Abstract: Objective To investigate expression of YAP in idiopathic membranous nephropathy (IMN). Methods Expression of YAP protein in IMN patients and normal renal tissues was detected by immunohistochemistry. An injury model of the human podocyte line MPC5 was established in vitro with C5b-9. Expression of YAP protein in podocytes was detected by Western blot. siRNA transient transfection was used to silence YAP gene expression in podocytes. The transfection efficiency was assessed by qRT-PCR and Western blot. Podocytes were divided into four groups: control, C5b- 9, C5b-9+si-NC and C5b-9+si-YAP groups. A CCK-8 assay was used to assess the proliferation activity, annexin V-FITC double staining combined with flow cytometry was used to assess apoptosis, DCFH-DA staining was used to detect the content of reactive oxygen species (ROS). Western blot was used to measure the apoptosis rate. The expression of podocyte marker protein nephrin, WT1, tight junction protein ZO-1, phenotype transition protein snail and fibronectin was detected by Western blot. Results Compared with normal renal tissue, the expression of YAP in IMN was increased significantly (P< 0.05). With prolongation of the C5b-9 stimulation time, the expression level of YAP protein was increased in podocytes (P< 0.05). After si-YAP transfection, the mRNA and protein levels of YAP in podocytes were decreased significantly (P<0.05). Compared with the control group, cell proliferation in C5b-9, C5b-9+si-NC and C5b-9+si-YAP groups was decreased significantly, while the apoptosis rate and ROS content were increased significantly ( P< 0.05). However, compared with C5b-9 and C5b-9+si-NC groups, cell proliferation in the C5b-9+si-YAP group was increased significantly and the ROS content in cells was decreased significantly (P<0.05). Expression of nephrin, WT1 and ZO-1 in C5b-9, C5b-9+ si-NC and C5b-9 + si-YAP groups was significantly lower than that in the control group ( P< 0.05). Compared with C5b-9 and C5b-9+si-NC groups, the protein expression of nephrin, WT1 and ZO-1 in the C5b-9+si-YAP group was increased significantly, while the protein expression of Snail and fibronectin was decreased significantly ( P< 0.05). Conclusions This study showed that YAP protein expression in glomeruli of IMN patients is significantly increased and silencing YAP gene expression in podocytes significantly improves C5b-9-damaged induced functions and inhibits apoptosis.

Abstract: Objective To study the effect of icariin ( ICA) on apoptosis and inflammation of leukemic mouse macrophages (RAW264. 7) induced by oxidized low-density lipoprotein (ox-LDL), and to clarify the anti-arterial effect of ICA and the role of atherosclerosis (AS). Methods RAW264. 7 cells were treated with ox-LDL to induce foam cell models. The effects of low, medium, and high doses of ICA on RAW264. 7 cell viability, apoptosis, foaming and secretion of inflammatory factors IL-1β, IL-6 and TNF-α were investigated. Western blot was used to assess the effect of ICA on protein expression of Bcl-2, Bax, Caspase-3, IκBα and NF-κB p65. Results ICA improved cell viability and reduced apoptosis, the formation of foamy macrophages, secretion of inflammatory factors IL-1β, IL-6, TNF-α, Bcl-2, Caspase-3 and NF-κB p65 protein expression, and up-regulated protein expression of Bax and IκBα. Conclusions ICA reduces apoptosis of foamy macrophages and inhibits the expression of inflammatory factors, thereby delaying the development of atherosclerosis.

