Free Radical Biology and Medicine最新文献_第2页

Exploring biomarkers of systemic oxidative stress and placental insufficiency in pregnant women with inflammatory bowel diseases

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-13 DOI: 10.1016/j.freeradbiomed.2025.03.017

Hannah J. Holstein , Dianne G. Bouwknegt , Marijn C. Visschedijk , Marian L.C. Bulthuis , Marjan Reinders-Luinge , Mirthe H. Schoots , Harry van Goor , Sanne J. Gordijn , Gerard Dijkstra , Arno R. Bourgonje

Background

Inflammatory bowel disease (IBD) often presents during the fertile age and may affect pregnancy outcomes. Both IBD and selected pregnancy complications involve oxidative stress. Soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) serve as biomarkers of placental insufficiency, while free thiols (FT) reflect systemic oxidative stress. This study aimed to assess the dynamics of FT, sFlt-1, and PlGF before, during, and shortly after pregnancy, and their relationships with disease- and pregnancy outcomes in patients with IBD.

Methods

This retrospective cohort study included pregnant women with and without IBD. FTs were measured with colorimetric detection; sFlt-1 and PlGF were measured using immunofluorescent assays. Extensive clinical data were collected, including pregnancy complications and IBD parameters.

Results

A total of 40 patients and 14 non-IBD controls participated, covering 57 IBD and 14 control pregnancies. Serum FT levels were significantly lower in patients with ulcerative colitis during pregnancy (p = 0.007) and decreased compared to pre-conceptional levels (p = 0.005), indicating increased oxidative stress. sFlt-1/PlGF ratios were higher in patients with small-for-gestational-age infants (p = 0.015). Post-pregnancy FT levels were lower in patients experiencing disease exacerbations during pregnancy (p = 0.046), whereas sFlt-1/PlGF ratios were numerically higher (p = 0.063). IBD severity correlated with lower FT levels regarding surgical history (p = 0.066) and biologic use (p = 0.033).

Conclusions

This study demonstrates increased systemic oxidative stress in patients with IBD during pregnancy, as reflected by lower FT levels compared to pre-conceptional values and non-IBD controls. Prospective validation is required to evaluate the utility of these biomarkers in predicting pregnancy complications and informing clinical decisions.

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引用次数: 0

Role of manganese in brain health and disease: Focus on oxidative stress

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-12 DOI: 10.1016/j.freeradbiomed.2025.03.013

Airton C. Martins , Gustavo H. Oliveira-Paula , Alexey A. Tinkov , Anatoly V. Skalny , Yousef Tizabi , Aaron B. Bowman , Michael Aschner

Manganese (Mn) is an essential trace element crucial for various physiological processes, but excessive exposure can lead to significant health concerns, particularly neurotoxicity. This review synthesizes current knowledge on Mn-induced oxidative stress and its role in cellular dysfunction and disease. We discuss how Mn promotes toxicity through multiple mechanisms, primarily through reactive oxygen species (ROS) generation, which leads to oxidative stress and disruption of cellular processes. The review examines key pathways affected by Mn toxicity, including mitochondrial dysfunction, endoplasmic reticulum stress, inflammasome activation, and epigenetic modifications. Recent studies have identified promising therapeutic compounds, including both synthetic and natural substances such as probucol, metformin, curcumin, resveratrol, and daidzein, which demonstrate protective effects through various mechanisms, including antioxidant enhancement, mitochondrial function preservation, and epigenetic pathway modulation. Understanding these mechanisms provides new insights into potential therapeutic strategies for Mn-induced disorders. This review also highlights future research directions, emphasizing the need for developing targeted therapies and investigating combination approaches to address multiple aspects of Mn toxicity simultaneously.

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引用次数: 0

Corrigendum to "Clozapine-N-oxide protects dopaminergic neurons against rotenone-induced neurotoxicity by preventing ferritinophagy-mediated ferroptosis" [Free Radic. Biol. Med. 212 (2024) 384-402].

