Free Radical Biology and Medicine最新文献

{"title":"Neuroprotective Role of CHCHD2 in Parkinson's Disease: Insights into the GPX4-Related Ferroptosis Pathway","authors":"Fang Wang ,&nbsp;Xuanzhuo Liu ,&nbsp;Mingyi Chen ,&nbsp;Xiaoxin Xu ,&nbsp;Ying Yang ,&nbsp;Qiuhong Xu ,&nbsp;Huili Zhu ,&nbsp;Anding Xu ,&nbsp;Mahmoud A. Pouladi ,&nbsp;Xiaohong Xu","doi":"10.1016/j.freeradbiomed.2024.11.034","DOIUrl":"10.1016/j.freeradbiomed.2024.11.034","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, characterized by pathogenesis involving mitochondrial dysfunction, oxidative stress, and ferroptosis. Unfortunately, there are currently no effective interventions to slow down the progression of PD. The mitochondrial protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), which is implicated in neurodegeneration and serves as a biomarker for PD, has been reported to have neuroprotective effects against oxidative stress, but the potential molecular mechanisms involved remain elusive. In this study, we uncovered a critical mechanism by which CHCHD2 protected neuronal cells against oxidative stress with the ferroptosis pathway playing a pivotal role, as determined through tandem mass tags (TMT)-based proteomic analysis. The overexpression of CHCHD2 was observed to enhance cell viability, reduce levels of lipid peroxidation and reactive oxygen species (ROS), and upregulate the expression of the ferroptosis negative regulatory protein Glutathione peroxidase 4 (GPX4) in PD cells. Conversely, CHCHD2 knockdown led to reduced cell viability, elevated lipid peroxidation, and a decreased expression of GPX4. Additionally, CHCHD2 overexpression ameliorated motor function impairment, reduced α-synuclein levels, and mitigated dopaminergic (DA) neuron loss in the substantia nigra and striatum of PD mice. Importantly, we show that the inhibitory effect of CHCHD2 on ferroptosis in PD is related to the GPX4 signaling pathway. In summary, our study elucidates the neuroprotective role of CHCHD2 in regulating the GPX4-related ferroptosis pathway in PD, providing new targets and ideas for future PD drug development and therapy.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681351","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":"Itaconic acid ameliorates necrotizing enterocolitis through the TFEB-mediated autophagy-lysosomal pathway","authors":"Baozhu Chen ,&nbsp;Yufeng Liu ,&nbsp;Shunchang Luo ,&nbsp;Jialiang Zhou ,&nbsp;Yijia Wang ,&nbsp;Qiuming He ,&nbsp;Guiying Zhuang ,&nbsp;Hu Hao ,&nbsp;Fei Ma ,&nbsp;Xin Xiao ,&nbsp;Sitao Li","doi":"10.1016/j.freeradbiomed.2024.11.035","DOIUrl":"10.1016/j.freeradbiomed.2024.11.035","url":null,"abstract":"<div><div>Excessive autophagy has been implicated in the pathogenesis of necrotizing enterocolitis (NEC), yet the molecular underpinnings of the autophagy-lysosomal pathway (ALP) in NEC are not well characterized. This study aimed to elucidate alterations within the ALP in NEC by employing RNA sequencing on intestinal tissues obtained from affected infants. Concurrently, we established animal and cellular models of NEC to assess the therapeutic efficacy of itaconic acid (ITA). Our results indicate that the ALP is significantly disrupted in NEC. Notably, ITA was found to modulate the ALP, enhancing autophagic flux and lysosomal function, which consequently alleviated NEC symptoms. Further analysis revealed that ITA's beneficial effects are mediated through the promotion of TFEB nuclear translocation, thereby augmenting the ALP. These findings suggest that targeting the ALP with ITA to modulate TFEB activity may represent a viable therapeutic approach for NEC.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 251-265"},"PeriodicalIF":7.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686455","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":"Hydrogen peroxide diffusion across the red blood cell membrane occurs mainly by simple diffusion through the lipid fraction","authors":"Florencia Orrico ,&nbsp;Ana C. Lopez ,&nbsp;Nicolás Silva ,&nbsp;Mélanie Franco ,&nbsp;Isabelle Mouro-Chanteloup ,&nbsp;Ana Denicola ,&nbsp;Mariano A. Ostuni ,&nbsp;Leonor Thomson ,&nbsp;Matias N. Möller","doi":"10.1016/j.freeradbiomed.2024.11.031","DOIUrl":"10.1016/j.freeradbiomed.2024.11.031","url":null,"abstract":"<div><div>Hydrogen peroxide (H₂O₂) is an oxidant produced endogenously by several enzymatic pathways. While it can cause molecular damage, H₂O₂ also plays a role in regulating cell proliferation and survival through redox signaling pathways. In the vascular system, red blood cells (RBCs) are notably efficient at metabolizing H₂O₂. In addition to a robust antioxidant defense, we recently determined that human RBCs also have a high membrane permeability to H₂O₂ that is independent of aquaporin 1 or aquaporin 