP level, bone volume fraction, trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression increased, the trends of the corresponding indicators in the DKK-1 group were opposite to the above (P<0.05); compared with the CGD-H group, the femoral tissue of the CGD-H DKK-1 group was severely damaged, CTX-I level and osteoclast activity increased, BGP level, bone volume fraction, bone trabecular thickness, bone mineral density, bone trabecular number, osteoblast activity, Wnt, β-catenin protein expression decreased (P<0.05). Conclusion: CGD may improve OP of rats by activating the Wnt/β-Catenin pathway.
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Acupoint catgut embedding affects the level of inflammation in rheumatoid arthritis through PD-1/OX40 signaling pathway
Chen Li-chuan, Duan bo, Yu Zhao, Ma Zhi-yi, Meng Qian-wen
Abstract:
Objective: This experiment studied the effect and mechanism of acupoint catgut embedding on rheumatoid arthritis by regulating PD-1 / OX40 signal pathway. Methods: 25 female SD rats were induced with complete Freund's adjuvant to establish rheumatoid arthritis model rats, and then treated with acupoint catgut embedding and drug therapy. The rats were divided into 5 groups: control group, model group, leflunomide group, acupoint catgut embedding group and acupoint catgut embedding leflunomide group. The degree of inflammation was judged by evaluating the arthritis index; The contents of serum IL-6 and IL-8 were detected by ELISA; He staining was used to observe synovitis cell infiltration, smooth abdominal tissue, fibrous tissue, macrophage proliferation and angiogenesis; The contents of PD-1 / OX40 and CD4 cd28-pd-1lowox40 T cell subsets were detected by flow cytometry. Results: except the control group, there were erythema and moderate swelling from ankle to metatarsal or metacarpal joint in each group. After 14 days, there was no significant change in the score of the model group, but the inflammatory factor scores of leflunomide group, acupoint catgut embedding group and acupoint catgut embedding leflunomide group began to decline, and the acupoint catgut embedding leflunomide group decreased the fastest. The contents of IL-6 and IL-8 in serum of model group increased significantly (P < 0.01), and the contents of IL-6 and IL-8 in serum of rats in flutamide group, acupoint catgut embedding group and acupoint catgut embedding leflunomide group decreased significantly (P < 0.01). The synovial tissue of the model group was damaged, with a large number of inflammatory cell infiltration, vascular dilatation and fibroblast proliferation. After leflunomide and acupoint catgut embedding treatment, the inflammatory cell infiltration in the synovial tissue of the model group was significantly reduced and the vascular proliferation was inhibited, and the effect was the most obvious when Leflunomide and acupoint catgut embedding worked together. In the model group, the content of pd-1lowox40 decreased significantly (P < 0.01), the content of CD4 cd28-pd-1lowox40 T cells increased significantly (P < 0.01), and the content of pd-1lowox40 in acupoint catgut embedding group and leflunomide acupoint catgut embedding group increased significantly (P < 0.01) The content of CD4 cd28-pd-1lowox40 T cells in acupoint catgut embedding group and acupoint catgut embedding leflunomide group decreased significantly (P < 0.01). Conclusion: acupoint catgut embedding can improve the symptoms of rheumatoid arthritis, and has the effect of combined treatment with leflunomide. Its mechanism may be related to PD-1 / OX40 signal pathway.
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Left to right shunt slows cardiac remodeling in rats with pulmonary hypertension
Abstract:
【Abstract】Objective: The prognosis of patients with left-to-right shunt congenital heart disease associated pulmonary hypertension is significantly better than that of idiopathic pulmonary hypertension, but the specific mechanism is unclear. The purpose of this project is to make a rat model of idiopathic pulmonary hypertension and congenital heart disease with pulmonary hypertension, and compare the similarities and differences between the two models in pulmonary vascular remodeling and cardiac remodeling. Methods: Male SD rats were divided into three groups: control group (n=8), monocrotaline (MCT) group (50mg/kg) to simulate idiopathic pulmonary hypertension (n=8); Cervical arteriovenous shunt surgery monocrotaline (MCT) group (50mg/kg) simulated left to right shunt congenital heart disease with pulmonary hypertension (n=8). Three weeks after the establishment of the model, echocardiography, left and right cardiac catheter pressure measurement and lung histopathological staining were performed to compare the cardiac and pulmonary phenotypes of the rats. Results: Compared with the control group, there was no significant difference between the MCT group and the operation MCT group in the right ventricular hypertrophy, right ventricular dysfunction, mean pulmonary artery pressure, pulmonary vascular remodeling and other indicators 3 weeks after operation. But in many indexes related to left heart, the rats in the operation MCT group were significantly better than those in the simple MCT group. Compared with the control group, the left ventricular lumen diameter (LVID; d) and left ventricular ejection fraction (EF%) in the operation MCT group did not decrease in the diastolic period; The maximum rate of increase of right ventricular internal pressure (MAX dp/dt) and the maximum rate of decrease of left ventricular internal pressure (MIN dp/dt) in the operation MCT group were lower than those in the simple MCT group. Conclusion: Left to right shunt surgery can not change MCT-induced pulmonary hypertension and right heart remodeling, but can produce left heart compensation, which may be beneficial to the prognosis of patients. The animal model of this project establishes the basis for studying the different pathological mechanisms of idiopathic pulmonary hypertension and pulmonary hypertension associated with congenital heart disease.
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Monkeypox virus infection and the animal model of Monkeypox
Abstract:
Monkeypox is an infectious disease caused by Monkeypox virus （MPXV） infection. The host of MPXV remains unclear, and rodents and nonhuman primates consider the potential hosts. Monkeypox is rapidly spreading globally. However, the animal models for Monkeypox have not developed in the last decades in China. MPXV is a pathogen that seriously threat to human health. Its transmission among the population has presented new characteristics. Therefore, this article describes the discovery of MPXV and the early epidemic, different types of infection and co-infection. In addition, the experimental infection and animal models for Monkeypox in rodents and nonhuman primates were expounded in this paper.
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The expression of IGHG1 in acute myeloid leukemia THP-1 cell and the influences on cell proliferation, apoptosis and invasion by regulating TGF-β/Smad pathway
Abstract:
Objective To investigate the expression of immunoglobulin γ-1 heavy chain constant region (IGHG1) in acute myeloid leukemia (AML) THP-1 cell and its influences on cell proliferation, apoptosis and invasion by regulating the transforming growth factor β (TGF-β)/Smad pathway. Methods The bone marrow specimens of 9 children with AML, the bone marrow specimens of 8 children with fracture,human bone marrow stromal cells HS-5 and human AML cells THP-1, HL60 were used as research objects,Western Blot was used to detect IGHG1 protein expression; THP-1 cells were divided into: blank group (cells without any treatment), si-NC group, si-IGHG1-1 group, si-IGHG1-2 group, si-IGHG1-3 group, TGF-β group,si-IGHG1-1 TGF-β group,si-IGHG1-1 TGF-β LY364947 group, CCK-8 method was used to detect cell proliferation; apoptosis was detected by flow cytometry; Transwell experiment was used to detect cell invasion ; Western blot was used to detect the protein expression of IGHG1, TGF-β, p-Smad2, and p-Smad3 in each group of cells. Results Compared with the bone marrow of children with fracture, the expression level of IGHG1 protein [(0.24?.03) vs (0.87?.12] in the bone marrow of children with AML was significantly higher (P<0.05); compared with HS-5 cell, the expression level of IGHG1 protein in human AML cells THP-1, HL60 was significantly increased [(0.89?.14)(0.75?.08) vs (0.21?.02)] (P<0.05); compared with the blank group , the OD450 value (24, 48, 72h) of THP-1 cells, the number of invaded cells, and the protein expression of TGF-β, p-Smad2, and p-Smad3 were significantly reduced in the si-IGHG1-1 group, and the apoptosis rate was increased (P<0.05), while the corresponding indexes in TGF-β group were opposite (P<0.05); the TGF-β reversed the effects of silencing IGHG1 on the proliferation, apoptosis and invasion of THP-1 cells; compared with si-IGHG1-1 TGF-β group, TGF-β, p-Smad2, p-Smad3 protein, OD450 values (24, 48, 72 h) and invasion number of cells decreased significantly in si-IGHG1-1 TGF-β LY364947 group, and the cell apoptosis rate was increased (P<0.05). Conclusions IGHG1 is highly expressed in AML cells. Silencing IGHG1 can inhibit the proliferation and invasion of AML cells, and promote the apoptosis of AML cells. This mechanism may be related to the inhibition of TGF-β/Smad pathway.
