Redox Biology最新文献

{"title":"PNKP targeting engages the autophagic machinery through STING and STAT3 to potentiate ferroptosis and chemotherapy in TNBC","authors":"Avi Maimon ,&nbsp;Pier Giorgio Puzzovio ,&nbsp;Yaron Vinik ,&nbsp;Gavriel-David Hannuna ,&nbsp;Sara Donzelli ,&nbsp;Daniela Rutigliano ,&nbsp;Giovanni Blandino ,&nbsp;Sima Lev","doi":"10.1016/j.redox.2025.103775","DOIUrl":"10.1016/j.redox.2025.103775","url":null,"abstract":"<div><div>The polynucleotide kinase/phosphatase (PNKP) is a DNA repair enzyme possessing bifunctional DNA 3′-phosphatase and DNA 5′-kinase activities. It plays an important role in the rejoining of single- and double-strand DNA breaks and is considered as a potential therapeutic target for different cancer types. Here we show that PNKP is highly expressed in triple negative breast cancer (TNBC) and associated with poor prognosis and chemoresistance. Targeting of PNKP enhanced ferroptosis in TNBC, which was associated with increased labile iron pool and ROS and concomitantly decreased in intracellular glutathione, SCD1 and GPX4 levels. Transcriptomic profiling and mechanistic data indicate that PNKP targeting robustly enhances the lysosomal and the autophagic machinery by activating STING and concurrently inhibiting STAT3, thereby increasing ferritinophagy, intracellular iron level and modulating the expression of key ferroptosis regulators. Importantly, PNKP and STAT3 are rapidly phosphorylated, colocalize, and interact upon ferroptosis induction or doxorubicin treatment, the first line treatment for TNBC patients. Targeting PNKP together with doxorubicin synergistically inhibited the growth of TNBC in an animal model and of TNBC-patients derived organoids. These results offer a promising therapeutic combination for TNBC and highlight the clinical potential of PNKP targeting and ferroptotic death for TNBC therapy.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103775"},"PeriodicalIF":11.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738285","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}

{"title":"Advances in KEAP1-based PROTACs as emerging therapeutic modalities: Structural basis and progress","authors":"Jing Chen ,&nbsp;Disheng Feng ,&nbsp;Rui Zhu ,&nbsp;Hua Li ,&nbsp;Lixia Chen","doi":"10.1016/j.redox.2025.103781","DOIUrl":"10.1016/j.redox.2025.103781","url":null,"abstract":"<div><div>Kelch-like ECH-associated protein 1 (KEAP1) functions as a substrate adaptor for the Cullin 3-RING E3 ligase complex, mediating the ubiquitination and subsequent proteasomal degradation of nuclear factor erythroid 2-related factor 2 (NRF2). This regulatory mechanism maintains cellular redox homeostasis by preventing NRF2 overactivation. Proteolysis-targeting chimeras (PROTACs) have emerged as a novel therapeutic strategy that harnesses the ubiquitin-proteasome system for targeted protein degradation. Recent advancements have expanded the repertoire of E3 ligases exploitable for PROTAC design, with KEAP1 identified as a promising candidate. This review provides a comprehensive overview of the structural and functional characteristics of KEAP1, detailing its interactions with NRF2 and Cullin 3. The development of KEAP1- recruiting PROTACs utilizing ligands derived from different classes of known KEAP1 inhibitors—including short peptides, covalent small molecules (e.g., CDDO derivatives), and non-covalent inhibitors (e.g., KI696)—is discussed, highlighting the potential to diversify the available E3 ligase recruiters. Recent progress in developing KEAP1-based PROTACs targeting BRD4, CDK9, FAK, Tau and KEAP1 itself is highlighted, with particular emphasis on ligand optimization strategies employed to enhance degradation efficacy and specificity. Elucidating the structural basis of KEAP1 interactions provides crucial insights for advancing PROTAC applications. However, current challenges in KEAP1-based targeted protein degradation warrant further investigation to fully realize its therapeutic potential. Future research should focus on optimizing KEAP1 ligand properties and exploring novel protein targets amenable to degradation via KEAP1 recruitment to further advance this innovative therapeutic modality.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103781"},"PeriodicalIF":10.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702216","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}

