Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury DOI Creative Commons

Guihong Shi,

Yiyao Cao,

Jianye Xu

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103532 - 103532

Published: Feb. 5, 2025

Traumatic brain injury (TBI) triggers a robust inflammatory response that is closely linked to worsened clinical outcomes. S100A8/A9, also known as calprotectin or myeloid-related protein-8/14 (MRP8/14), an alarmin primarily secreted by activated neutrophils with potent pro-inflammatory property. In this study, we explored the roles of S100A8/A9 in modulating neuroinflammation and influencing TBI outcomes, delving into underlying mechanisms. S100A8/A9-enriched were present injured tissue patients, elevated plasma levels correlated poorer neurological function. Furthermore, using mouse model, demonstrated treatment selective inhibitor Paquinimod significantly mitigated neuronal death, thereby improving prognosis mice. Mechanistically, found conjunction neutrophil activation infiltration brain, enhances reactive oxygen species (ROS) production within neutrophils, accelerating PAD4-mediated extracellular trap (NET) formation, which turn exacerbates neuroinflammation. These findings suggest amplifies neuroinflammatory responses promoting NET formation neutrophils. Inhibition effectively attenuated NET-mediated neuroinflammation; however, when PAD4 was overexpressed adenovirus, leading increased anti-inflammatory effects inhibition markedly diminished. Further experiments knockout mice confirmed reduction NETs could substantially alleviate S100A8/A9-driven Finally, established suppression mediated through AMPK/Nrf2/HO-1 signaling pathway. underscore critical pathological role emphasize need for further exploration potential therapeutic strategy TBI.

Language: Английский

Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1α/ASK1/JNK signaling pathway in mice with traumatic brain injury DOI Creative Commons

Guihong Shi,

Liang Liu,

Yiyao Cao

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Sept. 30, 2023

Neuroinflammation is one of the most important pathogeneses in secondary brain injury after traumatic (TBI). Neutrophil extracellular traps (NETs) forming neutrophils were found throughout tissue TBI patients and elevated plasma NET biomarkers correlated with worse outcomes. However, biological function underlying mechanisms NETs TBI-induced neural damage are not yet fully understood. Here, we used Cl-amidine, a selective inhibitor to investigate role TBI.Controlled cortical impact model was performed establish TBI. 2'3'-cGAMP (an activator stimulating Interferon genes (STING)), C-176 (a STING inhibitor), Kira6 [a selectively phosphorylated inositol-requiring enzyme-1 alpha [IRE1α] inhibitor] administrated explore mechanism by which promote neuroinflammation neuronal apoptosis Peptidyl arginine deiminase 4 (PAD4), an essential enzyme for neutrophil trap formation, overexpressed adenoviruses cortex mice 1 day before The short-term neurobehavior tests, magnetic resonance imaging (MRI), laser speckle contrast (LSCI), Evans blue extravasation assay, Fluoro-Jade C (FJC), TUNEL, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), western blotting, quantitative-PCR this study.Neutrophils form presenting circulation at 3 days Cl-amidine treatment improved neurological functions, reduced cerebral lesion volume, edema, restored blood flow (CBF) In addition, exerted neuroprotective effects attenuating BBB disruption, inhibiting immune cell infiltration, alleviating death Moreover, inhibited microglia/macrophage pro-inflammatory polarization promoted anti-inflammatory Mechanistically, ligand abolished neuroprotection via IRE1α/ASK1/JNK signaling pathway Importantly, overexpression PAD4 promotes or IRE1α effectively neurodestructive TBI.Altogether, first demonstrate that inhibition ameliorated neuroinflammation, apoptosis, deficits STING-dependent Thus, may provide promising therapeutic approach early management

Language: Английский

Citations

42
Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke DOI Creative Commons

Mingxu Duan,

Ya Xu,

Yuanshu Li

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: April 18, 2024

Abstract The notion that the central nervous system is an immunologically immune-exempt organ has changed over past two decades, with increasing evidence of strong links and interactions between peripheral immune system, both in healthy state after ischemic hemorrhagic stroke. Although primary injury stroke certainly important, limited therapeutic efficacy, poor neurological prognosis high mortality have led researchers to realize secondary damage may also play important roles influencing long-term neuroinflammatory process one most influences on disease progression. Here, we summarize stroke, particular, how activates recruits components, review recent advances corresponding approaches clinical studies, emphasizing importance role

Language: Английский

Citations

17
Bioactive natural products in COVID-19 therapy DOI Creative Commons
Zhonglei Wang, Ning Wang, Liyan Yang

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 19, 2022

The devastating COVID-19 pandemic has caused more than six million deaths worldwide during the last 2 years. Effective therapeutic agents are greatly needed, yet promising magic bullets still do not exist. Numerous natural products (cordycepin, gallinamide A, plitidepsin, telocinobufagin, and tylophorine) have been widely studied play a potential function in treating COVID-19. In this paper, we reviewed published studies (from May 2021 to April 2022) relating closely bioactive (isolated from medicinal plants, animals products, marine organisms) therapy

