Redox Biology最新文献_第9页

Thioredoxin-mimetic peptide attenuates epilepsy progression and neurocognitive deficits 硫氧还毒素模拟肽减轻癫痫进展和神经认知缺陷

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-10 DOI: 10.1016/j.redox.2026.104021

Prince Kumar Singh , Shweta Maurya , Aseel Saadi , Sereen Sandouka , Taige Zhang , Orya Kadosh , Yara Sheeni , Valeria Martin , Daphne Atlas , Tawfeeq Shekh-Ahmad

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, in which oxidative stress and neuroinflammation play central roles in driving disease progression and pharmacoresistance. Approximately 30–40 % of patients are resistant to current antiseizure medications, which suppress symptoms but do not prevent epilepsy development or modify its progression. There is an urgent need for therapies with true disease-modifying potential. TXM-CB3 (CB3), a thioredoxin-mimetic tripeptide, has been reported to modulate redox and inflammatory pathways. In this study, we evaluated the therapeutic potential of CB3 in preclinical models of temporal lobe epilepsy, focusing on its capacity to suppress seizures, preserve neuronal integrity, and mitigate epilepsy-associated behavioral impairments.

We first examined CB3 in an in vitro model of low-Mg²⁺-induced epileptiform activity, where pretreatment with CB3 (50, 100 μM) attenuated oxidative activity and reduced proinflammatory cytokine expression (IL-6, IL-1β, TNF-α), while enhancing IL-10 levels. In vivo, early CB3 intervention (20 mg/kg/day, i.p.) following kainic acid-induced status epilepticus significantly delayed seizure onset, reduced seizure frequency and cumulative burden, and preserved hippocampal neuronal integrity. Treated animals also showed improved locomotor activity, reduced anxiety-like behavior, and better performance in spatial working memory tasks. In established chronic epilepsy, CB3 treatment (20 mg/kg/day, i.p.) produced a sustained reduction in recurrent seizure activity and seizure burden, with additional effects on anxiety-like behavior, though memory and learning deficits remained unchanged.

Together, these findings highlight CB3's potential as a disease-modifying therapy. By reducing seizure recurrence, preserving neuronal integrity, and alleviating selected behavioral impairments, CB3 offers therapeutic benefits that extend beyond conventional ASMs and warrants further investigation for translation into clinical epilepsy treatment.

癫痫是一种以反复发作为特征的慢性神经系统疾病，其中氧化应激和神经炎症在驱动疾病进展和药物耐药中起核心作用。大约30-40%的患者对目前的抗癫痫药物有耐药性，这些药物抑制症状，但不能预防癫痫的发生或改变其进展。迫切需要具有真正疾病改善潜力的治疗方法。TXM-CB3 （CB3）是一种模拟硫氧还毒素的三肽，据报道可调节氧化还原和炎症途径。在这项研究中，我们评估了CB3在颞叶癫痫临床前模型中的治疗潜力，重点关注其抑制癫痫发作、保持神经元完整性和减轻癫痫相关行为障碍的能力。

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引用次数: 0

BMX-001, a clinically relevant radioprotector, can reverse radiation-induced fibrosis when given three weeks after radiation, in part, by restoring methylation BMX-001是一种临床相关的放射保护剂，在放射后三周给予，部分通过恢复甲基化，可以逆转辐射诱导的纤维化

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-10 DOI: 10.1016/j.redox.2026.104020

Molly S. Myers , Elizabeth A. Kosmacek , Chia Sin Liew , Alexander J. Lushnikov , Arpita Chatterjee , Luis A. Marky , Jean-Jack M. Riethoven , Rebecca E. Oberley-Deegan