Abstract: Objective To investigate the protective effect of quercetin pretreatment on hepatic ischemia- reperfusion injury by autophagy mediated via the AMPK/ mTOR signaling pathway. Methods Rats were randomly divided into control, model, quercetin, chloroquine (autophagy inhibitor) and quercetin+chloroquine groups. Three days before the operation, the quercetin group was administered 0. 1 g / kg quercetin, the chloroquine group was intraperitoneally injected with 0. 02 g / kg chloroquine, the quercetin+chloroquine group was administered quercetin by gavage and chloroquine was injected intraperitoneally at 3 days, and the control and model groups were administered an equal volume of solvent once a day. The rat model of hepatic ischemia-reperfusion was established and rats were sacrificed at 6 hours after reperfusion. Liver function indexes, which included glutamic pyruvate transaminase (ALT) and aspartate acyltransferase (AST), were measured by an automatic biochemical analyzer. Pathological changes of liver tissue were observed by hematoxylin eosin (HE) staining. The serum levels of inflammatory factors, which included interleukin ( IL-6), tumor necrosis factor-α (TNF-α) and IL-1β were measured by enzyme-linked immunosorbent assays. The autophagy rate was calculated by monosulfonamide (MDC) staining. Expression of Beclin1 protein and the phosphorylation of AMPK and mTOR proteins in liver tissue were detected by Western blot. Results In the control group, the liver tissue structure was complete, hepatocytes were arranged in order, and there was no significant necrosis. Compared with the control group, the liver tissue structure of the model group was disordered, the arrangement of hepatocytes was loose, and necrosis had appeared, the levels of ALT and AST, contents of IL-6, TNF-α and IL-1β, phosphorylation level of mTOR protein were significantly higher (P<0.05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly lower (P<0.05). Compared with the model group, the above pathological damage of liver tissue in the quercetin group was alleviated significantly, the levels of ALT and AST, the contents of IL-6, TNF-α, IL-1β and the phosphorylation level of mTOR protein were significantly lower (P< 0. 05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly higher (P<0.05). In the chloroquine group, the above pathological damage of liver tissue was aggravated significantly, the levels of ALT and AST, contents of IL-6, TNF-α and IL-1β and phosphorylation level of mTOR protein were significantly higher (P<0. 05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly lower ( P< 0.05). Compared with the quercetin group, the pathological damage of liver tissue in the quercetin + chloroquine group was more serious, the levels of ALT and AST, contents of IL-6, TNF-α and IL-1β. and phosphorylation level of mTOR protein were significantly higher (P<0.05) and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly lower (P<0. 05). Compared with the chloroquine group, the pathological damage of liver tissue in the quercetin+chloroquine group was significantly reduced, the levels of ALT and AST, the contents of IL-6, TNF- α and IL-1β, and phosphorylation level of mTOR protein were significantly lower (P< 0.05), and the autophagy rate, expression level of Beclin1 protein, and phosphorylation level of AMPK protein were significantly higher ( P< 0.05). Conclusions Quercetin pretreatment may activate autophagy mediated by the AMPK/ mTOR signaling pathway in liver tissue of rats with hepatic ischemia-reperfusion injury, thereby reducing the inflammatory response and alleviating liver injury.

Abstract: Objective To investigate the effect of pancreatic kininogenase on myocardial injury, oxidative stress, and fibrosis in rats with myocardial ischemia-reperfusion injury. Methods SD rats were divided into sham, model and drug- treated groups. The heart rate (HR), left ventricular systolic pressure (LVSP), and short-axis contraction rate (FS) of rats were measured in each group. HE staining was used to detect myocardial pathological lesions. ELISA were used to detect the contents of creatine kinase isoenzyme (CK-MB), myoglobin (Mb) and cardiac troponin I (cTnI). Assay kits were used to detect the contents of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH). Western blot was used to assay the expression levels of mitochondrial pathway apoptosis-related and fibrosis marker proteins. Masson staining was used to observe myocardial tissue fibrosis. RT-PCR was used to assay the expression levels of α-smooth muscle actin (α- SMA), transforming growth factor-β1 (TGF-β1) and fibronectin (FN). Results Compared with the model group, HR, LVSP and FS in 3 and 6 U/ kg PKase groups were significantly increased (P<0.05), pathological damage of myocardial tissue was significantly improved, the contents of CK-MB, Mb, MDA and cTnI were significantly reduced (P<0.05), SOD and GSH contents were increased (P<0.05), the degree of myocardial fibrosis was significantly improved, Bax / Bcl-2, cas-9, cas-3, α-SMA, TGF-β1 and FN levels were reduced significantly (P< 0.05). Conclusions Pancreatic kininogenase relieves myocardial injury, oxidative stress and fibrosis in rats with myocardial ischemia-reperfusion injury.

