Genetic and Molecular Aspects of Ischemic Stroke

International Journal of Current Science Research and Review, Journal Year: 2024, Volume and Issue: 07(07)

Published: July 12, 2024

Stroke remains a leading cause of disability and death worldwide, with significant public health implications. Ischemic stroke is classified into various subtypes based on etiology, including large-artery atherosclerosis, small-vessel occlusion, cardioembolism. The middle cerebral artery often the most affected. concept ischemic core penumbra crucial in understanding pathology, where suffers irreversible damage, at high risk if reperfusion not timely. Genetic predispositions play role stroke, heritability estimates around 37.9%. Monogenic causes account for 1-5% cases, while polygenic factors are more prevalent. Genome-wide association studies (GWAS) have identified numerous genetic loci associated revealing complex architecture disease. Molecular pathways such as neuroinflammation, excitotoxicity, oxidative stress, apoptosis, autophagy involved pathophysiology stroke. Understanding these offers potential therapeutic targets. This review aims to synthesise recent provide insights future directions research clinical practice emphasising importance personalised medicine targeted therapies.

Language: Английский

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Association of metabolites on ischemic stroke subtypes: a 2-sample Mendelian randomization study

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 29, 2024

Background Metabolomics is increasingly being utilized in IS research to elucidate the intricate metabolic alterations that occur during ischemic stroke (IS). However, establishing causality these associations remains unclear between metabolites and subtypes. In this study, we employ Mendelian randomization (MR) identify specific investigate potential causal relationships Methods MR analysis was conducted using genome-wide association study (GWAS) summary data. We obtained 1,091 blood 309 metabolite ratios from GWAS Catalog (GCST90199621-90201020), which gene sequencing data 8,299 individuals Canadian Longitudinal Study. statistics for subtypes include large artery (LAS), cardioembolic (CES), small vessel (SVS) MEGASTROKE consortium included 446,696 cases of European ancestry 406,111 controls ancestry. The primary inverse-variance weighted (IVW) method. To validate our results, performed supplementary analyses employing MR-Egger, median, simple mode, mode methods. Heterogeneity pleiotropy were assessed through Cochran’s Q test, MR-Egger intercept leave-one-out analysis. Results possible serum risk discovery significant links 33 3 distinct Conclusion Metabolites show as circulating biomarkers offer promise clinical applications prevention screening These discoveries notably advance comprehension molecular processes create avenues investigating targeted treatment approaches future.

Language: Английский

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Fine mapping-based multi-omics analysis interprets the gut-lung axis function of SGLT2 inhibitors

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 10, 2024

Currently, Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrate additional effects beyond glucose control on the gut microbiota and circulating metabolites. The metabolites have been found to be useful in elucidating potential biological mechanisms of pulmonary diseases. Therefore, our study aims investigate mediating SGLT2 inhibition 10 diseases through Mendelian randomization (MR) research.

Language: Английский

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Shared genetic correlations between kidney diseases and sepsis

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: July 17, 2024

Clinical studies have indicated a comorbidity between sepsis and kidney diseases. Individuals with specific mutations that predispose them to conditions are also at an elevated risk for developing sepsis, vice versa. This suggests potential shared genetic etiology has not been fully elucidated.

Language: Английский

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From serum metabolites to the gut: revealing metabolic clues to susceptibility to subtypes of Crohn’s disease and ulcerative colitis

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 8, 2024

Inflammatory bowel disease (IBD) is a common chronic inflammatory characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases intestinal system, so we aimed assess causal relationship between blood susceptibility IBD subtypes.

Language: Английский

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Immune cells, circulating inflammatory factors and neurodevelopmental disorders: a bidirectional mendelian randomization and mediation analysis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

The roles of various immune cells and circulating inflammatory factors in neurodevelopmental disorders (NDDs) remain controversial. Therefor we employed a two sample bidirectional mendelian randomization mediation method to explore the causal relationships between cells, factors, NDDs. All data were originated from GWAS datasets. We found significant positive relationship 13 ASD, including six CD8 + T cell, one CD3 CD20 B CD38 plasmacytoid DC. 9 showed with ASD: four interleukins (IL-7, IL-2, IL-18) negatively associated, while five positively such as TNF-α. 14 exhibited ADHD. on naive CD8br CD4 activated Treg CD27-expressing associated ASD. Four CD40-expressing monocytes 7 had ADHD: Fibroblast Growth Factor 23 levels (FGF-23), CD40L receptor levels, Glial Cell Line-Derived Neurotrophic levels(GDNF), TNF-α more important among these. Mediation analysis identified 12 mediating relationships, three showing strong evidence: Natural killer cell 2B4 (19.9%), (11%) Eotaxin (-5.95%). There strongly Inflammatory mediated pathways

Language: Английский

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Mendelian randomization study of urolithiasis: exploration of risk factors using human blood metabolites

BMC Urology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Aug. 28, 2024

Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood. In our study, we employed bi-directional two-sample Mendelian randomization (MR) analysis to investigate associations metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as primary approach, complemented by several other estimators including MR-Egger, median, colocalization MR-PRESSO. Furthermore, study included replication meta-analysis. Finally, conducted pathway elucidate potential pathways. After conducting multiple tests for correction, glycerol might contribute dehydroisoandrosterone sulfate (DHEA-S) inhibit this process. had shown relationship. Among protective were lipids (dehydroisoandrosterone 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine 2-aminobutyrate), keto acid (acetoacetate) carbohydrate (mannose). risk (1-palmitoylglycerophosphoethanolamine, cortisone), (erythronate), peptide (pro-hydroxy-pro) fatty (eicosenoate). reverse MR analysis, demonstrated statistically significant butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine leucylalanine. However, it worth noting that none of exhibited statistical significance after corrections. Additionally, identified one urolithiasis. results obtained demonstrate relevance two urolithiasis, well identify potentially its development. Given high prevalence further investigations are encouraged mechanisms these explore novel therapeutic strategies.

Language: Английский

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