Network analysis and experimental verification of Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair in the treatment of non-alcoholic fatty liver disease.

CONTEXT: There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear. OBJECTIVE: Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD. METHODS: The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein-protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments. RESULTS: Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. DISCUSSION AND CONCLUSION: The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy.

LncRNA HOTAIR accelerates free fatty acid-induced inflammatory response in HepG2 cells by recruiting SRSF1 to stabilize MLXIPL mRNA.

LncRNA HOTAIR has been reported to be associated with metabolic diseases of the liver. However, the effect of HOTAIR on non-alcoholic fatty liver disease (NAFLD) inflammation and its potential mechanism have not been reported. Genes and proteins expression were detected by qRT-PCR and Western blot respectively. The level of inflammatory cytokines was assessed by ELISA. HepG2 cell viability was detected by MTT assay. TG level and lipid accumulation were measured by Assay Kit and Oil red O staining, respectively. Direct binding relationship between HOTAIR and Serine/arginine splicing factor 1 (SRSF1), SRSF1 and MLX interacting protein like (MLXIPL) were confirmed by RNA-pull down and RIP assay. HOTAIR was highly expressed in free fatty acids (FFA)-treated HepG2 cells. HOTAIR knockdown alleviated FFA-induced inflammation of HepG2 cells. Then further analysis showed that HOTAIR and SRSF1 had a mutual binding relationship, and HOTAIR maintained MLXIPL mRNA stability via recruiting SRSF1 in HepG2 cells. Moreover, the inhibitory effect of HOTAIR knockdown on FFA-induced inflammation in HepG2 cells was reversed by MLXIPL overexpression. HOTAIR accelerates inflammation of FFA-induced HepG2 cells by recruiting SRSF1 to stabilize MLXIPL mRNA, which will help to find new effective strategies for NAFLD therapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00614-x.

Electronic Interactive Games for Glycemic Control in Individuals With Diabetes: Systematic Review and Meta-Analysis.

BACKGROUND: Several electronic interventions have been used to improve glycemic control in patients with diabetes. Electronic interactive games specific to physical activity are available, but it is unclear if these are effective at improving glycemic control in patients with diabetes. OBJECTIVE: This study aimed to determine the effects of electronic game-based interventions on glycemic control in patients with diabetes. METHODS: Relevant studies that were published before April 1, 2023, were searched from 5 databases: PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Eligibility criteria included prospective studies examining the relationship between electronic games with physical activities or diet education and glycemic control as the outcome. The risk of bias was assessed using the Cochrane risk-of-bias tool. All analyses were conducted using RevMan5.4.1. Depending on the heterogeneity across studies, the pooled effects were calculated using fixed-effects or random-effects models. RESULTS: Participants from 9 studies were included and assessed. Glycated hemoglobin (HbA1c) and fasting blood glucose improved in the intervention group, although the analysis revealed no significant reduction in HbA1c (-0.09%, 95% CI -0.29% to 0.10%) or fasting blood glucose (-0.94 mg/dL, 95% CI -9.34 to 7.46 mg/dL). However, the physical activity of individuals in the intervention group was significantly higher than that of those in the control group (standardized mean difference=0.84, 95% CI 0.30 to 1.38; P=.002). Other outcomes, such as weight and blood lipids, exhibited no significant improvement (all P>.05). CONCLUSIONS: Electronic games had a good impact on participants' physical activity and offered an advantage in glycemic control without reaching statistical significance. Electronic games are convenient for reminders and education. Low-intensity exercise games may not be considered a better adjuvant intervention to improve diabetes self-management care.