Antioxidants & redox signaling最新文献

{"title":"Fecal Microbiota Transplantation in Mice Exerts a Protective Effect Against Doxorubicin-Induced Cardiac Toxicity by Regulating Nrf2-Mediated Cardiac Mitochondrial Fission and Fusion.","authors":"Jiedong Zhou, Jinjin Hao, Zuoquan Zhong, Juntao Yang, Tingting Lv, Bingjie Zhao, Hui Lin, Jufang Chi, Hangyuan Guo","doi":"10.1089/ars.2023.0355","DOIUrl":"10.1089/ars.2023.0355","url":null,"abstract":"<p><p><b><i>Aims:</i></b> The relationship between the gut microbiota and cardiovascular system has been increasingly clarified. Fecal microbiota transplantation (FMT), used to improve gut microbiota, has been applied clinically for disease treatment and has great potential in combating doxorubicin (DOX)-induced cardiotoxicity. However, the application of FMT in the cardiovascular field and its molecular mechanisms are poorly understood. <b><i>Results:</i></b> During DOX-induced stress, FMT alters the gut microbiota and serum metabolites, leading to a reduction in cardiac injury. Correlation analysis indicated a close association between serum metabolite indole-3-propionic acid (IPA) and cardiac function. FMT and IPA achieve this by facilitating the translocation of Nfe2l2 (Nrf2) from the cytoplasm to the nucleus, thereby activating the expression of antioxidant molecules, reducing reactive oxygen species production, and inhibiting excessive mitochondrial fission. Consequently, mitochondrial function is preserved, leading to the mitigation of cardiac injury under DOX-induced stress. <b><i>Innovation:</i></b> FMT has the ability to modify the composition of the gut microbiota, providing not only protection to the intestinal mucosa but also influencing the generation of serum metabolites and regulating the Nrf2 gene to modulate the balance of cardiac mitochondrial fission and fusion. This study comprehensively demonstrates the efficacy of FMT in countering DOX-induced myocardial damage and elucidates the pathways linking the microbiota and the heart. <b><i>Conclusion:</i></b> FMT alters the gut microbiota and serum metabolites of recipient mice, promoting nuclear translocation of Nrf2 and subsequent activation of downstream antioxidant molecule expression, while inhibiting excessive mitochondrial fission to preserve cardiac integrity. Correlation analysis highlights IPA as a key contributor among differentially regulated metabolites.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"1-23"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116773","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":"YTHDF2 Promotes Cardiac Ferroptosis <i>via</i> Degradation of SLC7A11 in Cardiac Ischemia-Reperfusion Injury.","authors":"Ping Pang, Wei Si, Han Wu, Jiaming Ju, Kuiwu Liu, Chunlei Wang, Yingqiong Jia, Hongtao Diao, Linghua Zeng, Weitao Jiang, Yang Yang, Yuting Xiong, Xue Kong, Zhengwei Zhang, Feng Zhang, Jinglun Song, Ning Wang, Baofeng Yang, Yu Bian","doi":"10.1089/ars.2023.0291","DOIUrl":"10.1089/ars.2023.0291","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"889-905"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949607","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":"<i>Beclin 1</i> Haploinsufficiency Ameliorates High-Fat Diet-Induced Myocardial Injury <i>via</i> Inhibiting Alternative Mitophagy.","authors":"Xiaofang Zeng, Jing Sun, Famei Li, Liming Peng, Chenglong Zhang, Xiaowei Jiang, Lihuang Zha, Anandharajan Rathinasabapathy, Jun Ren, Zaixin Yu, Lin Wang, Xiangwei Liu","doi":"10.1089/ars.2023.0399","DOIUrl":"10.1089/ars.2023.0399","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"906-925"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thiol-Based Modification of MarR Protein VnrR Regulates Resistance Toward Nitrofuran in <i>Vibrio cholerae</i> By Promoting the Expression of a Novel Nitroreductase VnrA and of NO-Detoxifying Enzyme HmpA.","authors":"Xiaoman Yang, Mingjie Qian, Ying Wang, Zixin Qin, Mei Luo, Guozhong Chen, Chunrong Yi, Yao Ma, Xiaoyun Liu, Zhi Liu","doi":"10.1089/ars.2022.0205","DOIUrl":"10.1089/ars.2022.0205","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Epidemiological investigations have indicated low resistance toward nitrofuran in clinical isolates, suggesting its potential application in the treatment of multidrug-resistant bacteria. Therefore, it is valuable to explore the mechanism of bacterial resistance to nitrofuran. <b><i>Results:</i></b> Through phenotypic screening of ten multiple antibiotic resistance regulator (MarR) proteins in <i>Vibrio cholerae</i>, we discovered that the regulator VnrR (VCA1058) plays a crucial role in defending against nitrofuran, specifically furazolidone (FZ). Our findings demonstrate that VnrR responds to FZ metabolites, such as hydroxylamine, methylglyoxal, hydrogen peroxide (H₂O₂), β-hydroxyethylhydrazine. Notably, VnrR exhibits reversible responses to the addition of H₂O₂ through three cysteine residues (Cys180, Cys223, Cys247), leading to the derepression of its upstream gene, <i>vnrA</i> (<i>vca1057</i>). Gene <i>vnrA</i> encodes a novel nitroreductase, which directly contributes to the degradation of FZ. Our study reveals that <i>V. cholerae</i> metabolizes FZ <i>via</i> the <i>vnrR-vnrA</i> system and achieves resistance to FZ with the assistance of the classical reactive oxygen/nitrogen species scavenging pathway. <b><i>Innovation and Conclusion:</i></b> This study represents a significant advancement in understanding the antibiotic resistance mechanisms of <i>V. cholerae</i> and other pathogens. Our findings demonstrate that the MarR family regulator, VnrR, responds to the FZ metabolite H₂O₂, facilitating the degradation and detoxification of this antibiotic in a thiol-dependent manner. These insights not only enrich our knowledge of antibiotic resistance but also provide new perspectives for the control and prevention of multidrug-resistant bacteria.