Archives of Toxicology最新文献

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A review of the scientific literature on experimental toxicity studies of COVID-19 vaccines, with special attention to publications in toxicology journals. 有关 COVID-19 疫苗实验毒性研究的科学文献综述,特别关注在毒理学期刊上发表的文章。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-03 DOI: 10.1007/s00204-024-03854-8
Jose L Domingo
{"title":"A review of the scientific literature on experimental toxicity studies of COVID-19 vaccines, with special attention to publications in toxicology journals.","authors":"Jose L Domingo","doi":"10.1007/s00204-024-03854-8","DOIUrl":"https://doi.org/10.1007/s00204-024-03854-8","url":null,"abstract":"<p><p>Since the reports of the first cases of COVID-19, in less than 5 years, a huge number of documents regarding that disease and the coronavirus (SARS-CoV-2), responsible for the infection, have been published. The tremendous number of scientific documents covers many topics on different issues directly related to COVID-19/SARS-CoV-2. The number of articles-including reviews-reporting adverse/side effects of the approved COVID-19 vaccines is considerable. A wide range of adverse/side effects have been reported in humans after COVID-19 vaccination: thrombotic events/thrombocytopenia, myocarditis/pericarditis, cutaneous reactions, immune-mediated effects, psychiatric adverse events, systemic lupus erythematosus, reproductive toxicity, and other miscellaneous adverse effects. In contrast, information on nonclinical studies conducted to assess the potential toxicity/adverse effects of the COVID-19 vaccines in laboratory animals, is comparatively very scarce. The present review was aimed at revising the scientific literature regarding the studies in laboratory animals on the toxic/adverse effects of COVID-19 vaccines. In addition, the investigations reported in those specific toxicology journals with the highest impact factors have been examined one by one. The results of the present review indicate that most nonclinical/experimental studies on the adverse/toxic effects of the COVID-19 vaccines and/or potential candidates showed-in general terms-a good safety profile. Only in some animal studies were certain adverse effects found. However, a rather surprising result has been the limited number of available (in the databases PubMed and Scopus) nonclinical studies performed by the companies that have been the largest manufacturers of mRNA vaccines in the world. It is assumed that these studies have been conducted. However, they have not been published in scientific journals, which does not allow the judgment of the international scientific community, including toxicologists.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevated blood-ethanol concentration promotes reduction of aliphatic ketones (acetone and ethyl methyl ketone) to secondary alcohols along with slower oxidation to aliphatic diols. 血液中乙醇浓度的升高会促进脂肪族酮类(丙酮和乙基甲基酮)还原成仲醇,同时减慢脂肪族二元醇的氧化速度。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-03 DOI: 10.1007/s00204-024-03860-w
A W Jones
{"title":"Elevated blood-ethanol concentration promotes reduction of aliphatic ketones (acetone and ethyl methyl ketone) to secondary alcohols along with slower oxidation to aliphatic diols.","authors":"A W Jones","doi":"10.1007/s00204-024-03860-w","DOIUrl":"https://doi.org/10.1007/s00204-024-03860-w","url":null,"abstract":"<p><p>Many people convicted for drunken driving suffer from an alcohol use disorder and some traffic offenders consume denatured alcohol for intoxication purposes. Venous blood samples from people arrested for driving under the influence of alcohol were analyzed in triplicate by headspace gas chromatography (HS-GC) using three different stationary phases. The gas chromatograms from this analysis sometimes showed peaks with retention times corresponding to acetone, ethyl methyl ketone (2-butanone), 2-propanol, and 2-butanol in addition to ethanol