FREE RADICAL BIOLOGY AND MEDICINE自由基生物学与医学
FREE RADICAL BIOLOGY AND MEDICINE(英文缩写 FREE RADICAL BIO MED),ISSN 0891-5849,eISSN 1873-4596,中文译名:自由基生物学与医学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 8.101 | Q1 |
| 2022 | 7.400 | Q1 |
| 2023 | 7.100 | Q1 |
| 2024 | 8.200 | Q1 |
| 2025 | 8.000 | Q1 |
FREE RADICAL BIOLOGY AND MEDICINE 最新收录文献
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1. Ergothioneine promotes functional recovery after spinal cord injury by stabilizing VPS35 to suppress mitochondrial damage-driven neuroinflammation and oxidative stress.
1. 麦角硫因通过稳定VPS35抑制线粒体损伤驱动的神经炎症和氧化应激，促进脊髓损伤后功能恢复PMID:日期:2026-10-03Spinal cord injury (SCI) triggers a complex secondary injury cascade involving neuroinflammation, oxidative stress, and mitochondrial dysfunction. These interconnected pathological processes exacerbate neuronal damage and hinder functional recovery. However, effective therapeutic strategies targeting these interrelated pathways remain limited. Ergothioneine (EGT), a naturally occurring antioxidant with potent cytoprotective properties and a favorable safety profile, has emerged as a promising candidate for SCI intervention, yet its mechanisms of action in this context remain unclear. A mouse model of contusive SCI was established to evaluate the neuroprotective potential of ergothioneine. Mice received a moderate contusion injury at the T10 spinal segment by using a weight-drop impactor (5 g × 5 cm). Animals were randomly divided into four groups (n=6 per group): Sham, SCI+vehicle, SCI+50 mg/kg EGT, and SCI+100 mg/kg EGT, with EGT administered intraperitoneally for 7 consecutive days starting at 6 h post-injury. Functional recovery was assessed using behavioral tests, histological analyses, and electrophysiological recordings. Proteomic profiling, limited proteolysis-mass spectrometry (LiP-MS), molecular docking, and molecular dynamics simulations were employed to identify direct molecular targets of ergothioneine. In vitro studies using LPS-stimulated BV-2 microglia were conducted to investigate its effects on mitochondrial function, oxidative stress, and inflammatory responses. VPS35 knockdown experiments were performed to validate its mechanistic involvement. Ergothioneine treatment, particularly at 100 mg/kg, significantly improved locomotor recovery, preserved tissue integrity, and enhanced electrophysiological function in SCI mice. It markedly suppressed microglia-mediated neuroinflammation and oxidative stress, as indicated by reduced pro-inflammatory cytokine expression and decreased reactive oxygen species (ROS) production. Mechanistically, VPS35 was identified as a direct binding target of ergothioneine. Ergothioneine stabilized VPS35 expression, maintained mitochondrial membrane potential, reduced mitochondrial ROS generation, and alleviated mitochondrial dysfunction in activated microglia. Notably, VPS35 knockdown significantly attenuated these protective effects, demonstrating that ergothioneine exerts its actions in a VPS35-dependent manner. Our study demonstrates that EGT confers neuroprotection after SCI by targeting VPS35, stabilizing mitochondria, and suppressing microglia-driven neuroinflammation and oxidative damage. These findings nominate EGT as a promising, well-tolerated therapeutic candidate for translational SCI treatment.
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2. Coordinated Retinal Metabolic Remodeling Reveals Mitochondrial Stress and Redox Vulnerability in Experimental Myopia.
