Decreased serum SLC7A11 and GPX4 levels may reflect disease severity of acute ischaemic stroke DOI
Chuanpeng Liu,

Su Zheng,

Ping Zhang

et al.

Annals of Clinical Biochemistry International Journal of Laboratory Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Objective This study aimed to examine the levels of solute carrier family seven number 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in serum patients with acute ischaemic stroke (AIS) their relationship disease severity. Methods A total 148 AIS together healthy controls (HCs) were enrolled. The expression SLC7A11 GPX4 detected immediately as early possible. Radiographic severity was by Alberta Stroke Program Early CT Score (ASPECTS). Disease evaluated using modified Rankin Scale (mRS). High-sensitivity C-reactive protein (hs-CRP) matrix metalloproteinase-9 (MMP-9) also measured. correlation analysis conducted determine between clinical hs-CRP MMP-9. Furthermore, receiver operating characteristic (ROC) curve utilized assess potential diagnostic markers. Results Compared HC group, significantly lower group. Serum positively associated levels. group included 50 mild neurological impairment, 52 moderate 46 severe impairment. impairment had drastically higher compared those showed concentrations ROC demonstrated that both may act indicators for evaluating In addition, correlated ASPECTS. Both negatively well MMP-9 increased following comprehensive therapy. Conclusions Decreased reflect AIS.

Language: Английский

Neutrophil extracellular traps drive intestinal microvascular endothelial ferroptosis by impairing Fundc1-dependent mitophagy DOI Creative Commons
Chengnan Chu, Xinyu Wang, Chao Yang

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102906 - 102906

Published: Oct. 4, 2023

Microvascular endothelial damage caused by intestinal ischemia‒reperfusion (II/R) is a primary catalyst for microcirculation dysfunction and enterogenous infection. Previous studies have mainly focused on how neutrophil extracellular traps (NETs) ferroptosis cause epithelial injury, little attention has been given to NETs, from circulatory neutrophils, affect cells during II/R. This study aimed unravel the mechanisms through which NETs microvascular dysfunction. We first detected heightened local NET infiltration around microvasculature, accompanied increased cell ferroptosis, resulting in both human animal II/R models. However, administration of inhibitor ferrostatin-1 or inhibition via neutrophil-specific peptidylarginine deiminase 4 (Pad4) deficiency led positive outcomes, with reduced function recovery. Moreover, RNA-seq analysis revealed significant enrichment mitophagy- ferroptosis-related signaling pathways HUVECs incubated NETs. Mechanistically, elevated formation induced Fundc1 phosphorylation at Tyr18 cells, mitophagy inhibition, mitochondrial quality control imbalance, excessive ROS generation lipid peroxidation, Nevertheless, using activator urolithin A AAV-Fundc1 transfection could reverse this process ameliorate damage. demonstrate that NETosis result microcirculatory conclude suppressed can mitigate improving Fundc1-dependent mitophagy. Targeting be promising approach treating II/R-induced

Language: Английский

Citations

62
The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery DOI Open Access
Jiaxin Deng, Qian Liu,

L Ye

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116337 - 116337

Published: Feb. 28, 2024

In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive lead to an increase in and ultimately exacerbate MIRI by causing overproduction uncontrolled production mitochondria. Phosphatase tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing (FUNDC1) B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators Pink1 Parkin mitochondrial surface proteins involved ubiquitin-dependent pathway, while BNIP3 FUNDC1 receptor non-ubiquitin-dependent which play crucial role maintaining homeostasis quality. These can induce inhibit protect against but may also trigger insufficient mitophagy, thereby worsening condition. Understanding actions these provide valuable insights into pathological mechanisms underlying development. Based on above background, this article reviews through Pink1/Parkin pathway mediated led BNIP3, as well related drug treatment, aim effective strategies for prevention treatment

Language: Английский

Citations

35
Deciphering the Power of Resveratrol in Mitophagy: From Molecular Mechanisms to Therapeutic Applications DOI Open Access
Hongmei Liu, Yixuan Song, Huan Wang

