Redox Report最新文献_第2页

Elucidating the protective role of quercetin against lipopolysaccharide-induced necroptosis in broiler thymus: insights from Nrf2/PERK signaling based on network pharmacology and experimental validation. 阐明槲皮素对脂多糖诱导的肉鸡胸腺坏死的保护作用：基于网络药理学和实验验证的Nrf2/PERK信号的见解

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-31 Epub Date: 2026-04-27 DOI: 10.1080/13510002.2026.2663621

Yu Xia, Ruirui Xie, Xinyu Huo, Kai Chen, Shiping Li, Shiwen Xu, Shu Li

{"title":"Elucidating the protective role of quercetin against lipopolysaccharide-induced necroptosis in broiler thymus: insights from Nrf2/PERK signaling based on network pharmacology and experimental validation.","authors":"Yu Xia, Ruirui Xie, Xinyu Huo, Kai Chen, Shiping Li, Shiwen Xu, Shu Li","doi":"10.1080/13510002.2026.2663621","DOIUrl":"10.1080/13510002.2026.2663621","url":null,"abstract":"Objectives: Quercetin (QUE) possesses antioxidant, anti-inflammatory, and immunomodulatory functions. Nuclear factor erythroid 2-related factor 2 (Nrf2) can initiate protein kinase RNA-like ER kinase (PERK), leading to immune dysfunction and necroptosis. Our findings elucidate the therapeutic potential of QUE in attenuating LPS-induced injury in immune tissues.Methods: Broilers and MSB-1 cells were treated with LPS or/and QUE. We also treated MSB-1 cells with an Nrf2 inhibitor (ML385), a PERK activator (MK-28), and a necroptosis inhibitor (NSA) to further explore the detailed mechanism. In addition, we further conducted network pharmacology and bioinformatics to analyze the regulatory relationship between QUE and genes.Results: Combined analysis of network pharmacology and bioinformatics uncovered QUE regulates Nrf2 activation and its crosstalk with PERK signaling, influencing calcium homeostasis, necroptosis, and inflammation. Based on experimental validation, our findings demonstrated QUE treatment reduced LPS-induced imbalance in redox homeostasis through Nrf2 signaling pathway. QUE treatment downregulated the expression of cytokines linked to ERS, necroptosis, and inflammation. In addition, QUE treatment protected against LPS-induced immune function disorders.Conclusion: QUE treatment efficiently attenuated thymus immune disorders and necroptosis in broilers through Nrf2/PERK signaling. This investigation enriches biological function of QUE, providing a solid foundation for developing its potential application.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2663621"},"PeriodicalIF":7.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macrophage metabolic reprogramming via HIF-1α-glycolysis drives osteoblast ferroptosis and bone loss through an IL-6-STAT3-dependent redox axis. 通过hif -1α-糖酵解的巨噬细胞代谢重编程通过il -6- stat3依赖的氧化还原轴驱动成骨细胞铁凋亡和骨丢失。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-31 Epub Date: 2026-05-03 DOI: 10.1080/13510002.2026.2667673

Yifan Gu, Kun Wang, Yicong Wang, Ziru Wang, Yiheng Li, Lei Li, Shuai Jiang, Yu Zheng, Run Feng, Min Yang

