Free Radical Research最新文献_第2页

Molecular mechanism of METTL7B-mediated m6A modification in ferroptosis of non-small cell lung cancer cells. mettl7b介导的m6A修饰在非小细胞肺癌铁凋亡中的分子机制。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-02-01 Epub Date: 2026-03-12 DOI: 10.1080/10715762.2026.2629347

Rancen Tao, Zuo Liu, Zhenning Zhang, Zhenfa Zhang

{"title":"Molecular mechanism of METTL7B-mediated m6A modification in ferroptosis of non-small cell lung cancer cells.","authors":"Rancen Tao, Zuo Liu, Zhenning Zhang, Zhenfa Zhang","doi":"10.1080/10715762.2026.2629347","DOIUrl":"10.1080/10715762.2026.2629347","url":null,"abstract":"Nonsmall cell lung cancer (NSCLC) is the predominant form of lung cancer. Ferroptosis is a novel therapeutic target against treatment resistance in NSCLC. However, its regulation by m6A RNA modification remains incompletely elucidated. m6A RNA modification mediates mRNA stability, translation, and splicing to target transcripts. Methyltransferase like 7B (METTL7B) has been implicated in tumor progression, but its role in NSCLC ferroptosis via m6A modification has not been reported. We aimed to investigate the mechanism of METTL7B-mediated m6A modification in NSCLC cell ferroptosis. NSCLC cells (SK-MES-1/PC9/H1975/A549) and normal cells (BEAS-2B) were cultured. The expression of METTL7B, long non-coding RNA 02159 (LINC02159), and aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) was determined. After METTL7B knockdown, cell viability was measured by MTT assay; ferroptosis-related factors were analyzed. m6A quantification was performed. m6A enrichment on LINC02159 was analyzed. The interaction between LINC02159 and KAT2A was verified. KAT2A and H3K27ac enrichment on the ARNTL2 promoter was detected. The roles of LINC02159 and ARNTL2 were validated. METTL7B, LINC02159, and ARNTL2 were upregulated in NSCLC cells compared to BEAS-2B cells. METTL7B knockdown increased iron ions, reactive oxygen species, and malondialdehyde levels and decreased cell viability, superoxide dismutase, and glutathione levels. METTL7B potentially upregulated LINC02159 expression through m6A modification. LINC02159 may recruit KAT2A to enhance H3K27ac enrichment on the ARNTL2 promoter, thereby promoting ARNTL2 expression. Overexpression of LINC02159 or ARNTL2 partially reversed the pro-ferroptotic effects of METTL7B knockdown on NSCLC cells. In conclusion, METTL7B inhibits ferroptosis in NSCLC cells via the LINC02159/KAT2A/ARNTL2 axis in an m6A-dependent manner.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"157-168"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Retinoic acid reduces oxidative stress and enhances migration-related signaling in vascular endothelial cells. 维甲酸减少氧化应激，增强血管内皮细胞的迁移相关信号。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-02-01 Epub Date: 2026-04-13 DOI: 10.1080/10715762.2026.2657820

Kei Miyano, Shuichiro Okamoto, Sae Mishima, Shigeko Fushimi, Kumiko Terada, Akira Yamauchi, Futoshi Kuribayashi, Mizuho Kajikawa, Shin-Ichiro Nishimatsu, Momoe Itsumi

