Antioxidants & redox signaling最新文献

{"title":"Trilobatin, a Natural Dihydrochalcone, Stabilizes Nrf2 to Protect the Heart from Angiotensin II-Induced Oxidative and Hypertrophic Stress.","authors":"Yujiao Wu, Jiahao Li, Xin Wen, Dan Li","doi":"10.1177/15230864261483358","DOIUrl":"10.1177/15230864261483358","url":null,"abstract":"<p><strong>Aims: </strong>Oxidative stress-driven cardiac remodeling is a key pathological feature of heart failure and hypertensive heart disease, yet effective antioxidant therapies remain limited. This study aimed to determine whether the natural dihydrochalcone trilobatin (Tri) protects against angiotensin II (Ang II)-induced cardiac remodeling by alleviating oxidative stress and improving mitochondrial function, and to elucidate its underlying mechanisms.</p><p><strong>Results: </strong>Tri treatment significantly improved Ang II-induced cardiac dysfunction, restoring ejection fraction and fractional shortening, and reduced myocardial hypertrophy, as evidenced by decreased cardiomyocyte cross-sectional area and downregulation of hypertrophic markers, including atrial natriuretic peptide (<i>ANP</i>), B-type natriuretic peptide (<i>BNP</i>), and beta-myosin heavy chain <i>(β-MHC)</i>. Tri enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and upregulated downstream antioxidant genes, restoring redox balance and mitochondrial integrity. <i>In vitro</i>, Tri reduced reactive oxygen species and lipid peroxidation, preserved mitochondrial membrane potential, and improved bioenergetic function. Mechanistically, Tri directly targets Nrf2 and enhances its stability by suppressing ubiquitination, with T447 identified as a key interaction residue whose mutation attenuated Tri-induced Nrf2 signaling. Notably, silencing and inhibition of Nrf2 abolished Tri's protective effects, establishing Nrf2 as essential for its action.</p><p><strong>Innovation: </strong>This study introduces Tri as a novel Nrf2-stabilizing agent with dual antioxidant and mitochondrial-protective properties, offering a promising therapeutic strategy for oxidative stress-driven cardiovascular diseases. These findings bridge natural product pharmacology with redox biology and highlight a translational path toward heart failure intervention.</p><p><strong>Conclusion: </strong>We identify the dihydrochalcone compound Tri as a potent cardioprotective agent that stabilizes and activates Nrf2 signaling to counteract oxidative and hypertrophic stress. <i>Antioxid. Redox Signal.</i> 45, 776-791.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"776-791"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838926","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":"Mannose Ameliorates Radiation-Induced Intestinal Injury in Mice <i>via</i> Preventing Mitochondrial Dysfunction.","authors":"Yanqing Liu, Renjun Peng, Yiying Zhang, Jing Dai, Suhe Dong, Huijie Yu, Sinian Wang, Zhongmin Chen, Qisheng Jiang, Wei Li, Yining Yue, Jianan Wang, Jie Xu, Zhongtang Li, Fengsheng Li","doi":"10.1177/15230864261476850","DOIUrl":"10.1177/15230864261476850","url":null,"abstract":"<p><strong>Aims: </strong>Radiation-induced intestinal injury (RIII) severely compromises the quality of life in patients undergoing abdominal/pelvic radiotherapy and may necessitate treatment discontinuation. To date, there is no approved agent for the prevention or treatment of RIII. This study aims to clarify the protective effects of mannose on RIII and elucidate its mechanisms of action, in order to identify new safe and effective therapeutic agents and potential therapeutic targets for the prevention and treatment of RIII.</p><p><strong>Results: </strong>Here, we report that intraperitoneal administration of mannose, a natural bioactive monosaccharide, at 24, 12, and 2 h prior to lethal irradiation increased the survival rate of mice from 0% to 50%. Specifically, mannose pretreatment significantly blocked crypt cell apoptosis, preserved epithelial barrier integrity, attenuated intestinal inflammation, and enhanced crypt regeneration. Additionally, mannose treatment enhanced the survival of intestinal stem cells both <i>in vitro</i> and <i>in vivo</i> following radiation exposure. We further confirmed that mannose maintains mitochondrial homeostasis and alleviates cellular oxidative stress. Moreover, mannose facilitated the repair of DNA double-strand breaks, thereby inhibiting aberrant mitosis after radiation exposure. Additionally, preliminary evidence indicates that mannose does not affect the radiosensitivity of colorectal tumor cells or azoxymethane/dextran sodium sulfate-induced colorectal tumors in mice.Conclusion and Innovation:Given its low toxicity and wide availability, our findings suggest that mannose represents a promising protective strategy for RIII. <i>Antioxid. Redox Signal.