Abstract: Objective To investigate the role of the microRNA miR-488-3p in homocysteine-mediated hepatocyte autophagy through targeted regulation of the RAS oncogene family member RAP1A. Methods Human normal hepatocytes(HL-7702) were routinely cultured in vitro and administered 100 μmol / L Hcy for 24 h. Western blot was used to detect expression levels of autophagy-related proteins LC3, p62 and RAP1A in hepatocytes, whereas qRT-PCR was used to detect the expression of miR-488-3p and RAP1A in these cells. Following transfection of miR-488-3p inhibitor and mimics, qRTPCR and western blot were used to detect the transfection efficiency of miR-488-3p and its effect on LC3 and p62 protein expression. TargetScan was used to predict the correlation between miR-488-3p and RAP1A genes, whereas western blotting was used to detect changes in the expression of RAP1A, a potential downstream target protein of miR-488-3p. Pearson’s correlation coefficient was used to evaluate potential correlations between expression levels of miR-488-3p and autophagy-related proteins in hepatocytes. Results Compared with the control group, expression levels of autophagyrelated proteins LC3, RAP1A and miR-488-3p in the Hcy group were increased (P<0. 01), whereas expression of p62 was significantly decreased (P<0. 01). Following administration of miR-488-3p inhibitor and mimics, expression levels of LC3 and RAP1A proteins in the miR-488-3p inhibitor group were significantly decreased (P<0. 01) and expression of p62 was significantly increased (P<0. 01) compared with the NC-inhibitor group. Compared with the NC-mimics group, expression levels of LC3 and RAP1A proteins in the miR-488-3p mimics group were significantly increased ( P < 0. 01 ), and expression of p62 was significantly decreased (P<0. 01). Further mechanistic studies showed that RAP1A is a downstream target gene of miR-488-3p that is positively regulated by this miRNA. Pearson’ s correlation analysis indicated that the expression level of miR-488-3p was positively correlated with protein expression of LC3 ( r= 0. 9329, P= 0. 0002), but negatively correlated with p62 protein expression ( r= - 0. 8086, P= 0. 0083). Conclusions miR-488-3p is highly expressed in Hcy-mediated hepatocytes and can promote their autophagy by targeting expression of RAP1A.

Abstract: Objective To investigate the effect of dapagliflozin on the formation of atherosclerosis (AS) in apolipoprotein E knockout (ApoE^{- / -}) mice and the mechanism associated with sodium-hydrogen exchanger 1 (NHE1). Methods 24 6-week-old male ApoE^{- / -} mice were randomly divided into ordinary diet group, high-fat diet group, high-fatdiet+dapagliflozin group (10 mg / (kg·d) gavage) and high-fat diet+glimepiride group (0. 5 mg / ( kg·d) gavage). AS plaques in mouse aorta was observed by using HE staining after 8 weeks. The expression of sodium-glucose cotransporter 2 (SGTL2) in the aorta was measured by quantitative PCR and Western blot. NHE1 expression was detected by immunohistochemistry. Then, mouse macrophage cell line RAW 264. 7 cells were treated with dapagliflozin (10 μmol / L), amiloride (20 μmol / L) and lipopolysaccharide (100 ng / mL) for 24 h. The expression of NHE1 protein was analyzed by Western blot. The recovery rate ( NHE1 activity) from the NH4Cl-induced acid load was assayed by SNARF-1/ AM fluorescence method. TNF-α, IL-1β, IL-6, IL-10 secretion were determined by enzyme-linked immunosorbent assay. Results The AS plaque area in the aorta of the high-fat diet+dapagliflozin group was significantly lower than that of the high-fat diet group (P<0. 05). The expression of SGLT2 in the aortic plaques of each group was significantly decreased (P<0. 05). The plaque NHE1 expression in the high-fat diet+dapagliflozin group was lower than that in the high-fat diet group (P<0. 05). Compared with the LPS group, the LPS+dapagliflozin group had a significantly lower NHE1 protein level in the RAW 264. 7 cells ( P< 0. 05). SNARF-1 fluorescence assay indicated dapagliflozin inhibited NHE1 activity with decreasing intracellular pH (P<0. 05). ELISA showed that the contents of TNF-α, IL-1β and IL-6 in the cell supernatant were significantly decreased, whereas the content of IL-10 was significantly increased ( P< 0. 05 ). Conclusions Dapagliflozin inhibits AS plaque development and cytokine release by inhibiting NHE1 expression and its activity.