Abstract: Objective To explore the mechanism of capsaicin in inhibiting the invasion and migration of colon cancer cells by upregulating tumor metastasis suppressor 1 ( MTSS1). Methods Experiment 1: 10, 25, 50 and 100 μmol / L capsaicin groups were treated with capsaicin, whereas the control group was untreated and cultured at a constant temperature for 24 hours. Experiment 2: the control group was cultured normally, the 100 μmol / L capsaicin group was treated with 100 μmol / L capsaicin, 100 μmol / L capsaicin + control siRNA and 100 μmol / L capsaicin +MTSS1 siRNA groups were treated with 50 nmol / L control siRNA and MTSS1 siRNA, respectively, based on the 100 μmol / L capsaicin group. After transfection for 4 h, 100 μmol / L capsaicin-containing culture medium was added. Cell proliferation was assessed by CCK8 assays. Cell invasion was assessed by Transwell assays. Cell migration was assessed by a scratch test. The protein levels of transient receptor potential vanilloid 1 (TRPV1), MTSS1, matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot. Results After treatment with capsaicin at various concentrations, compared with the control group, cell proliferation in 25, 50 and 100 μmol / L capsaicin groups was higher, the protein levels of TRPV1 and MTSS1 in 10, 25, 50 and 100 μmol / L capsaicin groups were higher, and cell invasion, the percentage of migrated cells and the protein levels of MMP-2 and MMP-9 were lower (P<0.05). After RNA interference of MTSS1 and addition of 100 μmol / L capsaicin, compared with the control group, cell invasion, the percentage of migrated cells, and the protein levels of MMP-2 and MMP-9 were lower in 100 μmol / L capsaicin, 100 μmol / L capsaicin+control siRNA, 100 μmol / L capsaicin+MTSS1 siRNA groups (P<0. 05), and the protein level of MTSS1 was higher (P<0.05). Compared with 100 μmol / L capsaicin and 100 μmol / L capsaicin+control siRNA groups, cell invasion, the percentage of migrated cells, the protein levels of MMP-2 and MMP-9 were significantly higher in the 100 μmol / L capsaicin+MTSS1 siRNA group and the level of MTSS1 protein was lower (P<0.05). Conclusions Capsaicin inhibits the invasion and migration of colon cancer cells by upregulating the expression of MTSS1, thereby exerting a protective effect against colon cancer.

Abstract: Objective To explore the effects of compound Gastrodia honey cyclic glycopeptide tablets on T lymphocyte subsets, early renal injury, and angiotensin II receptor type 1 ( AT1R) / Smad3 proteins in essential hypertensive rats. Methods The study was divided into three groups: normal (NC), model ( SHR) and drug (TMGT) groups. Changes in blood pressure, T lymphocyte subsets in peripheral blood, IL-6 and TNF-α in serum, pathology in renal tissue, AT1R/ Smad3 protein expression were assessed. Expression of AT1R/ Smad3 mRNA was detected. Results Compared with the NC group, tail artery pressure in the SHR group was increased at 2, 4 and 8 weeks after administration (P<0. 05). However, no significant difference was found between SHR and TMGT groups at week 0 (P<0.05). At 2, 4 and 8 weeks after administration, systolic blood pressure of the tail artery in the SHR group was significantly higher than that in the NC group, and the tail vein of the TMGT group was systolic after treatment. Blood pressure in the SHR group was significantly lower than that in the SHR group ( P< 0.05). The ratio of CD4⁺ / CD8⁺ cells in the SHR group was significantly higher than that in the NC group ( P< 0.05). The ratio of CD4⁺ / CD8⁺ cells in the TMGT group was significantly lower than that in the SHR group after treatment (P<0.05). Compared with the NC group, the serum levels of IL-6 and TNF-α in the SHR group were increased significantly (P<0.05) and those in the TMGT group were decreased significantly ( P< 0.05). Renal tissue of the SHR group was more seriously damaged than that of the NC group with glomerular hypertrophy and basement membrane thickening, a large number of glomeruli became vacuoles, capillary stenosis and occlusion. After treatment, renal tissue of the TMGT group was significantly improved compared with that of the SHR group. Compared with the NC group, protein and mRNA expression of Smad3 and AT1R in renal tissue of the SHR group was increased significantly (P< 0. 05) and that of Smad3 and AT1R in renal tissue of the TMGT group was decreased significantly ( P< 0.05). Conclusions Compound Gastrodia honey cyclic glycopeptide tablets effectively regulate T lymphocyte subsets, improve immune functions, alleviate early renal injury caused by hypertension, and inhibit the expression of Smad3 and AT1R proteins in renal tissue to treat hypertension.

