Antioxidants最新文献

{"title":"Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension.","authors":"Hoon-In Choi, In Ae Jung, Soo Wan Kim","doi":"10.3390/antiox14010100","DOIUrl":"10.3390/antiox14010100","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) and hypertension are interconnected, worsening each other. Recent studies have shown that the reduction of peroxiredoxin 5 (Prdx5) accelerates kidney fibrosis, a hallmark of CKD. This study aims to observe whether the deficiency of Prdx5 also contributes to the worsening of CKD-related hypertension. Angiotensin II (Ang II, 1000 ng/kg/day) was infused into Prdx5 wild-type (WT) and Prdx5 knock out (KO) mice (each group; n = 6). The blood pressure was higher in the Ang-II-infused Prdx5 KO mice than in the WT mice. Ang-II-induced ROS/RNS generation and fibrotic marker expressions were also higher in the Prdx5 KO mice. In particular, the expression of the sodium-chloride cotransporter (NCC), an ion transport protein important for sodium retention in the distal convoluted tubule, and the NCC's phosphorylation at Thr53 were increased in the kidney of Ang-II-infused Prdx5 KO. The activity of an WNK4-SPAK/OSR1, upstream activator of the NCC, was also increased. In 209/mDCT cells, the knockdown of Prdx5 (siPrdx5) increased the activity of Ang-II-mediated WNK4-SPAK/OSR1-NCC signaling and Ang-II-mediated ROS generation, whereas Prdx5 overexpression showed opposite results. In conclusion, Prdx5 negatively regulates the WNK4-SPAK/OSR1-NCC signaling axis, indicating its potential as a candidate for antihypertensive drug development through NCC regulation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Something Is Rotten in the State of Redox.","authors":"Ahmad Yaman Abdin, Mohamad Jawad Nasim, Claus Jacob","doi":"10.3390/antiox14010098","DOIUrl":"10.3390/antiox14010098","url":null,"abstract":"<p><p>Some say that science is an art, a craft, and a passion-and, one may add these days, often also a business [...].</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Roles of Reducing Systems in Protein Persulfidation and Depersulfidation.","authors":"Zhichao Liu, Nicolas Rouhier, Jérémy Couturier","doi":"10.3390/antiox14010101","DOIUrl":"10.3390/antiox14010101","url":null,"abstract":"<p><p>The oxidative modification of specific cysteine residues to persulfides is thought to be the main way by which hydrogen sulfide (H₂S) exerts its biological and signaling functions. Therefore, protein persulfidation represents an important thiol-switching mechanism as other reversible redox post-translational modifications. Considering their reductase activity but also their connections with proteins that generate H₂S and its related molecules, the glutaredoxin (GRX) and thioredoxin (TRX)-reducing systems have potential dual roles in both protein persulfidation and depersulfidation. In this review, we will first focus on recent advances describing the physiological pathways leading to protein persulfidation before discussing the dual roles of the physiological TRX and glutathione/GRX-reducing systems in protein persulfidation/depersulfidation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of Cognitive Benefits and Anti-Anxiety Effects of <i>Phytolacca americana</i> Fruits in a Zebrafish (<i>Danio rerio</i>) Model of Scopolamine-Induced Memory Impairment.","authors":"Lucia-Florina Popovici, Ion Brinza, Florentina Gatea, Georgiana Ileana Badea, Emanuel Vamanu, Simona Oancea, Lucian Hritcu","doi":"10.3390/antiox14010097","DOIUrl":"10.3390/antiox14010097","url":null,"abstract":"<p><p><i>Phytolacca americana</i> fruits exhibit a wide range of biological activities, including antimicrobial, anti-inflammatory, and anticancer properties. This study aims to investigate the phenolic profile of hydroethanolic extracts from both fresh (PEC) and dried (PEU) fruits of <i>P. americana</i> using high-performance liquid chromatography (HPLC) and to evaluate their impact on anxiety-like behavior, memory, oxidative stress, and cholinergic status in zebrafish (<i>Danio rerio</i>, Tübingen