and the internal standard (1-propanol). Further investigations showed that these drink-driving suspects had consumed an industrial alcohol (T-Red) for intoxication purposes, which contained > 90% w/v ethanol, acetone (~ 2% w/v), 2-butanone (~ 5% w/v) as well as Bitrex to impart a bitter taste. In n = 75 blood samples from drinkers of T-Red, median concentrations of ethanol, acetone, 2-butanone, 2-propanol and 2-butanol were 2050 mg/L (2.05 g/L), 97 mg/L, 48 mg/L, 26 mg/L and 20 mg/L, respectively. In a separate GC analysis, 2,3-butanediol (median concentration 87 mg/L) was identified in blood samples containing 2-butanone. When the redox state of the liver is shifted to a more reduced potential (excess NADH), which occurs during metabolism of ethanol, this favors the reduction of low molecular ketones into secondary alcohols via the alcohol dehydrogenase (ADH) pathway. Routine toxicological analysis of blood samples from apprehended drivers gave the opportunity to study metabolism of acetone and 2-butanone without having to administer these substances to human volunteers.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease. 全球长间距核元素-1 DNA甲基化、金属暴露与慢性肾病之间的关系。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-05-16 DOI: 10.1007/s00204-024-03780-9
Yu-Mei Hsueh, Mei-Chieh Chen, Ying-Chin Lin, Chih-Yin Wu, Horng-Sheng Shiue, Sheng-Lun Hsu, Hsi-Hsien Chen, Ya-Li Huang
{"title":"Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.","authors":"Yu-Mei Hsueh, Mei-Chieh Chen, Ying-Chin Lin, Chih-Yin Wu, Horng-Sheng Shiue, Sheng-Lun Hsu, Hsi-Hsien Chen, Ya-Li Huang","doi":"10.1007/s00204-024-03780-9","DOIUrl":"10.1007/s00204-024-03780-9","url":null,"abstract":"<p><p>Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Carbon nanotubes conjugated with cisplatin activate different apoptosis signaling pathways in 2D and 3D-spheroid triple-negative breast cancer cell cultures: a comparative study. 与顺铂共轭的碳纳米管在二维和三维球状三阴性乳腺癌细胞培养物中激活不同的凋亡信号通路:一项比较研究。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-05-13 DOI: 10.1007/s00204-024-03779-2
Madalina Andreea Badea, Mihaela Balas, Daniela Ionita, Anca Dinischiotu
{"title":"Carbon nanotubes conjugated with cisplatin activate different apoptosis signaling pathways in 2D and 3D-spheroid triple-negative breast cancer cell cultures: a comparative study.","authors":"Madalina Andreea Badea, Mihaela Balas, Daniela Ionita, Anca Dinischiotu","doi":"10.1007/s00204-024-03779-2","DOIUrl":"10.1007/s00204-024-03779-2","url":null,"abstract":"<p><p>The type of experimental model for the in vitro testing of drug formulations efficiency represents an important tool in cancer biology, with great attention being granted to three-dimensional (3D) cultures as these offer a closer approximation of the clinical sensitivity of drugs. In this study, the effects induced by carboxyl-functionalized single-walled carbon nanotubes complexed with cisplatin (SWCNT-COOH-CDDP) and free components (SWCNT-COOH and CDDP) were compared between conventional 2D- and 3D-spheroid cultures of human breast cancer cells. The 2D and 3D breast cancer cultures were exposed to various doses of SWCNT-COOH (0.25-2 μg/mL), CDDP (0.158-1.26 μg/mL) and the same doses of SWNCT-COOH-CDDP complex for 24 and 48 h. The anti-tumor activity, including modulation of cell viability, oxidative stress, proliferation, apoptosis, and invasion potential, was explored by spectrophotometric and fluorometric methods, immunoblotting, optical and fluorescence microscopy. The SWCNT-COOH-CDDP complex proved to have high anti-cancer efficiency on 2D and 3D cultures by inhibiting cell proliferation and activating cell death. A dose of 0.632 μg/mL complex triggered different pathways of apoptosis in 2D and 3D cultures, by intrinsic, extrinsic, and reticulum endoplasmic pathways. Overall, the 2D cultures showed higher susceptibility to the action of complex compared to 3D cultures and SWCNT-COOH-CDDP proved enhanced anti-tumoral activity compared to free CDDP.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk. 多组学和多阶段整合发现了一种与矽肺病风险相关的新型变体。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-05-29 DOI: 10.1007/s00204-024-03795-2
