TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis

Biomaterials, Journal Year: 2022, Volume and Issue: 284, P. 121484 - 121484

Published: March 25, 2022

Retinal ischemia-reperfusion injury (IRI) is one of the main pathogenic mechanisms glaucoma, which are largely unknown, including neuroinflammation and neuronal death in pathological process. In our previous studies, mesenchymal stem cells (MSCs) have been reported to play anti-inflammatory neuroprotective roles. Additionally, conditioned culture medium (CM) MSCs stimulated by TNF-α achieved better antiallergic effects an experimental allergic conjunctivitis mouse model. However, there urgent need for cell-free therapy approaches, like exosomes, reduce side autoimmunity. The present study aimed elucidate pathways involving TNF-α-stimulated gingival MSC (GMSC)-exosomes (TG-exos), modulating inflammatory microglia alleviating apoptosis. this study, exosomes from CM GMSCs were isolated ultracentrifugation injected into vitreous mice. results showed that intraocular injection TG-exos mice with IRI notably reduced inflammation cell loss than G-exos (GMSC-exosomes). Similar observed vitro. microRNA (miR) arrays, it was found miR-21-5p acted as a crucial factor neuroprotection anti-inflammation. Following target prediction dual-luciferase assay suggested played role combining programmed 4 (PDCD4), regulated long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) competing endogenous (ceRNA). This demonstrates new therapeutic pathway against delivering miR-21-5p-enriched through MEG3/miR-21-5p/PDCD4 axis paves way establishment approach glaucoma.

Language: Английский

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Designing nanozymes for in vivo applications

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(10), P. 849 - 868

Published: July 18, 2024

Language: Английский

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Integrative Approaches in Acute Ischemic Stroke: From Symptom Recognition to Future Innovations

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2617 - 2617

Published: Sept. 23, 2023

Among the high prevalence of cerebrovascular diseases nowadays, acute ischemic stroke stands out, representing a significant worldwide health issue with important socio-economic implications. Prompt diagnosis and intervention are milestones for management this multifaceted pathology, making understanding various stroke-onset symptoms crucial. A key role in is emphasizing essential multi-disciplinary team, therefore, increasing efficiency recognition treatment. Neuroimaging neuroradiology have evolved dramatically over years, multiple approaches that provide higher morphological aspects as well timely cerebral artery occlusions effective therapy planning. Regarding treatment matter, pharmacological approach, particularly fibrinolytic therapy, has its merits challenges. Endovascular thrombectomy, game-changer management, witnessed advances, technologies like stent retrievers aspiration catheters playing pivotal roles. For select patients, combining endovascular strategies offers evidence-backed benefits. The aim our comprehensive study on to efficiently compare current therapies, recognize novel possibilities from literature, describe state art interdisciplinary approach stroke. As we aspire holistic patient emphasis not just medical but also physical mental health, community engagement. future holds promising innovations, artificial intelligence poised reshape diagnostics treatments. Bridging gap between groundbreaking research clinical practice remains challenge, urging continuous collaboration research.

Language: Английский

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Role of microglia in stroke

Glia, Journal Year: 2024, Volume and Issue: 72(6), P. 1016 - 1053

Published: Jan. 4, 2024

Abstract Microglia play key roles in the post‐ischemic inflammatory response and damaged tissue removal reacting rapidly to disturbances caused by ischemia working restore lost homeostasis. However, modified environment, encompassing ionic imbalances, disruption of crucial neuron–microglia interactions, spreading depolarization, generation danger signals from necrotic neurons, induce morphological phenotypic shifts microglia. This leads them adopt a proinflammatory profile heighten their phagocytic activity. From day three post‐ischemia, macrophages infiltrate core while microglia amass at periphery. Further, inflammation prompts metabolic shift favoring glycolysis, pentose‐phosphate shunt, lipid synthesis. These shifts, combined with intake, drive droplet biogenesis, fuel anabolism, enable proliferation. Proliferating release trophic factors contributing protection repair. some accumulate lipids persistently transform into dysfunctional potentially harmful foam cells. Studies also showed that either display impaired apoptotic cell clearance, or eliminate synapses, viable endothelial Yet, it will be essential elucidate viability engulfed cells, features local extent damage, temporal sequence. Ischemia provides rich variety region‐ injury‐dependent stimuli for microglia, evolving time generating distinct phenotypes including those exhibiting traits others showing pro‐repair features. Accurate profiling phenotypes, alongside more precise understanding associated conditions, is necessary step serve as potential foundation focused interventions human stroke.

