The impact of glycolysis on ischemic stroke: from molecular mechanisms to clinical applications

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 24, 2025

Ischemic stroke (IS), a leading cause of disability and mortality worldwide, remains significant challenge due to its complex pathogenesis. Glycolysis, central metabolic pathway, plays critical role in bridging the gap between dysfunction neurological impairment. During ischemic conditions, glycolysis replaces oxidative phosphorylation as primary energy source for brain tissue. However, ischemia–reperfusion state, neuronal cells show particular reliance on aerobic glycolysis. Immune cells, such monocytes, also contribute atheromatous plaque formation thrombi through increased Given glycolysis’s involvement various pathological stages IS, it offers potential improved diagnosis, treatment, prevention. This review comprehensively explores different phases addresses existing controversies, discusses diagnostic therapeutic applications. By elucidating intricate relationship this aims provide novel insights future research clinical advancements.

Language: Английский

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Identification immune-related hub genes in diagnosing atherosclerosis with ischemic stroke through comprehensive bioinformatics analysis and machine learning

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Atheroma plaques are major etiological factors in the pathogenesis of ischemic stroke (IS). Emerging evidence highlights critical involvement immune microenvironment and dysregulated inflammatory responses throughout IS progression. Consequently, therapeutic strategies targeting specific immune-related markers or signaling pathways within this hold significant promise for management. We integrated Weighted Gene Co-expression Network Analysis (WGCNA), CIBERSORT, machine learning (LASSO/Random Forest) to identify disease-associated modules hub genes. Immune infiltration analysis evaluated gene-immune cell correlations, while protein-protein interaction (PPI) ROC curve analyses assessed diagnostic performance. Comprehensive bioinformatics identified three genes-OAS2, TMEM106A, ABCB1-with high prognostic value stroke. profiling revealed correlations between these genes distinct populations, underscoring their roles modulating microenvironment. The performance gene panel was robust, achieving an area under (AUC) calculated as 0.9404 (p < 0.0001; 95% CI: 0.887-0.9939) atherosclerotic plaques, demonstrating superior accuracy compared conventional biomarkers. By integrating with multi-omics bioinformatics, we established a novel three-gene signature (OAS2, ABCB1) precise diagnosis atherosclerosis These exhibit dual utility may influence disease progression through modulation. Our findings provide foundation developing targeted therapies biomarker-driven clinical tools.

Language: Английский

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Exploring neuroprotective effects of PP2 in ischemic stroke via bioinformatics and experimental validation

Neurological Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: May 12, 2025

Ischemic stroke is a leading cause of mortality and disability worldwide, yet effective therapeutic options remain limited. In this study, bioinformatics analyses were used to identify potential targets small-molecule compounds for ischemic stroke. A mouse model cerebral ischemia was subsequently validate their neuroprotective efficacy. Bioinformatics methods analyze key signaling pathways hub genes associated with Additionally, the Connectivity Map (CMap) database queried treatment. Finally, middle artery occlusion/reperfusion (MCAO/R) employed further evaluate effects identified compounds. GO KEGG pathway enrichment revealed that such as TNF, NF-κB, IL-17 play crucial roles in PPI network analysis five genes-IL-1β, IL-6, ICAM-1, Jun, Fos-all closely neuroinflammatory responses. The compound PP2, selective Src kinase inhibitor, by CMap database. MCAO/R model, PP2 exhibited significant effects. It reduced infarct volume brain edema improved neurological function. Mechanistically, inhibited phosphorylation, thereby suppressing NF-κB reducing levels pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6. This study identifies promising target highlights value drug discovery mechanistic research.

Language: Английский

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Role of inflammatory cytokines and the gut microbiome in vascular dementia: insights from Mendelian randomization analysis

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

Published: Aug. 23, 2024

Background Both inflammatory cytokines and the gut microbiome are susceptibility factors for vascular dementia (VaD). The trends in overall changes dynamics of composition influenced by a variety factors, making it difficult to fully explain different effects both on subtypes VaD. Therefore, this Mendelian randomization (MR) study identified members that influence risk developing VaD their causal effects, investigated whether mediators affecting Methods We obtained pooled genome-wide association (GWAS) data 196 microbiota 41 used GWAS six subtypes, namely, (mixed), (multiple infarctions), (other), (subcortical), (sudden onset), (undefined). inverse-variance weighted (IVW) method as primary MR analysis method. conducted sensitivity analyses reverse examine associations, enhancing reliability stability conclusions. Finally, we multivariable (MVMR) assess direct VaD, performed mediation explore were potential mediators. Results Our two-sample revealed relationships between microbiota: 7 14 constituents positively correlated with increased subtype risk, while 2 11 negatively decreased risk. After Bonferroni correction, interleukin-18 was an infarctions); macrophage migration inhibitory factor onset); interleukin-4 (other); Ruminiclostridium 6 Bacillales (undefined), respectively; Negativicutes Selenomonadales (mixed); Melainabacteria infarctions). Sensitivity no multilevel or heterogeneity inverse causality microbiota. MVMR results further confirmed , remain significant. Mediation showed not Conclusion This helps us better understand pathological mechanisms suggests value targeting increases decreases prevention intervention.

Language: Английский

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Exploring the Narrative Account of Vascular Dementia: Prequels, Sequels, Parasequels and Consequels in Neurodegenerative Development

SAR Journal - Science and Research, Journal Year: 2024, Volume and Issue: unknown, P. 128 - 135

Published: June 28, 2024

This paper explores the narrative account of vascular dementia, using prequels, sequels, parasequels and consequels to illustrate its neurodegenerative development. It analyzes aphasia, lethologica, prosopagnosia, Charles Bonnet’s Syndrome, unravelling progression dementia. Drawing from literature clinical observations, it examines condition's arc, showcasing diverse manifestations trajectories. By conceptualizing dementia narratively, offers insights into cognitive impairment's evolving nature interplay neurological symptoms. Understanding this framework enhances comprehension promotes holistic approaches diagnosis, treatment, caregiver support.

Language: Английский

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