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We investigated the mechanism whereby double‐negative T cells (DNTs) regulate Treg/Th17 balance to promote the progression of liver fibrosis. Liver fibrosis was induced with carbon tetrachloride (CCl4) in mice. Mouse DNTs were isolated, amplified and injected. The proportions of iTreg (CDF4+CD25+Foxp3+) and Th17 (CD4+IL‐17A+) in peripheral mononuclear cells, spleen and liver were analyzed by flow cytometry, and the cytokine levels were determined through enzyme‐linked immunosorbent assay (ELISA). DNTs could promote the Th17 differentiation and inhibit the iTreg differentiation. The role of DNTs in promoting liver fibrosis progression and tissue inflammation was exerted through activation of IκBa. The use of IL‐17A monoclonal antibody enabled suppression of the DNTs effects, reduction of the Th17 proportion and alleviation of liver fibrosis. Hal could suppress the Th17 differentiation and the effect of DNTs. DNTs can promote the Th17 differentiation through IL‐17A and inhibit iTreg differentiation, thereby facilitating the liver fibrosis progression and microenvironmental inflammation. DNTs are a kind of important immunocytes that promote the liver fibrosis progression. [ABSTRACT FROM AUTHOR]

We investigated the role and mechanism of ginsenoside RD (GRD) in acute liver injury. Network pharmacology was used to analyze the correlations among GRD‐liver injury‐pyroptosis targets. A mouse model of acute liver injury was established by lipopolysaccharide + d‐galactose（LPS + d/Gal). After pretreatment with GRD, the changes in mouse liver function were detected. The histopathological changes were assayed by hematoxylin and eosin and Masson staining, the tissue expressions of inflammatory cytokines were detected by enzyme‐linked immunosorbent assay, and the protein expressions were assayed by immunohistochemical staining and Western blotting. Meanwhile, mechanism research was conducted using STAT3‐knockout transgenic mice and STAT3‐IN13, a STAT3 inhibitor. GRD inhibited liver injury, mitigated tissue inflammation, and suppressed STAT3‐mediated pyroptosis in mice. After applying STAT3‐knockout mouse model or STAT3‐IN13, GRD did not further inhibit the liver injury. GRD can resist liver injury by inhibiting the STAT3‐mediated pyroptosis, which is one of the hepatoprotective mechanisms of GRD. [ABSTRACT FROM AUTHOR]

We investigate the mechanism of action of astragalin (AST) in the treatment of Alzheimer's disease (AD). Network pharmacology was conducted to analyze the relationships among AST, AD, and neuroinflammation, The APP/PS1 transgenic mice with AD were used in the experiments; to be specific, the influence of AST on the behavior of mice was analyzed by Morris water maze and eight‐arm radial maze tests, the tissue inflammatory factor levels were detected by ELISA, and pathological changes were analyzed by H&E and immunohistochemical staining. Analysis results of network pharmacology suggested that AST exerted the multi‐target effect on neuroinflammation in AD. Through molecular docking and dynamics analyses, COX2 might be the target of AST. Moreover, animal experimental results demonstrated that AST improved the behavior of AD mice, and enhanced the motor and memory abilities, meanwhile, it suppressed the expression of inflammatory factors in tissues and the activation of microglial cells. this study discovers that AST can suppress microglial cell activation via COX2 to improve neuroinflammation in AD. [ABSTRACT FROM AUTHOR]

