Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe最新文献_第3页

Role of abnormal mitochondrial DNA in Cancer: A review of molecular changes and therapeutic opportunities 异常线粒体DNA在癌症中的作用：分子变化和治疗机会的综述

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-06-24 DOI: 10.1016/j.arres.2025.100134

Md. Sanower Hossain , Mohammad Touhidul Islam , Md. Abid Hossain , Kajima Rifat , Saila Kabir Maeesa , Mamunur Rahman , Md. Rezaul Islam , Raihana Edros , Sheikh Zahir Raihan , Chrismawan Ardianto , Long Chiau Ming , Bey Hing Goh , Mohd Yusri Bin Mohd Yunus , Jun Haslinda Shariffuddin

Mitochondria are cellular organelles that play vital roles in a cell's energy production and metabolism. Researchers have made significant progress in understanding mitochondrial dynamics and their effects on human health in recent years. The mitochondrial genome or respiratory chain induces mitochondrial illnesses. Mitochondrial DNA (mtDNA) is a crucial component of mitochondria, and its relationship with cancer has received much attention in recent years. Although there is currently no cure for mitochondrial disorders, various treatment options, such as physiotherapy, hearing aids, pacemakers, and sodium bicarbonate injections, are available for managing symptoms. Diet and exercise can help patients with mitochondrial dysfunction. Individuals with pyruvate dehydrogenase insufficiency benefit from a ketogenic diet and a high-fat, low-carbohydrate diet. Cancer is linked to mitochondrial dynamics, including fusion and fission. These pathways affect cancer stem cell proliferation and recurrence. New cancer therapies may be developed by targeting the proteins involved in mitochondrial fusion and fission. Although some trials have already been conducted, additional research is needed to establish this phenomenon as a full treatment option.

线粒体是细胞的细胞器，在细胞的能量产生和代谢中起着至关重要的作用。近年来，研究人员在了解线粒体动力学及其对人类健康的影响方面取得了重大进展。线粒体基因组或呼吸链诱发线粒体疾病。线粒体DNA （mtDNA）是线粒体的重要组成部分，其与癌症的关系近年来受到广泛关注。虽然目前还没有治愈线粒体疾病的方法，但有各种治疗选择，如物理治疗、助听器、起搏器和碳酸氢钠注射，可用于控制症状。饮食和运动可以帮助患有线粒体功能障碍的患者。丙酮酸脱氢酶不足的个体可以从生酮饮食和高脂肪、低碳水化合物饮食中获益。癌症与线粒体动力学有关，包括融合和裂变。这些途径影响肿瘤干细胞的增殖和复发。针对参与线粒体融合和裂变的蛋白质，可能会开发出新的癌症治疗方法。虽然已经进行了一些试验，但需要进一步的研究来确定这种现象是否可以作为一种完整的治疗选择。

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引用次数: 0

Impact of cell culture conditions on NRF2 (nuclear factor E2 p45-related factor 2)-driven reporter gene expression 细胞培养条件对NRF2（核因子E2 p45相关因子2）驱动的报告基因表达的影响

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-06-09 DOI: 10.1016/j.arres.2025.100136

Barbara Braunböck-Müller, Elke H Heiss

For the identification and characterization of compounds that modulate the activation status of the stress-responsive and cytoprotective transcription factor NRF2 (nuclear factor E2 p45-related factor 2), ARE (antioxidant response element)-driven reporter gene assays serve as convenient tools. NRF2 signaling is susceptible to various factors, including cellular energy status, circadian rhythm, and mechanical or oxygen tension. These parameters are often inadequately accounted for in routine 2D cell culture and screening processes, potentially limiting the relevance of the obtained data or identified hits. Therefore, we investigated whether NRF2-driven luminescence readings from a ARE-luciferase reporter gene markedly differ from routine culture conditions when stably transfected HepG2 cells are cultivated in plasma-like medium, exhibit altered mechanotransduction, are synchronized, or grown in spheroids. While NRF2 signaling is consistently activated by the synthetic triterpenoid CDDO-IM under all tested conditions, the baseline (indicative for the initial cellular stress status/Nrf2 activity) and/or the extent of inducible luciferase activity (activation amplitude conferred by the NRF2 activator) varies across different cultivation conditions.