Radiation provides excellent tumor control in prostate cancer yet unavoidably harms adjacent healthy tissue via the generation of reactive oxygen species (ROS). Radiation-induced ROS is known to impact fibroblasts long after radiation, resulting in radiation-induced fibrosis (RIF), which can cause incontinence and other side effects that reduce patient quality of life. BMX-001, a manganese porphyrin designed to mimic superoxide dismutase, is in clinical trials as a selective radioprotector when given before and during radiation therapy. However, there have been no studies evaluating BMX-001 when given after radiation for its impacts on RIF. Mice were given pelvic radiation (7.5 Gy for 5 consecutive days) followed by BMX-001 three weeks after radiation. Fibroblasts and tissues were isolated two months following radiation. We found that BMX-001 returned radiation-induced alterations in fibroblast morphology to normal and reversed markers of fibroblast activation and senescence. BMX-001 also decreased collagen deposition six months after radiation. Because these changes persisted for a long period of time, we speculated that BMX-001 may affect fibroblast epigenetics. We found that overall, radiation resulted in reduced methylation two months after radiation, and BMX-001 administered three weeks after radiation modulated radiation-altered methylation patterns back to normal and restored normal expression of a fibrosis-associated gene CAMK2β. BMX-001 also decreased radiation-induced DNA adduct 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is known to interfere with methylation. BMX-001 was able to prevent DNA oxidation and restore normal methylation patterns in an oligonucleotide model of DNA oxidation and methylation. This study reveals the feasibility of agents to reverse fibrosis in pelvic radiation and suggests that BMX-001 may be effective when given after radiation.

放疗在前列腺癌中提供了良好的肿瘤控制，但不可避免地会通过产生活性氧（ROS）损害邻近的健康组织。已知辐射诱导的ROS在辐射后很长时间内会影响成纤维细胞，导致辐射诱导纤维化（RIF），这可能导致尿失禁和其他降低患者生活质量的副作用。BMX-001是一种锰卟啉，设计用于模拟超氧化物歧化酶，在放射治疗之前和期间作为选择性放射保护剂进行临床试验。然而，目前还没有研究评估放射后给予BMX-001对RIF的影响。小鼠盆腔放射（7.5 Gy，连续5天），放射3周后给予BMX-001。放射两个月后分离成纤维细胞和组织。我们发现BMX-001将辐射诱导的成纤维细胞形态改变恢复为正常和逆转的成纤维细胞活化和衰老标记。BMX-001在放疗后6个月也能减少胶原沉积。由于这些变化持续了很长一段时间，我们推测BMX-001可能影响成纤维细胞的表观遗传学。我们发现，总的来说，放疗后两个月导致甲基化降低，而BMX-001在放疗后三周被放疗调节，甲基化模式改变恢复正常，并恢复了纤维化相关基因CAMK2β的正常表达。BMX-001还降低了辐射诱导的DNA加合物8-羟基-2 ' -脱氧鸟苷（8-OHdG），这是已知的干扰甲基化的物质。在DNA氧化和甲基化的寡核苷酸模型中，BMX-001能够防止DNA氧化并恢复正常的甲基化模式。本研究揭示了药物逆转盆腔放疗纤维化的可行性，并提示BMX-001在放疗后给予可能有效。

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引用次数: 0

Intercellular mitochondrial transfer rewires redox signaling and metabolic plasticity: mechanisms, disease relevance and therapeutic frontiers 细胞间线粒体转移重新连接氧化还原信号和代谢可塑性：机制，疾病相关性和治疗前沿

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-09 DOI: 10.1016/j.redox.2026.104019

Jiahui Wang , Rongqing Li , Li Qian

Intercellular mitochondrial transfer is recognized as a central mechanism that shapes redox homeostasis, metabolic plasticity, and cellular resilience across multiple tissues. Through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junction channels (GJCs), and cell fusion, mitochondria move between donor and recipient cells to restore bioenergetic capacity, buffer oxidative stress, and tune redox-sensitive signaling networks. Recent work has begun to clarify the regulatory framework governing donor-recipient specificity, cargo selection, and the stress-activated cues that trigger organelle exchange. Mitochondrial transfer also exerts distinct, context-dependent influences on disease trajectories. It mitigates injury in neurological damage, ischemia-reperfusion conditions, immune dysfunction, aging, and inflammatory pain, largely by reprogramming mitochondrial function and reactive oxygen species (ROS) dynamics. Conversely, in cancer, mitochondrial acquisition enhances metabolic flexibility, invasiveness, and resistance to therapy. Current therapeutic approaches, including mitochondrial transplantation, EV-based delivery systems, and mitochondria-enhanced immune cells, highlight the translational potential of manipulating mitochondrial exchange, yet face challenges such as mitochondrial fragility, inefficient targeting, and immunogenicity. Deeper mechanistic insight into how mitochondrial transfer remodels redox signaling and metabolic adaptation will be essential for converting this biological process into next-generation organelle-level interventions for redox-driven disorders.

