Free Radical Biology and Medicine最新文献

{"title":"Bisphenol A induces hepatotoxicity via a LAMP3-dependent impairment of mitophagic processing and reduced PI3K-AKT-mTOR signaling.","authors":"Bin Lu, Yuhui Shi, Xingzhi Chen, Yongheng Huang, Jie Ding, Mingxing Xu, Yuan Feng, Nan Lin","doi":"10.1016/j.freeradbiomed.2026.10.024","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.024","url":null,"abstract":"<p><p>Bisphenol A (BPA) is a ubiquitous environmental toxicant, but the mechanisms underlying BPA-associated hepatic injury remain incompletely understood. This study investigated the involvement of lysosome-associated membrane protein 3 (LAMP3) in mitophagy-related alterations and downstream survival signaling. Human hepatocellular carcinoma-derived Huh7 and PLC5 cells and a mouse model of 4-week BPA exposure were used. Cell proliferation and apoptosis were assessed using CCK-8, EdU, TUNEL, and flow cytometry; mitochondrial function and morphology were evaluated using JC-1, MitoTracker, reactive oxygen species detection, and transmission electron microscopy. RNA sequencing identified BPA-responsive genes, followed by LAMP3 loss- and gain-of-function experiments and chloroquine (CQ) treatment. BPA exposure was associated with proliferative arrest, apoptosis, mitochondrial dysfunction, increased oxidative stress, accumulation of acidic vesicular organelles, an increased LC3B-II/I ratio, and p62 accumulation-a pattern consistent with impaired late-stage mitophagic processing. LAMP3 was strongly upregulated after BPA exposure. LAMP3 silencing attenuated mitochondrial and cellular injury, reduced p62, increased LysoTracker signal, and increased PI3K-AKT-mTOR phosphorylation; CQ attenuated these protective changes. Conversely, LAMP3 overexpression aggravated BPA-associated injury and produced marker changes consistent with impaired autophagic processing. Together, these findings support LAMP3 as a contributor to BPA-associated cellular injury in the Huh7 and PLC5 models studied and suggest an association between LAMP3-related lysosomal alterations, impaired mitophagic processing, and reduced PI3K-AKT-mTOR signaling. Because dynamic mitophagic flux was not directly measured and LAMP3 was not targeted in vivo, the proposed pathway requires confirmation using tandem flux reporters, primary human hepatocytes, and in vivo genetic models.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192654","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":"Redox resilience in skeletal muscle aging: cellular adaptations and exercise-mediated homeostasis.","authors":"Eva Tamayo-Torres, Miriam Martinez-Canton, Silvana Soto-Rodriguez, Abril Gorgori-Gonzalez, Julian Carretero, Juan Ignacio Cervera-Miguel, Olga Laosa, Leocadio Rodriguez-Mañas, Maria Carmen Gomez-Cabrera","doi":"10.1016/j.freeradbiomed.2026.10.023","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.023","url":null,"abstract":"<p><p>Aging progressively impairs skeletal muscle function, leading to sarcopenia, frailty, and loss of independence. Although oxidative stress has long been considered a central driver of muscle aging, increasing evidence indicates that reactive oxygen species (ROS) also serve essential signaling functions that coordinate mitochondrial remodeling, proteostasis, metabolism, and tissue repair. Consequently, age-related muscle dysfunction is increasingly understood as reflecting impaired adaptive redox signaling rather than excessive oxidant production alone. In this review, we propose the concept of redox resilience as an integrative framework describing the capacity of skeletal muscle to preserve structural integrity and functional performance through the dynamic regulation of oxidant production, antioxidant defenses, and redox-sensitive signaling in response to physiological challenges. We discuss how aging disrupts this resilience through impaired redox-sensitive signaling, including the attenuation of exercise-induced Nrf-2 activation, together with alterations in the multicellular organization of skeletal muscle. Recent advances in single-cell and single-nucleus transcriptomics have revealed that muscle aging involves profound remodeling of specialized myonuclear populations, stromal cells, immune cells, and intercellular communication networks, highlighting the multicellular complexity of skeletal muscle aging and providing a framework to investigate how redox-dependent processes may interact with tissue-wide signaling networks. We further examine how regular physical exercise reinforces redox resilience by promoting transient ROS-mediated signaling through NADPH oxidases, activation of Nrf-2 and PGC-1α-dependent pathways, mitochondrial quality control, and metabolic remodeling. These adaptations enhance the capacity of skeletal muscle to respond to physiological stress while preserving tissue homeostasis. Finally, we discuss future perspectives for targeting adaptive redox networks to promote healthy muscle aging and propose that restoring redox resilience may preserve physiological ROS signaling while strengthening endogenous antioxidant responses and limiting excessive oxidative damage, thereby contributing to the maintenance of muscle function and health span.