AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA‐PI3K‐Akt Axis DOI
Yafen Zhang, Yan Li,

Fengli Liu

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(8)

Published: Dec. 1, 2024

ABSTRACT Cerebral ischemia/reperfusion injury is one of the main causes neuronal damage. Neuron ferroptosis and microglia polarization are considered as critical processes during cerebral ischemia/reperfusion. Adipocyte enhancer‐binding protein 1 (AEBP1) usually acts a transcriptional repressor which involved in various diseases. However, it still remains unknown whether AEBP1 could have important roles regulating neuron injury. The oxygen‐glucose deprivation reperfusion (OGD/R)‐treated cells middle artery occlusion (MCAO)‐treated mice were used vitro vivo models. differentially expressed factors analyzed according to GEO datasets. Relative mRNA expression levels detected by qRT‐PCR western blot analysis. Cell viability was measured CCK‐8 assay. ROS, GSH iron contents using specifical assay kits. CD26 CD206 immunofluorescence Inflammatory cytokines ELISA. association between PRKCA assessed luciferase reporter ChIP analyses. damage TTC staining neurological deficit score. Transcription factor increased OGD/R‐treated HT22 BV2 cells. silencing attenuated OGD/R‐induced cell through increasing viability, GPX4 levels, decreasing ACSL4 levels. knockdown promoted M2 CD206‐positive Arg‐1 level, reducing iNOS, TNF‐α, IL‐1β IL‐6 transcriptionally repressed expression, further regulated PI3K/Akt signaling activation. Inhibition or reversed effects on polarization. downregulation infarct size scores MCAO‐treated mice. mitigated activating signaling, indicating potentially protective action

Language: Английский

Identification of Novel Biomarkers for Ischemic Stroke Through Integrated Bioinformatics Analysis and Machine Learning DOI

Juan Jia,

Liang Niu, Peng Feng

et al.

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: Jan. 25, 2025

Language: Английский

Citations

1
Association of TAB2 gene polymorphism with endometrial cancer susceptibility and clinical analysis DOI Open Access
Siyu Long, Yanyun Wang

Journal of Turkish Society of Obstetric and Gynecology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Transforming growth factor-β-activated kinase 1 binding protein 2 (TAB2) plays a vital role in inflammatory pathways. It has also been considered potential target for the enhancement of antiestrogen effects. Previous evidence indicated that TAB2 gene variants are associated with several diseases, whereas their correlation endometrial cancer (EC) is unclear. This study aims to initially explore association between polymorphisms (rs237028 /AG, rs521845 T/G, and rs652921 T/C) EC. Polymerase chain reaction-restriction fragment length polymorphism was applied determine genotype composition allele frequencies variant 270 EC patients 294 healthy controls. The G related increase risk [p=0.08, odds ratio (OR): 0.72, 95% confidence interval (CI): 0.56-0.91]. Moreover, different genetic models (p=0.017, OR: 0.63, CI: 0.44-0.91 codominant model; p=0.0051, 0.61, 0.43-0.87 dominant model). For rs237028, percentage AG highly differentiated tumours (G1) significantly higher than moderately, poorly (G2/G3) (p=0.031, 0.77, 0.45-1.30). Our results showed TAB2, risk, suggesting may play crucial prognosis.

Language: Английский

Citations

0
Dexmedetomidine pretreatment alleviates brain injury in middle cerebral artery occlusion (MCAO) model rats by activating PI3K/AKT/NF-κB signaling pathway DOI
Wei Gao,

Xue Lv,

Hao Li

et al.

Journal of Toxicology and Environmental Health, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: Feb. 24, 2025

Cerebral ischemia-reperfusion injury (CIRI) is a prevalent clinical complication associated with reperfusion following ischemic stroke resulting in neuronal damage and cognitive impairment. Dexmedetomidine (DEX), highly selective α2-adrenoceptor agonist sedative, analgesic properties, frequently utilized as sedative anesthetic surgeries, believed to play crucial role the prognosis of patients suffering from CIRI. However, mechanism underlying DEX CIRI remains be determined. This study aimed investigate neuroprotective effects Dex rats In treatment group, (50 µg/kg) was administered intraperitoneally 30 min prior surgery. Middle cerebral artery occlusion (MCAO) used model occurred for 2 h followed by blood 24, 72, 120 or 168 h. Neurological function assessed Longa neurological score test demonstrated significantly reduced scores increased % infarct size MCAO group which blocked suggesting that might effective treating stroke. animals, 2,3,5-triphenyltetrazolium chloride (TTC) showed large marked areas infarction were diminished DEX. Using Western blot analysis, results protein expression levels TNF-α IL-6 accompanied PI3K/AKT signaling pathway. pretreatment reversed evidenced decrease elevated PI3K/AKT/NF-κB Data improved neuromotor performance functions animals consequences diminishing inflammation activation

Language: Английский

Citations

0
Immune function in mice enhanced by lamb soup colloidal nanoparticles: Plasma immune, metabolomics, signaling pathways DOI
Jianing Fu, Shaobo Li, Ling Liu

et al.

