Redox Report最新文献

Objective: Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.

Methods: We constructed the MIRI rat model and hypoxia/reoxygenation (H/R) injury cardiomyocytes model. RT-PCR and Western blot were used to investigate the expression of the fat mass and obesity-associated (FTO) gene. Electrocardiogram, echocardiography, triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to assess the model and the effect of FTO overexpression. The generation of reactive oxygen species (ROS) and the levels of superoxide dismutase (SOD2), mitochondrial transcription factor (TFAM) and cytochrome c oxidase I (COXI) were detected to assess the oxidative stress and mitochondrial biogenesis. RNA immunoprecipitation (RIP) and RNA pulldown assays were used to identify the interaction of FTO and PGC-1a. The m6A dot blot, methylated RNA immunoprecipitation PCR (MeRIP-PCR) and RNA stability analysis were used to analyze the regulation of methylation of PGC-1a by FTO.

Results: FTO was downregulated in MIRI rats and H/R induced cardiomyocytes. Overexpression of FTO inhibited ROS level and increased the expression of SOD2, TFAM and COXI in vitro and in vivo. In addition, PGC-1a was identified as a downstream target of FTO. FTO enhanced the stability of PGC-1a mRNA through removing the m6A modification.

Conclusion: Our study revealed the role of FTO regulates the oxidative stress and mitochondrial biogenesis via PGC-1a in MIRI, which may provide a new approach to mitigating MIRI.

Objective: This review aims to explore the roles and mechanisms of cytochrome P450 subfamily 1 (CYP1) enzymes in acute lung injury (ALI), and to discuss their potential as therapeutic targets.

Methods: A comprehensive literature search was conducted using PubMed and Web of Science to identify relevant studies on the involvement of CYP1 enzymes-specifically CYP1A and CYP1B1-in various forms of ALI, including hyperoxic lung injury, sepsis-associated ALI, and COVID-19 pneumonia.

Results: CYP1 enzymes, induced by the aromatic hydrocarbon receptor (AhR), contribute differentially to ALI. CYP1A enzymes exhibit protective effects, whereas CYP1B1 promotes lung injury, potentially through oxidative stress-related pathways such as Nrf2, NF-κB, and MAPK signaling.

Conclusion: The distinct functions of CYP1 isoforms in ALI suggest their clinical relevance, highlighting the potential for isoform-specific targeting in the treatment of acute respiratory conditions.

Background: Melatonin is a powerful free radical scavenger, with cardioprotective effects; however, the mechanism of this cardioprotective activity remains unclear. We hypothesized that melatonin inhibits ferroptosis and protects cardiomyocytes through suppression of the ataxia telangiectasia mutated (ATM)/p53 signaling pathway and reduction of lipid peroxidation.

Methods: Forty-two rat hearts were randomly assigned to a control group or one of six experimental groups (I/R, I/R + melatonin, I/R + melatonin + chloroquine diphosphate5, I/R + chloroquine diphosphate1, I/R + chloroquine diphosphate5, I/R + chloroquine diphosphate25). Thirty C57/BL6 male mice were assigned to 5 groups, with the same grouping as rats. The hearts were reperfused, after which the levels of creatine kinase MB, malondialdehyde, superoxide dismutase, iron, and glutathione/ glutathione oxidized were measured. Triphenyl tetrazolium chloride (TTC) staining, Hematoxylin and eosin staining, X-ray electron microscopy, western blotting, and immunofluorescence were performed to evaluate the effects of melatonin treatment on the pathology, microstructure, and antioxidant enzymes of the myocardium (ferritin heavy chain 1 (FTH1), SLC7A11 (XCT), superoxide dismutase-2 (SOD-2), and glutathione peroxidase 4 (GPX4), p53, and p-p53).

Results: Ischemia/reperfusion increased myocardial lipid peroxidation, iron and p53 contents, as well as damage to the myocardial pathology and mitochondrial structure, and decreased the expression levels of antioxidant enzymes. Melatonin treatment alleviated these effects, which were reversed by chloroquine diphosphate.

Conclusions: These findings suggest that melatonin pretreatment protects cardiomyocytes from I/R injury by inhibiting cell ferroptosis via suppression of the ATM/p53 signaling pathway.

Background: Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure. Sesamin (Ses), a natural polyphenolic compound, possesses diverse pharmacological properties. This study was to explore the effects of Ses on APAP-induced liver injury and the underlying molecular mechanism.

