Redox Biology最新文献

{"title":"Non-thermal atmospheric pressure plasma-irradiated cysteine protects cardiac ischemia/reperfusion injury by preserving supersulfides","authors":"Akiyuki Nishimura ,&nbsp;Tomohiro Tanaka ,&nbsp;Kakeru Shimoda ,&nbsp;Tomoaki Ida ,&nbsp;Shota Sasaki ,&nbsp;Keitaro Umezawa ,&nbsp;Hiromi Imamura ,&nbsp;Yasuteru Urano ,&nbsp;Fumito Ichinose ,&nbsp;Toshiro Kaneko ,&nbsp;Takaaki Akaike ,&nbsp;Motohiro Nishida","doi":"10.1016/j.redox.2024.103445","DOIUrl":"10.1016/j.redox.2024.103445","url":null,"abstract":"<div><div>Ischemic heart disease is the main global cause of death in the world. Abnormal sulfide catabolism, especially hydrogen sulfide accumulation, impedes mitochondrial respiration and worsens the prognosis after ischemic insults, but the substantial therapeutic strategy has not been established. Non-thermal atmospheric pressure plasma irradiation therapy is attracted attention as it exerts beneficial effects by producing various reactive molecular species. Growing evidence has suggested that supersulfides, formed by catenation of sulfur atoms, contribute to various biological processes involving electron transfer in cells. Here, we report that non-thermal plasma-irradiated cysteine (Cys∗) protects mouse hearts against ischemia/reperfusion (I/R) injury by preventing supersulfide catabolism. Cys∗ has a weak but long-lasting supersulfide activity, and the treatment of rat cardiomyocytes with Cys∗ prevents mitochondrial dysfunction after hypoxic stress. Cys∗ increases sulfide-quinone oxidoreductase (SQOR), and silencing SQOR abolishes Cys∗-induced supersulfide formation and cytoprotection. Local administration of mouse hearts with Cys∗ significantly reduces infarct size with preserving supersulfide levels after I/R. These results suggest that maintaining supersulfide formation through SQOR underlies cardioprotection by Cys∗ against I/R injury.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103445"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiosensitizing capacity of fenofibrate in glioblastoma cells depends on lipid metabolism","authors":"Bayan Alkotub ,&nbsp;Lisa Bauer ,&nbsp;Ali Bashiri Dezfouli ,&nbsp;Khouloud Hachani ,&nbsp;Vasilis Ntziachristos ,&nbsp;Gabriele Multhoff ,&nbsp;Morteza Hasanzadeh Kafshgari","doi":"10.1016/j.redox.2024.103452","DOIUrl":"10.1016/j.redox.2024.103452","url":null,"abstract":"<div><div>Despite advances in multimodal therapy approaches such as resection, chemotherapy and radiotherapy, the overall survival of patients with grade 4 glioblastoma (GBM) remains extremely poor (average survival time &lt;2 years). Altered lipid metabolism, which increases fatty acid synthesis and thereby contributes to radioresistance in GBM, is a hallmark of cancer. Therefore, we explored the radiosensitizing effect of the clinically approved, lipid-lowering drug fenofibrate (FF) in different GBM cell lines (U87, LN18). Interestingly, FF (50 μM) significantly radiosensitizes U87 cells by inducing DNA double-strand breaks through oxidative stress and impairing mitochondrial membrane integrity, but radioprotects LN18 cells by reducing the production of reactive oxygen species (ROS) and stabilizing the mitochondrial membrane potential. A comparative protein and lipid analysis revealed striking differences in the two GBM cell lines: LN18 cells exhibited a significantly higher membrane expression density of the fatty acid (FA) cluster protein transporter CD36 than U87 cells, a higher expression of glycerol-3-phosphate acyltransferase 4 (GPAT4) which supports the production of large lipid droplets (LDs), and a lower expression of diacylglycerol O-acyltransferase 1 (DGAT1) which regulates the formation of small LDs. Consequently, large LDs are predominantly found in LN18 cells, whereas small LDs are found in U87 cells. After a combined treatment of FF and irradiation, the number of large LDs significantly increased in radioresistant LN18 cells, whereas the number of small LDs decreased in radiosensitive U87 cells. The radioprotective effect of FF in LN18 cells could be associated with the presence of large LDs, which act as a sink for the lipophilic drug FF. To prevent uptake of FF by large LDs and to ameliorate its function as a radiosensitizer, FF was encapsulated in biomimetic cell membrane extracellular lipid vesicles (CmEVs) which alter the intracellular trafficking of the drug. In contrast to the free drug, CmEV-encapsulated FF was predominantly enriched in the lysosomal compartment, causing necrosis by impairing lysosomal membrane integrity. Since the stability of plasma and lysosomal membranes is maintained by the presence of the stress-inducible heat shock protein 70 (Hsp70) which has a strong affinity to tumor-specific glycosphingolipids, necrosis occurs predominantly in LN18 cells having a lower membrane Hsp70 expression density than U87 cells.