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The relationship between atmospheric pollutants and some adverse pregnancy outcomes
jinjian, Chang Hui, Huang Hehuan, Peng Rui, Zhang Xiaoan
Abstract:
With the rapid development of China's economy and the continuous acceleration of urbanization, the problem of air pollution is becoming increasingly prominent, which has a great impact on human health. In recent years, a large number of research work has emerged both domestically and internationally, and research results have shown a certain correlation between exposure to atmospheric pollutants during pregnancy and adverse pregnancy outcomes. The impact of air pollution on the health and embryonic development of pregnant women has received more attention. This article mainly provides a brief review on the impact of atmospheric pollutants on some adverse pregnancy outcomes and their possible biological mechanisms.
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Research Progress on Model Organism Zebrafish in Neurodegenerative Diseases
Huang Kongli, Su Shijie, Wang Yuting, LIU ZHUANGZHUANG, CAO DANDAN, WANG PEI, CHEN GUANLIN, Wang Qi
Abstract:
Neurodegenerative disease （NDD）is a chronic and progressive neurological disease characterized by the loss of a large number of specific neurons. It mainly includes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Although the lesions and etiologies of different types of neurodegenerative diseases are different, delayed neurodegenerative lesions and cell loss in specific brain areas are their common characteristics. For this reason, it is collectively referred to as neurodegenerative diseases. In recent years, zebrafish have attracted increasing attention from society as a new type of model organism. Although there are some differences between zebrafish and human central nervous systems, zebrafish neural conduction systems, neuronal and glial cell types, and disease-related gene homology are very similar to those of humans. Zebrafish has been widely used in the study of neurodegenerative diseases, and some achievements have been made in this field to improve our understanding of these diseases, but because of the complexity, multi-factors and multi-gene regulation of neurodegenerative diseases, the etiology and pathogenesis of zebrafish are not clear, so the treatment of this kind of disease has always been a difficult problem. By consulting relevant literature from home and abroad in recent years, this study reviews recent advances in neurodegenerative diseases using zebrafish as a model organism.
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Progress in irisin and its upstream and downstream antidepressants
Sangjiala, Lishanshan, Cuixin, Renqingqing, Houruiling, Panxingfang, Wangshenjun, Zhao
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Depression is the main cause of disability, and the adverse effects on people are difficult to eliminate. Despite the increasing number of antidepressants, depression is still not adequately treated clinically, and new mechanisms still need to be explored. As the beneficial effects of irisin on the nervous system are gradually elucidated, studies have found that irisin has an antidepressant effect, and irisin may become a new target for the treatment of depression. This study aims to explore the mechanism of irisin and its upstream and downstream antidepressants, by reviewing the existing studies to explain the link between depression and irisin, propose the potential mechanism of SIRT1 / PGC-1α mediating FNDC5/Irisin to regulate BDNF and promote neurogenesis to improve depression, and provide a new idea for the study of irisin and its upstream and downstream antidepressants.
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Advances of CREB in the regulation of memory through synaptic plasticity and its relation with Alzheimer’s disease
Luo Zhuohui, pang shuo, Zhang lianfeng
Abstract:
Alzheimer’s disease is an irreversible heterogeneous neurodegenerative disease. AD patients are featured with memory loss and impaired synaptic plasticity. With a view to cAMP responsive element-binding protein which is intimately associated with synaptic plasticity. this assay summarized progress on the structure, signal pathway, downstream genes and relative memory regulation. The involvement of CREB in AD development would serve as references for AD researches based on synaptic plasticity improvement.
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Research progress on the regulation of lymphangiogenesis and its role in myocardial infarction
Abstract:
Lymphatic system plays an important role in regulating interstitial fluid homeostasis, lipid metabolism and immune function. After myocardial infarction, enhanced lymphangiogenesis accelerates the clearance of infiltrating immune cells, reduces the production of pro-inflammatory cytokines, reduces edema, inflammation, and fibrosis, and promotes the recovery of damaged heart function. Vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 are components of the lymphangiogenesis pathway and play a critical role in maintaining tissue fluid balance and myocardial function after cardiac injury. Lymphatic vessels are closely related to the immune system. Different immune cell groups can stimulate or inhibit lymphatic remodeling. Macrophages are congenital immune cells widely distributed in organs and tissues, and play an important role in various physiological and pathological processes such as organ development, host defense, acute and chronic inflammation, tissue homeostasis and remodeling. More mechanisms of lymphangiogenesis need to be identified to provide effective targets for clinical stimulation of lymphangiogenesis to treat heart disease. This paper reviews the basic pathological changes of the heart and lymphatic vessels after myocardial infarction, the regulatory factors of lymphangiogenesis, and the influence of macrophages on lymphangiogenesis.
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Effects of LncRNA FGD5-AS1 targeting and regulating miR-129-5p on the proliferation, apoptosis, migration and invasion of oral squamous cell carcinoma cells
Abstract:
Objective To investigate the effects of long non-coding RNA (LncRNA) FGD5-AS1 on the proliferation, apoptosis, migration and invasion of oral squamous cell carcinoma (OSCC) cells through targeted regulation of miR-129-5p. Methods The expression of FGD5-AS1 in OSCC was analyzed by online database. The tumor tissues, normal tissues, and the human oral mucosal cells (HOK) and OSCC cells (SCC-9, HSC-4, SCC-25, CAL-27) cultured in vitro from 30 OSCC patients collected in our hospital were used as research subjects, qRT-PCR method was performed to detect the expression of FGD5-AS1 and miR-129-5p. The CAL-27 cell line with the highest FGD5-AS1 expression was randomly separated into Control group (normal culture, no transfection), si-NC group (transfected with si-NC), si-FGD5-AS1 group (transfected with si-FGD5-AS1), si-FGD5-AS1 NC inhibitor group (co-transfected with si-FGD5-AS1 and NC inhibitor) and si-FGD5-AS1 miR-129-5p inhibitor group (co-transfected with si-FGD5-AS1 and miR -129-5p inhibitor), CCK-8 method and clone formation assay were used to detect the proliferation ability of CAL-27 cells; the apoptosis level of CAL-27 cells was detected by flow cytometry; the migration ability of CAL-27 cells was detected by wound-healing assay; Transwell chamber was used to detect the invasion ability of CAL-27 cells; and dual luciferase reporter experiment verified the targeting relationship between FGD5-AS1 and miR-129-5p; the expression of high mobility group protein B1(HMGB1) was detected by Western blot. In vivo xenograft tumor model was constructed and divided into sh-NC group, sh-FGD5-AS1 group, miR-129-5p inhibitor group, and sh-FGD5-AS1 miR-129-5p inhibitor group. Tumor volume and tumor were detected. QRT-pcr was used to detect the expression of FGD5-AS1 and miR-129-5p in transplanted tumor tissues. The expression of HMGB1 and Ki67 was detected by immunohistochemistry. Results Database analysis showed that the expression level of FGD5-AS1 in OSCC tumor tissues was 4 times higher than that in normal tissues, and FGD5-AS1 expression was associated with poor grade in OSCC patients. Compared with normal tissues or human oral mucosal cells, the expression of FGD5-AS1 in tumor tissues and OSCC cell lines was significantly increased, and the expression of miR-129-5p was significantly decreased (P<0.05), the CAL-27 cells with the highest expression level of FGD5-AS1 were selected for transfection experiments. Compared with the Control group and the si-NC group, the apoptosis rate of the si-FGD5-AS1 group was significantly increased, and the OD value (48 h, 72 h, 96 h), scratch healing rate and the number of invaded cells were significantly reduced (P<0.05). MiR-129-5p was the target gene of FGD5-AS1. Inhibiting the expression of miR-129-5p was able to reverse the effects of interference FGD5-AS1 on the proliferation, apoptosis, migration and invasion of OSCC cells, thereby restoring the cancer-promoting effect of FGD5-AS1. After FGD5-AS1 was disrupted, HMGB1 expression was down-regulated by significantly enhancing miR-129-5p expression (P<0.05). In vivo experiments showed that FGD5-AS1 silencing significantly inhibited the growth and expression of HMGB1 and Ki67 (P<0.05), inhibition of miR-129-5p was the opposite; Inhibition of miR-129-5p reversed the inhibition of FGD5-AS1 on tumor growth and expression of HMGB1 and Ki67 (P<0.05). Conclusions FGD5-AS1 is up-regulated in OSCC cells. Interfering with FGD5-AS1 can inhibit proliferation, migration and invasion of OSCC cells and promote apoptosis by targeting miR-129-5p / HMGB1 axis.
