Unlocking the therapeutic capabilities of GPCR in the treatment of ischemic stroke: A translational literature DOI Creative Commons

Brunda Girish,

B S Nikitha,

K Roopa

et al.

Medicine in Drug Discovery, Journal Year: 2024, Volume and Issue: 24, P. 100197 - 100197

Published: Aug. 23, 2024

GPCRs are a class of membrane proteins that essential to signal transduction, and this is vital process in many different physiologies. The significant mortality rate widespread occurrence stroke highlight the need accelerate research develop viable treatment agents. A promising prospect for development new approaches increasing comprehension pathophysiology crucial roles played by GPCRs. Because blood clot, glial cells' vascular supply abruptly cut off, which sets off series events include inflammation neuronal damage ultimately lead cell death. Numerous therapeutic treatments, including thrombolytic agents like tissue plasminogen activator urokinase, have been discovered as potential neuroprotective medicines; however, their use restricted because modest window. Accepting pertinent factors ischemic stroke, we explore medicinal promise GPCR-targeted treatments shortcomings ought be resolved order translate these discoveries clinical cases.

Language: Английский

Kaempferol Treatment and Rehabilitation Training Recover the Neurological and Motor Functions in Cerebral Ischemic Injury-induced Rats via MyD88/TLR-4 Pathway DOI Creative Commons

Jingwen Shao,

Shaoyi Qu,

JingWang

et al.

Pharmacognosy Magazine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Background Cerebral ischemic stroke, a devastating neurological condition, occurs when the blood supply to specific region of brain is interrupted, leading cascade complex physiological and biochemical processes that ultimately result in cellular dysfunction tissue damage. Purpose This study was dedicated assessing beneficial activities kaempferol along with rehabilitation training improving cerebral stroke-induced complications experimental rat model. Materials Methods The rats underwent middle artery occlusion initiate stroke. subsequently treatment alone or combination. rats’ neurobehavioral, balance beam, rotary stick scores were evaluated. concentrations inflammation-associated proteins apoptotic protein levels assessed hippocampal tissues using commercial diagnostic kits. Results combination significantly decreased Furthermore, successfully diminished levels. It regulated pro- anti-apoptotic Conclusion present research highlighted can enhance regaining neurobehavioral motor functions findings may facilitate advancement as new therapeutic candidate treat

Language: Английский

Citations

0
Association between C-reactive protein-albumin-lymphocyte index and stroke: an NHANES analysis (1999–2010) DOI Creative Commons
Yizhou Chen, Meifang Liu, Yi Zhang

et al.

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

Published: April 2, 2025

Objective This cross-sectional study is based on the NHANES (1999–2010) database and aims to explore potential relationship between CALLY index stroke in U.S. population. Methods utilized data from (1999–2010), including 17,511 American participants after cleaning. Laboratory markers related were obtained through standardized biological sample collection analysis procedures performed by trained professionals. Stroke status was determined self-reported questionnaires. Various statistical methods employed examine association stroke, as well its predictive efficacy for risk, multivariable logistic regression, subgroup analysis, RCS ROC analysis. Results Among analyzed, our findings revealed a nonlinear L-shaped negative risk. In Model 3, higher significantly associated with lower risk (OR: 0.99, 95% CI: 0.98–0.99, p = 0.045). Additionally, highest quartile (Q4) of had 25% likelihood compared those lowest (Q1) 0.75, 0.58–0.97, 0.030). Furthermore, demonstrated that superior performance SIRI SII indices. Conclusion A reduced may be linked stroke. demonstrates The provides valuable insights future prevention management strategies.

Language: Английский

Citations

0
Neuroinflammation and energy metabolism: a dual perspective on ischemic stroke DOI Creative Commons
Lei Wen, Hao Zhuang, Weiyi Huang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 10, 2025

Ischemic stroke is a prevalent form of cerebrovascular accident, with its pathogenesis involving the intricate interplay between neuroinflammation and energy metabolism. Cerebral ischemia disrupts oxygen supply, triggering metabolic dysregulation activating neuroinflammatory responses, ultimately resulting in cellular damage. This review provides an exhaustive analysis complex mechanisms ischemic stroke, particular focus on interaction The interruption supply due to cerebral initiates activates including release inflammatory cytokines activation immune cells, contributing damage further disturbances. Studies indicate that metabolism significantly impairs neural cell function interacts neuroinflammation, exacerbating brain injury. Therapeutic strategies primarily concentrate modulating suppressing emphasizing importance in-depth research into their provide theoretical foundation for new treatment stroke. Future should how balance anti-inflammatory regulation minimize promote recovery.

Language: Английский

Citations

0
Identification immune-related hub genes in diagnosing atherosclerosis with ischemic stroke through comprehensive bioinformatics analysis and machine learning DOI Creative Commons
Ming Zhang, Lijun Tang, Shi-Yu Long

et al.

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

Published: April 30, 2025

Background 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. Methods 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. Results 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. Conclusion 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

Citations

0
Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke DOI Creative Commons
Jiangjun Zhang, Zhong Chen, Qi Chen

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(8), P. 1848 - 1848

Published: April 18, 2024

In recent years, the frequency of strokes has been on rise year by and become second leading cause death around world, which is characterized a high mortality rate, recurrence disability rate. Ischemic account for large percentage strokes. A reperfusion injury in ischemic complex cascade oxidative stress, neuroinflammation, immune infiltration, mitochondrial damage. Conventional treatments are ineffective, presence blood–brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers turning their attention nano-drug systems. Functionalized systems have widely studied applied study cerebral diseases due favorable biocompatibility, efficiency, strong specificity, specific targeting ability. this paper, we briefly describe pathological process injuries focus therapeutic research progress strokes, aiming provide certain references understand (NDDSs).