细胞间线粒体转移被认为是形成多组织氧化还原稳态、代谢可塑性和细胞弹性的中心机制。通过隧道纳米管（TNTs）、细胞外囊泡（ev）、间隙连接通道（GJCs）和细胞融合，线粒体在供体和受体细胞之间移动，以恢复生物能量能力，缓冲氧化应激，并调节氧化还原敏感信号网络。最近的工作已经开始阐明控制供体-受体特异性、货物选择和触发细胞器交换的应激激活线索的监管框架。线粒体转移也对疾病轨迹产生独特的、依赖于环境的影响。它主要通过重编程线粒体功能和活性氧（ROS）动力学来减轻神经损伤、缺血再灌注条件、免疫功能障碍、衰老和炎症性疼痛等损伤。相反，在癌症中，线粒体获得增强了代谢灵活性、侵袭性和对治疗的抵抗力。目前的治疗方法，包括线粒体移植、基于ev的输送系统和线粒体增强免疫细胞，强调了操纵线粒体交换的翻译潜力，但面临着线粒体脆弱性、低效靶向和免疫原性等挑战。深入了解线粒体转移如何重塑氧化还原信号和代谢适应的机制，对于将这一生物过程转化为下一代氧化还原驱动疾病的细胞器水平干预至关重要。

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引用次数: 0

Fibroblast circSamd4 promotes cardiac fibrosis via activating plasminogen activator inhibitor-1 成纤维细胞circSamd4通过激活纤溶酶原激活物抑制剂-1促进心脏纤维化。

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-09 DOI: 10.1016/j.redox.2026.104018

Yan Chen , Zhewei Zhang , Yue Cheng , Xiaofeng Chen , Junteng Zhou , Zisong Wei , Han Yao , Shuwen Zhang , Qihang Kong , Hao Tang , Wenchao Wu , Zhichao Zhou , Xiaoqiang Tang , Xiaojing Liu

Cardiac fibrosis remains an unresolved clinical issue in patients with heart diseases. CircRNAs have emerged as potential targets for treatment of heart diseases. Exploring the functional circRNAs in fibroblast activation is one of the ways to develop innovative drugs for the treatment of cardiac fibrosis. This study aimed to screen for fibroblast-related circRNAs in cardiac fibrosis and elucidate their roles and underlying mechanisms. By screening for fibrosis-responsible circular RNAs (circRNAs), we identified a highly conserved circRNA, circular RNA Sterile alpha motif domain containing 4 (circSamd4), that drives cardiac fibrosis. circSamd4 is prominently expressed in cardiac fibroblasts (CFs) and is upregulated in the fibrotic hearts of humans and mice. Fibroblast-specific silencing of circSamd4 reduced cardiac fibroblast activation and alleviates cardiac fibrosis. Conversely, overexpression of circSamd4 in fibroblasts exacerbates cardiac fibrosis and rescues cardiac function. Bioinformatics and functional analyses revealed that circSamd4 regulates the plasminogen activation. Plasminogen activator inhibitor-1 (PAI-1, encoded by Serpine1) is a key effector of plasminogen activation and redox homeostasis and contributes to fibrotic diseases. Here, PAI-1 serves as a leading functional downstream factor of circSamd4 because PAI-1 is highly expressed in cardiac fibroblasts and contributes to circSamd4 functions in regulating fibroblast activation and cardiac fibrosis. Mechanistically, circSamd4 functions as a sponge for miR-1894-3p to trigger Serpine1 expression and subsequent fibroblast activation, and cardiac fibrosis. Therefore, we identified a fibroblast-specific circSamd4-miR-1894-3p-Serpine1 axis driving fibroblast activation and cardiac fibrosis. Adeno-associated virus (AAV)-mediated knockdown of circSamd4 or Serpine1 alleviated cardiac fibrosis and cardiac dysfunction. These findings suggest that circSamd4 and Serpine1 are promising therapeutic targets for inhibiting cardiac fibrosis.

