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Impact of genetic variability on NADPH oxidase activity: An extensive genotype-phenotype assessment. 遗传变异对NADPH氧化酶活性的影响:一项广泛的基因型-表型评估。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2025-06-28 DOI: 10.1080/10715762.2025.2526057
Tana Takacova, Markus Anton Schirmer
{"title":"Impact of genetic variability on NADPH oxidase activity: An extensive genotype-phenotype assessment.","authors":"Tana Takacova, Markus Anton Schirmer","doi":"10.1080/10715762.2025.2526057","DOIUrl":"https://doi.org/10.1080/10715762.2025.2526057","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidative stress is implicated in various diseases, and the NADPH oxidase enzyme complex (NOX) is a significant source of reactive oxygen species (ROS). Research linking genetic polymorphisms to enzyme activity has produced conflicting results.</p><p><strong>Methods: </strong>We aimed to establish a robust protocol to assess NOX activity in vitro under highly standardized conditions and correlate these measurements with genetic polymorphisms catalogued by the 1000 Human Genome and HapMap projects. Lymphoblastoid cell lines (LCLs) served as a model system with samples from healthy participants from three Caucasian populations. NOX activity stimulated by phorbol 12-myristate 13-acetate was measured using chemiluminescence in 290 LCLs (198 in a training and 92 in a test set) through a series of multiply repeated measurements per LCL comprising in total over 1,500 NOX activity assessments. The association between NOX activity and single nucleotide polymorphisms (SNPs) in the NOX subunit genes <i>CYBA</i>, <i>CYBB</i>, <i>NCF1</i>, <i>NCF2</i>, and <i>NCF4</i> was subsequently examined.</p><p><strong>Results: </strong>Out of 639 valid polymorphic markers, 314 had a minor allele frequency of ≥5%, and 15 SNPs showed a statistically significant correlation with NOX activity in the training set. However, these 15 associations were not confirmed in the test set (all p ≥ 0.1). Additional analyses treating all 290 LCLs as a single cohort yielded three associations at p < 0.01, i.e. CYBA rs1017828, NCF1 rs191081238, and NCF4 rs4821544. However, statistical significance could not be called for any of these genetic markers upon adjustment for multiple testing, regardless whether a co-dominant, dominant or recessive allelic effect was assumed.</p><p><strong>Conclusion: </strong>Our results do not support a reproducible impact of common genetic diversity in NOX subunits on the enzyme activity in subjects of Caucasian origin. This study represents the largest evaluation concerning relationships between NOX genetic variants and enzyme activity to date.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527088","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
Redox modulation by a synthetic thiol compound reduces LPS-induced pro-inflammatory cytokine expression in macrophages via AP-1/NLRP3 axis and influences the crosstalk with endothelial cells. 合成巯基化合物的氧化还原调节通过AP-1/NLRP3轴降低lps诱导的巨噬细胞中促炎细胞因子的表达,并影响与内皮细胞的串扰。
IF 2.9 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-07-11 DOI: 10.1080/10715762.2025.2529914
Sofia Masini, Michela Bruschi, Michele Menotta, Barbara Canonico, Mariele Montanari, Daniela Ligi, Francesca Monittola, Ferdinando Mannello, Giovanni Piersanti, Rita Crinelli, Mauro Magnani, Alessandra Fraternale
{"title":"Redox modulation by a synthetic thiol compound reduces LPS-induced pro-inflammatory cytokine expression in macrophages via AP-1/NLRP3 axis and influences the crosstalk with endothelial cells.","authors":"Sofia Masini, Michela Bruschi, Michele Menotta, Barbara Canonico, Mariele Montanari, Daniela Ligi, Francesca Monittola, Ferdinando Mannello, Giovanni Piersanti, Rita Crinelli, Mauro Magnani, Alessandra Fraternale","doi":"10.1080/10715762.2025.2529914","DOIUrl":"10.1080/10715762.2025.2529914","url":null,"abstract":"<p><p>Perturbation in redox status elicits multiple cellular pathways, including those involved in the inflammatory response. A thiol-based molecule (I-152), releasing N-acetyl-cysteine (NAC) and β-mercaptoethylamine (MEA), was exploited as a redox-modulating agent, and its effects on pro-inflammatory cytokine expression and secretion in lipopolysaccharide (LPS)-stimulated macrophages (MΦ) were investigated. I-152 inhibited cytokine gene expression as well as protein secretion of the most important inflammatory cytokines in three different MΦ models <i>in vitro</i> and <i>ex vivo</i>. It alleviated inflammation <i>via</i> the c-Jun/AP-1 and NF-κB signaling pathways, depending on the dose, and regulated NLRP3 inflammasome expression, leading to decreased IL-1β and IL-18 release and reduced pyroptotic cell death. Consequently, the influence of redox-modulated MΦ secretome on the crosstalk with endothelial cells was evaluated. Co-culture experiments between THP-1 MΦ, that had been pretreated with I-152 before LPS stimulation, and Human Vascular Endothelial Cells (HUVECs) showed reduced VCAM/ICAM expression in these cells in concomitance with a less oxidized and inflamed MΦ proteomic portrait. Overall, our findings suggest that I-152 redox modulation could target the AP-1/NLRP3 axis, affecting LPS-induced inflammation in MΦ and influencing HUVEC responses, revealing a complex and bidirectional interchange.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"487-505"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590818","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
Antioxidant properties of 34 alkaloids of natural origin: a density functional theory study. 34种天然生物碱的抗氧化性能:密度泛函理论研究。
IF 2.9 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-07-31 DOI: 10.1080/10715762.2025.2539764
Andrey A Buglak, Taisiya A Telegina
{"title":"Antioxidant properties of 34 alkaloids of natural origin: a density functional theory study.","authors":"Andrey A Buglak, Taisiya A Telegina","doi":"10.1080/10715762.2025.2539764","DOIUrl":"10.1080/10715762.2025.2539764","url":null,"abstract":"<p><p>The antioxidant properties of 34 plant alkaloids in gas phase, ethanol and water have been evaluated using density functional theory (DFT). The computations have been made according to three different single electron mechanisms: (1) H-atom transfer (HAT); (2) electron transfer followed by H<sup>+</sup> transfer (SET-PT); and (3) sequential H<sup>+</sup>-loss electron transfer (SPLET). As a result, the highest antioxidant activity was established for evodiamine. Global reactivity in terms of hardness/softness has been calculated also, as well as Fukui indices of local reactivity. Structural aspects related to H, electron and proton loss have been regarded in sufficient details. In terms of global softness, palmatine, dehydroevodiamine and chelerythrine have been determined as the most reactive molecules, whereas C7 atom of evodiamine has been found to be the most reactive atom. All the findings are in agreement with the recent experimental and theoretical studies on alkaloid antioxidant activity and can be compared with the results for ascorbic acid, which was used as a reference compound.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"531-544"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706895","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
Low-temperature plasma modulates seed germination through reactive oxygen species in dose-dependent manner. 低温等离子体通过活性氧以剂量依赖的方式调节种子萌发。
IF 2.9 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-08-08 DOI: 10.1080/10715762.2025.2544800
Seungil Park, Bae Young Choi, You-Bin Seol, Jaewook Kim