为了鉴定和表征调节应激反应和细胞保护转录因子NRF2（核因子E2 p45相关因子2）激活状态的化合物，ARE（抗氧化反应元件）驱动的报告基因检测是一种方便的工具。NRF2信号易受多种因素影响，包括细胞能量状态、昼夜节律、机械或氧张力。在常规的2D细胞培养和筛选过程中，这些参数通常没有得到充分的考虑，可能会限制所获得数据或确定命中的相关性。因此，我们研究了nrf2驱动的荧光素酶报告基因的发光读数是否与常规培养条件显著不同，当稳定转染的HepG2细胞在血浆样培养基中培养，表现出改变的机械转导，同步或在球体中生长时。虽然NRF2信号在所有测试条件下都被合成的三萜CDDO-IM激活，但基线（指示初始细胞应激状态/ NRF2活性）和/或诱导荧光素酶活性的程度（NRF2激活剂赋予的激活幅度）在不同的培养条件下有所不同。

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引用次数: 0

Redox signalling and microRNA feedback in exercise-mediated skeletal muscle remodelling 运动介导的骨骼肌重构中的氧化还原信号和microRNA反馈

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-05-27 DOI: 10.1016/j.arres.2025.100133

Qin Xia , Katarzyna Goljanek-Whysall , Brian McDonagh

Exercise induces the acute generation of reactive oxygen species (ROS) in skeletal muscle, which can regulate a range of redox signalling pathways that determine the adaptive response to exercise. The redox environment can directly affect excitation contraction coupling, calcium handling and inflammation but also regulate key signalling pathways involved in mitochondrial quality control and proteostasis. Additionally, exercise-induced regulation of microRNAs (miRs) levels can provide a feedback mechanism to fine tune the adaptive response. Endogenous ROS produced during exercise arise from diverse sources including NADPH oxidases (NOX), mitochondria, xanthine oxidase (XO) and phospholipase A2 (PLA2). As high levels of ROS can potentially be damaging, there is a sophisticated, organelle-specific antioxidant network in skeletal muscle that includes superoxide dismutases (SODs), catalases (CATs), peroxiredoxins (PRDXs) and glutathione peroxidases (GPXs). Due to their abundance, location and catalytic activity, emerging evidence highlights the potential role of the PRDX family as central mediators in coordinating the redox signalling cascade as a result of increased ROS generation. Several exercise related miRs contain binding sites for redox sensitive and exercise associated transcription factors (TFs), moreover some miRs can target these TFs, providing a potential feedback mechanism to maintain cellular homeostasis following disruption of the redox environment. The interconnected roles of redox signalling and miRs are discussed in exercise-induced skeletal muscle adaptations. Furthermore, the therapeutic potential of targeting these interconnected pathways to mitigate muscle ageing and dysfunction, can provide valuable insights into strategies for optimising muscle health and enhancing healthspan.

运动诱导骨骼肌急性生成活性氧（ROS），可调节一系列氧化还原信号通路，决定运动的适应性反应。氧化还原环境可以直接影响兴奋收缩耦合、钙处理和炎症，但也调节涉及线粒体质量控制和蛋白质平衡的关键信号通路。此外，运动诱导的microrna （miRs）水平调节可以提供一种反馈机制来微调适应性反应。运动过程中产生的内源性ROS有多种来源，包括NADPH氧化酶（NOX）、线粒体、黄嘌呤氧化酶（XO）和磷脂酶A2 （PLA2）。由于高水平的活性氧可能具有潜在的破坏性，骨骼肌中存在一个复杂的、细胞器特异性的抗氧化网络，包括超氧化物歧化酶（sod）、过氧化氢酶（cat）、过氧化物还毒素（PRDXs）和谷胱甘肽过氧化物酶（GPXs）。由于它们的丰富度、位置和催化活性，新出现的证据强调了PRDX家族在协调氧化还原信号级联过程中作为中心介质的潜在作用，这是由于ROS生成增加的结果。一些运动相关的miRs含有氧化还原敏感转录因子和运动相关转录因子（tf）的结合位点，而且一些miRs可以靶向这些tf，提供了一种潜在的反馈机制来维持氧化还原环境破坏后的细胞稳态。氧化还原信号和miRs在运动诱导的骨骼肌适应中的相互作用进行了讨论。此外，靶向这些相互关联的途径来缓解肌肉衰老和功能障碍的治疗潜力，可以为优化肌肉健康和延长健康寿命的策略提供有价值的见解。

