Free Radical Biology and Medicine最新文献

{"title":"YY1 promotes diabetic vascular calcification via m⁶A-Binding protein HNRNPC.","authors":"Bo Yang, Xiang Mao, Liqun Ren, Lihua Li, Chen Shao, Xinyue Wang, Xinyang Shi, Suining Xu, Zhongqun Wang","doi":"10.1016/j.freeradbiomed.2026.05.316","DOIUrl":"10.1016/j.freeradbiomed.2026.05.316","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is one of the most common and fastest-growing diseases worldwide, and diabetic atherosclerotic calcification is a frequent and fatal complication, the underlying mechanisms of which remain unclear. In this study, we investigated the mechanism by which HNRNPC regulates diabetic vascular calcification.</p><p><strong>Methods: </strong>We retrieved datasets GSE211722, GSE84012, and GSE74755 from the GEO database and performed probe-to-gene name conversion. Based on expression profile data and aortic transcriptomic data from diabetic and non-diabetic mice, RNA m6A methylation-related regulatory genes were screened, and violin plots and heatmaps were generated accordingly. Differential genes identified from the expression profiles and experimental groups were subjected to intersection analysis to ultimately identify the target gene. We also enrolled coronary heart disease patients meeting predefined inclusion criteria to analyze the correlation between coronary artery calcium scores and serum HNRNPC levels. Subsequently, through transcription factor prediction and validation using single-cell transcriptomic data from the anterior tibial arteries of diabetic amputation patients, transcription factors of HNRNPC were identified. The role of HNRNPC in diabetic atherosclerotic calcification was further investigated by establishing an in vitro model of smooth muscle cells under high-glucose conditions and an in vivo model of diabetic atherosclerotic calcification in ApoE^-/- mice.</p><p><strong>Results: </strong>Analysis of GEO datasets and diabetic mouse transcriptomic data identified HNRNPC as the only overlapping differentially expressed m6A methylation regulatory gene from both sources. Clinical investigations revealed that serum HNRNPC levels and coronary artery calcium scores were elevated in diabetic patients and exhibited a positive correlation. In vitro and in vivo experiments demonstrated that inhibiting HNRNPC reduced the expression of the osteogenic marker RUNX2 and decreased calcium deposition, whereas HNRNPC overexpression promoted calcification. By integrating bioinformatics analysis with cellular (MOVAS) and animal (ApoE^-/- mice) models, the transcription factor YY1 was revealed to play a pivotal role in vascular calcification. During calcification, YY1 expression was upregulated, and it directly bound to and activated the HNRNPC promoter, thereby enhancing HNRNPC transcription. Silencing YY1 significantly suppressed calcium deposition and osteogenic marker expression, whereas overexpressing HNRNPC reversed this effect, confirming that YY1 drives smooth muscle cell calcification by regulating HNRNPC expression.</p><p><strong>Conclusion: </strong>We demonstrate a previously unrecognized role of HNRNPC as a key driver of diabetic atherosclerotic calcification. Specifically, the transcription factor YY1 promotes calcification by mediating HNRNPC's function.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"964-979"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148028974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"An enzyme kinetic model for quantitative interpretation of the role of nicotinamide nucleotide transhydrogenase (NNT) in cell physiology\" [Free Rad. Biol. Med. 254 (2026) 660-675].","authors":"Zhuohui Gan, Inge van der Stelt, Sander Grefte, Maria Suarez Diez, Werner J H Koopman, Jaap Keijer","doi":"10.1016/j.freeradbiomed.2026.08.033","DOIUrl":"10.1016/j.freeradbiomed.2026.08.033","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"988"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In response to: Personalized antioxidant supplementation improves muscle strength, physical activity, and quality of life in patients with FSHD1: A real-world longitudinal study. Laoudj-Chenivesse D, Arbogast S, Raynaud De Mauverger E, Fedou C, Debroize E, Hugon G, Pincemail J, Picot MC, Cristol JP, Mercier J, Portet F. Free Radic Biol Med. 2026 Feb 28; 248: 424-435.","authors":"N C Voermans, G Stimpson, E Bugiardini, J Dumonceaux, C A A Hewamadduma, M Oskoui, P Oosterhoff, V Sansone, J Statland, J Vissing, B Schoser, L Servais","doi":"10.1016/j.freeradbiomed.2026.06.035","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.06.035","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"255 ","pages":"980-982"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"O-GlcNAc transferase orchestrates oocyte maturation by modulating the activity of mitochondrial respiratory chain complex I\" [Free Radic. Biol. Med. 248 (2026) 194-209, FRB 17667].","authors":"Zhiming Ding, Caiyun Wu, Xuanxi Li, Yan Xu, Xiaoxiao Su, Huihui Ou, Cong Ma, Zuying Xu, Ping Zhou, Yunxia Cao, Huifen Xiang","doi":"10.1016/j.freeradbiomed.2026.08.031","DOIUrl":"10.1016/j.freeradbiomed.2026.08.031","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"987"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Aloe-emodin mitigates cisplatin-induced acute kidney injury by Nrf2-mediated ferroptosis regulation\" [Free Radic. Biol. Med. 241 (2025) 104-116].","authors":"Qiangfang Dai, Yang Xiang, Rongrong Qiang, Gen Li, Yuxuan Song, Yanxin Yu, Jing Liu, Mengdi Lv, Wenqi Liu, Jumei Zhao, Xiaoli Wei, Xiaolong Liu","doi":"10.1016/j.freeradbiomed.2026.08.045","DOIUrl":"10.1016/j.freeradbiomed.2026.08.045","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"989-992"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In response to the letter to the editor by Voermans et al. regarding the article entitled: Personalized antioxidant supplementation improves muscle strength, physical activity, and quality of life in patients with FSHD1: A real-world longitudinal study. Arbogast S, Raynaud De Mauverger E, Fedou C, Debroize E, Hugon G, Pincemail J, Picot MC, Cristol JP, Mercier J, Portet F. Free Radic Biol Med. 2026 Feb 28;248:424-435.","authors":"Dalila Laoudj-Chenivesse, Sandrine Arbogast, Eric Raynaud De Mauverger, Christine Fedou, Emma Debroize, Gérald Hugon, Joël Pincemail, Marie-Christine Picot, Jean-Paul Cristol, Jacques Mercier, Florence Portet","doi":"10.1016/j.freeradbiomed.2026.08.034","DOIUrl":"10.1016/j.freeradbiomed.2026.08.034","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"983-986"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Ginkgolide B-loaded detachable microneedles attenuate androgenetic alopecia by suppressing endoplasmic reticulum stress via the Nrf2/ HO-1 pathway\" [Free Radic. Biol. Med. 256, (2026), 1-14].","authors":"Zhan Wang, Cheng Zheng, Wenzhen Li, Kaung Myat Kyaw, Yunmin Zhu, Yihan Lin, Zhen Lin, Di Wu, Zhiqi Hu, Yang Sun, Kaitao Li","doi":"10.1016/j.freeradbiomed.2026.08.051","DOIUrl":"10.1016/j.freeradbiomed.2026.08.051","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"993"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misfolding of cystathionine beta-synthase impairs mitochondrial homeostasis and cellular bioenergetics.","authors":"Ela Mijatovic, Thilo M Philipp, Karim Zuhra, Maria Petrosino, Anna Kieronska-Rudek, Ana Kitanovic, Renata Collard, Sidneia S Santos, Tatjana Kleele, Csaba Szabo, Tomas Majtan","doi":"10.1016/j.freeradbiomed.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.09.002","url":null,"abstract":"<p><p>Homocystinuria (HCU) is an inborn error of metabolism and a conformational disorder chiefly caused by the missense mutations in the cystathionine beta-synthase (CBS) gene. These mutations often cause CBS destabilization, misfolding and dysfunction resulting in CBS deficiency and pathological accumulation of homocysteine. Morphological changes in mitochondria were described in HCU patients and mouse models; however, their functional significance has remained unknown. Here, we characterized the impact of CBS deficiency due to expression of the most common HCU-causing variant CBS I278T on mitochondrial function using three cellular models of HCU: mouse hepatocytes, human fibroblasts and newly developed CRISPR/Cas9-modified HEK293 cells. We found that the expression of the CBS I278T variant resulted in unfolded protein response, oxidative stress and impaired cellular energy metabolism in all three cellular models of HCU. Mitochondrial respiration and ATP production were substantially impaired. Bioenergetic deficit correlated morphologically with mitochondrial swelling and loss of cristae and functionally with the decreased membrane potential and cytosolic mitochondrial DNA release. Impaired clearance of damaged, non-functional mitochondria was caused by the compromised mitophagy activation and dysfunctional lysosomes. Methionine restriction substantially reduced plasma total homocysteine and rescued mitochondrial function of hepatocytes isolated from the treated Tg-I278T HCU mice. Importantly, CBS knockout HEK293 cells showed normal proteostasis and mitochondrial function indicating that CBS I278T misfolding is the main cause and trigger of the described pathological phenotype. These findings provide the first mechanistic insight into the impaired cellular bioenergetics in HCU.