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192603","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":"Sdhd hypermethylation promotes succinate accumulation and NLRP3-related pyroptosis in septic lung injury.","authors":"Yan Fan, Haiyan Zhang, Shuqi Meng, Shuang Li, Lintao Lou, Keliang Xie, Jiang Xie","doi":"10.1016/j.freeradbiomed.2026.10.022","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.022","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (Si-ALI) involves metabolic and inflammatory dysregulation; however, its underlying mechanisms remain unclear. Here, we investigated the role of succinate accumulation and epigenetic silencing of succinate dehydrogenase subunit D (SDHD) in Si-ALI using septic mice, macrophages, and a publicly available transcriptomic dataset from patients with sepsis. Succinate supplementation increased lung inflammation, macrophage pyroptosis, and mortality in septic mice. Analysis of the GSE54514 dataset showed reduced SDHD expression in patients with sepsis. In septic mice, Sdhd overexpression reduced succinate accumulation, pyroptosis, lung injury, and mortality. In macrophages, Sdhd overexpression reduced oxidative mitochondrial DNA (ox-mtDNA) release and NLRP3-related pyroptosis. Mechanistically, sepsis-induced upregulation of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) was associated with Sdhd promoter hypermethylation and reduced Sdhd expression. Pharmacological DNMT inhibition with SGI-1027 reversed Sdhd promoter hypermethylation, restored Sdhd expression, reduced succinate accumulation and pyroptosis, and ameliorated lung injury. These findings support a DNMT-SDHD-succinate axis in sepsis-induced lung injury and suggest that targeting this pathway may represent a potential therapeutic target for Si-ALI.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192617","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":"Integrated Roles of The Thioredoxin-related Protein of 14 kDa, TRP14, in Sulfur Amino Acid Metabolism, Protein Posttranslational Modifications and Signaling.","authors":"Juan Sastre, Avia J Simmons, Antonio Miranda-Vizuete, Elias S J Arnér, Peter Nagy, Antonio Martínez-Ruiz, Edward E Schmidt","doi":"10.1016/j.freeradbiomed.2026.10.033","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.033","url":null,"abstract":"<p><p>Thioredoxins and glutaredoxins are typically small \"redoxin\" proteins that play predominant roles in shuttling reducing power from the primary nicotinamide adenine dinucleotide phosphate (NADPH)-dependent disulfide reductases, thioredoxin reductase (TrxR, TXNRD) and glutathione disulfide-reductase (Gsr) to diverse downstream substrates. Cells can have dozens to hundreds of redoxin proteins, which in combination will reduce a vast array of substrates, including proteins, metabolites, and others. Whereas there is considerable overlap between different redoxins and their preferred substrates, the thioredoxin-related protein of 14 kDa, TRP14 (also named TXNDC17), has unique characteristics that support its critical roles in cysteine acquisition and mediation of redox-regulation in cellular signaling. TRP14 is particularly efficient at cystine reduction and at modulating protein nitrosylation, cysteinylation, and persulfidation, yet it does not effectively reduce many common redoxin substrates including redox enzymes and oxidative stress-induced protein-disulfides. We propose that this functional specialization allows TRP14 to support its essential roles in cysteine acquisition and signaling under both normal and oxidative stress conditions, in the latter case, wherein other redoxins likely become overwhelmed resolving oxidative stress. Specialized attributes of TRP14 are reviewed and discussed here.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180424","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":"Hepatic HSD17B6 promotes lipid accumulation and M1 macrophage polarization via the 9-cis-retinoic acid and RXRα axis.","authors":"Xiaona Cheng, Kaikai Lu, Zizhen Guo, Luyun Yang, Keyu Yang, Kexin Cheng, Litao Wu, Chunyan Yin, Muhammad Shahzad, Dongmin Li","doi":"10.1016/j.freeradbiomed.2026.10.029","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.029","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly prevalent and lacks effective therapies. Hydroxysteroid 17-beta dehydrogenase 6 (HSD17B6), a liver-enriched enzyme involved in retinoid and steroid metabolism, has not been functionally characterized in MASH pathogenesis.