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Behavioral assessment in the parkinson’s model of nonhuman primates
Abstract:
Parkinson's disease is a neurodegenerative disease, can cause a series of patients with symptoms of movement and the movement, behind the pathogenesis is unclear, to explore the mechanism behind these phenotypic requires an appropriate animal model of rodents in the movement and the movement is very difficult to accurately simulate the patient symptoms, causes related to preclinical studies have limitations, in translational medicine. Non-human primate animal models can make up the gap between rodents and humans, thus the non-human primate PD model of movement and the movement symptoms, is very important to research on mechanism and therapy, this review summarizes the different behavior in quantitative way, and compared the advantages and disadvantages between different methods, for studying the PD monkey model provides a behavioral testing for help.
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Advances in the construction of animal models of severe asthma
Wei Dandan, Wang Liting, Long Jie, Chen Yanjiao, Wang Yu, Yang Yongqing, Xu Yudong
Abstract:
Severe asthma (SA), which requires high doses of glucocorticoids in combination with other medications to maintain symptom control or is uncontrollable even with these treatments, is currently a challenge in the clinical management of asthma. The establishment of a stable and reproducible experimental animal model that highly mimics the pathophysiological and clinical characteristics of patients with severe asthma is a key fundamental link in deepening the study on the pathogenesis of severe asthma, identifying potential therapeutic targets and developing targeted drugs. This paper reviews the experimental studies related to the construction of animal models of severe asthma in the past 10 years, and summarizes the recent progress in the establishment and evaluation of animal models of severe asthma from three aspects: animal selection, animal model construction protocols, and model pathological phenotypes. To summarize and analyze the latest progress in the construction of SA animal models, and provide a reference for SA basic research based on animal models.
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Research progress in experimental models of pulmonary arterial hypertension
xiejincheng, Chenjianying, Dengshaodong, Xiao mengyuan
Abstract:
Pulmonary hypertension is a chronic progressive disease that, if not treated promptly, can ultimately lead to right heart failure and even death In order to explore the pathogenesis of pulmonary arterial hypertension and find more effective treatment methods, it is necessary to establish a suitable experimental model. In this paper, Pubmed, CNKI and other databases were used to search relevant literature, and the preparation methods and research progress of various experimental models of pulmonary arterial hypertension in recent years were summarized. The preparation methods of the models were classified to show the pathological characteristics of the disease more directly. On this basis, the present situation and existing problems of the in vitro and in vivo model of pulmonary arterial hypertension were discussed, in order to provide reference for the pathogenesis and clinical research of pulmonary arterial hypertension.
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Research progress of experimental premenstrual dysphoria model in rodents
Abstract:
Premenstrual dysphoric disorder (PMDD) is a subtype of Premenstrual syndrome with high prevalence in women during their reproductive life. It includes physical symptoms such as breast tenderness, headache as well as serious emotional symptoms such as anxiety, depression and irritability. These symptoms are menstrual specific, they appear before menstruation and disappear within a week after it ends. PMDD threatens the health of female patients all over the world, In The Diagnostic and Statistical Manual of Mental Disorder(Fifth edition ed,DSM-5）, PMDD is identified as one of the five types of depression. At present, studies on the pathological mechanism of PMDD mainly focus on hormone and receptor expression, which is the theoretical basis of the animal model establishment, as well. Animal model that can model after clinical symptoms of human beings is a very important to connect basic research to clinical research, which is also crucial to explore the pathogenesis and develop appropriate drugs. Although many kinds of animal models of PMDD have been used in experimental studies, there are still many limitations, which resulting in a barrier to further investigation of PMDD. Therefore, this review arranged the known pathogenesis research of PMDD and discuss the existing animal models of PMDD, aims to provide reference for PMDD related mechanism research and drug development.
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Analysis of animal models of keratitis based on the characteristics of clinical conditions of traditional Chinese and Western medicine
Abstract:
Abstract: Keratitis is a common ophthalmic disease with a high rate of blindness. This paper reviews a large number of relevant literature of animal models of keratitis, summarizes and analyzes the mechanism of existing animal models of keratitis, and evaluates the clinical anastomosis degree of traditional Chinese and Western medicine in combination with the established clinical diagnostic standards of traditional Chinese and Western medicine, analyzes its advantages and disadvantages, and puts forward some suggestions. It is found that most of the existing models are based on Western medical theories, and lack the diagnostic standards of traditional Chinese medicine. The model is mostly modeled by a single factor, which cannot well simulate the real lesion process of the disease; The diagnosis of the model lacks apparent indicators; It is recommended that animals be modeled by combining disease evidence. It is very important to prepare animal models of keratitis with high clinical compatibility and establish perfect evaluation standards, which can help us better understand the occurrence and development of keratitis in modern medical experiments, and effectively prevent and treat it.
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Study on the uptake and transport properties of euscaphic acid in Caco-2 cell model based on UPLC-TQ-MS
wangning, xieli, ding wenhuan, tian li
Abstract:
ABSTRACT: Objective Caco-2 cell model was established to explore euscaphic acid uptake and transport mechanism in this study. Methods Ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry(UPLC-TQ-MS) was employed to determine the content of euscaphic acid. The effects of different time and temperature on its uptake were investigated. Based on the results of the uptake studies, the effects of different concentrations, P-gp inhibitors, chelating agents and pH values on its bidirectional transport were explored. Results The uptake of euscaphic acid was (8.38 ?0.87) μg穖g-1 for 180 min on the Caco-2 cell model at 37 癈. The apparent permeability coefficient (Papp values) of euscaphic acid for low, medium and high concentrations were(61.41 ?.92)?0-4、(146.90?4.91)?0-4 and (167.18?.72)?0-4 cm穝-1 respectively, which were positively correlated with the concentrations. P-gp inhibitors and chelating agents had no effect on its Papp values. Weakly acidic environment (pH6.00) significantly increased its Papp value, and the efflux rate (ER) ranged from 0.8–1.4. Conclusion The above results indicate that euscaphic acid has good transmembrane permeability in Caco-2 cell model, and the uptake mode is mainly passive diffusion. It is not a substrate of P-gp and there is no cellular bypass transport. This research may provide an experimental basis for the in vivo intestinal absorption of medicines containing euscaphic acid.
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Mechanism of taxifolin regulating endoplasmic reticulum stress PERK-ATF4 pathway to reduce myocardial hypertrophy in hypertensive rats
yujinyu, hanjing, zhangying, yuwen
Abstract:
【Abstract】 Objective To investigate the impact and molecular mechanism of taxifolin (TAX) on myocardial hypertrophy in spontaneously hypertensive rats (SHR). Methods Twenty-four SHRs were separated into SHR control group (SHR group), TAX group (20 mg/kg), and TAX PERK activator CCT020312 (CCT) group (20 mg/kg TAX 2 mg/kg CCT), 8 per group; another 8 normal blood pressure Wistar-Kyoto (WKY) rats were regarded as the normal control group (WKY group), and all were given corresponding drugs for 8 weeks of continuous intervention. During the experiment, the changes in blood pressure of the rats were observed, and after the intervention, the thickness of the diastolic ventricular septum (IVSd), the thickness of the systolic ventricular septum (IVSs), and the left ventricular ejection fraction (LVEF) were detected by echocardiography to determine the degree of myocardial hypertrophy and cardiac function, then the cardiac index and left ventricular index were calculated, hematoxylin-eosin (HE) staining, wheat germ agglutinin (WGA) staining and Masson staining were performed to evaluate the pathological changes of myocardial tissue, real-time quantitative PCR (qRT-PCR) was performed to detect the expressions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), type I collagen α1 chain (COL1A1) and type III collagen α1 chain (COL3A1) mRNA in myocardial tissues, Western blot was performed to detect the expressions of protein kinase R-like endoplasmic reticulum kinase (PERK)-activator of transcription 4 (ATF4) pathway-related proteins in cardiac muscle. Results After the intervention, compared with the WKY group, the systolic blood pressure (SBP), diastolic blood pressure (DBP), IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, collagen volume fraction (CVF), myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expressions, glucose-regulated protein 78 (GRP78), ATF4, C/EBP homologous protein (CHOP) protein levels and p-PERK/PERK ratio in the SHR group increased (all P<0.05), LVEF decreased (P<0.05); compared with SHR group, the SBP, DBP, IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, CVF, myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expressions, GRP78, ATF4, CHOP protein levels and p-PERK/PERK ratio in TAX group decreased (all P<0.05), LVEF increased (P<0.05); CCT020312 partially reversed the protective effects of TAX on cardiac function and cardiac hypertrophy. Conclusion TAX can improve hypertensive myocardial hypertrophy by inhibiting endoplasmic reticulum stress (ERS), and its mechanism may be related to inhibiting PERK-ATF4 pathway.
