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

Mapping transcriptomic signatures downstream of mitochondrial superoxide dismutase SOD2 in OVCA433 multicellular aggregates 绘制OVCA433多细胞聚集体中线粒体超氧化物歧化酶SOD2下游转录组特征

IF 2.7

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 : 2025-12-01 Epub Date: 2025-11-01 DOI: 10.1016/j.arres.2025.100141

Amal Taher Elhaw , Priscilla W. Tang , Shriya Kamlapurkar , Sarah Al-Saad , Sneha Srinivasan , Danyang Li , George C. Tseng , Adam C. Straub , Nadine Hempel

During metastatic spread, tumor cells adapt to evade anchorage-independent cell death by upregulating mitochondrial antioxidant systems. We previously showed that ovarian cancer cells upregulate mitochondrial manganese superoxide dismutase (SOD2) following detachment and multicellular aggregate (MCA) formation. SOD2 scavenges mitochondrial superoxide and manipulates cellular hydrogen peroxide levels, both functions necessary for metastasis. Here, we investigated SOD2′s metastatic function by assessing its transcriptomic effects in OVCA433 ovarian cancer cells cultured in low-attachment conditions that induce MCAs, mimicking anchorage-independent states in malignant ascites. SOD2 siRNA-mediated knockdown effects in MCAs were compared to adherent culture conditions. RNA sequencing and pathway analysis revealed that SOD2 lies upstream of pro-metastatic pathways, including PI3K/AKT signaling. Notably, in MCAs, cytokine and immune cell signaling pathways were more significantly enriched following SOD2 knockdown. We previously identified SIRT3 as an important SOD2 activity regulator in MCAs. While SIRT3 knockdown resulted in minor transcriptional changes, we identified that FOXO3 and ELF4 transcription factors, important for stress response and immune regulation, are downregulated by both SIRT3 and SOD2 knockdown. Comparing SOD2 knockdown transcriptional changes to the Cancer Genome Atlas, we found SOD2 expression strongly associates with pro-tumorigenic immune signaling in serous ovarian cancer specimens, including genes identified downstream of SOD2 from our siRNA screen. Moreover, SOD2 expression correlated with signatures related to pro-tumorigenic neutrophil and T-regulatory cell populations. Our data suggest SOD2 positively regulates pro-metastatic pathways, and those identified in MCAs more closely reflect gene expression profiles associated with SOD2 expression in patient tumors.

在转移扩散过程中，肿瘤细胞通过上调线粒体抗氧化系统来适应逃避锚定非依赖性细胞死亡。我们之前的研究表明，卵巢癌细胞在脱离和多细胞聚集（MCA）形成后上调线粒体锰超氧化物歧化酶（SOD2）。SOD2清除线粒体超氧化物并控制细胞过氧化氢水平，两者都是转移所必需的功能。在这里，我们通过评估SOD2在OVCA433卵巢癌细胞中的转录组效应来研究SOD2的转移功能，OVCA433卵巢癌细胞在低附着条件下培养，诱导MCAs，模拟恶性腹水中锚定不依赖的状态。将MCAs中SOD2 sirna介导的敲低效应与贴壁培养条件进行比较。RNA测序和通路分析显示，SOD2位于促转移通路的上游，包括PI3K/AKT信号通路。值得注意的是，在MCAs中，SOD2敲除后，细胞因子和免疫细胞信号通路更加显著地富集。我们之前发现SIRT3是MCAs中重要的SOD2活性调节因子。虽然SIRT3敲低导致了轻微的转录变化，但我们发现对应激反应和免疫调节重要的FOXO3和ELF4转录因子被SIRT3和SOD2敲低下调。将SOD2敲低转录变化与癌症基因组图谱进行比较，我们发现在浆液性卵巢癌标本中，SOD2表达与致瘤性免疫信号密切相关，包括从我们的siRNA筛选中鉴定出的SOD2下游基因。此外，SOD2的表达与促肿瘤中性粒细胞和t调节细胞群相关的特征相关。我们的数据表明，SOD2正调节促转移途径，而在MCAs中发现的这些途径更密切地反映了患者肿瘤中与SOD2表达相关的基因表达谱。

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引用次数: 0

Oxidative stress-induced cytotoxicity and the role of dietary antioxidants in farm animals: A review 农场动物氧化应激诱导的细胞毒性和膳食抗氧化剂的作用：综述