{"title":"Macrophage metabolic reprogramming via HIF-1α-glycolysis drives osteoblast ferroptosis and bone loss through an IL-6-STAT3-dependent redox axis.","authors":"Yifan Gu, Kun Wang, Yicong Wang, Ziru Wang, Yiheng Li, Lei Li, Shuai Jiang, Yu Zheng, Run Feng, Min Yang","doi":"10.1080/13510002.2026.2667673","DOIUrl":"10.1080/13510002.2026.2667673","url":null,"abstract":"Background: Postmenopausal osteoporosis (PMOP) is characterized by exacerbated bone resorption and inadequate bone formation, with macrophage-driven inflammation playing a key role. However, how immunometabolic reprogramming of macrophages modulates osteoblast fate remains unknown.Methods: Using integrated single-cell and bulk transcriptomics, we identified a hypermetabolic macrophage subpopulation in PMOP marrow reliant on HIF-1α-glycolysis. We pharmacologically disrupted this axis with the HDAC inhibitor valproic acid (VPA) and validated its function using the HIF-1α stabilizer DMOG. The paracrine effects on osteoblasts were assessed via conditioned medium, focusing on ferroptosis and differentiation. Therapeutic efficacy was tested in ovariectomized rats.Results: VPA upregulated HIF1AN, enhancing its binding to HIF-1α and promoting its degradation. This suppressed glycolytic flux and M1 polarization, reducing IL-6 secretion. The altered secretome protected osteoblasts from ferroptosis by inhibiting the IL-6/p-STAT3/HIF-1α/TFRC axis and rebalancing GPX4/ACSL4. Osteogenic differentiation was restored. In OVX rats, VPA improved bone mass and microstructure, effects abolished by DMOG.Conclusion: We unveil a macrophage-centric immunometabolic checkpoint that is linked to osteoblast ferroptosis via IL-6/STAT3 signaling. Targeting this HIF-1α-glycolysis axis, exemplified by VPA, represents a novel therapeutic strategy for PMOP.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2667673"},"PeriodicalIF":7.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ligustroflavone alleviates chronic kidney disease by inhibiting ferroptosis through the GSK3β/NRF2 signaling pathway. 川芎酮通过GSK3β/NRF2信号通路抑制铁下垂，减轻慢性肾脏疾病。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-02-25 DOI: 10.1080/13510002.2026.2636421

Wen Zhang, Shaofan Wang, Yaru Wang, Sutianyi Li, Mingyue Chen, Jiayu Song, Yunwen Yang

{"title":"Ligustroflavone alleviates chronic kidney disease by inhibiting ferroptosis through the GSK3β/NRF2 signaling pathway.","authors":"Wen Zhang, Shaofan Wang, Yaru Wang, Sutianyi Li, Mingyue Chen, Jiayu Song, Yunwen Yang","doi":"10.1080/13510002.2026.2636421","DOIUrl":"10.1080/13510002.2026.2636421","url":null,"abstract":"Objectives: Chronic kidney disease (CKD) is a global public health concern, characterized by a gradual decline in kidney function, with death of renal tubular epithelial cells (RTECs) as a key pathological mechanism. This study investigated the protective effect of ligustroflavone in CKD and its potential molecular mechanisms.Methods: In vivo, the unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN) mouse models were employed to assess the effects of ligustroflavone. In vitro, RTECs were treated with erastin. Western blotting, qRT-PCR, immunofluorescence (IF), and immunohistochemistry (IHC) were performed to detect renal tubular injury both in vivo and in vitro.Results: In vivo, ligustroflavone treatment significantly improved renal tubular damage and interstitial fibrosis in mice. Furthermore, our results demonstrated that ligustroflavone alleviated ferroptosis of RTECs by inhibiting GSK3β activity and reducing lipid peroxidation in mice. In vitro, ligustroflavone treatment inhibited erastin-induced ferroptosis in RTECs. In addition, ligustroflavone inhibited activation of myofibroblasts induced by ferroptosis of RTECs. Mechanistically, ligustroflavone exerted it's protect effects through the GSK3β/NRF2 pathway by inhibiting GSK3β and activating NRF2, thereby promoting GPX4 expression and suppressing ferroptosis.Conclusions: In summary, ligustroflavone inhibits ferroptosis in RTECs and confers protection in CKD. These findings suggest that ligustroflavone holds promise as a potential therapeutic agent for CKD.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2636421"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12943817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The hippo-YAP1/TEAD1-SLC7A5 axis: uncovering a novel therapeutic target for oxalate-induced renal tubular ferroptosis. 海马- yap1 /TEAD1-SLC7A5轴：揭示草酸盐诱导肾小管铁下垂的新治疗靶点

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-03-15 DOI: 10.1080/13510002.2026.2643967

Junyi Yang, Zhilong Ma, Wenlong Wan, Dongfeng Yuan, Jiabo Li, Yongqi Wang, Baokang Wang, Guoruiyu Lyu, Yang Xun, Xiao Yu