</div><div>In summary, our findings indicate that the lipid metabolism of tumor cells can affect the radiosensitizing capacity of FF when encountered either as a free drug or as a drug loaded in biomimetic lipid vesicles.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103452"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liraglutide and GLP-1(9–37) alleviated hepatic ischemia-reperfusion injury by inhibiting ferroptosis via GSK3β/Nrf2 pathway and SMAD159/Hepcidin/FTH pathway","authors":"Chenqi Lu ,&nbsp;Cong Xu ,&nbsp;Shanglin Li ,&nbsp;Haiqiang Ni ,&nbsp;Jun Yang","doi":"10.1016/j.redox.2024.103468","DOIUrl":"10.1016/j.redox.2024.103468","url":null,"abstract":"<div><div>Ferroptosis plays a pivotal role in the pathogenesis of ischemia-reperfusion injury (IRI). Liraglutide, as a GLP-1 receptor (GLP-1R) agonist, has exhibited extensive biological effects beyond its hypoglycemic action. Recent studies have shed light on the regulatory influence of Liraglutide on ferroptosis, yet the precise underlying mechanism remains elusive. GLP-1(9–37), as a metabolite of GLP-1, has a low affinity to GLP-1R. Its effect on ferroptosis remains unknown. In this study, we investigated the effects of Liraglutide and GLP-1(9–37) on the ferroptosis during hepatic ischemia-repferfusion (I/R), as well as the underlying specific mechanisms. We found that the administration of Liraglutide alleviated I/R-induced liver injury with less iron accumulation and lower lipid peroxidation, which was not entirely dependent on the presence of GLP-1R. Similarly, GLP-1(9–37) also exhibited these effects. Besides, both of them increased GPX4 expression and decreased COX2 expression. These effects were reversed by a High-Iron Diet. In vitro study showed similar results. In mechanism study, we found that both Liraglutide and GLP-1(9–37) treatment promoted the nuclear translocation of Nrf2 by inhibiting GSK-3β, thereby reducing lipid peroxides. Furthermore, they increased FTH and FTL expression via the SMAD159/Hepcidin pathway, which contributed to the decreased iron accumulation. In conclusion, this study determined that both Liraglutide and GLP-1(9–37) alleviated hepatic ischemia-reperfusion injury (HIRI) by suppressing ferroptosis via the activation of the GSK3β/Nrf2 pathway and the SMAD159/Hepcidin/FTH pathway.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103468"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of iron metabolism by new chemicals interacting with the iron regulatory system","authors":"Yoshiaki Tsuji ,&nbsp;Jun Ninomiya-Tsuji ,&nbsp;Maurice Y.F. Shen ,&nbsp;Benjamin R. DiFrancesco","doi":"10.1016/j.redox.2024.103444","DOIUrl":"10.1016/j.redox.2024.103444","url":null,"abstract":"<div><div>Despite the vital role of iron and vulnerability of iron metabolism in disease states, it remains largely unknown whether chemicals interacting with cellular proteins are responsible for perturbation of iron metabolism. We previously demonstrated that cisplatin was an inhibitor of the iron regulatory system by blocking IRP2 (iron regulatory protein 2) binding to an iron-responsive element (IRE) located in the 3′- or 5′-UTR (untranslated region) of key iron metabolism genes such as transferrin receptor 1 (TfR1) and ferritin mRNAs. To guide the development of new chemical probes to modulate the IRP-IRE regulatory system, we used an artificial intelligence (AI)-based ligand design and screened a chemical library composed of cysteine-reactive warheads. Using wild type and mutant IRE-luciferase reporter cells, we identified new IRP-IRE inhibitors such as V004-0872 harboring chloroacetamide, while its analog V011-6261 with chloropropanamide completely lost the inhibitory activity. V004-0872 inhibited the human IRP2 via Cys512 and caused decreased iron levels through reciprocal TfR1 downregulation and ferritin upregulation. V004-0872 increased production of mitochondrial reactive oxygen species (ROS) and exhibited cytotoxicity that was inhibited by N-acetyl cysteine but not the ferroptosis inhibitor ferrostatin-1. Furthermore, we found that widely used haloketone protease inhibitors and acetamide herbicides inhibit the IRP-IRE system. Since IRP2 overexpression is responsible for iron excess conditions to promote growth of several cancers and exacerbation of iron-overload diseases, these results and new compounds lay the groundwork for new reagents and strategies to limit the availability of iron and oxidative stress in iron-overloaded disease conditions.