Pub Date : 2026-01-12DOI: 10.1016/j.redox.2026.104014
Yanting Zhou , Yuheng Zou , Xiao Zhong , Hongyan Li , Jingyi Yang , Hui Meng , Weiyao Xie , Pan Yao , Xiaoai Wu , Huawei Cai , Lin Li , Changning Wang , Wei Zhang , Ping Bai
Histone deacetylase 6 (HDAC6) represents a compelling target in major depressive disorder (MDD) pathophysiology, yet in vivo investigation has been constrained by inadequate imaging capabilities. Here, we report the development and validation of [18F]PB200, a novel positron emission tomography (PET) radiotracer specifically targeting brain HDAC6. PB200 was engineered with nanomolar affinity, high HDAC6 selectivity, and excellent blood-brain barrier permeability. [18F]PB200 was successfully synthesized in a radiochemical yield of 13 ± 4 % and validated through in vitro autoradiography and in vivo PET imaging across rodent and non-human primate models. We subsequently employed [18F]PB200 alongside TSPO-targeted [18F]FEPPA PET imaging in a chronic unpredictable mild stress (CUMS) mouse model of depression. This dual-tracer approach, complemented by in vitro experiments, revealed significant HDAC6 upregulation occurring concurrently with enhanced neuroinflammatory markers, including microglial activation and elevated pro-inflammatory cytokines. Our findings provide the first in vivo molecular imaging evidence directly linking HDAC6 upregulation to depressive pathophysiology and associated neuroinflammation. This work illuminates the molecular relationship between depression and neuroinflammation while establishing [18F]PB200 as a valuable tool for evaluating HDAC6-targeted therapeutic interventions, potentially advancing precision diagnosis and treatment approaches for depression.
{"title":"Development of a novel HDAC6 PET imaging agent uncovers associations between HDAC6 overexpression and neuroinflammation in depression","authors":"Yanting Zhou , Yuheng Zou , Xiao Zhong , Hongyan Li , Jingyi Yang , Hui Meng , Weiyao Xie , Pan Yao , Xiaoai Wu , Huawei Cai , Lin Li , Changning Wang , Wei Zhang , Ping Bai","doi":"10.1016/j.redox.2026.104014","DOIUrl":"10.1016/j.redox.2026.104014","url":null,"abstract":"<div><div>Histone deacetylase 6 (HDAC6) represents a compelling target in major depressive disorder (MDD) pathophysiology, yet <em>in vivo</em> investigation has been constrained by inadequate imaging capabilities. Here, we report the development and validation of [<sup>18</sup>F]PB200, a novel positron emission tomography (PET) radiotracer specifically targeting brain HDAC6. PB200 was engineered with nanomolar affinity, high HDAC6 selectivity, and excellent blood-brain barrier permeability. [<sup>18</sup>F]PB200 was successfully synthesized in a radiochemical yield of 13 ± 4 % and validated through <em>in vitro</em> autoradiography and <em>in vivo</em> PET imaging across rodent and non-human primate models. We subsequently employed [<sup>18</sup>F]PB200 alongside TSPO-targeted [<sup>18</sup>F]FEPPA PET imaging in a chronic unpredictable mild stress (CUMS) mouse model of depression. This dual-tracer approach, complemented by <em>in vitro</em> experiments, revealed significant HDAC6 upregulation occurring concurrently with enhanced neuroinflammatory markers, including microglial activation and elevated pro-inflammatory cytokines. Our findings provide the first <em>in vivo</em> molecular imaging evidence directly linking HDAC6 upregulation to depressive pathophysiology and associated neuroinflammation. This work illuminates the molecular relationship between depression and neuroinflammation while establishing [<sup>18</sup>F]PB200 as a valuable tool for evaluating HDAC6-targeted therapeutic interventions, potentially advancing precision diagnosis and treatment approaches for depression.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104014"},"PeriodicalIF":11.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.redox.2026.104023
Anna Gremme , Emely Gerisch , Dominik Wieland , Julia Hillebrand , Franziska Drews , Marcello Pirritano , Ann-Kathrin Weishaupt , Janina Fuss , Vera Schwantes , Johannes Scholz , Vivien Michaelis , Alicia Thiel , Gawain McColl , Bernhard Michalke , Martin Simon , Heiko Hayen , Julia Bornhorst
Although the redox active essential trace element iron (Fe) is involved in many important biological processes, an overexposure can lead to the excessive formation of reactive oxygen and nitrogen species (RONS). Thus, total Fe accumulation, as for example observed in neurodegenerative diseases or diseases as hemochromatosis, can lead to adverse consequences, especially if the antioxidant system is weakened. This system, and especially the most abundant antioxidant in organisms, glutathione (GSH), can be impaired by excess RONS levels, which is relevant during aging and in the context of neurodegenerative diseases. In this study, we demonstrate the consequences of Fe overdosing or/and GSH depletion in Caenorhabditis elegans (C. elegans) on Fe homeostasis, mitochondrial mass, phospho- and sphingolipidome, and on the neurotransmitter levels of acetylcholine, serotonin, dopamine, and γ-aminobutyric acid. In order to investigate this, we treated L4 nematodes with Fe(III) ammonium citrate (FAC) for 24 h or/and diethyl maleate (DEM) for 2 h or 24 h. While FAC treatment alone did not affect mitochondrial mass and cardiolipin content, it increased the amount of several lipid classes and the neurotransmitter acetylcholine. Treatment with DEM alone resulted in GSH depletion by 70 % and was associated with decreased mitochondrial mass and increased Fe(II), lipid, acetylcholine, and serotonin levels. Genes involved in GSH biosynthesis, Fe homeostasis, mitochondrial stress response, lipid biosynthesis, and neurotransmitter regulation are differentially expressed after DEM treatment. In addition, we were able to determine the GSH-DEM product in the nematode using HPLC-MS/MS. Although FAC treatment increased total Fe content in the nematode fivefold, the combined treatment with DEM showed no further effects compared to treatment with FAC or DEM alone. Together, these findings highlight the consequences of an impaired intracellular redox system on mitochondria, lipidome, and neurological endpoints, and identify several pathways, metabolites, and potential compensatory as well as long lasting effects.
