Antioxidants & redox signaling最新文献

{"title":"L-Ergothioneine Attenuates Nephrolithiasis by Modulating Redox Signaling and Mitochondrial Function in Cystine and Calcium Oxalate Models.","authors":"Clara Mayayo-Vallverdú, Marta Vecino-Pérez, Esther Prat, Sandra Cutanda-Tesouro, Aida Ormazabal, Rafael Artuch, Sara Larriba, Miguel A Asensi, Manuel Palacín, Federico V Pallardó, Pablo M Garcia-Rovés, Virginia Nunes, Raúl Estévez","doi":"10.1177/15230864261431276","DOIUrl":"10.1177/15230864261431276","url":null,"abstract":"<p><strong>Aims: </strong>Nephrolithiasis is a major global health challenge, with oxidative stress and mitochondrial dysfunction emerging as key drivers of renal injury and stone formation. l-ergothioneine (l-Erg), a naturally occurring antioxidant transported by OCTN1, has shown promising effects in cystinuria models, preventing stone formation. Despite evidence supporting an indirect mechanism of action, key mechanistic aspects have yet to be fully clarified. This study aimed to evaluate whether l-Erg can prevent stone progression in cystinuria and in other types of lithiasis, such as calcium oxalate nephrolithiasis, and to further elucidate its mechanistic basis.</p><p><strong>Results: </strong>Using mouse models, l-Erg significantly reduced cystine stone growth and renal inflammation, and its combination with d-penicillamine enhanced stone dissolution and mitigated drug-related toxicity. In calcium oxalate nephrolithiasis, l-Erg decreased crystal deposition, preserved renal architecture, normalized glutathione levels, and restored mitochondrial respiration. Transcriptomic analysis revealed downregulation of immune pathways and activation of cell cycle genes, suggesting attenuation of inflammation and promotion of tubular repair.</p><p><strong>Innovation: </strong>This study is the first to demonstrate that l-Erg exerts renoprotective effects through combined antioxidant and mitochondrial mechanisms in two major forms of nephrolithiasis and introduces a dual therapeutic approach combining an antioxidant with a cystine-solubilizing agent.</p><p><strong>Conclusion: </strong>By targeting oxidative stress and mitochondrial dysfunction, l-Erg represents a promising therapeutic strategy for nephrolithiasis, either alone or as an adjunct to current treatments. <i>Antioxid. Redox Signal.</i> 44, 878-891.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"878-891"},"PeriodicalIF":6.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430379","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":"Mitofusin 2 Is Required for the Maturation of Embryonic Stem Cell-Derived Cardiomyocytes via a GRP75-Dependent Suppression of the ROS/PI3K/AKT/mTOR Axis.","authors":"Zhenping Li, Ka Chun Cheung, Yanxiang Qi, Hin Shing Lam, Xiaoqian Wu, Ellen Ngar-Yun Poon, Suk Ying Tsang","doi":"10.1177/15230864261426010","DOIUrl":"10.1177/15230864261426010","url":null,"abstract":"<p><strong>Aims: </strong>Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have the potential for use in cell-based therapy, disease modeling, and drug toxicity testing. However, under the conventional differentiation protocol, PSC-CMs are immature and differ from adult cardiomyocytes in electrophysiological characteristics, calcium kinetics, cellular morphology, metabolism, and gene expression. MFN2 tethers sarcoplasmic reticulum (SR) and mitochondria and mediates their interaction <i>via</i> mitochondria-associated endoplasmic reticulum membranes, which tunes the cytosolic Ca²⁺ and reactive oxygen species (ROS) signaling. We aim to investigate if MFN2 would regulate murine embryonic stem cell-derived cardiomyocyte (mESC-CM) maturation, and if yes, what are the underlying mechanisms.</p><p><strong>Results: </strong>MFN2 knockdown caused detrimental effects on mESC-CM maturation in terms of structure, cytosolic calcium kinetics, electrophysiology, and metabolism. Mechanistically, MFN2 knockdown increased proliferative capacity, increased ROS and activated PI3K/AKT/mTOR activity, and these were all reversed by the ROS scavenger N-acetylcysteine. Meanwhile, MFN2 knockdown decreased the IP3R-VDAC coupling mediated by GRP75. Importantly, GRP75 overexpression restored the decreased IP3R-VDAC coupling, reversed the increased cellular ROS, and reversed the increased PI3K/AKT/mTOR activity caused by MFN2 knockdown. Rapamycin, an mTOR inhibitor, reduced the increased proliferative capacity and restored the impaired electrophysiology caused by MFN2 knockdown.