Redox Biology最新文献_第10页

Retraction notice to “Endogenous H2S targets mitochondria to promote continual phagocytosis of erythrocytes by microglia after intracerebral hemorrhage” [Redox Biology 56 (2022) 102442] 关于“内源性H2S靶向线粒体促进脑出血后小胶质细胞持续吞噬红细胞”的撤回通知[氧化还原生物学56 (2022)102442]

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-28 DOI: 10.1016/j.redox.2025.103985

Xiaoling Yan , Meijun He , Hui Huang , Qi Wang , Yu Hu , Xiaoying Wang , Meng Jin , Yi Wang , Yiqing Xia , Yi Li , Gang Chen , Jian Cheng , Jia Jia

引用次数: 0

Retraction notice to “Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats” [Redox Biology 27 (2019) 101170] “人脂肪源性干细胞远程移植通过调节自发性高血压大鼠巨噬细胞极化诱导心肌肥厚消退”撤回通知[氧化还原生物学27(2019)101170]。

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-22 DOI: 10.1016/j.redox.2025.103983

Tsung-Ming Lee , Horng-Jyh Harn , Tzyy-Wen Chiou , Ming-Hsi Chuang , Chun-Hung Chen , Chi-Hsuan Chuang , Po-Cheng Lin , Shinn-Zong Lin

引用次数: 0

Resistance-based training improves mitochondrial capacity and redox balance in aging adults, independent of polyphenol supplementation 基于阻力的训练可改善老年人线粒体能力和氧化还原平衡，无需多酚补充

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-17 DOI: 10.1016/j.redox.2025.103972

Mathias Flensted-Jensen , Cecilie Moe Weinreich , Ann-Sofie Kleis-Olsen , Filip Hansen , Nadia Stenner Skyggelund , Jeppe Rahbek Pii , Ryan Whitlock , Anders Karlsen , Arthur Ingersen , Dace Reihmane , Daniela Weber , Tilman Grune , Olga Pivovarova-Ramich , Flemming Dela

Aging is associated with declines in skeletal muscle function, mitochondrial capacity, and changes in redox balance, which collectively contribute to frailty and chronic disease risk. This study investigated the effects of a 12-week resistance training (RT) program combined with a small dose of high-intensity interval training (HIIT), with or without polyphenol supplementation, on mitochondrial respiratory capacity (MRC) and oxidative stress in middle-aged and older adults (55–70 years). Forty-one participants were randomized to receive either a polyphenol supplement or a placebo for 30 days before the training intervention. Following the training intervention, aerobic capacity, lean mass, and strength improved significantly in both groups. Training also increased MRC in the placebo group but not in the polyphenol group, which displayed higher MRC following the supplementation phase, possibly reflecting either a supplement effect or baseline variation. The training resulted in a 20 % decrease in skeletal muscle H₂O₂ emission across both groups, suggesting enhanced mitochondrial efficiency or antioxidant defenses. However, gene expression of selected antioxidants was unchanged, and plasma oxidative stress markers malondialdehyde (MDA) increased, and 3-nitrotyrosine (3-NT) remained unchanged. Circulating antioxidants showed distinct changes with training, as ascorbic acid increased with training in both groups, while α-tocopherol increased only in the placebo group and β-cryptoxanthin and retinol declined in the polyphenol group, suggesting potential supplement–nutrient interactions. Uric acid increased in both groups, likely reflecting exercise-induced purine turnover. In conclusion, combined RT and HIIT improved mitochondrial bioenergetics and muscle redox balance in middle-aged and older adults, whereas polyphenol supplementation did not augment these adaptations and may have blunted some vitamin-related responses. These findings underscore resistance-based exercise as a potent intervention for maintaining physical and mitochondrial health with age.