{"title":"Consequences of iron exposure and glutathione depletion on redox balance, lipidome, and neurotransmission in C. elegans","authors":"Anna Gremme , Emely Gerisch , Dominik Wieland , Julia Hillebrand , Franziska Drews , Marcello Pirritano , Ann-Kathrin Weishaupt , Janina Fuss , Vera Schwantes , Johannes Scholz , Vivien Michaelis , Alicia Thiel , Gawain McColl , Bernhard Michalke , Martin Simon , Heiko Hayen , Julia Bornhorst","doi":"10.1016/j.redox.2026.104023","DOIUrl":"10.1016/j.redox.2026.104023","url":null,"abstract":"<div><div>Although the redox active essential trace element iron (Fe) is involved in many important biological processes, an overexposure can lead to the excessive formation of reactive oxygen and nitrogen species (RONS). Thus, total Fe accumulation, as for example observed in neurodegenerative diseases or diseases as hemochromatosis, can lead to adverse consequences, especially if the antioxidant system is weakened. This system, and especially the most abundant antioxidant in organisms, glutathione (GSH), can be impaired by excess RONS levels, which is relevant during aging and in the context of neurodegenerative diseases. In this study, we demonstrate the consequences of Fe overdosing or/and GSH depletion in <em>Caenorhabditis elegans</em> (<em>C. elegans</em>) on Fe homeostasis, mitochondrial mass, phospho- and sphingolipidome, and on the neurotransmitter levels of acetylcholine, serotonin, dopamine, and γ-aminobutyric acid. In order to investigate this, we treated L4 nematodes with Fe(III) ammonium citrate (FAC) for 24 h or/and diethyl maleate (DEM) for 2 h or 24 h. While FAC treatment alone did not affect mitochondrial mass and cardiolipin content, it increased the amount of several lipid classes and the neurotransmitter acetylcholine. Treatment with DEM alone resulted in GSH depletion by 70 % and was associated with decreased mitochondrial mass and increased Fe(II), lipid, acetylcholine, and serotonin levels. Genes involved in GSH biosynthesis, Fe homeostasis, mitochondrial stress response, lipid biosynthesis, and neurotransmitter regulation are differentially expressed after DEM treatment. In addition, we were able to determine the GSH-DEM product in the nematode using HPLC-MS/MS. Although FAC treatment increased total Fe content in the nematode fivefold, the combined treatment with DEM showed no further effects compared to treatment with FAC or DEM alone. Together, these findings highlight the consequences of an impaired intracellular redox system on mitochondria, lipidome, and neurological endpoints, and identify several pathways, metabolites, and potential compensatory as well as long lasting effects.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104023"},"PeriodicalIF":11.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.redox.2026.104022
Boshen Yang , Yizhi Chen , Xinjie Zheng , Taixi Li , Kaifan Niu , Zhixiang Wang , Xuanhao Xu , Qiya Huang , Xingyun Wang , Yuan Fang , Wei Liu , Zhenwei Yu , Dianhui Wei , YuanKang Zhu , Xian Jin , Chengxing Shen
Background
Triclosan (TCS), a widely used environmental antimicrobial agent, is associated with cardiovascular risks such as coronary heart disease; however, its effect on post-myocardial infarction (MI) prognosis remains unclear. This study investigated whether TCS exacerbated post-MI outcomes and the underlying mechanisms, with the goal of identifying potential preventive strategies.
Methods
MI models were established using mice with left anterior descending coronary artery ligation, alongside hypoxia-treated neonatal rat cardiomyocytes (NRCMs) and human AC16 cardiomyocytes. A comprehensive set of methodologies was employed, including RNA sequencing, echocardiography, Western blotting, co-immunoprecipitation, dual-luciferase reporter assays, molecular docking, quantitative real-time PCR, histological/immunofluorescence staining, and oxidative stress parameter analyses. Mechanistic investigations utilized Nur77 knockout mice, AAV9-based viral vectors targeting Nur77 and NTRK2, adenoviruses, plasmids, and small-molecule inhibitors/activators.
Results
Exposure to environmentally relevant TCS concentrations dose-dependently aggravated short- and long-term post-MI cardiac dysfunction and ventricular remodeling in both male and female mice. Mechanistically, TCS induced TRIM13-mediated K48-linked ubiquitination and proteasomal degradation of the nuclear receptor Nur77, leading to reduced transcription of NTRK2. Downregulated NTRK2 suppressed the AKT/mTOR/YY1 signaling cascade, ultimately decreasing PGC-1α expression and impairing mitochondrial function—specifically mitochondrial oxidative phosphorylation. This bioenergetic deficit triggered excessive reactive oxygen species (ROS) production, promoting lipid peroxidation and exacerbating cardiomyocyte ferroptosis, cellular senescence, and the senescence-associated secretory phenotype (SASP). These pathological effects collectively exacerbated acute post-MI injury and facilitated the progression of long-term ventricular remodeling. Validation in NRCMs and human AC16 cardiomyocytes confirmed conserved phenotypes and mechanisms. Pharmacological activation of PGC-1α with ZLN005 mitigated TCS-induced deterioration of short- and long-term post-MI cardiac function and attenuated ventricular remodeling.