</i> 45, 840-856.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"840-856"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700516","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":"Intercellular Mitochondria Transfer in Lung Diseases: New Mechanisms, Risks, Therapeutic Boundaries.","authors":"Jiwei Zhu, Xuan Lai, Wang Lv, Zihao Li, Jun Chen, Li Yu, Luming Wang, Jian Hu","doi":"10.1177/15230864261481713","DOIUrl":"10.1177/15230864261481713","url":null,"abstract":"<p><p><i>Significance:</i> Intercellular mitochondrial transfer (MT) is increasingly recognized as more than a mechanism of bioenergetic rescue. By modulating mitochondrial quality control, redox homeostasis, immune-cell metabolism, and cell-death susceptibility, MT may influence disease progression and therapeutic response in lung diseases.<i>Recent Advances:</i> Studies have shown that engineered enhancement of mitochondrial biogenesis and transfer can restore mitochondrial homeostasis and attenuate pulmonary fibrosis. In cancer, mitochondrial acquisition can enhance metastatic fitness, redox buffering, and immune escape, whereas directed MT to T cells can improve T-cell antitumor activity. Emerging evidence further links MT to the regulation of oxidative stress, ferroptosis sensitivity, and redox-dependent immune remodeling within the tumor microenvironment.<i>Critical Issues:</i> The biological consequences of MT remain highly context dependent. Transfer efficiency, persistence of transferred mitochondria, cargo quality, and long-term integration into recipient-cell mitochondrial networks remain insufficiently characterized. The same process may promote tissue repair in the injured lung while conferring metabolic advantages on malignant cells, thereby defining important therapeutic and safety boundaries.<i>Future Directions:</i> Future studies should clarify how mitochondrial cargo quality, recipient-cell identity, and microenvironmental state shape MT outcomes. Improved methods for tracking mitochondrial fate and assessing long-term functional integration will be essential for translating MT-based strategies into safe and effective clinical therapies. <i>Antioxid. Redox Signal.</i> 45, 879-907.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"879-907"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148824405","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":"Smart Cryopreservation: Antioxidants as Molecular Guardians of Fertility.","authors":"Elnaz Zand, Bing Zhang, Gang Zhao","doi":"10.1177/15230864261481042","DOIUrl":"10.1177/15230864261481042","url":null,"abstract":"<p><strong>Significance: </strong>Ovarian tissue cryopreservation (OTC) has emerged as an important fertility-preservation strategy for patients undergoing gonadotoxic treatment. However, this approach remains vulnerable to freeze-thaw-associated cellular injury driven by oxidative stress, mitochondrial dysfunction, cryoprotectant toxicity, and ischemia-reperfusion damage. Antioxidants have demonstrated potential as redox modulators, but clinical use necessitates careful consideration of dosage, timing, and tissue-specific redox biology. Importantly, excessive antioxidant supplementation may induce reductive stress, interfering with physiological redox signaling.</p><p><strong>Recent advances: </strong>Enzymatic antioxidants, including catalase and superoxide dismutase, and nonenzymatic antioxidants, including resveratrol, melatonin, <i>N</i>-acetylcysteine, and vitamins C and E, have been evaluated in OTC models. Studies using human ovarian tissue, including <i>ex vivo</i> and xenograft models, have reported promising effects on follicular morphology, steroidogenic activity, angiogenesis, and post-thaw apoptosis. Melatonin and resveratrol have demonstrated protective effects in preclinical models; however, direct evidence from cryopreserved human ovarian tissue remains limited. Because these agents act through distinct mechanisms, antioxidant selection should be matched to the specific oxidative-stress phenotype.Critical Issue:Considerable heterogeneity persists in antioxidant selection, concentration, timing, and delivery, and no standardized protocols are currently available. Antioxidant overexposure may cause paradoxical pro-oxidant effects or reductive stress, thereby disrupting redox-dependent signaling. Ethical and regulatory considerations require particular attention in pediatric fertility preservation.