</p><p><strong>Innovation: </strong>The current study is the first study to reveal that MFN2-mediated SR-mitochondrial interaction is required for the mESC-CM maturation through the ROS/PI3K/AKT/mTOR axis.</p><p><strong>Conclusion: </strong>MFN2 is required for the maturation of mESC-CMs through GRP75-dependent, mTOR-mediated suppression of proliferative capacity <i>via</i> the ROS/PI3K/AKT pathway. Our findings advance the understanding of PSC-CM maturation and provide novel insight for strategies to promote PSC-CM maturation. <i>Antioxid. Redox Signal.</i> 44, 799-821.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"799-821"},"PeriodicalIF":6.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472414","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":"Preconception Hydroxychloroquine Therapy Restores Placental Function and Improves Pregnancy Outcomes in Obstetric Antiphospholipid Syndrome.","authors":"Yanjun Cai, Mingjie Song, Qingfeng Lv, Hongli Liu, Yuan Wang, Weiyi Qi, Die Jing, Yu Xia, Xietong Wang","doi":"10.1177/15230864261424203","DOIUrl":"10.1177/15230864261424203","url":null,"abstract":"<p><strong>Aims: </strong>Obstetric antiphospholipid syndrome (OAPS), a representative autoimmune disorder driven by antiphospholipid antibodies (aPLs), afflicts 30% of patients with refractory to conventional antithrombotic treatment. Hydroxychloroquine (HCQ) offers adjunctive potential, yet its mechanistic action and critical treatment timing remain undefined. This study establishes the preventive efficacy of preconception HCQ initiation (HCQ-pre) and deciphers its fundamental rescue pathways in OAPS.</p><p><strong>Results: </strong>Clinical data suggested a potential advantage of HCQ-pre compared to post-conception administration (HCQ-post) in optimizing pregnancy outcomes for patients with OAPS. Modeling the pathology of OAPS using human trophoblast organoids revealed that HCQ-pre effectively reverses aPLs-mediated trophoblast dysfunction: increasing cytotrophoblast proliferation (Ki67⁺/TP63⁺) by 20% and restoring their differentiation into extravillous trophoblast (HLA-G⁺) to 93% of control levels, while HCQ-post shows markedly limited efficacy. Mechanistically, HCQ-pre preemptively corrected aPLs-induced redox imbalance by rescuing hypoxia-inducible factor 1-alpha-mediated hypoxia and replenishing antioxidant mediators (NRF2/SOD2/GPX4) <i>via</i> Hippo/YAP and Wnt/β-catenin signaling. Murine OAPS models established that HCQ-pre restores placental perfusion (90% of control levels) by enhancing spiral artery remodeling-with diminished efficacy observed at post-conception administration-thereby attenuating hypoperfusion-induced hypoxic damage and improving pregnancy outcomes.</p><p><strong>Innovation and conclusions: </strong>We redefine HCQ as a proactive placental resetter that neutralizes oxidative stress barriers preconception, thereby liberating trophoblast differentiation capacity. This work positions HCQ-pre as the critical intervention phase-a paradigm shift from reactive adjunct to preemptive root-cause interception, providing the mechanistic foundation for optimizing OAPS management through timely individualized prophylaxis. <i>Antioxid. Redox Signal.</i> 44, 748-769.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"748-769"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218324","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":"Thioredoxin-1 Inhibits Golgi Stress Induced by Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine.","authors":"Jiaoyang Duan, Xiaowei Sun, Yonghang Wei, Yue Pan, Liping Bai, Fang Yan, Jie Bai","doi":"10.1177/15230864261421607","DOIUrl":"10.1177/15230864261421607","url":null,"abstract":"<p><strong>Aims: </strong>Parkinson's disease (PD) is a common neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the aggregation of alpha-synuclein (α-syn) in Lewy bodies. Emerging studies find that disruption of the Golgi structure and Golgi stress are involved in PD. Thioredoxin-1 (Trx-1) is a redox regulatory protein that protects DA neurons from methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damage. However, whether Trx-1 can protect DA neurons against MPTP-induced Golgi stress is still unknown.