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引用次数: 0

Exogenously added recombinant CLIC proteins provide antioxidant protection to cells in culture 外源添加重组CLIC蛋白对培养细胞具有抗氧化保护作用

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-05-16 DOI: 10.1016/j.arres.2025.100132

KR Hossain, A Alghalayini, DR Turkewitz, C D’Amario, Catherine A Gorrie, M Wallach, SM Valenzuela

Chloride intracellular ion channels (CLICs) are a family of six human proteins that exist as both soluble and integral membrane proteins and are expressed across a range of different tissues throughout the body. CLIC1 and CLIC4 act as moonlighting proteins, exhibiting oxidoreductase enzymatic activity in addition to their membrane ion channel activity. Transient siRNA knockdown of either CLIC1 or CLIC4 in primary human dermal fibroblast (HDF), human epidermal keratinocyte (HKE) cells and in the stable murine fibroblast cell line, NIH/3T3, showed significant reduction in cell viability. Conversely, NIH/3T3 cells over-expressing CLIC1 or CLIC4 demonstrated that both proteins assist in protecting the cells from hydrogen peroxide (H₂O₂)-induced oxidative damage, resulting in reduced cell death and reduced Reactive Oxygen Species (ROS) generation. While the opposite effect was seen in cells where these proteins had been silenced using siRNA. We have also now demonstrated that by exogenously adding recombinant CLIC (rCLIC) proteins to either HDF or HKE cells in culture, both rCLIC1 and rCLIC4 proteins provided cellular antioxidant protection to the fibroblast and keratinocyte cells against H₂O₂-induced oxidative damage. Our study also demonstrates rCLIC1 and rCLIC4’s ability to act as skin cell protective antioxidant agents, arises from their oxidoreductase enzymatic activity. Our findings also showed exogenous addition of rCLIC1 or rCLIC4 to skin cells resulted in similar or greater protection against H₂O₂-induced oxidative damage when compared to other well-known endogenous antioxidants like glutaredoxin (Grx), Glutathione S-transferase-Omega (GST-Ω) and the antioxidant drug, N-acetylcysteine (NAC).

细胞内氯离子通道（CLICs）是一个由六种人类蛋白组成的蛋白家族，它们以可溶性和整体膜蛋白的形式存在，并在全身不同组织中表达。CLIC1和CLIC4作为兼职蛋白，除了具有膜离子通道活性外，还具有氧化还原酶活性。在原代人真皮成纤维细胞（HDF）、人表皮角质形成细胞（HKE）细胞和稳定的小鼠成纤维细胞系NIH/3T3中，瞬时siRNA敲低CLIC1或CLIC4均显示细胞活力显著降低。相反，过表达CLIC1或CLIC4的NIH/3T3细胞表明，这两种蛋白有助于保护细胞免受过氧化氢（H2O2）诱导的氧化损伤，从而减少细胞死亡和活性氧（ROS）的产生。而在使用siRNA沉默这些蛋白质的细胞中，则出现了相反的效果。我们现在也证明，通过外源性添加重组CLIC （rCLIC）蛋白到培养的HDF或HKE细胞中，rCLIC1和rCLIC4蛋白都能提供细胞抗氧化保护，使成纤维细胞和角质细胞免受h2o2诱导的氧化损伤。我们的研究还证明了rCLIC1和rCLIC4作为皮肤细胞保护抗氧化剂的能力，这源于它们的氧化还原酶酶活性。我们的研究结果还表明，与其他众所周知的内源性抗氧化剂如谷胱甘肽（Grx）、谷胱甘肽s -转移酶- omega （GST-Ω）和抗氧化药物n -乙酰半胱氨酸（NAC）相比，外源性添加rCLIC1或rCLIC4到皮肤细胞对h2o2诱导的氧化损伤具有相似或更强的保护作用。

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引用次数: 0

Glutathione deficiency and heart failure: a systematic review of human and animal evidence 谷胱甘肽缺乏和心力衰竭：对人类和动物证据的系统回顾

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-05-15 DOI: 10.1016/j.arres.2025.100131

Ali A. Al-Mubarak, Antonio Esquivel-Gaytan, Herman H.W. Silljé, Peter van der Meer, Nils Bomer

Background

Oxidative stress is an important factor underlying several pathophysiological mechanisms in heart failure (HF). Nevertheless, modulating oxidative stress is still a significant challenge due to the lack of specific and modifiable targets. A central component that is integrated into several processes is glutathione, an essential thiol-based compound that is integrated into redox homeostasis.

