Redox Report最新文献

{"title":"Scutellarin suppresses Mycobacterium tuberculosis-induced pyroptosis in macrophages by inhibiting the HIF-1α-mediated Warburg effect.","authors":"Jianchao Wu, Fanglin Liu, Jingjing Shen, Hemin Zhang, Yaqi Liu, Jinxia Sun, Guizhen Yang, Yuejuan Zheng, Xin Jiang","doi":"10.1080/13510002.2025.2565861","DOIUrl":"10.1080/13510002.2025.2565861","url":null,"abstract":"<p><strong>Background: </strong>Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a major global health threat due to prolonged treatment and drug-resistant strains. Host-directed therapy (HDT), which modulates host-pathogen interactions, offers potential to shorten treatment and limit resistance. This study investigates the effects of Scutellarin (SCU), a flavonoid from Scutellaria baicalensis, on Mtb-infected macrophages within the HDT framework.</p><p><strong>Methods: </strong>Anti-pyroptotic and anti-inflammatory effects of SCU were assessed in Mtb-infected THP-1 and J774A.1 macrophages, and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Mitochondrial function was evaluated by oxygen consumption rate(OCR), membrane potential, and superoxide levels; glycolytic activity was measured by proton efflux rate (GlycoPER). Expression of inflammasome-related markers was analyzed by Western blot, qPCR, ELISA, immunofluorescence, and flow cytometry. The role of hypoxia-inducible factor 1-alpha (HIF-1α) was examined via siRNA knockdown.</p><p><strong>Results: </strong>SCU inhibited NLRP3 inflammasome activation, reduced IL-1β and IL-18 secretion, and attenuating pyroptosis. It restored mitochondrial integrity by regulating p-DRP1, MFN2, and Cytochrome C expression, and suppressed HIF-1α-mediated glycolytic reprogramming. Silencing of HIF-1α confirmed its role in SCU's mechanism. In vivo, SCU reduced pulmonary inflammation and cytokine release in LPS-induced ALI.</p><p><strong>Conclusion: </strong>SCU alleviates Mtb-induced pyroptosis and inflammation in macrophages by inhibiting the HIF-1α-mediated Warburg effect.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2565861"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects of AgNPs and zileuton on PCOS via ferroptosis and inflammation mitigation.","authors":"Amira K Eltokhy, Rehab Ahmed Ahmed El-Shaer, Omnia Safwat El-Deeb, Eman E Farghal, Rowida Raafat Ibrahim, Rasha Elesawy, Marwa Mahmoud Awad, Radwa Ismail, Shaimaa M Motawea, Doaa Shatat, Yasser Mostafa Hafez, Hend Ahmed El Hanafy, Marwa Mohamed Atef","doi":"10.1080/13510002.2024.2445398","DOIUrl":"https://doi.org/10.1080/13510002.2024.2445398","url":null,"abstract":"<p><strong>Background: </strong>The most prevalent endocrine disorder affecting women is PCOS. Programmed death of ovarian cells has yet to be elucidated. Ferroptosis is a kind of iron-dependent necrosis featured by significantly Fe⁺²-dependent lipid peroxidation. The ongoing study aimed to reinforce fertility by combining therapy with AgNPs and (Zileuton) in PCOS rats' model.</p><p><strong>Methods: </strong>The study included 75 adult female rats divided into 5 groups; control, PCOS, PCOS treated with AgNPs, PCOS treated with Zileuton, and PCOS group treated with AgNPs and Zileuton. The study investigated the anti-ferroptotic, anti-inflammatory, antioxidant, antiapoptotic, histopathological and immunohistochemical examinations of COX-2 and VEGF.</p><p><strong>Results: </strong>The combination of AgNPs and Zileuton showed significant reduction of inflammatory mediators (IL-6, TNF-α, NFk-B) compared with diseased group (<i>P</i>-<i>value</i> < 0.05), regression of ferroptosis marks (Panx1 and TLR4 expression, Fe⁺² levels) compared with diseased group (<i>P</i>-<i>value</i> < 0.05), depression of apoptotic marker caspase 3 level compared with diseased animals (<i>P</i>-value < 0.05), depression of MDA level, elevation of HO-1, GPx4 activity, and reduction of Cox2 and VEGF as compared with the diseased, AgNPs or zileuton-treated groups (<i>P</i>-value < 0.05).</p><p><strong>Conclusion: </strong>The study showed that the combination of AgNPs and zileuton guards against, inflammation, apoptosis, and ferroptosis in PCO.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2445398"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: Prophylactic role of Enhydra fluctuans against arsenic-induced hepatotoxicity via antiapoptotic and antioxidant mechanisms.","authors":"","doi":"10.1080/13510002.2025.2538364","DOIUrl":"10.1080/13510002.2025.2538364","url":null,"abstract":"","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2538364"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation.","authors":"Jun Jin, Kai Wang, Chenxi Lu, Chenghao Yao, Feng Xie","doi":"10.1080/13510002.2025.2539030","DOIUrl":"10.1080/13510002.2025.2539030","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) are increasingly recognized in keloid pathogenesis. This study investigates the role and mechanisms of HOXA11-AS in keloid formation.