Study on the effect and mechanism of Swertia mussotii Franch. in the treatment of primary biliary cholangitis based on bioinformatics and in vitro experiments

Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.

Molecular mechanisms of noncoding RNA and epigenetic regulation in obesity with consequent diabetes mellitus development

Diabetes mellitus(DM)and obesity have become two of the most prevalent and challenging diseases worldwide,with increasing incidence and serious complications.Recent studies have shown that noncoding RNA(ncRNA)and epigenetic regulation play crucial roles in the pathogenesis of DM complicated by obesity.Identification of the involvement of ncRNA and epigenetic regulation in the pathogenesis of diabetes with obesity has opened new avenues of investigation.Targeting these mechanisms with small molecules or RNA-based therapies may provide a more precise and effective approach to diabetes treatment than traditional therapies.In this review,we discuss the molecular mechanisms of ncRNA and epigenetic regulation and their potential therapeutic targets,and the research prospects for DM complicated with obesity.

Effect of NBP on the serum inflammatory cytokines, oxidative stress, and NF in patients with ACI

Objective: To explore the effect of NBP on the serum inflammatory cytokines, oxidative stress, and NF in patients with acute cerebral infarction (ACI). Methods: A total of 118 patients with ACI who were admitted in our hospital from October 2016 to September 2017 were included in the study and randomized into the observation group and the control group, with 59 cases in each group. The patients in the control group were given blood pressure control, blood sugar control, micro-circulation improvement, anti-platelet aggregation, nerve nourishing, and lipid regulation. On the above basis, the patients in the observation group were given intravenous injection of NBP sodium chloride injection. The patients in the two groups were treated for 14 d. The morning fasting venous blood before treatment, 7 d and 14 d after treatment in the two groups was collected, and centrifuged for the serum. And IL-6, TFN-α, hs-CRP, SOD, MDA, NSE, VEGF, BDNF, and bFGF were measured. Results: 7 d and 14 d after treatment, the serum IL-6, TFN-α and hs-CRP in the observation group were significantly lower than those in the control group. Besides, 7 d and 14 d after treatment, the serum SOD in the observation group was significantly higher than that in the control group, while MDA was significantly lower than that in the control group. The serum NSE 7 d and 14 d after treatment in the observation group was significantly lower than that in the control group, while VEGF, BDNF, and bFGF were significantly higher than those in the control group. Conclusions: NBP in the treatment of ACI can down regulate the expression of inflammatory cytokines to play an anti-inflammatory effect, increase the antioxidant ability to remove OFR, improve the neurocyte metabolism, and effectively play the nerve protecting and prognosis improvement role.