3. In this work, we sought to further investigate the permeation mechanism of H₂O₂ through the membrane of human RBCs. First, we explored the role of other erythrocytic membrane proteins in H₂O₂ transport, including urea transporter B and ammonia transporter Rh proteins. However, no differences were found in H₂O₂ permeability in RBCs lacking these proteins compared to control RBCs. We then focused on the hypothesis that H₂O₂ diffuses through the lipid bilayer. To test this, we studied H₂O₂ permeability in RBCs from patients with Gaucher disease (GD), which accumulate sphingolipids in the membrane, affecting RBC morphology and deformability. We found that RBCs from GD patients exhibited lower H₂O₂ membrane permeability. In another approach, we treated normal RBCs with hexanol, which fluidizes the lipid fraction of the RBC membrane, and observed an increase in the permeability to H₂O₂. In contrast, hexanol had no effect on the rate of water efflux by aquaporin 1. Together, these results support the hypothesis that H₂O₂ diffusion through the RBC membrane occurs primarily through the lipid fraction.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 389-396"},"PeriodicalIF":7.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647390","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":"SIRT3 alleviates mitochondrial dysfunction and senescence in diabetes-associated periodontitis by deacetylating LRPPRC.","authors":"Hui Tang, Yi Zhou, Yu Ye, Lu Ma, Qian-Xuan Xiao, Jing-Qi Tang, Yan Xu","doi":"10.1016/j.freeradbiomed.2024.11.033","DOIUrl":"10.1016/j.freeradbiomed.2024.11.033","url":null,"abstract":"<p><p>Diabetes-associated periodontitis (DP) is recognized as an inflammatory disease that can lead to teeth loss. Uncontrolled chronic low-grade inflammation-induced senescence impairs the stemness of human periodontal stem cells (hPDLSCs). Sirtuin 3 (SIRT3), an NAD⁺-dependent deacetylase, is pivotal in various biological processes and is closely linked to aging and aging-related diseases. This study aims to explore the mechanism of SIRT3- related senescence and osteogenic differentiation of hPDLSCs under DP and explored the novelty therapeutic targets. Our study revealed that SIRT3 expression was markedly inhibited in periodontal ligament stem cells (PDLSCs) stimulated by high glucose and lipopolysaccharide. Both in vitro and in vivo, reduced SIRT3 expression accelerated cell senescence and impaired osteogenic differentiation of hPDLSCs. We demonstrated that SIRT3 binds to and deacetylates leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), thereby modulating senescence. Additionally, we found that LRPPRC regulates senescence by modulating oxidative phosphorylation and oxidative stress. The activation of SIRT3 by honokiol significantly delayed senescence and promoted alveolar bone regeneration in mice after DP. Our findings indicate that the activation of SIRT3 negatively regulates hPDLSCs senescence by deacetylating LRPPRC, suggesting SIRT3 as a promising therapeutic target for DP.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667585","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":"AQP1 mediates pancreatic β cell senescence induced by metabolic stress through modulating intracellular H2O2 level","authors":"Qihui Yan ,&nbsp;Haifeng Zhang ,&nbsp;Yunxiao Ma ,&nbsp;Lin Sun ,&nbsp;Zhiyue Chen ,&nbsp;Yinbei Zhang ,&nbsp;Weiying Guo","doi":"10.1016/j.freeradbiomed.2024.11.029","DOIUrl":"10.1016/j.freeradbiomed.2024.11.029","url":null,"abstract":"<div><div>Metabolic stress-induced pancreatic β cell senescence plays a pivotal role in the type 2 diabetes progression, and yet the precise molecular mechanisms remain elusive. Through cellular experiments and bioinformatics analyses, we identified aquaporin 1(AQP1)-mediated transmembrane transport of hydrogen peroxide as a key driver of glucolipotoxicity-induced senescence in MIN6 cells. A PPI network analysis was used to cross-reference 17 differentially expressed genes associated with type 2 diabetes from three independent GEO databases with 188 stress-induced senescence-related genes from CellAge. AQP1 was revealed as a critical molecular nexus connecting diabetes, oxidative stress, and cellular senescence. AQP1 inhibition, through Bacopaside II and si-AQP1, significantly reduced critical senescence markers in MIN6 cells, demonstrated by the reversal of glucolipotoxicity-induced upregulation of p16, p21, and p-γH2A.X, activation of the senescence-associated secretory phenotype genes, and an elevated percentage of senescence-associated-β-galactosidase positive cells. These effects were primarily mediated through oxidative stress MAPK signaling pathway modulation. AQP1 inhibition is crucial in alleviating glucolipotoxicity-induced β cell senescence. It underscores its potential as a molecular target for therapeutic strategies to delay pancreatic β cell senescence by modulating antioxidant pathways during metabolic stress.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 171-184"},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647374","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}