Abstract: Objective To explore the effect and mechanism of Xiaoshixionghuangsan in regulating NO levels to protect ischemic myocardium in mice. Methods C57BL/ 6J mice were randomly divided into Blank, sham, model (AMI), Xionghuang (XH), Xiaoshi (XS) and Xiaoshixionghuang ( XSXH) groups. Following establishment of the mouse myocardial infarction model, Blank, sham operation, and model groups were given normal saline, whereas the other groups were given corresponding intervention drugs. Serum levels of cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase ( LDH) were detected by ELISA at 12, 24 and 36 h after modeling. On the fourteenth day after modeling, total NO contents in serum were detected with an NO kit, pathological damage of the infarcted mouse myocardium was detected by hematoxylin and eosin staining, and the infarcted area was measured by 2,3,5-triphenyltetrazolium chloride staining. At 12 h and 14 days after Xiaoshixionghuang San administration, serum alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine, and urea nitrogen were detected by staining. Results Serum levels of cTnI, CK-MB and LDH in the XSXH group were significantly lower compared with AMI, XH and XS groups (P<0. 05). Serum NO levels in the sham group were high, but were significantly decreased in the AMI group (P<0. 05). Compared with the AMI group, NO levels in mice with myocardial infarction were significantly increased in XH and XS groups ( P< 0.01). Compared with single XS or XH, NO contents in the XSXH group were significantly increased ( P< 0. 001). Compared with the AMI group, myocardial infarct sizes in the XSXH group were significantly reduced (P<0. 05). In addition, the decoction markedly improved the degree of pathological damage to the myocardium in mice. Compared with the Blank group, indexes of liver and kidney function in the XH group were significantly increased (P<0. 01), and there was no significant difference in these indexes in the XSXH group (P>0. 05). Conclusions When the classical pathway L-Arginine-eNOS-NO pathway is inhibited during myocardial infarction, Xiaoshixionghuang San can regulate the level of NO in mice through the NO₃^--NO₂^--NO pathway to elicit a significant protective effect on ischemic mouse myocardium without obvious toxic effects on liver or kidney function.

Abstract: Objective To establish a stable mouse model of pneumonia enteritis caused by H1N1 influenza virus,and provide tools and means for study of the pathological basis of gastrointestinal influenza and antiviral drugs. Methods Experimental mice were randomly divided intofour groups ( n= 6): 10 TCID₅₀ , 1 TCID₅₀ , 0. 1 TCID₅₀ and control. All mice except the control group were intranasally infected with different doses of H1N1 influenza virus. After infection with the virus, the anal temperature and body weight of mice were measured every day, and their fur and mental state were observed for 7 consecutive days. After death, the organ index of mice was measured and mRNA expression of the H1N1 Mgene of influenza virus in lung tissue and ROR-γt in small intestine were detected by RT-PCR. Results Compared with the control group, the body weight of model group mice in 10 TCID₅₀ and 1 TCID₅₀ groups decreased significantly, the lung index increased significantly (P<0. 01), the thymus index decreased significantly (P<0. 01 and P<0. 05, respectively), and mRNA expression of the H1N1 M gene of influenza virus and ROR-γt in small intestine increased significantly (P<0. 01 and P< 0. 05, respectively). The mortality of 10 TCID₅₀ and 1 TCID₅₀ groups were 67% and 17%, respectively, while the other groups were 0. Although there were similar trends in indexes of the 0. 1 TCID₅₀ group, there was no significant difference. An infection dose of 1 TCID₅₀ was verified. Compared with the control group, the result of histological sections displayed serious pathological injuries in the lung and small intestine of the model group. Moreover, relative expression of IL-2, IL-6, IFN-γ and IL-17A in the lung tissue, as well as GM-CSF and IL-2 in small intestine, was significantly increased; in contrast, IL-6 and IL-33 in intestine were significantly decreased. Conclusions 1 TCID₅₀ virus infection was the best concentration for establishing a mouse pneumonia enteritis model. The establishment method of this model is stable and reliable, providing a good pathological model for antiviral research.