Food Research International, Journal Year: 2025, Volume and Issue: unknown, P. 116243 - 116243

Published: March 1, 2025

Language: Английский

Citations

0
Aconiti Lateralis Radix Praeparata ameliorates heart failure via PI3K/AKT/Bnip3 pathway DOI Creative Commons
Wenxiu Liu,

Xingju Zou,

Yang Zheng

et al.

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

Published: March 26, 2025

Background Chronic heart failure (CHF) is one of the leading causes high mortality worldwide. It characterized by pathological hypertrophy and poses a major threat to human health. Aconiti Lateralis Radix Praeparata widely used in ancient China treat CHF. However, pathology obscured, necessitating further exploration. Methods Prospective targets were predicted network analysis. A transverse aortic constriction (TAC) mice model was subsequently constructed determine effects aqueous extract (AEA) on The echocardiography performed investigate cardiac function. Histopathological analysis tissue conducted assess myocardial fibrosis. Nontargeted metabolomics analyze serum metabolites. phosphorylation level PI3K AKT, downstream such as Bnip3, p62, Atg5, LC3II measured Western blotting. In vitro , norepinephrine (NE) stimulate hypertrophy. Parameters reactive oxygen species levels, mitochondrial membrane potential, ATP concentration, CK/MB content detected H9c2 cells. Results AEA significantly alleviated Network indicated participation AKT CHF, modulated Praeparata. vivo administration effectively ameliorated performance, evidenced elevation ejection fraction. displayed diminishment collagen fiber. Metabolomics showed that several metabolites tetrahydroxycorticosterone, decylubiquinone taurocholic acid increased TAC serum. Additionally, levels expression Drp1, Opa1, Atg5 altered group. NE stimulation cell surface area deteriorated functions partially reversed results, mechanism associated with mitophagy. Conclusion This study revealed improved function via PI3K/AKT/Bnip3 pathway.

Language: Английский

Citations

0
Bavachinin attenuates cerebral ischemia/reperfusion injury in rats via its anti-inflammatory and antioxidant effects DOI

Amirhossein Atlasbaf,

Armin Hashem Kodehei,

Ensiyeh Bahadoran

et al.

Tissue and Cell, Journal Year: 2025, Volume and Issue: 95, P. 102886 - 102886

Published: March 30, 2025

Language: Английский

Citations

0
Folic Acid Promotes Peripheral Nerve Injury Repair via Regulating DNM3-AKT Pathway Through Mediating Methionine Cycle Metabolism DOI Creative Commons

Weibo Kang,

Yanli Zhang,

Wei Cui

et al.

NeuroMolecular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: March 31, 2025

Emerging evidence suggests that folic acid (FA) supports nerve repair, but its beneficial effects in peripheral injury (PNI) remains unclear. This study aims to investigate protective of FA against PNI and the underlying molecular mechanisms. High-performance liquid chromatography-tandem mass spectrometry was utilized for precise quantification metabolites. A sciatic crush model established rats, followed by assessments cell proliferation, apoptosis, motor function using CCK-8 assays, flow cytometry, balance beam test, respectively. Neuromorphological observations, electromyography, ELISA were conducted evaluate structural, electrophysiological, biochemical parameters. In vitro, restored methionine cycle Schwann cells neurons disrupted enzyme inhibition, improving viability, reducing preserving cellular structure. vivo, supplementation S-adenosylmethionine homocysteine levels a metabolism disorder enhanced function, neural morphology, neuron survival, electrophysiological recovery after PNI. Epigenetic analyses revealed modulated DNA methylation histone modifications DNM3 promoter, influencing gene expression. Furthermore, facilitated repair via DNM3-AKT pathway, regulating autophagy, oxidative stress-related enzymes. These findings highlight FA's potential promoting through metabolic epigenetic

Language: Английский

Citations

0
Integrative Proteomic and Phosphoproteomic Profiling Reveals Molecular Mechanisms of Hypoxic Adaptation in Brandt’s Voles (Lasiopodomys brandtii) Brain Tissue DOI Creative Commons
Panqin Wang,

Yongyan Liu,

Yimeng Du

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 527 - 527

Published: April 1, 2025

Rapid ascent to high altitudes by unacclimatized individuals significantly increases the risk of brain damage, given brain’s heightened sensitivity hypoxic conditions. Investigating hypoxia-tolerant animals can provide insights into adaptive mechanisms and guide prevention treatment hypoxic-ischemic injury. In this study, we exposed Brandt’s voles simulated (100 m, 3000 5000 7000 m) for 24 h performed quantitative proteomic phosphoproteomic analyses tissue. A total 3990 proteins 9125 phosphorylation sites (phospho-sites) were quantified. Differentially expressed (DE) analysis revealed that while protein abundance changes relatively modest, levels exhibited substantial alterations, suggesting rapidly regulate structure function through maintain cellular homeostasis under acute hypoxia. Clustering showed most co-expressed non-monotonic responses with increasing altitude, which enriched in pathways related cytokine secretion regulation glutathione metabolism, contributing reduced inflammation oxidative stress. contrast, phospho-sites monotonic changes, phospho-proteins glycolysis vascular smooth muscle contraction regulation. Kinase activity prediction identified nine hypoxia-responsive kinases, four belonging CAMK family. Immunoblot validated CAMK2A consistent predictions, may play a crucial role response. conclusion, work discovered cope hypoxia three key strategies: (1) enhance cerebral blood flow, (2) glycolytic activation increase energy production, (3) neuroprotective mechanisms.