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Study on tissue distribution difference of ligustrazine-Salvia miltiorrhiza before and after compatibility in acute myocardial ischemia model rats
lirong, goujian, liuting, gongzipeng, luyuan, liuchunhua, hunagyong, sunjia
Abstract:
Objective To investigate the difference in tissue distribution of ligustrazine hydrochloride and Salvia miltiorrhiza (Danshen) in Acute myocardial ischemia (AMI) rats. Methods AMI model was induced by subcutaneous injection of isoproterenol hydrochloride. UPLC-MS/MS method was used to determine the content differences of ligustrazine and danshensu in heart, liver, spleen, lung, kidney and brain tissues after single intravenous injection of Danshen injection (DGI), Ligustrazine injection (CGI) and Shenxiong glucose injection (SGI) at different time points. Results After intravenous injection, ligustrazine and danshensu were widely distributed in tissues of AMI rats and reached their peak rapidly. Before and after compatibility, the content of ligustrazine was the highest in brain tissue and the lowest in liver tissue. The content of danshensu in kidney tissue was the highest, and in brain tissue was the lowest, indicating that ligustrazine could penetrate the blood-brain barrier more easily than danshensu, and the main accumulation tissues were different. The AUC of ligustrazine and danshensu in the heart of the target organ was significantly increased (P < 0.001). Conclusion It is speculated that the combination of ligustrazine and salvia miltiorrhiza may enhance the therapeutic effect by increasing the distribution of main pharmacodynamic components in the heart, so that SGI can play a better role.
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The role of PI3K/Akt/mTOR signaling pathway in the pathogenesis of TRALI rats
liushuangchun, Zhang Xijiang, Chen Zaihuan, Wang Luqian, Lin Hairong
Abstract:
Objective: To study the effect of PI3K/Akt/mTOR signaling pathway on the pathogenesis of TRALI. Methods: Animal model was established by the method of trauma-blood loss-massive transfusion, and the pulmonary histopathological changes were detected by HE staining to determine whether the rats had pulmonary edema. The protein and mRNA expression levels of TNF-α, IL-6 and IL-1β in peripheral blood or lung tissues in TRALI rat models were detected by ELISA and qRT-PCR. The expression levels of PI3K/Akt/mTOR signaling pathway related proteins and apoptosis-related proteins Bax, Bcl-2 and Caspase3 were detected by western blotting. Results: Alveolar tissue structure was seriously damaged, the alveolar wall was thickened, there was pink edema fluid in the alveolar cavity, inflammatory cells infiltrated, edema was obvious in TRALI model rat. The expression levels of inflammatory cytokines TNF-α, IL-6 and IL-1β were significantly increased in peripheral blood and lung tissues (P<0.05); PI3K/Akt/mTOR signaling pathway was activated, the expression of p-mTOR/mTOR was significantly increased, and the expression of apoptotic protein Bax and Caspase 3 was inhibited, and the expression of anti-apoptotic protein Bcl-2 was increased (P<0.05). Conclusion: As a potential drug target, mTOR is an important means for clinical prevention and control of the occurrence and development of TRALI by defining the exact time target of its protective and damaging effects and selecting the optimal time of medication due to its complicated mechanism.
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Alterations of Gut Microbiota - Short Chain Fatty Acid Axis in IBS-D Rats and the Effect of Sodium Butyrate
zhan kai, Wu haomeng, zheng huan, qin shumin, Huang shaogang, yang yuanming
Abstract:
Objective To explore the alterations of gut microbiota - short chain fatty acid metabolic axis in IBS-D rat model, and to explore the effect of sodium butyrate on this axis. Methods Seventeen Wistar rats were randomly divided into three groups. The IBS-D rat model was induced by 4% acetic acid enema combined with restraint stress. During the modeling period, sodium butyrate was injected intraperitoneally. The fecal flora of rats was detected by 16sRNA technology, and the fecal short chain fatty acid content of rats was detected by liquid chromatography mass spectrometry (LC-MS). Results Compared with the normal group, the weight of the model group was decreased, AWR score and fecal water content have a significant increase, the relative abundance of intestinal probiotics was decreased，while that of g-Blautia was elevated, the fecal acetic acid content was increased significantly, and the contents of butyric acid and valeric acid was decreased significantly in the model group. After drug intervention, compared with the model group, the weight of rats in the sodium butyrate group was increased, the AWR score and fecal water content was decreased significantly, the relative abundance of g-Blautia was decreased significantly, and the fecal butyric acid and valeric acid content was obviously increased. Conclusions Sodium butyrate can alleviate diarrhea and colon visceral hypersensitivity in IBS-D rats by improving the imbalance of gut microbiota - short chain fatty acid metabolic axis.
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Advances in Ferroptosis-Based Therapy for Aging and Aging-Related Diseases
Zhou yongchang, Tao Siman, Chen Shengqiang, Pu Xiuying
Abstract:
Ferroptosis is a novel form of programmed cellular necrosis proposed in recent years, which is found in various diseases and seriously impacts on human health. Numerous studies have shown that inhibition or promotion of ferroptosis can improve many aging and aging-related diseases, and Traditional Chinese medicine plays an important role in this regard. This paper reviews the effects and mechanisms of Ferroptosis on aging and aging-related diseases, and compares the research progress of TCM in the treatment of ferroptosis-mediated aging and aging-related diseases in recent years, aiming to provide more options for the treatment and prevention of aging and aging-related diseases.
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Research progress in the pathogenesis of inflammatory bowel disease
Houxiaoting, Menghuan, Xuejiachen, Zhanghuamin, Wangkesi, Wangxude
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Inflammatory bowel disease (IBD) is a global idiopathic disease, involving the ileum, rectum and colon. IBD begins to appear early in clinical symptoms, including abdominal discomfort, diarrhea, hematochezia, fever, fatigue and weight loss. The diagnosis of IBD is based on the comprehensive evaluation of relevant clinical manifestations, endoscopic examination results and histopathological characteristics of pathological tissue specimens. Biological agents, oral corticosteroids, salicylic acid and surgery are the main conventional treatments for IBD. In recent years, considerable progress has been made in elucidating the pathogenesis of IBD. In clinical practice, it is considered that the complex interaction between genetic susceptibility, environmental factors and intestinal mucosal barrier leads to abnormal oxidative stress, autophagy and mucosal immune response. This paper briefly summarizes and expounds the research progress of genetic and environmental factors, intestinal mucosal barrier function, oxidative stress, autophagy dysfunction and adaptive immune response, so as to provide basis for further research and development of treatment methods and improvement of clinical treatment effect.
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Effect of Bushen Jianpi Kaixin formula on autophagy and apoptosis in AD rats
li ying, Wang Ying, Kong Mingwang
Abstract:
Objective To investigate the effects of Bushen Jianpi Kaixin Formula (BSJPKXF) on the learning and memory ability of Alzheimer s disease (AD) model rats and the related autophagy and apoptosis in cortex of AD model rats, and exploring the underlying mechanism of BSJPKXS. Method The 60 eligible rats were randomly divided into six groups (n = 10): control group, AD group, Bushen group (BS, 3.6g/kg·d), Jianpi group (JP, 4.05g/kg·d), Kaixin group (KX, 2.34g/kg·d) and Bushen Jianpi Kaixin group (BSJPKX, 9.99g/kg·d). AD mouse model was established by intraperitoneal injection of D-gal. The rats in BS group, JP group, KX group and BSJPKX group were gavaged with corresponding drugs once a day. The rats in control group and AD group were treated with equal amount of normal saline one time per day. After four weeks, the learning and memory ability was tested by Morris water maze. The open-field test was used for detecting the cognitive function in rats. The expression of LC3-I, LC3-II and Beclin in cerebral cortical tissues were detected by western bolt. The expression of Bax and Bcl-2 in cerebral cortical tissues were detected by immunohistochemistry. The related mRNA level of Beclin 1, P62, Bax and Bcl-2 in cerebral cortical tissues were detected by RT-PCR. Result Compared with the control group, D-gal significantly decreased the spatial learning and memory ability of rats in the AD group (P < 0.01), decreased the expression of Beclin, LC3-I/LC3-II, Bcl-2 and Bcl-2/Bax, increased the mRNA level of P62 and the expression of Bax (P < 0.01). After treatment, related to the AD model group, Bushen Jianpi Kaixin formula improved the spatial learning memory ability of rats in the BSJPKX group (P < 0.01), increased the expression of Beclin, LC3-I/LC3-II, Bcl-2 and Bcl-2/Bax, decreased the mRNA level of P62 and the expression of Bax (P < 0.01). Conclusion Bushen Jianpi Kaixin formula can improve cognitive impairment in AD rats. The mechanism is presumedly related to the reduction of neural autophagy and apoptosis.