{"title":"The hippo-YAP1/TEAD1-SLC7A5 axis: uncovering a novel therapeutic target for oxalate-induced renal tubular ferroptosis.","authors":"Junyi Yang, Zhilong Ma, Wenlong Wan, Dongfeng Yuan, Jiabo Li, Yongqi Wang, Baokang Wang, Guoruiyu Lyu, Yang Xun, Xiao Yu","doi":"10.1080/13510002.2026.2643967","DOIUrl":"10.1080/13510002.2026.2643967","url":null,"abstract":"Objectives: To systematically investigate the regulatory mechanisms of ferroptosis in renal tubular epithelial cells under high oxalate stress, focusing on identifying key upstream signaling pathways and their therapeutic potential.Methods: We employed HK-2 cell cultures and Glyoxylate-induced mouse models of oxalate nephropathy. Multi-omics approaches including 4D-label-free proteomics, RNA-sequencing, and CUT&Tag were integrated to identify regulatory networks. Functional validation utilized genetic manipulation, pharmacological intervention, chromatin immunoprecipitation, and dual-luciferase reporter assays.Results: High oxalate dose-dependently induced renal tubular ferroptosis and activated the Hippo pathway, leading to YAP1 phosphorylation and inactivation. Proteomic and multi-omics analyses identified YAP1 as a key regulator and SLC7A5 as its direct transcriptional target via TEAD1. High oxalate disrupted YAP1/TEAD1 binding to the SLC7A5 promoter, downregulating SLC7A5. Functional rescue confirmed that SLC7A5 loss mediated ferroptosis under YAP1 inhibition. Mechanistically, SLC7A5 downregulation restricted leucine availability and suppressed mTOR signaling, while leucine supplementation or mTOR reactivation reversed ferroptosis, demonstrating that SLC7A5 regulates ferroptosis via the leucine/mTOR axis.Conclusion: We establish the Hippo-YAP1/TEAD1-SLC7A5 axis as a master regulatory pathway controlling oxalate-induced ferroptosis. This pathway represents a promising therapeutic target for oxalate nephropathy and provides fundamental insights into stress-responsive ferroptosis regulation in kidney disease.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2643967"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased levels of systemic iron content in adult-onset interleukin-6 knockout mice. 白细胞介素-6基因敲除小鼠成年发病时全身铁含量水平升高。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2025-12-16 DOI: 10.1080/13510002.2025.2602306

Fali Zhang, Cuizhen Zhang, Qianqian Luo, Jia Li, Xiaoyan Qiu, Zhongming Qian

{"title":"Increased levels of systemic iron content in adult-onset interleukin-6 knockout mice.","authors":"Fali Zhang, Cuizhen Zhang, Qianqian Luo, Jia Li, Xiaoyan Qiu, Zhongming Qian","doi":"10.1080/13510002.2025.2602306","DOIUrl":"10.1080/13510002.2025.2602306","url":null,"abstract":"Background: Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in multiple metabolic disorders. IL-6 is well recognized to induce hepcidin expression and decreased serum iron through the JAK2/STAT3 pathway under inflammatory conditions. Targeted inhibition of IL-6 represents a potential therapeutic regimen for multiple diseases. The current study aimed to explore the physiological concentration of IL-6 in sustaining systemic iron homeostasis.Methods: IL-6-knockout mice (IL-6-/-) were established in the current study. Western blot measured the expression of key iron-related proteins in liver, kidney, spleen and duodenum, as well as hepatic hepcidin mRNA expression. Serum iron and hematologic parameters were detected. ELISA and Masson's trichrome staining were performed to detect renal TGF-β1 expression and collagen deposition. Furthermore, bone marrow-derived and peritoneal macrophages were prepared to identify the iron recycling.Results: Serum iron and tissue iron content were markedly elevated in IL-6-/- mice. Mechanistically, decreased renal erythropoietin (EPO) synthesis contributed to iron utilization, macrophage-mediated recycling of iron was markedly reduced, thereby resulting in systemic iron accumulation. However, IL-6-/- mice displayed increased Hepcidin expression via p-ERK activation and a significant reduction in duodenal iron uptake.Conclusion: This study highlighted the critical role of IL-6 in iron homeostasis both in physiological and pathological situations.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2602306"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice. Nrf2去summoylation通过减轻小鼠心肌铁下垂减轻心肌缺血再灌注损伤（MIRI）。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-02-06 DOI: 10.1080/13510002.2026.2624946