{"title":"Retinoic acid reduces oxidative stress and enhances migration-related signaling in vascular endothelial cells.","authors":"Kei Miyano, Shuichiro Okamoto, Sae Mishima, Shigeko Fushimi, Kumiko Terada, Akira Yamauchi, Futoshi Kuribayashi, Mizuho Kajikawa, Shin-Ichiro Nishimatsu, Momoe Itsumi","doi":"10.1080/10715762.2026.2657820","DOIUrl":"10.1080/10715762.2026.2657820","url":null,"abstract":"Despite the important role of retinoic acid (RA) in vascular development, its effects on the behavior of endothelial cells (ECs) lining blood vessels remain incompletely understood. In this study, we investigated the effects of RA on oxidative stress and migration, both of which are associated with angiogenesis, using EA.hy926 human ECs. RA suppressed hydrogen peroxide (H2O2) production by EA.hy926 cells in a treatment duration- and concentration-dependent manner without altering the expression of NADPH oxidase 4 (Nox4), the primary H2O2-generating enzyme. This suppression of oxidative stress resulted from a decrease in the intracellular levels of NADPH, the substrate for Nox4, induced by transcriptional downregulation of the glucose-6-phosphate dehydrogenase gene, which encodes the rate-limiting enzyme in NADPH production. RA also enhanced EC migration by increasing vascular endothelial growth factor receptor 2 (VEGFR-2) expression and stabilizing its endoplasmic reticulum-retained form, resulting in increased cell surface VEGFR-2 levels. Thus, RA treatment of ECs modulates angiogenesis-related functions by suppressing excessive oxidative stress and promoting VEGFR-2-dependent cell migration.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"212-224"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Carnosine alleviates high glucose-induced renal tubular cell pyroptosis by activating the AMPK/SIRT3/SOD2 pathway. 肌肽通过激活AMPK/SIRT3/SOD2通路减轻高糖诱导的肾小管细胞焦亡。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-02-01 Epub Date: 2026-03-22 DOI: 10.1080/10715762.2026.2640501

Kunxiao Zhao, Wenting Zhao, Xiuhong Hu, Jing Liu, Jie Feng, Qiongzhen Lin, Zhaoxu Hong

{"title":"Carnosine alleviates high glucose-induced renal tubular cell pyroptosis by activating the AMPK/SIRT3/SOD2 pathway.","authors":"Kunxiao Zhao, Wenting Zhao, Xiuhong Hu, Jing Liu, Jie Feng, Qiongzhen Lin, Zhaoxu Hong","doi":"10.1080/10715762.2026.2640501","DOIUrl":"10.1080/10715762.2026.2640501","url":null,"abstract":"Diabetic nephropathy (DN) is a major complication driven by inflammation and oxidative stress (OS); mitochondrial reactive oxygen species (mtROS)-activated NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome-induced pyroptosis is a key mechanism. Carnosine, notably an endogenous dipeptide with antioxidant and anti-glycation effects, has renoprotective potential but its mechanism remains unclear. High glucose (HG)-treated HK-2 cells were used as an in vitro model. We assessed cell viability, mtROS, and the expression of AMP-activated protein kinase (AMPK)/sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) and NLRP3 pathway proteins using Western blot and quantitative real-time PCR (qPCR). Pyroptotic cell death was confirmed by measuring the cleavage of gasdermin D (GSDMD) and lactate dehydrogenase (LDH) release. The roles of SIRT3 and AMPK were validated using small interfering RNA (siRNA) and a pharmacological inhibitor. Cellular adenosine triphosphate (ATP) levels were measured to assess the bioenergetic status. Carnosine reversed HG-induced decreases in cell viability and increases in mtROS. HG conditions also led to a significant depletion of cellular ATP, which was partially restored by carnosine. Mechanistically, carnosine activated the AMPK/SIRT3 axis, promoting the deacetylation and activation of SOD2. This suppressed NLRP3 inflammasome activation, evidenced by reduced levels of NLRP3, ASC, cleaved caspase-1, as well as reduced cleavage of GSDMD into its N-terminal fragment (GSDMD-N), reduced LDH release, and downstream cytokines. These protective effects were dependent on both AMPK and SIRT3. Carnosine protects renal tubular cells from HG-induced injury by alleviating mitochondrial OS and subsequent NLRP3 inflammasome-mediated pyroptosis through the activation of the AMPK/SIRT3/SOD2 signaling pathway. This activation is likely mediated by carnosine's ability to restore cellular bioenergetics.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"169-182"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Role of ferroptosis in 2, 4, 6-trinitrobenzenesulfonic acid induced ulcerative colitis: targeting iron metabolism for therapeutic gain. 铁下垂在2,4,6 -三硝基苯磺酸诱导的溃疡性结肠炎中的作用：靶向铁代谢以获得治疗效果。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-02-01 Epub Date: 2026-02-05 DOI: 10.1080/10715762.2026.2625102