Abstract: Objective To study the effect of hypoxia-inducible factor 1α (HIF-1α) on microglia M1 polarization and its mechanism. Methods Microglia (BV-2 cells) were randomly divided into six groups: control, 10, 50, 100, 200 and 500 μg / L recombinant HIF-1α groups. Morphological changes of BV-2 cells were observed by fluorescence confocal microscopy. Changes of nuclear factor (NF)-κB p65, p-STAT1 and TRAF6 protein contents after recombinant HIF-1α protein stimulation were quantitatively analyzed by Western blot. Results Compared with the control group, microglia cells stimulated by recombinant HIF-1α protein became larger, round or phagocytic, and their processes became thicker and shorter. Intracellular NF-κB p65 and TRAF6 proteins were significantly increased compared with the control group, and the result of groups with varying concentrations of recombinant HIF-1α protein stimulation were significantly different. Conclusions HIF-1α can stimulate microglial M1 polarization and there was a dose-effect relationship between different concentrations of recombinant HIF-1α, which may be related to the regulation of TRAF6 and NF-κB activation through the TLR4 / Myd88 / NF-κB pathway.

Abstract: Objective To investigate the protective effect and biological mechanism of miR-214 on neuronal injury induced by propofol anesthesia, and elucidate the underlying mechanisms of this process. Methods Seven-day-old male Sprague-Dawley rats were randomly divided into four groups (15 rats per group): normal saline (NS), propofol anesthesia thoracotomy exploration ( model), miR-NC and miR-214. With the exception of the NS group, all groups underwent establishment of the propofol anesthesia thoracotomy exploration model. In miR-NC and miR-214 groups, miR-NC-agomir or miR-214-agomir, respectively, were injected into hippocampus before anesthesia. Expression of mTORC1 in the hippocampus was detected by immunofluorescence, apoptosis was detected by TUNEL staining, and expression of miR-214 in hippocampus was analyzed by RT-qPCR. HT22 hippocampal neurons were transfected with an miR-214 inhibitor and mTORC1 inhibitor, and then exposed to propofol. Flow cytometry was used to analyze cell survival, whereas Western blot was used to analyze protein expression of TEFB and C-caspase3. Results Compared with the NS group, miR-214 in the hippocampus of the model group was significantly downregulated (P< 0.05) and apoptosis of hippocampal neurons was significantly increased (P< 0.05). Compared with the model group, apoptosis of hippocampal neurons in the miR-214 group was decreased ( P< 0.05). Bioinformatics prediction indicated the presence of a specific binding site between mTORC1 and miR-214. Compared with the NS group, expression of mTORC1 was increased in the model group ( P<0. 05), and miR-214 treatment significantly reduced expression of mTORC1 (P<0.05). In addition, compared with the NC group, si-mTORC1 transfection significantly reduced the apoptosis rate of HT22 hippocampal neurons exposed to propofol (P< 0.05), increased TFEB expression (P< 0.01), and decreased cleaved caspase 3 ( P< 0. 05). miR-214 inhibitor transfection significantly reversed the protective effect of si-mTORC1 and changes of TFEB and C-caspase3 protein expression induced by si-mTORC1 ( P< 0.05). Conclusions miR-214 attenuates propofol neurotoxicity through the mTORC1-TFEB pathway and improves the survival rate of neurons.