</p><p><strong>Methods: </strong>Transcriptomic analysis of PDCD4-deficient livers identified HSD17B6 as a key upregulated gene. Its expression was validated in human MASH liver samples and murine MASH models and localized primarily to hepatocytes via single-cell RNA sequencing. Hepatic 9-cis-retinoic acid (9cRA) was quantified by HPLC. Functional consequences of HSD17B6 modulation were assessed in stable gain- and loss-of-function hepatocyte models. Underlying mechanisms were dissected using siRNA silencing and pharmacological inhibitors.</p><p><strong>Results: </strong>PDCD4 deficiency upregulated HSD17B6, leading to increased hepatic 9cRA. 9cRA activated the nuclear receptor RXRα, which in turn promoted lipid accumulation by transactivating genes such as SCD1 and CD36. Concurrently, RXRα activation directly stimulated the transcription and secretion of the chemokine CXCL10 from hepatocytes, which drove M1 macrophage polarization via CXCR3. Both genetic and pharmacological inhibition of RXRα effectively mitigated HSD17B6-driven lipid dysregulation and macrophage-mediated inflammation.</p><p><strong>Conclusions: </strong>Using a PDCD4-deficient mouse model and complementary in vitro and human data, this study identifies HSD17B6 as an important contributor to hepatic lipid accumulation and inflammation in MASH. Mechanistically, HSD17B6 promotes these pathological processes through modulation of the 9cRA-RXRα signaling axis. These findings provide new insights into the metabolic-inflammatory crosstalk underlying MASH progression and suggest that the HSD17B6-RXRα pathway may represent a potential therapeutic target for mitigating hepatic steatosis and inflammation.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180339","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":"SOCS1/Wnt/IL-1β axis negatively regulates macrophage extracellular traps and M1 polarization through the TNF pathway in crystalline kidney injury.","authors":"Zefeng Xue, Yushi Sun, Bojun Li, Ting Rao, Yuan Ruan, Xiangjun Zhou, Fan Cheng","doi":"10.1016/j.freeradbiomed.2026.10.002","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.002","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Calcium oxalate (CaOx) crystals are known to induce kidney damage and trigger inflammatory responses. However, the role of macrophage extracellular traps (METs) in CaOx-induced kidney injury and the relationship between METs and the M1 polarization phenotype of macrophages remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A CaOx crystal deposition model was established in C57BL/6J mice using a high-calcium diet supplemented with vitamin D. Renal tissues from patients with CaOx stones and healthy controls were also collected. In vitro, mouse RAW264.7 macrophages (RAW cells) were stimulated with calcium oxalate monohydrate (COM) crystals or IL-1β. Immunofluorescence, flow cytometry, qRT-PCR, and western blotting were used to assess METs formation and M1 polarization. Genes regulating IL-1β expression were screened using TCMK-1 renal tubular epithelial cells. mRNA sequencing was performed in both cell types to identify relevant signaling pathways. In TCMK-1 cells and mouse kidneys, SOCS1 was overexpressed or knocked down using lentivirus or siRNA. CHIR-99021 and TNFR2-Fc were used to activate the Wnt signaling pathway and inhibit the TNF signaling pathway, respectively. In the in vivo model with regulated SOCS1 expression, METs levels and M1 polarization were quantified, and the potential feedback loop between METs and the TNF signaling pathway was examined through co-culture and sequential stimulation experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We found that renal tissues from patients with calcium oxalate stones and from mice with crystal deposition exhibited marked accumulation of macrophage extracellular traps (METs), identified as citH3&lt;sup&gt;+&lt;/sup&gt;/SYTOX-Green&lt;sup&gt;+&lt;/sup&gt; extracellular structures, accompanied by significantly increased M1-polarized (iNOS&lt;sup&gt;+&lt;/sup&gt;) macrophage infiltration. Calcium oxalate monohydrate (COM) crystals directly triggered MET formation and M1 polarization in RAW264.7 macrophages, and IL-1β stimulation alone was sufficient to reproduce these effects. METs themselves further promoted M1 polarization. In TCMK-1 renal tubular