Abstract: Objective To investigate the role and mechanism of ORMDL3 in neutrophil asthma through endoplasmic reticulum stress ( ERS)-mediated autophagy. Methods Adult male SD rats were randomly divided into control, model, model+NC siRNA, model+ORMDL3 siRNA, solvent control, model+solvent control, model+NC siRNA group+ solvent control, model + ORMDL3 siRNA + solvent control and model + ORMDL3 siRNA + agonist groups. The neutrophil asthma model was established by lipopolysaccharide and ovalbumin sensitization. An ORMDL3 siRNA lentivirus or negative control (NC)-siRNA lentivirus was administered through the airway and ERS agonist, carotene, or solvent was injected intraperitoneally. Airway function, 0. 2 s forced expiratory volume (FEV0. 2) / forced vital capacity (FVC), peak expiratory flow ( PEF), pathological changes of lung tissue and the expression levels of ORMDL3, ERS marker genes PERK, IRE1α, ATF6 and autophagy marker genes Beclin-1 and LC3 were analyzed. Results FEV0. 2 / FVC and PEF levels of the model group were lower than those of the control group and the expression levels of ORMDL3, PERK, IRE1α, ATF6, Beclin-1 and LC3-II/ LC3-I in lung tissue were higher than those of the control group (P<0.05). FEV0. 2 / FVC and PEF levels of the model+ORMDL3-siRNA group were higher than those of the model+NC-siRNA group and the expression levels of ORMDL3, ATF6, Beclin-1 and LC3-II/ LC3-I in lung tissue were lower than those of the model+NC-siRNA group (P<0. 05). The expression levels of PERK and IRE1α showed no difference compared with the model+NC-siRNA group (P> 0.05). FEV0. 2 / FVC and PEF levels in the model+ORMDL3 siRNA+agonist group were lower than those in the model +ORMDL3 siRNA+solvent group and the expression levels of Beclin-1 and LC3-II/ LC3-I in lung tissue were higher than those in the control group ( P< 0.05 ). Conclusions In the pathogenesis of neutrophil asthma, ORMDL3-induced autophagy through ERS ATF6 pathway is a possible molecular mechanism. Blocking ORMDL3 is a possible treatment method for neutrophil asthma.

Abstract: Objective In terms of the TLR/ NF-κB signaling pathway, we explored the effect of Bushen Yiqi Huayu granules on the formation of blood vessels in osteoporotic rats. Methods Sixty SPF female SD rats were randomly divided into sham operation, model, granule and positive control groups with 15 rats in each group. Except for the sham operation group, the other three groups were subjected to bilateral ovarian extraction to prepare an osteoporotic model. The sham operation group underwent surgery only without removing the ovaries as a control. Rats in the granule group were administered 5 g / kg Bushen Yiqi Huayu granules by gavage, rats in the positive control group were administered 0. 5 mg / kg alendronate sodium tablets by gavage, and rats in model and sham operation groups were administered a gavage with the same amount of normal saline. After 12 weeks of continuous administration, the rats were sacrificed. Femoral tissues of the rats were subjected to bone density testing, HE staining, Micro-CT three-dimensional reconstruction analysis, CD31 fluorescence immunoassay, and blood perfusion imaging analysis. Serum VEGF and HIF-1α concentrations were measured by ELISA. Western blot was used to detect expression of p50 / p-p50 and p65 / p-p65 protein. Results Compared with the sham operation group, rats in the model group had a low bone density (P< 0. 05), trabecular bone growth was sparse, blood vessel formation was slower, the number of blood vessels was smaller, serum VEGF and HIF-1α concentrations were significantly decreased (P<0. 05), and expression of p50 / p-p50 and p65 / p-p65 proteins in femoral tissues was increased significantly. Compared with the model group, the trabeculae of rats in granule and positive control groups grew well, the number of blood vessels was formed, bone density was increased significantly, serum levels of VEGF and HIF-1α were increased significantly (P<0. 05), and the protein levels of p50 / p-p50 and p65 / p-p65 were decreased significantly (P< 0. 05). Conclusions Bushen Yiqi Huayu granules may promote the angiogenesis in osteoporotic rats by regulating the TLR/ NF-κB signaling pathway and plays an important role in alleviating osteoporosis.