Abstract: Objective To investigate the estrogen-like protective effect and mechanism of quercetin on free fatty acids (FFA)-induced hepatocyte steatosis. Methods Cell viability was detected by CCK-8 assay, and lipid accumulation in hepatocytes was observed by Oil Red O staining. Following administration of various estrogen intervention paradigms to HepG2 cells, the optimal drug intervention was determined to be post-treatment. HepG2 cells were exposed to different concentrations of estrogen and quercetin in a post-treatment manner to determine the optimal concentration of drug intervention. Cells were randomly divided into four groups: Control, model (FFA), positive drug estrogen control (E2), and quercetin (Que). Triglyceride (TG) levels were determined using the glycerol phosphate oxidase peroxidase (GPOPAP) method. Reactive oxygen species (ROS) levels were detected using DCFH-DA. Protein contents of tumor necrosis factor α ( TNF-α) were measured by enzyme-linked immunosorbent assay. Expression levels of peroxisome proliferatoractivated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),carnitine palmitoyl transferase 1α (CPT1α), and acetyl-CoA carboxylase ( ACOX1) were measured by Real-time PCR. Results It was determined that 1 μmol / L estrogen and 30 μmol / L quercetin post-treatment of HepG2 cells was optimal for subsequent experiments. Compared with the control group, numbers of red lipid droplets and TG contents were significantly increased (P<0. 001); expression levels of PGC-1α, PPARα, CPT1α and ACOX1 mRNA were significantly decreased (P<0. 05); ROS levels were increased; and TNF-α protein levels were significantly increased (P<0. 01) in the FFA group. Compared with the FFA group, both the estrogen and quercetin group displayed significantly reduced levels of red lipid droplets and ROS. Moreover, both the estrogen group (P<0. 05) and quercetin group (P<0. 05) exhibited significantly decreased TG contents, and both the estrogen group ( P< 0. 001) and quercetin group ( P< 0. 01) exhibited significantly upregulated expression of PGC-1α. In addition, both the estrogen group ( P< 0. 001) and quercetin group ( P< 0. 01) displayed significantly decreased TNF-α protein contents and significantly upregulated expression levels of PPARα ( P< 0.01),CPT1α (P<0. 001), and ACOX1 (P<0. 001). There was no significant difference in the above indicators between the quercetin group and estrogen group. Conclusions Quercetin exerts an estrogen-like effect by inducing expression of PGC-1α, activating fatty acid β oxidation, reducing oxidative stress, and inhibiting inflammatory response, ultimately improving hepatic steatosis.

Abstract: Objective The exact pathogenesis of cerebral ischemia-reperfusion injury (CIRI) remains unclear. This study explored whether ginkgo biloba extract (GBE) can improve neurological function in a CIRI rat model and the related mechanisms. Methods The CIRI rat model was induced by middle cerebral artery occlusion for 2 h, followed by reperfusion for 22 h. Varying dosages of GBE were administered intraperitoneally for 15 days. Subsequently, CIRI model rats were scored for neurological function to evaluate the effect of GBE on their motor function. In addition, 2,3, 5-triphenyltetrazolium chloride staining was used to detect the volume of infarcted brain, Western blot was used to detect expression of autophagy marker proteins and apoptosis-related proteins, the serum activities of superoxide dismutase (SOD) and glutathione (GSHpx) and serum level of malonaldehyde was detected by ELISA. Results GBE significantly improved the neurological function scores of CIRI model rats, markedly reduced cerebral infarction volumes, and significantly upregulated the activities of serum SOD and GSH-px, while decreasing the level of MDA. In addition, GBE significantly increased protein expression of Beclin-1 and protein expression ratios of LC3-II/ LC3-I and Bcl-2/ Bax, while remarkedly reducing protein expression of Caspase-3. Conclusions GBE improved the motor dysfunction of CIRI model rats by inhibiting oxidative stress and apoptosis, as well as activating the autophagy system to achieve a protective effect on brain cells.