Objective

To establish the significance of glutathione and its availability in relation to HF.

Methods

A comprehensive search strategy using PubMed, Embase, and Web of Science was developed. All human studies with patients with HF and animal studies with evidence of significant cardiac remodelling and available measurements of glutathione were included.

Results

A total of 7656 articles were initially identified. Following first screening, 426 articles were selected for full assessment, out of which 217 reports were ultimately included in the analysis. There were 21 studies out of 25 that showed lower glutathione measures in patients with HF compared to controls, of which 18 reached statistical significance with an average reduction of 27.8 %. Regarding the animal evidence, 74.2 % and 79.3 % of the measurements in ischemic cardiomyopathy models and models with transverse aortic constriction, showed lower glutathione concentrations as compared to sham groups, respectively. Factors that positively influenced glutathione concentrations included all guideline-directed medical therapies, selenium, amlodipine, and N-acetylcysteine.

Conclusion

Glutathione deficiency is a common finding in the context of HF. As it is a measurable and modifiable component with various biological targets, investigating the effects of optimizing its concentration in patients with HF should be pursued.

背景氧化应激是心衰（HF）的几个病理生理机制的重要因素。然而，由于缺乏特异性和可修改的靶点，调节氧化应激仍然是一个重大挑战。谷胱甘肽是整合到几个过程中的一个中心成分，它是一种重要的硫醇基化合物，被整合到氧化还原稳态中。目的探讨谷胱甘肽在心衰中的意义及其可得性。方法利用PubMed、Embase和Web of Science开发综合检索策略。所有HF患者的人类研究和有明显心脏重构证据的动物研究以及可用的谷胱甘肽测量值均被纳入。结果共鉴定出7656篇。在第一次筛选之后，426篇文章被选中进行全面评估，其中217篇报告最终被纳入分析。25项研究中有21项显示HF患者的谷胱甘肽水平低于对照组，其中18项具有统计学意义，平均降低27.8%。关于动物证据，74.2%和79.3%的缺血性心肌病模型和主动脉横缩模型的测量结果分别显示谷胱甘肽浓度低于假手术组。对谷胱甘肽浓度有积极影响的因素包括所有指南指导的药物治疗、硒、氨氯地平和n -乙酰半胱氨酸。结论谷胱甘肽缺乏是心衰患者的常见症状。由于它是一种可测量和可改变的成分，具有多种生物学靶点，因此应继续研究优化其浓度在心衰患者中的作用。

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引用次数: 0

Global hotspots and prospective trends for chondrocyte metabolic changes and oxidative stress in osteoarthritis: A bibliometric analysis 骨关节炎中软骨细胞代谢变化和氧化应激的全球热点和未来趋势：文献计量学分析

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-04-06 DOI: 10.1016/j.arres.2025.100130

Wuyan Lu , Jieshen Huang , Zhonglin Zhang , Shuangmeng Jia , Weiqiao Zhao , Linxiao Li , Fengting Niu , Ke Fang , Zixin Cai , Yao Li , Yishu Lu , Lei Cui , Jiefeng Huang , Shuaijun Li

Osteoarthritis (OA) is a prevalent age-related degenerative joint disorder characterized by dysregulation of metabolism. While several studies have examined the metabolic changes in OA, there exists a lack of a comprehensive retrospective analysis of its current development, research hotspots, and future trends. In this study, we employed bibliometric approaches to retrospectively review the development, mechanisms, and future trends of metabolic changes in OA. We utilized VOSviewer software to quantitatively and visually depict: (a) annual temporal trends in literature and citation counts; (b) national/regional publications and collaborations; (c) institutional and author contributions; (d) journal contributions and relevance; (e) analysis of research hotspots and directions through keywords. By analyzing keywords and research hotspots, we systematically illustrated the influential factors of metabolic changes in OA, including inflammation, apoptosis, oxidative stress, and autophagy. Conclusively, the research field of metabolic changes in OA is rapidly expanding, and we aim to provide a more comprehensive and insightful perspective for targeting metabolic disorders in OA.