Abstract: Objective To investigate the effect of captopril on expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in spontaneously hypertensive rats. Methods WKY (Wistar Kyoto) rats were used as the blank control. Spontaneous hypertensive rats(SHR) were used as the model group. SHR aged 7 ~ 24 weeks were administered captopril (3. 375 g / (kg·d)) and observed at 32 weeks. Blood pressure, left ventricular mass index (LVMI), aortic diastolic function, serum nitrite ion (NO₂ - ), and mRNA and protein contents of iNOS and eNOS were measured. Results (1) The left ventricular mass index and serum NO₂ - concentration of SHR were higher than those of WKY rats at various weeks and relaxation of the aorta was significantly lower than in WKY rats. (2) mRNA expression changes: compared with WKY rats, mRNA expression of eNOS and iNOS in the myocardium and arteries of SH rats were higher at various weeks, among which the maximum value of eNOS / iNOS appeared at 18 weeks. After administration of captopril, mRNA expression of iNOS and eNOS in the myocardium and arteries was significantly reduced at 24 and 32 weeks. (3) Protein expression changes: compared with WKY rats, the iNOS protein content in the myocardium and arteries of 18 and 24 weeks SHR were increased significantly, and that of 24 weeks SHR and 18 and 24 weeks SHR was increased significantly. Protein expression of iNOS in arteries was significantly reduced at 18 and 24 weeks by captopril and the effect disappeared after discontinuation. iNOS protein expression was significantly reduced at 24 and 32 weeks. Additionally, at 32 weeks, eNOS protein expression was significantly reduced in arteries and increased in the myocardium. Conclusions The pathological state of hypertension can lead to overexpression of iNOS and eNOS, and accumulation of iNOS and eNOS affects the occurrence of hypertension. Along with the pathogenesis of SHR hypertension, the nitric oxide system has a certain correlation with left ventricular hypertrophy and endothelial function. Captopril inhibits the expression of iNOS and eNOS in vivo to a certain extent and improves the left ventricular fat thickness and endothelial function.

Abstract: Objective To observe expression of HIF-1α, RhoA and SOX9 proteins in kidneys and to determine their relationship with tubulointerstitial fibrosis in rats with adenine-induced chronic kidney disease. Methods Twenty rats were randomly divided into a control (Con) group and model group ( adenine-induced CKD rat model). The rats were sacrificed after 3 and 6 weeks. Morphological changes of the kidney were observed and the renal functions and 24 h urinary protein were assessed. Renal pathological changes were observed by HE staining and interstitial fibers of renal tubules were observed by Sirius red staining. Immunohistochemical staining was used to observe expression of HIF-1α, RhoA, SOX9, Col-I and α-SMA proteins in renal tissue. HIF-1α, RhoA, SOX9, Col-I and α-SMA mRNA levels in the kidney were measured by RT-PCR and the relationship between the expression levels of HIF-1α, RhoA and SOX9, and renal tubular interstitial fibrosis was analyzed. The expression level of SOX9 in serum of the two groups was measured by an ELISA. Results Compared with the Con group, 24 h urinary protein, serum BUN and Scr in the CKD group were increased significantly (P<0. 05). In the CKD group, HE staining and Sirius red staining showed obvious renal tubule dilatation, interstitial fibrosis and aggravation over time. Immunohistochemistry and RT-PCR showed that the expression of HIF-1 α, RhoA and SOX9 was increased in the CKD group and the serum level of SOX9 in the CKD group was higher than that in the control group, which was increased over time. Correlation analysis showed that the mRNA expression of HIF-1α, RhoA and SOX9 was correlated with Col-I and α-SMA, and there was a positive correlation among HIF-1α, RhoA and SOX9. Conclusions HIF-1α, RhoA and SOX9 are highly expressed in the adenine-induced CKD rat model, which may be closely related to the progression of renal interstitial fibrosis. Moreover, the serum level of SOX9 is expected to be a molecular marker for early diagnosis of CKD.