Conclusions
TCS exacerbates post-MI injury by disrupting the Nur77/NTRK2/PGC-1α axis, triggering mitochondrial dysfunction-mediated ferroptosis and senescence in cardiomyocytes of both male and female mice. Pharmacological activation of PGC-1α represents a potential strategy to counteract TCS-induced adverse outcomes after MI.
{"title":"Triclosan exacerbates post-myocardial infarction injury via Nur77 ubiquitination: Linking NTRK2/PGC-1α-mediated mitochondrial dysfunction to senescence and ferroptosis","authors":"Boshen Yang , Yizhi Chen , Xinjie Zheng , Taixi Li , Kaifan Niu , Zhixiang Wang , Xuanhao Xu , Qiya Huang , Xingyun Wang , Yuan Fang , Wei Liu , Zhenwei Yu , Dianhui Wei , YuanKang Zhu , Xian Jin , Chengxing Shen","doi":"10.1016/j.redox.2026.104022","DOIUrl":"10.1016/j.redox.2026.104022","url":null,"abstract":"<div><h3>Background</h3><div>Triclosan (TCS), a widely used environmental antimicrobial agent, is associated with cardiovascular risks such as coronary heart disease; however, its effect on post-myocardial infarction (MI) prognosis remains unclear. This study investigated whether TCS exacerbated post-MI outcomes and the underlying mechanisms, with the goal of identifying potential preventive strategies.</div></div><div><h3>Methods</h3><div>MI models were established using mice with left anterior descending coronary artery ligation, alongside hypoxia-treated neonatal rat cardiomyocytes (NRCMs) and human AC16 cardiomyocytes. A comprehensive set of methodologies was employed, including RNA sequencing, echocardiography, Western blotting, co-immunoprecipitation, dual-luciferase reporter assays, molecular docking, quantitative real-time PCR, histological/immunofluorescence staining, and oxidative stress parameter analyses. Mechanistic investigations utilized Nur77 knockout mice, AAV9-based viral vectors targeting Nur77 and NTRK2, adenoviruses, plasmids, and small-molecule inhibitors/activators.</div></div><div><h3>Results</h3><div>Exposure to environmentally relevant TCS concentrations dose-dependently aggravated short- and long-term post-MI cardiac dysfunction and ventricular remodeling in both male and female mice. Mechanistically, TCS induced TRIM13-mediated K48-linked ubiquitination and proteasomal degradation of the nuclear receptor Nur77, leading to reduced transcription of NTRK2. Downregulated NTRK2 suppressed the AKT/mTOR/YY1 signaling cascade, ultimately decreasing PGC-1α expression and impairing mitochondrial function—specifically mitochondrial oxidative phosphorylation. This bioenergetic deficit triggered excessive reactive oxygen species (ROS) production, promoting lipid peroxidation and exacerbating cardiomyocyte ferroptosis, cellular senescence, and the senescence-associated secretory phenotype (SASP). These pathological effects collectively exacerbated acute post-MI injury and facilitated the progression of long-term ventricular remodeling. Validation in NRCMs and human AC16 cardiomyocytes confirmed conserved phenotypes and mechanisms. Pharmacological activation of PGC-1α with ZLN005 mitigated TCS-induced deterioration of short- and long-term post-MI cardiac function and attenuated ventricular remodeling.</div></div><div><h3>Conclusions</h3><div>TCS exacerbates post-MI injury by disrupting the Nur77/NTRK2/PGC-1α axis, triggering mitochondrial dysfunction-mediated ferroptosis and senescence in cardiomyocytes of both male and female mice. Pharmacological activation of PGC-1α represents a potential strategy to counteract TCS-induced adverse outcomes after MI.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104022"},"PeriodicalIF":11.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1016/j.redox.2026.104021
Prince Kumar Singh , Shweta Maurya , Aseel Saadi , Sereen Sandouka , Taige Zhang , Orya Kadosh , Yara Sheeni , Valeria Martin , Daphne Atlas , Tawfeeq Shekh-Ahmad
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, in which oxidative stress and neuroinflammation play central roles in driving disease progression and pharmacoresistance. Approximately 30–40 % of patients are resistant to current antiseizure medications, which suppress symptoms but do not prevent epilepsy development or modify its progression. There is an urgent need for therapies with true disease-modifying potential. TXM-CB3 (CB3), a thioredoxin-mimetic tripeptide, has been reported to modulate redox and inflammatory pathways. In this study, we evaluated the therapeutic potential of CB3 in preclinical models of temporal lobe epilepsy, focusing on its capacity to suppress seizures, preserve neuronal integrity, and mitigate epilepsy-associated behavioral impairments.
We first examined CB3 in an in vitro model of low-Mg2+-induced epileptiform activity, where pretreatment with CB3 (50, 100 μM) attenuated oxidative activity and reduced proinflammatory cytokine expression (IL-6, IL-1β, TNF-α), while enhancing IL-10 levels. In vivo, early CB3 intervention (20 mg/kg/day, i.p.) following kainic acid-induced status epilepticus significantly delayed seizure onset, reduced seizure frequency and cumulative burden, and preserved hippocampal neuronal integrity. Treated animals also showed improved locomotor activity, reduced anxiety-like behavior, and better performance in spatial working memory tasks. In established chronic epilepsy, CB3 treatment (20 mg/kg/day, i.p.) produced a sustained reduction in recurrent seizure activity and seizure burden, with additional effects on anxiety-like behavior, though memory and learning deficits remained unchanged.