</p><p><strong>Future direction: </strong>Future studies need to compare antioxidant therapy with conventional treatments using clinically relevant endpoints such as graft survival, hormonal recovery, and live-birth rates. Combining patient features with redox analysis could allow for personalized therapy. Future studies also need to address the chromosomal integrity of oocytes. <i>Antioxid. Redox Signal.</i> 45, 792-820.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"792-820"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817216","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":"GRX2-Mediated Deglutathionylation of SIRT3 Alleviates Intestinal Ischemia/Reperfusion-Induced Mitochondrial Oxidative Damage.","authors":"Liangyuan Yin, Zhecheng Wang, Xuzi Zhao, Shili Ning, Feng Zhang, Zhao Chen, Chengjun Zhuang, Fengyuan Yang, Jihong Yao, Zhanyu Wang, Xiaofeng Tian","doi":"10.1177/15230864261476884","DOIUrl":"10.1177/15230864261476884","url":null,"abstract":"<p><strong>Aims: </strong>Mitochondrial oxidative damage is one of the factors that contributes to the pathological process of intestinal ischemia/reperfusion (II/R) injury. Glutaredoxin (GRX2), which serves as a crucial protein in maintaining mitochondrial redox homeostasis, affects the activity of downstream proteins through its deglutathionylation effect. Silent information regulator (SIRT3), a crucial deacetylase in mitochondria, has regulatory effects on the activity of various mitochondrial antioxidant enzymes. However, the precise regulatory mechanism underlying SIRT3 enzymatic activity is unknown. Our research is designed to explore GRX2-mediated SIRT3 deglutathionylation's role and mechanism in II/R injury.</p><p><strong>Results: </strong>GRX2 levels decreased after II/R injury, and GRX2 overexpression alleviated II/R-induced intestinal mucosal injury, mitochondrial oxidative damage, damage to mitochondrial structure and function, remote organ injury, and the systemic inflammatory response. GRX2 overexpression substantially decreased the S-glutathionylation of SIRT3 and increased its activity. The results of the incubation of recombinant SIRT3 with glutathione and H₂O₂ indicated that the S-glutathionylation of SIRT3 inhibited SIRT3 activity. Subsequently, SIRT3 mutant plasmids with cysteine-to-serine substitutions were constructed to screen for the S-glutathionylation sites of SIRT3 among the four cysteine residues in its amino acid sequence. The results demonstrated that C280 and C283 are the SIRT3 S-glutathionylation sites. The results of experiments using ischemic intestines from clinical cases confirmed the relationship between GRX2 and SIRT3.</p><p><strong>Innovation: </strong>This study demonstrates that GRX2 alleviates mitochondrial oxidative damage following II/R by reversing the S-glutathionylation of SIRT3.</p><p><strong>Conclusion: </strong>GRX2 is an important protective factor against II/R injury, and GRX2-mediated deglutathionylation of SIRT3 alleviates II/R-induced mitochondrial injury and intestinal damage. <i>Antioxid. Redox Signal.</i> 45, 721-738.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"721-738"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705248","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":"Mitochondrial Microautophagy: An Emerging Pathway in Maintaining Mitochondrial Homeostasis.","authors":"Huijia Zhang, Ying Chen, Junjie Jiang, Yarong Ding, Si Hu, Zhongzhi Zhou, Li Chen","doi":"10.1177/15230864261481794","DOIUrl":"10.1177/15230864261481794","url":null,"abstract":"<p><p><i>Background:</i>Mitochondrial quality control has traditionally been attributed to mitophagy. However, emerging evidence indicates that mitochondrial microautophagy represents a distinct quality control pathway. This pathway enables selective removal of damaged mitochondrial subdomains while preserving overall organelle integrity. Therefore, mitochondrial microautophagy can be viewed as a redox-adaptive, sub-organelle quality control system that responds to localized mitochondrial stress.