strain) treated with scopolamine (SCO, 100 μM). Acute administration of PEC and PEU (0.1, 0.5, and 1 mg/L) was conducted for one hour per day. In silico analyses were performed to evaluate the pharmacokinetic characteristics of the phenolic compounds discerned in the two extracts, using platforms such as SwissAdme, Molinspiration, ProToX-III, AdmetLab 3.0, PKCSM, and PASS. Anxiety-like behavior and memory performance were assessed through specific behavioral assays, including the novel tank test (NTT), light/dark test (LD), novel approach test (NAT), Y-maze, and novel object recognition (NOR). Subsequently, the activity of acetylcholinesterase (AChE) and the extent of oxidative stress in the zebrafish brain were investigated. Our findings suggest that both PEC and PEU possess anxiolytic effects, alleviating SCO-induced anxiety and enhancing cognitive performance in amnesic zebrafish. Furthermore, these extracts demonstrated the ability to mitigate cholinergic deficits by inhibiting AChE activity and supporting antioxidant defense mechanisms through increased activity of antioxidant enzymes and reduced lipid and protein peroxidation. These results highlight the potential use of <i>P. americana</i> fruit extracts in managing anxiety and cognitive impairments related to dementia conditions.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-Induced Reactive Oxygen Species: Their Role in Cancer Resistance and Emerging Therapies to Overcome It.","authors":"Eleicy Nathaly Mendoza, Maria Rosa Ciriolo, Fabio Ciccarone","doi":"10.3390/antiox14010094","DOIUrl":"10.3390/antiox14010094","url":null,"abstract":"<p><p>Normal tissues typically maintain partial oxygen pressure within a range of 3-10% oxygen, ensuring homeostasis through a well-regulated oxygen supply and responsive vascular network. However, in solid tumors, rapid growth often outpaces angiogenesis, creating a hypoxic microenvironment that fosters tumor progression, altered metabolism and resistance to therapy. Hypoxic tumor regions experience uneven oxygen distribution with severe hypoxia in the core due to poor vascularization and high metabolic oxygen consumption. Cancer cells adapt to these conditions through metabolic shifts, predominantly relying on glycolysis, and by upregulating antioxidant defenses to mitigate reactive oxygen species (ROS)-induced oxidative damage. Hypoxia-induced ROS, resulting from mitochondrial dysfunction and enzyme activation, exacerbates genomic instability, tumor aggressiveness, and therapy resistance. Overcoming hypoxia-induced ROS cancer resistance requires a multifaceted approach that targets various aspects of tumor biology. Emerging therapeutic strategies target hypoxia-induced resistance, focusing on hypoxia-inducible factors, ROS levels, and tumor microenvironment subpopulations. Combining innovative therapies with existing treatments holds promise for improving cancer outcomes and overcoming resistance mechanisms.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cobalt Protoporphyrin Downregulates Hyperglycemia-Induced Inflammation and Enhances Mitochondrial Respiration in Retinal Pigment Epithelial Cells.","authors":"Peng-Hsiang Fang, Tzu-Yu Lin, Chiu-Chen Huang, Yung-Chang Lin, Cheng-Hung Lai, Bill Cheng","doi":"10.3390/antiox14010092","DOIUrl":"10.3390/antiox14010092","url":null,"abstract":"<p><p>Diabetic retinopathy is characterized by hyperglycemic retinal pigment epithelial cells that secrete excessive pro-inflammatory cytokines and VEGF, leading to retinal damage and vision loss. Cobalt protoporphyrin (CoPP) is a compound that can reduce inflammatory responses by inducing high levels of HO-1. In the present study, the therapeutic effects of CoPP were examined in ARPE-19 cells under hyperglycemia. ARPE-19 cells were incubated in culture media containing either 5.5 mM (NG) or 25 mM (HG) glucose, with or without the addition of 0.1 µM CoPP. Protein expressions in samples were determined by either Western blotting or immunostaining. A Seahorse metabolic analyzer was used to assess the impact of CoPP