Language: Английский

Citations

57
Role of lipocalin 2 in stroke DOI Creative Commons
Ruoyu Zhao,

Pengju Wei,

Xin Sun

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106044 - 106044

Published: Feb. 17, 2023

Stroke is the second leading cause of death worldwide; however, treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) a secreted protein, belonging lipocalin superfamily, with multiple biological functions mediating innate immune response, inflammatory iron-homeostasis, cell migration and differentiation, energy metabolism, other processes body. LCN2 expressed at low levels brain under normal physiological conditions, but its expression significantly up-regulated acute stimulations chronic pathologies. An up-regulation has been found blood/cerebrospinal fluid patients ischemic/hemorrhagic stroke, could serve as potential biomarker for prediction severity stroke. activates reactive astrocytes microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, blood-brain barrier disruption, white matter injury, neuronal death. Moreover, involved injury induced by thrombin erythrocyte lysates, well microvascular thrombosis after hemorrhage. In this paper, we review role pathological ischemic stroke; intracerebral hemorrhage; subarachnoid stroke-related diseases, such vascular dementia depression, their underlying mechanisms. We hope that will help elucidate value therapeutic target

Language: Английский

Citations

34
Blood–brain crosstalk: the roles of neutrophils, platelets, and neutrophil extracellular traps in neuropathologies DOI
Ming‐Li Chou, Abdulkareem O. Babamale, Tara L. Walker

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(9), P. 764 - 779

Published: July 25, 2023

Language: Английский

Citations

25
Neuroprotective effects of cordycepin on MPTP-induced Parkinson's disease mice via suppressing PI3K/AKT/mTOR and MAPK-mediated neuroinflammation DOI
Linhai Wang,

Shu Tian,

Sisi Ruan

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 216, P. 60 - 77

Published: March 12, 2024

Language: Английский

Citations

12
Crosstalk Among Glial Cells in the Blood–Brain Barrier Injury After Ischemic Stroke DOI

Weizhuo Lu,

Jiyue Wen

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6161 - 6174

Published: Jan. 27, 2024

Language: Английский

Citations

11
Current Advances in the Functional Genes of Edible and Medicinal Fungi: Research Techniques, Functional Analysis, and Prospects DOI Creative Commons
Wenyun Li, Gen Zou, Dapeng Bao

et al.

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(5), P. 311 - 311

Published: April 25, 2024

Functional genes encode various biological functions required for the life activities of organisms. By analyzing functional edible and medicinal fungi, varieties fungi can be improved to enhance their agronomic traits, growth rates, ability withstand adversity, thereby increasing yield quality promoting industrial development. With rapid development gene research technology publication many whole-genome sequences related important traits have been mined, located, functionally analyzed. This paper summarizes advantages disadvantages different techniques application examples fungi; systematically reviews progress in processes such as mating type, mycelium fruit development, substrate utilization nutrient transport, environmental response, synthesis regulation active substances; proposes future directions fungi. The overall aim this study was provide a valuable reference further molecular breeding with high promote wide products food, medicine, industry.

Language: Английский

Citations

9
Cordycepin alleviates metabolic dysfunction-associated liver disease by restoring mitochondrial homeostasis and reducing oxidative stress via Parkin-mediated mitophagy DOI Creative Commons
Haiying Tian, Daojiang Yu,

Teng Xie

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: 232, P. 116750 - 116750

Published: Jan. 8, 2025

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) keeps rising with only a few drugs available. present study aims to investigate the effects and mechanisms cordycepin on MASLD. Male C57BL/6 mice were induced 90-day high-fat diet (HFD) intraperitoneal administration streptozotocin establish MASLD murine model. Then they randomly divided into HFD groups (15, 30, 45 mg/kg). Cordycepin was orally given for 30 days. Serum total cholesterol (TC), triacylglyceride (TG), aspartate aminotransferase (AST) levels measured. L02 cells by oleate acid (OA) or lipopolysaccharides (LPS), treated combined inhibitors including chloroquine, 3-Methyladenine, compound C. Atg7 Parkin knocked down in using siRNA. Oil Red O Nile staining measuring lipid deposition. Mitochondria visualized transfection mCherry-TOMM20-N10. Quantitative real-time PCR, Western blotting, immunofluorescence used determine expressions key molecules inflammation, metabolism, mitochondria homeostasis, oxidative stress. significantly mitigated deposition ballooning livers mice. TC, TG, AST decreased cordycepin. alleviated OA-induced LPS-induced inflammation cells, attenuated stress, promoted autophagy, maintained autophagic flux activating AMP-activated protein kinase (AMPK). reduced accumulation impaired enhancing Parkin-dependent mitophagy promoting mitochondrial biogenesis. alleviates restoring homeostasis reducing stress via Parkin-mediated mitophagy.

Language: Английский

Citations

1
β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury DOI Creative Commons
Lei Li,

Ruilong Peng,

Cong Wang

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 8, 2025

Neutrophils are the first responders among peripheral immune cells to infiltrate central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls dictate inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis landscape surrounding trauma in TBI mice has revealed significant alteration abundance β2 integrin (ITGB2), predominantly expressed by and closely associated with responses. Using fluid percussion (FPI) mouse model, we investigated therapeutic efficacy Rovelizumab, an agent blocks ITGB2. treatment demonstrated improvements neurologic function mice, attenuating blood–brain barrier permeability, mitigating oxidative stress mediator release, enhancing cerebral perfusion. Moreover, ITGB2 blockade effectively limited adherence, migration, infiltration neutrophils, impeded formation neutrophil extracellular traps (NETs) upon their activation. Finally, it was mediates these effects mainly through its interaction intercellular adhesion molecule-1 (ICAM 1) endotheliocyte. These findings collectively illuminate as crucial switch governs adverse post-TBI could be targeted improve clinical outcome patients.

Language: Английский

Citations

1