心脏纤维化仍然是心脏病患者未解决的临床问题。circrna已成为治疗心脏病的潜在靶点。探索成纤维细胞活化中的环状rna功能是开发治疗心脏纤维化的创新药物的途径之一。本研究旨在筛选心脏纤维化中成纤维细胞相关的环状rna，并阐明其作用和潜在机制。通过筛选与纤维化相关的环状RNA (circRNAs)，我们发现了一种高度保守的环状RNA，即含有4的环状RNA不育α基序结构域（circSamd4），它驱动心脏纤维化。circSamd4在心脏成纤维细胞（CFs）中显著表达，在人和小鼠的纤维化心脏中表达上调。circSamd4的成纤维细胞特异性沉默减少了心脏成纤维细胞的激活并减轻了心脏纤维化。相反，成纤维细胞中circSamd4的过表达会加剧心脏纤维化并挽救心脏功能。生物信息学和功能分析显示circSamd4调控纤溶酶原的激活。纤溶酶原激活物抑制剂-1 （PAI-1，由丝氨酸蛋白酶1编码）是纤溶酶原激活和氧化还原稳态的关键效应物，并参与纤维化疾病。在这里，PAI-1作为circSamd4的主要功能下游因子，因为PAI-1在心脏成纤维细胞中高表达，并有助于circSamd4调节成纤维细胞活化和心脏纤维化的功能。在机制上，circSamd4作为miR-1894-3p的海绵，触发Serpine1表达和随后的成纤维细胞激活，以及心脏纤维化。因此，我们确定了成纤维细胞特异性circSamd4-miR-1894-3p-Serpine1轴驱动成纤维细胞活化和心脏纤维化。腺相关病毒（AAV）介导的circSamd4或Serpine1基因敲低可减轻心脏纤维化和心功能障碍。这些发现表明circSamd4和Serpine1是抑制心脏纤维化的有希望的治疗靶点。

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引用次数: 0

Fructose-sweetened beverages induce diurnal redox dysregulation in pediatric MASLD 果糖甜饮料诱导儿童MASLD的每日氧化还原失调

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-08 DOI: 10.1016/j.redox.2026.104012

Helaina E. Huneault , Scott E. Gillespie , Zachery R. Jarrell , Shasha Bai , Ana Ramirez Tovar , Cristian Sanchez-Torres , Lucia A. Gonzalez-Ramirez , Kelsey C. Chatman , Thomas R. Ziegler , Dean P. Jones , Jean A. Welsh , Miriam B. Vos

Background

Plasma glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox couples undergo diurnal variation in adults and are more oxidized in obesity-related conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). There is limited research on redox in children and no data on redox responses to sugars, despite high sugar consumption in this population. This study aimed to describe the diurnal variation of redox couples in children, assess the impact of MASLD, and evaluate responses to fructose versus glucose beverages.

Methods

In a 2-day randomized, controlled, crossover feeding study, 26 children (12 with MASLD, 14 controls; aged 10–18 years) consumed isocaloric meals with fructose beverages (FB) on one day and glucose beverages (GB) (set as control) on another, following a washout period. Blood was collected every 2 h over 24 h and analyzed for Cys/CySS and GSH/GSSG. Redox potentials, E_h(Cys/CySS) and E_h(GSH/GSSG), were calculated using the Nernst equation. Linear mixed models assessed diurnal variation and effects of MASLD and beverage type.

Results

Plasma E_h(GSH/GSSG) and E_h(CyS/CySS) varied significantly over time after both FB and GB (p < 0.05). With FB, E_h(GSH/GSSG) was significantly more oxidized in children with MASLD (p = 0.034); this was not observed with GB. Among children with MASLD, FB also led to greater E_h(GSH/GSSG) oxidation and lower GSH levels overnight (p < 0.05). While E_h(Cys/CySS) showed a similar trend, differences did not reach statistical significance.

Conclusions

Our findings demonstrate that plasma redox states vary diurnally in children and are more oxidized in those with MASLD. Fructose intake increased oxidation of the GSH/GSSG redox couple and lowered GSH concentrations overnight, indicating heightened oxidative stress. These results identify fructose as a driver of redox imbalance in pediatric MASLD and support fructose reduction and glutathione restoration as therapeutic targets.