</p><p><strong>Results: </strong>We first made sure that MPTP led to the loss of DA neurons in the SNpc and motor impairment in mice, which was reversed in Trx-1 overexpression mice. Trx-1 overexpression suppressed Golgi apparatus fragmentation, α-syn aggregation, oxidative stress, and protein kinase C zeta expression increased by MPTP. Trx-1 overexpression restored the colocalization of Trx-1 and tyrosine hydroxylase with Golgi matrix protein 130 (GM130), decreased by MPTP. Moreover, Trx-1 overexpression suppressed the increased co-localization of Leucine-rich repeat kinase 2 and Ras-associated binding protein 29 with vacuolar protein sorting-associated protein 52 induced by MPTP. Trx-1 overexpression suppressed the expression changes of ADP-ribosylation factor 4 and heat shock protein 47, and their colocalization with GM130 induced by MPTP.</p><p><strong>Innovation: </strong>Our study reveals a novel mechanism, whereby Trx-1 inhibits Golgi stress in DA neuron induced by MPTP.</p><p><strong>Conclusions: </strong>These results suggest that Trx-1 may regulate the development of PD through inhibiting Golgi stress and is a potential new molecular target and therapeutic strategy for Golgi stress involved in PD. <i>Antioxid. Redox Signal.</i> 44, 661-675.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"661-675"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140589","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":"Metabolic Reprogramming and Ferroptosis: Unlocking New Therapeutic Frontiers in Cancer and Diabetes.","authors":"Yan Huo, Yaoxiong Xia, Qiuyi Zhang, Yanjie Li, Yu Zhao, Zhiyong Li, Danyu Zhu, Fangpei Ma, Zhun Gu, Nannan Zhang, Yanping Gao","doi":"10.1177/15230864261421487","DOIUrl":"10.1177/15230864261421487","url":null,"abstract":"<p><strong>Significance: </strong>Ferroptosis, an iron- and lipid peroxidation-dependent mode of programmed cell death, is presently realized as a converging mediator that bridges redox imbalance and metabolic dysfunction. Differing from apoptosis and necroptosis, ferroptosis involves iron homeostasis, glutathione depletion, and redox lipid damage. Thus, it becomes the intersection of metabolic reprogramming and redox signaling. Ferroptosis is a double-edged metabolic vulnerability and adaptive resistance pathway in malignancy.</p><p><strong>Recent advances: </strong>Oncogenic signaling cascades such as PI3K/Akt/mTOR and AMPK restructure glucose and lipid metabolism to regulate ferroptotic sensitivity, whereas cancer cells destabilize antioxidant defense pathways such as Xc^--GSH-GPX4 and FSP1-CoQ10-NAD(P)H pathways to evade ferroptotic cell death. Pharmacological inducers erastin, RSL3, and sorafenib reverse oxidative imbalance, enhance antitumor effect, and immune modulation in the tumor microenvironment. In diabetic mellitus complications, ferroptosis is responsible for β-cell deterioration, insulin resistance, and vascular injury. Hyperglycemia-induced oxidative stress and dysregulated GPX4 facilitate lipid peroxidation and ferroptotic cell death in pancreatic β-cells, while iron overload and mitochondrial dysfunctions facilitate ferroptotic injury in diabetic cardiomyopathy, nephropathy, retinopathy, and foot ulcer. These observations position ferroptosis as a crucial metabolically reorganized hub of organ damage.</p><p><strong>Critical issues: </strong>Despite rapid advancements, foundational challenges persist, including the identification of ferroptosis-specific biomarkers, tissue-specific thresholds, and mechanisms for neutralizing off-target toxicity.</p><p><strong>Future directions: </strong>Recently developed technologies such as CRISPR-based functional genomics, metabolomics, and AI-powered modeling represent new-age tools in defining ferroptosis networks and precision therapeutics design. Integration of the regulation of normal physiological ferroptosis into cancer and diabetes therapy has the potential to redefine redox-targeted therapy and metabolic medicine. <i>Antioxid. Redox Signal.