Chunmeng Jin, Xiaobo Tao, Wendi Zhang, Huiwen Xu, Yutong Wu, Qiong Chen, Siqi Li, Anhui Ning, Wei Wang, Qiuyun Wu, Minjie Chu
{"title":"Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk.","authors":"Chunmeng Jin, Xiaobo Tao, Wendi Zhang, Huiwen Xu, Yutong Wu, Qiong Chen, Siqi Li, Anhui Ning, Wei Wang, Qiuyun Wu, Minjie Chu","doi":"10.1007/s00204-024-03795-2","DOIUrl":"10.1007/s00204-024-03795-2","url":null,"abstract":"<p><p>Assessing the association between candidate single-nucleotide polymorphisms (SNPs) identified by multi-omics approaches and susceptibility to silicosis. RNA-seq analysis was performed to screen the differentially expressed mRNAs in the fibrotic lung tissues of mice exposed to silica particles. Following this, we integrated the SNPs located in the above human homologenes with the silicosis-related genome-wide association study (GWAS) data to select the candidate SNPs. Then, expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. Next, we validated the associations between the functional eQTL-SNPs and silicosis susceptibility by additional case-control study. And the contribution of the identified SNP and its host gene in the fibrosis process was further validated by functional experiments. A total of 12 eQTL-SNPs were identified in the screening stage. The results of the validation stage suggested that the variant T allele of rs419540 located in IL12RB1 significantly increased the risk of developing silicosis [additive model: odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.11-2.85, P = 0.017]. Furthermore, the combination of GWAS and the results of validation stage also indicated that the variant T allele of rs419540 in IL12RB1 was associated with increased silicosis risk (additive model: OR = 2.07, 95% CI 1.38-3.12, P < 0.001). Additionally, after knockdown or overexpression of IL12RB1, the levels of pro-inflammatory factors, such as IL-12, IFN-γ, and other pro-inflammatory factors, were correspondingly decreased or increased. The novel eQTL-SNP, rs419540, might increase the risk of silicosis by modulating the expression levels of IL12RB1.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro. 新型合成大麻素 5F-EDMB-PICA 体外第一阶段和第二阶段代谢物及代谢途径的鉴定。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-07-02 DOI: 10.1007/s00204-024-03790-7
Yujie Gao, Kaiting Shi, Peipei Wang, Xinyu Liu, Chenxi Liu, Liya Luo, Yanchen Lin, Lin Yang, Rongji Yang, Linchuan Liao
{"title":"Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro.","authors":"Yujie Gao, Kaiting Shi, Peipei Wang, Xinyu Liu, Chenxi Liu, Liya Luo, Yanchen Lin, Lin Yang, Rongji Yang, Linchuan Liao","doi":"10.1007/s00204-024-03790-7","DOIUrl":"10.1007/s00204-024-03790-7","url":null,"abstract":"<p><p>5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation. 杂食动物、素食者和严格生食者体内接触热引起的食物污染物:接触丙烯酰胺的生物标志物(血红蛋白加合物、尿巯基酸)及其内源性形成的新见解。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-05-31 DOI: 10.1007/s00204-024-03798-z
Bernhard H Monien, Nick Bergau, Fabian Gauch, Cornelia Weikert, Klaus Abraham
{"title":"Internal exposure to heat-induced food contaminants in omnivores, vegans and strict raw food eaters: biomarkers of exposure to acrylamide (hemoglobin adducts, urinary mercapturic acids) and new insights on its endogenous formation.","authors":"Bernhard H Monien, Nick Bergau, Fabian Gauch, Cornelia Weikert, Klaus Abraham","doi":"10.1007/s00204-024-03798-z","DOIUrl":"10.1007/s00204-024-03798-z","url":null,"abstract":"<p><p>The urinary mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) are short-term biomarkers of exposure from acrylamide and its metabolite glycidamide, respectively. The medium-term exposure to acrylamide and glycidamide is monitored by the adducts N-(2-carbamoylethyl)-Val (AA-Val) and