Redox Report最新文献

This study sought to ascertain if zinc nanoparticles (ZnNPs) could lessen the toxicity of azoxystrobin (AZ). This naturally occurring methoxyacrylate is one of the most often used fungicides in agriculture in male albino rats. Six sets of 60 mature male albino rats were randomly assigned: control (distilled water), Azoxystrobin formulation (AZOF), Azoxystrobin nano-formula (AZON), ZnNPs, AZOF + ZnNPs, and AZON + ZnNPs. Blood and tissues were obtained for further immunohistochemical, pathological, and biochemical examination. The results showed that exposure to AZOF and AZON significantly increased the levels of the oxidative stress indicators glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Additionally, AZOF significantly impacts liver function bioindicators, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. AZOF and AZON induced damage to the liver and kidney by disrupting vascular dilatation and causing hemorrhages, apoptosis, inflammatory lymphocytes, and necrosis. Furthermore, co-administration of ZnNPs with fungicides (AZOF and AZON) can gently enhance the alterations of oxidative stress and liver function bioindicators levels. These findings showed that ZnNPs could help male rats receiving AZ treat their histologically abnormal liver and kidney.

Background: Lung cancer is one of the leading causes of cancer-related deaths worldwide with limited treatment options available. The anti-tumor effects of the TrxR inhibitor Butaselen (BS/BS1801) on lung cancer and its underlying mechanisms remain unknown.

Methods: This study utilized lung cancer cell lines, LLC1-bearing mice models, and organoids to detect the inhibitory effects of BS on lung cancer. The ROS-induction and apoptotic role of BS on lung cancer cells and molecular mechanisms were assessed with flow cytometry, western blot, Co-IP, real-time PCR, ChIP, reporter gene assay, ELISA, and bisulfite pyrosequencing.

Results: BS can effectively inhibit lung cancer both in vitro and in vivo, by triggering ROS-induced apoptosis. The inactivation of NF-κB and MAPK signaling pathways, along with the activation of PI3K-Akt and HBP1 signaling pathways, are involved in BS's suppression of lung cancer. HBP1 is a novel downstream target of the Trx system. The activation of HBP1 by BS is dependent on ROS accumulation and further leads to the transcriptional inhibition of DNMT1 and the demethylation of the whole genome, as well as the promoters of p21 and HOXA9.

Conclusion: The TrxR/Trx inhibitor butaselen suppresses lung cancer by triggering ROS-induced apoptosis. This study provides a novel and effective regimen for treating lung cancer.

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized in keloid pathogenesis. This study investigates the role and mechanisms of HOXA11-AS in keloid formation.

Methods: Expression levels of HOXA11-AS and related proteins were measured in keloid tissues and fibroblasts using qRT-PCR, Western blot, and ELISA. Functional assays assessed cell proliferation, migration, fibrosis, and oxidative stress. RIP, ChIP, Co-IP, FISH, and luciferase assays were used to explore interactions among HOXA11-AS, YY1, Nrf2, EZH2, and DNMT1. An in vivo mouse xenograft model validated the findings.

Results: HOXA11-AS was upregulated in keloids. Silencing HOXA11-AS reduced fibroblast proliferation, migration, fibrosis, and oxidative stress. Its overexpression had the opposite effect, which was reversed by Nrf2 pathway inhibition. HOXA11-AS promoted the methylation of the Nrf2 promoter via DNMT1 recruitment, mediated by EZH2. YY1 enhanced HOXA11-AS transcription by binding to its promoter. The YY1/HOXA11-AS axis was confirmed in vivo.

Conclusion: YY1-induced HOXA11-AS drives keloid formation by promoting oxidative stress and inflammation through epigenetic suppression of Nrf2 signaling.

Objective: Chronic liver diseases (CLDs) are prevalent globally. The purpose of the current study was to elucidate the regulatory mechanisms underlying the pathophysiological processes in CLDs.

Methods and results: Using the GEO database, we identified cysteine and methionine metabolism as a commonly enriched pathway in some CLDs. We then confirmed that hepatic cystathionine γ-lyase (Cth), a key enzyme in this pathway, was significantly downregulated in some CLDs in humans and rodent models. Cth-deficient mice exhibited hepatic necroptosis, inflammation and mitochondrial impairment. Omics revealed methionine cycle dysregulation and reduced betaine, a methionine cycle metabolite. Betaine supplementation rewired the methionine cycle, and alleviated necroptosis, inflammation and mitochondrial impairment. Dysregulation of fatty acid β-oxidation, glycolysis and lipid biosynthesis caused by Cth deficiency was improved by betaine. Cth deficiency decreased Pparα, Nrf2, Pgc-1α, and Srebf2 (the transcription factors linked to mitochondria function and metabolism) expression while increasing Irf8 and Irf9, changes reversed by betaine. Histone methylation (H3K9me3, H3K27me3, H3K79me3) decreased, and acetylation (H3K27ac) increased with Cth deficiency, which betaine corrected. Irf8 and Irf9 and Ppara and Ppargc1a expression were regulated by H3K27me3 and H3K79me3 in hepatocytes, respectively.

