Interplay of cell death pathways and immune responses in ischemic stroke: insights into novel biomarkers DOI
Arian Daneshpour, Zoha Shaka, Nima Rezaei

et al.

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Stroke is a severe neurological disease and major worldwide issue, mostly manifesting as ischemic stroke (IS). In order to create effective treatments for IS, it imperative fully understand the underlying pathologies, existing therapeutic choices are inadequate. Recent investigations have shown complex relationships between several programmed cell death (PCD) pathways, including necroptosis, ferroptosis, pyroptosis, their correlation with immune responses during IS. However, this relationship still unclear. To address gap, review study explored cellular interactions in microenvironment of Then, validate prior findings uncover biomarkers, investigated bioinformatics studies. Several nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB), Toll-like receptor 4 (TLR4), receptor-interacting protein kinase (RIPK), were involved PCD-immune interactions. The studies reported key biomarkers such glutathione peroxidase (GPX4), NOD-like family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), TLR4, which important implications cuproptosis, necroptosis respectively. These associated PCD mechanisms oxidative stress inflammatory reactions. infiltration analysis consistently revealed significant pathways detrimental cells, neutrophils γδ T cells. Conversely, M2 macrophages helper showed protective effects. conclusion, considering intricate network emphasized necessity paradigm shift approaches injuries that related network.

Language: Английский

Exploring the Nexus: How Ferroptosis, Microglia, and Neuroinflammation Converge in Ischemic Stroke Pathogenesis DOI Creative Commons

Zhiyan Liu,

Xueyang Shen,

Mingming Li

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

0
Chuanxiong Rhizoma regulates ferroptosis and the immune microenvironment in ischemic stroke through the JAK-STAT3 pathway DOI Creative Commons
Qingjie Ge, Zhimin Wang,

Jiaxiang Yu

et al.

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

Published: Dec. 28, 2024

Ferroptosis is linked to various pathological conditions; however, the specific targets and mechanisms through which traditional Chinese medicine influences ischemic stroke (IS)-induced ferroptosis remain poorly understood. In this study, data from Gene Expression Omnibus disease target databases (OMIM, GeneCards, DisGeNet, TTD, DrugBank) were integrated with ferroptosis-related gene datasets. To identify key molecular of Chuanxiong Rhizoma (CX), drug ingredient databases, including PubChem TCMBank, employed map CX-related (CX-DEGs-FRG CX-IS-FRG). relevant signaling pathways analyzed using weighted co-expression network analysis, protein-protein interaction networks, Ontology, Kyoto Encyclopedia Genes Genomes pathway enrichment. The least absolute shrinkage selection operator regression support vector machine methods utilized intersecting genes, predictive accuracy core was evaluated receiver operating characteristic curve analysis. Immune cell infiltration in IS microenvironment assessed CIBERSORT, followed by docking CX's active components targets. JAK-STAT3 identified as a critical regulatory mechanism, five (ALOX5, PTGS2, STAT3, G6PD, HIF1A) emerged central IS-induced ferroptosis. Elevated CD8 + T cells neutrophils significantly correlated IS. Notably, mandenol myricanone demonstrated strong binding affinities these targets, validated results network-based conclusion, pathway, its regulation ALOX5, HIF1A, could play crucial role modulating immune responses These findings suggest that CX serve potential therapeutic approach for IS, targeting microenvironment.

Language: Английский

Citations

2
CLEC7A Knockdown Alleviates Ischemic Stroke by Inhibiting Pyroptosis and Microglia Activation DOI Creative Commons
Wei Li,

Xiaoli Feng,

Manyu Zhang

et al.

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(12)

Published: Dec. 23, 2024

Background: Ischemic stroke (IS) is the leading cause of mortality worldwide. Herein, we aimed to identify novel biomarkers and explore role C-type lectin domain family 7 member A (CLEC7A) in IS. Methods: Differentially expressed genes (DEGs) were screened using GSE106680, GSE97537, GSE61616 datasets, hub identified through construction protein-protein interaction networks. An IS model was established by middle cerebral artery occlusion reperfusion (MCAO/R). Neural function assessed triphenyl tetrazolium chloride, hematoxylin-eosin, terminal deoxynucleotidyl transferase-mediated nick-end labeling. cell counting kit used detect viability following oxygen-glucose deprivation/reperfusion (OGD/R). Inflammatory factors detected enzyme-linked immunosorbent assay. The mRNA protein expression levels reverse transcription-quantitative polymerase chain reaction western blotting, respectively. Results: Fc fragment Immunoglobulin G (IgG) receptor IIIa (FCGR3A), E (IgE) Ig (FCER1G), Complement component 5a 1 (C5AR1), CLEC7A, Plasminogen activator, urokinase (PLAU), C-C motif chemokine ligand 6 (CCL6) as important genes, from which CLEC7A selected primary subject this study. activation microglia pyroptosis observed MCAO/R with increased interleukin (IL)-1β, IL-18, tumor necrosis factor-α, lactate dehydrogenase. knockdown found promote BV2 cells inhibiting HT22 cells. also decreased infarct volume neurological deficit scores, alleviated injury neuronal apoptosis rats. inhibited microglial model. activator reversed effect on OGD/R-treated Conclusion: a promising biomarker alleviates activation.