Together, these findings highlight CB3's potential as a disease-modifying therapy. By reducing seizure recurrence, preserving neuronal integrity, and alleviating selected behavioral impairments, CB3 offers therapeutic benefits that extend beyond conventional ASMs and warrants further investigation for translation into clinical epilepsy treatment.
{"title":"Thioredoxin-mimetic peptide attenuates epilepsy progression and neurocognitive deficits","authors":"Prince Kumar Singh , Shweta Maurya , Aseel Saadi , Sereen Sandouka , Taige Zhang , Orya Kadosh , Yara Sheeni , Valeria Martin , Daphne Atlas , Tawfeeq Shekh-Ahmad","doi":"10.1016/j.redox.2026.104021","DOIUrl":"10.1016/j.redox.2026.104021","url":null,"abstract":"<div><div>Epilepsy is a chronic neurological disorder characterized by recurrent seizures, in which oxidative stress and neuroinflammation play central roles in driving disease progression and pharmacoresistance. Approximately 30–40 % of patients are resistant to current antiseizure medications, which suppress symptoms but do not prevent epilepsy development or modify its progression. There is an urgent need for therapies with true disease-modifying potential. TXM-CB3 (CB3), a thioredoxin-mimetic tripeptide, has been reported to modulate redox and inflammatory pathways. In this study, we evaluated the therapeutic potential of CB3 in preclinical models of temporal lobe epilepsy, focusing on its capacity to suppress seizures, preserve neuronal integrity, and mitigate epilepsy-associated behavioral impairments.</div><div>We first examined CB3 in an in vitro model of low-Mg<sup>2+</sup>-induced epileptiform activity, where pretreatment with CB3 (50, 100 μM) attenuated oxidative activity and reduced proinflammatory cytokine expression (IL-6, IL-1β, TNF-α), while enhancing IL-10 levels. In vivo, early CB3 intervention (20 mg/kg/day, i.p.) following kainic acid-induced status epilepticus significantly delayed seizure onset, reduced seizure frequency and cumulative burden, and preserved hippocampal neuronal integrity. Treated animals also showed improved locomotor activity, reduced anxiety-like behavior, and better performance in spatial working memory tasks. In established chronic epilepsy, CB3 treatment (20 mg/kg/day, i.p.) produced a sustained reduction in recurrent seizure activity and seizure burden, with additional effects on anxiety-like behavior, though memory and learning deficits remained unchanged.</div><div>Together, these findings highlight CB3's potential as a disease-modifying therapy. By reducing seizure recurrence, preserving neuronal integrity, and alleviating selected behavioral impairments, CB3 offers therapeutic benefits that extend beyond conventional ASMs and warrants further investigation for translation into clinical epilepsy treatment.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104021"},"PeriodicalIF":11.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1016/j.redox.2026.104020
Molly S. Myers , Elizabeth A. Kosmacek , Chia Sin Liew , Alexander J. Lushnikov , Arpita Chatterjee , Luis A. Marky , Jean-Jack M. Riethoven , Rebecca E. Oberley-Deegan
Radiation provides excellent tumor control in prostate cancer yet unavoidably harms adjacent healthy tissue via the generation of reactive oxygen species (ROS). Radiation-induced ROS is known to impact fibroblasts long after radiation, resulting in radiation-induced fibrosis (RIF), which can cause incontinence and other side effects that reduce patient quality of life. BMX-001, a manganese porphyrin designed to mimic superoxide dismutase, is in clinical trials as a selective radioprotector when given before and during radiation therapy. However, there have been no studies evaluating BMX-001 when given after radiation for its impacts on RIF. Mice were given pelvic radiation (7.5 Gy for 5 consecutive days) followed by BMX-001 three weeks after radiation. Fibroblasts and tissues were isolated two months following radiation. We found that BMX-001 returned radiation-induced alterations in fibroblast morphology to normal and reversed markers of fibroblast activation and senescence. BMX-001 also decreased collagen deposition six months after radiation. Because these changes persisted for a long period of time, we speculated that BMX-001 may affect fibroblast epigenetics. We found that overall, radiation resulted in reduced methylation two months after radiation, and BMX-001 administered three weeks after radiation modulated radiation-altered methylation patterns back to normal and restored normal expression of a fibrosis-associated gene CAMK2β. BMX-001 also decreased radiation-induced DNA adduct 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is known to interfere with methylation. BMX-001 was able to prevent DNA oxidation and restore normal methylation patterns in an oligonucleotide model of DNA oxidation and methylation. This study reveals the feasibility of agents to reverse fibrosis in pelvic radiation and suggests that BMX-001 may be effective when given after radiation.
