Human & experimental toxicology最新文献_第3页

RNF216 inhibits ferroptosis in lung adenocarcinoma by promoting p53 ubiquitination. RNF216通过促进p53泛素化抑制肺腺癌铁下垂。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-06-12 DOI: 10.1177/09603271251336793

Jiasheng Wu, Weiqiang Mo, Haiqin Wang, Jianping Jiang, Jing Zhao

{"title":"RNF216 inhibits ferroptosis in lung adenocarcinoma by promoting p53 ubiquitination.","authors":"Jiasheng Wu, Weiqiang Mo, Haiqin Wang, Jianping Jiang, Jing Zhao","doi":"10.1177/09603271251336793","DOIUrl":"https://doi.org/10.1177/09603271251336793","url":null,"abstract":"PurposeLung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer and a leading cause of cancer-related mortality worldwide. This study investigates the role of Ring Finger Protein 216 (RNF216) in LUAD progression.MethodsRNF216 expression was evaluated in LUAD tissues and cells. Functional assays evaluated cell viability, migration, invasion, and ferroptosis in vitro. Mechanistic investigations defined RNF216's role in regulating p53 ubiquitination and stability. In vivo, xenograft models evaluated tumor growth and ferroptosis.ResultsRNF216 was markedly overexpressed in LUAD tissues and cell lines. Functional studies demonstrated that silencing RNF216 suppressed LUAD cell proliferation, migration, and invasion while inducing ferroptosis, characterized by increased reactive oxygen species (ROS), lipid peroxidation (LPO), and intracellular Fe2+ accumulation. Mechanistically, RNF216 knockdown stabilized p53 by reducing its ubiquitination, thereby promoting ferroptosis. These findings were corroborated in vivo, where RNF216 silencing significantly inhibited tumor growth and enhanced ferroptosis in xenograft models.ConclusionsOur results establish RNF216 as a pivotal oncogenic driver that accelerates LUAD progression by suppressing ferroptosis through p53 ubiquitination. Targeting RNF216 may represent a promising therapeutic strategy to induce ferroptosis and combat LUAD.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251336793"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The safety assessment of N-trans-feruloyltyramine using In vitro genotoxicity studies and 90-day toxicity study in rats. 用体外遗传毒性研究和大鼠90天毒性研究评价n -反式阿魏乙胺的安全性。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-18 DOI: 10.1177/09603271251334452

Sungwon Lee, Srinivas Seekallu, Suresh Babu Venkataramaiah, Chandrashekar Mataguru Doreswamy, Mohan Cheluru Umesh, Sandeep Malleshappa, Sajeev Justin Dev, Ganadhal Puttaramaiah Chethankumara, Nagaraju Lohith, Gajanan Rajpal Deshmukh, Brian Premkumar, Brinda Mahadevan

{"title":"The safety assessment of N-trans-feruloyltyramine using In vitro genotoxicity studies and 90-day toxicity study in rats.","authors":"Sungwon Lee, Srinivas Seekallu, Suresh Babu Venkataramaiah, Chandrashekar Mataguru Doreswamy, Mohan Cheluru Umesh, Sandeep Malleshappa, Sajeev Justin Dev, Ganadhal Puttaramaiah Chethankumara, Nagaraju Lohith, Gajanan Rajpal Deshmukh, Brian Premkumar, Brinda Mahadevan","doi":"10.1177/09603271251334452","DOIUrl":"https://doi.org/10.1177/09603271251334452","url":null,"abstract":"IntroductionN-trans-feruloyltyramine (NFT) is a bioactive compound present in many plant sources. The purpose of the studies was to investigate adverse effects, if any, of NFT produced through precision fermentation.MethodsAn in vitro Ames test was performed with NFT using bacterial strains at concentrations up to 1580 µg/plate with and without S9. The in vitro micronucleus assay was performed in human peripheral blood cells in culture, with and without, metabolic activation at three different doses. In the subchronic toxicity study, adult Sprague Dawley rats (10/sex/group) were fed diets prepared with target doses of 0, 5000, 10,000 or 20,000 ppm of NFT for 90 days.ResultsIn the Ames assay, there were no NFT-related or concentration dependent increases in revertant colony numbers in any of the tester strains. In the in vitro micronucleus assay, there was no statistically significant increase in the number of binucleated cells with micronuclei compared to the vehicle control. NFT was found to be non-genotoxic when evaluated in the in vitro Ames and micronucleus assays. In the 90-day rodent study, NFT was well tolerated, with no related adverse findings observed at any of the dose levels tested. There were no NFT related adverse histopathological changes observed in the high dose group of both the sexes.ConclusionThe No observed adverse effect level of NFT was determined as 1474 mg/kg body weight/day in males and 1958 mg/kg body weight/day in females based on the actual intake at the dose levels tested and under the experimental conditions employed.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251334452"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Effect of grape seed extract ondoxorubicin-induced testicular andepididymal damage in rats". “葡萄籽提取物对多柔比星诱导的大鼠睾丸和附睾损伤的影响”的更正。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-08 DOI: 10.1177/09603271251341390

