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Background. Intracerebral hemorrhage (ICH, IH) is a stroke syndrome characterized by high mortality and disability rates. However, the apoptotic mechanisms underlying ICH remain incompletely understood. We employed bioinformatics methods to identify key apoptotic genes associated with ICH, thereby offering potential therapeutic targets and contributing to a deeper understanding of the pathogenic mechanisms of apoptosis in ICH. Materials and Methods. We retrieved microarray data of ICH patients from the Gene Expression Omnibus database and intersected it with apoptotic genes, filtering out apoptosis-related differentially expressed genes (ARDEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted, and a logic regression-based diagnostic model for ICH was constructed. Key genes were identified through least absolute shrinkage and selection operator regression after model validation. Subsequently, mRNA-transcription factor (mRNA-TF), mRNA–microRNA (mRNA–miRNA), mRNA-RNA-binding protein (mRNA-RBP), and mRNA-drug regulatory networks were established, followed by immune infiltration analysis. Results. We identified 29 ARDEGs related to ICH, primarily participating in biological processes such as the extrinsic apoptotic signaling pathway and neuroinflammatory response. The ICH model confirmed PPP1R15A, IL1R1, and TYROBP as key genes with diagnostic and therapeutic value. Thirteen immune cell types showed a correlation with ICH; notably, activated dendritic cells and CD56dim natural killer cells exhibited significant correlations, and key genes were positively correlated with all 13 immune cell types. The regulatory networks (mRNA-TF, mRNA–miRNA, mRNA-RBP, and mRNA-drug) provided insights into the apoptotic gene regulation mechanisms and potential drugs in ICH. Conclusion. Through bioinformatics analysis, we identified PPP1R15A, IL1R1, and TYROBP as crucial genes in the occurrence and progression of ICH, with the potential involvement of Activated dendritic cells and CD56dim natural killer cells in these processes.

Background: During Enterovirus type 71 (EV71) infection, the structural viral protein 1 (VP1) activates endoplasmic reticulum (ER) stress associated with peripheral myelin protein 22 (PMP22) accumulation and induces autophagy. However, the specific mechanism behind this process remains elusive. Methods: In this research, we used the VP1-overexpressing mouse Schwann cells (SCs) models co-transfected with a PMP22 silencing or Autocrine motility factor receptor (AMFR/gp78) overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and apoptosis. Results: The activity of gp78 could be influenced by EV71-VP1, leading to a decrease in the ubiquitination and degradation of PMP22, resulting in PMP22 accumulation in ER. In VP1-overexpressing mouse SCs, all three ER stress sensors, including pancreatic endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1) and the related downstream signals (C/EBP-homologous protein (CHOP) and Caspase 12) were activated, as well as the ER-resident chaperone Glucoseregulated protein 78 (GRP78). In addition, VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta (LC3B), while PMP22 silencing or gp78 overexpression reversed the phenomenon. Meanwhile, PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse SCs. Conclusion: Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse SCs. Therefore, the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection. [ABSTRACT FROM AUTHOR]