PMID:日期:2026-10-03Form-deprivation myopia (FDM) was initiated by retinal responses to abnormal visual input, but how retinal metabolism was coordinated with mitochondrial and redox homeostasis remains incompletely understood. We integrated transcriptomics, proteomics, untargeted and targeted metabolomics, U-C-glucose tracing, extracellular flux analysis, molecular validation, and transmission electron microscopy in a guinea pig FDM model. FDM retinas showed accumulation of glycolytic intermediates and lactate, increased glucose-derived carbon contribution to lactate, and upregulation of GLUT1, HK2, PFKFB3, PKM, and LDHA. Although oxidative-phosphorylation-related proteins were reduced and mitochondrial cristae were disrupted, basal, maximal, and ATP-linked oxygen consumption were not significantly decreased, indicating early mitochondrial stress rather than global respiratory failure. Glutathione abundance was reduced, whereas cystathionine, γ-glutamylphenylalanine, serine- and glycine-related metabolites, PHGDH, and SHMT2 were increased, consistent with remodeling of sulfur amino acid and one-carbon pathways in a redox-stressed metabolic environment. Lipidomics further showed increased triglycerides and membrane phospholipids, accompanied by increased CD36, FATP2, ACC1, and SCD1 and reduced PPARα, FADS1, FADS2, and ELOVL5, indicating a shift toward fatty acid uptake and synthesis at the expense of oxidation and polyunsaturated fatty acid processing. Together, these findings defined an early redox-vulnerable metabolic state in the myopic retina, in which enhanced glycolytic carbon use, compensatory amino acid remodeling, mitochondrial structural stress, and lipid redistribution occur in parallel. The identified network was hypothesis-generating and provided a framework for future cell-specific and intervention-based studies.
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3. MINOS1-Mediated Mitochondrial Remodeling: A Critical Regulator of Apoptosis in Hypoxic Intestinal Epithelium.
3. MINOS1介导的线粒体重塑：缺氧肠上皮细胞凋亡的关键调控因子PMID:日期:2026-10-03Intestinal epithelial cells (IECs) are highly vulnerable to mitochondrial dysfunction and lethal apoptosis under severe hypoxic stress. However, the upstream genetic determinants governing mucosal redox resilience remain poorly defined. To investigate the mechanisms of intestinal epithelial cell apoptosis under cobalt chloride ()-induced hypoxic conditions, we established a -induced lethal hypoxia model in IPEC-J2 cells and performed a genome-wide CRISPR-Cas9 screen. This screen identified MINOS1 as an essential gene for tolerance to -induced hypoxic cell death. Systematic cell phenotyping and transcriptomic analyses revealed that exposure triggers robust intrinsic apoptosis and oxidative stress, whereas MINOS1 ablation remodels the basal transcriptomic landscape to establish an adaptive pro-survival state. Ultrastructural observation via transmission electron microscopy and subcellular functional assays demonstrated that MINOS1 deficiency eliminates canonical crista junctions (CJs) and induces distinctive concentric, "onion-like" remodeling of the inner mitochondrial membrane. Under severe hypoxia, MINOS1-knockout (KO) enterocytes retained stable mitochondrial membrane potential (ΔΨm), suppressed pathological mitochondrial permeability transition pore (mPTP) opening, sustained antioxidant enzyme (SOD and CAT) activities, and abrogated intracellular ROS accumulation and lipid peroxidation. Pharmacological intervention with the mitochondria-targeted antioxidant Mitoquinone mesylate precisely phenocopied the cytoprotective phenotype of MINOS1 ablation, confirming a mitochondria-dependent redox regulatory mechanism. Crucially, subcellular fractionation assays verified that remodeled concentric mitochondrial membranes form a unique topological barrier that physically sequesters cytochrome c within mitochondria, blocking its cytosolic release and subsequent activation of caspase-9 and caspase-3. Accordingly, MINOS1-deficient enterocytes tolerate extreme hypoxic stress by structurally uncoupling mitochondrial oxidative stress from downstream apoptotic execution. Collectively, these findings establish MINOS1-dependent cristae topology as a fundamental biophysical gatekeeper of intestinal mucosal redox homeostasis, providing a novel structure-targeted therapeutic strategy for hypoxia-associated intestinal disorders.
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4. PM2.5 exposure impairs BMSC function and dysregulates mitochondrial oxidative stress: multi-omics insights into potential osteoporotic mechanisms.