骨关节炎（OA）是一种常见的与年龄相关的退行性关节疾病，其特征是代谢失调。虽然有一些研究对OA的代谢变化进行了研究，但对OA的发展现状、研究热点和未来趋势缺乏全面的回顾性分析。在这项研究中，我们采用文献计量学方法回顾性回顾OA代谢变化的发展、机制和未来趋势。我们利用VOSviewer软件定量和直观地描绘：(a)文献和引文数量的年度时间趋势；(b)国家/区域出版物和合作；(c)机构和作者的贡献；(d)期刊贡献和相关性；(e)通过关键词分析研究热点和方向。通过分析关键词和研究热点，系统阐述OA代谢变化的影响因素，包括炎症、细胞凋亡、氧化应激、自噬等。总之，OA代谢变化的研究领域正在迅速扩大，我们的目标是为针对OA代谢紊乱提供一个更全面、更深刻的视角。

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引用次数: 0

Linoleic acid, mitochondria, gut microbiome, and metabolic health: a mechanistic review 亚油酸、线粒体、肠道微生物组和代谢健康：一个机制综述

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-04-02 DOI: 10.1016/j.arres.2025.100128

Joseph Mercola

This hypothesis‐driven narrative review delineates the intricate mechanisms by which redox imbalance—encompassing both oxidative and reductive stresses—precipitates mitochondrial dysfunction in metabolic disorders. This review examines how excessive consumption of industrial seed oils rich in linoleic acid (LA) contributes to mitochondrial dysfunction, in part, by promoting peroxidation of lipids, including cardiolipin (CL), and altering mitochondrial bioenergetics. Such modifications destabilize electron transport chain (ETC) supercomplexes and elevate reactive oxygen species (ROS) generation, thereby compromising ATP production and overall mitochondrial efficiency. Additionally, we explore emerging evidence linking LA‐induced mitochondrial perturbations with gut dysbiosis, where impaired colonocyte metabolism disrupts the anaerobic niche critical for microbial balance, further propagating systemic inflammation. An integrative analysis of macronutrient quality and quantity suggests that strategic dietary modulation—particularly a marked reduction in LA intake—may restore mitochondrial redox homeostasis and improve metabolic health. By re-examining historical dietary trends alongside recent biochemical and clinical insights, this work underscores the critical role of mitochondrial membrane dynamics in metabolic pathophysiology and highlights targeted nutritional strategies to preserve mitochondrial integrity.

这一假说驱动的叙述性综述描述了氧化还原失衡——包括氧化应激和还原性应激——在代谢紊乱中引发线粒体功能障碍的复杂机制。这篇综述探讨了过量食用富含亚油酸（LA）的工业种子油是如何通过促进脂质过氧化（包括心磷脂（CL））和改变线粒体生物能量学来促进线粒体功能障碍的。这种修饰破坏了电子传递链（ETC）超复合物的稳定性，提高了活性氧（ROS）的产生，从而影响了ATP的产生和线粒体的整体效率。此外，我们探索了将LA诱导的线粒体扰动与肠道生态失调联系起来的新证据，其中结肠菌代谢受损破坏了对微生物平衡至关重要的厌氧生态位，进一步传播全身炎症。一项宏量营养素质量和数量的综合分析表明，战略性膳食调节——特别是显著减少LA摄入量——可能恢复线粒体氧化还原稳态，改善代谢健康。通过重新审视历史饮食趋势以及最近的生化和临床见解，这项工作强调了线粒体膜动力学在代谢病理生理学中的关键作用，并强调了有针对性的营养策略来保持线粒体的完整性。

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引用次数: 0

Measuring oxidative stress by the iridium reducing capacity assay (Ir-RCA) 用铱还原容量法测定氧化应激

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-03-26 DOI: 10.1016/j.arres.2025.100129

Leah N. Falk , William E. Bentley , Deanna L. Kelly , Gregory F. Payne , Eunkyoung Kim