Discussion: Our study indicates that CTH is the key factor for maintaining hepatocyte function and survival through homeostasis of the methionine cycle and immediately highlights a new potential target of hepatic protection therapy for some CLDs.

Background: Sensory neurons relay the pain signals to the brain via the nociceptive system. Notably, reactive oxygen species (ROS) serve as signaling molecules in the somatosensory system; however, their contribution to sensing noxious stimuli remains poorly understood.

Methods: Herein, the role of protein kinase G (PKG)1α, which is highly expressed in sensory neurons and serves as a ROS target, was investigated in sensory neurons in the processing of acute nociceptive pain. Cys42Ser PKG1α-knock-in (PKG1α-KI) mice, devoid of redox-dependent PKG1α activation, were subjected to behavioral testing, ROS detection assays, gene expression experiments, and imaging analyses.

Results: Interestingly, PKG1α-KI mice showed reduced behavioral responses to noxious heat and the transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist capsaicin. Moreover, capsaicin-induced sensory neuron stimulation upregulated ROS production and redox-dependent PKG1α activation. Calcium imaging results and patch-clamp recordings revealed that capsaicin-induced calcium flux and neuronal excitability was reduced in sensory neurons of PKG1α-KI mice.

Conclusion: Altogether, the findings of this study show the effects of redox-dependent PKG1α activation on capsaicin/TRPV1-mediated signaling in sensory neurons during acute nociceptive pain.

Objectives: Many countries in the world are entering society with an aging population. The kidney is one of the most sensitive organs in the body to aging. Kidney function gradually declines with aging. Renal aging is one of the main triggers of CDK. Therefore, many researchers in the field are looking for natural, green and healthy anti-renal-aging bioactive molecules.

Methods and results: Western-blot, ELISA and indirect immunofluorescence were performed to evaluate the biological activity of fucoxanthin against renal aging in vitro and in vivo models. First, in the in vitro model, we evaluated the effect of fucoxanthin on renal cell senescence. We found that fucoxanthin could alleviate the kidney cell senescence caused by H₂O₂ by detecting a series of senescence markers. In the in vivo model, the experimental results showed that fucoxanthin could alleviate the aging of the kidney by Sa-β-gal staining and detection of aging-related marker molecules. Furthermore, we also found that fucoxanthin could alleviate kidney fibrosis.

Conclusions: In this study, our results showed that fucoxanthin was able to alleviate renal aging in vivo and in vitro models, suggesting that fucoxanthin could be a functional food to treat and relieve kidney aging.

Mitochondrial health is maintained in a steady state through mitochondrial dynamics and autophagy processes. Recent studies have identified healthy mitochondria as crucial regulators of cellular function and survival. This process involves adenosine triphosphate (ATP) synthesis by mitochondrial oxidative phosphorylation (OXPHOS), regulation of calcium metabolism and inflammatory responses, and intracellular oxidative stress management. In the skeletal system, they participate in the regulation of cellular behaviors and the responses of osteoblasts, osteoclasts, chondrocytes, and osteocytes to external stimuli. Indeed, mitochondrial damage or dysfunction occurs in the development of a few bone diseases. For example, mitochondrial damage may lead to an imbalance in osteoblasts and osteoclasts, resulting in osteoporosis, osteomalacia, or poor bone production, and chondrocyte death and inflammatory infiltration in osteoarthritis are the main causes of cartilage degeneration due to mitochondrial damage. However, the opposite exists for osteosarcoma, where overactive mitochondrial metabolism is able to accelerate the proliferation and migration of osteosarcoma cells, which is a major disease feature. Bone is a dynamic organ and osteocytes play a fundamental role in all regions of bone tissue and are involved in regulating bone integrity. This review examines the impact of mitochondrial physiological function on osteocyte health and summarizes the microscopic molecular mechanisms underlying its effects. It highlights that targeted therapies focusing on osteocyte mitochondria may be beneficial for osteocyte survival, providing a new insight for the diagnosis, prevention, and treatment of diseases associated with osteocyte death.

Objectives: Asthma, a prevalent chronic disease, poses significant health threats and burdens healthcare systems. This study focused on the role of bronchial epithelial cells in asthma pathophysiology.

Methods: Bioinformatics was used to identify key asthmarelated genes. An ovalbumin-sensitized mouse model and an IL-13-stimulated Beas-2B cell model were established for further investigation.

Results: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a crucial gene in asthma. CEACAM5 expression was elevated in asthmatic mouse lung tissues and IL-13-stimulated Beas-2B cells, primarily in bronchial epithelial cells. CEACAM5 induced reactive oxygen species (ROS), lipid peroxidation, and ferroptosis. Interfering with CEACAM5 reduced ROS, malondialdehyde levels, and enhanced antioxidant capacity, while inhibiting iron accumulation and autophagy. Overexpression of CEACAM5 in IL-13-stimulated cells activated the JAK/STAT6 pathway, which was necessary for CEACAM5-induced autophagy, ROS accumulation, lipid peroxidation, and ferroptosis.

Conclusion: CEACAM5 promotes ferroptosis and autophagy in airway epithelial cells via the JAK/STAT6 pathway, exacerbating asthma symptoms. It represents a potential target for clinical treatment.

Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.