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-12 DOI: 10.1016/j.freeradbiomed.2025.03.008

Qingquan Sun, Yan Wang, Liyan Hou, Sheng Li, Jau-Shyong Hong, Qingshan Wang, Jie Zhao

引用次数: 0

The Nuclear-Mitochondrial Crosstalk in Aging: From Mechanisms to Therapeutics.

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-12 DOI: 10.1016/j.freeradbiomed.2025.03.012

Yifei Feng, Yan Lu

Aging is a complex physiological process characterized by an irreversible decline in tissue and cellular functions, accompanied by an increased risk of age-related diseases, including neurodegenerative, cardiovascular, and metabolic disorders. Central to this process are epigenetic modifications, particularly DNA methylation, which regulate gene expression and contribute to aging-related epigenetic drift. This drift is characterized by global hypomethylation and localized hypermethylation, impacting genomic stability and cellular homeostasis. Simultaneously, mitochondrial dysfunction, a hallmark of aging, manifests as impaired oxidative phosphorylation, excessive reactive oxygen species production, and mitochondrial DNA mutations, driving oxidative stress and cellular senescence. Emerging evidence highlights a bidirectional interplay between epigenetics and mitochondrial function. DNA methylation modulates the expression of nuclear genes governing mitochondrial biogenesis and quality control, while mitochondrial metabolites, such as acetyl-CoA and S-adenosylmethionine, reciprocally influence epigenetic landscapes. This review delves into the intricate nuclear-mitochondrial crosstalk, emphasizing its role in aging-related diseases and exploring therapeutic avenues targeting these interconnected pathways to counteract aging and promote health span extension.

衰老是一个复杂的生理过程，其特点是组织和细胞功能不可逆转地衰退，同时与衰老相关的疾病风险增加，包括神经退行性疾病、心血管疾病和代谢紊乱。这一过程的核心是表观遗传修饰，尤其是 DNA 甲基化，它调控基因表达并导致与衰老相关的表观遗传漂移。这种漂移的特点是全局低甲基化和局部高甲基化，影响基因组稳定性和细胞稳态。同时，作为衰老标志的线粒体功能障碍表现为氧化磷酸化受损、活性氧生成过多和线粒体 DNA 变异，从而导致氧化应激和细胞衰老。新出现的证据强调了表观遗传学与线粒体功能之间的双向相互作用。DNA 甲基化会调节管理线粒体生物生成和质量控制的核基因的表达，而线粒体代谢产物（如乙酰-CoA 和 S-腺苷蛋氨酸）会对表观遗传学景观产生相互影响。这篇综述深入探讨了核-线粒体之间错综复杂的相互作用，强调了它在衰老相关疾病中的作用，并探讨了针对这些相互关联的途径的治疗方法，以对抗衰老并促进健康寿命的延长。

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引用次数: 0

Chrysophanol delays aging via insulin/IGF-1 signaling pathway

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-12 DOI: 10.1016/j.freeradbiomed.2025.03.011

Hongjiao Zhang , Jun Xiong , Qingyao Wang , Qiuyu Song , Lingjie Meng , Han Zhang , Yuxin Bao , Fang Liu , Yi Xiao

Aging is inevitable processes which play a significant role in the development of various diseases, including cardiovascular diseases, neurodegenerative disorders, and cancers. The extension of lifespan and the improvement of age-related diseases can potentially be achieved by targeting evolutionarily conserved pathways and mechanisms through pharmacological interventions. Chrysophanol (Chr), a naturally occurring anthraquinone compound primarily derived from rhubarb of the Polygonaceae family, exhibits a wide range of pharmacological activities, including anti-cancer, anti-inflammatory, and anti-bacterial effects. However, its role in regulating aging remains unclear. In this study, we discovered that Chr extends both lifespan and healthspan in Caenorhabditis elegans by activating the DAF-2/DAF-16 insulin signaling pathway. Furthermore, we observed that Chr promoted longevity in natural aging mice, doxorubicin-induced aging mice, and transgenic mice through the conserved Insulin/IGF-1 signaling pathway. Additionally, Chr also influenced senescence-associated secretory phenotypes (SASPs) and enhanced the expression of antioxidant genes, contributing to delayed aging. These findings highlight that Chr exerts anti-aging effects from C. elegans to mammals via the evolutionarily conserved Insulin/IGF-1 signaling pathway, positioning Chr as a promising candidate for the prevention and treatment of aging and age-related diseases.