{"title":"Protective effect of hydroxytyrosol against hyperglycemia-induced phosphatidylserine exposure in human erythrocytes: focus on dysregulation of calcium homeostasis and redox balance","authors":"Rosaria Notariale ,&nbsp;Claudia Moriello ,&nbsp;Nicola Alessio ,&nbsp;Vitale Del Vecchio ,&nbsp;Luigi Mele ,&nbsp;Pasquale Perrone ,&nbsp;Caterina Manna","doi":"10.1016/j.redox.2025.103783","DOIUrl":"10.1016/j.redox.2025.103783","url":null,"abstract":"<div><div>Diabetes is a widespread chronic disease that poses serious health concerns due to its numerous associated complications, including an increased risk of cardiovascular diseases. Under conditions of prolonged hyperglycemia, erythrocytes (RBC) undergo the breakdown of the natural phospholipid asymmetry, triggered by cell surface exposure of phosphatidylserine (PS) associated with increased prothrombotic activity. The aim of the present study was to provide insights into the potential molecular mechanisms underlying, focusing on two phospholipid translocases, ATP-dependent flippase ATP11C and calcium-dependent scramblase PLSCR1. The possible protective effect exerted by the hydroxytyrosol (HT), a powerful phenolic antioxidant present in olive oil, was also tested. Exposure of intact human RBC to high glucose (25–50 mM) results in a dose-dependent increase in PS-exposing RBC, which can be prevented by HT at concentrations as low as 5 μM. Furthermore, our study reveals that PLSCR1 activity is significantly higher under hyperglycemic conditions. In line with this finding, immunocytochemical analysis indicates increased membrane expression of this enzyme. Both alterations can be prevented by HT pre-treatment. Conversely, no variation in ATP11C is observable. Importantly, intracellular calcium measurement reveals a significant rise, suggesting that dysregulation of calcium homeostasis may be a key mechanism underlying both the change in scramblase activity as well as the HT protective effect observed. In this case too, in fact, HT exhibits a protective effect. Accordingly, when cells are exposed to high glucose in a calcium-free medium no variation is observable. Finally, we report that HT is able to prevent glucose-induced alteration in redox balance by reducing ROS formation and the decline in intracellular glutathione, likely due to its high scavenging potential as well as to the proposed recycling process cycle that could regenerate reduced glutathione from its radical. All together our findings point to RBC as an additional target in the management of the cardiovascular complications associated with diabetes and indicate HT as nutritional/nutraceutical strategy for their prevention in diabetic patients.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103783"},"PeriodicalIF":10.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679011","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}

{"title":"Involvement of NRF2 and AMPK signaling in aging and progeria: a digest","authors":"Eleni Petsouki ,&nbsp;Vasileios Gerakopoulos ,&nbsp;Despoina D. Gianniou ,&nbsp;Elke H. Heiss ,&nbsp;Ioannis P. Trougakos","doi":"10.1016/j.redox.2025.103782","DOIUrl":"10.1016/j.redox.2025.103782","url":null,"abstract":"<div><div>Aging refers to a <em>gradual, continuous process of natural change</em> which is accompanied by progressive loss in physiological functions and an increased risk of frailty, disease, and death. Cells face a declining capacity to adapt homeostasis after perturbation, resulting among others in an imbalance in reactive species production and damage removal, as well as in energy or nutrient sensing and usage. NRF2 (Nuclear factor E2 p45‐related factor 2) is a transcription factor primarily known to regulate the expression of genes involved in cellular defense against oxidative, proteotoxic, or xenobiotic stress. AMPK (AMP-activated protein kinase), a serine/threonine kinase, serves as a central sensor of cellular energy status, maintaining ATP levels by tweaking the ratio of anabolic and catabolic pathways. Cooperativity between AMPK and NRF2 signaling, which goes beyond mere parallel activation in situations of cellular stress, has been previously described. This narrative short review zooms in the current understanding of NRF2 and AMPK signaling, alone or in concert, in aging and Hutchinson–Gilford Progeria Syndrome (HGPS), a genetic disorder characterized by premature aging.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103782"},"PeriodicalIF":10.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696745","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}