</i> 44, 676-711.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"676-711"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177617","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":"Dysregulated Copper Metabolism-Induced Cuproptosis Contributes to Mitochondrial Dysfunction and Macrophage Inflammatory Response in Acute Lung Injury.","authors":"Shuyang Chen, Zheng Zhou, Yajun Wang, Dong Yang, Jinjun Jiang, Shujing Chen","doi":"10.1177/15230864261425887","DOIUrl":"10.1177/15230864261425887","url":null,"abstract":"<p><strong>Aims: </strong>To determine whether dysregulated copper metabolism and cuproptosis contribute to acute lung injury (ALI), and to evaluate whether targeting copper homeostasis mitigates lung inflammation and injury.</p><p><strong>Results: </strong>Integrative analysis of RNA-seq data from patients with severe community-acquired pneumonia revealed increased enrichment of copper metabolism-related gene sets and differential expression of cuproptosis-related genes. Notably, immune deconvolution of patient RNA-seq data demonstrated prominent macrophage enrichment, suggesting that macrophages represent a major cell group in which dysregulated copper metabolism may occur during ALI. In a lipopolysaccharide (LPS)-induced mouse ALI model, lung copper levels were elevated, accompanied by molecular features of cuproptosis, including increased DLAT oligomerization and destabilization of Fe-S cluster proteins. Pretreatment with the copper chelator tetrathiomolybdate alleviated lung injury and inflammatory response, while suppressing cuproptosis-related molecular features <i>in vivo</i>. In alveolar macrophages, LPS challenge increased intracellular Cu⁺ concentration and promoted DLAT oligomerization, and impaired Fe-S protein stability. Mechanistically, both copper chelation and knockdown of upstream cuproptosis regulator reduced DLAT oligomerization, restored Fe-S proteins, alleviated mitochondrial dysfunction, and decreased CD86⁺ macrophage polarization. Importantly, altered expression of copper transporters was observed, suggesting a remodeling of copper metabolic homeostasis during ALI.</p><p><strong>Innovation and conclusion: </strong>This study identifies cuproptosis as a previously unrecognized driver of ALI, mechanistically linking copper dysregulation to mitochondrial damage and inflammatory activation of alveolar macrophages, and demonstrates the therapeutic benefit of copper chelation or cuproptosis suppression. <i>Antioxid. Redox Signal.</i> 44, 770-791.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"770-791"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316133","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":"Epitranscriptomic Control of Vascular Smooth Muscle Cell Ferroptosis by WTAP in the Pathogenesis of Vascular Restenosis.","authors":"Yanwei Yin, Fangmeng Lei, Zihe Dang, Shaoqing Cao, Zhikun Zhao","doi":"10.1177/15230864261424217","DOIUrl":"10.1177/15230864261424217","url":null,"abstract":"<p><strong>Aims: </strong>Vascular restenosis is a common complication following vascular interventions, driven by abnormal proliferation and phenotypic switching of vascular smooth muscle cells (VSMCs). Ferroptosis, an iron-dependent regulated cell death, has been implicated in VSMC dysfunction and vascular remodeling. However, the epitranscriptomic regulation of ferroptosis in VSMCs remains unclear.This study investigates the role of Wilms tumor suppressor gene WT1-associated protein (WTAP), a key N6-methyladenosine (m6A) RNA methylation regulator, in controlling ferroptosis of VSMCs during vascular restenosis.