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引用次数: 0

5-Methoxytryptophan Attenuates Oxidative Stress-Induced Downregulation of PINK1 and Mitigates Mitochondrial Damage and Apoptosis in Cardiac Myocytes.

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-10 DOI: 10.1016/j.freeradbiomed.2025.03.010

Chii-Ming Lee, Tung-Chun Chien, Juo-Shan Wang, Yu-Wei Chen, Chin-Yu Chen, Chen-Chin Kuo, Liang-Ting Chiang, Kenneth K Wu, Wan-Tseng Hsu

Mitochondrial dysfunction is a hallmark in the pathogenesis of various cardiovascular diseases. 5-Methoxytryptophan (5-MTP), an intrinsic amino acid metabolite, exerts cardioprotective effects potentially through the preservation of mitochondrial integrity. This study investigates the mechanisms and contexts in which 5-MTP positively impacts mitochondrial function using cultured human ventricular cardiomyocytes (HCMs) and HL-1 cardiac cells subjected to oxidative stress (OS). We first demonstrated that 5-MTP up-regulates the expression of PINK1, a key regulator of mitochondrial homeostasis. PINK1 knockdown attenuated the beneficial effects of 5-MTP on cardiomyocyte apoptosis. Furthermore, in cells exposed to OS, 5-MTP pretreatment led to a notable decrease in mitochondrial superoxide generation. Fluorescence imaging and network analysis showed that 5-MTP preserved mitochondrial membrane potential and enhanced mitochondrial network integrity. The reduction in the phosphorylation of dynamin-related protein 1, which is involved in mitochondrial fission, uncovered the role of 5-MTP in maintaining mitochondrial dynamics. Notably, 5-MTP attenuated OS-induced mitophagy, as evidenced by reduced mitophagy detection dye fluorescence and lower mitochondrial Parkin levels, suggesting that mechanisms beyond the PINK1/Parkin pathway are involved. Restoration of AKT phosphorylation and reduced mitochondrial Bax localization further revealed an additional pathway contributing to mitochondrial protection. Moreover, 5-MTP attenuated pro-apoptotic Bax levels and enhanced PINK1 expression in a rat model of ischemic cardiomyopathy, corroborating its cardioprotective role. Collectively, these findings demonstrate that 5-MTP mitigates mitochondrial dysfunction by integrating the roles of PINK1, AKT, and Bax, offering potential as a therapeutic agent to enhance cellular resilience in OS-driven mitochondrial damage.

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引用次数: 0

Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered liver lipid metabolism on a ketogenic diet

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-10 DOI: 10.1016/j.freeradbiomed.2025.03.009

Guogang Xu , Joseph Schell , Songhua Quan , Yucheng Gao , Sung-Jen Wei , Meixia Pan , Xianlin Han , Guiming Li , Daohong Zhou , Haiyan Jiang , Felix F. Dong , Erin Munkácsy , Nobuo Horikoshi , David Gius

