Cytoscape clusterprofiler6/2/2023 Variety of ischemic stroke experimental models by high-throughput With apoptosis, inflammation and metabolism were identified in a Rely on alterations in the transcription of various genes inducedīy ischemia and reperfusion. Important roles in the pathogenesis of CIRI, including free radicalįormation, inflammatory cells infiltration, mitochondrialĭysfunction and blood-brain-barrier disruption ( 3). Restoration of blood supply following ischemia, and peaks at ~24 hĪfter reperfusion ( 1, 2). ![]() These results may improve understanding of the potential molecular mechanism underlying the pathogenesis of CIRI at the genome‑wide level.Ĭerebral ischemia-reperfusion injury (CIRI) is aĬomplex pathophysiological process that occurs early in the The five novel CIRI‑related TFs were mainly associated with pathways of inflammation and responses to reperfusion, including the tumor necrosis factor signaling pathway (Gli2, Spi1 and Tfap2a, P=0.0035, 0.0035 and 0.048, respectively), interleuking‑17 signaling pathway (Cebpa, Gli2, Sp3, Spi1 and Tfap2a, P=0.019, 0.047, 0.019, 0.035 and 0.005, respectively) and fluid shear stress and atherosclerosis (Gli2, Sp3, Spi1 and Tfap2a, P=0.047, 0.046, 0.013 and 0.003, respectively). To the best of our knowledge, five TFs (Cebpa, Gli2, Sp3, Tfap2a and Spi1) were the first to be reported associated with CIRI in the present study. The results revealed a total of 13 CIRI‑related transcription factors (TFs), including CCAAT enhancer binding protein b (Cebpb), Cebpa, early growth response‑1, Fos, Rela, Jund, signal transduction and activator of transcription 5a/b, transformation related protein 53, GLI family zinc finger 2 (Gli2), Sp3, TF AP‑2 α (Tfap2a) and spleen focus forming virus proviral integration oncogene (Spi1). The present study systematically investigated the regulatory mechanism involved in the pathogenesis of CIRI using gene set enrichment analysis of the transient middle cerebral artery occlusion mouse stroke model. International Virtual Symposium on Healthy AgingCerebral ischemia‑reperfusion injury (CIRI) usually causes detrimental complications following reperfusion therapy in stroke patients. Heterogeneous nuclear ribonucleoprotein A1 in health and neurodegenerative disease: from structural insights to post-transcriptional regulatory roles. impact This work seeks to further advance on diagnosis of devastating age-associated degenerative state at early stage and also holds potential for uncovering molecular mechanisms to remedy and reverse the deleterious effects of Alzheimer’s disease. results Juxtaposing the DEGs, AS events, and modules of WGCNA uncovered significant genes and allowed to speculate concerning the potential mechanisms that lead to the typical Alzheimer’s disease profile, and the role of HNRNPA1 in it. Cytoscape visualized the networks thus aggregated. The pathways thus obtained underwent analysis on the subject of biological sense, and also the overlap with the DEGs by comparison in different states from the previous research (young vs. The software yielded modules-association of the genes, and these modules then went through pathway analysis on Gene Ontology and in Kyoto Encyclopedia of Genes and Genomes (KEGG) with clusterProfiler software. methods Sequenced, quality-controlled, indexed, and differential-expression analyzed genes entered the weighted gene co-expression network analysis (WGCNA) pipeline. Therefore, at next step, extracted co-expression networks and enrichment pathways showed the mechanisms of change and the place of gene in the pathway. aims/goals Initially, Differentially Expressed Gene (DEG) analysis, alternative splicing (AS) events, and sPLS-DA machine learning algorithm demonstrated a significant difference in expression profile by HNRNPA1 knockout mice. Specifically, investigating gene expression networks, which link to Alzheimer disease, and networks that alter by various genetic manipulations, in this case – the HNRNPA1 knockout – promise to shed light on the nature and flow of the pathology. ![]() International Virtual Symposium on Healthy Aging How to Cite?īackground HNRNPA1 is widely associated with neurodegenerative diseases (Bekenstein U, 2013), which in turn, commonly accompany senescence.
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