衰老与骨骼肌功能下降、线粒体能力下降和氧化还原平衡变化有关，这些因素共同导致身体虚弱和慢性疾病风险。本研究调查了为期12周的阻力训练（RT）计划与小剂量高强度间歇训练（HIIT）结合，有或没有补充多酚，对中老年人（55-70岁）线粒体呼吸能力（MRC）和氧化应激的影响。41名参与者在训练干预前30天随机接受多酚补充剂或安慰剂。在训练干预后，两组的有氧能力、瘦质量和力量均有显著改善。训练也增加了安慰剂组的MRC，但多酚组没有，多酚组在补充阶段显示出更高的MRC，可能反映了补充效果或基线变化。训练导致两组小鼠骨骼肌H2O2排放减少20% %，表明线粒体效率或抗氧化防御能力增强。然而，所选抗氧化剂的基因表达没有变化，血浆氧化应激标志物丙二醛（MDA）升高，3-硝基酪氨酸（3-NT）保持不变。循环抗氧化剂在训练中表现出明显的变化，抗坏血酸在两组中都随着训练而增加，而α-生育酚仅在安慰剂组中增加，而β-隐黄质和视黄醇在多酚组中下降，这表明可能存在补充营养素的相互作用。尿酸在两组中都有所增加，可能反映了运动引起的嘌呤转换。总之，联合RT和HIIT改善了中老年人的线粒体生物能量和肌肉氧化还原平衡，而多酚补充并没有增强这些适应，可能会减弱一些维生素相关的反应。这些发现强调了以阻力为基础的运动是一种有效的干预措施，可以随着年龄的增长保持身体和线粒体的健康。

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引用次数: 0

Activation of the integrated stress response contributes to developmental delay and seizures caused by mitochondrial prolyl-tRNA synthetase (PARS2) deficiency 综合应激反应的激活有助于线粒体脯氨酸- trna合成酶（PARS2）缺乏引起的发育迟缓和癫痫发作。

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-09 DOI: 10.1016/j.redox.2025.103966

Man Xu , Yuxin Liu , Runhua Ma , Wenlu Fan , Jingwei Duan , Huan Deng , Yanbin Ma , Wanzhong Ge

Mutations in mitochondrial aminoacyl-tRNA synthetases (mtARSs) causes mitochondrial defects and serious, progressive and usually lethal diseases with exceptional heterogeneous and tissue-specific clinical manifestations. However, the pathogenic mechanisms for specific mtARS related diseases are largely unknown and currently there is no highly effective treatment or cure for these diseases. In the present study, we generate Drosophila models with human mitochondrial prolyl-tRNA synthetase (PARS2) deficiency by knocking out or knocking down dPARS2, the Drosophila ortholog of human PARS2, and further characterize the disease-associated defects and explore the molecular basis of these phenotypes. Inactivation of dPARS2 in Drosophila causes developmental delay and seizure, two main clinical features in human PARS2 deficiency-associated patients. Biochemical analysis demonstrates that loss of dPARS2 activity results in reduced mitochondrial tRNA^Pro aminoacylation, decreased levels of OXPHOS complex proteins, defective assembly and altered enzyme activities of OXPHOS complexes. Interestingly, we discover that dPARS2 deficiency activates the integrated stress response (ISR), which reduces global protein translation and increases activity of ATF4 in our neuronal dPARS2 knockdown model. Importantly, blockade of ISR activation by genetic suppression of GCN2 kinase prevents developmental delay and seizure phenotypes in dPARS2-deficient flies. Furthermore, the genetic suppression of ATF4, the ISR key effector, also reverses these developmental and behavioral abnormalities associated with dPARS2 deficiency. Furthermore, a disease-associated PARS2 V95I variant causes mitochondrial dysfunction and ISR activation in human cells, verifying the findings in the Drosophila models. Together, these results not only provide evidence for PARS2 deficiency associated mitochondrial dysfunction, but also reveal a novel pathogenic mechanism involved in ISR activation in the PARS2 deficiency related disease, indicating a novel disease treatment approach by targeting ISR.