Oxidative stress appears to act globally and span body systems (e.g., nervous, immune, and endocrine). Currently, there is no single, generally-accepted measurement of oxidative stress. Many possible measurement approaches focus on the bottom-up analysis of individual molecules (e.g., reactive species, antioxidants, hormones or signaling molecules) or combinations of molecules (e.g., proteomics or metabolomics). Efforts to develop a global measurement of oxidative stress often detect a sample's ability to reduce a metal-ion (e.g., iron or copper) or quench a free radical. Here, we review results from a recently-developed iridium-reducing capacity assay (Ir-RCA) and suggest that this method offers several key benefits as a potential measurement of oxidative stress. First, the Ir-RCA employs simple optical and/or electrochemical measurements that can be extended to high throughput formats. Second, the Ir-RCA appears to be more sensitive than alternative global antioxidant assays. Third, the Ir-RCA measures stable molecular features of a sample. Fourth, the Ir-RCA has been “validated” by showing statistically significant differences in persons diagnosed with schizophrenia (N = 73) versus healthy controls (N = 45). Fifth, the Ir-RCA measurement of oxidative stress is “movable”: psychosocial stressors can increase this measure of oxidative stress, while beneficial dietary interventions can decrease this measure of oxidative stress. Limitations and future directions for the Ir-RCA are discussed.

氧化应激似乎是全球性的，横跨身体各个系统（如神经系统、免疫系统和内分泌系统）。目前，还没有单一的、普遍接受的氧化应激测量方法。许多可能的测量方法都侧重于对单个分子（如活性物种、抗氧化剂、激素或信号分子）或分子组合（如蛋白质组学或代谢组学）进行自下而上的分析。开发氧化应激整体测量方法的努力通常是检测样本还原金属离子（如铁或铜）或淬灭自由基的能力。在此，我们回顾了最近开发的铱还原能力测定法（Ir-RCA）的结果，并认为该方法作为一种潜在的氧化应激测量方法具有几大优点。首先，Ir-RCA 采用简单的光学和/或电化学测量方法，可扩展到高通量格式。其次，Ir-RCA 似乎比其他全球抗氧化检测方法更灵敏。第三，Ir-RCA 可测量样品的稳定分子特征。第四，Ir-RCA 已通过在精神分裂症患者（73 人）与健康对照组（45 人）中显示出统计学上的显著差异而得到 "验证"。第五，Ir-RCA 对氧化应激的测量是 "可移动的"：社会心理压力可增加氧化应激的测量，而有益的饮食干预可减少氧化应激的测量。本文讨论了 Ir-RCA 的局限性和未来发展方向。

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引用次数: 0

Repurposing Bacopa monnieri extracts containing Aquaporin-1 blockers to improve systemic oxidative stress: The BacOxy_I study 利用含有水通道蛋白-1阻滞剂的假马齿苋提取物改善全身氧化应激：BacOxy_I研究

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-03-20 DOI: 10.1016/j.arres.2025.100126

Hasnae Boughaleb , Roxane Verdoy , Amandine Pochet , Nathalie Fabian , Ramona Bella , Gopinath Muruganandam , Raphaël Frédérick , Karim Zouaoui Boudjeltia , Axelle Bourez , Cédric Delporte , Pierre Van Antwerpen , Annie Robert , Vincent Haufroid , Joseph P. Dewulf , Jean-Luc Balligand , Virginie Montiel

Objectives

To evaluate the efficacy of Bacopa monnieri (BM) containing Bacopaside II, a specific Aquaporin 1 (AQP1)-blocker, on systemic oxidative stress.

Background

AQP1, is a peroxiporin which facilitates hydrogen peroxide transmembrane passage. It is predominantly expressed in endothelial cells and erythrocytes.

Methods

BM extract was administered orally for 6 weeks to 20 healthy volunteers (Group A/B: 400/800 mg/day). Assessments occurred at baseline (V0), after 6 weeks of treatment (V4), and 4 weeks post-treatment (V6). Primary endpoint: ROS levels in erythrocytes post-H₂O₂ exposure (DCFDA fluorescence). Secondary endpoints: Oxidative stress and safety biomarkers, blood pressure monitoring. Bacopaside II metabolites in plasma were identified using liquid chromatography-mass spectrometry (LC-MS).