Abstract: Objective To observe the protective effect of mogroside V against acute lung injury in rats with meconium aspiration syndrome (MAS) and to explore its possible mechanism. Methods Forty-eight healthy Wistar rats were randomly divided into sham operation, model, low-, medium- and high-dose mogroside V groups (2. 5, 5 and 10 mg /kg) and a dexamethasone group (0. 5 mg / kg) with eight mice per group. MAS models were established by oral tracheal intubation. After modeling, low-, medium- and high-dose mogroside V groups, and the dexamethasone group were administered the indicated doses of drugs, whereas model and sham operation groups were administered the same volume of normal saline. Pathological changes of lung tissues were observed by HE staining. The wet-to-dry weight ratio (W/ D) of lung tissues was calculated. The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β in serum and bronchoalveolar lavage fluid were measured by ELISA. Malondialdehyde ( MDA) and activity of superoxide dismutase (SOD) in lung tissues were detected by colorimetry. Protein expression of c-Jun N-terminal kinase ( JNK) and phosphorylated JNK (p-JNK) in lung tissues was detected by Western blot. Results Compared with the sham operation group, the pathological score of lung tissues and W/ D were increased (P<0. 05), TNF-α, IL-6 and IL-1β levels were increased in bronchoalveolar lavage fluid and serum (P<0. 05), MDA and MPO were increased in lung tissues, the SOD level was decreased (P<0. 05), and p-JNK protein expression in lung tissues was upregulated in the model group (P<0. 05). Compared with the model group, the pathological score of lung tissues and W/ D were decreased ( P< 0. 05),TNF-α, IL-6 and IL-1β levels were decreased in bronchoalveolar lavage fluid and serum (P<0. 05), MDA and MPO were decreased in lung tissues, while the SOD level was increased in medium- and high-dose mogroside V groups, and the dexamethasone group (P<0. 05). p-JNK protein expression was downregulated in lung tissues in medium- and high-dose mogroside V groups (P<0. 05). Conclusions Mogroside V may reduce inflammatory and oxidative stress damage in MAS rats by inhibiting JNK phosphorylation and thus protect them against acute lung injury.

Abstract: Objective This study aimed to explore the role and potential mechanism of miR-30 in EMT of gallbladder cancer ( GBC). Methods qRT-PCR was used to measure the relative expression level of miR-30 in gallbladder epithelial cells and cancer cell lines. After overexpression of miR-30, MTT and colony formation assays were used to assess cell proliferation. Wound healing and Transwell assays were used to evaluate cell migratory and invasive abilities, respectively. Western blot was used to evaluate the expression levels of EMT-related proteins (E-cadherin, Ncadherin and Vimentin) and EMT-related transcription factors (Snail, Slug and Zeb2). A rescue experiment was carried to explore the regulatory relationship between miR-30 and Zeb2. Results miR-30 was significantly downregulated in two representative GBC cell lines ( GBC-SD and NOZ) ( P< 0.05). Overexpression of miR-30 inhibited GBC-SD cell proliferation, colony formation, migration, invasion and EMT ( P< 0.05). Overexpression of Zeb2 reverses the EMT inhibitory effect caused by miR-30 (P<0.05). Conclusions miR-30 attenuates EMT of GBC cells by targeting Zeb2,which indicates that miR-30 is a tumor suppressor and can be used as a novel therapeutic target for GBC.

Abstract: Objective To investigate the effects of shionone on Toll-like receptor (TLR) expression and immune responses in ovalbumin (OVA)-induced asthmatic rats. Methods Twenty-four SD rats were randomly divided into four groups (six rats per group): control, model, shionone and dexamethasone. The behavioral changes of young mice were observed, as was their lung histopathology after hematoxylin and eosin staining. mRNA expression of TLRs in plasma was detected by qPCR, and serum expression levels of inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin ( IL)-1β, IL-6, IL-4 and IL-13 were detected by ELISA. Results Rats in the model group were short of breath, sneezed,displayed a purple nose and mouth, secreted mucus and were hyperactive and irritable. In addition, these rats exhibited bronchial mucosa hyperemia edema, bronchial epithelial cell death, and large numbers of infiltrating inflammatory cells in the airway and lung tissue. After treatment with shionone and dexamethasone, young mice breathed more easily and exhibited decreased mucus secretion and irritability; however, aggression was increased in the dexamethasone group. The degree of hyperemia and edema of bronchial mucosa was relieved, and numbers of inflammatory cells around the airway and lung tissue were reduced. Compared with the model group, mRNA expression levels of TLR1, TLR9 and TLR10 in shionone and dexamethasone groups were significantly increased (P<0. 01), whereas mRNA expression levels of TLR2 ~ TLR8 were significantly decreased (P<0. 01). Levels of TNF-α, IL-1β, IL-6, IL-4 and IL-13 were significantly decreased (P<0. 01). Conclusions Shionone can improve the immune response of OVA-induced SD rats and alter the expression of TLRs, laying the foundation for further study of the mechanism of shionone on TLR signaling pathways.