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The evaluation of experimental animal studies on acupuncture for hypertension based on the SYRCLE’s tool and the ARRIVE guidelines
Tang wenjing, ZHANG Yue, LI Yuxi, ZHONG Dongling, JIN Rongjiang, ZHANG Lili, LI Juan
Abstract:
Objective To evaluate the risk of bias and reporting quality of animal experimental studies on acupuncture for hypertension, and analyze the deficiencies in experimental design, implementation and reporting, so as to decrease the risk of bias of researches and improve the reporting quality of animal studies. Methods Databases including China national knowledge infrastructure（CNKI）, Wanfang database（WANFANG）, Chinese science and technology periodical database（VIP）, Chinese biomedical literature database（CBM）, Web of Science, PubMed, Embase, and The Cochrane Library were searched from inception to October 8, 2022. Two researchers independently screened experimental studies related to acupuncture interventions in hypertensive animals according to eligibility criteria. The SYRCLE’s tool and the ARRIVE guidelines 2.0 were used to evaluate the risk of bias and reporting quality of the included literature. Excel 2019 was used to extract data and descriptive analysis was conducted according to the results. Results A total of 79 animal experiments on acupuncture for hypertension were included, among which 16 and 21 were published in Chinese core journals and science citation index（SCI）journals respectively. The result of SYRCLE’s tool showed that 5 of the 10 items were evaluated as well, while the rest were unclear risk or high risk of bias. Of the 79 included articles, the risk of bias of 19 articles were low, while the remaining studies had some risk of bias. The results of the ARRIVE guidelines 2.0 indicated that 19 of the 38 sub-items were well reported, while the rest were poorly reported.The reporting quality of 51 articles were good and the remaining studies were inadequately reported. Conclusions At present, the risk of bias of acupuncture intervention in hypertensive animal experiments is high and the reporting quality is generally low. The inadequate description of some important entries had impact on the reproducibility of the experiments and the translation of the results.The SYRCLE’s tool and ARRIVE guidelines 2.0 are recommended to be used as reference during experimental design and reporting, thus improving the standardization and reporting quality of acupuncture for hypertensive animals.
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Autophagy: the key mechanism of exercise in improving neurodegenerative diseases
Chen Xianghe, Qiu Xiao, Liu Chi, Shen Ziming, Zhou Xiangxiang
Abstract:
Autophagy regulation of neurological diseases is the focus of current research in the field of neuroscience. Autophagy disorder leads to protein expression, deposition and dysfunction such as Aβ、Tau、α-syn and causes neurodegenerative diseases such as AD, PD and HD. Exercise is an important means to improve neurodegenerative diseases, which is closely related to the up-regulated expression of LC3, Beclin-1, Lamp1 and other autophagic factors after the activation of AdipoR1/AMPK/TFEB, AMPK/mTOR and other pathways. Higher autophagy level can remove the deposition of Aβ、Tau、α-syn and other proteins in the brain and can improve the neurodegeneration, synaptic structure and function disorder caused by neurodegenerative diseases. This study reviewed and analyzed the mechanism of autophagy in the improvement of neurodegenerative diseases by exercise, which will provide a solid theoretical basis and new research ideas for the improvement of neurodegenerative diseases by exercise.
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Research advances of trophoblast cells in threatened abortion complicated with intrauterine hemorrhage
HuoYan, Zhu Jun nan, Fu Ya qi, Chen Ping, Xu Guang li
Abstract:
Threatened abortion complicated with intrauterine hemorrhage is a common disease during pregnancy.Its pathogenesis is related to the imbalance of maternal-fetal interface microenvironment and the obstruction of uterine spiral artery remodeling. Trophoblast cells are the outermost layer of the maternal-fetal interface microenvironment .Its proliferation, migration and invasion are closely related to normal pregnancy.It plays an irreplaceable role in immune tolerance and regulation, uterine spiral artery remodeling, and maintenance of maternal-fetal interface microenvironment.In recent years, trophoblast cells have become the main line of research in autoimmune diseases and other fields.Studies have found that it plays an important role in the diagnosis and treatment of threatened abortion complicated with intrauterine hemorrhage.This article reviews the research progress of trophoblast in the treatment of threatened abortion complicated with intrauterine hemorrhage.
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The mechanism of chemotherapy-induced thrombocytopenia in hematological malignant tumors
liliang, kong chun fang, jin cheng hao
Abstract:
Chemotherapy is the main cornerstone of hematological tumor therapy. However, foot therapy and high-dose chemotherapy drugs often cause bone marrow hematopoiesis inhibition, among which thrombocytopenia is more common, which can increase the risk of bleeding, delay follow-up treatment, increase treatment costs, and even endanger life. In recent years, more and more studies have found that anti-tumor drugs can mediate thrombocytopenia through cell aging, apoptosis, autophagy and ferroptosis. Therefore, this article reviews the mechanism of chemotherapy-induced thrombocytopenia in hematological malignant tumors in recent years.
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ZHANG Gedi, LIU Gengxin, LUO Fuli, YAN Ziyou
2023,33(7):17-25, DOI: 10. 3969 / j.issn.1671-7856. 2023. 07. 003
Abstract:
Objective To predict the mechanism of Shenshuai Prescription (SSR) in chronic kidney disease(CKD)-related myocardial injury using network pharmacology and molecular docking method. Methods We used the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and Herb herbal medicine identification database (http:/ / herb. ac. cn/ ), and the SwissTargetPrediction database to screen target information of active ingredients. We then used the UniProt database to screen for human targets and standard gene names. A drug active ingredient target network diagram was constructed using Cytoscape 3. 7. 2 software, and the GeneCards database was used to collect disease-related targets. The “ Shenshuai Recipe” against CKD myocardial injury gene target database was established using Venny 2. 1, and the STRING database was used to build the main component target interaction network and screen key targets. Cytoscape 3. 7. 2 software was imported for topology analysis and a protein-protein interaction network diagram was constructed. Finally, the DAVID platform was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) biological function annotation. Results After screening, there were 252 active compounds in SSR and 649 common targets of SSR and CKD myocardial injury, among which AKT Serine/ Threonine Kinase 1 (AKT1), Tumor Necrosis Factor (TNF), Mitogen-Activated Protein Kinase 3 (MAPK3), and Vascular Endothelial Growth Factor A (VEGFA) may be important targets of SSR in treating CKD myocardial injury. GO analysis identified 1485 Biological process items, 176 Cell component items, and 386 Molecular function items, of which plasma membrane, cytosol, and cytoplasm had the largest number of enriched genes, and 313, 304, 276 genes were distributed respectively. KEGG analysis indicated that HIF-1α, Lipid and atherosclerosis, AGE-RAGE signaling path in diagnostic complexes, phosphoinositide 3-kinase (PI3K)-AKT, and insulin resistance pathways might be involved in the mechanisms of SSR in treating CKD myocardial injury. Conclusions SSR might play a role in cardiorenal protection by participating in multiple mechanisms, including improving insulin resistance, improving lipid metabolism, antiatherosclerosis, and regulating the expression of inflammatory factors and vascular endothelial growth factor, with the PI3K/Akt and mitogen-activated protein kinase pathways being potentially important signal regulation pathways.