Results

BM intake reduced ROS levels in RBCs in Group B (T40 min: Mean Fluorescence Intensity of DCF V0=381 ± 43 a.u vs V4= 187 ± 69 a.u, p<0.01). Methemoglobin and oxidized Methionine 148 of Apolipoprotein A-1 levels decreased (Methemoglobin group B: V0= 0.900 ± 0.105 a.u vs V4= 0.233 ± 0.047 a.u; p<0.001, M148-ox/M148 ratio group B: V0= 0.06 ± 0.01 a.u. vs V4= 0.02 ± 0.00 a.u.; p<0.05). A reduction in blood pressure was observed in Group B (Systolic Blood Pressure V0=131 ± 15 mmHg vs SBP V4=116 ± 7 mmHg; p < 0.05). Two potential Bacopaside II metabolites with putative binding pockets on AQP1 were identified during the treatment.

Conclusion

A six-week oral intake of BM reduced systemic oxidative stress in healthy volunteers in a dose-dependent manner. Pharmacological blocking of AQP1 may help restore redox balance in the vasculature.

目的观察假马齿苋（Bacopa monnieri， BM）中含有特异性水通道蛋白1 （AQP1）阻断剂bacop皂苷II对全身氧化应激的影响。daqp1是一种促进过氧化氢跨膜通过的过氧化物蛋白。它主要在内皮细胞和红细胞中表达。方法健康志愿者20例（A/B组：400/800 mg/d），口服枸杞提取物6周。评估分别在基线（V0）、治疗6周后（V4）和治疗后4周（V6）进行。主要终点：h2o2暴露后红细胞中的ROS水平（DCFDA荧光）。次要终点：氧化应激和安全生物标志物，血压监测。采用液相色谱-质谱联用技术（LC-MS）对血浆中bacop皂苷II代谢物进行鉴定。结果bm摄入降低B组红细胞ROS水平（T40 min: DCF平均荧光强度V0=381±43 a.u vs V4= 187±69 a.u, p < 0.01）。B组高铁血红蛋白：V0= 0.900±0.105 a.u vs V4= 0.233±0.047 a.u；0.001， M148-ox/M148比值B组：V0= 0.06±0.01 a.u. vs V4= 0.02±0.00 a.u.；术中,0.05)。B组血压降低(收缩压V0=131±15 mmHg vs收缩压V4=116±7 mmHg；p & lt;0.05)。在治疗过程中，发现了两种潜在的Bacopaside II代谢物，这些代谢物可能与AQP1结合。结论连续6周口服BM可降低健康志愿者的全身氧化应激，且呈剂量依赖性。药物阻断AQP1可能有助于恢复血管中的氧化还原平衡。

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Recent updates on sickness during acute high-altitude hypoxic exposure and its management 急性高原缺氧暴露期间疾病的最新进展及其管理

Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe

Pub Date : 2025-03-19 DOI: 10.1016/j.arres.2025.100127

Swaraj Mohanty, Yasmin Ahmad

Chronic and intermittent hypoxia are the two different modalities of developing high-altitude(HA) sickness when an individual is exposed to varying environmental conditions. Exposure to this unusual environment has a great impact on cellular pathophysiology and molecular signaling. The severity of the physiological condition relays on the time and duration of stay at a particular altitude and the workload on an individual. The cellular homeostasis shows a variable trend in different tissues and at the systematic level which needs an in-depth understanding of the possible pharmacological and nonpharmacological management that will be helpful to overcome stressful conditions. In this review article, we have summarized the altered signaling and molecular pathways during chronic and intermittent hypoxia from reported in vitro and in vivo studies on high-altitude exposure and available management strategies.

当一个人暴露在不同的环境条件下时，慢性缺氧和间歇性缺氧是发生高海拔（HA）病的两种不同模式。暴露在这种不寻常的环境中会对细胞病理生理学和分子信号转导产生巨大影响。生理状况的严重程度取决于在特定海拔高度停留的时间和持续时间以及个人的工作量。细胞平衡在不同组织和系统水平上呈现出不同的趋势，这就需要深入了解可能的药物和非药物疗法，以帮助克服压力条件。在这篇综述文章中，我们总结了有关高海拔暴露和可用管理策略的体外和体内研究报告中有关慢性和间歇性缺氧期间信号传导和分子通路的改变。

引用次数: 0