线粒体氨酰基- trna合成酶（mtars）突变导致线粒体缺陷和严重的、进行性的、通常是致命的疾病，具有异常的异质和组织特异性的临床表现。然而，特定mtARS相关疾病的致病机制在很大程度上是未知的，目前还没有非常有效的治疗或治愈这些疾病。在本研究中，我们通过敲除或敲低人类PARS2的果蝇同源基因dPARS2，构建了人类线粒体脯氨酸- trna合成酶（PARS2）缺乏的果蝇模型，并进一步表征了疾病相关缺陷，探索了这些表型的分子基础。果蝇dPARS2失活导致发育迟缓和癫痫发作，这是人类PARS2缺陷相关患者的两个主要临床特征。生化分析表明，dPARS2活性的丧失导致线粒体tRNAPro氨基酰化减少，OXPHOS复合物蛋白水平下降，组装缺陷和OXPHOS复合物酶活性改变。有趣的是，在我们的神经元dPARS2敲低模型中，我们发现dPARS2缺失激活了综合应激反应（ISR），从而减少了全局蛋白翻译并增加了ATF4的活性。重要的是，通过基因抑制GCN2激酶来阻断ISR激活可以防止dpars2缺陷果蝇的发育迟缓和癫痫发作表型。此外，ISR关键效应因子ATF4的基因抑制也逆转了这些与dPARS2缺乏相关的发育和行为异常。此外，疾病相关的PARS2 V95I变体导致人类细胞的线粒体功能障碍和ISR激活，验证了果蝇模型中的发现。总之，这些结果不仅为PARS2缺陷相关的线粒体功能障碍提供了证据，而且揭示了在PARS2缺陷相关疾病中参与ISR激活的一种新的致病机制，提示了一种针对ISR的新的疾病治疗方法。

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引用次数: 0

Revisiting molecular hydrogen signaling in mitochondria: Is the Rieske protein the entry point or a downstream sentinel? 重新审视线粒体中的分子氢信号：Rieske蛋白是入口点还是下游哨兵？

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2026-01-05 DOI: 10.1016/j.redox.2026.104003

Sergej M. Ostojic

A recent study published in Redox Biology (Volume 88, December 2025, 103952) demonstrates that molecular hydrogen (H₂) rapidly suppresses mitochondrial Complex III activity through a mechanism involving the Rieske iron-sulfur protein (RISP) and subsequent LONP1-dependent proteolysis, challenging the long-standing view of H₂ as merely a selective radical scavenger. While these findings compellingly identify RISP as a key mediator of mitochondrial responses to H₂, its designation as the primary molecular target warrants broader consideration. From an evolutionary and structural standpoint, RISP belongs to a wider family of hydrogenase-like mitochondrial redox proteins that retain ancient iron-sulfur architectures. Proteins such as succinate dehydrogenase subunit B (SDHB), iron-sulfur subunits of Complex I, and CISD family [2Fe–2S] proteins share comparable redox logic and strategic positioning within mitochondrial bioenergetic networks. Here, these candidates are prioritized and placed into a hierarchical, testable framework, and specific comparative structural, biochemical, and proteostatic approaches are proposed to define the true molecular entry point of H₂ signaling in human mitochondria.

最近发表在《氧化还原生物学》（88卷，2025年12月，103952）上的一项研究表明，分子氢（H2）通过涉及Rieske铁硫蛋白（RISP）和随后的lonp1依赖性蛋白水解的机制，迅速抑制线粒体复合物III的活性，挑战了长期以来认为H2仅仅是一种选择性自由基清除剂的观点。虽然这些发现令人信服地确定了RISP是线粒体对H2反应的关键介质，但它作为主要分子靶点的指定需要更广泛的考虑。从进化和结构的角度来看，RISP属于一个更广泛的类似氢化酶的线粒体氧化还原蛋白家族，它保留了古老的铁硫结构。琥珀酸脱氢酶亚基B （SDHB）、复合物I的铁硫亚基和CISD家族[2Fe-2S]蛋白等蛋白质在线粒体生物能量网络中具有相似的氧化还原逻辑和战略定位。在这里，这些候选分子被优先排序并置于一个分层的、可测试的框架中，并提出了特定的比较结构、生化和蛋白质抑制方法来定义人类线粒体中H2信号的真正分子入口点。

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引用次数: 0

USP13 ameliorates myocardial infarction injury by inhibiting ferroptosis via stabilizing ALDOA USP13通过稳定ALDOA抑制铁下垂改善心肌梗死损伤

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.redox.2025.103995

Pengcheng Li , Delong Chen , Chenyun Zhang , Qinyan Gong , Abuduwufuer Yidilisi , Jiacheng Fang , Yuxuan Zhang , Junyan Jin , Jiniu Huang , Jun Jiang