{"title":"SIRT1-dependent regulation of mitochondrial metabolism participates in miR-30a-5p-mediated cardiac remodeling post-myocardial infarction","authors":"Chan Wu ,&nbsp;Yi-Xiang Hong ,&nbsp;Xiao-Cheng Zhang ,&nbsp;Jing-Zhou Li ,&nbsp;Yu-Ting Li ,&nbsp;Jun Xie ,&nbsp;Rui-Ying Wang ,&nbsp;Yan Wang ,&nbsp;Gang Li","doi":"10.1016/j.freeradbiomed.2024.11.030","DOIUrl":"10.1016/j.freeradbiomed.2024.11.030","url":null,"abstract":"<div><div>Myocardial infarction-triggered myocardial remodeling is fatal for therapies. The miR-30 family is an essential component of several physiological and pathological processes. Previous studies have proved that the miR-30 family may contribute to regulating myocardial infarction. This study aimed to demonstrate that the combination of miR-30a-5p and mitochondrial metabolism recapitulates the critical features for remodeling post-myocardial infarction. Using gain- and loss-of-function of miR-30a-5p in mice, we found miR-30a-5p is highly expressed in the heart and is reduced in infarcted hearts. Further evidence showed that miR-30a-5p acts as a protective molecule to maintain myocardial remodeling, fibrosis, and mitochondrial structure. Mitochondrial function, ATP production, and mitochondrial respiratory chain proteins were positively regulated by miR-30a-5p. Mechanistically, alterations in these properties depend on SIRT1, which modulates miR-30a-5p-regulated mitochondrial metabolism. Remarkably, reactivation of SIRT1 prevented miR-30a-5p deficiency-aggravated myocardial infarction-induced myocardial remodeling. These data identified miR-30a-5p as a critical modulator of mitochondrial function in cardiomyocytes and revealed that the miR-30a-5p-SIRT1-mitochondria network is essential for myocardial infarction-induced cardiac remodeling.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 117-128"},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667578","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 \"Mapping of oxidative modifications on the alpha-keto glutarate dehydrogenase complex induced by singlet oxygen: Effects on structure and activity\" [Free Radic. Biol. Med. 224 (2024) 723-739].","authors":"Qing Gao, Per Hägglund, Luke F Gamon, Michael J Davies","doi":"10.1016/j.freeradbiomed.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2024.11.013","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647388","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":"Iron promotes isocitrate dehydrogenase mutant glioma cell motility","authors":"Stephenson Boakye Owusu ,&nbsp;Emily Russell ,&nbsp;Akalanka B. Ekanayake ,&nbsp;Alexei V. Tivanski ,&nbsp;Michael S. Petronek","doi":"10.1016/j.freeradbiomed.2024.11.032","DOIUrl":"10.1016/j.freeradbiomed.2024.11.032","url":null,"abstract":"<div><div>Enriched iron metabolic features such as high transferrin receptor (TfR) expression and high iron content are commonly observed in aggressive gliomas and can be associated with poor clinical responses. However, the underlying question of how iron contributes to tumor aggression remains elusive. Gliomas harboring isocitrate dehydrogenase (IDH) mutations account for a high percentage (&gt;70 %) of recurrent tumors and cells with an acquired IDH mutation have been reported to have increased motility and invasion. This study aims to investigate how an acquired IDH mutation modulates iron metabolism and the implication(s) of iron on tumor cell growth. IDH mutant cells (U87^R132H) grow significantly faster which is accompanied with increased TfR expression and iron uptake <em>in vitro</em> compared to wild-type U87 cells. This phenotype is retained <em>in vivo</em>. Biomechanically, U87^R132H cells are significantly less stiff and supplementation with ferrous ammonium sulfate (Fe²⁺) augments membrane fluidity to drive U87^R132H cells into a super motile state. These findings provide insight into how an acquired IDH mutation may be able to modulate iron metabolism, allowing iron to serve as a biomechanical driver of tumor progression.