{"title":"BMX-001, a clinically relevant radioprotector, can reverse radiation-induced fibrosis when given three weeks after radiation, in part, by restoring methylation","authors":"Molly S. Myers , Elizabeth A. Kosmacek , Chia Sin Liew , Alexander J. Lushnikov , Arpita Chatterjee , Luis A. Marky , Jean-Jack M. Riethoven , Rebecca E. Oberley-Deegan","doi":"10.1016/j.redox.2026.104020","DOIUrl":"10.1016/j.redox.2026.104020","url":null,"abstract":"<div><div>Radiation provides excellent tumor control in prostate cancer yet unavoidably harms adjacent healthy tissue via the generation of reactive oxygen species (ROS). Radiation-induced ROS is known to impact fibroblasts long after radiation, resulting in radiation-induced fibrosis (RIF), which can cause incontinence and other side effects that reduce patient quality of life. BMX-001, a manganese porphyrin designed to mimic superoxide dismutase, is in clinical trials as a selective radioprotector when given before and during radiation therapy. However, there have been no studies evaluating BMX-001 when given after radiation for its impacts on RIF. Mice were given pelvic radiation (7.5 Gy for 5 consecutive days) followed by BMX-001 three weeks after radiation. Fibroblasts and tissues were isolated two months following radiation. We found that BMX-001 returned radiation-induced alterations in fibroblast morphology to normal and reversed markers of fibroblast activation and senescence. BMX-001 also decreased collagen deposition six months after radiation. Because these changes persisted for a long period of time, we speculated that BMX-001 may affect fibroblast epigenetics. We found that overall, radiation resulted in reduced methylation two months after radiation, and BMX-001 administered three weeks after radiation modulated radiation-altered methylation patterns back to normal and restored normal expression of a fibrosis-associated gene CAMK2β. BMX-001 also decreased radiation-induced DNA adduct 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is known to interfere with methylation. BMX-001 was able to prevent DNA oxidation and restore normal methylation patterns in an oligonucleotide model of DNA oxidation and methylation. This study reveals the feasibility of agents to reverse fibrosis in pelvic radiation and suggests that BMX-001 may be effective when given after radiation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104020"},"PeriodicalIF":11.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.redox.2026.104019
Jiahui Wang , Rongqing Li , Li Qian
Intercellular mitochondrial transfer is recognized as a central mechanism that shapes redox homeostasis, metabolic plasticity, and cellular resilience across multiple tissues. Through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junction channels (GJCs), and cell fusion, mitochondria move between donor and recipient cells to restore bioenergetic capacity, buffer oxidative stress, and tune redox-sensitive signaling networks. Recent work has begun to clarify the regulatory framework governing donor-recipient specificity, cargo selection, and the stress-activated cues that trigger organelle exchange. Mitochondrial transfer also exerts distinct, context-dependent influences on disease trajectories. It mitigates injury in neurological damage, ischemia-reperfusion conditions, immune dysfunction, aging, and inflammatory pain, largely by reprogramming mitochondrial function and reactive oxygen species (ROS) dynamics. Conversely, in cancer, mitochondrial acquisition enhances metabolic flexibility, invasiveness, and resistance to therapy. Current therapeutic approaches, including mitochondrial transplantation, EV-based delivery systems, and mitochondria-enhanced immune cells, highlight the translational potential of manipulating mitochondrial exchange, yet face challenges such as mitochondrial fragility, inefficient targeting, and immunogenicity. Deeper mechanistic insight into how mitochondrial transfer remodels redox signaling and metabolic adaptation will be essential for converting this biological process into next-generation organelle-level interventions for redox-driven disorders.
{"title":"Intercellular mitochondrial transfer rewires redox signaling and metabolic plasticity: mechanisms, disease relevance and therapeutic frontiers","authors":"Jiahui Wang , Rongqing Li , Li Qian","doi":"10.1016/j.redox.2026.104019","DOIUrl":"10.1016/j.redox.2026.104019","url":null,"abstract":"<div><div>Intercellular mitochondrial transfer is recognized as a central mechanism that shapes redox homeostasis, metabolic plasticity, and cellular resilience across multiple tissues. Through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junction channels (GJCs), and cell fusion, mitochondria move between donor and recipient cells to restore bioenergetic capacity, buffer oxidative stress, and tune redox-sensitive signaling networks. Recent work has begun to clarify the regulatory framework governing donor-recipient specificity, cargo selection, and the stress-activated cues that trigger organelle exchange. Mitochondrial transfer also exerts distinct, context-dependent influences on disease trajectories. It mitigates injury in neurological damage, ischemia-reperfusion conditions, immune dysfunction, aging, and inflammatory pain, largely by reprogramming mitochondrial function and reactive oxygen species (ROS) dynamics. Conversely, in cancer, mitochondrial acquisition enhances metabolic flexibility, invasiveness, and resistance to therapy. Current therapeutic approaches, including mitochondrial transplantation, EV-based delivery systems, and mitochondria-enhanced immune cells, highlight the translational potential of manipulating mitochondrial exchange, yet face challenges such as mitochondrial fragility, inefficient targeting, and immunogenicity. Deeper mechanistic insight into how mitochondrial transfer remodels redox signaling and metabolic adaptation will be essential for converting this biological process into next-generation organelle-level interventions for redox-driven disorders.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104019"},"PeriodicalIF":11.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.redox.2026.104018