Language: Английский

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Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(733)

Published: Feb. 7, 2024

Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there limited knowledge of the molecular and spatial characteristics nonneuronal cells, well interactions between cell types in ischemic brain. Here, we used transcriptomics to study hemisphere mice stroke sequenced transcriptomes 19,777 spots, allowing us both visualize transcriptional landscape within tissue identify gene expression profiles linked specific histologic entities. Cell identified by single-cell RNA sequencing confirmed enriched annotation ischemia-associated peri-infarct area hemisphere. Analysis ligand-receptor communication revealed galectin-9 cell-surface glycoprotein CD44 (LGALS9-CD44) critical signaling pathway injury microglia macrophages main source galectins stroke. Extracellular vesicle–mediated Lgals9 delivery improved long-term functional recovery photothrombotic mice. Knockdown Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation remyelination. In summary, our provides detailed cellular characterization peri-infact murine model potential treatment target that warrants further investigation.

Language: Английский

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Association between the systemic immunity-inflammation index and stroke: a population-based study from NHANES (2015–2020)

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Background The systemic immunity-inflammation index(SII) is a new indicator of composite inflammatory response. Inflammatory response an important pathological process in stroke. Therefore, this study sought to investigate the association between SII and Methods We collected data on participants with stroke from 2015–2020 cycle National Health Nutrition Examination Survey (NHANES) for cross-sectional investigation. Multivariate linear regression models were used test Fitted smoothing curves threshold effect analysis applied describe nonlinear relationship. Results A total 13,287 included our study, including 611 (4.598%) In multivariate analysis, we found significant positive stroke, odds ratio (OR) [95% CI] associating prevalence was [1.02 (1.01, 1.04)] (P < 0.01). subgroup interaction experiments, that relationship not significantly correlated among different population settings such as age, gender, race, education level, smoking status, high blood pressure, diabetes coronary heart disease trend > 0.05). Moreover, inflection point 740 (1,000 cells /µl) by using two-segment model. Conclusions This implies increased levels are linked To confirm findings, more large-scale prospective investigations needed.

Language: Английский

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A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse

Journal of Clinical Medicine, Journal Year: 2019, Volume and Issue: 8(9), P. 1295 - 1295

Published: Aug. 23, 2019

Drugs of abuse are associated with stroke, especially in young individuals. The major classes drugs linked to stroke cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along androgenic anabolic steroids (AASs). Both ischemic hemorrhagic have been reported due drug abuse. Several common mechanisms identified, such as arrhythmias cardioembolism, hypoxia, vascular toxicity, spasm effects on the thrombotic mechanism, causes for stroke. For acute hypertension, aneurysm formation/rupture angiitis-like changes implicated. In AAS abuse, effect blood pressure is rather substance specific, whereas increased erythropoiesis usually leads thromboembolism. Transient vasospasm, caused by could lead Opiates often cause infective endocarditis, resulting hypereosinophilia accompanied pyogenic arthritis, provoking Genetic variants risk cocaine fact that case reports cannabis-induced refer population very alarming.

Language: Английский

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Immunothrombosis and thromboinflammation in host defense and disease

Platelets, Journal Year: 2020, Volume and Issue: 32(3), P. 314 - 324

Published: Sept. 8, 2020

Platelets are increasingly being recognized for playing roles beyond thrombosis and hemostasis. Today we know that they mediate inflammation by direct interactions with innate immune cells or secretion of cytokines/chemokines. Here review their neutrophils monocytes/macrophages in infection sepsis, stroke, myocardial infarction venous thromboembolism. We discuss new platelet surface receptors like GPVI GPIb also look at contributions to the formation neutrophil extracellular traps (NETs) as well deep vein during infection, e.g. COVID-19 patients.

Language: Английский

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Role of platelet biomarkers in inflammatory response

Biomarker Research, Journal Year: 2020, Volume and Issue: 8(1)

Published: Aug. 2, 2020

Abstract Beyond hemostasis, thrombosis and wound healing, it is becoming increasingly clear that platelets play an integral role in inflammatory response immune regulation. Platelets recognize pathogenic microorganisms secrete various immunoregulatory cytokines chemokines, thus facilitating a variety of effects regulatory functions. In this review, we discuss recent advances signaling platelet activation-related biomarkers settings application prospects to apply for disease diagnosis treatment.

Language: Английский

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Platelets as Mediators of Neuroinflammation and Thrombosis

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 6, 2020

Beyond platelets function in hemostasis, there is emerging evidence to suggest that contribute crucially inflammation and immune responses. Therefore, considering the detrimental role of inflammatory conditions severe neurological disorders such as multiple sclerosis or stroke, this review outlines involvement neuroinflammation. For this, distinct mechanisms platelet-mediated thrombosis are portrayed, focusing on interaction platelet receptors with other cells well brain endothelial cells. Furthermore, we draw attention intimate interplay between complement system plasmatic coagulation factors course Following thorough exposition preclinical approaches which aim at ameliorating disease severity after inducing experimental autoimmune encephalomyelitis (a counterpart mice) ischemia-reperfusion injury, clinical relevance neuroinflammation addressed. Thus, current future propitious translational strategies for treatment neuro-inflammatory diseases by affecting illustrated, emphasizing targeting could become an efficient adjunct therapy mitigate stroke associated injury.

Language: Английский

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