Akshata Devkar, Satish Mandlik, Deepa Mandlik

{"title":"Role of ferroptosis in 2, 4, 6-trinitrobenzenesulfonic acid induced ulcerative colitis: targeting iron metabolism for therapeutic gain.","authors":"Akshata Devkar, Satish Mandlik, Deepa Mandlik","doi":"10.1080/10715762.2026.2625102","DOIUrl":"10.1080/10715762.2026.2625102","url":null,"abstract":"Ulcerative colitis (UC), a major form of inflammatory bowel disease (IBD), is characterized by chronic inflammation and ulceration of the colonic mucosa. Its etiology is multifactorial, involving genetic, environmental, and immune factors. Recent evidence highlights the crucial role of ferroptosis, an iron-dependent regulated cell death pathway, in UC pathogenesis. Ferroptosis is marked by excessive accumulation of lipid peroxides, reactive oxygen species, and iron overload, all contributing to epithelial injury. The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model closely mimics human UC and demonstrates elevated free iron, increased malondialdehyde levels, and decreased glutathione peroxidase 4 expression hallmarks of ferroptotic damage. These molecular disturbances lead to oxidative stress, epithelial barrier dysfunction, and sustained inflammation. Importantly, ferroptosis inhibition shows therapeutic potential. Small-molecule inhibitors such as Ferrostatin-1 and Liproxstatin-1 effectively reduce mucosal damage and restore antioxidant balance, while iron chelators like deferoxamine alleviate iron overload and ROS generation. Moreover, natural compounds including curcumin, resveratrol, epigallocatechin-3-gallate, baicalein, and quercetin demonstrate anti-ferroptotic activity by modulating the nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 pathway, enhancing glutathione peroxidase 4 function, and maintaining iron homeostasis. Collectively, these findings establish ferroptosis as a pivotal mechanism in TNBS-induced UC, linking oxidative stress and iron dysregulation to mucosal injury. Targeting ferroptosis offers a promising therapeutic avenue for UC management, though further clinical and translational studies are needed to validate its efficacy and safety.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"117-146"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Acorus gramineus ethanol extract suppresses MITF-mediated melanogenesis under oxidative stress conditions. 灰菖蒲乙醇提取物在氧化应激条件下抑制mitf介导的黑色素生成。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-02-01 Epub Date: 2026-04-04 DOI: 10.1080/10715762.2026.2649026

Hyeong Jun Jeong, Chang Soon Huh

{"title":"Acorus gramineus ethanol extract suppresses MITF-mediated melanogenesis under oxidative stress conditions.","authors":"Hyeong Jun Jeong, Chang Soon Huh","doi":"10.1080/10715762.2026.2649026","DOIUrl":"10.1080/10715762.2026.2649026","url":null,"abstract":"Acorus gramineus has long been used in East Asia and exhibits diverse biological activities, yet its effects on melanogenesis under oxidative stress remain unclear. This study evaluated the antioxidant capacity of Acorus gramineus ethanol extract (AGEE) and its regulatory effects on melanogenesis in B16F1 melanoma cells under normal and oxidative stress conditions. AGEE showed concentration-dependent antioxidant activity in DPPH radical scavenging, reducing power, hydroxyl radical scavenging, and lipid peroxidation assays, while maintaining low cytotoxicity up to 25 µg/mL. In cell-free systems, AGEE directly inhibited mushroom tyrosinase activity and L-DOPA oxidation. In cellular models, AGEE significantly reduced melanin production under both basal and H2O2-induced oxidative stress conditions, with stronger inhibition observed in oxidatively damaged cells, even during α-MSH stimulation. Western blot analysis indicated that oxidative stress decreased melanogenesis-related proteins, including MITF, TYR, TRP-1, and TRP-2. Although α-MSH partially restored MITF expression, AGEE co-treatment attenuated α-MSH-induced MITF upregulation and suppressed downstream melanogenic enzymes in a concentration-dependent manner. Immunofluorescence analysis confirmed reduced MITF and TYR signals following AGEE treatment. Collectively, AGEE exerts multi-level inhibitory effects on melanogenesis via direct enzymatic inhibition, modulation of MITF-dependent pathways, and attenuation of oxidative stress. AGEE effectively suppresses melanogenic activation under both normal and oxidative stress conditions, with enhanced efficacy in redox-imbalanced environments. These findings suggest AGEE as a promising functional ingredient for managing oxidative stress-associated hyperpigmentation.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"201-211"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Follicular fluid oxidative stress and antioxidant defense in relation to maternal age, ovarian reserve, and in vitro fertilization outcomes. 卵泡液氧化应激和抗氧化防御与母亲年龄、卵巢储备和体外受精结果的关系