Yan Chen , Zhewei Zhang , Yue Cheng , Xiaofeng Chen , Junteng Zhou , Zisong Wei , Han Yao , Shuwen Zhang , Qihang Kong , Hao Tang , Wenchao Wu , Zhichao Zhou , Xiaoqiang Tang , Xiaojing Liu
Cardiac fibrosis remains an unresolved clinical issue in patients with heart diseases. CircRNAs have emerged as potential targets for treatment of heart diseases. Exploring the functional circRNAs in fibroblast activation is one of the ways to develop innovative drugs for the treatment of cardiac fibrosis. This study aimed to screen for fibroblast-related circRNAs in cardiac fibrosis and elucidate their roles and underlying mechanisms. By screening for fibrosis-responsible circular RNAs (circRNAs), we identified a highly conserved circRNA, circular RNA Sterile alpha motif domain containing 4 (circSamd4), that drives cardiac fibrosis. circSamd4 is prominently expressed in cardiac fibroblasts (CFs) and is upregulated in the fibrotic hearts of humans and mice. Fibroblast-specific silencing of circSamd4 reduced cardiac fibroblast activation and alleviates cardiac fibrosis. Conversely, overexpression of circSamd4 in fibroblasts exacerbates cardiac fibrosis and rescues cardiac function. Bioinformatics and functional analyses revealed that circSamd4 regulates the plasminogen activation. Plasminogen activator inhibitor-1 (PAI-1, encoded by Serpine1) is a key effector of plasminogen activation and redox homeostasis and contributes to fibrotic diseases. Here, PAI-1 serves as a leading functional downstream factor of circSamd4 because PAI-1 is highly expressed in cardiac fibroblasts and contributes to circSamd4 functions in regulating fibroblast activation and cardiac fibrosis. Mechanistically, circSamd4 functions as a sponge for miR-1894-3p to trigger Serpine1 expression and subsequent fibroblast activation, and cardiac fibrosis. Therefore, we identified a fibroblast-specific circSamd4-miR-1894-3p-Serpine1 axis driving fibroblast activation and cardiac fibrosis. Adeno-associated virus (AAV)-mediated knockdown of circSamd4 or Serpine1 alleviated cardiac fibrosis and cardiac dysfunction. These findings suggest that circSamd4 and Serpine1 are promising therapeutic targets for inhibiting cardiac fibrosis.
{"title":"Fibroblast circSamd4 promotes cardiac fibrosis via activating plasminogen activator inhibitor-1","authors":"Yan Chen , Zhewei Zhang , Yue Cheng , Xiaofeng Chen , Junteng Zhou , Zisong Wei , Han Yao , Shuwen Zhang , Qihang Kong , Hao Tang , Wenchao Wu , Zhichao Zhou , Xiaoqiang Tang , Xiaojing Liu","doi":"10.1016/j.redox.2026.104018","DOIUrl":"10.1016/j.redox.2026.104018","url":null,"abstract":"<div><div>Cardiac fibrosis remains an unresolved clinical issue in patients with heart diseases. CircRNAs have emerged as potential targets for treatment of heart diseases. Exploring the functional circRNAs in fibroblast activation is one of the ways to develop innovative drugs for the treatment of cardiac fibrosis. This study aimed to screen for fibroblast-related circRNAs in cardiac fibrosis and elucidate their roles and underlying mechanisms. By screening for fibrosis-responsible circular RNAs (circRNAs), we identified a highly conserved circRNA, <em>circular RNA Sterile alpha motif domain containing 4</em> (<em>circSamd4</em>), that drives cardiac fibrosis. <em>circSamd4</em> is prominently expressed in cardiac fibroblasts (CFs) and is upregulated in the fibrotic hearts of humans and mice. Fibroblast-specific silencing of <em>circSamd4</em> reduced cardiac fibroblast activation and alleviates cardiac fibrosis. Conversely, overexpression of <em>circSamd4</em> in fibroblasts exacerbates cardiac fibrosis and rescues cardiac function. Bioinformatics and functional analyses revealed that <em>circSamd4</em> regulates the plasminogen activation. Plasminogen activator inhibitor-1 (PAI-1, encoded by <em>Serpine1</em>) is a key effector of plasminogen activation and redox homeostasis and contributes to fibrotic diseases. Here, PAI-1 serves as a leading functional downstream factor of <em>circSamd4</em> because PAI-1 is highly expressed in cardiac fibroblasts and contributes to <em>circSamd4</em> functions in regulating fibroblast activation and cardiac fibrosis. Mechanistically, <em>circSamd4</em> functions as a sponge for miR-1894-3p to trigger <em>Serpine1</em> expression and subsequent fibroblast activation, and cardiac fibrosis. Therefore, we identified a fibroblast-specific <em>circSamd4</em>-miR-1894-3p-<em>Serpine1</em> axis driving fibroblast activation and cardiac fibrosis. Adeno-associated virus (AAV)-mediated knockdown of <em>circSamd4</em> or <em>Serpine1</em> alleviated cardiac fibrosis and cardiac dysfunction. These findings suggest that <em>circSamd4</em> and <em>Serpine1</em> are promising therapeutic targets for inhibiting cardiac fibrosis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104018"},"PeriodicalIF":11.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.redox.2026.104012
Helaina E. Huneault , Scott E. Gillespie , Zachery R. Jarrell , Shasha Bai , Ana Ramirez Tovar , Cristian Sanchez-Torres , Lucia A. Gonzalez-Ramirez , Kelsey C. Chatman , Thomas R. Ziegler , Dean P. Jones , Jean A. Welsh , Miriam B. Vos
Background
Plasma glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox couples undergo diurnal variation in adults and are more oxidized in obesity-related conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). There is limited research on redox in children and no data on redox responses to sugars, despite high sugar consumption in this population. This study aimed to describe the diurnal variation of redox couples in children, assess the impact of MASLD, and evaluate responses to fructose versus glucose beverages.