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-Induced Intercellular Mitochondrial Transfer: Redox Signaling as a Candidate Regulatory Mechanism.","authors":"Mei Ma, Jinze Tian, Zhe Wang, Ziyi Zhang, Yong Zhang, Hai Bo","doi":"10.1016/j.freeradbiomed.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.09.003","url":null,"abstract":"<p><p>Intercellular mitochondrial transfer has been recognized as an important mechanism for maintaining tissue homeostasis and adapting to stress. Mitochondria can cross cellular boundaries through tunneling nanotubes, extracellular vesicles, and free mitochondrial release. However, the physiological signals coordinating these pathways remain poorly defined. Exercise is a potent inducer of transient redox signaling, generating superoxide and hydrogen peroxide while modulating mitochondrial dynamic remodeling. This review integrates exercise redox biology with redox regulation of transfer machinery characterized in non-exercise models, proposing that exercise-induced redox signaling may function as a candidate regulatory mechanism. The framework emphasizes bidirectional redox coordination, in which oxidant pulses may activate export in donor cells and prepare recipient cells for uptake and antioxidant defense. Exercise-induced mitochondrial transfer has been directly demonstrated in the brain, while observations in skeletal muscle, adipose tissue, and heart remain suggestive but have not been confirmed in exercise models. These findings support a framework in which intercellular mitochondrial transfer contributes to metabolic signaling, antioxidant defense, and distributed quality control across organs. This model represents a working hypothesis requiring direct experimental validation through lineage tracing, tissue-specific mitochondrial reporters, and intravital imaging.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXC1 Drives Pulmonary Arterial Endothelial Cell Dysfunction and Vascular Remodeling through Transcriptional Activation of MACC1.","authors":"Sijia Li, Mingyu Yang, Hongyu Chen, Shifan Chen, Jielin Liao, Jiayan Liu, Ju Li, Yajuan Ran, Xiufeng Yu","doi":"10.1016/j.freeradbiomed.2026.08.037","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.08.037","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a progressive vascular disorder characterized by pulmonary vascular remodeling and endothelial dysfunction. Although several molecular regulators have been implicated in PAH pathogenesis, the key transcriptional networks governing these processes remain incompletely understood. This study aimed to investigate the role of the transcription factor forkhead box C1 (FOXC1) in PAH development and evaluate its potential as a therapeutic target.</p><p><strong>Methods: </strong>Bioinformatic analysis of single-cell RNA sequencing data (GSE293580) was performed to identify critical regulatory hubs in PAH endothelial cells. FOXC1 expression was validated in serum samples from patients with PAH and in multiple experimental PAH models, including hypoxia-, Sugen5416/hypoxia (SuHx)-, and monocrotaline (MCT)-induced models. The therapeutic effects of FOXC1 inhibition were evaluated using adeno-associated virus serotype 6 (AAV6)-mediated knockdown in vivo. In vitro functional assays using human pulmonary artery endothelial cells (hPAECs), together with chromatin immunoprecipitation quantitative PCR (ChIP-qPCR), were performed to elucidate the underlying molecular mechanisms.</p><p><strong>Results: </strong>FOXC1 was identified as a central transcriptional hub in endothelial cells from patients with idiopathic PAH. Circulating FOXC1 levels were positively correlated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PAH. In vivo, FOXC1 knockdown significantly alleviated right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling in both hypoxia- and SuHx-induced PAH models. Mechanistically, FOXC1 directly bound to the promoter region of MACC1 and transcriptionally activated its expression. Silencing MACC1 markedly attenuated the enhanced proliferation, migration, and angiogenic responses induced by FOXC1 overexpression in hPAECs.</p><p><strong>Conclusion: </strong>The FOXC1/MACC1 regulatory axis contributes to endothelial dysfunction and pulmonary vascular remodeling in PAH. Targeting this pathway may represent a potential therapeutic strategy for PAH treatment.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}