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Resveratrol (RES), a natural polyphenolic compound, has garnered significant attention for its therapeutic potential in various pathological conditions. This review explores how RES modulates mitophagy-the selective autophagic degradation of mitochondria essential maintaining cellular homeostasis. promotes the initiation and execution mitophagy by enhancing PINK1/Parkin-mediated mitochondrial clearance, reducing reactive oxygen species production, mitigating apoptosis, thereby preserving integrity. Additionally, regulates through activation key molecular targets such as AMP-activated protein kinase (AMPK), mechanistic target rapamycin (mTOR), deacetylases (SIRT1 SIRT3), quality control (MQC) pathways, demonstrating substantial effects multiple disease models. We provide detailed account biosynthetic pharmacokinetics, metabolic characteristics RES, focusing on role modulation implications medical applications. Potential adverse associated with clinical use are also discussed. Despite promising properties, application is limited issues bioavailability pharmacokinetic profiles. Future research should concentrate developing derivatives that precisely modulate mitophagy, unlocking new avenues therapy.

Language: Английский

Citations

3
Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects DOI Creative Commons
Pasquale Pagliaro, Cláudia Penna

Antioxidants, Journal Year: 2023, Volume and Issue: 12(7), P. 1396 - 1396

Published: July 7, 2023

Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. Calcium overload, levels, mitochondrial ROS are also involved in these MIRI processes, resulting irreversible opening permeability transition pore (mPTP). These mechanisms processes associated with NLRP3 inflammasome priming activation, which can induce cell death pyroptosis through up-regulation caspase-1 pathway IL-18 release. In addition, endothelial dysfunction, both presence absence MIRI, accompanied decreased nitric oxide production, overproduction, expression adhesion molecules leukocyte infiltration plays a central role, thus contributing, to alteration coronary flow, typical ischemic heart disease. Given intricate interrelationship between NLRP3, inhibitors reduce while oxidative stress inflammation. have been intensively studied as anti-inflammatory agents basic cardiovascular sciences. this review, we analyze interrelation disease effects some possible therapeutic condition. All compounds considered review need larger studies confirm their appropriate use clinical scenarios anti-ischemic drugs.

Language: Английский

Citations

26
Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis DOI Creative Commons
Maria P. Mogavero, Michele Salemi, Giuseppe Lanza

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109568 - 109568

Published: March 26, 2024

Highlights•This study analyzed pathways of differentially expressed mRNAs in people with RLS•Nine closely interconnected network groups emerged to be significantly dysregulated•Among them: infections, inflammation, immunology, neurodegeneration, and cancer•Infections could trigger inflammatory/immune reactions predisposed subjectsSummaryThe aim this was analyze signaling associated messenger RNAs restless legs syndrome (RLS). Seventeen RLS patients 18 controls were enrolled. Coding RNA expression profiling 12,857 gene transcripts by next-generation sequencing performed. Enrichment analysis pathfindR tool carried-out, p-adjusted ≤0.001 fold-change ≥2.5. Nine main different dysregulated RLS: cancer, neurotransmission biological, blood metabolic mechanisms. Genetic predisposition plays a key role evidence indicates its inflammatory nature; the high involvement mainly neurotropic viruses TORCH complex might genetically subjects activate series biological pathways—especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, ferroptosis—involved neurotransmitter mechanisms, synaptic plasticity, axon guidance, carcinogenesis, metabolism.Graphical abstract

Language: Английский

Citations

10
JP4-039 protects chondrocytes from ferroptosis to attenuate osteoarthritis progression by promoting Pink1/Parkin-dependent mitophagy DOI Creative Commons