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 109-116"},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647394","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":"Inducible and reversible SOD2 knockdown in mouse skeletal muscle drives impaired pyruvate oxidation and reduced metabolic flexibility","authors":"Ethan L. Ostrom ,&nbsp;Rudy Stuppard ,&nbsp;Aurora Mattson-Hughes ,&nbsp;David J. Marcinek","doi":"10.1016/j.freeradbiomed.2024.10.310","DOIUrl":"10.1016/j.freeradbiomed.2024.10.310","url":null,"abstract":"<div><h3>Introduction</h3><div>Skeletal muscle mitochondrial dysfunction is a key characteristic of aging muscle and contributes to age related diseases such as sarcopenia, frailty, and type 2 diabetes. Mitochondrial oxidative stress has been implicated as a driving factor in these age-related diseases, however whether it is a cause, or a consequence of mitochondrial dysfunction remains to be determined. The development of flexible genetic models is an important tool to test the mechanistic role of mitochondrial oxidative stress on skeletal muscle metabolic dysfunction. We characterize a new model of inducible and reversible mitochondrial redox stress using a tetracycline controlled skeletal muscle specific short hairpin RNA targeted to superoxide dismutase 2 (iSOD2).</div><div>Methods: iSOD2 KD and control (CON) animals were administered doxycycline for 3- or 12- weeks and followed for up to 24 weeks and mitochondrial respiration and muscle contraction were measured to define the time course of SOD2 KD and muscle functional changes and recovery.</div></div><div><h3>Results</h3><div>Maximum knockdown of SOD2 protein occurred by 6 weeks and recovered by 24 weeks after DOX treatment. Mitochondrial aconitase activity and maximum mitochondrial respiration declined in KD muscle by 12 weeks and recovered by 24 weeks. There were no significant differences in antioxidant or mitochondrial biogenesis genes between groups. Twelve-week KD showed a small, but significant decrease in muscle fatigue resistance. The primary phenotype was reduced metabolic flexibility characterized by impaired pyruvate driven respiration when other substrates are present. The pyruvate dehydrogenase kinase inhibitor dichloroacetate partially restored pyruvate driven respiration, while the thiol reductant DTT did not.</div></div><div><h3>Conclusion</h3><div>We use a model of inducible and reversible skeletal muscle SOD2 knockdown to demonstrate that elevated matrix superoxide reversibly impairs mitochondrial substrate flexibility characterized by impaired pyruvate oxidation. Despite the bioenergetic effect, the limited change in gene expression suggests that the elevated redox stress in this model is confined to the mitochondrial matrix.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 237-250"},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647392","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}

{"title":"Short-term exposure to low doses of aflatoxin B1 aggravates nonalcoholic steatohepatitis by TLR4-mediated necroptosis","authors":"Junya Zeng ,&nbsp;Li Chen ,&nbsp;Jiangyu Tang ,&nbsp;Junxin Xue ,&nbsp;Qi Wang ,&nbsp;Xinyu Feng ,&nbsp;Xingxiang Chen ,&nbsp;Kehe Huang ,&nbsp;Fang Gan","doi":"10.1016/j.freeradbiomed.2024.11.027","DOIUrl":"10.1016/j.freeradbiomed.2024.11.027","url":null,"abstract":"<div><div>Aflatoxin B1 (AFB1), a worldwide mycotoxin found in food and foodstuffs, is a potent hepatotoxin in humans and animals. Non-alcoholic fatty liver disease (NAFLD), a widespread disease, could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis, and even hepatocellular carcinoma (HCC). To date, little is known concerning the relationship between AFB1 and the progression of NAFLD. The effects of low doses of AFB1 on the development of NASH and their mechanism were investigated <em>in vivo</em> and <em>in vitro</em>. The results <em>in vivo</em> showed that AFB1 at 20 and 40 μg/kg.bw aggravated CDAHFD-induced NASH in mice as demonstrated by increasing the serum and liver lipid accumulation, liver inflammation and injury. The results <em>in vitro</em> showed that AFB1 at 1.0 μM aggravated FFA-induced lipid accumulation, inflammation and cell damage in HepG2 cells. In addition, RNA-seq indicated that necroptosis, Toll like receptor signaling and TNF-α signaling showed a significant change in KEGG pathway enrichment in AFB1 at 40 μg/kg.bw. AFB1 significantly upregulated the mRNA and protein levels of TLR4, RIPK3, p-RIPK3, MLKL and p-MLKL, and increased TUNEL positive cells. Also, immunofluorescence results showed that TUNEL, TLR4, TNF-α had co-localized with RIPK3, respectively. Necroptosis inhibitor (GSK-872) attenuated the aggravating effects of AFB1 on NASH. Knockout of TLR4 inhibited necroptosis and rescued the aggravating effects of AFB1 on NASH. These data indicate that low dose of AFB1 aggravated NASH via TLR4-mediated necroptosis. This suggests that low dose of AFB1 is potentially harmful to animals and humans, as they exacerbate NASH.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"226 ","pages":"Pages 129-142"},"PeriodicalIF":7.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643473","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}