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WANG Xing, CHEN Ziqi, LI Lin, LIAO Jinhua, WANG Xiaolin, LIU Jiangyuan, LIAO Donghua
2022,32(7):27-33,57, DOI: 10. 3969 / j.issn.1671-7856. 2022. 07. 004
Abstract:
Objective To observe the therapeutic effect of Zhenwu decoction on myocardial pathomorphology and cardiomyocyte apoptosis in rats with heart failure induced by coronary artery ligation, and to explore its effect on apoptosis- related proteins and the PI3K-AKT signaling pathway. Methods At 4 weeks after the operation, surviving rats were randomly divided into six groups with seven rats in each group as follows. (1) Sham operation group: normal saline was administered intragastrically for 28 days at 4 weeks after the operation. (2) model group: normal saline was administered intragastrically for 28 days after 4 weeks. (3) positive control group: 5 mg / kg losartan potassium was administered for 28 days after 4 weeks. ( 4) Zhenwu decoction low dose group: after 4 weeks, 6 g / kg Zhenwu decoction crude drug was administered for 28 days. ( 5 ) Zhenwu decoction middle dose group: 12 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. (6) Zhenwu decoction high dose group: 18 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. Changes in the electrocardiogram, color ultrasound, cardiomyocyte apoptosis, myocardial morphology, PI3K, AKT1 and p-AKT1 protein levels in myocardial tissue, immunohistochemical changes of Bax, Bcl-2, caspase 3, 8, 9 and BNP in the abdominal aorta were observed before and after modeling. Results ( 1) The ST segment of the heart failure model was elevated after coronary artery ligation, indicating that model establishment was successful. (2)The left ventricular mass index and BNP level of heart failure rats were increased significantly, and LVEF and LVFS were decreased significantly, whereas the left the ventricular mass index, BNP level, LVEF and LVFS were improved in the other groups. ( 3) Myocardial fibers in the model group were disordered and broken accompanied by cardiomyocyte swelling, hypertrophy. and inflammatory cell infiltration, which were relieved to various degrees in the other groups. Apoptosis in the model group was significant, which was alleviated after by Zhenwu decoction and positive control group drugs. (4)Compared with the model group, Bcl-2 was increased, and Bax and Caspase 3, 8, 9 were decreased in each treatment group. There was no significant difference in protein expression between Zhenwu decoction middle dose and sham operation groups. (5)Compared with the sham operation group, PI3K, p-AKT1 and AKT1 expression in the model group was increased, and Zhenwu decoction suppressed protein expression of PI3K, p- AKT1 and AKT1. Conclusions Zhenwu decoction reduces cardiomyocyte apoptosis and myocardial pathological changes in HF rats by regulating the PI3K-AKT pathway, enhancing myocardial contractility, and delaying the progression of heart failure.
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YUE Linzhi, MA Tao, DAI Yumei, DU Wenya, WANG Guofu, WU Lixian
2024,34(7):175-180, DOI: 10.3969/j.issn.1671-7856.2024.07.020
Abstract:
Ferroptosis is a newly discovered mode of programmed cell death characterized by the accumulation of intracellular iron-dependent lipid peroxidation. Current research has mainly focused on the role of ferroptosis in the field of cancer, but increasing evidence shows that ferroptosis is also related to the occurrence of infectious diseases. Ferroptosis has accordingly been detected in cases of COVID-19, tuberculosis, and cryptococcal meningitis, as well as other diseases.This article reviews the role of ferroptosis in infectious diseases, to provide new ideas for the prevention and treatment of ferroptosis-related infectious disease
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CAO Xiangwen, LI Min, YIN Qi, HAN Xuelian, WANG Yuan, ZHAO Guangyu
2024,34(6):151-160, DOI: 10.3969/j.issn.1671-7856.2024.06.020
Abstract:
The major histocompatibility complex (MHC) is closely related to immune regulation. MHC shows distinct genetic polymorphism, and there are also species differences in MHC restriction. The human MHC is called human leukocyte antigen (HLA), and the mouse MHC is called H-2. The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response. MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models. The development of HLA Ⅰ transgenic mouse model went through three stages, at present, the strategy of knocking out H-2K b and H-2D b or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules. In the construction of an HLA Ⅱ transgenic mouse model, the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted. With the optimization of construction strategies, MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment, and genetic disease-association studies, becoming a powerful tool for preclinical trials. In this paper, we summarize the relevant data on MHC transgenic mouse models, as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.
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WU Zhihang, TANG Mingzheng, LI Xiaofeng, RONG Yao, CUI Yan, PAN Haibang
2024,34(7):110-120, DOI: 10.3969/j.issn.1671-7856.2024.07.013
Abstract:
Digestive tract tumors are currently one of the most common types of cancer, including esophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Their prognoses are poor and the treatments require further improvement. Caveolin-1 (CAV1) has a dual regulatory effect on digestive tract tumors as a tumor suppressor and cancer promoter. CAV1 plays a major role in cell proliferation, invasion, metastasis, angiogenesis,and drug tolerance of digestive tract tumors. The regulation of CAV1 protein and its related signaling pathways may be a strategy for the treatment of digestive tract tumors. This review analyzes the relationship between CAV1 and digestive tract tumors in terms of structure, function, expression regulation, regulation of epithelial-mesenchymal transition, and drug resistance in digestive tract tumors to provide new ideas for the diagnosis and treatment of digestive tract tumors.
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KONG Weijiao, YAN Yiyue, ZHAO Peikai, MAO Xiaojian, WANG Ting
2024,34(6):18-27, DOI: 10.3969/j.issn.1671-7856.2024.06.003
Abstract:
Objective To analyze the dynamic changes to disease activity, colonic inflammation, histopathology,and serum cytokine levels in mice with chronic ulcerative colitis ( UC). Methods For UC induction, 2. 5% dextran sodium sulfate solution was provided ad libitum for 5 days, and to model remission, tap water was supplied for another 5 days in one induction cycle. Disease activity index (DAI), colon length, and pathological changes to colon tissue were determined. The levels of myeloperoxidase (MPO) in colon tissue and of cytokines such as IL-1β in serum and colon were detected. Results During the three cycles, disease activity was aggravated and colon length shortened in mice during the induction periods, both of which were relieved during the remission periods. The blood appeared was observed in the stool was earlier in cycles 2 and 3. The number of mice with stool blood increased, and their body weight decreased by a small amount briefly, then recovered rapidly. The degree of histopathological damage to the colon and MPO content in cycles 1 and 3 increased in the induction periods and decreased in the remission periods, with the magnitude of change smaller than that of the change in DAI values; and they increased in the remission period of cycle 2. During induction, the spleen index and serum levels of IL-1β, IL-6, and IL-17A increased continuously and were higher than those in the control group at the end of the experiment. Levels of TNF-α were increased in the induction periods and decreased in the remission periods,and the trend in IL-10 change was similar to that of TNF-α. TGF-β content increased and then decreased and was higher than that in the control group at the end of cycle 3. The colon contents of IL-1β, IL-6, and IL-17A showed similar trends of increasing and then decreasing, but there was no significant change in colon TNF-α. The concentration of IL-10 decreased during the induction periods and increased during the remission periods. Conclusions During the induction of chronic UC in mice, the symptoms of hematochezia and systemic inflammatory reactions gradually increased, and the mice showed an increase in tolerance and ability to resist mortality, weight loss, and histopathological injury to the colon. The onset and remission of colonic histopathological damage lags behind symptomatic changes, and there is a gradual shift in colonic inflammation to a pattern dominated by polymorphonuclear neutrophils (PMN) activation.
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LIU Shiyu, XU Yumin, XU Hongcai, LU Fangmei
2024,34(7):121-130, DOI: 10.3969/j.issn.1671-7856.2024.07.014
Abstract:
Mitochondria-associated membranes ( MAMs ) are a subcellular compartment involved in the communication and material exchange between the mitochondrial outer membrane and endoplasmic reticulum membrane.MAMs perform various biological processes in cells under different conditions. MAM-dysfunction-mediated calcium homeostasis imbalance, endoplasmic reticulum stress, mitophagy defects, mitochondrial fission / fusion dynamics imbalance, lipid metabolism disorders, and inflammatory responses are key pathogenic factors in Alzheimer’ s disease (AD). This article reviews the structure and function of MAMs, their involvement in AD pathology, and drug intervention targets, and discusses the role of MAMs in the pathogenesis of AD and the latest research into their mechanisms, to provide new ideas for the prevention and treatment of AD.
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WANG Lei, SONG Huiqian, LI Bin, LIANG Chao, CHEN Min, TIAN Yushu, WU Xuying, ZHANG Wenming, LIU Yunbo
2024,34(7):29-38, DOI: 10.3969/j.issn.1671-7856.2024.07.004
Abstract:
Objective To study the impact of a Western diet-type feed on biological indicators and histopathology in APOE- / - mice. Methods Forty-eight female and 48 male APOE- / - mice, and 48 female and 48 male C57BL/ 6J mice were divided into eight breeding groups: APOE- / - breeding feed group, APOE- / - Western dietary feed group, C57BL/ 6J breeding feed group, and C57BL/ 6J Western dietary feed group (24 male and 24 female mice per group). Mice were fed the respective diets from 3 weeks until the end of the experiment at 20 weeks. After the experiment, serum was collected for measurement of biochemical indicators. Aortas were removed for oil red O staining and gross examination and the aorta root was paraffin sectioned and stained with hematoxylin and eosin. Results A Western diet did not significantly increase body weight in APOE- / - mice, but did significantly improve the blood lipid index and total cholesterol, low-density lipoprotein,and high-density lipoprotein levels, and promoted the formation of atherosclerotic plaques. Male mice were suitable for modeling gross aortic plaques while female mice were suitable for modeling aortic arch root plaques. Conclusions A Western diet can promote atherosclerosis in APOE- / - mice, increase the aortic plaque area ratio, shorten modeling time,and improve modeling uniformity.