{"title":"Low-temperature plasma modulates seed germination through reactive oxygen species in dose-dependent manner.","authors":"Seungil Park, Bae Young Choi, You-Bin Seol, Jaewook Kim","doi":"10.1080/10715762.2025.2544800","DOIUrl":"10.1080/10715762.2025.2544800","url":null,"abstract":"<p><p>Atmospheric pressure low-temperature plasma treatment has been shown to enhance seed germination in various plant species. However, whether plasma treatment modulates seed dormancy status or affects the seed germination process remains unclear. Additionally, most studies have primarily focused on the positive effects of plasma on germination and growth, without addressing dose-dependent responses or underlying molecular mechanisms. To elucidate the effects of plasma treatment on seed germination at a molecular level, we analyzed the germination phenotype of fully ripened <i>Arabidopsis thaliana</i> seeds under germination-inhibitory conditions following plasma treatment. We observed that plasma treatment enhanced germination potential up to a critical threshold, beyond which prolonged treatment diminished the enhanced effect. Chemical staining assays identified that plasma treatment induced the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) at different time points. Machine-learning aided modeling revealed that ROS, rather than RNS, plays a key role in plasma-mediated germination induction. Furthermore, transcriptome analyses suggested candidate genes likely modulated by plasma treatment during seed germination, including glutathione and L-phenylalanine metabolism, abscisic acid signaling, and the tricarboxylic acid cycle. Our study provides the first molecular-level insights into how atmospheric pressure low-temperature plasma modulates seed germination.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"545-556"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783925","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
Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker for the prognosis of acute poisoning patients in the emergency Intensive-care unit: a prospective observational study. 尿8-氧-7,8-二氢鸟苷作为急诊重症监护病房急性中毒患者预后的潜在生物标志物:一项前瞻性观察研究
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-01 DOI: 10.1080/10715762.2025.2512463
Ya-Min Dang, Chao-Jie Chen, Ya-Qing Ma, Hong-Lei Liu, Wei Wen, Jin-Hua Quan, Ren-Ai Xu, Jun Dong, Zhong-Qiu Lu, Jian-Ping Cai
{"title":"Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker for the prognosis of acute poisoning patients in the emergency Intensive-care unit: a prospective observational study.","authors":"Ya-Min Dang, Chao-Jie Chen, Ya-Qing Ma, Hong-Lei Liu, Wei Wen, Jin-Hua Quan, Ren-Ai Xu, Jun Dong, Zhong-Qiu Lu, Jian-Ping Cai","doi":"10.1080/10715762.2025.2512463","DOIUrl":"10.1080/10715762.2025.2512463","url":null,"abstract":"<p><p>Acute poisoning remains a significant cause of admission to the emergency intensive-care unit (EICU). Despite a reduced mortality rate, attention is increasingly focusing on the impact of post-intensive-care syndrome (PICS) on readmission. Due to the significant role of oxidative stress (OS) in the pathological mechanisms of poisoning, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) may hold great potential as biomarkers for OS biomarkers to evaluate the severity and prognosis of poisoning. Therefore, we investigated the longitudinal changes of urinary 8-oxoGuo levels during hospitalization in poisoned patients, their association with organ failure, and their predictive value for 30-day readmission risk. In total, 43 poisoning patients were enrolled from the EICU of the First Affiliated Hospital of Wenzhou Medical University between July 2021 and November 2022. The 30-day readmission rate was 18.6%. Group-based trajectory modeling (GBTM) was used to explore the potential trajectories of urinary OS markers and organ failure scores during hospitalization. Spearman's correlation analysis revealed a significant association between a high trajectory of 8-oxoGuo/creatinine (Cr) and the increased severity of overall organ failure, as well as respiratory and coagulation dysfunctions. Binary logistic regression analysis indicated that a high 8-oxoGuo/Cr trajectory, high respiratory failure score trajectory, and 8-oxoGuo/Cr values at three key points in disease progression (including admission, transfer from EICU, and discharge), along with 8-oxodGuo/Cr levels at admission, were all risk factors for 30-day readmission. The 8-oxoGuo/Cr value at discharge exhibited the best predictive performance. The urinary 8-oxoGuo/Cr ratio may serve as a potential biomarker for prognostic evaluations in patients with poisoning.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"392-408"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157859","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