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103444"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis","authors":"Jinxing Lv ,&nbsp;Tiantian Wu ,&nbsp;Jiajia Xue ,&nbsp;Cong Shen ,&nbsp;Wenxin Gao ,&nbsp;Xia Chen ,&nbsp;Yueshuai Guo ,&nbsp;Mingxi Liu ,&nbsp;Jun Yu ,&nbsp;Xiaoyan Huang ,&nbsp;Bo Zheng","doi":"10.1016/j.redox.2024.103484","DOIUrl":"10.1016/j.redox.2024.103484","url":null,"abstract":"<div><div>Male infertility, frequently driven by oxidative stress, impacts half of infertile couples globally. Despite its significance, the precise mechanisms governing this process remain elusive. In this study, we demonstrate that ASB1, the substrate recognition subunit of a ubiquitin ligase, is highly expressed in the mouse testis. Mice lacking the <em>Asb1</em> gene exhibit severe fertility impairment, characterized by oligoasthenoteratozoospermia. Subsequent investigations unveiled that <em>Asb1</em> knockout (<em>Asb1</em>-KO) mice encountered excessive oxidative stress and decreased hydrogen sulfide (H₂S) levels in their testes, and severe sperm DNA damage. Notably, the compromised fertility and sperm quality in <em>Asb1</em>-KO mice was significantly ameliorated by administering NaHS, a H₂S donor. Mechanistically, ASB1 interacts with ELOB to induce the instability of sulfide-quinone oxidoreductase (SQOR) by enhancing its K48-linked ubiquitination on residues K207 and K344, consequently triggering proteasomal degradation. This process is crucial for preserving H₂S homeostasis and redox balance. Overall, our findings offer valuable insights into the role of ASB1 during spermiogenesis and propose H₂S supplementation as a promising therapeutic approach for oxidative stress-related male infertility.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103484"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142889267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing oral care: Reactive oxygen species (ROS)-Regulating biomaterials for combating infection and inflammation","authors":"Wei Zhao ,&nbsp;Yu Zhang ,&nbsp;Jing Chen ,&nbsp;Danrong Hu","doi":"10.1016/j.redox.2024.103451","DOIUrl":"10.1016/j.redox.2024.103451","url":null,"abstract":"<div><div>The human oral cavity is home to a delicate symbiosis between its indigenous microbiota and the host, the balance of which is easily perturbed by local or systemic factors, leading to a spectrum of oral diseases such as dental caries, periodontitis, and pulp infections. Reactive oxygen species (ROS) play crucial roles in the host's innate immune defenses. However, in chronic inflammatory oral conditions, dysregulated immune responses can result in excessive ROS production, which in turn exacerbates inflammation and causes tissue damage. Conversely, the potent antimicrobial properties of ROS have inspired the development of various anti-infective therapies. Therefore, the strategic modulation of ROS by innovative biomaterials is emerging as a promising therapeutic approach for oral infection and inflammation. This review begins by highlighting the state-of-the-art of ROS-regulating biomaterials, which are designed to generate, scavenge, or modulate ROS in a bidirectional manner. We then delve into the latest innovations in these biomaterials and their applications in treating a range of oral diseases, including dental caries, endodontic and periapical conditions, periodontitis, peri-implantitis, and oral candidiasis. The review concludes with an overview of the current challenges and future potential of these biomaterials in clinical settings. This review provides novel insights for the ongoing development of ROS-based therapeutic strategies for oral diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103451"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Little strokes fell big oaks: The use of weak magnetic fields and reactive oxygen species to fight cancer","authors":"Margit Egg ,&nbsp;Thomas Kietzmann","doi":"10.1016/j.redox.2024.103483","DOIUrl":"10.1016/j.redox.2024.103483","url":null,"abstract":"<div><div>The increase in early-stage cancers, particularly gastrointestinal, breast and kidney cancers, has been linked to lifestyle changes such as consumption of processed foods and physical inactivity, which contribute to obesity and diabetes - major cancer risk factors. Conventional treatments such as chemotherapy and radiation often lead to severe long-term side effects, including secondary cancers and tissue damage, highlighting the need for new, safer and more effective therapies, especially for young patients.