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JIANG Huan, BAI Wenya, SHAO Jianlin
2024,34(7):101-109, DOI: 10.3969/j.issn.1671-7856.2024.07.012
Abstract:
Ferroptosis is a newly cell death mode discovered in recent years, involving in a variety of pathophysiological processes, such as ischemia reperfusion injury, neurodegenerative diseases and tumors, etc. At present,there is a lack of effective method to prevent and treat ischemic stroke worldwide, and ferroptosis which is involved in cerebral ischemia reperfusion injury. 50 articles were included in this paper after searching the related literature, which published in databases such as PubMed, Wanfang, VIP and CNKI in recent years. Discussing the iron metabolism and the concept, mechanism and regulation of ferroptosis, the role of ferroptosis in the mechanism of cerebral ischemia reperfusion injury, and the method of inhibiting ferroptosis, this paper attempts to provide reference for finding a new potential treatment for ischemic stroke from the direction of inhibiting ferroptosis.
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HU Jiajia, YANG Zhuanfang, SUN Xizhe, YUAN Juanjuan, CHENG Yan, ZHANG Yu, YIN Litian
2024,34(6):1-10, DOI: 10.3969/j.issn.1671-7856.2024.06.001
Abstract:
Objective We investigated the effects of ICAM5 in the hippocampus on the alcohol drinking preference of mice, and the potential mechanisms. Methods An alcohol two-bottle choice model was developed in 8-week-old male C57BL/ 6J mice, which were randomly divided to two groups: water group and alcohol group. The protein expression of ICAM5 in the hippocampus, amygdala, and medial prefrontal cortex was detected. An ICAM5-overexpressing adeno-associated virus was constructed and injected into the hippocampus by stereotaxic method. The expression level of ICAM5 protein in the hippocampus was detected by immunofluorescence and Western blot. We then detected the alcohol preference and locomotor activity of mice with a conditioned place preference (CPP) experiment, open field test, and lossof-righting reflex test. Western blot analysis was used to identify the neuron F-actin / G-actin ratio. Using Golgi staining, the morphology of dendritic spines was identified. Results The expression of ICAM5 in the hippocampus of alcohol two-bottle choice model mice in the alcohol group was considerably lower than that of the water group ( P<0. 001). The specific expression of ICAM5 in the hippocampus of mice was observed by fluorescence microscopy. In the open field experiment,the staying time and moving distance of the AAV-ICAM5 group were significantly increased compared with those of the control group ( P<0. 01). In the CPP experiment, the residence time of AAV-ICAM5 mice in the alcohol-paired compartment was significantly lower than that of control mice ( P<0. 001). In the loss-of-righting reflex experiment,overexpression of ICAM5 significantly reduced sedation latency ( P<0. 01), but significantly shortened the duration of sedation (P<0. 001). Compared with AAV-mCherry +Water group, the ratio of F-actin / G-actin in the hippocampus was significantly increased after drinking ( P<0. 01 ), but after ICAM5 overexpression, their F-actin / G-actin ratio was significantly decreased (P<0. 001). Compared with AAV-mCherry + Water group, the density of dendritic spines in the hippocampal CA1 region was increased (P<0. 001), but the density of dendritic spines in the AAV-ICAM5+Alcohol group was significantly decreased (P<0. 01). Conclusions ICAM5 modulated the expression of cytoskeleton proteins to change the structural plasticity of dendritic spines, which contributed to alcohol-drinking and locomotor behavioral changes in mice.
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GUO Xiaojing, WANG Yan, ZHANG Li, PEI Fei, ZHANG Bo, QIN Huan, WANG Shujin, LI Xiaotong
2024,34(6):144-150, DOI: 10.3969/j.issn.1671-7856.2024.06.019
Abstract:
Skeletal muscle wasting refers to a loss of skeletal muscle mass and function. Mitochondrial quality control (MQC) is the basis by which normal physiological mitochondrial function is maintained and mainly involves the regulation of mitochondrial biogenesis, mitochondrial dynamics ( fission / fusion), and mitophagy. MQC maintains muscle homeostasis by regulating the relative stability of mitochondrial shape, quantity, and quality. As an economical and effective treatment for muscular atrophy, exercise interventions are widely used, but the relationship between exercise intervention and MQC is not clear. This paper discusses the role of mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in skeletal muscle atrophy and related molecular targets. We thoroughly analyze the mechanisms by which MQCmediated exercise can improve the skeletal muscle atrophy caused by aging, disuse, and cancer cachexia in order to provide theoretical guidance for intervention.
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2024,34(7):157-167, DOI: 10.3969/j.issn.1671-7856.2024.07.018
Abstract:
Chemotherapy resistance in leukemia is an urgent clinical therapeutic challenge. Ferroptosis is a unique mode of cell death driven by iron-dependent phospholipid peroxidation. Leukemia is characterized by increased oxidative stress and iron overload, suggesting that leukemia cells might be susceptible to ferroptosis and indicating a possible therapeutic approach. Ferroptosis has been extensively studied in recent years and used in the treatment of various types of leukemia. Several studies have demonstrated an association between the regulatory pathways of ferroptosis and the mechanisms of leukemia drug resistance. The induction of ferroptosis through different pathways can effectively reduce the resistance of various types of leukemia cells to chemotherapeutic drugs, and thus improve their clinical efficacy. In this article, we review the regulatory mechanisms of ferroptosis and analyze the association between oxidative stress and iron metabolism pathways of ferroptosis and the mechanism of leukemia drug resistance. We also summarize the experimental studies and clinical applications of ferroptosis for the treatment of various types of drug-resistant leukemias, with the aim of providing new ideas and directions for the study of ferroptosis and a new strategy to reverse chemotherapy resistance in patients with leukemia in the future.
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TANG Zining, CHEN Xiangchi, LIU Xuewu, ZHOU Zhimin, LI Qiao, XIAO Sa, JIANG Dejian, PENG Dongdong
2024,34(6):63-72, DOI: 10.3969/j.issn.1671-7856.2024.06.008
Abstract:
Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies. Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group, and cyclophosphamide +fungal infection low, medium, and high dose groups, with 12 animals in each group. General clinical observations were performed daily, and the serum levels of immunoglobulin (Ig)G and IgM and galactomannan (GM) were detected by ELISA on the 3rd and 7th days of modeling. Simultaneously, the ratio of CD4+ and CD8+cells, content of white blood cells (WBCs) and neutrophils (Neu) in peripheral blood, the Aspergillus niger load in alveolar lavage, and morphological changes to rat lung tissue were observed. Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling, and rats in the cyclophosphamide + fungal infection group also had shortness of breath and audible wet rhonchi in the lungs. Compared with the normal control group, rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+, WBC, Neu, IgG, and IgM in the blood, and their proportion of CD8+cells was significantly higher ( P<0. 05, P<0. 01 ). Compared with the cyclophosphamide control group, rats in the cyclophosphamide+fungal infection medium- and high-dose groups had significantly reduced blood levels of IgG, IgM, and CD4+ cells (P<0. 05, P<0. 01); while the cyclophosphamide+fungal infection low-, medium-, and high-dose groups had significantly reduced blood levels of WBC and Neu (P<0. 05, P<0. 01). Additionally, rats in the cyclophosphamide+fungal infection medium- and high-dose groups had significantly increased blood CD8+ cells (P<0. 05, P<0. 01), Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide + fungal infection low-, medium-, and high-dose groups compared with the cyclophosphamide control group (P<0. 05, P<0. 01). The lung tissues of the cyclophosphamide+fungal infection low-, medium-, and high-dose groups showed mycelial distribution and destruction of alveolar epithelium, increase of bronchial epithelial cup cells in the alveoli, and infiltration of inflammatory cells, and the degree of lesions was positively correlated with the modeling dose. Conclusions In this study, we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease. The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time, confirming that cellular immunity plays an important role in the pathogenesis of the disease. At the same time, Ig can also affect the development of invasive pulmonary aspergillosis, and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.
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LI Yanjin, XIAO Liying, WU Daoxiong, GUAN Rong, YAN Chunlang, LEI Wen
2024,34(6):172-178, DOI: 10.3969/j.issn.1671-7856.2024.06.022
Abstract:
Pulmonary hypertension ( PH ) is a progressive disease characterized by pulmonary vascular remodeling. Current treatments for PH remain suboptimal, and there is an urgent need to better decipher the underlying pathomechanisms to identify new therapeutic targets. MicroRNA (miRNA) are key components in the post-transcriptional machinery that mediates cellular functions and mainly act by regulating the expression of downstream target genes.Numerous in vivo and in vitro studies have demonstrated the involvement of miRNA and their regulators in PH development.However, there is no unified model for the mechanism of miRNA’ s regulation of pulmonary vascular remodeling. Therefore, this article provides a review on the mechanisms of miRNA in PH characterized in recent years.