<i>Scope of Review:</i> In this review, we integrate recent mechanistic, imaging, and molecular studies to establish an updated framework of mitochondrial microautophagy. We describe this process as a sequential pathway involving damage sensing, mitochondria-lysosome contact formation, lysosomal membrane remodeling, selective degradation, and metabolic recycling. Localized reactive oxygen species (ROS) serve as important signals during this process. ROS define specific damage microdomains and facilitate selective mitochondrial component recognition. Subsequent cargo delivery and degradation are regulated by multiple molecular modules. These modules include the ubiquitin-autophagy-related protein 8 system, vacuolar-type H⁺-ATPase-dependent membrane remodeling, Ras-related in brain-endosomal sorting complexes required for transport signaling, the spermatogenesis-associated 18/mitochondria-eating protein pathway, and the mechanistic target of rapamycin complex 1-transcription factor EB and nuclear factor erythroid 2-related factor 2 stress-response networks.<i>Outstanding Questions:</i> Despite substantial progress, several fundamental questions remain unresolved. The mechanisms underlying cargo recognition require further clarification. The existence of specific redox-sensitive receptors remains to be determined. In addition, future technological advances will provide deeper insights into this pathway.<i>Conclusions:</i> Understanding mitochondrial microautophagy may reveal new therapeutic opportunities for mitochondrial dysfunction-associated disorders, including neurodegeneration, ischemic injury, metabolic disorders, and aging. <i>Antioxid. Redox Signal.</i> 45, 857-878.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"857-878"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878866","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":"Resveratrol Alleviates Chronic Intermittent Hypoxia-Induced Lung Injury by Inhibiting Ferroptosis via SIRT1-Dependent Modulation of the EGR1/GLS2 Axis.","authors":"Fan Wei, Jia Chen, Xiaoyu Deng, Wenqian Chen, Yaqi Liu, Qichang Lin, Ningfang Lian","doi":"10.1177/15230864261477032","DOIUrl":"10.1177/15230864261477032","url":null,"abstract":"<p><strong>Aims: </strong>Obstructive sleep apnea (OSA)-associated chronic intermittent hypoxia (CIH) induces lung injury, partly through ferroptosis. Although resveratrol (Res) exhibits antioxidant activity, its mechanism in mitigating ferroptosis under CIH remains unclear. This study aimed to determine whether Res attenuates CIH-induced lung injury by suppressing ferroptosis and to elucidate the role of Sirtuin 1 (SIRT1)-dependent modulation of the early growth response factor 1 (EGR1)/glutaminase 2 (GLS2) axis.</p><p><strong>Results: </strong>CIH models were established using Sprague-Dawley rats and human bronchial epithelial BEAS-2B cells, treated with optimal doses of Res. <i>In vivo</i>, Res treatment significantly attenuated alveolar structural damage, enhanced glutathione (GSH) biosynthesis, and upregulated the expression of glutathione peroxidase 4 (GPX4). <i>In vitro</i>, Res reversed CIH-induced ferroptotic phenotypes and restored mitochondrial morphological integrity in BEAS-2B cells. Mechanistically, Res activated SIRT1. Integrated analysis of RNA sequencing and the FerrDb database identified EGR1 as a pivotal downstream effector of SIRT1-mediated ferroptosis regulation. Rescue experiments demonstrated that EGR1 knockdown abrogated the anti-ferroptotic effects conferred by both Res treatment and SIRT1 overexpression, indicating that SIRT1 suppresses ferroptosis <i>via</i> EGR1 upregulation. Furthermore, bioinformatics prediction and dual-luciferase reporter assays confirmed that EGR1 directly binds to and transcriptionally activates the promoter of GLS2. Consequently, GLS2 knockdown attenuated the protective effects of Res, whereas GLS2 overexpression augmented GSH production and suppressed ferroptosis.</p><p><strong>Innovation and conclusion: </strong>Res alleviates CIH-induced lung injury by inhibiting ferroptosis <i>via</i> SIRT1-dependent modulation of the EGR1/GLS2 axis. These findings reveal a novel mechanism in OSA pathophysiology and highlight Res as a promising therapeutic candidate for CIH-induced lung injury. <i>Antioxid. Redox Signal.</i> 45, 757-775.