As a progressive chronic disease, the effective treatment for non‐alcoholic fibre liver disease (NAFLD) has not yet been thoroughly explored at the moment. The widespread use of Gynostemma pentaphyllum (Thunb) for its anti‐insulin resistance effect indicates that potential therapeutic value may be found in Thunb for NAFLD. Hence, this research aims to discover the latent mechanism of Thunb for NAFLD treatment. To achieve the goal of discovering the latent mechanism of Thunb for NAFLD treatment, molecular docking strategy integrated a network phamacology was adopted in the exploration. We acquire Thunb compounds with activeness from TCMSP database. We collect the putative targets of Thunb and NAFLD to generate the network. Key targets and mechanism are screened by PPI analysis, GO and KEGG pathway enrichment analyses. Molecular docking simulation is introduced into the study as assessment method. Through network analysis and virtual screening based on molecular docking, 2 targets (AKT 1 and GSK3B) are identified as key therapeutic targets with satisfying binding affinity. Main mechanism is believed to be the biological process and pathway related to insulin resistance according to the enrichment analyses outcomes. Particularly, the P13K–AKT signalling pathway is recognized as a key pathway of the mechanism. In conclusion, the study shows that Thunb could be a potential treatment against NAFLD and may suppress insulin resistance through the P13K–AKT signalling pathway. The result of the exploration provides a novel perspective for approaching experimental exploration.
Background: Reactive arthritis (ReA) is sterile arthritis triggered by bacterial gastrointestinal or urogenital infections. Although the pathogenesis of ReA remains unclear, genetic factors seem to play an important role. Different killer cell immunoglobulin-like receptors (KIRs) and their corresponding specific histocompatibility leukocyte antigen-C (HLA-C) ligand genotypes have been implicated in susceptibility and resistance to infections and autoimmune diseases but have, thus far, not been investigated in ReA. Methods: This study was conducted in 138 ReA patients (65 females, 73 males); aged 18–69 years (mean, 37 years) and 151 randomly selected healthy control individuals matched for ethnicity, age and sex. These subjects were genotyped for KIR genes and HLA-C alleles by polymerase chain reaction with sequence-specific primers. Results: The frequencies of inhibitory KIR2DL2 and KIR2DL5 were significantly lower in the ReA patients than in the controls (p = .005 and p = .033, respectively). The presence of more than seven inhibitory KIR genes was protective (p = .016). Moreover, we found that activating KIR2DS1 alone or in combination with the HLA-C1C1 genotype (which indicates the absence of the HLA ligands for their homologous inhibitory receptor KIR2DL1) is associated with susceptibility to ReA (p = .039 and p = .011, respectively), whereas KIR2DL2 in combination with the HLA-C1 ligand is associated with protection against ReA (p = .039). Conclusion: These observations indicate that high levels of activating and low levels of inhibitory KIR signals may affect the functions of NK cells and T cells. This imbalance enables the innate and adaptive immune responses of the host to be easily triggered by pathogens, resulting in the overproduction of local and systemic cytokines that contribute to the pathogenesis of ReA.
Objective: B‐cell activating factor (BAFF) is a key regulator of primary Sjögren's syndrome (pSS), which is characterized by B‐lymphocyte hyperactivity. BAFF, also known as tumor necrosis factor ligand superfamily member 13B, is encoded by TNFSF13B. This study aimed to explore the possible relationships between five single‐nucleotide polymorphisms (SNPs) of TNFSF13B (rs9514827, rs1041569, rs9514828, rs1224141, and rs12583006) and pSS susceptibility.Methods: We searched the following databases for articles on TNFSF13B polymorphism and pSS published up to January 2023: PubMed, Cochrane, Elsevier, Web of Science, CNKI, CQVIP, and WanFang. The odds ratios (with 95% confidence intervals) of genotypes and SNP alleles of TNFSF13B were investigated in patients with pSS to determine their relationships with pSS.Results: This meta‐analysis employing the fixed‐effect model comprised three studies of pSS patients and randomly selected healthy controls (HCs), revealing statistically significant relationships between pSS susceptibility and two SNPs: rs1041569 and rs12583006. Because rs1041569 was not in Hardy‐Weinberg equilibrium in the HC group, it was eliminated from the analysis.Conclusions: Polymorphisms in the BAFF (TNFSF13B) gene were related to vulnerability to pSS among pSS patients and HCs alike. The SNP rs12583006 was significantly related to pSS susceptibility in pSS patients.