Redox Biology最新文献

{"title":"Bariatric surgery blunts nitrate-mediated improvements in cardiovascular function of overweight women by interfering with gastric S-nitrosothiol formation","authors":"Jéssica Maria Sanches-Lopes, Alessandra Cássia-Barros, Sandra Oliveira Conde-Tella, Eduardo Barbosa Coelho, Rafael Kemp, Riccardo Lacchini, Martin Feelisch, Wilson Salgado Júnior, Jose Eduardo Tanus-Santos","doi":"10.1016/j.redox.2024.103440","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103440","url":null,"abstract":"Inorganic nitrate (NO<ce:inf loc=\"post\">3</ce:inf><ce:sup loc=\"post\">−</ce:sup>) and nitrate-rich foods have been shown to exert antioxidative effects and lower blood pressure in experimental animal models and human clinical studies. The specific handling of nitrate, including its enterosalivary recirculation, secretion into saliva, oral microbial reduction to nitrite (NO<ce:inf loc=\"post\">2</ce:inf><ce:sup loc=\"post\">−</ce:sup>), and the pH-dependent nitrosative capacity in the stomach have all been recognized as being important for nitrate's beneficial effects. Obesity is of major health concern worldwide and associated with increased cardiovascular risk; whether nitrate lowers blood pressure and improves endothelial function in this setting has not been investigated. We here tested the hypotheses that i) nitrate elicits cardiovascular benefits in overweight women; and ii) these beneficial effects would be diminished in women who underwent bariatric Roux-en-Y gastric bypass (RYGB) surgery. Our controlled clinical trial included 15 women with prior RYGB surgery and 15 overweight female controls. All participants received a single dose of 0.1 mmol/kg/day nitrate in the form of a beetroot extract for 14 days. Blood collection, 24-h ambulatory blood pressure measurements and endothelial function tests were performed before and after nitrate treatment. Plasma nitrite, nitrate, and S-nitrosothiol (RSNO) concentrations were determined by ozone-based reductive chemiluminescence while thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were measured using plate-reader based assays. Nitrate reduced blood pressure and improved endothelial function in controls, but not in women with prior bariatric surgery. Nitrate also increased circulating nitrate/nitrite and RSNO levels in controls, but the latter was blunted following RYGB surgery despite even larger increases in nitrite concentrations. Similarly, nitrate increased antioxidant responses in controls but not in women with prior bariatric surgery. This is the first study to show that nitrate exerts beneficial cardiovascular effects in obesity and that the morphological/functional modifications elicited by RYGB surgery abrogates nitrate's effectiveness by preventing gastric RSNO formation.","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"18 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142691092","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":"Corrigendum to \"FBXL4 protects against HFpEF through Drp1-Mediated regulation of mitochondrial dynamics and the downstream SERCA2a\" [Redox Biol. 70 (2024) 103081].","authors":"Miyesaier Abudureyimu, Xuanming Luo, Lingling Jiang, Xuejuan Jin, Cuizhen Pan, Wei Yu, Junbo Ge, Yingmei Zhang, Jun Ren","doi":"10.1016/j.redox.2024.103430","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103430","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":" ","pages":"103430"},"PeriodicalIF":10.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692439","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":"Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation","authors":"Yang Chen, Mingchao Zhang, Ruoyu Jia, Bin Qian, Chenyang Jing, Caihong Zeng, Dihan Zhu, Zhihong Liu, Ke Zen, Limin Li","doi":"10.1016/j.redox.2024.103439","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103439","url":null,"abstract":"Podocyte injury is a critical event in the pathogenesis of diabetic nephropathy (DN). Hyperglycemia, oxidative stress, inflammation, and other factors contribute to podocyte damage in DN. In this study, we demonstrate that signaling regulatory protein alpha (SIRPα) plays a pivotal role in regulating the metabolic and immune homeostasis of podocytes. Deletion of SIRPα in podocytes exacerbates, while transgenic overexpression of SIRPα alleviates, podocyte injury in experimental DN mice. Mechanistically, SIRPα downregulation promotes pyruvate kinase M2 (PKM2) phosphorylation, initiating a positive feedback loop that involves PKM2 nuclear translocation, NF-κB activation, and oxidative stress, ultimately impairing aerobic glycolysis. Consistent with this mechanism, shikonin ameliorates podocyte injury by reducing PKM2 nuclear translocation, preventing oxidative stress and NF-κB activation, thereby restoring aerobic glycolysis.","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"64 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142691094","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":"Corrigendum to \"Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation\" [Redox Biol. 69 (2024) 102983].","authors":"Hongchen Zhang, Yuan Feng, Yanfang Si, Chuanhao Lu, Juan Wang, Shiquan Wang, Liang Li, Wenyu Xie, Zheming Yue, Jia Yong, Shuhui Dai, Lei Zhang, Xia Li","doi":"10.1016/j.redox.2024.103432","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103432","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":" ","pages":"103432"},"PeriodicalIF":10.