Abstract: Objective To study the protective mechanism of 1, 25 (OH)₂D₃ in experimental autoimmune thyroiditis rats based on the TLR2 / NF-κB signaling pathway. Methods Rats were randomly divided into control, model, and selenium yeast tablet control groups, and 1,25(OH)₂D₃ low, medium and high dose groups. Except for the control group, the rats were injected subcutaneously with thyroglobulin (PTg) to establish an autoimmune thyroiditis model. The low, medium and high dose groups of 1,25(OH)₂D₃ were injected intraperitoneally with 0. 5, 1. 0 and 1. 5 μg / kg 1,25 (OH)₂D₃ , the control and model groups were injected with the same amount of distilled water and selenium yeast tablets, and the control group was injected with the same amount of selenium yeast suspension ( once a day) for 4 weeks. Thyroid function factors, serum inflammatory factors, thyroid autoantibodies, TLR2 / NF-κB signaling pathway-related protein levels, and gene expression were analyzed. Results Compared with autoimmune thyroiditis rats, serum free thyroid glycine, free thyroxine, thyroid-stimulating hormone, thyroglobulin antibody, and thyroid peroxidase antibody, and interleukin (IL)-6, IL-12, tumor necrosis factor α (TNF-α), thyroid tissue TLR2, MyD88, TRAF-6 and NF-κB mRNA and protein expression were reduced, and IL-10 was increased in 1,25(OH)₂D₃ group rats. The difference between high dose 1,25(OH)₂D₃ and model groups was statistically significant (P< 0.05). Conclusions 1,25(OH)₂D₃ improves the thyroid functions of rats with autoimmune thyroiditis and increases the level of autoimmune antibodies. The mechanism may be related to inhibition of the TLR2 / NF-κB signaling pathway by 1, 25 (OH)₂D₃ , which regulates the release of inflammatory factors such as IL-6, IL-10, IL-12 and TNF-α.

Abstract:Animal experiments are a major part of medical education. At present, there are some problems in the laboratory animal ethics teaching mode, such as low popularization and limited teaching method. To resolve these problems, we focused on education of laboratory animal ethics and 3R theory ( reduction, replacement, and refinement) to help medical students enhance their laboratory animal ethics knowledge. The flipped classroom design of animal ethics is a student-leading classroom. Before class, a teacher transfers knowledge to students on an online platform. In class, the teacher guides the student groups to discuss and analyze the animal experiment protocol to enhance the research ability of students.

Abstract:Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, and its incidence is increasing yearly. Glucose metabolism reprogramming is the most representative metabolic feature of tumors, which has unique characteristics of energy metabolism. In the case of sufficient oxygen, tumor cells prefer glycolysis over highly productive mitochondrial oxidative phosphorylation. Current studies have shown that non-coding RNA (ncRNA) directly targets glucose transport protein and key enzyme to change glucose metabolism or indirectly changes glucose metabolism by regulating cancer-related signaling pathways during the occurrence and development of OSCC. This article reviews the mechanism of ncRNA in the regulation of aerobic glycolysis in OSCC.

Abstract:Atherosclerosis (AS) is a common cardiovascular disease that can cause serious complications and is one of the most common causes of patient death. The inflammatory response is involved in the pathogenesis of atherosclerosis and leukotrienes (LTs) are important inflammatory mediators that play immunomodulatory and proinflammatory roles in the inflammatory signaling pathway. Leukotrienes are closely related to atherosclerosis. Leukotriene B4 ( LTB4), cysteinyl leukotrienes, and the 5-lipoxygenase (5-LOX) pathway trigger a plaque formation disorder that promotes AS by inducing neutrophil aggregation, enhancing endothelial cell permeability, and mediating nuclear calcium signal transduction in vascular smooth muscle. Additionally, obstructive sleep apnea (OSA) and diabetes that produce LTs are associated with AS. Intermittent hypoxia in patients with OSA increases production of LTB4 and expression of 5-lipoxygenase. Increased matrix metalloproteases in diabetic patients promote expression of 5-LOX and LTB4. This article discussed the current research on the roles of LTs and related substances in the metabolic pathway in the pathogenesis of atherosclerosis and its treatment. Thus, some new treatment strategies aimed at LTs for anti-AS effects have been proposed, which include inhibition of LT receptors, the 5-LOX pathway and LTA4 hydrolytic enzyme.

