Prognostic analysis of m6A-related genes as potential biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease with limited treatment options. N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, there are few studies on m6A in IPF. This project mainly explores the prognostic value of m6A-related genes as potential biomarkers in IPF, in order to establish a set of accurate prognostic prediction model. In this study, we used GSE28042 dataset in GEO database to screen out 218 m6A-related candidate genes with high IPF correlation and high differential expression through differentially expressed gene analysis, WGCNA and m6A correlation analysis. The genes associated with the prognosis of IPF were screened out by univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis, and the multivariate Cox model of prognostic risk of related genes was constructed. We found that RBM11, RBM47, RIC3, TRAF5 and ZNF14 were key genes in our model. Finally, the prognostic prediction ability and independent prognostic characteristics of the risk model were evaluated by survival analysis and independent prognostic analysis, and verified by the GSE93606 dataset, which proved that the prognostic risk model we constructed has a strong and stable prediction efficiency.

Simvastatin Alleviates Intestinal Ischemia/Reperfusion Injury by Modulating Omi/HtrA2 Signaling Pathways.

PURPOSE: The objective of this research was to survey the therapeutic action of simvastatin (Sim) on intestinal ischemia/reperfusion injury (II/RI) by modulating Omi/HtrA2 signaling pathways. METHODS: Sprague Dawley rats were pretreated with 40 mg/kg Sim and then subjected to 1 hour of ischemia and 3 hours of reperfusion. The blood and intestinal tissues were collected, pathologic injury was observed, the contents of serum tumor necrosis factor-α and interleukin-6 (IL-6) were estimated, and superoxide dismutase, methane dicarboxylic aldehyde, and cysteinyl aspartate specific proteinase-3 (caspase-3) levels, as well as the expressions of Omi/HtrA2 and caspase-3, were measured in the intestinal tissues. RESULTS: Sim preconditioning mitigated the damnification of intestinal tissues by decreasing oxidative stress, inflammatory damage, and apoptosis and downregulating the expression of Omi/HtrA2 compared to the ischemia/reperfusion group, while Sim+Ucf-101 significantly augmented this effect. CONCLUSION: These results suggest that Sim may alleviate intestinal ischemia/reperfusion injury by modulating Omi/HtrA2 signaling pathways.

Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis.

Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. Atrasentan (Atr) has potential therapeutic values for DN. MicroRNAs (miRNAs) function as vital regulators in the pathophysiology of kidney diseases including DN. Our present study aimed to further explore whether Atr could alleviate kidney injury by regulating microRNA-21(miR-21)/forkhead box O1 (FOXO1) in DN mouse models and cell models. Blood glucose concentration and ACR ratio were determined by matching commercial kits. MiR-21 and FOXO1 mRNA level was measured by RT-qPCR assay. Protein levels of FOXO1, LC3Ⅰ, LC3Ⅱ and p62 were measured by western blot assay. Cell apoptotic index was examined by flow cytometry. The interaction of miR-21 and FOXO1 was tested by bioinformatics analysis, luciferase assay and RIP assay. We found that Atr alleviated kidney injury by inhibiting miR-21 expression and promoting autophagy in DN mice. Moreover, miR-21 loss suppressed apoptosis and induced autophagy in high glucose (HG)-treated podocytes. And, Atr inhibited cell apoptosis and improved cell autophagic activity by downregulating miR-21 in HG-cultured podocytes. Moreover, FOXO1 was identified as a target of miR-21. MiR-21 exerted its pro-apoptosis and anti-autophagy effects by targeting FOXO1 in HG-cultured podocytes. Atr enhanced FOXO1 expression by downregulating miR-21 in HG-cultured podocytes. We concluded that Atr mitigated kidney injury in DN mice and alleviated HG-mediated apoptosis increase and autophagy inhibition in podocytes by regulating miR-21/FOXO1 axis, further elucidating the molecular basis by which Atr hampered DN progression.