Astrocyte-derived exosomal miR-378a-5p mitigates cerebral ischemic neuroinflammation by modulating NLRP3-mediated pyroptosis

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

Published: Aug. 8, 2024

This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia.

Language: Английский

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Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke

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

Published: June 20, 2024

Abstract Background Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating impact edaravone on functional outcomes and systematic inflammatory response AIS patient. Methods All participants were recruited from AISRNA (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 December 2022. The patients divided into two groups based whether they received (37.5 mg/12 hours, IV) within 48 h after onset. Inflammatory was determined by detecting levels cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, IL-1β) 14 days Results Eighty-five included study. Patients treated with showed a significantly higher proportion modified Rankin Scale score < 2 compared to those who did not receive this (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving injection exhibited lower expression interleukin (IL)-1β, along IL-4 IL-10 during phase ( 0.05). These trends observed for IL-2, factor-α, IFN-α > Conclusions Treatment resulted favorable outcome 90 post-stroke onset when without intervention; it also suppressed proinflammatory factors while increasing anti-inflammatory levels. Trial registration ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .

Language: Английский

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Curdione combined with borneol treats bacterial mixed HPV infection by regulating the crosstalk among immune cells

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

Published: Jan. 22, 2025

Background Human papillomavirus (HPV) infection is a worldwide reproductive system disease. Baofukang suppository, traditional herbal preparation that includes curdione and borneol, has been reported to treat bacterial vaginosis (BV) HPV in China. However, the therapeutic mechanism still unknown. This study aims explore molecular mechanisms of borneol treating infection. Methods We conducted retrospective cohort analysis medical records from single-center involving 205 patients, focusing on correlation between clearance co-infection with other pathogens, confirming efficacy suppository. Bioinformatics network pharmacology approaches were employed identify targets suppository for BV/HPV co-infections. qRT-PCR, Western blot, immunofluorescence staining, flow cytometry utilized validate along associated immune changes. Finally, confirmed vivo using an LPS/TC-1 cervical orthotopic injection model. Results Curdione selectively inhibit secretion interleukin-6 (IL-6) interleukin-1β (IL-1β) by macrophages. The reduction IL-6 IL-1β levels effectively inhibits expression CD274 (Programmed death ligand 1, PD-L1) infected epithelial cells inhibiting STAT3 phosphorylation, thereby suppressing their evasion capabilities. Furthermore, enhance tumor necrosis factor α (TNF-α) caspase 1 (CASP1) macrophages, as well interleukin 12 (IL-12) 23 (IL-23) dendritic (DCs). these inflammatory factors promotes migration differentiation T site infection, completing cells. Conclusion main components progression occurrence cancer modulating communication innate adaptive immunity, promoting recruitment recognition CD8 + eliminate HPV-infected

Language: Английский

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Cerebellar Pathology in Forensic and Clinical Neuroscience

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102697 - 102697

Published: Feb. 1, 2025

Language: Английский

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Edaravone alleviates Pseudomonas aeruginosa associated-acute lung injury by inhibiting inflammation and promoting anti-microbial peptide production

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114511 - 114511

Published: March 31, 2025

Language: Английский

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Edaravone dexborneol protected neurological function by targeting NRF2/ARE and NF-κB/AIM2 pathways in cerebral ischemia/reperfusion injury

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

Published: April 25, 2025

Edaravone dexborneol (Eda-Dex), a promising neuroprotectant composed of edaravone and (+)-borneol, has been clinically applied in stroke treatment. However, the mechanism action Eda-Dex remains unclear. A rat model cerebral ischemia/reperfusion injury (CIRI) was created through middle artery occlusion. Neurological scoring, TTC staining, laser speckle imaging were used to assess neurological deficits, infarct size blood flow (CBF). Behavioral tests, including open field test, elevated plus maze, novel object recognition conducted animal behavior. Western blotting ELISA employed levels expression components NRF2/ARE NF-κB/AIM2 pathways specific cytokines. The oxidative stress markers analyzed via commercially available kits. HE Nissl immunohistochemistry pathological alterations brain. dramatically reduced deficit score size, increased CBF, attenuated anxiety-like behavior improved cognitive function CIRI rats. significantly relieved inflammatory response it upregulated NRF2, NQO1, HO-1, SLC7A11 downregulated NF-κB, AIM2, ASC caspase 1 infarcted Moreover, clearly damage, rescued neurons, activation microglia astrocytes. results this study confirm that exerts neuroprotective effects by synergistically inhibiting inflammation

Language: Английский

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Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 104, P. 102638 - 102638

Published: Dec. 12, 2024

Language: Английский

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M1 Microglia-Derived Exosomes Promote A1 Astrocyte Activation and Aggravate Ischemic Injury via circSTRN3/miR-331-5p/MAVS/NF-κB Pathway

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

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Electroacupuncture alleviates cerebral ischemia injury by regulating PI3K/AKT/NF-κB signaling in microglia of ischemic stroke rats

Neuroreport, Journal Year: 2024, Volume and Issue: 36(1), P. 22 - 30

Published: Dec. 4, 2024

This study aimed to investigate the potential of electroacupuncture as an intervention for inducing 'Awakening and Opening Brain' in rats with stroke models induced by middle cerebral artery occlusion/reperfusion (MCAO/R). The efficacy alleviating ischemic injury was evaluated using Longa scores, triphenyl tetrazolium chloride staining, hematoxylin eosin staining. Non-targeted metabolomics analysis conducted identify differential metabolite changes before after treatment MCAO/R rats. Network pharmacology then performed correlate these metabolites stroke. PI3K/AKT/NF-κB signaling pathway identified a key target. In vivo experiments further validated mechanism which promotes M2 microglial polarization through inhibition demonstrated that reduces brain damage inhibits inflammation modulating promoting microglia from M1 M2.

Language: Английский

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MiR-122 overexpression alleviates oxygen–glucose deprivation-induced neuronal injury by targeting sPLA2-IIA

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

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