</div><div>Weak electromagnetic fields (WEMF) offer a promising non-invasive approach to cancer treatment. While WEMF have been used therapeutically for musculoskeletal disorders for decades, their role in oncology is still emerging. WEMFs affect multiple cellular processes through mechanisms such as the radical pair mechanism (RPM), which alters reactive oxygen species (ROS) levels, mitochondrial function, and glycolysis, among others.</div><div>This review explores the potential of WEMF in conjunction with reactive oxygen species as a cancer therapy, highlighting WEMFs selective targeting of cancer cells and its non-ionizing nature, which could reduce collateral damage compared to conventional treatments. In addition, synchronization of WEMF with circadian rhythms may further enhance its therapeutic efficacy, as has been demonstrated in other cancer therapies.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103483"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142888256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Dvl2 deficiency promotes NOD1-Driven pyroptosis and exacerbates inflammatory liver injury","authors":"Xiaoye Qu ,&nbsp;Dongwei Xu ,&nbsp;Tao Yang ,&nbsp;Yizhu Tian ,&nbsp;Christopher T. King ,&nbsp;Xiao Wang ,&nbsp;Mingwei Sheng ,&nbsp;Yuanbang Lin ,&nbsp;Xiyun Bian ,&nbsp;Changyong Li ,&nbsp;Longfeng Jiang ,&nbsp;Qiang Xia ,&nbsp;Douglas G. Farmer ,&nbsp;Bibo Ke","doi":"10.1016/j.redox.2024.103455","DOIUrl":"10.1016/j.redox.2024.103455","url":null,"abstract":"<div><div>Dishevelled 2 (Dvl2) is a key mediator of the Wingless/Wnt signaling pathway that regulates cell proliferation, migration, and immune function. However, little is known about the role of macrophage Dvl2 in modulating NOD1-mediated pyroptosis and hepatocyte death in oxidative stress-induced inflammatory liver injury. In a mouse model of oxidative stress<em>-induced liver inflammation</em>, mice with myeloid-specific Dvl2 knockout (Dvl2^M−KO) displayed exacerbated ischemia/reperfusion (IR) stress-induced hepatocellular damage with increased serum ALT levels, oxidative stress, and proinflammatory mediators. Unlike in Dvl2^FL/FL controls, Dvl2^M−KO enhanced NOD1, caspase-1, GSDMD, and NF-κB activation in liver macrophages after IR. Interestingly, IR stress enhanced YAP colocalized with HSF1 in Dvl2^FL/FL macrophages, while macrophage Dvl2 deficiency reduced YAP and HSF1 colocalization in the nucleus under inflammatory conditions. Importantly, Dvl2 deletion diminished nuclear YAP interacted with HSF1 and augmented NOD1/caspase-1 and GSDMD activation in response to inflammatory stimulation. However, Dvl2 activation increased YAP interaction with HSF1 and activated HSF1 target gene eEF2, inhibiting NOD1/caspase-1, GSDMD, and NF-κB activity. Moreover, macrophage eEF2 deletion increased the NOD1-caspase-1 interaction, GSDMD activation, HMGB1 release, and hepatocyte LDH release after macrophage/hepatocyte co-culture. Adoptive transfer of eEF2-expressing macrophages in Dvl2^M−KO mice alleviated IR-triggered liver inflammation and hepatocellular damage. Therefore, macrophage Dvl2 deficiency promotes NOD1-mediated pyroptosis and exacerbates IR-induced hepatocellular death by disrupting the YAP-HSF1 axis. eEF2 is crucial for modulating NOD1-driven pyroptosis, inflammatory response, and hepatocyte death. Our findings underscore a novel role of macrophage Dvl2 in modulating liver inflammatory injury and imply the therapeutic potential in organ IRI and transplant recipients.