Despite the central role of deubiquitinases (DUBs) in maintaining protein homeostasis, their important role in post-myocardial infarction (MI) remodeling remains incompletely characterized. Our study identifies a DUB, ubiquitin-specific protease 13 (USP13), as a stress-responsive regulator exhibiting significant downregulation in MI-induced cardiac injury. USP13 deficiency aggravated cardiac ferroptosis and cardiac dysfunction after MI surgery. Mechanistically, USP13 directly bound to fructose-bisphosphate aldolase A (ALDOA) via its ubiquitin-specific protease domain. USP13 regulated K48-linked deubiquitination and the stability of ALDOA at K13, thereby preventing its degradation via the proteasomal pathway and restraining ferroptosis in cardiomyocytes. Moreover, specifical overexpression the endogenous USP13 in mouse hearts attenuated MI-induced cardiac injury. We confirmed that USP13 inhibited MI-induced cardiac injury by deubiquitinating and stabilizing ALDOA. These findings suggest that USP13 may serve as a promising therapeutic target for myocardial infarction, providing a foundation for developing novel treatment strategies focused on ferroptosis.

尽管去泛素酶（DUBs）在维持蛋白质稳态中起着核心作用，但它们在心肌梗死后重构中的重要作用仍未完全确定。我们的研究确定了DUB，泛素特异性蛋白酶13 (USP13)，作为应激反应调节因子，在mi诱导的心脏损伤中表现出显著的下调。USP13缺乏加重心肌梗死术后心肌铁下垂和心功能障碍。从机制上讲，USP13通过其泛素特异性蛋白酶结构域直接与果糖二磷酸醛缩酶A （ALDOA）结合。USP13调节k48相关的去泛素化和K13处ALDOA的稳定性，从而通过蛋白酶体途径阻止其降解，抑制心肌细胞的铁凋亡。此外，小鼠心脏中特异性过表达内源性USP13可减轻心肌梗死引起的心脏损伤。我们证实USP13通过去泛素化和稳定ALDOA抑制mi诱导的心脏损伤。这些发现表明，USP13可能作为心肌梗死的一个有希望的治疗靶点，为开发以铁下垂为重点的新治疗策略提供了基础。

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引用次数: 0

Superoxide signals for the mitophagy of dysfunctional mitochondria to maintain quality control 功能失调线粒体自噬的超氧化物信号以维持质量控制

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.redox.2025.103979

William M. Curtis, Patrick C. Bradshaw

The mechanism of selecting dysfunctional mitochondria for mitophagy is only partially understood. Evidence suggests the mechanism involves reactions of superoxide (O₂⁻•), hydrogen peroxide (H₂O₂), nitric oxide (NO•), peroxynitrite (ONOO⁻), carbonate radicals (•CO₃⁻), nitrogen dioxide radicals (•NO₂), hydroxyl radicals (•OH), oxygen (•O₂• or O₂), and carbon dioxide (CO₂). However, the larger picture of how these reactions are organized to induce mitophagy is unclear. Extensive evidence suggests that increased mitochondrial matrix O₂⁻• is associated with the mitophagy of dysfunctional organelles. In most cells, mitochondrial O₂⁻• is mainly produced by the reaction of O₂ with free radical intermediate forms of coenzyme Q (CoQ) and flavins, which are generated in substantial amounts in the inner membrane and matrix space of dysfunctional mitochondria. Mitochondrial O₂⁻• plays two key roles in orchestrating mitophagy. First, it is dismutated by mitochondrial matrix superoxide dismutase 2 (SOD2) to H₂O₂. This diffusible messenger directs the nuclear and cytoplasmic compartments to prepare for mitophagy, including the generation of cytoplasmic NADPH and glutathione and the increased synthesis of membrane-diffusible NO•. Second, mitochondrial matrix space O₂⁻• readily reacts with NO• to form ONOO⁻, which initiates a cascade of free radical reactions culminating in mitochondrial membrane depolarization and PINK1 and Parkin-driven mitophagy. Compelling observations that support the proposed mechanism are given. This mechanism could be targeted for the treatment of diseases characterized by dysfunctional mitophagy, such as Parkinson's disease. Because of the central role of mitochondrial O₂⁻• as a sentinel for selective mitophagy, we have named this hypothesis the superoxide sentinel hypothesis of mitochondrial quality control.