IF 2.7

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 : 2025-09-01 Epub Date: 2025-07-29 DOI: 10.1016/j.arres.2025.100138

Muhammad Khan , Maida Mushtaq , Muhammad Usman , Muhammad Aziz Ur Rahman , Guobo Quan

Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and antioxidant defenses, impairs animal health, immunity, reproduction, and productivity. This review summarizes the roles of key dietary antioxidants vitamin A, melatonin, essential trace minerals (copper, zinc, magnesium), flavonoids, polyphenols, and L-carnitine, in mitigating oxidative stress in farm animals. Vitamin A supports epithelial integrity, scavenges ROS, and upregulates antioxidant enzymes via redox-sensitive transcription factors. Melatonin functions as a potent free radical scavenger and activates the Nrf2 pathway to enhance antioxidant enzyme expression. Copper, zinc, and magnesium act as cofactors for enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), helping maintain redox homeostasis. Flavonoids and polyphenols, including quercetin, curcumin, and EGCG, exert antioxidant effects by scavenging ROS, chelating metal ions, and enhancing endogenous defense pathways. L-carnitine improves mitochondrial function, reduces ROS generation, and enhances glutathione activity, especially during stress conditions such as heat, transport, or weaning. Supplementation with these compounds across species has been shown to increase antioxidant enzyme activity, reduce oxidative biomarkers like malondialdehyde (MDA), and improve immunity, metabolic efficiency, and performance. These natural or synthetic antioxidants offer promising nutritional strategies to improve oxidative stability, health, and productivity in farm animals. Their integration into feed programs provides a sustainable and cost-effective approach to improving animal welfare and resilience under intensive production systems.

氧化应激是由活性氧（ROS）和抗氧化防御之间的不平衡引起的，会损害动物的健康、免疫、繁殖和生产力。本文综述了主要膳食抗氧化剂维生素A、褪黑素、必需微量矿物质（铜、锌、镁）、类黄酮、多酚和左旋肉碱在减轻农场动物氧化应激中的作用。维生素A支持上皮完整性，清除活性氧，并通过氧化还原敏感转录因子上调抗氧化酶。褪黑素作为一种有效的自由基清除剂，激活Nrf2通路，增强抗氧化酶的表达。铜、锌和镁作为酶抗氧化剂的辅助因子，如超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx），帮助维持氧化还原稳态。黄酮类和多酚类物质，包括槲皮素、姜黄素和EGCG，通过清除活性氧、螯合金属离子和增强内源性防御途径发挥抗氧化作用。左旋肉碱改善线粒体功能，减少ROS生成，增强谷胱甘肽活性，特别是在热、运输或断奶等应激条件下。跨物种补充这些化合物已被证明可以增加抗氧化酶活性，降低丙二醛（MDA）等氧化生物标志物，并提高免疫力、代谢效率和性能。这些天然或合成的抗氧化剂为改善农场动物的氧化稳定性、健康和生产力提供了有前途的营养策略。将它们纳入饲料计划为在集约化生产系统下改善动物福利和恢复力提供了可持续和具有成本效益的方法。

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引用次数: 0

Altered activity of leukocytes derived from circulating blood immediately after revascularization in peripheral artery disease 外周动脉疾病患者血运重建后循环血液中白细胞活性的改变

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 : 2025-09-01 Epub Date: 2025-06-28 DOI: 10.1016/j.arres.2025.100137

Kozo Takeuchi , Kimiko Kazumura , Akihiro Yoshida , Tappei Furuta , Kazunori Hayashi , Masashi Nagai , Yukiko Hatano , Michitaka Naito , Etsushi Matsushita

Endovascular treatment (EVT) is an effective therapeutic option for patients with peripheral artery disease (PAD). However, EVT is associated with inflammatory adverse effects, and the systemic oxidative status after EVT remains unclear. In this pilot study, we compared the activity of leukocytes derived from circulating blood before and immediately after (within 1 h of) EVT in 30 cases with PAD. The ankle-brachial index (ABI) improved immediately after EVT (p < 0.001), suggesting successful revascularization. The levels of leukocyte-produced superoxide radicals (O₂^•−) increased (p < 0.05), those of hypochlorite ions (OCl⁻) remained unchanged, and the OCl⁻/O₂^•− levels reduced (p < 0.001) immediately after EVT. We observed two subtypes of alterations in leukocyte activity immediately after EVT: type A exhibiting increased levels of both O₂^•− and OCl⁻, and type B showing increased O₂^•− levels, while relatively small changes in OCl⁻ levels. In addition, the interleukin-6 levels increased (p < 0.05) immediately after EVT. Moreover, EVT increased the leukocyte count (p < 0.001) and dynamically changed the balance of leukocyte components, with a notable increase in the neutrophil percentage. These findings and results of our correlation analyses imply that inflammatory response and/or ischemia–reperfusion potentially alters O₂^•−production by leukocytes. This study contributes to the understanding of the pathophysiology of EVT-associated systemic oxidative events, which includes vascular inflammation and ischemia–reperfusion injury. The findings can support further development of diagnostic and therapeutic strategies for the health conditions after EVT.