</p><p><strong>Results: </strong>A balloon injury rat model and platelet-derived growth factor-BB-stimulated VSMCs were used to mimic vascular restenosis. WTAP expression and global m6A levels were assessed. Functional assays evaluated the effects of WTAP overexpression on ferroptosis markers, reactive oxygen species (ROS), lipid peroxidation, and VSMC proliferation. Mechanistic studies explored WTAP-mediated m6A modification of the long non-coding RNA growth arrest specific 5 (GAS5), its interaction with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), and downstream regulation of interferon regulatory factor 4 (IRF4) and ferritin heavy chain 1 (FTH1).WTAP expression and global m6A levels were significantly reduced in restenotic tissues and cells. WTAP overexpression restored m6A modification on GAS5, enhancing its stability <i>via</i> YTH domain family member 1. GAS5 inhibited EZH2-mediated H3K27me3 repression of IRF4, which transcriptionally activated FTH1, suppressing ferroptosis. WTAP overexpression decreased ROS, lipid peroxidation, and VSMC proliferation, while knockdown of GAS5 or IRF4 partially reversed these effects.</p><p><strong>Innovation: </strong>Our study is the first to identify that the WTAP/GAS5/IRF4 axis suppresses PDGF-BB-induced cell proliferation by inhibiting ferroptosis in VSMCs, and alleviates vascular restenosis caused by balloon injury.</p><p><strong>Conclusion: </strong>WTAP epitranscriptomically regulates VSMC ferroptosis <i>via</i> the GAS5/EZH2/IRF4/FTH1 axis, revealing a novel mechanism in vascular restenosis pathogenesis and a potential therapeutic target. <i>Antioxid. Redox Signal.</i> 44, 726-747.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"726-747"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363708","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":"Thioredoxin 1 Suppresses TXNIP-Driven Control of Glucose Metabolism in Human Cells.","authors":"Shayida Maimaiti, Markus Dagnell, Lucia Coppo, Wenchao Zhao, Peter Geserick, Kai Kappert, Elias S J Arnér","doi":"10.1177/15230864261421616","DOIUrl":"10.1177/15230864261421616","url":null,"abstract":"<p><strong>Aims: </strong>Cytosolic thioredoxin 1 (Trx1, TXN, TRX) is a central player in redox control. Thioredoxin interacting protein (TXNIP), an α-arrestin regulating glucose metabolism and inflammation, is widely regarded to inhibit TRX activity. However, the interactions between the two proteins across various cellular contexts remain poorly understood; in addition, only a limited number of studies have yet been conducted in human primary cells. We thus aimed here to investigate the functional relationship between TRX and TXNIP in human primary cells. We studied whether TXNIP inhibits TRX cellular activity in these primary cells and how this interaction influences cellular redox biology or glucose metabolism.</p><p><strong>Results: </strong>In primary cells, TXNIP deficiency did not increase cellular TRX activity. Instead, TXNIP deficiency elevated PGC-1α and PDK4 transcripts, increased PDHA1 Ser293 phosphorylation, and raised basal GLUT4, consistent with enhanced glucose uptake and restrained flux through the pyruvate dehydrogenase complex. Conversely, lowering TRX expression levels triggered higher TXNIP levels. This in turn correlated with suppressed transcripts for PGC-1α and PDK4, a lower extent of PDHA1 phosphorylation at Ser293, and decreased glucose uptake.</p><p><strong>Innovation: </strong>Our findings suggest that TXNIP, against common belief, may not necessarily be an endogenous inhibitor of TRX but, rather, that TRX can be an inhibitor of TXNIP.</p><p><strong>Conclusion: </strong>This study reveals that the key intracellular redox protein TRX inversely regulates TXNIP, suggesting that modulation of the TRX system may provide a previously unrecognized therapeutic avenue for modulation of glucose metabolism. <i>Antioxid. Redox Signal.</i> 44, 643-660.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"643-660"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281680","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":"Dietary Antioxidants and Cardiovascular Health: Insights from a 14-Year UK Biobank Trajectory Analysis.","authors":"Ru Fu, Tao Liu, Ye Chen, Miao Huang, Xiaogang Li, Weihong Jiang","doi":"10.1177/15230864261421605","DOIUrl":"10.1177/15230864261421605","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the impact of the composite dietary antioxidant index (CDAI) on the progression from hypertension (HT) to cardiovascular diseases (CVDs) and subsequent death.