{"title":"15-Lipoxygenase-dependent radiomitigation by NO●-Donors suppresses ferroptosis in intestinal Epithelium: Multiomics MS imaging and LC-MS evidence","authors":"Yulia Y. Tyurina ,&nbsp;Hua Tian ,&nbsp;Haider H. Dar ,&nbsp;Mert Akdogan ,&nbsp;Ecem Saritas ,&nbsp;Vladimir A. Tyurin ,&nbsp;Louis J. Sparvero ,&nbsp;Alexander A. Kapralov ,&nbsp;Galina Shurin ,&nbsp;Renee Fisher ,&nbsp;Michael W. Epperly ,&nbsp;Kunal Singh ,&nbsp;Yuri L. Bunimovich ,&nbsp;Joel S. Greenberger ,&nbsp;Valerian E. Kagan ,&nbsp;Hülya Bayir","doi":"10.1016/j.redox.2025.103777","DOIUrl":"10.1016/j.redox.2025.103777","url":null,"abstract":"<div><div>Threats of irradiation (IR) exposure increase the need for radiomitigators. An important contributor to radiation injury is ferroptosis, triggered by the disbalanced redox metabolism. We showed that 15-lipoxygenase (15-LOX) catalyzed peroxidation of arachidonoyl-phosphatidyl-ethanolamine is an essential ferroptotic response of ileum to total body IR (TBI). Given that nitric oxide (NO^● ) can suppress ferroptosis by inhibiting 15-LOX and by directly scavenging lipid radicals, we tested NO^●-donors with optimized half decay times as radiomitigators. Here, we report that diethylenetriamine-NONOate (DETA-NONOate) (with a half decay-time of 20 hr) acted as an effective radiomitigator when administered 24 hr after exposure to TBI (9.25Gy) and markedly prolonged survival of C57BlJ6 mice by - i) decreasing the levels of pro-ferroptotic HOO-PUFA-PE signals, and ii) decreasing the expression of 15-LOX2 – in the ileum on day 4 after TBI. Redox lipidomics LC-MS and two mass spectrometric imaging (MSI) protocols: i) single-cell multi-omics Dual C₆₀/gas cluster ion beam (GCIB) secondary ion mass spectrometry (SIMS), and ii) matrix-assisted laser desorption ionization (MALDI)-MSI, visualized DETA-NONOate's effectiveness in suppressing TBI-induced HOO-PUFA-PE production and preserving intestinal epithelium structural integrity. In vitro, NO^● donors were effective in suppressing PUFA-PE peroxidation and ferroptotic death in human intestinal epithelial cells (FHs 74 Int) exposed to radiation (8Gy) plus enzymatic (15-LOX2) pro-ferroptotic stimulation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103777"},"PeriodicalIF":10.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687131","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}

{"title":"Metal-organic framework-mediated antioxidant enzyme delivery in disease treatment","authors":"Jiang Yayun ,&nbsp;Ge Qianqian ,&nbsp;Sun Xihang ,&nbsp;Hong Yang ,&nbsp;Hou Zhenping ,&nbsp;Li Yuying ,&nbsp;Ma Xiancheng ,&nbsp;Jiang Qian ,&nbsp;Shi Pengjun","doi":"10.1016/j.redox.2025.103778","DOIUrl":"10.1016/j.redox.2025.103778","url":null,"abstract":"<div><div>Excessive reactive oxygen species (ROS) induce oxidative stress (OS), resulting in biomolecular damage. ROS are closely linked to diseases such as inflammatory bowel disease (IBD), diabetes, and cancer. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glucose oxidase (GOX) play crucial roles in alleviating OS by effectively reducing ROS levels through synergistic action. However, these antioxidant enzymes exhibit poor stability in complex biological environments and lack adequate targeting capability, thereby limiting their applications in disease treatment. Metal-organic frameworks (MOFs) serve as carriers that significantly enhance enzyme stability and targeting ability, thereby boosting catalytic efficiency and therapeutic outcomes. This review discusses the classification of antioxidant enzymes and their role in ROS regulation, the types and physicochemical properties of MOFs, and the assembly methods of enzyme@MOF systems. Furthermore, it examines the potential of integrating MOFs with antioxidant enzymes for the treatment of diseases associated with OS. Although the strategy of enzyme immobilization with MOFs shows great application prospects, further optimization is required in terms of biocompatibility, long-term stability, and delivery efficiency to promote the clinical translation of these results.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103778"},"PeriodicalIF":10.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664830","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}