Pro-inflammatory properties of M1 phenotypes of human macrophages: prolongation of myeloperoxidase-mediated oxidative stress. 人巨噬细胞M1表型的促炎特性:延长髓过氧化物酶介导的氧化应激。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-18 DOI: 10.1080/10715762.2025.2519528
Maria D Yurkanova, Nastasia V Kosheleva, Arina A Teplova, Peter S Timashev, Irina I Vlasova
{"title":"Pro-inflammatory properties of M1 phenotypes of human macrophages: prolongation of myeloperoxidase-mediated oxidative stress.","authors":"Maria D Yurkanova, Nastasia V Kosheleva, Arina A Teplova, Peter S Timashev, Irina I Vlasova","doi":"10.1080/10715762.2025.2519528","DOIUrl":"10.1080/10715762.2025.2519528","url":null,"abstract":"<p><p>Macrophages and neutrophils are the main immune cells of the acute stage of inflammation. Upon their activation, membrane-bound NADPH oxidase produces superoxide anion radical, which is converted to H<sub>2</sub>O<sub>2</sub> by superoxide dismutase (SOD). In this study, we compared the production of hydrogen peroxide by two phenotypes of pro-inflammatory human M1 macrophages and neutrophils activated with phorbol-12-myristate 13-acetate. Macrophages were obtained from blood monocytes (monocyte-derived macrophages (MDM)) differentiated into MDM using GM- or M-CSF growth factors and polarized into the M1 state, receiving GM_M1, M_M1, respectively. The total level of H<sub>2</sub>O<sub>2</sub> production measured in the presence of horseradish peroxidase differed significantly between two types of macrophages. Only GM_M1 macrophages had a level of H<sub>2</sub>O<sub>2</sub> production comparable to neutrophils. GM_M1 appear at the site of inflammation after neutrophils, they continue the work of neutrophils in creating a pro-inflammatory environment: they produce several times more H<sub>2</sub>O<sub>2</sub> and pro-inflammatory cytokines than M_M1, which arrive at inflammatory site later. Upon activation, MDM_M1 formed big blot-like and smaller dense spheroid-like aggregates. Activated neutrophils secrete the enzyme myeloperoxidase (MPO), which synthesizes the very potent oxidant hypochlorous acid (HOCl) only in the presence of H<sub>2</sub>O<sub>2</sub>. Neutrophils are short lived cells, MPO can use H<sub>2</sub>O<sub>2</sub> produced by activated cultured MDM to synthesize HOCl at physiologically relevant concentrations to prolong oxidative stress.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"452-461"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316308","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
Utilization of the nitroxyl radical TEMPOL to assess scavenging activities of lipid-soluble antioxidants against radicals initiated by the thermal decomposition of 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) in ethanol. 利用硝基自由基TEMPOL评价脂溶性抗氧化剂对2,2'-偶氮唑(2,4-二甲基戊腈)(AMVN)在乙醇中热分解引发的自由基的清除能力。
IF 2.9 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-07-22 DOI: 10.1080/10715762.2025.2531978
Keizo Takeshita, Ayaka Segawa, Kurumi Tokunaga, Ayaka Inamori, Ayako Matsuo, Yuhei Ohta, Shoko Okazaki
{"title":"Utilization of the nitroxyl radical TEMPOL to assess scavenging activities of lipid-soluble antioxidants against radicals initiated by the thermal decomposition of 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) in ethanol.","authors":"Keizo Takeshita, Ayaka Segawa, Kurumi Tokunaga, Ayaka Inamori, Ayako Matsuo, Yuhei Ohta, Shoko Okazaki","doi":"10.1080/10715762.2025.2531978","DOIUrl":"10.1080/10715762.2025.2531978","url":null,"abstract":"<p><p>To develop a simple and sensitive method for assessing the radical-scavenging activity of lipophilic antioxidants, the decay of the electron spin resonance (ESR) signal of 4-hydroxy-2,2,6,6-tetramethylpiperidine-<i>N</i>-oxyl radical (TEMPOL) was investigated as an indicator of radical reactions. The ESR signal