The mechanism study of Miao medicine Tongfengting decoction in the treatment of gout based on network pharmacology and molecular docking.

AIM: This study sought to clarify the mechanism of action of Miao medicine Tongfengting decoction in the treatment of gout through network pharmacology and molecular docking by searching for its key targets and related pathways. METHODS: The active ingredients of Miao medicine Tongfengting Decoction were obtained from the TCMSP data platform, searched the relevant databases for gout-related targets,using String and Cytoscape 3.9 to build a "compound-cross-target-disease" network diagram,performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis in the DAVID database, and performed the docking analysis using PyMoL 2.3.0 and AutoDock. RESULTS: After screening, 298 main targets of the Miao medicine Tongfengting decoction for gout were identified. The target network is established, and the topology of protein-protein interaction (PPI) network is analyzed. The enrichment analysis of KEGG pathway showed that these targets were related to Pathways in cancer, PI3K Akt signaling pathway, MAPK signaling pathway and other pathways. Molecular docking showed that the target protein had good binding power with the main active components of the compound of Miao medicine Tongfengting Decoction. CONCLUSION: Miao medicine Tongfengting decoction probably regulates immune mechanism using a multi-component, multi-target, and multi-pathway strategy to reduce inflammatory response and exert its therapeutic effect on gout.

LncRNA HOTTIP from synovial fibroblast-derived exosomes: A novel molecular target for rheumatoid arthritis through the miR-1908-5p/STAT3 axis.

Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. HOTTIP, a long noncoding RNA (lncRNA), participates in cell proliferation and invasion. However, the correlation between HOTTIP and RA remains unclear. Therefore, this study aimed to clarify how HOTTIP works in RA and to investigate its role in the development of RA. Flow cytometry was used to analyze cell cycle progression. Binding between HOTTIP, signal transducer and activator of transcription 3 (STAT3) and miR-1908-5p was demonstrated by dual-luciferase assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T cell differentiation-related proteins. We found that HOTTIP was upregulated in rheumatoid arthritis synovial fibroblasts (RASFs). HOTTIP directly bound to miR-1908-5p and negatively modulated miR-1908-5p expression while positively regulating STAT3. The effects of HOTTIP overexpression on regulating the balance of the Th17/Treg cell ratio were partly reversed by miR-1908-5p overexpression. In addition, in vivo experiments demonstrated that overexpression of HOTTIP aggravated inflammation in RA mice, which was demonstrated by hematoxylin and eosin (HE) staining and the increased expression levels of CD4+ interleukin (IL)-17+, forkhead Box P3 (FOXP3) and retinoid-related orphan receptor gamma-t (RORγt). In summary, our study suggests that HOTTIP plays a damaging role in RA by promoting inflammation, which may be related to the regulation of miR-1908-5p expression and the STAT3 signaling pathway. These results suggest that the regulation of HOTTIP may be a promising therapeutic strategy for RA.

Association of maternal folate intake during pregnancy with infant asthma risk.

Several studies assessed the association of maternal folate intake with infant asthma risk, but the findings are controversial. We performed a meta-analysis to clarify the association between maternal folate intake and infant asthma risk. PubMed and SCOPUS databases were searched for related studies published until August 2018. Fixed-effects models were applied to pool relative risks (RRs) and their corresponding 95% confidence intervals (CIs) due to the low heterogeneity. We also adopted generalized least-squares trend (GLST) estimation for the dose-response analysis. In our study, a total of 10 studies with maternal folate intake and 5 studies with blood folate concentration were included. We found that maternal folate intake during pregnancy was significantly related to the risk of infant asthma (RR = 1.11; 95% CI = 1.06-1.17). Similar results were found for geographic region from Europe (RR = 1.08; 95% CI = 1.01-1.16) and North America (RR = 1.20; 95% CI = 1.11-1.30) in subgroup analyses. Meanwhile, the dose-response analysis showed a linear relationship between maternal folic acid intake during pregnancy and infant asthma risk. This meta-analysis indicates that maternal folate intake during pregnancy could increase infant asthma risk. Therefore, the adverse effect of folic acid on infant asthma should not be ignored when it is supplemented during pregnancy to prevent birth defects.