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"926-942"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094858","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":"Impact of Mitochondrial Architecture, Function, Redox Homeostasis, and Quality Control on Organismic Aging: Lessons from a Fungal Model System.","authors":"Heinz D Osiewacz","doi":"10.1089/ars.2023.0487","DOIUrl":"10.1089/ars.2023.0487","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Mitochondria are eukaryotic organelles with various essential functions. They are both the source and the targets of reactive oxygen species (ROS). Different branches of a mitochondrial quality control system (mQCS), such as ROS balancing, degradation of damaged proteins, or whole mitochondria, can mitigate the adverse effects of ROS stress. However, the capacity of mQCS is limited. Overwhelming this capacity leads to dysfunctions and aging. Strategies to interfere into mitochondria-dependent human aging with the aim to increase the healthy period of life, the health span, rely on the precise knowledge of mitochondrial functions. Experimental models such as <i>Podospora anserina</i>, a filamentous fungus with a clear mitochondrial aging etiology, proved to be instrumental to reach this goal. <b><i>Recent Advances:</i></b> Investigations of the <i>P. anserina</i> mQCS revealed that it is constituted by a complex network of different branches. Moreover, mitochondrial architecture and lipid homeostasis emerged to affect aging. <b><i>Critical Issues:</i></b> The regulation of the mQCS is only incompletely understood. Details about the involved signaling molecules and interacting pathways remain to be elucidated. Moreover, most of the currently generated experimental data were generated in well-controlled experiments that do not reflect the constantly changing natural life conditions and bear the danger to miss relevant aspects leading to incorrect conclusions. <b><i>Future Directions:</i></b> In <i>P. anserina</i>, the precise impact of redox signaling as well as of molecular damaging for aging remains to be defined. Moreover, natural fluctuation of environmental conditions needs to be considered to generate a realistic picture of aging mechanisms as they developed during evolution.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"948-967"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450765","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":"Oxidative Stress, Endothelial Dysfunction, and <i>N</i>-Acetylcysteine in Type 2 Diabetes Mellitus.","authors":"Xin Li, Junyong Zou, Aiping Lin, Jingshu Chi, Hong Hao, Hong Chen, Zhenguo Liu","doi":"10.1089/ars.2023.0524","DOIUrl":"10.1089/ars.2023.0524","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Endothelial dysfunction is closely associated with the development and progression of CVDs. Patients with diabetes mellitus (DM) especially type 2 DM (T2DM) exhibit a significant endothelial cell (EC) dysfunction with substantially increased risk for CVDs. <b><i>Recent Advances:</i></b> Excessive reactive oxygen species (ROS) and oxidative stress are important contributing factors to EC dysfunction and subsequent CVDs. ROS production is significantly increased in DM and is critically involved in the development of endothelial dysfunction in diabetic patients. In this review, efforts are made to discuss the role of excessive ROS and oxidative stress in the pathogenesis of endothelial dysfunction and the mechanisms for excessive ROS production and oxidative stress in T2DM. <b><i>Critical Issues:</i></b> Although studies with diabetic animal models have shown that targeting ROS with traditional antioxidant vitamins C and E or other antioxidant supplements provides promising beneficial effects on endothelial function, the cardiovascular outcomes of clinical studies with these antioxidant supplements have been inconsistent in diabetic patients. <b><i>Future Directions:</i></b> Preclinical and limited clinical data suggest that <i>N</i>-acetylcysteine (NAC) treatment may improve endothelial function in diabetic patients. However, well-designed clinical studies are needed to determine if NAC supplementation would effectively preserve endothelial function and improve the clinical outcomes of diabetic patients with reduced cardiovascular morbidity and mortality. With better understanding on the mechanisms of ROS generation and ROS-mediated endothelial damages/dysfunction, it is anticipated that new selective ROS-modulating agents and effective personalized strategies will be developed for the management of endothelial dysfunction in DM.