选择功能失调线粒体进行线粒体自噬的机制只被部分理解。有证据表明，其机制涉及超氧化物（O2−•）、过氧化氢（H2O2）、一氧化氮（NO•）、过氧亚硝酸盐（ONOO−）、碳酸盐自由基（•CO3−）、二氧化氮自由基（•NO2）、羟基自由基（•OH）、氧（•O2•或O2）和二氧化碳（CO2）的反应。然而，这些反应是如何组织起来诱导有丝分裂的更大图景尚不清楚。大量证据表明，线粒体基质O2−•的增加与功能失调细胞器的线粒体自噬有关。在大多数细胞中，线粒体O2−•主要由O2与辅酶Q （CoQ）和黄素的自由基中间形式反应产生，黄素在功能障碍线粒体的内膜和基质空间中大量产生。线粒体O2−•在协调线粒体自噬中起着两个关键作用。首先，它被线粒体基质超氧化物歧化酶2 （SOD2）歧化成H2O2。这个可扩散的信使指导细胞核和细胞质室为有丝分裂做准备，包括细胞质NADPH和谷胱甘肽的产生以及膜可扩散NO•的合成增加。其次，线粒体基质空间O2−•很容易与NO•反应形成ONOO−，从而引发一系列自由基反应，最终导致线粒体膜去极化和PINK1和帕金森驱动的线粒体自噬。给出了支持所提议机制的令人信服的观察结果。这种机制可以靶向治疗以线粒体自噬功能失调为特征的疾病，如帕金森病。由于线粒体O2−•作为选择性线粒体自噬的前哨的核心作用，我们将这一假说命名为线粒体质量控制的超氧化物前哨假说。

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引用次数: 0

The G9a-TRIM21 axis exacerbates diabetic renal ischemia-reperfusion injury by inducing methylation-dependent ubiquitination and degradation of FoxO3a to promote oxidative stress and pyroptosis G9a-TRIM21轴通过诱导甲基化依赖性泛素化和FoxO3a降解促进氧化应激和焦亡，加重糖尿病肾缺血再灌注损伤

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-08 DOI: 10.1016/j.redox.2025.103964

Qingyuan Zheng , Xuke Qin , Shiyu Huang , Zhiwei Yan , Jin Liu , Yufeng Xiong , Xiaojie Zhao , Xinmiao Ni , Haonan Mei , Jun Jian , Jingsong Wang , Qianxue Lu , Zhiyuan Chen , Xiuheng Liu , Shanshan Wan , Hao Liu , Lei Wang

Introduction

Diabetic renal ischemia-reperfusion injury (RIRI) is a severe surgical complication with particularly poor outcomes in diabetic patients. The histone methyltransferase G9a has been implicated in various pathological processes, but its role in diabetic RIRI remains unclear. Emerging evidence suggests that non-histone protein methylation may play crucial roles in cellular responses to ischemic injury.

Objectives

This study aimed to investigate the functional role of G9a in diabetic RIRI and elucidate its molecular mechanisms, with particular focus on its regulation of FoxO3a stability, oxidative stress and cellular pyroptosis.

Methods

We established diabetic RIRI models using G9a conditional knockout mice and HK-2 cells under high glucose conditions. Renal function was assessed through serum creatinine and BUN measurements. Histopathological evaluation and molecular analyses were performed to examine tissue damage and pyroptosis markers. Mechanistic studies included mass spectrometry identification of G9a-interacting proteins, co-immunoprecipitation to verify protein interactions, and ubiquitination assays to characterize post-translational modifications. Site-directed mutagenesis was employed to identify critical residues in FoxO3a regulation.

Results

G9a expression was significantly upregulated in diabetic RIRI models. Genetic ablation of G9a attenuated renal injury and reduced oxidative stress and pyroptosis in both in vivo and in vitro models. Mechanistically, G9a directly interacted with and methylated FoxO3a at lysine 262, which facilitated its recognition by the E3 ubiquitin ligase TRIM21. TRIM21 subsequently mediated K48-linked polyubiquitination of FoxO3a at lysine 176, leading to proteasomal degradation. This G9a-mediated FoxO3a degradation promoted oxidative stress, NLRP3 inflammasome activation and pyroptosis. Importantly, pharmacological inhibition of G9a with BIX-01294 or FoxO3a overexpression significantly ameliorated diabetic RIRI.

Conclusion

Our study reveals a novel G9a-TRIM21-FoxO3a regulatory axis in diabetic RIRI, where G9a-mediated methylation licenses FoxO3a ubiquitination and degradation, thereby promoting pyroptosis and oxidative stress. These findings identify G9a as a potential therapeutic target for preventing or treating diabetic kidney ischemia-reperfusion injury.