PMID:日期:2026-10-03Although PM2.5 exposure has been increasingly linked to osteoporosis, the underlying mechanisms remain incompletely understood. This study aimed to investigate the toxic effects and molecular mechanisms of PM2.5 on bone marrow mesenchymal stem cells (BMSCs). Rat BMSCs were exposed to PM2.5. Cytotoxicity, cytoskeletal integrity, migration, mitochondrial function, and osteogenic differentiation were assessed using a range of in vitro assays. Transcriptomic and metabolomic profiling were performed, followed by integrated pathway analyses. Hub genes within the cAMP pathway were validated by qPCR, and the functional role of this pathway was confirmed by Forskolin rescue experiments. PM2.5 impaired BMSC homeostasis, reducing viability, cytoskeletal integrity, proliferation, and migration, while suppressing osteogenic differentiation via the β-catenin/Runx2 pathway. Mechanistically, PM2.5 disrupted mitochondrial homeostasis and elevated ROS. Transcriptomics identified 2372 DEGs (911 up, 1461 down), and metabolomics revealed 171 DEMs (109 up, 62 down), predominantly lipids (28.19%) and organic acids (26.17%). Integrated multi-omics highlighted cAMP signaling as a key pathway. PPI-identified hub genes were validated by qPCR. Forskolin-mediated activation of the cAMP/PKA pathway rescued PM2.5-induced signaling suppression, restored viability, attenuated ROS, preserved mitochondrial membrane potential, and recovered migration and osteogenic differentiation, suggesting a causal role of cAMP/PKA pathway inhibition in PM2.5-induced BMSC dysfunction. These findings indicate that PM2.5 impairs BMSC osteogenic capacity and mitochondrial homeostasis via suppression of the cAMP/PKA pathway, suggesting this signaling axis as a potential contributor to PM2.5-associated osteoporotic pathogenesis.
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5. Superoxide dismutase 2 haplodeficiency alters spermatogenesis and early development in mice.
5. 超氧化物歧化酶2单倍体缺陷改变小鼠精子发生和早期发育PMID:日期:2026-10-01Elevated levels of ROS are closely associated with impaired male fertility. Although spermatogenesis involves high mitochondrial oxygen consumption and consequent ROS generation, the precise mechanism by which oxidative stress contributes to sperm dysfunction remain poorly understood. Here we demonstrate for the first time that haplodeficiency of mitochondrial antioxidant enzyme SOD2/MnSOD show alterations in reproductive physiology. Colonies of Sod2 mice exhibited reduced litter size and prolonged breeding-to-parturition period, effects observed exclusively when males carried the transgene. Sod2 expression increased progressively along the spermatogenic lineage from spermatogonia to spermatozoa. Using transgenic mice expressing the mitochondrial biosensor mito-roGFP2-Orp1, we identified an inverse gradient of HO consistent with expression of the mitochondrial antioxidant enzyme expression. Both, Sod2 haplodeficient and Sod2 overexpressing mice displayed alterations in the spermatogenic series and in the seminiferous tubules stage distribution relative to wild type animals, but this was not correlated with a reduction in sperm count, motility, or viability. Notably, sperm from Sod2 mice exhibited reduced fertilization rate and significantly decreased early pre-embryonic viability during first stages following in vitro fertilization. Collectively, these findings indicate that impaired mitochondrial redox homeostasis due to Sod2 haplodeficiency compromises early embryonic development, leading to reduced reproductive success, and identify SOD2 as a potential marker of sperm functional quality.
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6. Modulation of intracellular heme metabolism enhances artesunate-induced cytotoxicity in CD44v-positive cervical cancer cells.
PMID:日期:2026-09-28In this study, we investigated the role of intracellular heme metabolism in regulating artesunate (ATS)-induced cytotoxicity to overcome therapeutic resistance in refractory cervical cancer. CD44v-positive CaSki cells exhibited resistance to both cisplatin and the ferroptosis inducer erastin, associated with elevated antioxidant capacity and impaired iron mobilization. Although ATS cytotoxicity was enhanced by exogenous heme, stimulation of endogenous heme biosynthesis with 5-aminolevulinic acid (ALA) increased intracellular heme levels and lipid peroxidation but failed to significantly enhance cell death. Targeting canonical antioxidant pathways, including reduction of glutathione (GSH) availability and inhibition of nuclear factor erythroid 2-related factor 2 (NRF2) or glutathione peroxidase 4 (GPX4), produced variable but incomplete sensitization to ATS in CaSki cells. In contrast, simultaneous stimulation of heme biosynthesis with ALA and inhibition of heme degradation with zinc protoporphyrin IX markedly increased intracellular labile heme levels and produced the strongest sensitization to ATS among the treatment conditions examined in CaSki cells. These findings support a role for intracellular heme availability in modulating the heme-dependent bioactivation and cytotoxic efficacy of ATS and suggest that the extent of labile heme accumulation may influence ATS responsiveness in CaSki cells. Collectively, our results suggest that coordinated modulation of heme biosynthesis and degradation can enhance ATS cytotoxicity and may provide a strategy for sensitizing therapy-resistant cervical cancer cells to ATS.