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"968-989"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric Oxide: Regulation and Function in Neutrophil Immune Responses.","authors":"Sachin Kumar, Madhu Dikshit","doi":"10.1089/ars.2022.0220","DOIUrl":"10.1089/ars.2022.0220","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"998-1024"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511545","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":"Red Blood Cells as Therapeutic Target to Treat Sickle Cell Disease.","authors":"Shruti Bhatt, Donovan A Argueta, Kalpna Gupta, Suman Kundu","doi":"10.1089/ars.2023.0348","DOIUrl":"10.1089/ars.2023.0348","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Sickle cell disease (SCD) is the most common inherited diathesis affecting mostly underserved populations globally. SCD is characterized by chronic pain and fatigue, severe acute painful crises requiring hospitalization and opioids, strokes, multiorgan damage, and a shortened life span. Symptoms may appear shortly after birth, and, in less developed countries, most children with SCD die before attaining age 5. Hematopoietic stem cell transplant and gene therapy offer a curative therapeutic approach, but, due to many challenges, are limited in their availability and effectiveness for a majority of persons with SCD. A critical unmet need is to develop safe and effective novel targeted therapies. A wide array of drugs currently undergoing clinical investigation hold promise for an expanded pharmacological armamentarium against SCD. <b><i>Recent Advances:</i></b> Hydroxyurea, the most widely used intervention for SCD management, has improved the survival in the Western world and more recently, voxelotor (R-state-stabilizer), l-glutamine, and crizanlizumab (anti-P-selectin antibody) have been approved by the Food and Drug Administration (FDA) for use in SCD. The recent FDA approval emphasizes the need to revisit the advances in understanding the core pathophysiology of SCD to accelerate novel evidence-based strategies to treat SCD. The biomechanical breakdown of erythrocytesis, the core pathophysiology of SCD, is associated with intrinsic factors, including the composition of hemoglobin, membrane integrity, cellular volume, hydration, andoxidative stress. <b><i>Critical Issues and Future Directions:</i></b> In this context, this review focuses on advances in emerging nongenetic interventions directed toward the therapeutic targets intrinsic to sickle red blood cells (RBCs), which can prevent impaired rheology of RBCs to impede disease progression and reduce the sequelae of comorbidities, including pain, vasculopathy, and organ damage. In addition, given the intricate pathophysiology of the disease, it is unlikely that a single pharmacotherapeutic intervention will comprehensively ameliorate the multifaceted complications associated with SCD. However, the availability of multiple drug options affords the opportunity for individualized therapeutic regimens tailored to specific SCD-related complications. Furthermore, it opens avenues for combination drug therapy, capitalizing on distinct mechanisms of action and profiles of adverse effects.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"1025-1049"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395931","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":"Is Mitochondrial DNA Copy Number from Human Blood Associated with Iron Deposits in the Brain?","authors":"Qu Tian, David A Zweibaum, Luke C Pilling, Francesco Casanova, Yong Qian, Janice L Atkins, David Melzer, Jun Ding, Luigi Ferrucci","doi":"10.1089/ars.2023.0529","DOIUrl":"10.1089/ars.2023.0529","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"990-997"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Donor Age Have Effects on Senescence Biomarkers in Kidney-Transplanted Patients?","authors":"Juan López-Pérez, Juan Miguel Suarez-Rivero, Inés Muela-Zarzuela, Raquel de la Varga-Martínez, Aurora Aguilera, Teresa Garcia, Antonio Nieto-Díaz, Auxiliadora Mazuecos, Mario D Cordero","doi":"10.1089/ars.2023.0470","DOIUrl":"10.1089/ars.2023.0470","url":null,"abstract":"<p><p>Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs, which increase the risk of graft rejection and several complications compared with older individuals who receive kidneys from donors of similar age or younger. This article focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements. We studied 61 patients subjected to renal transplant isolating blood samples 24 h before, and 24 h, 3 days, 7 days, 3 months, and 6 months after transplant. The patients were divided into three groups: older donor than the patient (Old Donor), younger donor than the patient (Young Donor), and similar age (Matched). We studied different senescence markers such as p16, p21, interleukin 6 (IL-6), and senescence-associated secretory phenotype (SASP) release. Young patients who receive older organs showed increased mRNA and protein expression of the senescence makers. Hence, increased SASP release was also observed in patients from older donor. In contrast, older patients who receive younger organs showed a slow but consistent improvement in their initial senescent phenotype. In addition, macrophage cell model treated with blood-derived serum from patients 6 months after the transplant showed a pro-senescence environment in macrophages proposed by the SASP from the patients. These results lead the hypothesis that senolytics could reduce the presence of senescent cells and mitigate the complications associated with the transplantation of older organs in young patients.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"751-758"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650179","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}