Xie Ya,

Zhongyang Lv,

Weitong Li

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 132 - 144

Published: March 1, 2025

Osteoarthritis (OA) is the most common degenerative joint disease, and its main pathological mechanism articular cartilage degeneration. The purpose of this study was to investigate role mitophagy in pathogenesis chondrocyte ferroptosis OA. expressions related proteins (GPX4, FTH1, COX2) ubiquitin-dependent (PARKIN, PINK1) intact injured areas OA were analyzed. Nitro oxide JP4-039, a mitochondrial targeting antioxidant, has bifunctional mitochondria. Then we evaluated potential protective effect JP4-039 using destabilization medial meniscus (DMM)-induced model, as well tert-butyl hydrogen peroxide (TBHP)-treated primary mouse chondrocytes human explants. concentrations iron lipid peroxidation expression drivers damaged cartilages significantly higher than those cartilage. Pink1/Parkin-dependent decreased area negatively correlated with ferroptosis. Then, toxicity effectiveness are tested determine working concentration. Next, at molecular biological level, found that showed anti-chondrocyte Moreover, it verified on DMM-induced model mice, could delay progression Finally, re-verified vivo vitro inhibit by promoting mitophagy. inhibits delays progression.

Language: Английский

Citations

1
Orexin‐A mediates glioblastoma proliferation inhibition by increasing ferroptosis triggered by unstable iron pools and GPX4 depletion DOI Creative Commons

Rengzheng Huan,

Jiqin Zhang,

Jianhe Yue

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(9)

Published: April 29, 2024

Abstract Glioblastoma (GBM) represents a prevalent form of primary malignant tumours in the central nervous system, but options for effective treatment are extremely limited. Ferroptosis, as most enriched programmed cell death process glioma, makes critical difference glioma progression. Consequently, inducing ferroptosis has become an appealing strategy tackling gliomas. Through utilization multi‐omics sequencing data analysis, flow cytometry, MDA detection and transmission electron microscopy, impact orexin‐A on GBM was assessed. In this report, we provide first evidence that exerts inhibitory effects proliferation via induction ferroptosis. This is achieved by instigating unsustainable increase iron levels depletion GPX4. Moreover, regulation TFRC, FTH1 GPX4 expression through targeting NFE2L2 appears to be one potential mechanisms underlying orexin‐A‐induced

Language: Английский

Citations

6
ALDH2 polymorphism and myocardial infarction: From alcohol metabolism to redox regulation DOI Creative Commons

Reece J. Lamb,

Kayleigh Griffiths, Gregory Y.H. Lip

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 259, P. 108666 - 108666

Published: May 17, 2024

Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation reactive oxygen species (ROS) during the early reperfusion phase is thought to trigger lipid peroxidation and disrupt redox homeostasis, injury. Whilst mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) chiefly recognised for its central role in ethanol metabolism, substantial experimental evidence suggests an additional cardioprotective ALDH2 independent alcohol intake, which mitigates injury by detoxifying breakdown products including aldehydes, malondialdehyde (MDA) 4-hydroxynonenal (4-HNE). Epidemiological that mutant variant with reduced activity highly prevalent East Asian population increases AMI risk. Additional studies have uncovered strong association between coronary heart disease this variant. It appears polymorphism (in particular, ALDH2*2/2 carriers) has potential wide-ranging effects on thiol reactivity, tone therefore numerous redox-related signaling processes, resilience cope lifestyle-related environmental stressors, ability whole body achieve balance. In review, we summarize journey from reductase linked via pre-clinical aimed at stimulating reduce clinical protective heart.

Language: Английский

Citations

6
Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome DOI
Li Chen, Linshen Mao,

Jin-Yi Xue

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 355, P. 122998 - 122998

Published: Aug. 20, 2024

Language: Английский

Citations

5
Cardioprotective potential of transcription factor PRRX1 silencing against myocardial ischemia/reperfusion injury by regulating excessive mitophagy and ferroptosis through FKBP5-p38 MAPK axis DOI

Yongpeng Fang,

Xudong Niu,

Weifang Zhao

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167766 - 167766

Published: March 3, 2025

Language: Английский

Citations

0