Methods
In a 2-day randomized, controlled, crossover feeding study, 26 children (12 with MASLD, 14 controls; aged 10–18 years) consumed isocaloric meals with fructose beverages (FB) on one day and glucose beverages (GB) (set as control) on another, following a washout period. Blood was collected every 2 h over 24 h and analyzed for Cys/CySS and GSH/GSSG. Redox potentials, Eh(Cys/CySS) and Eh(GSH/GSSG), were calculated using the Nernst equation. Linear mixed models assessed diurnal variation and effects of MASLD and beverage type.
Results
Plasma Eh(GSH/GSSG) and Eh(CyS/CySS) varied significantly over time after both FB and GB (p < 0.05). With FB, Eh(GSH/GSSG) was significantly more oxidized in children with MASLD (p = 0.034); this was not observed with GB. Among children with MASLD, FB also led to greater Eh(GSH/GSSG) oxidation and lower GSH levels overnight (p < 0.05). While Eh(Cys/CySS) showed a similar trend, differences did not reach statistical significance.
Conclusions
Our findings demonstrate that plasma redox states vary diurnally in children and are more oxidized in those with MASLD. Fructose intake increased oxidation of the GSH/GSSG redox couple and lowered GSH concentrations overnight, indicating heightened oxidative stress. These results identify fructose as a driver of redox imbalance in pediatric MASLD and support fructose reduction and glutathione restoration as therapeutic targets.
{"title":"Fructose-sweetened beverages induce diurnal redox dysregulation in pediatric MASLD","authors":"Helaina E. Huneault , Scott E. Gillespie , Zachery R. Jarrell , Shasha Bai , Ana Ramirez Tovar , Cristian Sanchez-Torres , Lucia A. Gonzalez-Ramirez , Kelsey C. Chatman , Thomas R. Ziegler , Dean P. Jones , Jean A. Welsh , Miriam B. Vos","doi":"10.1016/j.redox.2026.104012","DOIUrl":"10.1016/j.redox.2026.104012","url":null,"abstract":"<div><h3>Background</h3><div>Plasma glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox couples undergo diurnal variation in adults and are more oxidized in obesity-related conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). There is limited research on redox in children and no data on redox responses to sugars, despite high sugar consumption in this population. This study aimed to describe the diurnal variation of redox couples in children, assess the impact of MASLD, and evaluate responses to fructose versus glucose beverages.</div></div><div><h3>Methods</h3><div>In a 2-day randomized, controlled, crossover feeding study, 26 children (12 with MASLD, 14 controls; aged 10–18 years) consumed isocaloric meals with fructose beverages (FB) on one day and glucose beverages (GB) (set as control) on another, following a washout period. Blood was collected every 2 h over 24 h and analyzed for Cys/CySS and GSH/GSSG. Redox potentials, E<sub>h</sub>(Cys/CySS) and E<sub>h</sub>(GSH/GSSG), were calculated using the Nernst equation. Linear mixed models assessed diurnal variation and effects of MASLD and beverage type.</div></div><div><h3>Results</h3><div>Plasma E<sub>h</sub>(GSH/GSSG) and E<sub>h</sub>(CyS/CySS) varied significantly over time after both FB and GB (p < 0.05). With FB, E<sub>h</sub>(GSH/GSSG) was significantly more oxidized in children with MASLD (p = 0.034); this was not observed with GB. Among children with MASLD, FB also led to greater E<sub>h</sub>(GSH/GSSG) oxidation and lower GSH levels overnight (p < 0.05). While E<sub>h</sub>(Cys/CySS) showed a similar trend, differences did not reach statistical significance.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that plasma redox states vary diurnally in children and are more oxidized in those with MASLD. Fructose intake increased oxidation of the GSH/GSSG redox couple and lowered GSH concentrations overnight, indicating heightened oxidative stress. These results identify fructose as a driver of redox imbalance in pediatric MASLD and support fructose reduction and glutathione restoration as therapeutic targets.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104012"},"PeriodicalIF":11.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-08DOI: 10.1016/j.redox.2026.104013
Jie Feng, Feng Liang, Yongguang Zhou, Shihao Wen, Yue Chen, Binjie Ge, Wenjing Zhang, Jie Wang, Runyu Chen, Yin Zhang, Jianghui Li, Wu Wang, Guoqiang Tan
Here, we demonstrate that excess zinc disrupts bacterial redox sensing by specifically disassembling the [2Fe–2S] cluster of SoxR – a master oxidative stress sensor in Escherichia coli. This impairment couples zinc overload to dysregulated oxidative defense, revealing a previously unrecognized metal-redox crosstalk mechanism. Using electron paramagnetic resonance (EPR) and UV–visible spectroscopy, we demonstrated that excess zinc specifically disrupts the assembly of the [2Fe–2S] cluster in redox-sensitive SoxR. Additionally, we assessed the expression levels of genes within this pathway using quantitative real-time PCR (qPCR) and quantified intracellular zinc and iron levels by inductively coupled plasma mass spectrometry (ICP-MS) to evaluate the roles of SoxS and the zinc uptake transporter ZnuACB in maintaining zinc homeostasis. Furthermore, we investigated the roles of SoxR, SoxS, and ZnuACB in bacterial zinc homeostasis through plate growth assays and gene knockout experiments. We establish that zinc excess disassembles SoxR [2Fe–2S] clusters as a molecular switch that dysregulates the SoxS-ZnuACB/SOD axis, converting zinc toxicity into oxidative vulnerability. This mechanistic insight exposes a bacterial Achilles' heel: targeting Fe–S cluster integrity disrupts redox-metal homeostasis, providing a strategy to combat antibiotic-resistant pathogens.