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8. PAQR3 promotes diabetic tubulointerstitial fibrosis by suppressing STUB1-mediated NOX4 ubiquitination.
PMID:日期:2026-09-26Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease, and tubulointerstitial fibrosis (TIF) represents its final pathological hallmark. Progestin and adipoQ receptor 3 (PAQR3) has been implicated in metabolism and inflammation, but its role in DKD remains largely unexplored. Here, we report that PAQR3 expression is markedly upregulated in the kidneys of STZ-induced diabetic mice and in high glucose-stimulated NRK-52E tubular epithelial cells, correlating with the onset of tubular epithelial-mesenchymal transition (EMT) and fibrosis. Functional studies demonstrated that PAQR3 overexpression via AAV delivery in db/db mice significantly exacerbated renal dysfunction, fibrotic lesions, and EMT, whereas PAQR3 knockdown in cultured tubular cells attenuated the EMT phenotype. Mechanistically, PAQR3 selectively increased NOX4 protein levels without affecting its mRNA expression, leading to enhanced ROS production and oxidative stress. Notably, PAQR3 suppressed STUB1-mediated NOX4 ubiquitination, thereby stabilizing NOX4 protein. Collectively, these findings suggest that PAQR3 modulates NOX4 protein stability by suppressing its ubiquitination and the PAQR3-STUB1-NOX4 axis may contribute to TIF progression in DKD.
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9. SMS2 inhibition alleviates endothelial dysfunction and atherosclerosis via promoting NFE2L1 expression to suppress ferroptosis.
PMID:日期:2026-09-25Sphingomyelin synthase 2 (SMS2) is a key enzyme in sphingomyelin synthesis and is implicated in atherosclerosis (AS). Both endothelial dysfunction (ED) and ferroptosis contribute to AS, but their relationship with SMS2 remains unclear. To explore this, we inhibited SMS2 with Ly93 and then performed RNA sequencing to assess its relationship with ferroptosis, as well as the expression, cholesterol homeostasis, and alternative splicing of NFE2L1 in endothelial cells. We also validated the relationship between SMS2, ferroptosis, and NFE2L1 in ApoE mice and clinical atherosclerotic plaque samples. Results showed that SMS2 inhibition by Ly93 reduced ferroptosis and ED. SMS2 inhibition also decreased cholesterol accumulation, enhanced skipping-exon (SE) alternative splicing of NFE2L1, and increased L-NFE2L1 levels; knockdown of L-NFE2L1 reversed these effects. In ApoE mice, endothelial-specific SMS2 overexpression worsened ED and plaque formation while reducing NFE2L1/GPX4 expression. Conversely, the ferroptosis inhibitor Fer-1 attenuated both ED and plaque burden. In unstable human plaques, SMS2 was elevated, whereas NFE2L1, GPX4, and SLC7A11 were reduced. Collectively, these findings suggest that SMS2 inhibition promotes L-NFE2L1 expression, and this effect is mediated, at least in part, by the suppression of cholesterol accumulation-driven alternative splicing of the NFE2L1 splicing event, a process that ultimately reduces oxidative stress. This depress ED via ferroptosis and ultimately decrease AS, identifying SMS2 as a potential therapeutic target.
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10. Icariin binds to Hk2 to suppress pro-inflammatory polarization of alveolar macrophages by influencing the Hk2/Hk3/Pgk1/glycolysis axis in HDM-induced asthma.
PMID:日期:2026-09-23Allergic 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. To investigate the protective effects of ICA against HDM-induced asthma and determine its effects on AMs. 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. 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. 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.