Acetyl-CoA Synthetase Short Chain Family Member-1 (ACSS1) catalyzes the ligation of acetate and coenzyme A to generate acetyl-CoA in the mitochondria to produce ATP through the tricarboxylic acid (TCA) cycle. We recently generated an ACSS1-acetylation (Ac) mimic knock-in mouse, where lysine 635 was mutated to glutamine (K635Q), which structurally and biochemically mimics an acetylated lysine. ACSS1 enzymatic activity is regulated, at least in part, through the acetylation of lysine 635 in mice (lysine 642 in humans), a Sirtuin 3 deacetylation target. We challenged our Acss1^K635Q knock-in mice with a three-week ketogenic diet. While both wild-type and Acss1^K635Q knock-in mice were in ketosis with similar blood glucose levels, the Acss1^K635Q mice exhibited elevated blood acetate and liver acetyl-CoA. In addition, and importantly, compared to wild-type mice, the liver in the Acss1^K635Q mice displayed a much more predominant liver steatosis morphology and accumulation of lipid drops, as measured by H&E and Oil Red O staining. RNAseq analysis identified that genes related to mitochondrial respiratory chain complexes and oxidative stress were significantly overexpressed in the Acss1^K635Q mice on a KD. Finally, lipidomics analysis revealed very different lipid profiles for these groups, including a dramatic increase in triacylglycerides (TAGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and cardiolipins in the Acss1^K635Q liver.

{"title":"Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered liver lipid metabolism on a ketogenic diet","authors":"Guogang Xu , Joseph Schell , Songhua Quan , Yucheng Gao , Sung-Jen Wei , Meixia Pan , Xianlin Han , Guiming Li , Daohong Zhou , Haiyan Jiang , Felix F. Dong , Erin Munkácsy , Nobuo Horikoshi , David Gius","doi":"10.1016/j.freeradbiomed.2025.03.009","DOIUrl":"10.1016/j.freeradbiomed.2025.03.009","url":null,"abstract":"<div><div>Acetyl-CoA Synthetase Short Chain Family Member-1 (ACSS1) catalyzes the ligation of acetate and coenzyme A to generate acetyl-CoA in the mitochondria to produce ATP through the tricarboxylic acid (TCA) cycle. We recently generated an ACSS1-acetylation (Ac) mimic knock-in mouse, where lysine 635 was mutated to glutamine (K635Q), which structurally and biochemically mimics an acetylated lysine. ACSS1 enzymatic activity is regulated, at least in part, through the acetylation of lysine 635 in mice (lysine 642 in humans), a Sirtuin 3 deacetylation target. We challenged our <em>Acss1</em><sup><em>K635Q</em></sup> knock-in mice with a three-week ketogenic diet. While both wild-type and <em>Acss1</em><sup><em>K635Q</em></sup> knock-in mice were in ketosis with similar blood glucose levels, the <em>Acss1</em><sup><em>K635Q</em></sup> mice exhibited elevated blood acetate and liver acetyl-CoA. In addition, and importantly, compared to wild-type mice, the liver in the <em>Acss1</em><sup><em>K635Q</em></sup> mice displayed a much more predominant liver steatosis morphology and accumulation of lipid drops, as measured by H&E and Oil Red O staining. RNAseq analysis identified that genes related to mitochondrial respiratory chain complexes and oxidative stress were significantly overexpressed in the <em>Acss1</em><sup><em>K635Q</em></sup> mice on a KD. Finally, lipidomics analysis revealed very different lipid profiles for these groups, including a dramatic increase in triacylglycerides (TAGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and cardiolipins in the <em>Acss1</em><sup><em>K635Q</em></sup> liver.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"232 ","pages":"Pages 260-268"},"PeriodicalIF":7.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614271","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}

引用次数: 0

Trimethylamine N-oxide (TMAO) treatment triggers premature ovarian insufficiency (POI) via the activation of mitochondrial pathway apoptosis in granulosa cells

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-06 DOI: 10.1016/j.freeradbiomed.2025.03.007

