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Aims: It is estimated that 11.5% of patients with stroke (STR) were at risk of suffering poststroke epilepsy (PSE) within 5 years. Gut microbiota is shown to affect health in humans by producing metabolites. The association between dysregulation of gut microbiota and STR/PSE remains unclear. The aim of this study was to identify potential gut microbiota and functional component in STR and PSE, which may provide a theoretical foundation for diagnosis and treatment of STR and PSE., Methods: The fresh stool samples were collected from 19 healthy controls, 27 STR patients, and 20 PSE patients for 16S rRNA gene sequencing. Analysis of amplicon sequence variant and community diversity was performed, followed by the identification of dominant species, species differences analysis, diagnostic, and functional analysis of species in STR and PSE., Results: Community diversity was decreased in STR and PSE. Some disordered profiles of gut microbiota in STR and PSE were identified, such as the increase of Enterococcus and the decrease of butyricicoccus in STR, the increase of Escherichia Shigella and Clostridium innocuum-group and the decrease of Faecalibacterium in PSE, and the decrease of Anaerostipes in both STR and PSE. Moreover, potential diagnostic biomarkers for STR (butyricicoccus), PSE (Faecalibacterium), STR, and PSE (NK4A214_group and Veillonella) were identified. Several significantly dysfunctional components were identified, including l-tryptophan biosynthesis in STR, fatty acid biosynthesis in PSE, and Stress_Tolerant and anaerobic in both STR and PSE., Conclusion: The disturbed gut microbiota and related dysfunctional components are closely associated with the progression of STR and PSE., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Ischemic stroke (IS) causes severe neurological impairments and physical disabilities and has a high economic burden. Our study aims to identify the key genes and upstream regulators in IS by integrated microarray analysis., Methods: An integrated analysis of microarray studies of IS was performed to identify the differentially expressed genes (DEGs) in IS compared to normal control. Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression of DEGs., Results: From two Gene Expression Omnibus datasets obtained, we obtained 1526 DEGs (534 up-regulated and 992 down-regulated genes) between IS and normal control. The results of functional annotation showed that Oxidative phosphorylation and Alzheimer's disease were significantly enriched pathways in IS. Top four transcription factors (TFs) with the most downstream genes including PAX4, POU2F1, ELK1, and NKX2-5. The expression of six genes (ID3, ICAM2, DCTPP1, ANTXR2, DUSP1, and RGS2) was detected by qRT-PCR. Except for DUSP1 and RGS2, the other four genes in qRT-PCR played the same pattern with that in our integrated analysis., Conclusions: The dysregulation of these six genes may involve with the process of ischemic stroke (IS). Four TFs (PAX4, POU2F1, ELK1 and NKX2-5) were concluded to play a role in IS. Our finding provided clues for exploring mechanism and developing novel diagnostic and therapeutic strategies for IS., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

A previous study described the important regulatory roles of microRNAs (miRNAs) in ischemic stroke. However, the functional significance of long non-coding RNA (lncRNAs) in ischemic stroke was largely unknown. This study aimed to identify lncRNA profiling and elucidate the regulatory mechanisms in the pathophysiology of stroke. RNA sequencing was performed on the blood of three ischemic stroke patients and three normal controls. Differential expression analysis was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). After further correlation and co-expression analysis, the corresponding co-expression networks and miRN-lncRNA-mRNA interaction network were then constructed. The expression of DElncRNAs and DEmRNAs was verified in Gene Expression Omnibus. RNA sequencing and subsequent bioinformatics analysis produced a total of 61 DElncRNAs (14 upregulated and 47 downregulated) and 673 DEmRNAs (432 upregulated and 241 downregulated). LOC105372881 and LOC101929707 were the most highly increased and decreased lncRNAs in ischemic stroke. LncRNA-mRNA co-expression networks were constructed according to 3,008 positively co-expressed and 607 negatively co-expressed lncRNA-mRNA pairs. The DElncRNAs may play roles in the pathways of glycolysis/gluconeogenesis, arrhythmogenic right ventricular cardiomyopathy, adherens junction, lysosome, and hematopoietic cell lineage by regulating their co-expressed mRNAs. Combined with previous data, a miRNA-lncRNA-mRNA interaction network for ischemic stroke was constructed. Based on GSE22255, the expression of six DElncRNAs (CEBPA-AS1, LINC00884, HCG27, MATN1-AS1, HCG26, and LINC01184) and 11 DEmRNAs (TREML4, AHSP, PI3, TESC, ANXA3, OAS1, OAS2, IFI6, ISG15, IFI44L, and LY6E) was similar to the current sequencing data. This study is the first to identify blood lncRNAs in human ischemic stroke using RNA sequencing. The findings may be the foundation for understanding the potential role of lncRNAs in ischemic stroke.