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YANG Zhenjie, SA Chula, YU Tianyuan, ZHANG Yingqi, ZHANG Runlong, , CHEN Jinping, LIU Jiayue, ZHANG Hanyu, SUN Jiawei
2024,34(7):1-9, DOI: 10.3969/j.issn.1671-7856.2024.07.001
Abstract:
Objective To explore the analgesic initiation mechanism of three-manipulation and three-acupoint tuina in model rats with minor chronic constriction injury (CCI). Methods Fifty-six SD rats were divided randomly into eight groups: normal group, sham group, model 1 group, model 2 group, tuina 1 group, tuina 2 group, tuina 1 + transient receptor potential vanilloid-1 (TRPV1) antagonist group, and tuina 2 + transient receptor potential ankyrin 1 (TRPA1) antagonist group. The model, tuina, and tuina + antagonist groups were established with minor CCI models. The tuina and tuina + antagonist groups received the three-method three-point intervention ( point method, dial method, kneading method, Yinmen point, Chengshan point, Yanglingquan point) 7 days after modeling. The model and sham groups were subjected to grasping restraint, and the normal group received no intervention. After the respective interventions, each group was tested for changes in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) to detect different types of pain. The nitric oxide (NO) content of the dorsal root ganglion (DRG) was determined by the nitrate reductase method, and changes in protein and gene expression levels of components of the TRPV1 / TRPA1-NO-cGMPprotein kinase G (PKG) signaling pathway in the DRG of each group were determined by enzyme-linked immunosorbent assay, Western blot, and qPCR. Results Compared with the model group, MWT and TWL were prolonged in the tuina 1 and tuina 2 groups. Expression levels of TRPV1, TRPA1, NO, soluble guanylate cyclase-β, cGMP, and PKG1 in the DRG were significantly decreased in the tuina 1, tuina 2, tuina 1 + TRPV1 antagonist, and tuina 2 + TRPA1 antagonist groups. Conclusions Tuina can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one-time intervention. Tuina can exert immediate and continuous analgesic effects via the TRPV1 / TRPA1-NO-cGMP-PKG signaling pathway.
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JI Shaoxiu, ZHANG Hengyao, ZHANG Yuan, WEN Li
2024,34(6):113-118, DOI: 10.3969/j.issn.1671-7856.2024.06.015
Abstract:
Liver fibrosis is a key pathological process in the progression of chronic liver disease to cirrhosis and even liver cancer. The occurrence of liver fibrosis is a highly integrated and dynamic pathological process result ing from the interactions of many cells and cytokines. The Notch signaling pathway is an evolutionarily conserved intercellular signal transduction mechanism that plays important roles in regulating the development and tissue renewal of multicellular animals.Multiple studies have shown that Notch signal transduction participates in the formation of liver fibrosis in a variety of ways.Therefore, this paper reviews the role of Notch signaling in cells involved in the formation of liver fibrosis to explain the function of this signaling pathway in liver fibrosis.
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LI Peng, HUANG Minli, TAN Dengxu, ZHANG Caiqin, ZHANG Yongbin, SHI Changhong
2024,34(6):40-46, DOI: 10.3969/j.issn.1671-7856.2024.06.005
Abstract:
Objective To construct a patient-derived pancreatic tumor organoid ( PDO) and evaluate its effectiveness. Methods We collected fresh surgical specimens from pancreatic cancer patients for PDO culture and compared the pathological and genetic characteristics of the PDO model with those of primary tumors. The PDO model was used to evaluate the efficacy of clinical chemotherapy drugs, and the effectiveness of the model was assessed. Results A PDO model of pancreatic cancer was successfully established. Histomorphological analysis indicated that the PDO model maintained the basic pathological characteristics of the primary tumor. Whole-exon sequencing showed that both the organoids and original tumor tissue remained consistent in their gene mutation type and characteristics. Drug screening tests revealed that the PDO model had good sensitivity to gemcitabine and irinotecan. Conclusions A pancreatic cancer PDO was successfully constructed that reflected the histological and genetic characteristics of the original tumor. The model was shown to be effective for drug sensitivity experiments in vitro and is expected to have implications for precision medicine assays.
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ZHU Yu, SU Yingshi, LIU Xi, HE Baoguo, QIN Lei
2024,34(6):73-81, DOI: 10.3969/j.issn.1671-7856.2024.06.009
Abstract:
Objective To establish a model of long-term atrazine (ATR)-induced liver injury in mice and to evaluate the hepatotoxic effects induced by ATR. Methods C57BL/ 6-N male mice were randomly divided into a control group and 1. 5 mg / L and 150 mg / L ATR dose (ATR-L, ATR-H) groups. After 35 and 63 days, serum liver function biochemical indexes and inflammatory factors were detected, the hepatosomatic ratio was calculated, and the histopathology and ultrastructure of the liver were observed. Lipid peroxidation levels and antioxidant capacity, the activities of major phase I metabolic enzymes and phase II detoxification enzymes, and the expression of related proteins in liver tissues were detected. Results Compared with the control group, the ATR groups showed significant changes in the AST/ ALT ratio,levels of pro-inflammatory factors CCL2, TNF-α and IL-6, H2O2 content and activities of the metabolic enzymes NCR,CYT b5, and UDPGT ( P<0. 05). In the 150 mg / L ATR group, GGT content, peroxide levels ( as indicated by malondialdehyde), and CYP1A2 expression were significantly increased (P<0. 01), while GSH content was significantly decreased (P<0. 05), and hepatocyte injury and mitochondrial vacuolation were more serious when compared to control and 1. 5 mg / L groups. Conclusions In a mouse model of low-dose ATR liver injury, both 1. 5 mg / L and 150 mg / L ATR exposure induced liver injury in mice, with 150 mg / L ATR inducing the maximum metabolic toxicity in the liver after 63 days
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MA Lingju, CHI Hongyang, WU Xinxue, MA Fujun, TIAN Yancheng, ZHAO Caiqi, HE Tianyu, PENG Hongjian, JIANG Yideng, YANG Li, HUANG Hui, MA Shengchao
2024,34(6):11-17, DOI: 10.3969/j.issn.1671-7856.2024.06.002
Abstract:
Objective To study the role of ubiquitin-conjugating enzyme 9 ( UBC9) in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier (SUMO) modification. Methods First, the effects of homocysteine at different concentrations (0 μmol / L, 50 μmol / L, 100 μmol / L, 150 μmol / L and 200 μmol / L) on the viability and pyrodeath of mouse macrophages (RAW264. 7) were detected by CCK-8 and Western blot. Western blot was used to detect the expression levels of UBC9, SUMO-1, and the inflammatory cytokine IL-1β in different groups of cells. qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9, pyrogen-related protein, and SUMO-1 after RNA interference. Results After stimulation with 100 μmol / L homocysteine, the effect of macrophage activity was minimal, and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression (P<0. 05). Compared with the Control group, the Hcy group’ s expression of IL-1β and SUMO-1 was increased (P<0. 01). Compared with the Control group, the Hcy group’ s UBC9 protein and mRNA levels were increased (P<0. 05). The expression of NLRP3, Caspase-1, IL-1β, UBC9, and SUMO-1 was decreased in the siUBC9 + Hcy group compared with the si-NC+Hcy group (P<0. 01). Conclusions Homocysteine induces pyroptosis in macrophages, and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.
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XIE Youcheng, XIAO Shufang, LIN Xuemei, CHEN Shun, XU Jin, WANG Fei
2024,34(6):106-112, DOI: 10.3969/j.issn.1671-7856.2024.06.014
Abstract:
Septic cardiomyopathy ( SIC) is an organ dysfunction frequently observed in sepsis and characterized by high mortality and poor prognosis. Understanding the complex pathogenesis of SIC and developing effective therapeutic tools are critical issues that require attention. Previous studies have demonstrated the significant role of mitochondrial dysfunction in the development of SIC. In the presence of SIC, and the mitochondrial dysfunction that result, the aberrant regulation of the mitochondrial quality control system (MQC) can exacerbate cardiomyocyte injury. Recent studies have demonstrated that the MQC maintains the dynamics of mitochondrial homeostasis through its regulation of mitochondrial biogenesis, fusion / fission, and autophagy. This article provides an overview of the role of MQC in SIC pathogenesis,reviews the latest studies in the field, and analyzes MQC’s potential as a therapeutic target.