Yuanhong Peng , Yingjin Wang , Jiangshan Hu , Zhijie Wang , Yue Liu , Zhide Ding

Premature ovarian insufficiency (POI) is characterized by follicular development failure or follicular dysplasia, therefore causing the lack of normal ovarian function before 40 years of age. Trimethylamine N-oxide (TMAO) is a metabolite of high choline diet rich in red meat and directly associated with gut microbiota. Correlation of TMAO level with female fertility decline has been shown; however, its mechanism is largely unknown. To unveil the mechanism by which TMAO affects female reproductive function, we established a TMAO-treated mouse model which exhibited the pathological manifestations of POI including increased follicle-stimulating hormone and luteinizing hormone levels, decreased estradiol and anti-Müllerian hormone levels, reduced growing and mature follicles, increased atretic follicles, and decreased fertility. Meanwhile, these mice showed an increased apoptosis ratio and damaged mitochondrial function in granulosa cells, the nursing and supporting cells for oocyte development. Moreover, TMAO treatment significantly elevated oxidative stress and reduced antioxidative capacity in granulosa cells, whereas the antioxidants N-acetylcysteine alleviated such detriment. Mechanism investigation demonstrated that TMAO treatment up-regulated phosphatase and tensin homolog expression levels in granulosa cells, thereby inhibiting the phosphorylation of AKT and subsequently causing high expression of BCL-2-associated X protein, a key molecule in the mitochondria pathway, leading to increased cell apoptosis. Our findings documented the pathological mechanism of TMAO-induced POI, which may provide a potential target for curing POI clinically.

{"title":"Trimethylamine N-oxide (TMAO) treatment triggers premature ovarian insufficiency (POI) via the activation of mitochondrial pathway apoptosis in granulosa cells","authors":"Yuanhong Peng , Yingjin Wang , Jiangshan Hu , Zhijie Wang , Yue Liu , Zhide Ding","doi":"10.1016/j.freeradbiomed.2025.03.007","DOIUrl":"10.1016/j.freeradbiomed.2025.03.007","url":null,"abstract":"<div><div>Premature ovarian insufficiency (POI) is characterized by follicular development failure or follicular dysplasia, therefore causing the lack of normal ovarian function before 40 years of age. Trimethylamine N-oxide (TMAO) is a metabolite of high choline diet rich in red meat and directly associated with gut microbiota. Correlation of TMAO level with female fertility decline has been shown; however, its mechanism is largely unknown. To unveil the mechanism by which TMAO affects female reproductive function, we established a TMAO-treated mouse model which exhibited the pathological manifestations of POI including increased follicle-stimulating hormone and luteinizing hormone levels, decreased estradiol and anti-Müllerian hormone levels, reduced growing and mature follicles, increased atretic follicles, and decreased fertility. Meanwhile, these mice showed an increased apoptosis ratio and damaged mitochondrial function in granulosa cells, the nursing and supporting cells for oocyte development. Moreover, TMAO treatment significantly elevated oxidative stress and reduced antioxidative capacity in granulosa cells, whereas the antioxidants N-acetylcysteine alleviated such detriment. Mechanism investigation demonstrated that TMAO treatment up-regulated phosphatase and tensin homolog expression levels in granulosa cells, thereby inhibiting the phosphorylation of AKT and subsequently causing high expression of BCL-2-associated X protein, a key molecule in the mitochondria pathway, leading to increased cell apoptosis. Our findings documented the pathological mechanism of TMAO-induced POI, which may provide a potential target for curing POI clinically.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"232 ","pages":"Pages 214-230"},"PeriodicalIF":7.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585461","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

Glucose protects cultured retinal cells from oxidative injury via the pentose phosphate pathway

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-05 DOI: 10.1016/j.freeradbiomed.2025.03.006

John P.M. Wood , Glyn Chidlow , Robert J. Casson

Purpose

Oxidative injury has been implicated in a range of common retinal neurodegenerative disorders. Protecting the retina from such an insult could therefore prove clinically beneficial. We sought to investigate whether glucose, acting via the pentose phosphate pathway (PPP), was able to counteract oxidative cytotoxicity to retinal cells in culture.

Experimental

Mixed retinal neuron-glial cultures were prepared from Sprague-Dawley rat neonates and used at 7 days in vitro; neuron-only and Müller glial cell-only mono-cultures were subsequently prepared from these cultures. At appropriate stages, cultures were treated with t-butyl hydroperoxide (tbH; 10 nM-1 mM) in glucose/pyruvate-free DMEM to induce oxidative stress. Some cultures were co-treated with glucose. Additional compounds were co-applied to inhibit glycolysis, PPP, cystine uptake, glutathione biosynthesis and glutathione reductase (GR). The effect of glucose on stimulation of reactive oxygen species (ROS), as well as levels of glutathione and NADPH were also investigated.