Background: MicroRNAs (miRNAs) are part of the brain's response to ischemia. This study aimed to screen potential miRNAs for the prediction and novel treatments of ischemic stroke., Methods: Two mRNA and 1 miRNA microarray expression profile data were downloaded from the Gene Expression Omnibus database. Then, differentially expressed mRNAs and miRNAs were identified. Based on the miRNA-target pairs predicted, an miRNA-target interaction network was established. Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment) was applied to interpret the function of the miRNA targets., Results: In total, 16 differentially expressed miRNAs and 1345 differentially expressed genes were identified in ischemic stroke, respectively. Importantly, 445 miRNA-target pairs with an inverse correlation of expression were obtained, and the miRNA functional synergistic network was generated. Two miRNAs (miR-145 and miR-122) may represent potential biomarkers in ischemic stroke by being involved in the process of postischemic neuronal damage and thrombosis, respectively. Three novel miRNAs (miR-99b, miR-542-3p, and miR-455-5p) were deregulated, suggesting their roles in the pathological processes of ischemic stroke. Functional annotation indicated that apoptotic signaling cascades play an important role in patients with ischemic stroke., Conclusion: miR-145 and miR-122 represent new biomarkers and underlying targets for the prevention and treatment of ischemic stroke., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic stroke (IS) is a global health issue linked to lipid metabolism and immune cell responses. This study uses Mendelian randomization (MR) to identify genetic risk factors for IS subtypes using comprehensive genetic data from lipidomic and immune cell profiles. Methods: We assessed genetic susceptibility to IS across 179 lipids and 731 immune cell phenotypes using instrumental variables (IVs) from recent genome-wide association studies. A two-sample MR approach evaluated correlations, and a two-step MR mediation analysis explored the role of immune cell phenotypes in the lipid-IS pathway. Sensitivity analyses, including MR-Egger and Cochran Q tests, ensured robust results. Results: Genetic IVs for 162 lipids and 614 immune cell phenotypes were identified. Significant genetic causality was found between 35 lipids and large artery stroke (LAS), with 12 as risk factors (sterol esters, phosphatidylcholines, phosphatidylethanolamines) and 23 as protective factors (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols). For small vessel stroke (SVS), 8 as risk factors (sterol esters, phosphatidylcholines), and 2 as protective factors (phosphatidylinositol, sphingomyelin). For cardioembolic stroke (CS), 2 as risk factors, and 4 as protective factors. Mediation analysis revealed that CCR2 on granulocytes, CD11c on CD62L+ myeloid dendritic cells, and FSC-A on granulocytes mediated the lipid-immune cell-LAS pathway, while CD4 on activated CD4 regulatory T cells and CD4 on activated & secreting CD4 regulatory T cells mediated the lipid-immune cell-SVS pathway. Conclusion: This study identifies genetic links between specific lipids and IS subtypes, highlights immune cells' role in IS risk and mediation, suggests new therapeutic targets, and uncovers IS genetic drivers. [ABSTRACT FROM AUTHOR]