Abstract: Objective To investigate the effect of celecoxib on the secretion of MH7A inflammatory factor in fibroblast-like synoviocytes in rheumatoid arthritis (RA) induced by tumor necrosis factor-α (TNF-α). Methods MH7A cells were treated with 0, 2. 5, 5, 10, 20 or 40 μmol / L celecoxib for 24 h before detecting cell viability by MTT assay to screen non-toxic concentration. Enzyme-linked immunosorbent assay, real-time fluorescent quantitative PCR, and Western blot were used to detect levels of interleukin ( IL)-6, IL-1β, microRNA (miR)-129-5p, and high mobility group box-1 protein (HMGB1) in the supernatant of TNF-α-induced MH7A cells treated with 2. 5, 5 and 10 μmol / L celecoxib. A double-luciferase reporter gene assay was used to detect the targeting relationship between miR-129-5p and HMGB1, and transfection of miR-129-5p mimics or HMGB1 siRNA into MH7A cells was performed to observe the effect of miR-129-5p overexpression or downregulation of HMGB1 expression on TNF-α-induced inflammatory factor secretion in MH7A cells. In addition, an miR-129-5p inhibitor was transfected into MH7A cells induced by TNF-α to observe the effect of low miR-129-5p expression on TNF-α-induced secretion of inflammatory factors in MH7A cells treated with 10 μmol / L celecoxib. Results Compared with 0 μmol / L, the activity of MH7A cells treated with 2. 5, 5 and 10 μmol / L celecoxib exhibited no significant difference (P> 0. 05). However, the activity of MH7A cells decreased significantly after 20 and 40 μmol / L celecoxib treatment (P<0. 05). Under induction by TNF-α, 2. 5, 5 and 10 μmol / L celecoxib inhibited IL-6 and IL-1β levels in the supernatant of MH7A cells, as well as expression of HMGB1 protein, and promoted the expression of miR-129-5p in a concentration-dependent manner. miR-129-5p can target and bind to HMGB1 to negatively regulate its expression. After overexpression of miR-129-5p or downregulation of HMGB1 expression, levels of IL-6 and IL-1β in the supernatant of MH7A cells induced by TNF-α were significantly decreased ( P< 0. 05). Low expression of miR-129-5p significantly reversed the inhibitory effects of 10 μmol / L celecoxib on TNF-α-induced IL-6 and IL-1β levels in the supernatant of MH7A cells. Conclusions Celecoxib can inhibit TNF-α-induced inflammatory factor secretion by MH7A cells, and its mechanism may be related to the regulation of miR-129-5p / HMGB1.