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-02-01 Epub Date: 2026-02-16 DOI: 10.1080/10715762.2026.2629303

Oya Korkmaz, Seda Karabulut, Pelin Macit, Cagri Cakici

{"title":"Follicular fluid oxidative stress and antioxidant defense in relation to maternal age, ovarian reserve, and in vitro fertilization outcomes.","authors":"Oya Korkmaz, Seda Karabulut, Pelin Macit, Cagri Cakici","doi":"10.1080/10715762.2026.2629303","DOIUrl":"10.1080/10715762.2026.2629303","url":null,"abstract":"Oxidative stress within the follicular microenvironment plays a critical role in oocyte quality and reproductive outcomes. This prospective study examines the association between follicular fluid redox status, maternal age, ovarian reserve, and clinical outcomes in women undergoing in vitro fertilization. Follicular fluid samples were obtained from women undergoing fresh embryo transfer cycles and analyzed for oxidative damage markers (malondialdehyde (MDA), nitric oxide, ischemia-modified albumin, and sialic acid) and antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiol-disulfide homeostasis). Participants were stratified according to maternal age (≤35 vs. >35 years), serum estradiol levels on the day of human chorionic gonadotropin trigger (≤90th vs. >90th percentile), and clinical pregnancy outcome. Anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels were recorded as indicators of ovarian reserve. Women aged >35 years exhibited significantly higher MDA and sialic acid levels, accompanied by reduced antioxidant enzyme activities. Cycles resulting in clinical pregnancy showed lower oxidative stress and higher antioxidant capacity compared with non-pregnant cycles. Malondialdehyde levels correlated positively with age and FSH, while antioxidant parameters correlated positively with AMH and pregnancy outcome. Receiver operating characteristic analysis demonstrated moderate discriminative ability of MDA, SOD, CAT, and GSH for clinical pregnancy. These findings indicate that age-related redox imbalance in follicular fluid is associated with diminished ovarian reserve and reduced in vitro fertilization success. Assessment of follicular fluid oxidative stress parameters may provide clinically relevant insights into female reproductive potential.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"147-156"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Non-thermal plasma prevents IgE-mediated Ca²⁺ influx and allergic response in RBL-2H3 cells. 非热血浆阻止ige介导的Ca2+内流和RBL-2H3细胞的过敏反应。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-01-01 Epub Date: 2026-01-19 DOI: 10.1080/10715762.2026.2617894

Tomohiro Otsuka, Ibuki Tomonaga, Koji Watabe, Tetsuro Kamiya, Hiroyuki Tanaka, Hiromasa Tanaka, Hirokazu Hara

