Identification of biomarkers associated with immune-propionate metabolism in nonalcoholic fatty liver disease.

The mechanisms of the effect of propionate metabolism and immunity on nonalcoholic fatty liver disease (NAFLD) have not been adequately studied. Firstly, differentially expressed-propionate metabolism-related genes (DE-PMRGs) were selected by overlapping PMRGs and differentially expressed genes (DEGs) between the simple steatosis (SS) and health control (HC) groups. Then, common genes were selected by overlapping DE-PMRGs and key module genes obtained from weighted gene co-expression network analysis (WGCNA). Subsequently, the biomarkers were screened out by machine learning algorithms. The expression of the biomarkers was validated by quantitative Real-time PCR. In total, 5 biomarkers (JUN, LDLR, CXCR4, NNMT, and ANXA1) were acquired. The nomogram constructed based on 5 biomarkers had good predictive power for the risk of SS. Next, 5 biomarkers, 11 miRNAs, and 149 lncRNAs were encompassed in the ceRNA regulatory network. The expression of biomarkers was significantly higher in the HC group than in the SS group, which was consistent with the results in the GSE89632 and GSE126848 datasets. In this study, 5 immune and propionate metabolism-related biomarkers (JUN, LDLR, CXCR4, NNMT, and ANXA1) were screened out to provide a basis for exploring the prediction of diagnosis of NAFLD.

LPS-TLR4/MD-2-TNF-α signaling mediates alcohol-induced liver fibrosis in rats.

Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)-tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2-TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin-eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2-TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2-TNF-α signaling pathway.

Eradication of Helicobacter Pylori Infections and GERD: A systematic review and meta-analysis.

BACKGROUND/AIMS: This study evaluates the association between the eradication of Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: Relevant studies were identified by conducting literature search in PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases. The prevalence rates of gastroesophageal reflux, heartburn, epigastric pain, and nausea were extracted from the identified research articles and were used in meta-analysis of relative risks (RR) to achieve an overall effect size of the relationship between H. pylori eradication and GERD. RESULTS: A total of 19 randomized controlled trials were included in this meta-analysis. The prevalence of gastroesophageal reflux was significantly higher in patients with H. pylori eradication compared with patients without it (RR: 1.54, 95% CI: 1.06-2.24; p=0.02). A subgroup analysis did not identify any significant difference in GERD prevalence in studies conducted outside China (RR: 1.62, 95% CI: 0.98-2.68) or in China (RR: 1.30, 95% CI: 0.76-2.22). There were no significant differences in heartburn (RR: 1.03, 95% CI: 0.88-1.20), epigastric pain (RR: 0.98, 95% CI: 0.13-7.56), or nausea (RR: 0.44, 95% CI: 0.07-2.72) risk between patients with and without H. pylori eradication. CONCLUSION: Eradication of H. pylori infection is found to be associated with GERD, although regional differences may exist in the prevalence. Well-designed studies especially those with stratification of patients' basic conditions are needed to seek refined evidence of the association between H. pylori eradication and the GERD.