Language: Английский

Citations

0
Neuroprotective Effects of Peanut Skin Extract Against Oxidative Injury in HT-22 Neuronal Cells DOI Creative Commons
Jinlan Huang, Yue Zhou, Hui Xu

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 544 - 544

Published: April 8, 2025

Background: Oxidative stress is a key therapeutic target in neurological disorders. As processing wastes from the peanut industry, skins are great sources of antioxidants and possess potential neuroprotection. Methods: We prepared skin extract (PSE) investigated its protective effects against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury HT-22 neuronal cells. Results: PSE was rich phenolic compounds (123.90 ± 0.46 mg GAE/g), comprising flavonoids (75.97 0.23 RE/g) proanthocyanidins (53.34 1.58 PE/g), displayed potent radical scavenging activities chemical-based assays. In cells, pretreatment restored balance endogenous antioxidant defense disrupted by t-BHP, as evidenced significant reductions ROS generation lipid peroxidation levels, along with enhanced antioxidants. Specifically, 25 μg/mL reduced levels 53.03%, decreased MDA content 78.82%, superoxide dismutase (SOD) activity 12.42%, improved ratio glutathione (GSH) to oxidized (GSSG) 80.34% compared t-BHP group. Furthermore, rescued mitochondrial membrane collapse, inhibited cytochrome c (Cyt.c) release, prevented subsequent apoptotic death. Notably, neuroprotective efficacy comparable that edaravone, an approved drug. Mechanistic investigations combining network pharmacology experimental validation revealed PI3K/Akt/Nrf2 signaling pathway played pivotal role mediating PSE. Compared t-BHP-treated µg/mL significantly upregulated PI3K/Akt phosphorylation, expression Nrf2, downstream proteins heme oxygenase-1 (HO-1) NAD(P)H dehydrogenase quinone 1 (NQO1). Conclusions: Collectively, these findings demonstrate natural agent oxidative-related

Language: Английский

Citations

0
Remote Ischemic Postconditioning Improve Cerebral Ischemia–Reperfusion Injury Induced Cognitive Dysfunction through Suppressing Mitochondrial Apoptosis in Hippocampus via TK/BK/B2R-Mediated PI3K/AKT DOI Creative Commons
Haocheng Qin,

Lu S,

Baoxue Zhou

et al.

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

Published: April 14, 2025

Remote ischemic postconditioning (RIPostC) is known to improve motor function recovery in animal models, but its efficacy alleviating cognitive impairment caused by stroke remains unclear. This study aims investigate the beneficial role of RIPostC recovering induced cerebral ischemia-reperfusion injury (CIRI). Building upon our previous research findings, we proved that TK/BK/B2R pathway crucial for understanding crosstalk between and RIPostC. Additionally, vitro experiments were conducted using oxygen glucose deprivation/re-oxygenation (OGD/r) HT-22 cell model, which revealed mechanism suppressed mitochondrial apoptosis was mainly through activation B2R/PI3K/AKT signaling pathway, thereby protecting neurons hippocampus from damage. To effect on following stroke, established a rat model left middle artery occlusion reperfusion (MCAO/r). 48 h after MCAO/r, rats subjected 3 circles therapy daily 12 consecutive days. HOE140 used antagonize bradykinin 2 receptor (B2R). Cognitive assessed modified neurological severity score, Morris water maze, novel object recognition test. Local infarct volume measured MRI scanning. The rate hippocampal quantified TUNEL staining. Protein expression levels kallikrein (TK) apoptosis-related proteins, Cyt c, Bcl-2, Bax, cleaved caspase-3, caspase-9, detected tissue Western blot (WB). (BK) serum penumbra an enzyme-linked immunosorbent (ELISA) assay. In experiments, line OGD/r simulate ischemia. WB performed detect proteins PI3K/AKT proteins. cells Annexin-V/PI flow cytometry viability kit. JC-1 staining reactive species evaluate condition. inhibited LY294002. significantly upregulated concentrations TK BK hippocampus. Behavioral tests demonstrated days promoted MCAO/r rats. Through analysis, found effectively reduced results showed neurons. However, therapeutic reversed B2R antagonist HOE14, indicating mediated neuroprotective Cell further confirmed BK/B2R attenuated ischemia-hypoxia cells. vivo activated pathway. Finally, PI3K inhibitor LY294002 anti-apoptotic BK/B2R. alleviated dysfunction associated with CIRI regulating TK/BK/B2R-medated conclusion, represents promising strategy combating inhibiting Moreover, suggest may have broader protective against other ischemia-reperfusion-related diseases.

Language: Английский

Citations

0