{"title":"Non-thermal plasma prevents IgE-mediated Ca2+ influx and allergic response in RBL-2H3 cells.","authors":"Tomohiro Otsuka, Ibuki Tomonaga, Koji Watabe, Tetsuro Kamiya, Hiroyuki Tanaka, Hiromasa Tanaka, Hirokazu Hara","doi":"10.1080/10715762.2026.2617894","DOIUrl":"10.1080/10715762.2026.2617894","url":null,"abstract":"Non-thermal plasma (NTP) has been reported to exhibit various biological effects, including hemostatic, anticancer, and wound-healing properties. However, the effects of NTP on allergic responses in mast cells and basophils have not been sufficiently investigated. In this study, we examined the effects of NTP on immunoglobulin E (IgE)-mediated degranulation and cytokine expression in the basophilic cell line RBL-2H3. To induce degranulation and cytokine expression as part of allergic reactions, we treated the cells with 2,4-dinitrophenylated bovine serum albumin (BSA) after sensitization or with the Ca2+ ionophore A23187. Cells were also treated with NTP-activated acetated Ringer's solution (PAA). Degranulation was measured by quantifying the β-hexosaminidase (β-hex) activity. PAA treatment inhibited both antigen stimulation- and A23187-induced degranulation in RBL-2H3 cells, and suppressed antigen-induced mRNA expression of cytokines, including IL-4, IL-6, and TNF-α. Antigen stimulation caused disintegration of the F-actin cytoskeleton, and PAA treatment suppressed these morphological changes. Cotreatment with PAA and catalase blocked the inhibitory effects of PAA on antigen stimulation-induced degranulation. PAA also inhibited A23187-induced extracellular signal-regulated kinase (ERK) phosphorylation and antigen stimulation- or store-operated Ca2+ entry inducer thapsigargin-induced cellular Ca2+ influx. These results indicate that PAA effectively inhibits immunological responses in allergic cells - such as degranulation and cytokine expression - by suppressing ERK phosphorylation and Ca2+ influx. These findings suggest that PAA may be an effective therapeutic option for treating patients with allergic diseases.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"39-49"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mechanistic and kinetic insights into the radical scavenging capacity and Keap1-Nrf2 inhibition potency of A-type avenanthramides: DFT and molecular docking. a型avenanthrides自由基清除能力和Keap1-Nrf2抑制能力的机制和动力学研究：DFT和分子对接。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-01-01 Epub Date: 2026-02-08 DOI: 10.1080/10715762.2026.2625091

Jiayi Li, Guirong Wang, Zhennan Zhang, Shuang Jin, Fengwei Ai, Lin An, Haiyang Zhong, Ling Zhang, Youguang Zheng, Hongli Liu, Yunsheng Xue

{"title":"Mechanistic and kinetic insights into the radical scavenging capacity and Keap1-Nrf2 inhibition potency of A-type avenanthramides: DFT and molecular docking.","authors":"Jiayi Li, Guirong Wang, Zhennan Zhang, Shuang Jin, Fengwei Ai, Lin An, Haiyang Zhong, Ling Zhang, Youguang Zheng, Hongli Liu, Yunsheng Xue","doi":"10.1080/10715762.2026.2625091","DOIUrl":"10.1080/10715762.2026.2625091","url":null,"abstract":"Avenanthramides (AVAs), unique polyphenols in oats, have received much attention due to their biologically beneficial properties. Herein, density functional theory (DFT) calculations and molecular docking were performed to elucidate the structure-antioxidant capacity relationship and underlying mechanism of A-type AVAs under physiological conditions. Further, the interaction effects between AVAs and Kelch-like ECH-associated protein 1 (Keap1) for activating the Nrf2-ARE (nuclear factor-E2-related factor 2-antioxidant response element) signaling pathway were explored. The results showed that the representative A-type AVA 2 cd displayed excellent HOO• scavenging capacity in water at physiological pH with an overall rate constant (koverall = 2.97 × 107 M-1 s-1) higher than that of reference antioxidants Trolox and BHT, while moderate capacity in lipid-like media. Formal hydrogen atom transfer (fHAT) mechanism is more favored in lipid media, whereas in aqueous solution at physiological pH, the hydrogen transfer from dianion species plays a dominant role (99.4%) in the overall reactivity. The results also highlighted the effects of central double bond, hydroxyl, carboxyl and solvents in antiradical processes. Molecular docking and DFT calculations showed that 2c and 2 cd can bind strongly to Keap1 through hydrogen bonding and cysteine residues based covalent binding, which disrupts the Keap1-Nrf2 interaction. Collectively, 2c and 2 cd are promising candidates as multifunctional antioxidant with radical trapping and Nrf2 activation effects.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"91-105"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

6-Gingerol alleviates NNK-induced lung carcinogenesis by boosting antioxidation and reducing inflammation. 6-姜辣素通过增强抗氧化和减少炎症减轻nnk诱导的肺癌。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-01-01 Epub Date: 2026-01-02 DOI: 10.1080/10715762.2025.2610944