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103455"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-532-3p protects human decidual mesenchymal stem cells from oxidative stress in recurrent spontaneous abortion via targeting KEAP1","authors":"Hong Zhou ,&nbsp;Jiaxin Zhou ,&nbsp;ShanShan Liu ,&nbsp;Jing Niu ,&nbsp;Jinghua Pan ,&nbsp;Ruiman Li","doi":"10.1016/j.redox.2025.103508","DOIUrl":"10.1016/j.redox.2025.103508","url":null,"abstract":"<div><h3>Background</h3><div>Human decidual mesenchymal stem cells (hDMSCs) play crucial roles in pregnancy. The decreased resistance of hDMSCs to oxidative stress is a key factor contributing to recurrent spontaneous abortion (RSA). miRNAs have essential functions in the proliferation and apoptosis of decidual tissues. However, the miRNAs involved in regulating oxidative stress in hDMSCs remain unclear.</div></div><div><h3>Methods</h3><div>Decidual tissues and hDMSCs were collected from patients with RSA and early pregnancy miscarriages. We assessed the antioxidant capacity of hDMSCs in both groups by detecting relevant indicators. Furthermore, differentially expressed miRNAs in hDMSCs were analyzed through miRNA sequencing. We evaluated the interaction between hsa-miR-532-3p and KEAP1 using a luciferase reporter assay. A mouse model of RSA was constructed for confirmation. Finally, we analyzed the correlations between serum hsa-miR-532-3p levels and the clinical features of pregnant women with RSA.</div></div><div><h3>Results</h3><div>miRNA sequencing revealed 44 miRNAs whose expression was downregulated and 9 miRNAs whose expression was upregulated in hDMSCs from the RSA group compared with those from the control group. The overexpression of hsa-miR-532-3p led to a significantly increased antioxidant capacity in hDMSCs. The knockdown or overexpression of hsa-miR-532-3p led to the upregulation or downregulation of KEAP1 expression, respectively. In a mouse model, the overexpression of hsa-miR-532-3p reduced embryo absorption rates in RSA mice, decreased KEAP1 expression levels in decidual tissues, and concurrently enhanced the resistance to oxidative stress. Furthermore, in patients diagnosed with RSA, serum hsa-miR-532-3p levels were significantly and negatively correlated with the gestational age.</div></div><div><h3>Conclusions</h3><div>Our study revealed a lower expression level of hsa-miR-532-3p in the hDMSCs of patients with RSA. Moreover, hsa-miR-532-3p protects hDMSCs from oxidative stress by targeting the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (KEAP1/NRF2) pathway. Hsa-miR-532-3p is closely related to gestational age and has good predictive value for identifying RSA.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103508"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143145355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AKRs confer oligodendrocytes resistance to differentiation-stimulated ferroptosis","authors":"Valentina Saverio ,&nbsp;Emanuele Ferrario ,&nbsp;Romina Monzani ,&nbsp;Mara Gagliardi ,&nbsp;Francesco Favero ,&nbsp;Davide Corà ,&nbsp;Claudio Santoro ,&nbsp;Marco Corazzari","doi":"10.1016/j.redox.2024.103463","DOIUrl":"10.1016/j.redox.2024.103463","url":null,"abstract":"<div><div>Ferroptosis is a recently characterized form of cell death that has gained attention for its roles in both pathological and physiological contexts. The existence of multiple anti-ferroptotic pathways in both neoplastic and healthy cells, along with the critical regulation of iron metabolism involved in lipid peroxides (lipid-ROS) production—the primary mediators of this cell death process—underscores the necessity of precisely controlling or preventing accidental/unwanted ferroptosis. Conversely, dysregulated iron metabolism and alterations in the expression or activity of key anti-ferroptotic components are linked to the development and progression of various human diseases, including multiple sclerosis (MS). In MS, the improper activation of ferroptosis has been associated with the progressive loss of myelinating oligodendrocytes (myOLs). Our study demonstrates that the physiological and maturation-dependent increase in iron accumulation within oligodendrocytes acts as a pro-ferroptotic signal, countered by the concurrent expression of AKR1C1. Importantly, MS-related neuroinflammation contributes to the down-regulation of AKR1C1 through miRNA-mediated mechanisms, rendering mature oligodendrocytes more vulnerable to ferroptosis. Together, these findings highlight the role of ferroptosis in MS-associated oligodendrocyte loss and position AKR1C1 as a potential therapeutic target for preserving oligodendrocyte integrity and supporting neuronal function in MS patients.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103463"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}