Results

Oxidative stress resulted in cytotoxicity to both retinal neurons and glial cells. Glucose was able to abrogate the toxicity to glial cells in mono-cultures and mixed cultures, but could only provide protection to neurons in the mixed cultures when glial cells were also present. Glucose was additionally shown to prevent stimulation of ROS and oxidative stress-induced depletions of glutathione and NADPH. Inhibition of PPP, cystine uptake or GR all diminished the protective response of glucose.

Conclusion

Glucose prevented oxidative stress to retinal cells via the PPP. Neurons were not subjected to glucose-induced protection except when glial cells were present, implying the passage of a transmissible mediator or other protective action between the two cell types.

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引用次数: 0

Selenium-loaded porous silica nanospheres improve cardiac repair after myocardial infarction by enhancing antioxidant activity and mitophagy

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine

Pub Date : 2025-03-05 DOI: 10.1016/j.freeradbiomed.2025.03.004

Taixi Li , Xijian Liu , Boshen Yang , Zhixiang Wang , Yizhi Chen , Xian Jin , Chengxing Shen

Myocardial infarction (MI) is the leading cause of death globally, often resulting to significant loss of cardiac function. A key factor in the pathological progression of MI is the excessive generation of reactive oxygen species (ROS) by dysfunctional mitochondria. However, no antioxidant therapy has been approved for clinical treatment of MI to date. In this study, selenium-loaded porous silica nanospheres (Se@PSN) are synthesized as a novel therapeutic approach for MI. These nanospheres are capable of neutralizing various ROS, thereby reducing hypoxia-induced myocardial cell damage. Additionally, Se@PSN promote the upregulation of antioxidant proteins, providing sustained intracellular ROS scavenging, which helps reduce infarct size and preserve cardiac function post-MI. The sustained antioxidant effects of Se@PSN are attributed to their ability to safeguard mitochondrial function by modulating oxidative phosphorylation, mitochondrial dynamics, and mitophagy. The activation of mitophagy by Se@PSN is achieved through the upregulation of HIF-1α expression. In conclusion, Se@PSN show significant potential for clinical translation as a novel therapeutic strategy for MI.

{"title":"Selenium-loaded porous silica nanospheres improve cardiac repair after myocardial infarction by enhancing antioxidant activity and mitophagy","authors":"Taixi Li , Xijian Liu , Boshen Yang , Zhixiang Wang , Yizhi Chen , Xian Jin , Chengxing Shen","doi":"10.1016/j.freeradbiomed.2025.03.004","DOIUrl":"10.1016/j.freeradbiomed.2025.03.004","url":null,"abstract":"<div><div>Myocardial infarction (MI) is the leading cause of death globally, often resulting to significant loss of cardiac function. A key factor in the pathological progression of MI is the excessive generation of reactive oxygen species (ROS) by dysfunctional mitochondria. However, no antioxidant therapy has been approved for clinical treatment of MI to date. In this study, selenium-loaded porous silica nanospheres (Se@PSN) are synthesized as a novel therapeutic approach for MI. These nanospheres are capable of neutralizing various ROS, thereby reducing hypoxia-induced myocardial cell damage. Additionally, Se@PSN promote the upregulation of antioxidant proteins, providing sustained intracellular ROS scavenging, which helps reduce infarct size and preserve cardiac function post-MI. The sustained antioxidant effects of Se@PSN are attributed to their ability to safeguard mitochondrial function by modulating oxidative phosphorylation, mitochondrial dynamics, and mitophagy. The activation of mitophagy by Se@PSN is achieved through the upregulation of HIF-1α expression. In conclusion, Se@PSN show significant potential for clinical translation as a novel therapeutic strategy for MI.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"232 ","pages":"Pages 292-305"},"PeriodicalIF":7.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572588","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}

引用次数: 0