{"title":"Ether lipids and sphingolipids drive sex-specific human aging dynamics","authors":"Joaquim Sol ,&nbsp;Anna Fernàndez-Bernal ,&nbsp;Natalia Mota-Martorell ,&nbsp;Meritxell Martín-Garí ,&nbsp;Èlia Obis ,&nbsp;Alba Juanes ,&nbsp;Victoria Ayala ,&nbsp;Jordi Mayneris-Perxachs ,&nbsp;Rafel Ramos ,&nbsp;Víctor Pineda ,&nbsp;Josep Garre-Olmo ,&nbsp;Manuel Portero-Otín ,&nbsp;José Manuel Fernández-Real ,&nbsp;Josep Puig ,&nbsp;Mariona Jové ,&nbsp;Reinald Pamplona","doi":"10.1016/j.redox.2025.103779","DOIUrl":"10.1016/j.redox.2025.103779","url":null,"abstract":"<div><div>Aging is a dynamic process characterized by complex molecular changes, including shifts in lipid metabolism. To systematically define lipidome dynamics with age and identify sex-specific lipidomic signatures, we performed targeted lipidomic profiling of plasma samples from 1030 adults aged 50–98 years, analyzing 543 lipid species across all lipid classes using high-throughput mass spectrometry and assessing the circulating fatty acid composition by gas chromatography.</div><div>Our results reveal age-related lipidomic shifts, with ceramides and ether-linked phospholipids most affected. We identified three aging crests (55–60, 65–70, 75–80 years), with the 65–70 years crest dominant in men and the 75–80 years crest in women. Lipid enrichment analyses highlight acylcarnitines, sphingolipids and ether-linked phospholipids as key contributors, with functional indices indicating compositional shifts in lipid species.</div><div>These findings suggest an impairment of lipid functional categories, including loss of dynamic properties, alterations in bioenergetics, antioxidant defense, cellular identity, and signaling platforms. This study underscores the non-linear nature of lipid metabolism in aging and provides a foundation for identifying biomarkers and interventions to promote healthy aging.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103779"},"PeriodicalIF":10.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664829","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}

{"title":"Sulfhydrylated albumin mitigates Acetaminophen-induced liver injury by restoring the integrated H2S-albumin thiol antioxidant network","authors":"Xin Wang ,&nbsp;Yang Sui ,&nbsp;Rui Jiang ,&nbsp;Yijun Xu ,&nbsp;Mika Suda ,&nbsp;Jie Cheng ,&nbsp;Yingyu Zhang ,&nbsp;Zhuheng Shi ,&nbsp;Jianglin Fan ,&nbsp;Jian Yao","doi":"10.1016/j.redox.2025.103774","DOIUrl":"10.1016/j.redox.2025.103774","url":null,"abstract":"<div><div>Acetaminophen (APAP) overdose is the leading cause of acute liver failure and a major global health issue. APAP hepatotoxicity is primarily driven by oxidative stress resulting from the depletion of hepatic glutathione (GSH). Given that hydrogen sulfide (H₂S) and albumin are crucial components of the thiol antioxidant system, we hypothesized they play a critical role in the body's defense against APAP-induced liver injury (AILI). This study aimed to test this hypothesis and explore novel therapeutic approach. Administration of APAP to mice induced significant hepatic damage, associated with marked local and systemic oxidative stress, evidenced by elevated serum transaminases and oxidative injury markers. Furthermore, APAP exposure disrupted the hepatic H₂S-generating system, leading to reduced expression of H₂S-synthesizing enzymes and decreased levels of H₂S and protein persulfidation (-SSH) in both liver and serum. Pharmacological inhibition of endogenous H₂S production dramatically exacerbated APAP hepatotoxicity and mortality. Conversely, supplementation with a modified persulfide-rich albumin (Alb-SSH) significantly alleviated hepatocyte injury. These findings were similarly observed in cultured hepatocytes. Mechanistic analysis revealed that Alb-SSH increased H₂S levels by releasing H₂S and restoring H₂S-synthesizing enzymes. It improved both hepatic and systemic oxidative status and rebalanced the intra- and extracellular GSH/GSSG ratio. At the molecular level, Alb-SSH directly scavenged reactive oxygen species and integrated with the GSH/GSSG system via thiol-disulfide exchange reactions. Collectively, our study establishes H₂S and Alb-SSH as integral components of a coordinated thiol antioxidant network that counteracts AILI. Supplementation with Alb-SSH represents a promising therapeutic strategy for AILI and other oxidative stress-associated diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103774"},"PeriodicalIF":10.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670901","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}