treatment on mitochondrial respiration in ARPE-19 cells in NG or HG media. ARPE-19 cells cultured in NG media displayed different cell morphology than those cultured in HG media. CoPP treatment induced high HO-1 expressions and significantly enhanced the viability of ARPE-19 cells under hyperglycemia. Moreover, CoPP significantly downregulated expressions of inflammatory and apoptotic markers and significantly upregulated mitochondrial respiration in APRPE-19 cells under hyperglycemia. CoPP treatment significantly enhanced cell viability in ARPE-19 cells under hyperglycemia. The treatment also downregulated the expressions of pro-inflammatory and upregulated mitochondrial respiration in the hyperglycemic cells.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species.","authors":"Chenxia Han, Yaling Wu, Juan Rong, Qing Xia, Dan Du","doi":"10.3390/antiox14010095","DOIUrl":"10.3390/antiox14010095","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism. Considerable preclinical and clinical studies have been conducted over many decades to investigate the role of XO in the pathogenesis of AP and its potential targeting therapeutic value. There is no doubt that the ROS generated by irreversibly activated XO participates in the local pancreas and multiple organ failure during AP. However, the optimal timing and doses for therapeutic interventions targeting XO in animal studies and the clinic, as well as the additional molecular mechanisms through which XO contributes to disease onset and progression, including metabolic regulation, remain to be elucidated. This review summarized the benefits and contradictions of using XO inhibitors in animal models, offered mechanisms other than ROS, and discussed the difficulties faced in clinical trials. We hope to provide a perspective on the future worthwhile basic and clinical research on XO by analyzing its chemical and biological characteristics, as well as the progress of its regulatory mechanisms in AP.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis Transcriptional Regulation and Prognostic Impact in Medulloblastoma Subtypes Revealed by RNA-Seq.","authors":"Christophe Desterke, Yuanji Fu, Jenny Bonifacio-Mundaca, Claudia Monge, Pascal Pineau, Jorge Mata-Garrido, Raquel Francés","doi":"10.3390/antiox14010096","DOIUrl":"10.3390/antiox14010096","url":null,"abstract":"<p><p>Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3. Using two independent medulloblastoma RNA-sequencing cohorts (MB-PBTA and MTAB-10767), we investigated the expression of ferroptosis-related molecules through multiple approaches, including Weighted Gene Co-Expression Network Analysis (WGCNA), molecular subtype stratification, protein-protein interaction (PPI) networks, and univariable and multivariable overall survival analyses. A prognostic expression score was computed based on a cross-validated ferroptosis signature. In training and validation cohorts, the regulation of the ferroptosis transcriptional program distinguished the four molecular subtypes of medulloblastoma. WGCNA identified nine gene modules in the MB tumor transcriptome; five correlated with molecular subtypes, implicating pathways related to oxidative stress, hypoxia, and trans-synaptic signaling. One module, associated with disease recurrence, included epigenetic regulators and nucleosome organizers. Univariable survival analyses identified a 45-gene ferroptosis prognostic signature associated with nutrient sensing, cysteine and methionine metabolism, and trans-sulfuration within a one-carbon metabolism. The top ten unfavorable ferroptosis genes included <i>CCT3</i>, <i>SNX5</i>, <i>SQOR</i>, <i>G3BP1</i>, <i>CARS1</i>, <i>SLC39A14</i>, <i>FAM98A</i>, <i>FXR1</i>, <i>TFAP2C</i>, and <i>ATF4</i>. Patients with a high ferroptosis score showed a worse prognosis, particularly in the G3 and SHH subtypes. The PPI network highlighted IL6 and CBS as unfavorable hub genes. In a multivariable overall survival model, which included gender, age, and the molecular subtype classification, the ferroptosis expression score was validated as an independent adverse prognostic marker (hazard ratio: 5.8; <i>p</i>-value = 1.04 × 10^-9). This study demonstrates that the regulation of the ferroptosis transcriptional program is linked to medulloblastoma molecular subtypes and patient prognosis. A cross-validated ferroptosis signature was identified in two independent RNA-sequencing cohorts, and the ferroptosis score was confirmed as an independent and adverse prognostic factor in medulloblastoma.