Abstract:Primary biliary cholangitis ( PBC) is an incurable rare autoimmune liver disease with low incidence and an unclear pathogenesis. Studies have shown that external environmental factors have led to a yearly increase in incidence. Therefore, it is of great significance to establish an animal model with similar pathogenesis to study the pathogenesis and treatment of PBC. After reading relevant domestic and foreign literature over the past 20 years, we summarized the method to establish PBC animal models induced by various exogenous substances. Various exogenous (2- OA-BSA, polyI:C, N. aromaticivorans, AMA antigen and BDP ) and analyze the characteristics of various modeling method. Induction method of PBC animal models are summarized and the characteristics of various modeling method were analyzed. We provide a reference for researchers to choose more suitable animal models, explore the pathogenesis of PBC and develop new drugs.

Abstract:Social defeat stress is a social stress method based on the subordination relationship between species. It leads to depression-like and other behavioral changes through frustrating behaviors between individuals of the same animal or different strains. Currently, few studies examine anti-social defeat drugs and the existing animal models have certain shortcomings and there is no uniform standard. This article reviews recent research on the application of social defeat animal models and their pathogenesis and provides a reference animal model for the development of anti-social defeat drugs.

Abstract:As a major type of phagocyte, neutrophils are involved in many physiological and pathological processes that include inflammation, phagocytosis of pathogens, elimination of tumor cells, and removal of necrotic tissue debris, which are closely related to the ion channels in neutrophils. This review discusses various types of ion channels and their roles in neutrophils, which include voltage-gated proton channels, potassium channels, ATP-gated P2X₁ channels and chloride channels. With a focus on the ionic conductance mediated by partial ion channels in neutrophils, the pathological processes of neutrophils mediated by each channel are summarized. Recent findings are discussed from a functional perspective to contribute to selecting therapeutic targets.

Abstract:A poor prognosis in cancer patients is closely related to tumor invasion and metastasis, which is affected by many factors. A prerequisite for tumor metastasis is the breakdown of the extracellular matrix (ECM), which is a natural cellular barrier. Matrix metalloproteinase-2 ( MMP2) has a unique enzymatic activity with the ability to break through the ECM, which may promote tumor metastasis. MMP2 influences tumor invasion, metastasis and patient prognosis through various regulatory pathways in different malignant tumors and may be a marker for predicting cancer metastasis. This review demonstrates the role of MMP2 in tumor invasion and metastasis and proposes MMP2 as a new target for the diagnosis and treatment of malignant tumors.

Abstract:This article reviews dynamic pathological changes of the total blood-brain barrier (BBB) in the process of ischemic stroke as well as the destruction process of BBB in the process of ischemic stroke and the progress of current experimental method in the quantification of BBB destruction.

Abstract:Telomeres are at the ends of eukaryotes chromosomes, protect chromosomes integrity in replication. Telomeres shorten with mitosis, telomerase prolong telomeres in cells, such as embryonic stem cell. There are two protein complexes binding on telomeres: shelterin complex and CST complex. Telomerase synthesize telomeres use its RNA components. Both the telomere binding proteins and the telomerase play great role in maintaining telomere length and stability. Although telomere sequences are similar in different species, telomere and telomerase functions are not related in physiological and/ or pathological conditions. Here we review the composition and function of telomere binding protein and telomerase, to understand the biological function of telomere and provide scientific basis for the treatment of telomere dysfunction.

Abstract:Narcolepsy is a chronic nervous system disease with arousal sleep disorder. Its specific pathogenesis is unclear and it is difficult to treat by traditional Chinese and western medicines. Animal models are important to study the neuropathological mechanism and potential treatment of paroxysmal narcolepsy. This article summarizes the preparation method, evaluation, and application scope of existing animal models of paroxysmal narcolepsy to provide a reference for basic experimental research of the disease. It also provides ideas to optimize the preparation of paroxysmal narcolepsy animal models.