引用次数: 0

Human health risk assessment of heavy metals in different compartments of vegetables from Erbil City-Iraq. 伊拉克埃尔比勒市不同蔬菜中重金属的人体健康风险评估。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-06-17 DOI: 10.1177/09603271251351421

Bashdar Abuzed Sadee

{"title":"Human health risk assessment of heavy metals in different compartments of vegetables from Erbil City-Iraq.","authors":"Bashdar Abuzed Sadee","doi":"10.1177/09603271251351421","DOIUrl":"https://doi.org/10.1177/09603271251351421","url":null,"abstract":"IntroductionThe consumption of vegetables is a key route for increasing the content of potentially toxic heavy metals in the food chain. This article aimed to quantify the concentrations of As, Se, Cd, Cr, Co, Cu, Ni, and Pb in different parts of vegetables harvested from Erbil city.MethodologyThe total concentrations of As, Cd, Cr, Co, Cu, Ni, and Pb in various vegetable parts were pursued by ICP-MS analysis.ResultsThe values of heavy metals in different parts of the analyzed vegetables ranged from 0.052 to 2.106 mg/kg for As, 0.024 to 5.899 mg/kg for Se, 0.014 to 0.753 mg/kg for Cd, 0.441 to 89.400 mg/kg for Cr, 0.052 to 2.693 mg/kg for Co, 0.737 to 39.120 mg/kg for Cu, 0.301 to 63.880 mg/kg for Ni, and 0.032 to 1.782 mg/kg for Pb. The Hazard Quotient (HQ) values for As, Cr, Cu, and Ni in the edible parts of most vegetables exceeded one, while those for Se, Co, Cd, and Pb were below one.DiscussionIn contrast to Se, Co, Cd, and Pb, the HQ values for As, Cr, and Pb indicate a potential health risk when consuming these edible parts of the vegetables. The Hazard Index (HI) for all edible parts of the analyzed vegetable samples exceeded one. The cancer risk (CR) of As, Cd, Cr and Ni were higher than 1.0 × 10-4 which indicating carcinogenic risk. As a result, regular consumption of these vegetables is regarded as unsafe and not advisable.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251351421"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical characteristics and the risk factors analysis in patients with delayed encephalopathy after acute carbon monoxide poisoning. 急性一氧化碳中毒后迟发性脑病的临床特点及危险因素分析。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-03 DOI: 10.1177/09603271251332234