of TEMPOL was decreased in ethanol, but not in acetonitrile, by the pyrolysis of 2,2'-azobis(2,4-dimethylvaleronitrile). Signal decay in ethanol was suppressed by degassing and did not occur in the presence of the spin trapping agent 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-<i>N</i>-oxide (DEPMPO). Spin trapping with DEPMPO showed the formation of peroxyl, alkoxyl, and alkyl radical adducts during the reaction, with peroxyl radical adducts decreasing in the presence of TEMPOL. These results indicate that TEMPOL signal decay occurs by reactions involving ethanol-derived peroxyl radicals. The TEMPOL signal decay was remarkably inhibited by 0.01 mmol/L 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), which is lower than the Trolox concentration used in the ESR-spin trapping method reported previously. Inhibition by methyl gallate was markedly stronger than Trolox, while the effects of 2,6-di-<i>tert</i>-butyl-<i>p</i>-cresol and resveratrol were minor. The order of inhibition of TEMPOL signal decay by antioxidants correlated to some extent with the order of suppression of peroxyl radical adduct formation by DEPMPO spin trapping. Therefore, the peroxyl radical-scavenging activities of lipid-soluble antioxidants may be evaluated with high sensitivity by examining the inhibitory activity of TEMPOL decay caused by radical reactions in ethanol. The measurement time was less than 5 min.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"506-517"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674306","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
Protective effects of sinensetin against oxidative stress damage induced by AAPH in the brain-gut. 青肠素对AAPH诱导的脑-肠氧化应激损伤的保护作用。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-10 DOI: 10.1080/10715762.2025.2514799
Tingting Jin, Menghui He, Na Li, Ying He, Feng He
{"title":"Protective effects of sinensetin against oxidative stress damage induced by AAPH in the brain-gut.","authors":"Tingting Jin, Menghui He, Na Li, Ying He, Feng He","doi":"10.1080/10715762.2025.2514799","DOIUrl":"10.1080/10715762.2025.2514799","url":null,"abstract":"<p><p>Sinensetin (SIN for short) is one of the most common polymethoxyflavonoids found in citrus fruits. Recently, it has been extensively studied due to its ability to prevent or treat a wide range of diseases, including diabetes, obesity, neurological disorders, and cancer. Oxidative stress is closely related to the pathogenesis of many diseases. Based on literature research and the results of our previous experiments, we found that flavonoids have significant antioxidant effects. This study found that sinensetin alleviated AAPH-induced oxidative stress in zebrafish and alleviated intestinal and brain damage (including brain neurons, vascular development, and blood-brain barrier integrity). This study is of great significance for further study of the relationship between gut-brain changes and oxidative stress. This study provides a practical and convenient tool for real-time tracking of the protective effect of natural products on the <i>in vivo</i> oxidative stress model induced by AAPH. In addition, it paves the way for the discovery of more antioxidants in the future.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"409-425"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208129","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
Dioscin induces ferroptosis to suppress the metastasis of gastric cancer through the SLC7A11/GPX4 axis. 薯蓣皂苷诱导铁下垂通过SLC7A11/GPX4轴抑制胃癌转移。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-13 DOI: 10.1080/10715762.2025.2515202
Doudou Lu, Ling Yuan, Zhaozhao Wang, Duojie Xu, Fandi Meng, Shumin Jia, Yahong Li, Weiqiang Li, Yi Nan