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688658","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":"Corrigendum to \"Genome-wide transcriptional effects of deletions of sulphur metabolism genes in Drosophila melanogaster\" [Redox Biol. 36 (2020) 101654].","authors":"O Zatsepina, D Karpov, L Chuvakova, A Rezvykh, S Funikov, S Sorokina, A Zakluta, D Garbuz, V Shilova, M Evgen'ev","doi":"10.1016/j.redox.2024.103431","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103431","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":" ","pages":"103431"},"PeriodicalIF":10.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676700","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":"Corrigendum to \"Complement receptor 3 mediates NADPH oxidase activation and dopaminergic neurodegeneration through a Src-Erk-dependent pathway\" [Redox Biol. 14 (2018) 250-260].","authors":"Liyan Hou, Ke Wang, Cong Zhang, Fuqiang Sun, Yuning Che, Xiulan Zhao, Dan Zhang, Huihua Li, Qingshan Wang","doi":"10.1016/j.redox.2024.103429","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103429","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":" ","pages":"103429"},"PeriodicalIF":10.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676617","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":"DKK3 as a diagnostic marker and potential therapeutic target for sarcopenia in chronic obstructive pulmonary disease.","authors":"Zilin Wang, Mingming Deng, Weidong Xu, Chang Li, Ziwen Zheng, Jiaye Li, Liwei Liao, Qin Zhang, Yiding Bian, Ruixia Li, Jinrui Miao, Kai Wang, Yan Yin, Yanxia Li, Xiaoming Zhou, Gang Hou","doi":"10.1016/j.redox.2024.103434","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103434","url":null,"abstract":"<p><p>Sarcopenia, characterized by the progressive loss of muscle mass and function, significantly affects patients with chronic obstructive pulmonary disease (COPD) and worsens their morbidity and mortality. The pathogenesis of muscle atrophy in patients with COPD involves complex mechanisms, including protein imbalance and mitochondrial dysfunction, which have been identified in the muscle tissues of patients with COPD. DKK3 (Dickkopf-3) is a secreted glycoprotein involved in the process of myogenesis. However, the role of DKK3 in the regulation of muscle mass is largely unknown. This study investigated the role of DKK3 in COPD-related sarcopenia. DKK3 was found to be overexpressed in cigarette smoking-induced muscle atrophy and in patients with COPD. Importantly, plasma DKK3 levels in COPD patients with sarcopenia were significantly higher than those without sarcopenia, and plasma DKK3 levels could effectively predict sarcopenia in patients with COPD based on two independent cohorts. Mechanistically, DKK3 is secreted by skeletal muscle cells that acts in autocrine and paracrine manners and interacts with the cell surface-activated receptor cytoskeleton-associated protein 4 (CKAP4) to induce mitochondrial dysfunction and myotube atrophy. The inhibition of DKK3 by genetic ablation prevented cigarette smoking-induced skeletal muscle dysfunction. These results suggest that DKK3 is a potential target for the diagnosis and treatment of sarcopenia in patients with COPD.</p>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"103434"},"PeriodicalIF":10.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688662","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":"Aβ1-42 promotes microglial activation and apoptosis in the progression of AD by binding to TLR4","authors":"Rui-xia Dou ,&nbsp;Ya-min Zhang ,&nbsp;Xiao-juan Hu ,&nbsp;Fu-Lin Gao ,&nbsp;Lu-Lu Zhang ,&nbsp;Yun-hua Liang ,&nbsp;Yin-ying Zhang ,&nbsp;Yu-ping Yao ,&nbsp;Li Yin ,&nbsp;Yi Zhang ,&nbsp;Cheng Gu","doi":"10.1016/j.redox.2024.103428","DOIUrl":"10.1016/j.redox.2024.103428","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is one of the most common age-related neurodegenerative diseases and the most devastating form of senile dementia. It has a complex mechanism and no effective treatment. Exploring the pathogenesis of AD and providing ideas for treatment can effectively improve the prognosis of AD. Microglia were incubated with β-amyloid protein 1-42 (Aβ_1-42) to construct an AD cell model. After microglia were activated, cell morphology changed, the expression level of inflammatory factors increased, cell apoptosis was promoted, and the expression of microtubule-associated protein (Tau protein) and related proteins increased. By up-regulating and down-regulating Toll-like receptor 4 (TLR4), the cells were divided into TLR4 knockdown negative control group(Lv-NC group), TLR4 knockdown group(Lv-TLR4 group), TLR4 overexpression negative control group(Sh-NC group), and TLR4 overexpression group(Sh-TLR4 group). The expression of inflammatory factors was detected again. It was found that compared with the Lv-NC group, the expression of various inflammatory factors in the Lv-TLR4 group decreased, cell apoptosis was inhibited, and the expression of Tau protein and related proteins decreased. Compared with the Sh-NC group, the expression of inflammatory factors in the Sh-TLR4 group increased, cell apoptosis was promoted, and the expression of Tau protein and related proteins increased. These results indicate that Aβ_1-42 may promote microglial activation and apoptosis by binding to TLR4. Reducing the expression of TLR4 can reduce the occurrence of inflammatory response in AD cells and slow down cell apoptosis. Therefore, TLR4 is expected to become a new target for the prevention and treatment of AD.