Pure total flavonoids from citrus alleviate oxidative stress and inflammation in nonalcoholic fatty liver disease by regulating the miR-137-3p/NOXA2/NOX2 pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become a global health issue owing to its large disease population and high morbidity. We previously reported that the improvement in oxidative stress (OS) using pure total flavonoids from citrus (PTFC), flavonoids isolated from the peel of Citrus changshan-huyou Y.B. Chan, is a crucial strategy for NAFLD treatment. However, OS-associated intervention pathways in NAFLD remain unclear. METHODS: In this study, we used microRNA (miR)- and mRNA-sequencing to identify the pathway by which PTFC improve OS in NAFLD. Clinical data, mimic/inhibitor assays, and a dual-luciferase reporter assay were selected to verify the regulatory relationships of this pathway. Moreover, in vivo and in vitro experiments were used to confime the regulatory effect of PTFC on this pathway. RESULTS: miR-seq, mRNA-seq, and bioinformatics analyses revealed that the miR-137-3p/neutrophil cytosolic factor 2 (NCF2, also known as NOXA2)/cytochrome b-245 beta chain (CYBB, also known as NOX2) pathway may be a target pathway for PTFC to improve OS and NAFLD. Additionally, bivariate logistic regression analysis combining the serum and clinical data of patients revealed NOX2 and NOXA2 as risk factors and total antioxidant capacity (indicator of OS level) as a protective factor for NAFLD. miR-137-3p mimic/inhibitor assays revealed that the upregulation of miR-137-3p is vital for improving cellular steatosis, OS, and inflammation. Dual-luciferase reporter assay confirmed that NOXA2 acts as an miR-137-3p sponge. These results co-determined that miR-137-3p/NOXA2/NOX2 is an essential pathway involved in NAFLD pathogenesis, including lipid accumulation, OS, and inflammation. In vivo and in vitro experiments further confirmed that the miR-137-3p/NOXA2/NOX2 pathway is regulated by PTFC. CONCLUSION: PTFC alleviates OS and inflammation in NAFLD by regulating the miR-137-3p/NOXA2/NOX2 pathway.

The Function and Role of the Th17/Treg Cell Balance in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder. The pathogenesis of IBD is not yet clear. Studies have shown that the imbalance between T helper 17 (Th17) and regulatory T (Treg) cells, which differentiate from CD4+ T cells, contributes to IBD. Th17 cells promote tissue inflammation, and Treg cells suppress autoimmunity in IBD. Therefore, Th17/Treg cell balance is crucial. Some regulatory factors affecting the production and maintenance of these cells are also important for the proper regulation of the Th17/Treg balance; these factors include T cell receptor (TCR) signaling, costimulatory signals, cytokine signaling, bile acid metabolites, and the intestinal microbiota. This article focuses on our understanding of the function and role of the balance between Th17/Treg cells in IBD and these regulatory factors and their clinical significance in IBD.