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>YY1-induced HOXA11-AS drives keloid formation by promoting oxidative stress and inflammation through epigenetic suppression of Nrf2 signaling.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2539030"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystathionine γ-lyase downregulation promotes liver injury and necroptosis through reprogramming of methionine cycle.","authors":"Cichun Wu, Wei Zhang, Wenhu Liu, Zhengshan Tang, Shifang Peng, Lei Fu, Xin Ni","doi":"10.1080/13510002.2025.2531650","DOIUrl":"10.1080/13510002.2025.2531650","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods and results: </strong>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 (<i>Cth</i>), a key enzyme in this pathway, was significantly downregulated in some CLDs in humans and rodent models. <i>Cth</i>-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 <i>Cth</i> deficiency was improved by betaine. <i>Cth</i> deficiency decreased Pparα, Nrf2, Pgc-1α, and Srebf2 (the transcription factors linked to mitochondria function and metabolism) expression while increasing <i>Irf8</i> and <i>Irf9</i>, changes reversed by betaine. Histone methylation (H3K9me3, H3K27me3, H3K79me3) decreased, and acetylation (H3K27ac) increased with <i>Cth</i> deficiency, which betaine corrected. Irf8 and Irf9 and Ppara and Ppargc1a expression were regulated by H3K27me3 and H3K79me3 in hepatocytes, respectively.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2531650"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-dependent activation of protein kinase G1α contributes to transient receptor potential cation channel subfamily V member 1-mediated acute nociceptive pain behavior.","authors":"Tim Berg, Katharina Metzner, Nabil Bahrami, Elena Wang, Maximilian Koch, Philip Eaton, Achim Schmidtko, Wiebke Kallenborn-Gerhardt","doi":"10.1080/13510002.2025.2549954","DOIUrl":"https://doi.org/10.1080/13510002.2025.2549954","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"1-17"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucoxanthin alleviates renal aging by regulating the oxidative stress process and the inflammatory response <i>in vitro</i> and <i>in vivo</i> models.","authors":"Xiaomei Zhang, Weidong Qiang, Yongxin Guo, Jingli Gong, Huan Yu, Di Wu, Pengxiang Tang, Ma Yidan, Huifeng Zhang, Xin Sun","doi":"10.1080/13510002.2025.2511458","DOIUrl":"10.1080/13510002.2025.2511458","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods and results: </strong>Western-blot, ELISA and indirect immunofluorescence were performed to evaluate the biological activity of fucoxanthin against renal aging <i>in vitro</i> and <i>in vivo</i> models. First, in the <i>in vitro</i> 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 <i>in vivo</i> 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.</p><p><strong>Conclusions: </strong>In this study, our results showed that fucoxanthin was able to alleviate renal aging <i>in vivo</i> and <i>in vitro</i> models, suggesting that fucoxanthin could be a functional food to treat and relieve kidney aging.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2511458"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO1-NMNAT3 axis dysregulation promotes doxorubicin cardiotoxicity: NAD⁺ replenishment as a redox-targeted antioxidant therapy.","authors":"Fang Cheng, Minzhu Zhao, Qi Wang, Hongli Xiong, Kai Yu, Chong Chen, Ying Zhu, Yemiao Chen, Jianbo Li","doi":"10.1080/13510002.2025.2565033","DOIUrl":"10.1080/13510002.2025.2565033","url":null,"abstract":"<p><strong>Objectives: </strong>Doxorubicin (DOX) induces dose-dependent cardiotoxicity, primarily through oxidative stress and metabolic dysregulation. Although NAD⁺ deficiency has been implicated in cardiovascular pathology, its role in DOX-induced cardiotoxicity (DIC) remains poorly understood. This study investigated NAD⁺ metabolism dysregulation as a redox-sensitive mechanism in DIC pathogenesis.</p><p><strong>Methods: </strong>Human cardiomyocytes (AC16), mouse atrial myocytes (HL-1), and C57BL/6 mice were used to establish the DIC model. The role and mechanism of NAD⁺ in DIC were investigated using a range of methods.</p><p><strong>Results: </strong>Using integrated <i>in vitro</i> and <i>in vivo</i> models, we demonstrated that DOX induces myocardial oxidative damage accompanied by NAD⁺ depletion. Exogenous NAD⁺ supplementation mitigated the DOX-induced cardiomyocyte death and redox imbalance. Mechanistically, pharmacological CD38 inhibition with 78C or genetic silencing failed to restore the NAD⁺ pool, whereas nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) overexpression, combined with nicotinamide mononucleotide (NMN) administration, effectively rescued NAD⁺ levels and attenuated oxidative stress. Computational and functional analyses identified FOXO1 as a transcriptional repressor of NMNAT3 following DOX exposure.