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"757-775"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711224","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":"Immune Checkpoint Inhibitor-Induced Cardiovascular Disease: The Role of Accelerated Senescence in Vascular Dysfunction.","authors":"Bernardo Casso-Chapa, Angelica Paniagua-Bojorges, Nicolas L Palaskas, Kevin T Nead, Venkata S K Samanthapudi, Jonghae Lee, Gilbert Mejia, Oanh Hoang, Jung Hyun Kim, Steven H Lin, Anita Deswal, Joerg Herrmann, Guangyu Wang, James L Kirkland, Sunil Krishnan, Ying H Shen, Syed Wamique Yusuf, Cezar A Iliescu, Abhishek Jain, Norma Alicia Vazquez González, Keila Carolina Ostos Mendoza, Nordin M J Hanssen, Menno P J de Winther, Laurent Yvan-Charvet, Roza I Nurieva, Keri Schadler, Efstratios Koutroumpakis, John P Cooke, Sivareddy Kotla, Nhat-Tu Le, Jun-Ichi Abe","doi":"10.1177/15230864251410546","DOIUrl":"https://doi.org/10.1177/15230864251410546","url":null,"abstract":"<p><strong>Significance: </strong>Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by reactivating antitumor immunity and improving outcomes across multiple malignancies. Yet, clinical observations and preclinical studies suggest that ICIs may increase long-term cardiovascular disease risk, including hypertension, atherosclerosis, and thrombosis. The underlying mechanisms remain incompletely defined, highlighting the need for focused investigation into the vascular consequences of immune activation.</p><p><strong>Recent advances: </strong>ICI-induced immune activation disrupts vascular and immune homeostasis through persistent production of reactive oxygen species (ROS), mitochondrial dysfunction, and accumulation of cell-free DNA (cfDNA). Sustained T-cell activation enhances ROS generation, driving DNA damage and senescence in both endothelial and immune cells. ICIs may also promote endothelial-to-mesenchymal transition (EndoMT) through chronic oxidative and inflammatory signaling, contributing to fibrosis, vascular stiffness, and chronic inflammation. Transforming growth factor-beta, although immunosuppressive in many contexts, can drive profibrotic and EndoMT programs within the vasculature. Other cytokines and regulators, including interleukin-17 and regulator of calcineurin 1, have been implicated in vascular remodeling, atherosclerosis, and hypertension.</p><p><strong>Critical issues: </strong>The relative roles of ROS, mitochondrial dysfunction, cfDNA-driven inflammation, and EndoMT in ICI-associated vascular senescence remain unclear. While inflammation-induced vascular damage is well-recognized, direct ICI-specific mechanisms require stronger evidence. How senescent endothelial and immune cells influence therapy resistance and remodeling of the tumor microenvironment also remains to be defined.</p><p><strong>Future directions: </strong>Mitochondrial and cytosolic ROS sources-arising from electron leakage during oxidative phosphorylation and NADPH oxidases activity-shape immune signaling and sustain T-cell activation during checkpoint blockade. The DNA damage response kinases ataxia-telangiectasia mutated and ATM- and Rad3-related, activated by oxidative and replicative stress, engage p53-dependent senescence pathways in endothelial and immune cells. Future studies should evaluate biomarkers such as cfDNA and thrombospondin-1 and explore senescence-targeting or redox-modulating interventions that may alleviate cardiovascular toxicity without diminishing antitumor efficacy. This review outlines mechanistic pathways linking ICIs to vascular dysfunction and senescence, integrating preclinical data with emerging clinical insights. It distinguishes established processes from ICI-specific hypotheses and identifies key gaps requiring clinical validation. <i>Antioxid. Redox Signal.</i> 45, 821-839.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":"45 16-18","pages":"821-839"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134940","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":"Selenium-Binding Protein 1 Deficiency Inhibits the Antitumor Immunity of Dendritic Cells.","authors":"Shuang Han, Yi Li, Jie Meng, Jie Dai, Zhu Zeng, Yi Jia","doi":"10.1177/15230864261476887","DOIUrl":"10.1177/15230864261476887","url":null,"abstract":"<p><strong>Aims: </strong>Selenium-binding protein 1 (SELENBP1) correlates positively with the prognosis of patients with colitis and colon cancer. SELENBP1-deficient dendritic cells (DCs) promote regulatory T cell differentiation and exert direct immunomodulatory functions. This study aimed to investigate whether SELENBP1-deficient DCs mediate antitumor immune function by affecting CD8⁺ T cell activation or exhaustion.