血浆谷胱甘肽/谷胱甘肽二硫（GSH/GSSG）和半胱氨酸/胱氨酸（Cys/CySS）氧化还原对在成人中发生昼夜变化，并且在肥胖相关疾病（包括代谢功能障碍相关的脂肪变性肝病（MASLD））中更容易氧化。关于儿童氧化还原的研究有限，没有关于糖对氧化还原反应的数据，尽管这一人群的糖摄入量很高。本研究旨在描述儿童氧化还原对的日变化，评估MASLD的影响，并评估对果糖和葡萄糖饮料的反应。

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引用次数: 0

Zinc overload disrupts SoxR [2Fe–2S] clusters to drive redox-metallic crosstalk via SoxS-ZnuACB in Escherichia coli 在大肠杆菌中，锌超载破坏SoxR [2Fe-2S]簇，通过SoxS-ZnuACB驱动氧化还原-金属串扰

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-08 DOI: 10.1016/j.redox.2026.104013

Jie Feng, Feng Liang, Yongguang Zhou, Shihao Wen, Yue Chen, Binjie Ge, Wenjing Zhang, Jie Wang, Runyu Chen, Yin Zhang, Jianghui Li, Wu Wang, Guoqiang Tan

Here, we demonstrate that excess zinc disrupts bacterial redox sensing by specifically disassembling the [2Fe–2S] cluster of SoxR – a master oxidative stress sensor in Escherichia coli. This impairment couples zinc overload to dysregulated oxidative defense, revealing a previously unrecognized metal-redox crosstalk mechanism. Using electron paramagnetic resonance (EPR) and UV–visible spectroscopy, we demonstrated that excess zinc specifically disrupts the assembly of the [2Fe–2S] cluster in redox-sensitive SoxR. Additionally, we assessed the expression levels of genes within this pathway using quantitative real-time PCR (qPCR) and quantified intracellular zinc and iron levels by inductively coupled plasma mass spectrometry (ICP-MS) to evaluate the roles of SoxS and the zinc uptake transporter ZnuACB in maintaining zinc homeostasis. Furthermore, we investigated the roles of SoxR, SoxS, and ZnuACB in bacterial zinc homeostasis through plate growth assays and gene knockout experiments. We establish that zinc excess disassembles SoxR [2Fe–2S] clusters as a molecular switch that dysregulates the SoxS-ZnuACB/SOD axis, converting zinc toxicity into oxidative vulnerability. This mechanistic insight exposes a bacterial Achilles' heel: targeting Fe–S cluster integrity disrupts redox-metal homeostasis, providing a strategy to combat antibiotic-resistant pathogens.

在这里，我们证明了过量的锌通过特异性地分解SoxR的[2Fe-2S]簇来破坏细菌的氧化还原感应，SoxR是大肠杆菌中的一种主氧化应激传感器。这种损伤将锌超载与氧化防御失调结合在一起，揭示了一种以前未被认识到的金属-氧化还原串扰机制。利用电子顺磁共振（EPR）和紫外可见光谱，我们证明了过量的锌特异性地破坏了氧化还原敏感的SoxR中[2Fe-2S]簇的组装。此外，我们利用实时荧光定量PCR （qPCR）和电感耦合等离子体质谱（ICP-MS）定量细胞内锌和铁水平来评估SoxS和锌摄取转运蛋白ZnuACB在维持锌稳态中的作用。此外，我们通过平板生长试验和基因敲除实验研究了SoxR、SoxS和ZnuACB在细菌锌稳态中的作用。我们发现过量的锌会破坏SoxR [2Fe-2S]簇，作为一个分子开关，失调SoxS-ZnuACB/SOD轴，将锌毒性转化为氧化易损。这种机制揭示了细菌的阿喀琉斯之踵：靶向Fe-S簇完整性破坏氧化还原金属稳态，提供了一种对抗抗生素抗性病原体的策略。

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引用次数: 0

Redox-sensitive N6-methyladenosine RNA epitranscriptomic mechanisms in environmental stress and hazard 环境胁迫和危害中的氧化还原敏感n6 -甲基腺苷RNA表转录组学机制

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-07 DOI: 10.1016/j.redox.2026.104017