{"title":"Gastric cancer adapts high lipid microenvironment via suppressing PPARG-FABP1 axis after arriving in the lymph node","authors":"Yinan Liu ,&nbsp;Liang Tang ,&nbsp;Baifu Peng ,&nbsp;Shaoji Zhao ,&nbsp;Ziling Shao ,&nbsp;Kaiyu Sun ,&nbsp;Jinning Ye ,&nbsp;Wei Chen ,&nbsp;Jianbo Xu","doi":"10.1016/j.redox.2025.103759","DOIUrl":"10.1016/j.redox.2025.103759","url":null,"abstract":"<div><h3>Aim</h3><div>Gastric cancer (GC) primarily metastasizes through lymphatic channels, although lymphatic metastasis remains relatively inefficient. Changes in cellular metabolism, known as metabolic reprogramming, plays a significant role in the adaptive survival of cells during the process. Therefore, understanding the mechanism underlying metabolic reprogramming in lymph node (LN) metastasis is crucial for the development of targeted therapies for advanced gastric cancer. This study aimed to investigate the metabolic adaptations of GC cells during LN metastasis, with a particular focus on lipid metabolism reprogramming.</div></div><div><h3>Methods</h3><div>Non-targeted lipidomic sequencing, combined with tumor cell flow sorting and RNA sequencing, was used to explore differences in lipid microenvironments and changes in lipid metabolism pathways between lymph nodes and primary tumors. Single-cell sequencing data were analyzed to confirm these results. Transmission electron microscopy, BODIPY 581/591 staining, and ferroptosis inhibitors were used to confirm the effects of arachidonic acid (AA) on ferroptosis sensitivity in gastric cancer. Public databases and ChIP-qPCR tests were used to investigate the role of PPARγ pathway in regulating FABP1 transcription.</div></div><div><h3>Results</h3><div>Lipid metabolism pathway was inhibited following lymph node metastasis, with reduced lipid catabolites observed in the lymph nodes. Single-cell data also supported these findings. Physiological concentrations of AA were shown to increase ferroptosis sensitivity, lipid peroxidation, and mitochondrial damage in gastric cancer cells. FABP1 was significantly downregulated in lymph nodes, which mediated the uptake of AA, mitochondrial destruction, and lipid peroxidation. Further analysis revealed that PPARγ, a regulator of FABP1 transcription, was significantly downregulated after lymph node metastasis. Furthermore, our findings revealed that AA reduced the stability of PPARγ protein.</div></div><div><h3>Conclusion</h3><div>The high concentration of AA in the lymph nodes microenvironment can increase the sensitivity of gastric cancer cells to ferroptosis. Mechanically, AA inhibits the PPARγ pathway to downregulate FABP1 expression, thereby suppressing AA uptake and preventing ferroptosis of gastric cancer cells.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103759"},"PeriodicalIF":10.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664826","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}

{"title":"Reactive oxygen species in polycystic ovary syndrome: Mechanistic insights into pathogenesis and therapeutic opportunities","authors":"Huanju Liu ,&nbsp;Lihao Jin ,&nbsp;Xiaoya Wang ,&nbsp;Junling Shi ,&nbsp;Yujie He ,&nbsp;Ningxia Sun ,&nbsp;Fu Yang","doi":"10.1016/j.redox.2025.103776","DOIUrl":"10.1016/j.redox.2025.103776","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS), a common yet intricate endocrine disorder, presents persistent clinical challenges due to its complex pathogenesis. Reactive oxygen species (ROS), highly reactive molecules, have emerged as critical contributors to PCOS development and represent potential therapeutic targets. This review comprehensively explores the diverse roles of ROS in PCOS pathogenesis, particularly their contributions to metabolic dysfunction and hormonal imbalance. It further assesses the therapeutic potential of ROS-targeted interventions, summarizing antioxidant therapy advancements, underlying mechanisms, and current challenges. By consolidating recent research, this review highlights the profound significance of ROS in PCOS, aiming to inspire innovative pathogenesis research, improve clinical management, and establish a robust theoretical foundation for more effective PCOS treatment strategies.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103776"},"PeriodicalIF":10.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670986","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}