Zhuo Qu, Yan Ding, Lei Zhang, Jiachen Sun, Tianyuan Wang, Chunlin Zhuang

{"title":"6-Gingerol alleviates NNK-induced lung carcinogenesis by boosting antioxidation and reducing inflammation.","authors":"Zhuo Qu, Yan Ding, Lei Zhang, Jiachen Sun, Tianyuan Wang, Chunlin Zhuang","doi":"10.1080/10715762.2025.2610944","DOIUrl":"10.1080/10715762.2025.2610944","url":null,"abstract":"With lung cancer rates climbing steadily, the development of effective prevention strategies has become more crucial than ever. Our previous research has revealed that ginger oil possesses potential lung cancer preventive activity, demonstrating inhibitory effects against tobacco carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice. 6-Gingerol, a bioactive compound from ginger (Zingiber officinale Rosc.), exhibits multiple pharmacological activities. However, the preventive efficacy of 6-Gingerol against tobacco carcinogen-induced lung cancer remains unclear. This study investigated the chemopreventive effects of 6-Gingerol on NNK-induced lung tumorigenesis in A/J mice and Beas-2b cells. Results indicated that 6-Gingerol significantly reduced lung tumor count and improved tissue structure compared to NNK alone. In vitro, 6-Gingerol protected Beas-2b cells from NNK-induced damage. Mechanistically, 6-Gingerol activated the Nrf2 pathway, enhancing antioxidant enzyme expression and reducing oxidative stress. Additionally, 6-Gingerol exhibited anti-inflammatory effects by inhibiting the NNK-activated TLR4/NF-κB pathway. In conclusion, 6-Gingerol shows significant chemopreventive effects against NNK-induced lung cancer via activating Nrf2 and suppressing TLR4/NF-κB, underscoring its potential as a preventive agent functional food in lung cancer development.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Spermidine diminishes lipopolysaccharide-induced myocardial ferroptosis through the Keap1-Nrf2/HO-1 pathway. 亚精胺通过Keap1-Nrf2/HO-1途径减少脂多糖诱导的心肌铁下垂。

IF 2.9 3区生物学

Free Radical Research Pub Date : 2026-01-01 Epub Date: 2026-01-21 DOI: 10.1080/10715762.2026.2620031

Jun He, Xiaohong Zhang, Hongxin Jiang, Zhaoyu Liu, Yuwen Dai, Pin Zhao, Jianke Kuai

{"title":"Spermidine diminishes lipopolysaccharide-induced myocardial ferroptosis through the Keap1-Nrf2/HO-1 pathway.","authors":"Jun He, Xiaohong Zhang, Hongxin Jiang, Zhaoyu Liu, Yuwen Dai, Pin Zhao, Jianke Kuai","doi":"10.1080/10715762.2026.2620031","DOIUrl":"10.1080/10715762.2026.2620031","url":null,"abstract":"Spermidine (SPD) is a naturally-occurring polyamine with a range of unique properties including anti-inflammatory, antioxidant, and cardioprotective effects. Ferroptosis, a form of cell death that is regulated by reactive oxygen species (ROS), plays a pivotal role in sepsis-induced cardiomyopathy. However, the interplay among spermidine levels, septic myocardial injury, and ferroptosis is unclear. This study aimed to investigate the effect of spermidine on ferroptosis and the underlying mechanisms of lipopolysaccharide (LPS)-induced acute myocardial damage during sepsis. A septic myocardial injury model was established using LPS treatment of H9c2 cells and C57BL/6 mice. Spermidine mitigated LPS-induced myocardial injury, decreased inflammatory responses and oxidative stress, and inhibited cardiomyocyte ferroptosis in both cellular and animal models. Spermidine reduced intracellular iron and malondialdehyde levels, while elevating glutathione levels and the expression of cardiac ferroptosis-related proteins. SPD was found to suppress lipid peroxidation and ferroptosis by activating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Silencing Nrf2 ceased the inhibitory effect of SPD on ferroptosis in H9c2 cells. Spermidine exerted a protective effect against LPS-induced acute myocardial injury and may ameliorate LPS-induced septic myocardial ferroptosis via the Nrf2 pathway.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"50-66"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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