Redox Biology最新文献

{"title":"Antrodia cinnamomea triterpenoids attenuate cardiac hypertrophy via the SNW1/RXR/ALDH2 axis","authors":"Yinghua Ma ,&nbsp;Yunxia Wang ,&nbsp;Gulinigaer Anwaier ,&nbsp;Nuerbiye Tuerdi ,&nbsp;Yangchang Wu ,&nbsp;Yinyue Huang ,&nbsp;Boyang Qin ,&nbsp;Haoyue Ma ,&nbsp;Qiao Zhang ,&nbsp;Dalei Wu ,&nbsp;Kewu Zeng ,&nbsp;Rong Qi","doi":"10.1016/j.redox.2024.103437","DOIUrl":"10.1016/j.redox.2024.103437","url":null,"abstract":"<div><div>Aldehyde dehydrogenase 2 (ALDH2), a pivotal enzyme in the metabolism of toxic aldehydes produced by oxidative stress, has been demonstrated to play a cardioprotective role in cardiovascular diseases. <em>Antrodia cinnamomea</em> triterpenoids (ACT) is a medicinal mushroom with anti-inflammatory and antioxidant properties, and our previous study found that ACT can exert anti-fatty liver effects by regulating ALDH2. This study aimed to elucidate the impact of ACT and its monomer on cardiac hypertrophy and investigate the relationship between its pharmacological mechanism and ALDH2. Through examining cardiac morphology and expression levels of hypertrophic biomarkers, ACT significantly reduced myocardial hypertrophy induced by angiotensin II (Ang II) and transverse aortic constriction (TAC)surgery in wild-type mice, but not in ALDH2 knockout mice. <em>In vitro</em>, ACT and its monomeric dehydrosulphurenic acid (DSA) inhibited the hypertrophic phenotype of Ang II-stimulated neonatal cardiac myocytes (NRCMs) in an ALDH2-dependent manner. Regarding the pharmacological mechanism, it was observed that ACT and DSA restored ALDH2 expression and activity in myocardial tissues of WT-Ang II/TAC mice and Ang II-induced NRCMs. Furthermore, it inhibited oxidative stress and improved mitochondrial quality control (MQC) homeostasis in an ALDH2-dependent manner. We screened SNW1, a transcriptional coactivator, as a DSA-binding protein by “target fishing” and cellular enthusiasm transfer assay techniques and validated that SNW1 promoted ALDH2 transcription and translation levels through synergistic interaction with the transcription factor RXR. In conclusion, the findings demonstrate that ACT/DSA upregulates ALDH2 expression <em>via</em> regulating SNW1/RXR, thereby inhibiting oxidative stress and maintaining MQC homeostasis, and then protects against cardiac hypertrophy.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103437"},"PeriodicalIF":10.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706961","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":"RSL3 sensitizes glioma cells to ionizing radiation by suppressing TGM2-dependent DNA damage repair and epithelial-mesenchymal transition","authors":"Xuanzhong Wang ,&nbsp;Weiyan Shi ,&nbsp;Mengxin Li ,&nbsp;Ying Xin ,&nbsp;Xin Jiang","doi":"10.1016/j.redox.2024.103438","DOIUrl":"10.1016/j.redox.2024.103438","url":null,"abstract":"<div><div>RAS-selective lethal small molecule 3 (RSL3) is a small-molecule compound that triggers ferroptosis by inactivating glutathione peroxidase 4. However, its effect on the radioresistance of glioma cells and the underlying mechanisms remains unclear. In this study, we found that RSL3 sensitized glioma cells to ionizing radiation (IR) and enhanced IR-induced DNA double-strand breaks (DSBs). Inhibition of ferroptosis pathways partly prevented the clonogenic death caused by the IR/RSL3 combination but did not alleviate the DNA DSBs, indicating that RSL3 promotes IR-induced DNA DSBs via a non-ferroptotic mechanism. We demonstrated that transglutaminase 2 (TGM2) plays a vital role in the radiosensitization effect of RSL3 on glioma cells. Treatment with RSL3 downregulated TGM2 in a dose-dependent manner. Overexpression of TGM2 not only alleviated DNA DSBs but also inhibited clonogenic death caused by the IR/RSL3 combination. Mechanistically, RSL3 triggered oxidative stress in glioma cells, which promoted the S-gluthathionylation of TGM2 via upregulation of glutathione S-transferase P1(GSTP1), culminating in the