</p><p><strong>Conclusion: </strong>This study establishes the dysregulation of the FOXO1-NMNAT3 axis as a key mechanism underlying NAD⁺ depletion in DIC. Targeting this axis through NAD⁺ replenishment, particularly by activating NMNAT3, offers a novel redox-based therapeutic strategy against DIC.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2565033"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps drive osteoporosis via NCF2-dependent signaling: integrated transcriptomics with mechanistic validation.","authors":"Xiangyun Guo, Liang Wang, Shuangliu Chen, Chuanrui Sun, Jinran Qin, Qingqing Liu, Yiwen Gan, Yan Li, Zikai Jin, Xu Wei, Yili Zhang","doi":"10.1080/13510002.2025.2534745","DOIUrl":"10.1080/13510002.2025.2534745","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and immune responses play key roles in osteoporosis (OP) pathogenesis. Osteoimmunology highlights immune dysregulation as a significant contributor to OP, but the specific biological mechanisms linking immune dysfunction to bone loss remain unclear. Understanding these mechanisms is essential for targeted therapies.</p><p><strong>Methods: </strong>We established a rat OP model via bilateral ovariectomy. Transcriptomic sequencing (RNA-seq) identified differentially expressed genes (DEGs), and summary data-based Mendelian randomization (SMR) analysis validated their causal associations with OP. Primary neutrophils isolated from bone marrow and differentiated HL-60 neutrophil-like cells were induced to form neutrophil extracellular traps (NETs), and siRNA was employed to knock down the NCF2 gene. Conditioned media from these neutrophils were subsequently applied to primary osteoblasts to evaluate effects on osteogenic differentiation.</p><p><strong>Results: </strong>RNA-seq identified 4,497 DEGs (1,606 upregulated, 2,891 downregulated) in OP rats, significantly enriched in immune response and NETs formation pathways. NETs markers (NE, MPO, CitH3) were markedly elevated in OP bone tissue and stimulated neutrophils. SMR analysis identified VDAC1, PLCG2, and NCF2 as key genes significantly associated with OP risk, experimentally validated at the tissue and cellular levels. Knockdown of NCF2 reduced NETs formation in neutrophil-like cells and alleviated NETs-induced osteoblast differentiation impairment. Drug prediction and molecular docking analyses demonstrated high affinity and pharmacological potential targeting these genes.</p><p><strong>Conclusions: </strong>This study unveils the link between NETs formation and OP, highlighting NCF2 as crucial players. These findings provide new insights into immune inflammation's role in bone metabolism and pave the way for targeted OP therapies.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2534745"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression, localization and regulation of NADPH oxidases in pancreatic beta cells.","authors":"Davidson Correa de Almeida, Eloisa Aparecida Vilas-Boas, Paulo Henrique Coelho Ferreira, Sandra Mara Ferreira, Angelo Rafael Carpinelli, Fernanda Ortis","doi":"10.1080/13510002.2025.2568300","DOIUrl":"10.1080/13510002.2025.2568300","url":null,"abstract":"<p><strong>Objectives: </strong>Reactive oxygen species (ROS) are short-lived and act in a site-specific manner, underscoring the importance of identifying the subcellular localization of their sources. ROS-generating NADPH oxidases (NOX) regulate pancreatic beta cell (dys)function. However, their subcellular localization and cytokine-mediated regulation in these cells remain largely unknown. We characterized the expression, subcellular localization and time-dependent cytokine-induced regulation of NOX isoforms in beta cells.</p><p><strong>Methods: </strong>Isoforms were studied via RT-qPCR, immunoblotting and immunofluorescence in rat islets and beta cell lines.</p><p><strong>Results: </strong>Beta cells express DUOX1 and DUOX2 proteins and <i>Duoxa2</i> transcripts; lacking <i>Duoxa1</i> expression. In INS-1E cells, NOX1 and DUOX1 localize in the endoplasmic reticulum (ER); DUOX2 in insulin vesicles; and NOX2 and NOX4 in vesicles, ER and plasma membrane. In INS-1E, cytokines increased expression of <i>Nox1</i> and <i>Duox1</i> at 4-8 h (returning to baseline at 16 h) and <i>Nox2</i> and <i>p47phox</i> at 8 h (persisting until 24 h). <i>Duox(a)2</i>, <i>p67phox</i> and <i>p40phox</i> were downregulated and DUOX1 upregulated at 16-24 h.</p><p><strong>Conclusion: </strong>The absence of <i>Duoxa1</i> in beta cells might lead to DUOX1 mismatching, impairing its trafficking and activity. NOXs in beta cells are diverse in subcellular localization and cytokine-induced regulation, suggesting their isoform-specific involvement in beta cell function, stress and apoptosis.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2568300"},"PeriodicalIF":7.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}