Yán Wāng

Oxidative stress is a central driver of environmental stress responses and disease pathogenesis. Increasing evidence indicates that RNA epigenetic regulation, particularly N⁶-methyladenosine (m⁶A) modification, represents a critical interface linking redox imbalance to cellular dysfunction. Arsenic, a prototypical redox-active toxicant, provides a robust model for understanding how environmental oxidative stress disrupts m⁶A-mediated post-transcriptional control. Recent studies demonstrate that arsenic-induced redox perturbation reshapes the expression and activity of m⁶A writers (METTL3/METTL14), erasers (FTO/ALKBH5), and readers (YTHDF/YTHDC families), leading to widespread alterations in mRNA stability, translation, and metabolic reprogramming. Mechanistic findings from cellular and animal models implicate m⁶A-dependent pathways in modulating oxidative stress responses, mitochondrial function, inflammation, and senescence—biological processes fundamental to redox biology. These insights reveal that m⁶A is not merely a downstream marker of stress, but an active mediator of adaptive and maladaptive responses to redox disruption. Despite significant progress, population-level evidence and high-resolution mapping of RNA modifications under oxidative conditions remain limited. Future work integrating advanced epitranscriptomic profiling, multi-omics approaches, and exploration of additional RNA modifications (m⁷G, m¹A, m⁵C) will be essential for defining how redox-sensitive RNA regulation shapes disease risk. Collectively, this review highlights m⁶A modification as a dynamic regulatory node connecting environmental redox stress to gene expression control, providing new mechanistic insight and potential targets for intervention in redox-related diseases.

氧化应激是环境应激反应和疾病发病机制的核心驱动因素。越来越多的证据表明，RNA表观遗传调控，特别是n6 -甲基腺苷（m6A）修饰，是连接氧化还原失衡和细胞功能障碍的关键界面。砷是一种典型的氧化活性毒物，为理解环境氧化应激如何破坏m6a介导的转录后控制提供了一个强大的模型。最近的研究表明，砷诱导的氧化还原扰动重塑了m6A写子（METTL3/METTL14）、擦子（FTO/ALKBH5）和读子（YTHDF/YTHDC家族）的表达和活性，导致mRNA稳定性、翻译和代谢重编程的广泛改变。来自细胞和动物模型的机制发现暗示m6a依赖通路在调节氧化应激反应、线粒体功能、炎症和衰老——氧化还原生物学基础的生物学过程中起着重要作用。这些见解揭示了m6A不仅是应激的下游标记，而且是氧化还原破坏的适应性和非适应性反应的积极介质。尽管取得了重大进展，但群体水平的证据和氧化条件下RNA修饰的高分辨率制图仍然有限。未来的工作将整合先进的表转录组学分析、多组学方法和探索额外的RNA修饰（m7G、m1A、m5C），这对于确定氧化还原敏感的RNA调控如何影响疾病风险至关重要。总之，本综述强调m6A修饰是连接环境氧化还原应激与基因表达控制的动态调控节点，为氧化还原相关疾病的干预提供了新的机制见解和潜在靶点。

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引用次数: 0

Atypical thioredoxin Patrx2 enhances alginate production in mucoid Pseudomonas aeruginosa 非典型硫氧还蛋白Patrx2增强粘液样铜绿假单胞菌海藻酸盐的产生

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-06 DOI: 10.1016/j.redox.2026.104010

Marie M. Grandjean, James N. Sturgis, Edwige B. Garcin, Moly Ba, Olivier Bornet, Christophe Bordi, Latifa Elantak, Corinne Sebban-Kreuzer

Pseudomonas aeruginosa, an opportunistic human pathogen, is known for its ability to respond and adapt to its environment, employing intricate adaptation mechanisms that can lead to the formation of complex biofilms. Redox processes play a pivotal role in bacterial adaptation mechanisms. The cytoplasm of most organisms is recognized for maintaining a reducing environment through thiol-disulfide oxidoreductases. In Pseudomonas aeruginosa, we have identified an unusual cytoplasmic thioredoxin named Patrx2. What sets Patrx2 apart is its active site, which contains a consensus sequence, CGHC, identical to the characteristic motif of protein disulfide isomerases (PDIs) found in eukaryotic cells. Our investigations have unveiled that Patrx2, unlike canonical thioredoxins, exhibits disulfide isomerase activity in vitro and displays physicochemical properties, as well as a structural conformation of its catalytic site, reminiscent of PDIs. Using a mutant transposon library, we found that the expression of patrx2 is regulated by the alternative sigma factor AlgU, which is implicated in the formation of alginate biofilms in P. aeruginosa. We further demonstrated strong patrx2 expression in a mucoid strain we constructed, carrying the clinically relevant mucA22 mutation frequently found in cystic fibrosis patients. Furthermore, our results showed a significant decrease in alginate synthesis in a patrx2 mutant in this mucoid strain, this effect was also observed in the C34S catalytic variant, suggesting a role for Patrx2's catalytic site in this phenotype. The study of Patrx2, an atypical thioredoxin expressed within an alginate biofilm, underscores the importance of redox regulation in adaptation mechanisms. The induction of Patrx2's expression in alginate-producing biofilms highlights its potential relevance in redox-regulated adaptation mechanisms.