{"title":"Dioscin induces ferroptosis to suppress the metastasis of gastric cancer through the SLC7A11/GPX4 axis.","authors":"Doudou Lu, Ling Yuan, Zhaozhao Wang, Duojie Xu, Fandi Meng, Shumin Jia, Yahong Li, Weiqiang Li, Yi Nan","doi":"10.1080/10715762.2025.2515202","DOIUrl":"10.1080/10715762.2025.2515202","url":null,"abstract":"<p><p>The prognosis of gastric cancer (GC) remains poor due to metastases and resistance to chemotherapy. Ferroptosis is a novel cell death regulation mode characterized by iron dependence and lipid peroxidation. Dioscin, a compound extracted from the Paris polyphylla rhizomes roots, has been shown to have an inhibitory effect on cancers. However, whether it induces ferroptosis to participate in anti-cancer metastasis remains unclear. The ability of gastric cancer cells to invade and migrate was evaluated by wound healing and transwell assays. Malondialdehyde (MDA), glutathione (GSH) assay kit, and dichlorofluorescin diacetate (DCFH-DA) fluorescent probes were used to detect ferroptosis in gastric cancer cells. The expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods. The rescue assay was performed by adding Ferrostatin-1 (Fer-1) co-treatment to verify that Dioscin inhibited gastric cancer metastasis by participating in ferroptosis. Dioscin inhibited gastric cancer cells' wound healing, migration, and invasion process. In addition, Dioscin increased the level of reactive oxygen species (ROS) and MDA while decreasing GSH level, and induced ferroptosis of gastric cancer cells. Fer-1, an inhibitor of ferroptosis, could reverse the effect of Dioscin. In terms of mechanism, Dioscin induced ferroptosis through SLC7A11/GPX4 axis and was involved in the regulation of inhibiting metastasis of gastric cancer. These results suggested that Dioscin was involved in anti-cancer metastasis by inducing ferroptosis.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"426-441"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215327","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
Selenomethionine enhances transplant organ preservation by attenuating oxidative stress-induced proteolysis in rats. 硒代蛋氨酸通过减弱大鼠氧化应激诱导的蛋白水解而增强移植器官保存。
IF 3.6 3区 生物学
Free Radical Research Pub Date : 2025-05-01 Epub Date: 2025-06-11 DOI: 10.1080/10715762.2025.2516844
Paul Emir Hasuoka, Franco Tonelli, Leonardo Mariño-Repizo, Pablo Pacheco
{"title":"Selenomethionine enhances transplant organ preservation by attenuating oxidative stress-induced proteolysis in rats.","authors":"Paul Emir Hasuoka, Franco Tonelli, Leonardo Mariño-Repizo, Pablo Pacheco","doi":"10.1080/10715762.2025.2516844","DOIUrl":"10.1080/10715762.2025.2516844","url":null,"abstract":"<p><p>Selenomethionine (SeMet) increases glutathione peroxidase (GPx) activity, a seleno-enzyme with an antioxidant function that counteracts reactive oxygen species (ROS). After ablation, transplant organs generate ROS during irrigation-reperfusion injury. GPx1 can be downregulated during hypoxia in ablated organs. ROS can oxidize proteins, inducing proteolysis, which compromises the transplant outcome. SeMet administration to living donors can decrease proteolysis in transplant organs, improving their preservation. Accordingly, SeMet was administered to rats for 7 days. After this period, the liver, heart, and kidneys were ablated, and proteins extracted at different <i>postmortem</i> intervals (PMI). Total protein analysis showed a lower protein concentration decrease in kidneys and heart from SeMet-supplemented rats after a 6 hs PMI. Molecular weight changes of proteins to proteolysis products (PPs) were studied by size exclusion chromatography (SEC). SeMet decreased PPs (<29.5 kDa) in the liver, kidneys, and heart. Specific analysis of GPx1 proteolysis by affinity chromatography coupled to inductively coupled plasma mass spectrometry (AF-ICP-MS) showed that SeMet administration decreased GPx1 proteolysis 24% in the liver and 16.8% in the heart. SeMet administration reduced the proteolysis velocity of GPx1 (V<sub>GPx1</sub>) in heart. SeMet administration to living donors for seven days decreased proteolysis in transplant organs, improving its conservation.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"442-451"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233691","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}
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