Qinyun Shi, Weifeng Yao, Wenlong Zhang, Jiaqian Xu, Xiyu Wang, Xiangyun Wei, Shuming Hu, Qiuju Fan, Huan Yang, Xiaoling Wu, Rong Cai

{"title":"Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice.","authors":"Qinyun Shi, Weifeng Yao, Wenlong Zhang, Jiaqian Xu, Xiyu Wang, Xiangyun Wei, Shuming Hu, Qiuju Fan, Huan Yang, Xiaoling Wu, Rong Cai","doi":"10.1080/13510002.2026.2624946","DOIUrl":"10.1080/13510002.2026.2624946","url":null,"abstract":"Objectives: Reperfusion, an essential therapeutic strategy for salvaging ischemic myocardium in ischemic heart disease, paradoxically exacerbates myocardial injury. Ferroptosis is a pivotal mechanism underlying myocardial ischemia-reperfusion injury (MIRI). Nrf2 can regulate ferroptosis, which could undergo SUMOylation at lysine 110 (K110) and was subsequently de-SUMOylated by Senp1. This study aimed to determine whether Nrf2 de-SUMOylation could mitigate MIRI by inhibiting myocardial ferroptosis.Methods: Nrf2 K110R mice, mimicking Nrf2 de-SUMOylation, were generated. Mice cardiac morphology and function were observed by hematoxylin-eosin staining (HE) and echocardiography under normal and MIRI conditions. Ferroptosis inhibitor liproxstatin-1 (Lip-1) was used to demonstrate ferroptosis participation in Nrf2 de-SUMOylation regulated MIRI. In vitro, SUMO1/sentrin-specific protease 1 Senp1 KO H9C2 cells were subjected to RSL3-induced ferroptosis to explore underlying mechanism.Results: Nrf2 K110R mice showed normal cardiac morphology and function at baseline. However, de-SUMOylation of Nrf2 alleviated myocardial ferroptosis, resulting in a reduction of MIRI severity in MIRI mice. The administration of Lip-1 attenuated the differences in MIRI between Nrf2 wild-type and K110R mice. Mechanistically, Nrf2 de-SUMOylation was associated with a reduction in Transferrin receptor (Tfr) expression level, thereby mitigating ferroptosis in cardiomyocytes.Conclusion: This study highlighted the role of Nrf2 SUMOylation in promoting ferroptosis during MIRI and identified Nrf2 de-SUMOylation as a potential therapeutic target for MIRI.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2624946"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective role of fatty acid oxidation against epithelial barrier dysfunction in allergic asthma. 脂肪酸氧化对过敏性哮喘上皮屏障功能障碍的保护作用。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-01-19 DOI: 10.1080/13510002.2026.2613534

Muyun Wang, Yanan He, Haiyang Hu, Di Wu, Ximing Liao, Jing Gao, Shaoyong Gao, Huiming Yin, Kian Fan Chung, Qiang Li, Kun Wang, Wei Gao