Language: Английский

Citations

2
Role and mechanisms of mast cells in brain disorders DOI Creative Commons
Xuanyu Huang, Ziwei Lan, Zhiping Hu

et al.

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

Published: Aug. 26, 2024

Mast cells serve as crucial effector within the innate immune system and are predominantly localized in skin, airways, gastrointestinal tract, urinary reproductive tracts, well brain. Under physiological conditions, brain-resident mast secrete a diverse array of neuro-regulatory mediators to actively participate neuroprotection. Meanwhile, primary source molecules causing brain inflammation, also function “first responders” injury. They interact with neuroglial neurons facilitate release numerous inflammatory mediators, proteases, reactive oxygen species. This process initiates amplifies immune-inflammatory responses brain, thereby contributing regulation neuroinflammation blood-brain barrier permeability. article provides comprehensive overview potential mechanisms through which may modulate neuroprotection their pathological implications various neurological disorders. It is our contention that inhibition cell activation disorders could represent novel avenue for therapeutic breakthroughs.

Language: Английский

Citations

1
Lower Melatonin Indicates Poor Short-term Prognosis in Patients with Acute Ischemic Stroke DOI
Qian Sun,

Sheng-nan Chen,

Siyuan Yu

et al.

Current Neurovascular Research, Journal Year: 2024, Volume and Issue: 21(2), P. 148 - 156

Published: March 12, 2024

Aims: We evaluated endogenous melatonin levels in the acute phase of cerebral infarction and explored impact possible changes on prognosis patients. Methods: This study recruited ischemic stroke (AIS) patients from Department Second Affiliated Hospital Soochow University between December 2019 June 2021, along with healthy control subjects. Salivary samples were collected each participant 7 pm 10 pm, fasting plasma was following morning to measure inflammatory markers. The assessed through follow-up three months after discharge. relationship markers assessed, followed by an analysis effect patient prognosis. Results: enrolled a total 160 participants, including 120 AIS aged 50 years or older (61.7% male) 40 age-matched controls (55.0% male). group exhibited lower salivary at 19 (P = 0.002), 20 < 0.001), 21 22 0.001) o’clock, average level also 0.001). Logistic regression models indicated association low poor demonstrated good predictive ability for Conclusion: Melatonin compared controls. In addition, associated poorer among

Language: Английский

Citations

0
Interplay of cell death pathways and immune responses in ischemic stroke: insights into novel biomarkers DOI
Arian Daneshpour, Zoha Shaka, Nima Rezaei

et al.

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Stroke is a severe neurological disease and major worldwide issue, mostly manifesting as ischemic stroke (IS). In order to create effective treatments for IS, it imperative fully understand the underlying pathologies, existing therapeutic choices are inadequate. Recent investigations have shown complex relationships between several programmed cell death (PCD) pathways, including necroptosis, ferroptosis, pyroptosis, their correlation with immune responses during IS. However, this relationship still unclear. To address gap, review study explored cellular interactions in microenvironment of Then, validate prior findings uncover biomarkers, investigated bioinformatics studies. Several nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB), Toll-like receptor 4 (TLR4), receptor-interacting protein kinase (RIPK), were involved PCD-immune interactions. The studies reported key biomarkers such glutathione peroxidase (GPX4), NOD-like family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), TLR4, which important implications cuproptosis, necroptosis respectively. These associated PCD mechanisms oxidative stress inflammatory reactions. infiltration analysis consistently revealed significant pathways detrimental cells, neutrophils γδ T cells. Conversely, M2 macrophages helper showed protective effects. conclusion, considering intricate network emphasized necessity paradigm shift approaches injuries that related network.

Language: Английский

Citations

0