Methods: In vivo, C57BL/6J mice were treated with different doses of Ses for 28 days. After overnight food deprivation, mice were intraperitoneally injected with a single dose of APAP. In vitro, the AML12 and HepG2 cells were pre-treated with Ses and then treated with APAP.

Results: Ses dramatically alleviated APAP-induced hepatocellular injury in vitro and in vivo. Proteomic analysis suggested that the differentially expressed proteins were enriched in ferroptosis, autophagy, and FoxO signaling pathways between the APAP group and the Ses-treated groups. We subsequently found that ferroptosis was significantly inhibited, and autophagy was significantly enhanced in the Ses-treated group. Consistently, Ses obviously reduced the expression of Foxo1. However, hepatocyte-specific knockout Foxo1 abolished the effect of Ses on hepatocyte autophagy and ferroptosis caused by APAP in mice.

Conclusions: Our findings demonstrate that Ses attenuates APAP-induced hepatotoxicity through Foxo1, which mediates both the activation of autophagy and the inhibition of ferroptosis. It provides a new strategy for the prevention and treatment of drug-induced liver injury.

Inflammatory bowel disease (IBD) is a chronic autoimmune condition whose pathogenesis has not been fully elucidated, and current treatments are not definitive and often carry several side effects. The Complementary and Alternative Medicine (CAM) offers a new approach to conventional medicine. However, their clinical application and mechanisms remain limited.Objective: The aim of this review is to evaluate the anti-inflammatory, impact on microbiota and antioxidant efficacy of currently available CAM for IBD.Methods: The literature collection was obtained from Google Scholar, MEDLINE, PubMed and Web of Science (WOS). Studies in both human and animal models, published in English language between 2018 and 2024, were selected. Sixty-seven studies were included in the current review after inclusion and exclusion screening processes.Results: Mostly, studies showed significant anti-inflammatory, gut microbiota restoring, antioxidant effects of polyphenols, polysaccharides, emodin, short-chain fatty acids (SCFA; including butyrate, propionate and acetate), and probiotics although some contrasting results were noted. Current evidence shows that polyphenols exhibit the most consistent result in alleviating IBD pathophysiology, primarily due to their significant SCFA-elevating effect.Discussion: Future studies may focus on human studies, narrowing down on individual factors which may change natural product's metabolism. Further research studies are also essential to obtain therapeutic recommendations.

Oxidative stress, characterized by an imbalance between excessive reactive oxygen species (ROS) production and impaired antioxidant defenses, is closely linked to the pathogenesis of various otorhinolaryngological disorders. Mitochondria, as the primary site of cellular energy production, play a crucial role in modulating oxidative stress. Mitochondrial dysfunction exacerbates ROS generation, leading to cellular damage and inflammatory responses. In otorhinolaryngological diseases, oxidative stress is strongly associated with conditions such as hearing loss, allergic rhinitis, and chronic sinusitis, where oxidative damage and tissue inflammation are key pathological features. Recent studies have highlighted the potential of antioxidant therapies to mitigate oxidative stress and restore homeostasis, offering promising avenues for alleviating symptoms in these diseases. However, despite the encouraging results from early-stage research, the clinical efficacy of antioxidant interventions remains to be fully established. This review provides an overview of the role of oxidative stress in otorhinolaryngological diseases and evaluates the therapeutic potential of antioxidant strategies.

Background: Acetaminophen (APAP) is a widely used antipyretic and analgesic agent, and acute exposure can lead to renal injury. Sesamin (Ses) is known for its various health benefits. However, it remains unclear whether Ses exerts a protective effect against APAP-induced kidney injury.

Methods: In vivo, C57BL/6 mice were pretreated with Ses and injected intraperitoneally with APAP. In vitro, human kidney proximal tubule cells 2 were pretreated with Ses, and then models of kidney injury induced by APAP were established. Kidney damage was evaluated by morphological, inflammation, oxidative stress and protein analyzes.

Results: Ses significantly improved APAP-induced nephrotoxicity in vitro and in vivo models. Transcriptomic analysis revealed that the differentially expressed genes were enriched in ferroptosis and apoptosis signaling pathways, identifying heme oxygenase 1 (HMOX1) as a core protein. In the Ses-treated group, ferroptosis and apoptosis were significantly inhibited, while HMOX1 was effectively restored. In cell experiments, both the HMOX1 agonist hemin and Ses attenuated ferroptosis and apoptosis. HMOX1 inhibitor Zinc Protoporphyrin significantly eliminated the protective effect of Ses.