</p><p><strong>Methods: </strong>This prospective study included 100,193 participants (median age 55) initially free of HT and CVDs from the UK Biobank. The CDAI was calculated from the intake of six dietary antioxidants, including manganese, selenium, zinc, and vitamins A, C, and E. Multivariable Cox regression analysis assessed the relationship between CDAI and the risks of HT, CVDs, and all-cause mortality. Multistate models were used to examine the impact of CDAI levels on CVD progression trajectories.</p><p><strong>Results: </strong>During a median follow-up of 14.10 years, 11,998 participants developed HT, 3656 developed CVDs, and 4169 died. CDAI was inversely associated with the risk of adverse outcomes, including HT, CVDs, and death. Compared with the lowest CDAI quartile, the adjusted hazard ratios (HRs; confidence intervals [CIs]) for the highest quartile in transitions from baseline to HT, to CVDs, and to death were 0.913 (0.868-0.960), 0.890 (0.799-0.992), and 0.850 (0.767-0.942), respectively. An association between the highest quartile CDAI and reduced risk was also observed in transitions from HT to CVDs (HR: 0.698; 95% CI: 0.558-0.872) and from HT to death (HR: 0.803; 95% CI: 0.648-0.995). Mediation analysis indicates that the reduction in CVD and mortality risk associated with CDAI primarily depends on its direct effect rather than its indirect effect through HT.</p><p><strong>Conclusions: </strong>The CDAI influences the progression of CVD trajectories, underscoring the need for dietary adjustments to elevate CDAI levels in CVD health management. <i>Antioxid. Redox Signal.</i> 44, 712-725.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"712-725"},"PeriodicalIF":6.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140628","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":"Hemoglobin Oxidation and Heme in Atherosclerosis-Link Between Intraplaque Hemorrhage and Progression of Complicated Atherosclerotic Lesion.","authors":"Tamás Gáll, Jázon György Balla, Dávid Pethő, György Balla, József Balla","doi":"10.1177/15230864261443852","DOIUrl":"10.1177/15230864261443852","url":null,"abstract":"<p><strong>Significance: </strong>Solid evidence has demonstrated the pathophysiologic role of hemoglobin (Hb) oxidation and heme in the remodeling of arterial tissue in complicated atherosclerotic lesions with hemorrhage. Oxidation of Hb to ferric and ferryl states and subsequent accumulation of ferryl hemoglobin, heme released from globin, peptides derived from fragmentation of globin result in cellular activation and dysfunction, as well as polarization of resident cells and macrophages-all of which drive plaque formation and instability.</p><p><strong>Recent advances: </strong>Oxidized Hb and heme are endogenous pro-atherogenic agonists that target vascular endothelial cells, smooth muscle cells, neutrophils, and macrophages. Rearrangement of the actin cytoskeleton, disruption of intercellular integrity, activation of proinflammatory genes involving nuclear factor kappa B, the c-Jun N-terminal kinase, and the p38 mitogen-activated protein kinase signal transduction pathways are key events leading to endothelial dysfunction. Polarization of macrophages involves cellular responses toward inflammation, calcification, and angiogenesis. Pathways affected include gene changes associated with phosphoinositide 3-kinase signaling, lipid transport, tissue remodeling, and vascularization. This review focuses on the maladaptive cellular responses to Hb oxidation and its products, together with oxidation of low-density lipoprotein and plaque lipid material implicated in the progression of the complicated atherosclerotic lesion, and provides insights into the potential adaptive molecular mechanisms.</p><p><strong>Critical issues: </strong>Identification of molecular targets and novel therapeutic applications are needed to prevent remodeling of vascular tissue in the hemorrhaged complicated atherosclerotic lesion.</p><p><strong>Future directions: </strong>Future research should focus on the red blood cell infiltration of early lesions as a source of extracellular Hb-bearing danger signals. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"15230864261443852"},"PeriodicalIF":6.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687571","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}