epithelial cells, we identified SOCS1 as a negative regulator of IL-1β transcription acting through the Wnt signaling pathway; accordingly, SOCS1 overexpression in mice markedly reduced renal MET burden and M1 macrophage infiltration in oxalate nephropathy. Mechanistically, IL-1β activated the TNF signaling pathway, which was both necessary and sufficient for MET release and subsequent M1 polarization. In turn, METs sustained TNF pathway activity, establishing a positive feedback loop that amplified both MET formation and M1 polarization. Disruption of TNF signaling abrogated this loop and significantly attenuated M1 polarization in vitro and in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In the renal microenvironment of CaOx crystal deposition, IL-1β induces METs formation by activating the TNF signaling pathway and promotes M1 polarization. In turn, METs sustain the ","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180459","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":"Glucosamine and selenium differentially regulate glutathione, lipid peroxidation, and mitochondrial function during glutamate stress in retinal neural cells.","authors":"Ying-Jen Chen, Yuan-Yuei Chen, Shu-Ting Liu, Chen-Jung Wu, Yi-Lin Chiu","doi":"10.1016/j.freeradbiomed.2026.10.031","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.031","url":null,"abstract":"<p><p>Glutamate can disrupt cystine-dependent glutathione metabolism and promote oxidative and mitochondrial dysfunction in neural cells. We integrated human multiple-sclerosis optic-chiasm transcriptomics (GSE100297), glutamate-treated primary-neuron RNA sequencing (GSE255041), R28 differential-expression summaries, a normal human optic-nerve single-nucleus atlas (GSE236566), and R28 retinal precursor-cell experiments to characterize glucosamine (GlcN) and selenium responses. Human tissue showed enriched unfolded-protein-response, oxidative-stress, apoptosis, and ferroptosis programs, whereas glutamate-treated neurons predominantly exhibited amino-acid stress, unfolded-protein response, oxidative stress, and apoptosis, with weaker concordant ferroptosis enrichment. Glutamate reduced R28 metabolic activity, GSH/GSSG, and mitochondrial respiration and increased DCFH-DA and BODIPY-C11 oxidation. GlcN (2.5 mM) shifted the glutamate dose-response curve rightward and preserved GSH/GSSG and respiration, but lowered basal metabolic activity, mitochondrial membrane potential, and ATP-based viability. GlcN increased the LC3B-II/LC3B-I ratio, while changes in PCNA-normalized NRF2-related protein signals were modest. Ferrostatin-1 (Fer-1) partially restored respiration during glutamate exposure and was associated with higher ATP-based viability. RSL3 and erastin markedly reduced viability without glutamate; Fer-1 substantially restored viability, whereas GlcN did not. Selenium (1 μM) partially reduced RSL3-associated loss of viability without glutamate; the selenium-associated viability gain diminished during glutamate co-exposure (adjusted interaction P=0.0342). Selenium showed dose-dependent effects: 1 and 5 μM preserved metabolic activity, 5 μM reduced lipid oxidation, and 20 μM increased basal lipid oxidation. GlcN increased global O-GlcNAc modification approximately 3.6-fold and altered gp130 migration. In normal human optic nerve, redox/lipid-peroxidation programs were highest in myeloid cells, whereas hexosamine/O-GlcNAc capacity and SLC7A11 expression were prominent in astrocytic-stromal compartments. These findings identify distinct functional responses to GlcN and selenium within a mixed glutamate-stress phenotype that includes a ferrostatin-sensitive component. The GPX4 dependence of GlcN-mediated protection against glutamate remains unresolved.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180392","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":"GLS2 Promotes Early Ferroptosis Followed by Apoptosis and p53 Signaling in Renal Ischemia-Reperfusion Injury.","authors":"Kazuki Ishiwata, Sawako Suzuki, Chiwei Lee, Noriko Yamanaka, Ichiro Manabe, Masashi Yamaguchi, Kumiko Naito, Yutaro Ruike, Yoshiro Maezawa, Hiroki Nakanishi, Akitoshi Nakayama, Takashi Miki, Tomoaki Tanaka, Koutaro Yokote","doi":"10.1016/j.freeradbiomed.2026.10.015","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.015","url":null,"abstract":"<p><p>Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), particularly in the settings of kidney transplantation and perioperative care. In IRI-induced AKI, ferroptosis, an iron-dependent, lipid peroxidation-driven form of regulated cell death, occurs early in proximal tubular epithelial cells; however, the precise molecular mechanisms