{"title":"Zinc overload disrupts SoxR [2Fe–2S] clusters to drive redox-metallic crosstalk via SoxS-ZnuACB in Escherichia coli","authors":"Jie Feng, Feng Liang, Yongguang Zhou, Shihao Wen, Yue Chen, Binjie Ge, Wenjing Zhang, Jie Wang, Runyu Chen, Yin Zhang, Jianghui Li, Wu Wang, Guoqiang Tan","doi":"10.1016/j.redox.2026.104013","DOIUrl":"10.1016/j.redox.2026.104013","url":null,"abstract":"<div><div>Here, we demonstrate that excess zinc disrupts bacterial redox sensing by specifically disassembling the [2Fe–2S] cluster of SoxR – a master oxidative stress sensor in <em>Escherichia coli</em>. This impairment couples zinc overload to dysregulated oxidative defense, revealing a previously unrecognized metal-redox crosstalk mechanism. Using electron paramagnetic resonance (EPR) and UV–visible spectroscopy, we demonstrated that excess zinc specifically disrupts the assembly of the [2Fe–2S] cluster in redox-sensitive SoxR. Additionally, we assessed the expression levels of genes within this pathway using quantitative real-time PCR (qPCR) and quantified intracellular zinc and iron levels by inductively coupled plasma mass spectrometry (ICP-MS) to evaluate the roles of SoxS and the zinc uptake transporter ZnuACB in maintaining zinc homeostasis. Furthermore, we investigated the roles of SoxR, SoxS, and ZnuACB in bacterial zinc homeostasis through plate growth assays and gene knockout experiments. We establish that zinc excess disassembles SoxR [2Fe–2S] clusters as a molecular switch that dysregulates the SoxS-ZnuACB/SOD axis, converting zinc toxicity into oxidative vulnerability. This mechanistic insight exposes a bacterial Achilles' heel: targeting Fe–S cluster integrity disrupts redox-metal homeostasis, providing a strategy to combat antibiotic-resistant pathogens.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104013"},"PeriodicalIF":11.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/j.redox.2026.104017
Yán Wāng
Oxidative stress is a central driver of environmental stress responses and disease pathogenesis. Increasing evidence indicates that RNA epigenetic regulation, particularly N6-methyladenosine (m6A) modification, represents a critical interface linking redox imbalance to cellular dysfunction. Arsenic, a prototypical redox-active toxicant, provides a robust model for understanding how environmental oxidative stress disrupts m6A-mediated post-transcriptional control. Recent studies demonstrate that arsenic-induced redox perturbation reshapes the expression and activity of m6A writers (METTL3/METTL14), erasers (FTO/ALKBH5), and readers (YTHDF/YTHDC families), leading to widespread alterations in mRNA stability, translation, and metabolic reprogramming. Mechanistic findings from cellular and animal models implicate m6A-dependent pathways in modulating oxidative stress responses, mitochondrial function, inflammation, and senescence—biological processes fundamental to redox biology. These insights reveal that m6A is not merely a downstream marker of stress, but an active mediator of adaptive and maladaptive responses to redox disruption. Despite significant progress, population-level evidence and high-resolution mapping of RNA modifications under oxidative conditions remain limited. Future work integrating advanced epitranscriptomic profiling, multi-omics approaches, and exploration of additional RNA modifications (m7G, m1A, m5C) will be essential for defining how redox-sensitive RNA regulation shapes disease risk. Collectively, this review highlights m6A modification as a dynamic regulatory node connecting environmental redox stress to gene expression control, providing new mechanistic insight and potential targets for intervention in redox-related diseases.
{"title":"Redox-sensitive N6-methyladenosine RNA epitranscriptomic mechanisms in environmental stress and hazard","authors":"Yán Wāng","doi":"10.1016/j.redox.2026.104017","DOIUrl":"10.1016/j.redox.2026.104017","url":null,"abstract":"<div><div>Oxidative stress is a central driver of environmental stress responses and disease pathogenesis. Increasing evidence indicates that RNA epigenetic regulation, particularly N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification, represents a critical interface linking redox imbalance to cellular dysfunction. Arsenic, a prototypical redox-active toxicant, provides a robust model for understanding how environmental oxidative stress disrupts m<sup>6</sup>A-mediated post-transcriptional control. Recent studies demonstrate that arsenic-induced redox perturbation reshapes the expression and activity of m<sup>6</sup>A writers (METTL3/METTL14), erasers (FTO/ALKBH5), and readers (YTHDF/YTHDC families), leading to widespread alterations in mRNA stability, translation, and metabolic reprogramming. Mechanistic findings from cellular and animal models implicate m<sup>6</sup>A-dependent pathways in modulating oxidative stress responses, mitochondrial function, inflammation, and senescence—biological processes fundamental to redox biology. These insights reveal that m<sup>6</sup>A is not merely a downstream marker of stress, but an active mediator of adaptive and maladaptive responses to redox disruption. Despite significant progress, population-level evidence and high-resolution mapping of RNA modifications under oxidative conditions remain limited. Future work integrating advanced epitranscriptomic profiling, multi-omics approaches, and exploration of additional RNA modifications (m<sup>7</sup>G, m<sup>1</sup>A, m<sup>5</sup>C) will be essential for defining how redox-sensitive RNA regulation shapes disease risk. Collectively, this review highlights m<sup>6</sup>A modification as a dynamic regulatory node connecting environmental redox stress to gene expression control, providing new mechanistic insight and potential targets for intervention in redox-related diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104017"},"PeriodicalIF":11.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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