Conclusion: Ses alleviates APAP-induced renal injury by mediating the inhibition of ferroptosis and apoptosis via HMOX1. This study provides a new strategy for the prevention and treatment of drug-induced renal injury.

Reactive nitrogen species (RNS) play a pivotal role in tumorigenesis through complex regulatory networks within the tumor microenvironment (TME). This review summarizes recent advances in understanding RNS-mediated mechanisms, focusing on core components and their concentration-dependent bidirectional effects on tumor cell proliferation, apoptosis, invasion, and metabolism. It explores RNS sources in the TME, including autonomous synthesis by tumor cells and secretion by immune cells (e.g., TAMs, TANs), and their modulation of key signaling pathways (e.g., PI3 K/Akt, NF-κB, HIF-1α). Additionally, the review discusses RNS-mediated regulation of immune responses and angiogenesis, highlighting their dual roles in promoting tumor progression and enabling immune evasion. Finally, it outlines potential clinical applications, such as RNS-targeted diagnostic probes and therapeutic strategies (e.g., iNOS inhibitors, NO donors), providing a foundation for precision oncology.

Background: Oxidative stress plays a critical role in the degeneration of midbrain dopaminergic (DA) neurons in Parkinson's disease (PD). However, therapies targeting redox mechanisms are hindered by a lack of scalable and inexpensive redox-focused preclinical models.

Methods: We stably expressed the glutathione-specific redox-sensitive fluorescent protein Grx-roGFP2 in SH-SY5Y and BE(2)-M17 neuroblastoma cell lines. We developed an improved differentiation protocol using staurosporine and dbcAMP to enhance dopaminergic-like characteristics, assessed by DA marker expression, and characterized responses to PD-relevant toxins.

Results: BE(2)-M17 cells expressed higher DA markers than SH-SY5Y cells, and the improved protocol further increased DA markers. Differentiated neuroblastoma cells with dopaminergic-like features showed greater sensitivity to MPP+ and paraquat, with reduced viability, increased oxidative stress, glutathione oxidation, decreased TH expression, and altered neuronal morphology, paralleling patterns observed in PD-related oxidative injury. roGFP2 enabled robust, real-time redox monitoring, correlating oxidative stress with phenotype. Sublethal toxin exposure caused mitochondrial alterations and redox shifts. Pretreatment with N-acetyl-L-cysteine (NAC) mitigated oxidative stress, improved viability, and partially restored TH expression and morphology.

Conclusion: This neuroblastoma-based model with dopaminergic-like features enables scalable, real-time redox monitoring and detailed phenotypic analyses. It expands access to redox biology platforms for investigating neurodegeneration and evaluating antioxidant therapeutic strategies relevant to neurodegeneration.

Periodontitis, a common dental illness, causes periodontal tissue inflammation and irreversible bone loss, inevitably resulting in tooth loss. Hyperhomocysteinaemia (HHcy), defined as blood total homocysteine (Hcy) levels greater than 15 µmol/L, is linked to increased cardiovascular disease risk. Mounting evidence indicates a connection between HHcy and periodontitis; however, the underlying processes remain unknown. Herein, we explored the mechanisms by which HHcy exacerbates periodontal tissue inflammation and osteoclast formation. In an animal model of periodontitis treated with HHcy, periodontal attachment loss was aggravated, and both systemic and gingival tissue inflammation levels tended to increase; additionally, antioxidant-related proteins were suppressed and expressed at low levels, whereas oxidative damage-related protein expression increased. In RAW264.7 cells treated with LPS or LPS + Hcy, the LPS + Hcy group presented increased reactive oxygen species (ROS) fluorescence intensity, and Nrf2/HO-1 signalling pathway suppression was associated with inflammatory cytokine (TNF-α) expression. In monocyte osteoclasts treated with Rankl or Rankl + Hcy, the Rankl + Hcy group presented Nrf2/HO-1 signalling pathway suppression, an increase in osteoclast-related proteins (NFATc-1 and CTSK), and a more pronounced osteoclastic phenotype. Therefore, HHcy may exacerbate inflammation severity and osteoclast generation in periodontitis by promoting ROS production and inhibiting the Nrf2/HO-1 signalling pathway.