Abstract: Objective To explore the mechanism of melatonin regulating Th1 / Th2 immune balance via targeting nuclear factor ( NF)-κB signaling pathway in mice with gastric cancer. Methods Gastric cancer cells ( 50 μg, approximately 1×10⁶ cells) were injected subcutaneously into the left forelimb of mice. After 7 days of modeling, tumor formation was felt, indicating that the model of transplanted gastric cancer tumor was successfully established. Ten healthy mice were used as the control group, whereas successfully modeled mice were divided into model and model+melatonin groups (n= 10 mice per group). The model+melatonin group was subcutaneously injected daily with melatonin (10 mg / kg, 1 time / d, 21 d), whereas the other groups were injected with the same amount of normal saline. Tumor volumes and masses were measured using a vernier caliper and balance, respectively. Proliferation and apoptosis of gastric cancer cells in tumor tissues were assessed by immunohistochemical detection of Ki67 and Bcl2. Levels of interferon ( IFN)-γ and interleukin ( IL)-4 in peripheral blood were detected by ELISA. Ratios of Th1 to Th2 cells in peripheral blood were detected by flow cytometry. Levels of NF-κB mRNA and protein were detected by qPCR and Western blot, respectively, in tumor tissues and lymphocytes. Results Contrast with the control group, the tumor volumes and masses, Ki67 and Bcl2 staining intensities, IL-4 levels, percentage of Th2 cells, NF-κB mRNA and protein expression levels were significantly increased (P<0. 05), and the IFN-γ levels, the percentage of Th1 cells and Th1 / Th2 ratio were significantly decreased in model and model+melatonin groups (P<0. 05). Contrast with model group, tumor volumes and masses, Ki67 and Bcl2 staining intensities, IL-4 levels, percentage of Th2 cells, NF-κB mRNA and protein expression levels were significantly decreased (P<0. 05) and the IFN-γ levels, the percentage of Th1 cells and Th1 / Th2 ratio were significantly increased in the model+melatonin group (P< 0. 05). Conclusions Melatonin may inhibit tumor growth in mouse models of gastric cancer and regulate the balance of Th1 / Th2 by regulating the NF-κB pathway.

Abstract:Pyroptosis, a pro-inflammatory programmed mode of cell death that relies on caspases, is accompanied by the massive release of pro-inflammatory factors. There are two main signaling pathways in pyroptosis: the classical pathway mediated by Caspase-1 and non-classical pathway mediated by Caspases-4, 5 and 11. In addition, Caspase-3 and Caspase-8 can induce pyroptosis by cleaving Gasdermin E and Gasdermin D, respectively. Recent studies have shown that pyroptosis plays an important role in the occurrence and development of cardiovascular diseases. This article briefly summarizes the relationship between pyroptosis and cardiovascular diseases including atherosclerosis, myocardial ischemia /reperfusion, heart failure, hypertension, and diabetic cardiomyopathy. In addition, we review Traditional Chinese Medicine interventions explored in recent years to provide new ideas for the prevention and treatment of cardiovascular diseases that embrace the advantages of Traditional Chinese Medicine.

Abstract:There are many problems in the clinical treatment of depression, such as the high toxicity and side effects of drugs, and high relapse rate after medication withdrawal. Accordingly, there is an urgent need for the application of Traditional Chinese Medicine approaches. Likewise, increased basic research of Traditional Chinese Medicine is also needed. However, use of animal experiments for basic research creates some problems. In particular, animal models of depression based on modern medical etiology and pathology theory cannot be well applied to research of Traditional Chinese Medicines. Therefore, disease and syndrome models are often combined to construct a combination model of disease and syndrome suitable for animal experiments of Traditional Chinese Medicines. This article describes the preparation of a combination disease and syndrome model that uses correlative research as the starting point to make it more scientifically and reasonably applied to innovative research of Traditional Chinese Medicines.

Abstract:Exosomes are small vesicles that can be secreted by most cells. Exosomes and their miRNA, mRNA and proteins play an important role in intercellular communication. Specifically, exosomes play an immunoregulatory role, participate in the pathogenesis and immunotherapy of autoimmune diseases, and can be used as effective biomarkers for diagnosis of diseases. In addition, exosomes can be used as biological carriers for drug delivery. Systemic sclerosis (SSc) is a complex autoimmune disease whose pathogenesis includes vascular damage, immune abnormalities, and fibrosis of internal organs and skin. In recent years, good progress has been made in the study of the pathogenesis of SSc, which has promoted research on clinical treatments. This article reviews the composition and function of exosomes, and their potential role in the pathogenesis, diagnosis and treatment of SSc.