Language: Английский

Citations

3
The interplay between cytokines and stroke: a bi-directional Mendelian randomization study DOI Creative Commons
Yingying Jiang, Qingying Liu,

Chunyang Wang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 26, 2024

Stroke, the second leading cause of death and disability, causes massive cell in brain followed by secondary inflammatory injury initiated disease associated molecular patterns released from dead cells. Nonetheless, evidence regarding causal relationship between cytokines stroke subtypes is obscure. To leverage large scale genetic association data to investigate interplay circulating stroke, we adopted a two-sample bi-directional Mendelian randomization (MR) analysis. Firstly, performed forward MR analysis examine associations genetically determined 31 with 6 subtypes. Secondly, conducted reverse check cytokines. In analysis, suggests that 21 were significantly certain subtype risk |β| ranging 1.90 × 10−4 0.74. our results found five (intracerebral hemorrhage (ICH), artery atherosclerosis ischemic (LAAS), lacunar (LS), cardioembolic (CEI), small-vessel (SV)) caused changes 16 1.08 0.69. particular, those statistically C-reactive protein (CRP). addition, ICH, LAAS, LS SV correlated vascular endothelial growth factor (VEGF), while LS, CEI related fibroblast (FGF). Moreover, integrated these factors (IL-3Rα, IL-6R, IL-6Rα, IL-1Ra, insulin-like factor-1(IGF-1), IL-12Rβ2) can be used as predictors some specific As well as, IL-16 C–C motif chemokine receptor 7 (CCR7) prognostic stroke. Our findings identify potential pharmacological opportunities, including perturbation for both predicting post treatment effects. comprehensive search existing publicly available GWAS database, have good population-generalizability.

Language: Английский

Citations

2
A potential role of gut microbiota in stroke: mechanisms, therapeutic strategies and future prospective DOI
Manpreet Kaur, Khadga Raj Aran,

Raju Paswan

et al.

Psychopharmacology, Journal Year: 2024, Volume and Issue: 241(12), P. 2409 - 2430

Published: Oct. 27, 2024

Language: Английский

Citations

2
M1 Microglia-Derived Exosomes Promote A1 Astrocyte Activation and Aggravate Ischemic Injury via circSTRN3/miR-331-5p/MAVS/NF-κB Pathway DOI Creative Commons
Zhongyuan Li, Pengfei Xu, Yang Deng

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 9285 - 9305

Published: Nov. 1, 2024

After ischemic stroke (IS), microglia and astrocytes undergo polarization, transforming into a pro-inflammatory phenotype (M1 or A1). According to previous studies, exosomes might play an important role in the interplay between M1 A1 after IS.

Language: Английский

Citations

2
MiR-122 overexpression alleviates oxygen–glucose deprivation-induced neuronal injury by targeting sPLA2-IIA DOI Creative Commons
Yuanfang Yu, Li Pan, Mengyuan Chen

et al.

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

Published: May 10, 2024

Background Ischemic stroke (IS) is a neurological disease with significant disability and mortality. MicroRNAs were proven to be associated cerebral ischemia. Previous studies have demonstrated miR-122 downregulation in both animal models of IS the blood patients. Nonetheless, role mechanism miR-122-5p remain unclear. Methods We established primary human mouse astrocytes, along HT22 hippocampal neuronal cells, through oxygen–glucose deprivation/reoxygenation (OGD/R) treatment. To assess impact miR-122, we employed CCK8 assays, flow cytometry, RT-qPCR, western blotting, ELISA evaluate cell viability, apoptosis, reactive oxygen species (ROS) generation, cytokine expression. A dual-luciferase reporter gene assay was investigate interaction between sPLA2-IIA. Results Overexpression resulted decreased reduced cleaved caspase-3 expression, increased viability astrocytes cells subjected OGD/R. RT-qPCR analyses decrease mRNA levels interleukin (IL)-6 tumor necrosis factor (TNF)-α following overexpression. Moreover, overexpression reversed OGD/R-induced ROS 8-OHdG formation astrocytes. Additionally, protein expression inducible nitric oxide synthase (iNOS). Furthermore, found that attaches 3′-UTR sPLA2-IIA, thereby downregulate its Conclusion Our study demonstrates miR-122-mediated inhibition sPLA2-IIA attenuates injury by suppressing alleviating post-ischemic inflammation, reducing production. Thus, miR-122/sPLA2-IIA axis may represent promising target for

Language: Английский

Citations

1
Potential diagnostic biomarkers for immunogenic cell death in elderly female patients with ischemic stroke: identification and analysis DOI Creative Commons
Lihua Qin, Sheng Li,

Xi Cao

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 24, 2024

Abstract Ischemic stroke (IS) is of increasing concern given the aging population and prevalence unhealthy lifestyles, with older females exhibiting higher susceptibility. This study aimed to identify practical diagnostic markers, develop a model for immunogenic cell death (ICD)-associated IS, investigate alterations in immune environment caused by hub genes. Differentially expressed genes associated ICD IS were identified based on weighted gene co-expression network analysis identification significant modules. Subsequently, machine learning algorithms employed screened genes, which further assessed using Gene Ontology, Kyoto Encyclopedia Genes Genomes, Set Enrichment Analysis. A nomogram mode lwas then constructed diagnosis, its value was receiver operating characteristic curve. Finally, infiltration within patients pan-cancer expression patterns evaluated. Three ( PDK4, CCL20 , FBL ) identified. The corresponding diagnosis could effectively female (area under curve (AUC) = 0.9555). Overall, three exhibit good (AUC > 0.8). are significantly extent cells infiltration. Moreover, strong link exists between prognosis. Cumulatively, these results indicate that ICD-related critically influence progression females, presenting novel therapeutic targets personalized treatment.

Language: Английский

Citations

1