{"title":"Protective role of fatty acid oxidation against epithelial barrier dysfunction in allergic asthma.","authors":"Muyun Wang, Yanan He, Haiyang Hu, Di Wu, Ximing Liao, Jing Gao, Shaoyong Gao, Huiming Yin, Kian Fan Chung, Qiang Li, Kun Wang, Wei Gao","doi":"10.1080/13510002.2026.2613534","DOIUrl":"10.1080/13510002.2026.2613534","url":null,"abstract":"Background: Fatty acid oxidation (FAO) is implicated in lung diseases, but its role in bronchial asthma is not fully understood. We investigated its effect on airway epithelial barrier integrity.Methods: Using a house dust mite (HDM)-induced murine asthma model and HDM, IL-4, IL-13, or TNF-α stimulated human primary bronchial epithelial cells (BECs) and bronchial epithelial (Beas-2b) cells, we modulated FAO with L-carnitine (agonist) and Etomoxir (inhibitor). BECs and Beas-2b cells were infected with lentivirus-mediated CPT1A shRNA prior to stimulation. Barrier function, mitochondrial oxidative stress, inflammation, and metabolism were assessed.Results: FAO level in lungs negatively correlated with increased inflammation and tissue injury in HDM-induced asthmatic mice (all p < 0.05), while positively regulating tight junction protein expression. In BECs and Beas-2b cells, Etomoxir treatment and CPT1A knockdown exacerbated the impairment of FAO caused by various stimulants (all p < 0.05). Furthermore, FAO negatively regulated HDM/cytokine-induced epithelial barrier damage, hyperactive inflammatory response, and mitochondrial dysfunction in Beas-2b cells (all p < 0.05). In contrast, treatment with L-carnitine significantly alleviated these pathophysiological features in both in vivo and in vitro models.Conclusion: FAO plays a protective role in the occurrence and development of asthma by maintaining airway epithelial cell homeostasis and barrier function.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2613534"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12821354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Urolithin A alleviates vascular remodeling through mitochondrial SIRT3-mediated SOD2 deacetylation and antioxidation in hypertensive rats. 尿素A通过线粒体sirt3介导的SOD2去乙酰化和抗氧化作用减轻高血压大鼠血管重构。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-02-06 DOI: 10.1080/13510002.2026.2622255

Min Dai, Yi-Ming Wang, Hong-Ke Dong, Xiao-Yu Xu, Jing-Xiao Wang, Guo-Qing Zhu, Fen Zheng

{"title":"Urolithin A alleviates vascular remodeling through mitochondrial SIRT3-mediated SOD2 deacetylation and antioxidation in hypertensive rats.","authors":"Min Dai, Yi-Ming Wang, Hong-Ke Dong, Xiao-Yu Xu, Jing-Xiao Wang, Guo-Qing Zhu, Fen Zheng","doi":"10.1080/13510002.2026.2622255","DOIUrl":"10.1080/13510002.2026.2622255","url":null,"abstract":"Objectives: Urolithin A (UA) is a natural polyphenolic compound produced by gut bacteria. Vascular remodeling contributes to hypertension, and vascular smooth muscle cells (VSMCs) proliferation and migration are important processes in vascular remodeling.Methods: VSMCs were obtained from the thoracic aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Intraperitoneal injections of UA (50 mg/kg, every 2 days for 4 weeks) were performed in SHR.Results: UA attenuated proliferation and migration, reduced mitochondrial reactive oxygen species (mitoROS) levels, and increased SOD2 activity in VSMCs of SHR, which were prevented by SOD2 knockdown. UA promoted mitochondrial short-length SIRT3 (SL-SIRT3) production and SOD2 deacetylation. SIRT3 inhibitor 3-TYP abolished the effects of UA on SOD2 deacetylation, mitoROS levels and VSMCs proliferation and migration. Repeated intraperitoneal injection of UA every 2 days for 4 weeks attenuated vascular remodeling and hypertension, increased SL-SIRT3 levels and SOD2 activity, and reduced SOD2 acetylation and mitoROS levels in aorta and mesenteric arteries of SHR.Conclusion: UA attenuates VSMCs proliferation and migration in SHR by increasing mitochondrial SL-SIRT3 level, and subsequent SOD2 deacetylation and mitoROS reduction in SHR. Long-term administration of UA attenuates vascular remodeling, hypertension and oxidative stress in SHR.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2622255"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tramadol induced hypoxia signaling and paraptosis-like cell death in breast cancer cells via HIF-1α and ATF4 dependent pathways. 曲马多通过HIF-1α和ATF4依赖途径诱导乳腺癌细胞缺氧信号和凋亡样细胞死亡。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-01-12 DOI: 10.1080/13510002.2025.2588866