</p><p><strong>Results: </strong>Our findings revealed that SELENBP1 deficiency in mice accelerates colon cancer progression, characterized by reduced numbers of activated DCs and cytotoxic CD8⁺ T cells, increased intratumoral exhaustion-related factors, and impaired CD8⁺ T cell tumor-killing capacity. Adoptive-transfer experiments showed that SELENBP1 deficiency impairs DC antitumor activity, which may be associated with decreased intratumoral DCs, reduced cytotoxic CD8⁺ T cells, and increased dysfunctional T cell phenotypes. Moreover, <i>in vitro</i> cell experiments showed that the phosphatidylinositol 3-kinase/protein kinase B and hypoxia-inducible factor-1-alpha pathways are involved in DC migration as well as DC-mediated phenotypic dysfunction of CD8⁺ T cells. In addition, <i>SELENBP1</i> expression in conventional DCs correlated positively with cytotoxic CD8⁺ T cells.</p><p><strong>Innovation: </strong>This study is the first to investigate the antitumor immune function of SELENBP1 in DCs.</p><p><strong>Conclusion: </strong><i>In vitro</i> experiments showed that SELENBP1 deficiency impairs DC migration and maturation, resulting in decreased cytotoxic CD8⁺ T cells and increased dysfunctional T cell phenotypes. This phenomenon may underlie the accelerated colon tumor progression observed upon global SELENBP1 ablation or adoptive transfer of SELENBP1-deficient DCs. In brief, SELENBP1 deficiency impairs DC-mediated antitumor immune function. <i>Antioxid. Redox Signal.</i> 45, 739-756.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"739-756"},"PeriodicalIF":6.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676873","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":"A Vaginal Secretion-Derived Metabolite Drives HMOX1/Fe²⁺ Axis-Mediated Ferroptosis in Mucosal Damage of Senile Vaginitis.","authors":"Jiaxiong Li, Xiaomeng Tan, Yao Rao, Mayi Huang, Yueyue Gui, Guanghua Wang, Jin Qiu, Jiehua Ma","doi":"10.1177/15230864261483991","DOIUrl":"10.1177/15230864261483991","url":null,"abstract":"<p><strong>Aims: </strong>Senile vaginitis is a common clinical condition with limited treatment options. Estrogen deficiency leads to atrophy of the vaginal walls and thinning of the mucosa. It is noteworthy that although vaginal atrophy is an almost universal consequence of menopause, many postmenopausal women do not develop genitourinary symptoms. These observations collectively indicate that estrogen-independent pathogenic mechanisms are involved. In our preliminary study, through metabolomic screening, we identified three functionally relevant metabolites, namely guggulsterone (GS), umbelliprenin, and inosinic acid. This study seeks to elucidate the pathogenic mechanism of GS in senile vaginitis and to unveil novel therapeutic avenues for this condition.</p><p><strong>Results: </strong>Cellular and animal experiments confirm that GS elevates intracellular ferrous iron (Fe²⁺), malondialdehyde, and reactive oxygen species levels in vaginal epithelial cells, thereby inducing ferroptosis and upregulating the expression of inflammatory factors in vaginal tissues. Consequently, these processes compromise vaginal mucosal integrity, thereby exacerbating epithelial atrophy and the progression of inflammation. Treatment with the ferroptosis inhibitor ferrostatin-1 partially reversed the accumulation of Fe²⁺, lipid peroxides, and cellular oxidative stress. By utilizing a combination of lipidomic mass spectrometry, molecular docking, and surface plasmon resonance, it was collectively demonstrated that GS directly binds to heme oxygenase 1 (HMOX1). Utilizing VK2/E6E7 cell models with lentivirus-mediated HMOX1 knockdown and overexpression, this study demonstrates that GS might contribute to ferroptosis in vaginal epithelial cells by upregulating HMOX1 expression. Notably, treatment with MG132 potentiated the GS-induced upregulation of HMOX1, whereas the autophagy-lysosome inhibitor bafilomycin A1 had no significant effect. These findings suggest that GS may upregulate HMOX1 levels by inhibiting its degradation through the proteasome pathway.</p><p><strong>Innovation and conclusion: </strong>Collectively, these findings establish GS as a critical regulator of vaginal epithelial cell ferroptosis through HMOX1 targeting, revealing new therapeutic avenues for senile vaginitis. <i>Antioxid. Redox Signal.</i> 45, 618-635.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"618-635"},"PeriodicalIF":6.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862906","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}