Ziang Han, Sumeng Shi, Yan Zhang, Ding Yuan, Zhigao Xu, Yanxia Gao

{"title":"Clinical characteristics and the risk factors analysis in patients with delayed encephalopathy after acute carbon monoxide poisoning.","authors":"Ziang Han, Sumeng Shi, Yan Zhang, Ding Yuan, Zhigao Xu, Yanxia Gao","doi":"10.1177/09603271251332234","DOIUrl":"10.1177/09603271251332234","url":null,"abstract":"IntroductionAcute carbon monoxide poisoning (ACMP) remains a leading cause of morbidity and mortality from fatal inhaled poisoning. Delayed encephalopathy after ACMP (DEACMP) has become one of the most complex and serious complications.MethodsIn this research, an observational study was performed from January 2016 to December 2019 to investigate the potential relevant risk factors of DEACMP with data collected from Level 3 medical facilities located in Northern China. Within the 4-year data collection period, the final study cohort consisted of 240 (117 males, 123 females).ResultsUni-variable analysis identified older age, medical history of cerebrovascular accident, basic disease of diabetes, and longer duration of loss of consciousness as relevant factors for DEACMP; while multivariable logistic regression revealed that the older age (OR, 1.45; 95% CI, 1.25-1.69; P < 0.01), longer duration of loss of consciousness (OR, 1.39; 95% CI, 1.36-1.45; P < 0.01), and cerebrovascular accidents occurring (OR, 1.23; 95% CI, 1.03-1.47; P = 0.04) were independent predictors for DEACMP.DiscussionFurthermore, additional research is needed to testify to the relevance and to elucidate the potential pathogenesis, consequently determining the clinical guideline and approving the best prevention and treatment strategy for DEACMP.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the role of rare earth elements (praseodymium, samarium, lanthanum, and terbium) and oxidative stress in polycystic ovary syndrome: A case-control study. 探讨稀土元素（镨、钐、镧和铽）和氧化应激在多囊卵巢综合征中的作用：一项病例对照研究。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-16 DOI: 10.1177/09603271251342280

Manal Abudawood

{"title":"Exploring the role of rare earth elements (praseodymium, samarium, lanthanum, and terbium) and oxidative stress in polycystic ovary syndrome: A case-control study.","authors":"Manal Abudawood","doi":"10.1177/09603271251342280","DOIUrl":"https://doi.org/10.1177/09603271251342280","url":null,"abstract":"BackgroundPraseodymium (Pr), Samarium (Sm), Lanthanum (La), and Terbium (Tb) are rare earth elements (REEs) that can accumulate in the body and induce oxidative stress (OS), which may contribute to polycystic ovary syndrome (PCOS), a condition affecting 116 million women worldwide. With the increasing use of REEs, understanding their role in PCOS is crucial.DesignThis case-control study included 56 PCOS cases and 50 healthy controls, with confounding factors such as age, BMI, and hormones controlled. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure serum levels of Pr, Sm, La, and Tb, and Pearson correlation was performed to explore their relationship with oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD).ResultA significant increase in serum levels of Pr, Sm, La, and Tb was observed in PCOS cases compared to controls (p < 0.05). The 95% confidence intervals (CIs) for the differences in serum Pr, Sm, La, and Tb levels were [0.0008, 0.0032], [0.0002, 0.0091], [0.0019, 0.0073], and [0.0002, 0.0129], respectively. Additionally, serum levels of MDA were significantly elevated, accompanied by reduction in the antioxidant markers-GSH and SOD (p < 0.001). Elevated REE levels were positively correlated with increased MDA and negatively correlated with GSH and SOD, indicating increased oxidative stress.ConclusionThese findings suggest that oxidative stress-induced metal intoxication may play a critical role in the development of PCOS. Future studies should explore the clinical significance of REE exposure and its potential as a target for preventive strategies in PCOS management.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251342280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice. 综合肠道微生物群和血清代谢组学揭示草甘膦诱导的小鼠肝损伤。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251326877

Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu

{"title":"Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice.","authors":"Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu","doi":"10.1177/09603271251326877","DOIUrl":"10.1177/09603271251326877","url":null,"abstract":"IntroductionGlyphosate (GLP) is one of the most widely used herbicides in the world. However, its underlying effects on the liver remain unclear. This study aims to investigate the toxic effects and the gut microbiome- and serum metabolite-related mechanisms of GLP on the liver in mice.Methods16S rDNA sequencing and UPLC-Q-TOF-MS/MS were used to investigate the mechanisms of GLP toxicity in mice administered with 0, 50, 250 and 500 mg/kg/day GLP for 30 days.ResultsGLP induced hepatocyte edema and ballooning as well as inflammatory cell infiltration. Exposure to GLP resulted in increased levels of serum ALT, TBIL, DBIL, and GLU. Microbiota analysis at the phylum level demonstrated that the proportions of Patescibacteria decreased in the GLP-treated group. The genus-level analysis identified 11 different genera, with eight decreased and three increased in the GLP-exposed group. Metabolomics analysis of serum showed 42 differential metabolites between the GLP and control groups. The metabolic pathway enrichment analysis revealed that the pentose phosphate pathway (PPP) and pyrimidine metabolism were significantly activated. Spearman analysis showed that the changes in the differential metabolites of the PPP and pyrimidine metabolism and gut microbiota were strongly associated with the biochemical index.DiscussionIn conclusion, GLP exposure induces hepatic injury through alterations in the gut microbiome and metabolic pathways, particularly by activating the pentose phosphate pathway and pyrimidine metabolism.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251326877"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thanks to Reviewers. 感谢评论者。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251315241

引用次数: 0

High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response. 高剂量维生素C可通过激活内质网应激反应诱导急性淋巴细胞白血病细胞凋亡。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-29 DOI: 10.1177/09603271251345656

Hui Meng Sun, Yanan Jiang, Kaiping Luo, Dong Hui Xing, Yixin Zhai, Xiang He, Wenqi Wu, Zhigang Zhao

{"title":"High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response.","authors":"Hui Meng Sun, Yanan Jiang, Kaiping Luo, Dong Hui Xing, Yixin Zhai, Xiang He, Wenqi Wu, Zhigang Zhao","doi":"10.1177/09603271251345656","DOIUrl":"https://doi.org/10.1177/09603271251345656","url":null,"abstract":"IntroductionHigh-dose Vitamin C has shown significant anti-tumor effects in various cancers, including hematological malignancies. However, its therapeutic efficacy against acute lymphoblastic leukemia (ALL) remains underexplored.MethodsALL cell lines and normal bone marrow mononuclear cells were treated with Vitamin C to assess cell viability, apoptosis, proliferation, and cell cycle progression. Colony formation assays evaluated long-term growth. Additionally, transgenic mouse models were employed to evaluate the in vivo antitumor activity of high-dose Vitamin C in ALL. Western blotting, ROS detection 2',7'-Dichlorofluorescin diacetate (DCFH-DA), and RNA sequencing with GSEA were conducted to explore Vitamin C's mechanism of action.ResultsOur results demonstrated that high-dose Vitamin C exhibited potent cytotoxicity toward ALL cells at relatively low concentrations (200 μM) while sparing normal human bone marrow mononuclear cells even at concentrations as high as 1 mM. Vitamin C effectively inhibited ALL cell line proliferation, induced apoptosis, and disrupted cell cycle progression. We further identified that the increased expression of Solute Carrier Family 23 Member 1 (SLC23A1) in ALL cells enhanced their sensitivity to Vitamin C. In SLC23A1 knockout cells, treatment with 200 μM Vitamin C significantly restored cell viability and reduced apoptosis compared to controls. Mechanistically, high-dose Vitamin C induced apoptosis in ALL cells by activating the ER stress response through the PERK/CHOP pathway.ConclusionTaken together, our findings suggest that high-dose Vitamin C demonstrated significant anti-leukemic effects in ALL, showing cytotoxicity at 200 μM. Furthermore, SLC23A1 may serve as a potential biomarker for predicting the therapeutic response to Vitamin C treatment in ALL patients.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251345656"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction: Association of miR-9-5p and NFIC in the progression of gastric cancer. 撤回：miR-9-5p和NFIC在胃癌进展中的关联。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-08 DOI: 10.1177/09603271251336600

引用次数: 0