Zih-Syuan Wu, Shih-Ming Huang, Yi-Hsuan Huang

{"title":"Tramadol induced hypoxia signaling and paraptosis-like cell death in breast cancer cells via HIF-1α and ATF4 dependent pathways.","authors":"Zih-Syuan Wu, Shih-Ming Huang, Yi-Hsuan Huang","doi":"10.1080/13510002.2025.2588866","DOIUrl":"10.1080/13510002.2025.2588866","url":null,"abstract":"Objectives: Tramadol, a clinically approved analgesic widely used for managing postoperative pain, has recently been shown to possess anticancer properties in several tumor models, especially in breast cancer. In this study, we explored the intricate molecular mechanisms by which tramadol induces cytotoxicity in breast cancer cell lines.Methods: Two invasive ductal carcinoma lines MCF-7 and MDA-MB-231 were used to verify the molecular cytotoxicity of tramadol using cell viability analysis, flow cytometry analysis, real-time polymerase chain reaction, western blotting, Seahorse biogenetic, and transmission electron microscopy analyses.Results: Our findings demonstrate that tramadol induces the normoxic stabilization and nuclear translocation of hypoxia-inducible factor- 1 alpha (HIF-1α) to activate hypoxia responsive genes. Concurrently, tramadol triggers endoplasmic reticulum (ER) stress and activates the p-eIF2α/ATF4/CHOP signaling axis, leading to the generation of reactive oxygen species, impaired autophagy, mitochondrial dysfunction, including mitochondrial membrane depolarization and the decline of ATP production, cytoplasmic vacuolization, and lipid droplet accumulation which is characteristics of paraptosis-like cell death. Notably, the knockout of HIF-1α or ATF4 significantly reduced tramadol-induced cytotoxicity, highlighting their crucial roles in mediating these cellular responses.Conclusion: Tramadol induced breast cancer cell death via paraptosis which highlights its therapeutic potential in targeting resistant cancer subtypes such as triple-negative breast cancer.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2588866"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12798667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prophylactic quercetin administration attenuates pulmonary fibrosis via ferroptosis-resistant priming of alveolar epithelial cells. 预防性给予槲皮素可通过肺泡上皮细胞抗铁致凋亡的启动来减轻肺纤维化。

IF 7.4 2区生物学

Redox Report Pub Date : 2026-12-01 Epub Date: 2026-02-16 DOI: 10.1080/13510002.2026.2632434

Yang Qiao, Xie Cheng, Zixin Luo, Weilu Huang, Zheng Zhang, Kangkang Ren, Xinping Xu, Huan He, Ming He, Lu Yin

{"title":"Prophylactic quercetin administration attenuates pulmonary fibrosis via ferroptosis-resistant priming of alveolar epithelial cells.","authors":"Yang Qiao, Xie Cheng, Zixin Luo, Weilu Huang, Zheng Zhang, Kangkang Ren, Xinping Xu, Huan He, Ming He, Lu Yin","doi":"10.1080/13510002.2026.2632434","DOIUrl":"10.1080/13510002.2026.2632434","url":null,"abstract":"Background: Idiopathic pulmonary fibrosis (IPF) carries high mortality and short survival, presenting significant clinical challenges. Current treatments primarily target to mitigate IPF progression, with insufficient focus on prevention.Methods: We established bleomycin (BLM)-induced IPF model in mice and alveolar epithelial cells. Quercetin (QUE) was administered under two mutually exclusive dosing windows: preventive (pre-BLM only) and therapeutic (post-BLM only).Results: Prophylactic QUE administration in mice prior to BLM challenge achieved fibrosis reduction comparable to post-injury treatment, while better mitigating peaks of epithelial damage, ferroptosis, and senescence. The preventive regimen also accelerated GSH and GPx4 recovery. Mechanistically, QUE triggers adaptive stress in healthy alveolar epithelial cells, evidenced by mild ROS elevation and oxidative stress response pathway activation. This adaptive stress minimally impacts cellular viability, proliferation, clonogenicity, apoptosis, or senescence in healthy cells. Instead, it primes 14-3-3γ-mediated phosphorylation to enhance NRF2 nuclear translocation, driving sustained elevation of GSH and GPx4 and conferring ferroptosis resistance, thereby limiting fibrogenesis. Crucially, co-administration of Mito-TEMPO or Z-VAD-FMK suppressed QUE-induced ROS but concurrently abolished prevention against BLM injury, confirming preconditioning via adaptive stress as the core mechanism.Conclusions: Our findings unveil QUE as a promising preventive agent against IPF, mediated through alveolar epithelial preconditioning to enhance ferroptosis resistance.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2632434"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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