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103428"},"PeriodicalIF":10.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648929","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":"Role of Hippo/ACSL4 axis in ferroptosis-induced pericyte loss and vascular dysfunction in sepsis.","authors":"Yiyan Liu, Daiqin Bao, Han She, Zisen Zhang, Shifeng Shao, Zhengbin Wu, Yue Wu, Qinghui Li, Li Wang, Tao Li, Liangming Liu","doi":"10.1016/j.redox.2024.103353","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103353","url":null,"abstract":"<p><p>Sepsis is a critical condition characterized by a systemic inflammatory response to infection, often leading to severe vascular dysfunction and high mortality. One of the hallmarks of vascular dysfunction in sepsis is increased vascular permeability and the loss of pericytes, which are essential for maintaining vascular integrity. Despite the significance of pericyte loss in sepsis, the primary type of cell death responsible and the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate these mechanisms by focusing on ferroptosis, a form of programmed cell death, and its regulation through the Hippo/ACSL4 axis. Our research confirmed significant pericyte loss in patients with sepsis. Through advanced single-cell analysis and proteomics, ferroptosis was identified as a key differentiating cell death type between sepsis and sham samples. Further metabolomics analysis revealed that Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) plays a pivotal role in the ferroptosis of pericytes during sepsis. In vitro experiments demonstrated that downregulation of ACSL4 effectively reduced lipopolysaccharide (LPS)-induced lipid peroxidation, restored pericyte viability, and improved endothelial permeability. In vivo studies with pericyte-specific ACSL4 knockout mice showed a marked decrease in pericyte loss and enhanced vascular barrier function following sepsis induction. To translate these findings into potential therapeutic strategies, we developed pericyte-targeting liposomes encapsulating ACSL4 shRNA adenovirus. These liposomes successfully restored pulmonary vascular barrier function and significantly reduced pericyte loss in septic conditions. The results of this study underscore the crucial role of ACSL4 in mediating ferroptosis in pericytes and highlight the therapeutic potential of targeting ACSL4 to mitigate vascular dysfunction in sepsis.</p>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"103353"},"PeriodicalIF":10.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682313","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":"Fluorescent gold nanoclusters possess multiple actions against atherosclerosis.","authors":"Yi-Nan Lee, Yih-Jer Wu, Cheng-Huang Su, Bo-Jeng Wang, Sheng-Hsun Yang, Hsin-I Lee, Yen-Hung Chou, Ting-Yi Tien, Chao-Feng Lin, Wen-Hsiung Chan, Ching-Hu Chung, Shin-Wei Wang, Hung-I Yeh","doi":"10.1016/j.redox.2024.103427","DOIUrl":"https://doi.org/10.1016/j.redox.2024.103427","url":null,"abstract":"<p><p>Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles. We evaluated the 8-week effects of FANC in Western-type diet-fed ApoE-deficient mice by either continuous intraperitoneal delivery (20 μM, 50 μl weekly) or via drinking water (300 nM). FANC reduced aortic atheroma burden, serum total cholesterol, and oxidative stress markers malondialdehyde and 4-hydroxynonenal levels. FANC attenuated hepatic lipid deposit, with changed expression of lipid homeostasis-related genes HMGCR, SREBP, PCSK9, and LDLR in a pattern similar to mice treated with ezetimibe. FANC also inhibited intestinal cholesterol absorption, resembling the action of ezetimibe. The lipid-lowering and anti-atherosclerotic effects of FANC reappeared in Western-type diet-fed LDLr-deficient mice. FANC bound insulin receptor β (IRβ) via DHLA, leading to AKT activation. However, unlike insulin, which also bound IRβ to activate AKT to induce HO-1, activation of AKT by FANC was independent of HO-1 expression in human aortic endothelial cells (HAECs). Alternatively, FANC up-regulated NRF2, interfered the binding of KEAP1 to NRF2, and promoted KEAP1 degradation to free NRF2 for nuclear entry to induce HO-1 that suppressed the expression of ICAM-1 and VCAM-1. Consistently, FANC suppressed ox-LDL-induced enhanced attachment of THP-derived macrophages onto HAECs. In macrophages, FANC up-regulated ABCA1, and reversed ox-LDL-induced suppression of cholesterol efflux. FANC effected in vitro at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis.</p>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"103427"},"PeriodicalIF":10.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681525","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}