血管内治疗（EVT）是外周动脉疾病（PAD）患者的有效治疗选择。然而，EVT与炎症不良反应有关，EVT后的全身氧化状态尚不清楚。在这项初步研究中，我们比较了30例PAD患者EVT前后（EVT后1小时内）循环血液中白细胞的活性。EVT后踝臂指数（ABI）立即改善(p <；0.001)，提示血运重建成功。白细胞产生的超氧自由基（O2•−）水平升高(p <；0.05)，次氯酸盐离子（OCl−）保持不变，OCl−/O2•−水平降低(p <；0.001)。我们观察到EVT后白细胞活性的两种变化亚型：A型显示O2•−和OCl−水平升高，B型显示O2•−水平升高，而OCl−水平变化相对较小。此外，白细胞介素-6水平升高(p <；0.05)。此外，EVT增加白细胞计数(p <；0.001)，并动态改变白细胞成分的平衡，中性粒细胞百分比显著增加。这些发现和我们的相关分析结果表明，炎症反应和/或缺血再灌注可能改变白细胞的O2•−产生。本研究有助于了解evt相关的全身氧化事件的病理生理学，包括血管炎症和缺血再灌注损伤。研究结果可以支持进一步制定EVT后健康状况的诊断和治疗策略。

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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 : 2025-09-01 Epub 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

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 : 2025-09-01 Epub 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

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 : 2025-09-01 Epub 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

Deciphering of the reactive oxygen species (ROS) induced calpain activation in cancer progression and its therapeutic potential 破译活性氧（ROS）在癌症进展中诱导的钙蛋白酶激活及其治疗潜力

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 : 2025-06-01 Epub Date: 2025-03-04 DOI: 10.1016/j.arres.2025.100124

Krishna Samanta , Ivan Ahel , Pulak Kar

Mitochondrial signalling plays a fundamental role in orchestrating essential intracellular functions, including cellular respiration, proliferation, nucleic acid synthesis, and oxidative stress management. The activation of calpain, a group of Ca²⁺-dependent cysteine proteases, by ROS-induced oxidative stress is linked to cancer progression. Calpain can be activated by ROS either through intracellular Ca²⁺ elevation or via oxidative modifications of the protease, altering protein susceptibility to calpain cleavage. In tumour cell biology, ROS-activated calpains influence cell survival, migration, proliferation, apoptosis, and invasiveness. Several studies report unusual calpain expression in cancer cells. Various anticancer drugs induce cytotoxicity by activating calpain, significantly impacting cancer treatment strategies. This unique review explores the perspective of ROS-induced calpain activation and its pivotal role in cancer progression and therapeutics.

线粒体信号在协调细胞内基本功能，包括细胞呼吸、增殖、核酸合成和氧化应激管理中起着重要作用。ros诱导的氧化应激激活钙蛋白酶（一组Ca2+依赖性半胱氨酸蛋白酶）与癌症进展有关。ROS可以通过细胞内Ca2+升高或蛋白酶的氧化修饰激活Calpain，从而改变蛋白质对Calpain裂解的敏感性。在肿瘤细胞生物学中，ros激活的钙蛋白酶影响细胞存活、迁移、增殖、凋亡和侵袭性。一些研究报道了癌细胞中异常的钙蛋白酶表达。各种抗癌药物通过激活钙蛋白酶诱导细胞毒性，显著影响癌症治疗策略。这篇独特的综述探讨了ros诱导的钙蛋白酶激活及其在癌症进展和治疗中的关键作用。

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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 : 2025-06-01 Epub 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 : 2025-06-01 Epub 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 : 2025-06-01 Epub 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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