Bellamya purificata is an important medicinal value and economically farmed species in China. However, because little is known about the genetic characteristics of this species, the utilization of high-quality germplasm resources is hindered. The study examined the genetic differentiation between, and the structure of 12 B. purificata populations in Guangxi using 7 microsatellite DNA markers. High genetic diversity occurred in each population, with mean observed heterozygosity 0.655 and a mean expected heterozygosity 0.832. Analysis of molecular variance reveals genetic diversity to be greater within (95.2%) than among populations (4.8%). Genetic differentiation between populations is weak (Fst = 0.048, P < 0.001), with mixing of genetic clusters prevalent at the level of the individual. Genetic flow exists between populations (Nm = 3.084–11.778), with Longshui and Guilin populations exchanging frequently. A Mantel test reveals a low correlation between geographic and genetic distances (r = 0.2482, P < 0.071), suggesting that dispersal between neighboring populations facilitates population exchange. No significant heterozygosity excess was observed for any population (P > 0.05), indicating a lack of recent genetic bottlenecks. The results provide important genetic information for B. purificata, and data for potential germplasm discovery and aquaculture development. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the role of protein kinase HIPK2 in depression and its associated mechanism. The chronic unpredictable mild stress (CUSM) model was constructed to simulate mice with depression to detect the mouse behaviors. Moreover, by using mouse microglial cells BV2 as the model. After conditional knockdown of HIPK2, the depressive behavior disorder of mice was improved, meanwhile, neuroinflammation was alleviated, and the M1 cell proportion was reduced. Similar results were obtained after applying the HIPK2 inhibitor tBID or ASO‐HIPK2 treatment. HIPK2 was overexpressed in BV2 cells, which promoted M1 polarization of cells, while tBID suppressed the effect of HIPK2 and reduced the M1 polarized level in BV2 cells. Pull‐down assay results indicated that HIPK2 bound to STAT3 and promoted STAT3 phosphorylation. We found that HIPK2 can bind to STAT3 to promote its phosphorylation, which accelerates M1 polarization of microglial cells, aggravates the depressive neuroinflammation, and leads to abnormal behaviors. HIPK2 is promising as the new therapeutic target of depression. [ABSTRACT FROM AUTHOR]

Zeste 12 Homolog (SUZ12), as a transcription factor, has been found to be highly expressed in a variety of tumors and promote tumor progression. We focus on revealing its role and mechanism in gastric cancer. Cellular level studies were conducted in mouse gastric cancer MFC cells by performing overexpression of SUZ12, overexpression of CDK6, and treatment with CDK6 inhibitor, respectively. Changes in cell viability, invasion, metastasis and colony formation were detected, and the expression variations of cell cycle regulatory proteins CDK6, P21, and Cyclin D were determined. During the animal experimentation, a mouse xenograft model was established. After transplantation of SUZ12‐overexpressing MFC‐SUZ12, the tumor growth was compared with that in MFC, and the tissue expressions of CDK‐6, SUZ12, and Cyclin D were examined. Overexpression of SUZ12 could enhance the viability of MFC cells while upregulating their migration, invasion and colony formation abilities, which promoted the expression of CDK6, P21, and Cyclin D. CDK6 inhibitor, on the other hand, could suppress the effects of SUZ12 overexpression and weaken the cell viability and malignant behavior. Overexpression of CDK6 also promoted the MFC viability and malignant behavior. We found that SUZ12 exerted its effects by promoting the expression of downstream cyclin CDK6. At the animal level, the mice xenografted with SUZ12‐overexpressing MFC cells exhibited larger tumor volumes, as well as elevated cyclin expression. SUZ12 promotes the proliferation and malignant behavior of gastric cancer cells by regulating the expression of downstream CDK6. [ABSTRACT FROM AUTHOR]

This work aimed to investigate the role of helper T cell 1 (Th1) in chronic colitis and its immunoregulatory mechanism. The proportions of Th1 and Th2, and the levels of related cytokines in tissues from patients with inflammatory bowel disease (IBD; ulcerative colitis+Crohn's disease, UC+CD) were detected. DSS was used to induce the mouse model of IBD; thereafter, Th1 cells were induced in vitro and amplified before they were injected intraperitoneally. Later, the changes in life state and body weight of mice were observed, the proportion of M1 macrophages in mucosal tissues and mucosal barrier damage were detected. After treatment with macrophage scavenging agent (Clodronate Liposomes, CLL), the influence of Th1 on IBD mice was observed. Then, the intestinal macrophages were co-cultured with Th1 in vitro to observe the influence of Th1 on the polarization of intestinal macrophages. Besides, cells were treated with the STAT3 inhibitor to further detect the macrophage polarization level. Intestinal macrophages were later co-cultured with intestinal epithelial cells to observe the degree of epithelial cell injury. The Th1 proportions in intestinal tissues of UC and CD patients were higher than those in healthy subjects, but the difference in Th2 proportion was not significant. In the IBD mouse model, Th1 induced the M1 polarization of macrophages, aggravated the intestinal inflammatory response, and resulted in the increased mucosal barrier permeability. Pretreatment with CLL antagonized the effect of Th1 cells, reduced the intestinal tissue inflammatory response and mucosal barrier permeability.