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation and Transcriptome Profiling Reveal the Role of the Antioxidant Pathway and Lipid Metabolism in <i>Plectropomus leopardus</i> Skin Color Formation.","authors":"Yang Liu, Linna Wang, Zhentong Li, Linlin Li, Tangtang Ding, Shuai Chen, Pengfei Duan, Xinyi Wang, Yishu Qiu, Xiaoyu Ding, Yongsheng Tian","doi":"10.3390/antiox14010093","DOIUrl":"10.3390/antiox14010093","url":null,"abstract":"<p><p>Leopard coral grouper (<i>Plectropomus leopardus</i>), possessing a distinct red body color, is an important species in commercial markets; however, the high ratio of black individuals under intensive cultivation has limited the commercial value of the species. To dissect the regulatory mechanisms underlying the red skin trait in <i>P. leopardus</i>, gene expression and DNA methylation modifications were compared between red and black skin tissues after astaxanthin treatment. Astaxanthin effectively increased the redness value a* and body weight. Multi-omics analyses revealed the crucial roles of pathways related to antioxidants and lipid metabolism, particularly \"Tyrosine metabolism\", \"Melanogenesis\", \"Fatty acid metabolism\", \"Fatty acid elongation\", and \"Biosynthesis of unsaturated acids\", in red skin coloration. A molecular network for the regulation of red skin coloration in <i>P. leopardus</i> was constructed, and <i>pmel</i>, <i>tyr</i>, <i>tyrp1a</i>, <i>tyrp1b</i>, <i>dct</i>, <i>slc24a5</i>, <i>wnt1</i>, <i>acsl4</i>, <i>elovl1</i>, <i>elovl6l.1</i>, <i>elovl6l.2</i>, and <i>elovl7</i> were identified as key genes. Notably, <i>pmel</i>, <i>acsl4</i>, and <i>elovl7</i> were negatively regulated by differential DNA methylation. Our results provide new insight into the molecular and epigenetic mechanisms of body color variation, representing a significant step towards breeding for the red skin trait in <i>P. leopardus</i>.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-Antioxidant Activity Relationship of Polysaccharides Isolated by Microwave/Ultrasonic-Assisted Extraction from <i>Pleurotus ferulae</i>.","authors":"Hongjin Zhou, Zhongxiong Fan, Yuan Li, Xuelian Liu, Bo Wang, Jianguo Xing, Jiang He, Ruifang Zheng, Jinyao Li","doi":"10.3390/antiox14010091","DOIUrl":"10.3390/antiox14010091","url":null,"abstract":"<p><p>To investigate the structure-antioxidant activity relationship, <i>Pleurotus ferulae</i> polysaccharides were extracted using ultrasonic (U-PFPS) and microwave/ultrasonic-assisted methods (MU-PFPS). Compared to U-PFPS with a molecular weight of 1.566 × 10³ kDa, MU-PFPS exhibited a lower molecular weight of 89.26 kDa. In addition, unlike U-PFPS, which is primarily composed of glucose (Glu:Man:Gal = 91.1:3.5:5.4), MU-PFPS has a more balanced composition of Glu:Man:Gal in the ratio of 39.4:27.8:32.8 and contains more branched chains. Furthermore, antioxidant analysis revealed that high concentration (at concentrations above 600 μg/mL) MU-PFPS demonstrated stronger protective effects against oxidative damage in RAW264.7 cells than U-PFPS did. Collectively, these data suggest that lower molecular weight and higher branching degree of polysaccharides at appropriate concentrations may correlate with enhanced antioxidant enzyme activities. Our work provides a method for isolating polysaccharides with higher antioxidant activity and offers insights into the structure-activity relationship of polysaccharides, laying the foundation for future applications in polysaccharide modification and structural characterization.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}