underlying ferroptosis, its crosstalk with other forms of regulated cell death, and its clinical relevance remain incompletely understood. We previously identified glutaminase 2 (GLS2) as a key regulator of ferroptosis via α-ketoglutarate (αKG). Because GLS2 is expressed in renal tubular cells, we investigated the role of the GLS2-αKG-ferroptosis axis using Gls2 knockout (KO) mice and an in vitro hypoxia-reoxygenation model mimicking renal IRI. Compared with wild-type (WT) mice, KO mice showed markedly attenuated tubular injury, accompanied by reduced mitochondrial shrinkage and decreased chromatin condensation in tubular cell nuclei. At 12 h post-IRI, ferroptosis-associated gene expression and GLS2-αKG-driven lipid peroxidation were significantly reduced in KO mice. At 24 h post-IRI, p53 and apoptosis-related gene expression, as well as caspase-3 cleavage, were also reduced. Moreover, intraperitoneal administration of a ferroptosis inhibitor, as well as local glutaminase inhibition via glutaminase inhibitor-impregnated surgical gauze applied to the kidney during ischemia, attenuated ferroptosis, subsequent apoptosis, and tubular injury in vivo in WT mice. To assess the clinical relevance of these findings, we analyzed publicly available Gene Expression Omnibus (GEO) datasets and found increased PTGS2 and GLS2 expression in human kidneys following IRI. These findings suggest that targeting the GLS2-ferroptosis axis represents a promising therapeutic strategy for ischemic AKI.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164986","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 \"Glucocorticoids-driven mitochondrial GR translocation promotes heat stress-induced mastitis via the mtDNA-cGAS-STING-NF-κB/NLRP3 pathway\" [Free Radic. Biol. Med. 254, (2026), 714-729].","authors":"Yuhong He, Zeming Zhou, Xin Wei, Nier Su, Tingting Yang, Keyi Wang, Yushan Liu, Xuyang Li, Xiaoyu Hu, Yunhe Fu","doi":"10.1016/j.freeradbiomed.2026.10.009","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.10.009","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135142","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":"Icariin binds to Hk2 to suppress pro-inflammatory polarization of alveolar macrophages by influencing the Hk2/Hk3/Pgk1/glycolysis axis in HDM-induced asthma.","authors":"Xiaofei Zhu, Weifeng Tang, Lingling Deng, Bin Wang, YueRen Wu, Huahe Zhu, Wenjing Chen, Congcong Li, Nabijan Mohammadtursun, Mamatjan Abduwaki, Mammat Nurahmat, Jingcheng Dong","doi":"10.1016/j.freeradbiomed.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.09.009","url":null,"abstract":"<p><strong>Background: </strong>Allergic asthma is a common respiratory disorder in which glycolysis-driven pro-inflammatory polarization of alveolar macrophages (AMs) plays an important role. Icariin (ICA), a natural flavonoid glycoside, has mechanisms in house dust mite (HDM)-induced asthma that remain elusive.</p><p><strong>Objective: </strong>To investigate the protective effects of ICA against HDM-induced asthma and determine its effects on AMs.</p><p><strong>Methods: </strong>A murine model of HDM-induced asthma was established, and mice were treated with ICA. High-purity AMs were isolated for transcriptomic and untargeted metabolomic analyses. Surface plasmon resonance (SPR) and molecular docking were performed to assess the binding affinity between ICA and hexokinase 2 (Hk2). The involvement of the Hk2/Hk3/Pgk1 pathway was further validated in vitro using the Hk2 inhibitor 3-BrPA and lentiviral-mediated Hk2 overexpression.</p><p><strong>Results: </strong>ICA alleviated airway inflammation in asthmatic mice and suppressed the pro-inflammatory activation of AMs. Integrated multi-omics analyses showed that ICA restored glycolytic homeostasis by downregulating the Hk2/Hk3/Pgk1 pathway. SPR and molecular docking analyses confirmed direct binding of ICA to Hk2 with high affinity (KD = 27.65 μM). In vitro, ICA suppressed glycolytic flux and pro-inflammatory activation in AMs, effects that were also observed following intervention with 3-BrPA. Hk2 overexpression attenuated ICA's protective effects on AMs, supporting the involvement of the Hk2-mediated glycolytic pathway in ICA's anti-inflammatory activity.</p><p><strong>Conclusion: </strong>This study is the first to integrate transcriptomic and metabolomic analyses of AMs from ICA-treated asthmatic mice. The findings suggest that ICA alleviates HDM-induced asthma, potentially by binding to Hk2 and modulating the Hk2/Hk3/Pgk1 pathway, regulating glycolysis and inflammatory responses in AMs.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029949","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}