Abstract:TSPAN7, a quadruple transmembrane glycoprotein encoded by the tspan7 gene located on the X chromosome, is highly expressed in brain tissue and pancreas. TSPAN7 has been found to form Tspan-enriched microdomains or TSPAN networks in cell membranes, which are involved in the regulation of biological processes such as intra- and extracellular information and material exchange, cytoskeletal dynamics, cell motility and cell morphology. In tumor cells, TSPAN7 acts as a double-edged sword with the ability to either promote or suppress tumors through its altered expression in tumor cells. In immune cells, TSPAN7 can act as a positive regulator of actin nucleation and stabilization,and is involved in the morphogenesis of dendritic cells. In neuronal cells, TSPAN7 is involved in synaptic transmission and neuronal morphogenesis In pancreatic islet cells, TSPAN7 controls the entry of calcium (Ca²⁺) into pancreatic β-cells by regulating voltage-dependent Ca²⁺ channels, thus affecting insulin secretion. TSPAN7 is also involved in the development of many diseases such as tumors, psychiatric disorders, and type 1 diabetes. This article reviews the mechanisms of TSPAN7 in various diseases, with a view to providing new ideas for animal model development, disease diagnosis, and drug intervention.

Abstract:MicroRNAs ( miRNAs) are a class of endogenous non coding small RNA, with a length of 20 ~ 23 nucleotides. MicroRNA-125 (miR-125)is a highly conserved miRNA family, which is composed of miR-125a, miR-125b-1 and miR-125b-2. More and more evidences show that miR-125 participates in a variety of pathophysiological processes in vivo, regulates the homeostasis and differentiation of a variety of cells, including immune cells, and is closely related to a variety of autoimmune diseases, which is expected to become a new therapeutic target. This paper reviews the relationship between miR-125 family and autoimmune diseases and immune cells.

Abstract: Objective Breast cancer is the malignant tumor with the highest incidence in women in China, which seriously affects the physical and mental health of patients. The preparation of animal models of breast cancer conforming to clinical characteristics is of great importance to the study of its pathogenesis and treatment. Methods Using “ breast cancer” and “animal model” as search terms, we searched China National Knowledge Infrastructure (CNKI),Wanfang, VIP and PubMed databases’ entries describing models of Chinese and Western Medicine clinical diagnostic criteria for breast cancer. We summarized breast cancer animal models of existing varieties, characteristics, and modeling method. Then we evaluated the consistency according to the clinical symptoms of Traditional Chinese and Western Medicine for breast cancer. Results We found that the existing animal model preparation method are relatively simple and mostly based on chemotherapy-induced cancer modeling method. Accordingly, these method ignore the etiology of Traditional Chinese Medicine and lack of combination model of Traditional Chinese Medicine disease. This result in large differences from clinical multi-factor disease observations, limiting research and clinical application of Traditional Chinese Medicine for the prevention and treatment of breast cancer. Conclusions Evaluation of breast cancer models is mainly based on pathological diagnosis and the formation of tumor strain (body), which is different from the Western and Chinese diagnostic criteria of breast cancer. Therefore, it is necessary to further improve the evaluation system of animal models of breast cancer, improve existing models, and make the basic research of Traditional Chinese Medicine more suitable for clinical practice.

Abstract:Animal experiments not only serve as a basic process of the clinical transformation of new compounds,but also a key step in evaluating the safety and effectiveness of new drugs. Therefore, reasonable dose setting, animal model construction, and appropriate administration method are prerequisites to ensure reliable experimental data. However, in practice, scientific researchers have not formed a unified standard for the selection of animal experimental conditions,leading to deviations in efficacy evaluations and failure to effectively promote the transformation of new compounds into clinical practice. In view of this situation, the author takes the allogeneic tumor model constructed by 4T1 cells with the participation of cisplatin as an example to explore problems and possible solutions in the pharmacodynamic study of platinum compounds for the treatment of triple negative breast cancer. It is our hope that such findings will facilitate animal experiments that better serve clinical transformation.