proteasomal degradation of TGM2. This process resulted in the suppression of DNA repair mechanisms by impeding the nuclear accumulation of TGM2 and disrupting the interaction between TGM2 and topoisomerase IIα after irradiation. We also found that RSL3 inhibited glioma cell epithelial-mesenchymal transition (EMT) in both IR-treated and non-IR-treated cells. Overexpression of TGM2 prevented, while knockdown of TGM2 aggravated the EMT inhibition caused by RSL3, indicating that RSL3 also sensitized glioma cells to IR by inhibiting EMT via a TGM2-dependent mechanism. Furthermore, in mice bearing human U87 tumor xenografts, RSL3 administration synergized with IR to inhibit tumor growth, accompanied by TGM2 inhibition, DNA DSBs, and EMT inhibition in tumor tissues. Taken together, we demonstrated that RSL3 sensitizes glioma cells to IR by suppressing TGM2-mediated DNA repair and EMT.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103438"},"PeriodicalIF":10.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706484","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":"DKK3 as a diagnostic marker and potential therapeutic target for sarcopenia in chronic obstructive pulmonary disease","authors":"Zilin Wang ,&nbsp;Mingming Deng ,&nbsp;Weidong Xu ,&nbsp;Chang Li ,&nbsp;Ziwen Zheng ,&nbsp;Jiaye Li ,&nbsp;Liwei Liao ,&nbsp;Qin Zhang ,&nbsp;Yiding Bian ,&nbsp;Ruixia Li ,&nbsp;Jinrui Miao ,&nbsp;Kai Wang ,&nbsp;Yan Yin ,&nbsp;Yanxia Li ,&nbsp;Xiaoming Zhou ,&nbsp;Gang Hou","doi":"10.1016/j.redox.2024.103434","DOIUrl":"10.1016/j.redox.2024.103434","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroascorbic acid quantification in human plasma: Simultaneous direct measurement of the ascorbic acid/dehydroascorbic acid couple by UPLC/MS-MS","authors":"P.-C. Violet ,&nbsp;N. Munyan ,&nbsp;H.F. Luecke ,&nbsp;Y. Wang ,&nbsp;J. Lloyd ,&nbsp;K. Patra ,&nbsp;K. Blakeslee ,&nbsp;I.C. Ebenuwa ,&nbsp;M. Levine","doi":"10.1016/j.redox.2024.103425","DOIUrl":"10.1016/j.redox.2024.103425","url":null,"abstract":"<div><div>Ascorbic acid (AA, vitamin C) and dehydroascorbic acid (DHA) constitute a biological couple. No technique can accurately, independently, and simultaneously quantify both members of the couple in animal and human samples, thereby constraining advances in physiology and pathophysiology. Here we describe a new UPLC/MS/MS method to measure both compounds directly and independently in human plasma. Lower limits of quantification were 16 nM, with linear coefficients &gt;0.99 over a 100-fold concentration range. The method was stable and reproducible with &lt;10 % injection-to-injection variation. Use of isotopic labeled internal standards for both compounds ensured precision and accuracy. Plasma preparation required only 2 steps. In plasma samples from 14 anonymized subjects who met criteria for blood donation, mean concentrations were 6±2 μmol/L (mean ± SD) and 56 ± 14 μmol/L for DHA and AA respectively, with (DHA)/(AA + DHA) ratio of 9.8 %. This method represents a pioneering approach to measuring the AA/DHA couple in human plasma.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103425"},"PeriodicalIF":10.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706486","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":"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":"Schaftoside improves HFpEF through regulation the autophagy-lysosome pathway by allosterically targeting CaMKII-δ","authors":"Haiying Zhang ,&nbsp;Yanan Gao ,&nbsp;Min Zhang ,&nbsp;Zhexin Yuan ,&nbsp;Yu Chen ,&nbsp;Aiping Wang ,&nbsp;Xinxing Liu ,&nbsp;Shunchang Ji ,&nbsp;Jianfeng Jin ,&nbsp;Jingwei Liang ,&nbsp;Yan Liu","doi":"10.1016/j.redox.2024.103424","DOIUrl":"10.1016/j.redox.2024.103424","url":null,"abstract":"<div><div>Heart failure with preserved ejection fraction (HFpEF) presents a significant challenge to global healthcare systems due to its complex presentation. HFpEF presents with a normal or near-normal left ventricular ejection fraction, cardiac diastolic