No abstract

The present study enumerates the discovery and development of novel thiazolidin‐4‐one‐1,3,5‐triazine as neuro‐protective agent against cerebral ischemia–reperfusion injury in mice. These compounds showed significant inhibition of NF‐ĸB transcriptional activity in LPS‐stimulated RAW264.7 cells, displaying compound 8k as most potent inhibitor among the tested derivative. The compound 8k was further studied in in vivo middle cerebral artery occlusion (MCAO) mice model for neuro‐protective action. Results suggest that compound 8k causes attenuation of inflammation (TNF‐α, IL‐β, and IL‐6), oxidative stress (SOD, GSH, and MDA), and apoptosis (Bcl‐2, Bax, and cleaved caspase‐3) in MCAO mice in concentration‐dependent manner. Collectively, our results documented that compound 8k pre‐treatment protects cerebral I/R. This novel lead scaffold may be helpful for investigation of new neuro‐protective agent by inactivation of NF‐ĸB.

Background: We aimed to develop a diagnostic indicator of stroke based on serum miRNAs correlated to systolic blood pressure. Methods: Using miRNA expression profiles in GSE117604 from the Gene Expression Omnibus (GEO), we utilized the WGCNA to identify hub miRNAs correlated to systolic blood pressure (SBP). Differential analysis was applied to highlight hub differentially expressed miRNAs (DE-miRNAs), whereby we built a miRNA-based diagnostic indicator for stroke using bootstrap ranking Least Absolute Shrinkage and Selection Operator (LASSO) regression with 10-fold cross-validation. The classification value of the indicator was validated with receiver operating characteristic (ROC) analysis in both the training set and test set, as well as quantitative real-time PCR (qRT-PCR) for the feature miRNAs. Further, target genes of hub miRNAs and hub DE-miRNAs were retrieved for functional enrichment. Results: A total of 447 hub miRNAs in the blue modules were significantly correlated with systolic blood pressure (r = 0.32, false discovery rate = 10−6). Target genes predicted with the hub miRNAs were mostly implicated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) terms including mitogen-activated protein kinase (MAPK) pathway, senescence, and TGF-β signaling pathway. The diagnostic indicator with miR-4420 and miR-6793-5p showed remarkable performance in the training set (area under curve [AUC]= 0.953), as well as in the test set (AUC = 0.894). Results of qRT-PCR validated the diagnostic value of the two miRNAs embedded in the proposed indicator. Conclusions: We developed a panel of two miRNAs, which is a good diagnostic indicator for stroke. These results require further investigation.