糖尿病性肾缺血再灌注损伤（RIRI）是一种严重的手术并发症，在糖尿病患者中预后尤其差。组蛋白甲基转移酶G9a与多种病理过程有关，但其在糖尿病RIRI中的作用尚不清楚。新出现的证据表明，非组蛋白甲基化可能在缺血性损伤的细胞反应中起关键作用。

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引用次数: 0

Corrigendum to “KEAP1 C151 active site catalysis drives electrophilic signaling to upregulate cytoprotective enzyme expression” [Redox Biology 88 (2025) 103906] “KEAP1 C151活性位点催化驱动亲电信号上调细胞保护酶表达”的勘误表[Redox Biology 88(2025) 103906]。

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-30 DOI: 10.1016/j.redox.2025.104000

Matthew R. Schnell , Tianhua Zhai , Edwin R. Ragwan , Hannah Jung , Jiayu Zhang , Anthony F. Lagalante , Yan Kung , Daniel A. Kraut , Zuyi Huang , Aimee L. Eggler

引用次数: 0

Redox-active nitroxides enhance cisplatin efficacy against cervical cancer 氧化还原活性氮氧化物增强顺铂抗宫颈癌疗效

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-02-01 Epub Date: 2025-12-20 DOI: 10.1016/j.redox.2025.103989

Carl P. Soltau , Debottam Sinha , Lakshita P. Patil , Philip M. Moseley , Cassie L. Rayner , Nigel L. Barnett , Derek J. Richard , Steven E. Bottle , Ian H. Frazer , Alexander P. Martyn

Cisplatin remains the primary treatment for most cervical cancer cases, though its clinical efficacy is hindered by dose-dependent toxicity and incurring chemoresistance. The overexpression of the glucocorticoid receptor (GR) and cellular redox state is linked to increased resistance to chemotherapy in cervical cancer. This study explores the combinations of novel steroidal and nitroxide-based treatments to improve the efficacy of cisplatin against cervical cancer. Two lead nitroxide-functionalised prednisolone hybrids (CS91 and CS187) were identified for their potent anti-proliferative activity in multiple cervical squamous cell carcinoma (SCC) cell lines. These compounds exhibit comparable anti-proliferative activity to the parent nitroxides, while maintaining GR binding capability. When combined with cisplatin, CS91 and CS187 induced a dose-dependent reduction in cell viability across multiple cervical cancer cell lines, which was optimised to preserve above 80 % healthy cell viability but decrease cancer cell viability below 15 %. Mechanistic studies revealed that these compounds raised intracellular reactive oxygen species (ROS) levels, with further enhancement in combination with cisplatin. This combination approach was found to be synergistic, resulting in decreased glutathione (GSH) levels and increased DNA damage compared to cisplatin alone. In summary, nitroxide-based hybrids exhibit potent anti-proliferative effects and potentiate cisplatin efficacy through ROS-mediated mechanisms, offering a promising targeted strategy for cervical cancer treatment.

顺铂仍然是大多数宫颈癌病例的主要治疗方法，尽管其临床疗效受到剂量依赖性毒性和化疗耐药的阻碍。糖皮质激素受体（GR）的过度表达和细胞氧化还原状态与宫颈癌化疗耐药性增加有关。本研究探讨新型甾体和氮氧化物联合治疗提高顺铂治疗宫颈癌的疗效。两种氮化铅功能化强的松龙杂种（CS91和CS187）在多种宫颈鳞状细胞癌（SCC）细胞系中具有有效的抗增殖活性。这些化合物表现出与母体氮氧化物相当的抗增殖活性，同时保持GR结合能力。当与顺铂联合使用时，CS91和CS187诱导多种宫颈癌细胞系细胞活力的剂量依赖性降低，优化后可使健康细胞活力保持在80% %以上，但将癌细胞活力降低到15% %以下。机制研究表明，这些化合物提高细胞内活性氧（ROS）水平，并与顺铂联合进一步增强。这种联合方法被发现是协同的，与单用顺铂相比，导致谷胱甘肽（GSH）水平降低和DNA损伤增加。综上所述，基于氮氧化物的杂交体具有强大的抗增殖作用，并通过ros介导的机制增强顺铂的疗效，为宫颈癌治疗提供了一种有希望的靶向策略。

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引用次数: 0