dysfunction, and a metabolic profile characterized by impaired inflammation and oxidative stress. There have been few valuable drug targets reported for HFpEF to date. Here, we discovered that schaftoside, an active component from licorice, has a significant protective effect on the cardiac remodeling induced by continuous infusion of angiotensin II (AngII), which leads to the HFpEF phenotype. Mechanistically, schaftoside has demonstrated the ability to ameliorate lysosomal dysfunction in both <em>in vitro</em> and <em>in vivo</em> models, thereby activating autophagy. Bioinformatic analyses based on proteome and phosphoproteome suggested that Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) was a potential target for schaftoside. It was confirmed that schaftoside allosterically mediated CaMKII-δ conformation via targeting a unique active pocket near the ATP-binding site to inhibit protein phosphorylation and regulate the lysosomal autophagy pathway. Therefore, schaftoside represents the first small molecule identified to inhibit CaMKII-δ activity through allosteric inhibition, providing a novel candidate for alleviating cardiac metabolic imbalance in HFpEF.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103424"},"PeriodicalIF":10.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721738","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 ,&nbsp;Daiqin Bao ,&nbsp;Han She ,&nbsp;Zisen Zhang ,&nbsp;Shifeng Shao ,&nbsp;Zhengbin Wu ,&nbsp;Yue Wu ,&nbsp;Qinghui Li ,&nbsp;Li Wang ,&nbsp;Tao Li ,&nbsp;Liangming Liu","doi":"10.1016/j.redox.2024.103353","DOIUrl":"10.1016/j.redox.2024.103353","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 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":"OA","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 ,&nbsp;Yih-Jer Wu ,&nbsp;Cheng-Huang Su ,&nbsp;Bo-Jeng Wang ,&nbsp;Sheng-Hsun Yang ,&nbsp;Hsin-I Lee ,&nbsp;Yen-Hung Chou ,&nbsp;Ting-Yi Tien ,&nbsp;Chao-Feng Lin ,&nbsp;Wen-Hsiung Chan ,&nbsp;Ching-Hu Chung ,&nbsp;Shin-Wei Wang ,&nbsp;Hung-I Yeh","doi":"10.1016/j.redox.2024.103427","DOIUrl":"10.1016/j.redox.2024.103427","url":null,"abstract":"<div><div>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 <em>ApoE</em>-deficient mice by either continuous intraperitoneal delivery <strong>(</strong>20 μM, 50 μl weekly<strong>)</strong> 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 <em>LDLr</em>-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 <em>in vitro</em> at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of mitochondrial oxidative phosphorylation through tight control of cytochrome c oxidase in health and disease – Implications for ischemia/reperfusion injury, inflammatory diseases, diabetes, and cancer","authors":"Lucynda Pham ,&nbsp;Tasnim Arroum ,&nbsp;Junmei Wan ,&nbsp;Lauren Pavelich ,&nbsp;Jamie Bell ,&nbsp;Paul T. Morse ,&nbsp;Icksoo Lee ,&nbsp;Lawrence I. Grossman ,&nbsp;Thomas H. Sanderson ,&nbsp;Moh H. Malek ,&nbsp;Maik Hüttemann","doi":"10.1016/j.redox.2024.103426","DOIUrl":"10.1016/j.redox.2024.103426","url":null,"abstract":"<div><div>Mitochondria are essential to cellular function as they generate the majority of cellular ATP, mediated through oxidative phosphorylation, which couples proton pumping of the electron transport chain (ETC) to ATP production. The ETC generates an electrochemical gradient, known as the proton motive force, consisting of the mitochondrial membrane potential (ΔΨ_m, the major component in mammals) and ΔpH across the inner mitochondrial membrane. Both ATP production and reactive oxygen species (ROS) are linked to ΔΨ_m, and it has been shown that an imbalance in ΔΨ_m beyond the physiological optimal intermediate range results in excessive ROS production. The reaction of cytochrome <em>c</em> oxidase (COX) of the ETC with its small electron donor cytochrome <em>c</em> (Cyt<em>c</em>) is the proposed rate-limiting step in mammals under physiological conditions. The rate at which this redox reaction occurs controls