铜绿假单胞菌是一种机会性人类病原体，以其对环境的反应和适应能力而闻名，采用复杂的适应机制，可导致复杂生物膜的形成。氧化还原过程在细菌适应机制中起着关键作用。大多数生物体的细胞质被认为是通过巯基二硫氧化还原酶维持还原环境的。在铜绿假单胞菌中，我们发现了一种不寻常的细胞质硫氧还蛋白，命名为Patrx2。使Patrx2与众不同的是它的活性位点，它包含一个共识序列，CGHC，与真核细胞中发现的蛋白二硫异构酶（pdi）的特征基序相同。我们的研究发现，与典型硫氧还毒素不同，Patrx2在体外表现出二硫异构酶活性，并表现出物理化学性质，以及其催化位点的结构构象，使人想起pdi。利用突变转座子文库，我们发现patrx2的表达受备选sigma因子AlgU的调控，该因子与P. aeruginosa藻酸盐生物膜的形成有关。我们进一步在构建的粘液样菌株中证实了patrx2的强表达，该菌株携带囊性纤维化患者中常见的临床相关mucA22突变。此外，我们的研究结果显示，在这种粘液样菌株中，patrx2突变体的海藻酸盐合成显著减少，在C34S催化突变体中也观察到这种影响，这表明patrx2的催化位点在这种表型中发挥了作用。在藻酸盐生物膜中表达的非典型硫氧还蛋白Patrx2的研究强调了氧化还原调控在适应机制中的重要性。诱导Patrx2在海藻酸生成生物膜中的表达，突出了其在氧化还原调节的适应机制中的潜在相关性。

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引用次数: 0

Ferrostatin-1 protects against early sepsis-induced acute lung injury by suppressing lipid peroxidation–driven NINJ1-mediated DAMP release and neutrophil activation 铁抑素-1通过抑制脂质过氧化驱动的ninj1介导的DAMP释放和中性粒细胞激活，保护早期脓毒症诱导的急性肺损伤

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-06 DOI: 10.1016/j.redox.2026.104004

Fang Xiao , Donghua Li , Miao Yu , Yunfeng Zhu , Guorong Huang , Zhilei Huang , Yufang Wang , Jialin Li , Dongmei Zhong , Huan Ma , Kunyu Liao , Yongshan Liu , Yalin Zhang , Xiangdong Guan , Changjie Cai , Jing Tang , Tianqin Peng , Fu-Li Xiang , Jie Xu

Sepsis-induced acute lung injury (ALI) is a critical condition driven by neutrophil-dominated inflammation, lytic cell death and the subsequent DAMP release, etc. We tested whether the radical-trapping antioxidant Ferrostatin-1 (Fer-1) interrupts lipid peroxidation induced DAMP release and limits early lung injury in sepsis. We found that Fer-1 improved survival, preserved alveolar architecture, reduced lung-injury scores, and suppressed pulmonary inflammatory cytokine expression in a murine cecal ligation and puncture (CLP) model. Lung tissue RNA-sequencing showed that Fer-1 attenuated the CLP-induced inflammatory and chemotaxis transcriptome and significantly reduced neutrophil infiltration. In vitro, Fer-1 protected cells from lipid peroxidation–induced lytic death and impaired the release of large DAMPs associated with NINJ1 pathway, indicated Fer-1 acts upstream of NINJ1 to preserve membrane integrity. Fer-1 also directly lowered lipid peroxidation and reduced lipopolysaccharide (LPS)–induced IL-1β and IL-6 transcription and secretion in neutrophils, an effect reversed by pharmacological JNK/p38 activation. Together, our results indicate that Fer-1 functions as a dual-action modulator that prevents DAMP release and blunts neutrophil-driven inflammation escalation, thereby interrupting the lipid peroxidation–NINJ1–DAMP release axis, and mitigating early septic ALI.

