Purpose In recent years, Suxiao Jiuxin Pill (SJP) has emerged as a potential treatment for various cardiovascular diseases, the exact molecular mechanisms remain poorly characterized. Consequently, this study seeks to investigate the target genes associated with SJP's active components in AMI, as well as the underlying biological processes, utilizing network pharmacology (NP) and Mendelian randomization (MR) analysis. Methods To unravel SJP's targets and its regulatory mechanisms against AMI, we combined NP, MR, and molecular docking strategies. A rat MI model was established by ligating the LAD coronary artery at the designated site. PCR and immunofluorescent labeling were applied to ovserve the expression of NAMPT and FOS. Results Totally 44 DE-TGs were gained by intersecting 689 DEGs and 969 predicted target genes. Next, two key target genes, NAMPT and FOS, showing markedly upregulated expression in AMI samples. Observations showed that these genes were co-enriched in the “Leishmania Infection” and “Chemokine Signaling Pathway”. Moreover, these key target genes showed robust associations with various immune cells, of which NAMPT exhibited a strong positive correlation with neutrophils (cor = 0.65). Molecular docking revealed NAMPT bound to oleic acid (−5.9 kcal/mol) and FOS bound to pentadecanol (−5.4 kcal/mol). The PCR and immunofluorescence assay results showed that FOS was consistent with the predicted results. Echocardiographic assessments and inflammatory factor expression analyses confirmed that SJP ameliorated cardiac function and alleviated the inflammatory response in MI rats. Conclusion This work further delivers a fresh conceptual framework for deciphering the mechanistic basis of SJP's clinical utility in AMI management.
Yugen Shi, Wenjing Yi, Xue Feng et al.· Frontiers in Cardiovascular...· 0 citations
BACKGROUND
IgA nephropathy (IgAN) is an immune-inflammatory glomerulonephritis mediated by both genetic and environmental factors. Recent research indicates a close association between gut microbiota dysbiosis and IgAN development. Additionally, circulating inflammatory proteins also play a significant role in the progression of IgAN. However, the causal relationship among gut microbiota, circulating inflammatory proteins, and IgAN remains unclear.
METHODS
This study utilized publicly available Genome-Wide Association Study (GWAS) data for Mendelian randomization (MR) analysis to investigate the causal relationship among gut microbiota, circulating inflammatory proteins, and IgAN, as well as to examine the mediating role of circulating inflammatory proteins in the association between gut microbiota and IgAN. The primary analytical method employed in this study was Inverse Variance Weighted (IVW) analysis with specific attention given to Bayesian Weighted MR results and supported by MR-Egger regression, Weighted Median Model (WME), median model, and Simple Model (SM) approaches. Several sensitivity analyses were performed to evaluate the robustness of MR analysis findings.
RESULTS
(1) MR analysis of gut microbiota and IgAN indicates negative associations between g_Roseburia, g_Faecalibacterium, s_Odoribacter_splanchnicus, and s_Roseburia_unclassified with IgAN risk, while positive associations exist between s_Paraprevotella_unclassified and s_Lachnospiraceae_bacterium_7_1_58FAA with IgAN risk. (2) Circulating inflammatory proteins to IgAN in MR analysis showed that IL-10RA was negatively correlated with the risk of IgAN, while TSGP-CD5, FGF23, LIF, and TGF-α levels were positively correlated with the risk of IgAN. (3) Mediation analysis suggests that TGF-α serves as a mediator between s_Odoribacter_splanchnicus and the causality of IgAN. (4) The results of the reverse MR analysis suggest no significant causal effect of IgAN on gut flora and circulating inflammatory proteins. Sensitivity analyses consistently support the reliability of the study results.
CONCLUSION
Our research findings, obtained through genetic methods, substantiate the causal link between gut microbiota, circulating inflammatory proteins, and IgAN. The identification of biomarkers offers novel insights into the potential mechanisms underlying IgAN, which can be advantageous for early diagnosis and the development of more effective treatment strategies.
Pengpeng Dong, Xiao-Yu Li, Xue Feng et al.· International Urology and Ne...· 0 citations
