BSA-stabilized selenium nanoparticles ameliorate intracerebral hemorrhage's-like pathology by inhibiting ferroptosis-mediated neurotoxicology via Nrf2/GPX4 axis activation

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103268 - 103268

Published: July 17, 2024

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH critical for enhancing patient prognosis and survival rate. A novel form cell death called ferroptosis intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated significant preventive impact bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected system, neuroprotective effect on stroke mechanism remain unknown. Therefore, based favorable biocompatibility BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed perform BSA-SeNPs therapy. As expected, these could effectively improve cognitive deficits ameliorate hippocampal neuron. Furthermore, reverse morphology mitochondria enhanced mitochondrial function, evidenced by respiration function (OCR) membrane potential (MMP). Mechanistically, efficiently activate Nrf2 enhance expression antioxidant GPX4 at mRNA protein levels, further inhibit lipid peroxidation production erastin-induced ferroptotic damages. Taken together, this study not only sheds light clinical application but also provides its newly theoretical support strategy intervention treatment impairment following ICH.

Language: Английский

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The Dual Angiogenesis Effects via Nrf2/HO-1 Signaling Pathway of Melatonin Nanocomposite Scaffold on Promoting Diabetic Bone Defect Repair

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2709 - 2732

Published: March 1, 2024

Purpose: Given the escalating prevalence of diabetes, demand for specific bone graft materials is increasing, owing to greater tendency towards defects and more difficult defect repair resulting from diabetic disease (DBD). Melatonin (MT), which known its potent antioxidant properties, has been shown stimulate both osteogenesis angiogenesis. Methods: MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, contained within a 3D printing polycaprolactone/β-Tricalcium phosphate (PCL/β-TCP) scaffold. The osteogenic capacity nanocomposite scaffold under conditions demonstrated via in vitro vivo studies underlying mechanisms were investigated. Results: Physicochemical characterization experiments confirmed successful fabrication scaffold, can achieve long-lasting sustained release MT. that exhibited enhanced capacity, elucidated by dual angiogenesis effects activated through NF-E2–related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including enhancement enzyme activity reduce oxidative stress damage vascular endothelial cells (VECs) directly stimulating growth (VEGF) production, reversed angiogenesis-osteogenesis uncoupling promoted conditions. Conclusion: This study research prospective clinical implications as novel treating enhancing fusion individuals. Keywords: defect, melatonin, Nrf2/HO-1 effects,

Language: Английский

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Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 978 - 978

Published: Aug. 9, 2024

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The can recur frequently and tends to form tophus joints. Current therapeutic drugs for acute phase of GA have many side effects limitations, are unable prevent recurrent attacks formation, overall efficacy unsatisfactory. Therefore, we need advance research on microscopic mechanism seek safer more effective through relevant targets block process. shows that pathogenesis closely related NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, Ferroptosis. However, after synthesizing sorting out above mechanisms, it found presence ROS throughout almost entire spectrum micro-mechanisms gout process, which combines multiple immune responses a large network diagram complex tight connections involved studies shown cell necrosis, pathological signs be effectively suppressed modulating network-related targets. In this article, one hand, investigated generative generation its association with GA. On other explored potential treatment prevention provide reference ideas development highly

Language: Английский

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L-theanine abates oxidative stress and mitochondrial dysfunction in myocardial ischemia-reperfusion injury by positively regulating the antioxidant response

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 486, P. 116940 - 116940

Published: April 25, 2024

Language: Английский

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PNPO–PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1108 - 1127

Published: May 31, 2024

Abstract Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including hypoxia-inducible factor pathway, have been identified, those operating prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5′-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor regulates lysosomal activity macrophages. Decreased PNPO under reduced active form pyridoxal (PLP), inhibited acidification, macrophages led iron dysregulation, TET2 protein loss delayed resolution inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed hypoxia, resulting inhibition consequent proinflammatory phenotypes The PNPO–PLP axis creates a distinct layer sensing gradually shuts down metabolism response deprivation.

Language: Английский

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Amelioration of nitroglycerin-induced migraine in mice via Wuzhuyu decoction: Inhibition of the MZF1/PGK1 pathway and activation of NRF2 antioxidant response

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 326, P. 117930 - 117930

Published: Feb. 17, 2024

Language: Английский

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Methyl 3,4-dihydroxybenzoate alleviates oxidative damage in granulosa cells by activating Nrf2 antioxidant pathway

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 25, 2024

Abstract Oxidative damage induced granulosa cells (GCs) apoptosis was considered as a significant cause of compromised follicle quality, antioxidants therapy has emerged potential method for improving endometriosis pregnancy outcomes. Here, we found that GCs from patients show increased oxidative stress level. Methyl 3,4-dihydroxybenzoate (MDHB), small molecule compound is extracted natural plants, reversed tert-butyl hydroperoxide (TBHP) damage. Therefore, the aim this study to assess protective effect MDHB and its mechanisms. TUNEL staining immunoblotting cleaved caspase-3/7/9 showed attenuated TBHP apoptosis. Mechanistically, treatment decreased cellular mitochondria ROS production, improved mitochondrial function by rescuing membrane (MMP) ATP production. Meanwhile, protein upregulated expression vital antioxidant transcriptional factor Nrf2 enzymes SOD1, NQO1 GCLC inhibited state, further beneficial oocytes embryos quality. may represent drug candidate in protecting endometriosis, which can improve outcomes endometriosis-associated infertility.

Language: Английский

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Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats

Journal of Orthopaedic Surgery and Research, Journal Year: 2024, Volume and Issue: 19(1)

Published: June 28, 2024

Abstract Background Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired repair, resulting in age-related disorders. Ferroptosis, a unique iron-dependent form of programmed death, might participate the process senescence. However, whether ferroptosis plays role TSPC regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) provide significant advantages musculoskeletal inflammation regulation. The effects mechanism PL-Exos on are worthy further study. Methods Herein, we examined pathogenesis were isolated determined by TEM, particle size analysis, western blot mass spectrometry identification. We investigated function underlying mechanisms via blot, real-time quantitative polymerase chain reaction, immunofluorescence analysis vitro. was evaluated HE staining, Safranin-O biomechanical tests rotator cuff tear model rats. Results discovered involved senescent TSPCs. Furthermore, mitigated aging phenotypes TSPCs induced t-BHP preserved their proliferation tenogenic capacity. vivo animal results indicated improved tendon-bone healing properties mechanical strength. Mechanistically, activated AMPK phosphorylation downstream nuclear factor erythroid 2-related 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading suppression lipid peroxidation. inhibition or GPX4 blocked protective effect against t-BHP-induced Conclusion In conclusion, play crucial aging. AMPK/Nrf2/GPX4 activation found inhibit ferroptosis, consequently Our provided new theoretical evidence for potential application restrain promote regeneration.

Language: Английский

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Mercapto-NSAIDs Generate a Non-Steroidal Anti-Inflammatory Drug (NSAID) and Hydrogen Sulfide

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A new class of mercapto-NSAIDs that generate persulfide, H 2 S, and the NSAID is reported.

Language: Английский

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Keap1-independent Nrf2 regulation: a novel therapeutic target for treating kidney disease

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103593 - 103593

Published: March 12, 2025

Language: Английский

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