脓毒症引起的急性肺损伤（acute lung injury， ALI）是一种由中性粒细胞为主的炎症、溶解性细胞死亡及随后的DAMP释放等因素驱动的危重疾病。我们测试了自由基捕获抗氧化剂铁他汀-1 （ferr -1）是否阻断脂质过氧化诱导的DAMP释放并限制败血症的早期肺损伤。我们发现，在小鼠盲肠结扎和穿刺（CLP）模型中，fe -1提高了生存率，保留了肺泡结构，降低了肺损伤评分，并抑制了肺部炎症细胞因子的表达。肺组织rna测序显示，fe -1可减弱clp诱导的炎症和趋化转录组，并显著减少中性粒细胞浸润。在体外，fer1保护细胞免受脂质过氧化诱导的溶解性死亡，并破坏与NINJ1途径相关的大DAMPs的释放，表明fer1在NINJ1上游作用，以保持膜的完整性。fer1还直接降低脂质过氧化和脂多糖（LPS）诱导的中性粒细胞中IL-1β和IL-6的转录和分泌，这一作用被JNK/p38药理激活逆转。总之，我们的研究结果表明，fer1作为一种双作用调节剂，可以阻止DAMP释放并减弱中性粒细胞驱动的炎症升级，从而中断脂质过氧化- ninj1 - DAMP释放轴，减轻早期脓毒性ALI。

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引用次数: 0

Prenylterphenyllin, a regulator of P53, inhibits colorectal cancer progression through oxidative stress and energy metabolism pathway Prenylterphenyllin是P53的调节因子，通过氧化应激和能量代谢途径抑制结直肠癌的进展

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-06 DOI: 10.1016/j.redox.2025.103993

Yuhan Zhang , Yueqing Han , Songmao Li , Ruimin Shan , Ling Lin , Zhengyu Gu , Ruiyu wang , Yun Chen , Jiao Xiao , Fangmei An , Chupeng Hu , Chunyan He

Colorectal cancer (CRC) is one of the most prevalent and deadly cancers globally, with poor prognosis primarily due to metastasis and resistance to conventional therapies. This study evaluated the antitumor potential of prenylterphenyllin, a natural product derived from Aspergillus candidus. Prenylterphenyllin significantly reduced CRC cells viability and migration, while promoting apoptosis and cell-cycle arrest. Transcriptomic analysis showed activation of the p53 signaling pathway and inhibition of cell-cycle-related genes. Prenylterphenyllin also disrupted mitochondrial function and oxidative phosphorylation, increasing oxidative stress. In vivo, it suppressed tumor growth and lung metastasis without notable toxicity. These results highlight that prenylterphenyllin is a promising candidate for CRC therapy, capable of inhibiting tumor growth, migration, and metastasis while inducing apoptosis through the modulation of energy metabolism and oxidative stress. As a promising candidate, prenylterphenyllin may offer new therapeutic opportunities for CRC, particularly for metastatic disease. Collectively, this study identifies prenylterphenyllin as a novel therapeutic candidate for CRC and illuminates its promising therapeutic potential.

结直肠癌（CRC）是全球最常见和最致命的癌症之一，预后差主要是由于转移和对常规治疗的耐药性。本研究评估了从假丝曲霉中提取的天然产物丙烯基terphenyllin的抗肿瘤潜能。Prenylterphenyllin显著降低CRC细胞活力和迁移，同时促进细胞凋亡和细胞周期阻滞。转录组学分析显示p53信号通路的激活和细胞周期相关基因的抑制。Prenylterphenyllin还破坏线粒体功能和氧化磷酸化，增加氧化应激。在体内，它抑制肿瘤生长和肺转移，无明显毒性。这些结果表明，prenylterphenyllin是CRC治疗的一个有希望的候选药物，能够抑制肿瘤的生长、迁移和转移，同时通过调节能量代谢和氧化应激诱导细胞凋亡。作为一种有希望的候选药物，丙烯基terphenyllin可能为CRC，特别是转移性疾病提供新的治疗机会。总的来说，本研究确定了戊烯基terphenyllin作为CRC的一种新的治疗候选者，并阐明了其有希望的治疗潜力。

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引用次数: 0