ΔΨ_m and thus ATP and ROS production. Multiple mechanisms are in place that regulate this reaction to meet the cell's energy demand and respond to acute stress. COX and Cyt<em>c</em> have been shown to be regulated by all three main mechanisms, which we discuss in detail: allosteric regulation, tissue-specific isoforms, and post-translational modifications for which we provide a comprehensive catalog and discussion of their functional role with 55 and 50 identified phosphorylation and acetylation sites on COX, respectively. Disruption of these regulatory mechanisms has been found in several common human diseases, including stroke and myocardial infarction, inflammation including sepsis, and diabetes, where changes in COX or Cyt<em>c</em> phosphorylation lead to mitochondrial dysfunction contributing to disease pathophysiology. Identification and subsequent targeting of the underlying signaling pathways holds clear promise for future interventions to improve human health. An example intervention is the recently discovered noninvasive COX-inhibitory infrared light therapy that holds promise to transform the current standard of clinical care in disease conditions where COX regulation has gone awry.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103426"},"PeriodicalIF":10.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681831","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":"Time-restricted eating reveals a “younger” immune system and reshapes the intestinal microbiome in human","authors":"Yiran Chen ,&nbsp;Xi Li ,&nbsp;Ming Yang ,&nbsp;Chen Jia ,&nbsp;Zhenghao He ,&nbsp;Suqing Zhou ,&nbsp;Pinglang Ruan ,&nbsp;Yikun Wang ,&nbsp;Congli Tang ,&nbsp;Wenjing Pan ,&nbsp;Hai Long ,&nbsp;Ming Zhao ,&nbsp;Liwei Lu ,&nbsp;Weijun Peng ,&nbsp;Arne Akbar ,&nbsp;Irene XY. Wu ,&nbsp;Song Li ,&nbsp;Haijing Wu ,&nbsp;Qianjin Lu","doi":"10.1016/j.redox.2024.103422","DOIUrl":"10.1016/j.redox.2024.103422","url":null,"abstract":"<div><div>Time-restricted eating (TRE) has been shown to extent lifespans in drosophila and mouse models by affecting metabolic and anti-inflammatory activities. However, the effect of TRE on the human immune system, especially on immunosenescence, intestinal microbiome, and metabolism remains unclear. We conducted a 30-day 16:8 TRE single-arm clinical trial with 49 participants. Participants consumed daily meals from 9 a.m. to 5 p.m., provided by a nutrition canteen with a balanced, calorie-appropriate nutrition, which is designed by clinical nutritionists (ChiCTR2200058137). We monitored weight changes and weight-related parameters and focused on changes in the frequency of CD4⁺ senescent T cells, immune repertoire from peripheral blood, as well as serum metabolites and gut microbiota. We found that up to 95.9 % of subjects experienced sustained weight loss after TRE. The frequency of circulating senescent CD4⁺ T cells was decreased, while the frequency of Th1, Treg, Tfh-like, and B cells was increased. Regarding the immune repertoire, the proportions of T cell receptor alpha and beta chains were increased, whereas B cell receptor kappa and lambda chains were reduced. In addition, a reduced class switch recombination from immunoglobulin M (IgM) to immunoglobulin A (IgA) was observed. TRE upregulated the levels of anti-inflammatory and anti-aging serum metabolites named sphingosine-1-phosphate and prostaglandin-1. Additionally, several anti-inflammatory bacteria and probiotics were increased, such as <em>Akkermansia</em> and <em>Rikenellaceae</em>, and the composition of the gut microbiota tended to be “younger”. Overall, TRE showed multiple anti-aging effects, which may help humans maintain a healthy lifestyle to stay “young”. Clinical Trial Registration URL: <span><span>https://www.chictr.org.cn/showproj.html?proj=159876</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103422"},"PeriodicalIF":10.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676702","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}