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Ischemic stroke (IS) is a severe condition regulated by complex molecular alterations. This study aimed to identify potential nicotinamide adenine dinucleotide (NAD+) metabolism-associated diagnostic markers of IS and explore their associations with immune dynamics. Weighted Gene Co-expression Network Analysis and single-sample gene set enrichment analysis (ssGSEA) were employed to identify key gene modules on the GEO dataset (GSE16561). LASSO regression was used to identify diagnostic genes. A diagnostic model was then developed using the training dataset, and its performance was assessed using a validation dataset (GSE22255 dataset). Associations between hub genes and immune cells, immune response genes, and human leukocyte antigen (HLA) genes were assessed by ssGSEA. A regulatory network was constructed using mirBase and TRRUST databases. A total of 20 NAD+ metabolic genes exhibited noteworthy expression variations. Within the module notably associated with NAD+ metabolism, 19 specific genes were included in the diagnostic model, which was validated on the GSE22255 dataset (AUC: 0.733). There were significant disparities in immune cell populations, immune response genes, and HLA gene expression, all of which were associated with the hub genes. A regulatory network composed of 153 edges and 103 nodes was constructed. This study advances our understanding of IS by providing insights into NAD+ metabolism and gene interactions, contributing to potential diagnostic innovations in IS.

Background: Lymphocyte antigen 96 (LY96) plays an important role in innate immunity and has been reported to be associated with various neurological diseases. However, its role in Parkinson's disease (PD) remains unclear. Methods: Transcriptome data from a total of 49 patients with PD and 34 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database to analyse the expression pattern of LY96 and its relationship with gene function and immune-related markers. In addition, peripheral blood samples were collected from clinical patients to validate LY96 mRNA expression levels. Finally, an in vitro cell model of PD based on highly differentiated SH-SY5Y cells was constructed, with small interfering RNA-silenced LY96 expression, and LY96 mRNA level, cell viability, flow cytometry, and mitochondrial membrane potential assays were performed. Results: The results of the analyses of the GEO database and clinical samples revealed significantly abnormally high LY96 expression in patients with PD compared with healthy controls. The results of cell experiments showed that inhibiting LY96 expression alleviated adverse cellular effects by increasing cell viability, reducing apoptosis, and reducing oxidative stress. Gene set enrichment analysis showed that LY96 was positively correlated with T1 helper cells, T2 helper cells, neutrophils, natural killer T cells, myeloid-derived suppressor cells, macrophages, and activated CD4 cells, and may participate in PD through natural killer cell-mediated cytotoxicity pathways and extracellular matrix receptor interaction pathways. Conclusion: These findings suggested that LY96 might be a novel potential biomarker for PD, and offer insights into its immunoregulatory role.

Ischemic stroke (IS) is a severe condition regulated by complex molecular alterations. This study aimed to identify potential nicotinamide adenine dinucleotide (NAD+) metabolism-associated diagnostic markers of IS and explore their associations with immune dynamics. Weighted Gene Co-expression Network Analysis and single-sample gene set enrichment analysis (ssGSEA) were employed to identify key gene modules on the GEO dataset (GSE16561). LASSO regression was used to identify diagnostic genes. A diagnostic model was then developed using the training dataset, and its performance was assessed using a validation dataset (GSE22255 dataset). Associations between hub genes and immune cells, immune response genes, and human leukocyte antigen (HLA) genes were assessed by ssGSEA. A regulatory network was constructed using mirBase and TRRUST databases. A total of 20 NAD+ metabolic genes exhibited noteworthy expression variations. Within the module notably associated with NAD+ metabolism, 19 specific genes were included in the diagnostic model, which was validated on the GSE22255 dataset (AUC: 0.733). There were significant disparities in immune cell populations, immune response genes, and HLA gene expression, all of which were associated with the hub genes. A regulatory network composed of 153 edges and 103 nodes was constructed. This study advances our understanding of IS by providing insights into NAD+ metabolism and gene interactions, contributing to potential diagnostic innovations in IS. • Identified NAD+ metabolism-associated markers for ischemic stroke (IS). • Used WGCNA and ssGSEA for key gene modules on GSE16561 dataset. • Constructed a diagnostic model using LASSO regression on GSE22255 dataset. • Explored associations between hub genes, immune dynamics, and HLA genes. • Created a regulatory network using mirBase and TRRUST databases. [ABSTRACT FROM AUTHOR]

Lymphocyte antigen 96 (LY96) plays an important role in innate immunity and has been reported to be associated with various neurological diseases. However, its role in Parkinson's disease (PD) remains unclear. Transcriptome data from a total of 49 patients with PD and 34 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database to analyse the expression pattern of LY96 and its relationship with gene function and immune-related markers. In addition, peripheral blood samples were collected from clinical patients to validate LY96 mRNA expression levels. Finally, an in vitro cell model of PD based on highly differentiated SH-SY5Y cells was constructed, with small interfering RNA-silenced LY96 expression, and LY96 mRNA level, cell viability, flow cytometry, and mitochondrial membrane potential assays were performed. The results of the analyses of the GEO database and clinical samples revealed significantly abnormally high LY96 expression in patients with PD compared with healthy controls. The results of cell experiments showed that inhibiting LY96 expression alleviated adverse cellular effects by increasing cell viability, reducing apoptosis, and reducing oxidative stress. Gene set enrichment analysis showed that LY96 was positively correlated with T1 helper cells, T2 helper cells, neutrophils, natural killer T cells, myeloid-derived suppressor cells, macrophages, and activated CD4 cells, and may participate in PD through natural killer cell-mediated cytotoxicity pathways and extracellular matrix receptor interaction pathways. These findings suggested that LY96 might be a novel potential biomarker for PD, and offer insights into its immunoregulatory role. • This study for the first time indicates that LY96 can serve as a potential diagnostic biomarker for Parkinson's disease; • This study extends the discovered biological functions of LY96 ; • This study explores the changes in the immune environment in Parkinson's disease; • This study investigated the abnormal expression of immune cells caused by LY96 in Parkinson's disease for the first time. [ABSTRACT FROM AUTHOR]