N-(2-carbamoyl-2-hydroxyethyl)-Val (GA-Val) in hemoglobin (Hb), respectively. Three questions were addressed by application of these biomarkers in two diet studies including 36 omnivores, 36 vegans and 16 strict raw food eaters (abstaining from any warmed or heated food for at least four months): first, what is the internal acrylamide exposure following a vegan or a raw food diet in comparison to that in omnivores? Second, did the exposure change between 2017 and 2021? And third, what is the stability over time of AAMA/GAMA excretion compared to that of AA-Val/GA-Val levels in Hb between both time points? Median urinary AAMA excretion per day in non-smoking omnivores, vegans and raw food eaters were 62.4, 85.4 and 15.4 µg/day, respectively; the corresponding median AA-Val levels were 27.7, 39.7 and 13.3 pmol/g Hb, respectively. Median levels in strict raw food eaters were about 25% (AAMA excretion) and 48% (AA-Val) of those in omnivores. In comparison to 2017, AAMA and GAMA excretion levels were hardly altered in 2021, however, levels of AA-Val and GA-Val in 2021 slightly increased. There was a weak correlation between AAMA excretion levels determined four years apart (r<sub>S</sub> = 0.30), and a moderate correlation between levels of AA-Val (r<sub>S</sub> = 0.55) in this timeframe. Our data in strict raw food eaters confirm a significant endogenous formation to acrylamide in a size range, which is-based on the levels of AA-Val-distinctly higher than reported previously based on levels of urinary AAMA excretion. The relatively lower AAMA excretion in raw food eaters likely represents a lower extent of glutathione conjugation due to missing hepatic first-pass metabolism in case of endogenous formation of acrylamide, which leads to a higher systemic exposure.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. 用多组学方法阐明 okadaic 酸诱导的人 HepaRG 肝癌细胞的变化。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-06-04 DOI: 10.1007/s00204-024-03796-1
Leonie T D Wuerger, Heike Sprenger, Ksenia Krasikova, Markus Templin, Aaron Stahl, Uta M Herfurth, Holger Sieg, Albert Braeuning
{"title":"A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells.","authors":"Leonie T D Wuerger, Heike Sprenger, Ksenia Krasikova, Markus Templin, Aaron Stahl, Uta M Herfurth, Holger Sieg, Albert Braeuning","doi":"10.1007/s00204-024-03796-1","DOIUrl":"10.1007/s00204-024-03796-1","url":null,"abstract":"<p><p>Okadaic acid (OA), a prevalent marine biotoxin found in shellfish, is known for causing acute gastrointestinal symptoms. Despite its potential to reach the bloodstream and the liver, the hepatic effects of OA are not well understood, highlighting a significant research gap. This study aims to comprehensively elucidate the impact of OA on the liver by examining the transcriptome, proteome, and phosphoproteome alterations in human HepaRG liver cells exposed to non-cytotoxic OA concentrations. We employed an integrative multi-omics approach, encompassing RNA sequencing, shotgun proteomics, phosphoproteomics, and targeted DigiWest analysis. This enabled a detailed exploration of gene and protein expression changes, alongside phosphorylation patterns under OA treatment. The study reveals concentration- and time-dependent deregulation in gene and protein expression, with a significant down-regulation of xenobiotic and lipid metabolism pathways. Up-regulated pathways include actin crosslink formation and a deregulation of apoptotic pathways. Notably, our results revealed that OA, as a potent phosphatase inhibitor, induces alterations in actin filament organization. Phosphoproteomics data highlighted the importance of phosphorylation in enzyme activity regulation, particularly affecting proteins involved in the regulation of the cytoskeleton. OA's inhibition of PP2A further leads to various downstream effects, including alterations in protein translation and energy metabolism. This research expands the understanding of OA's systemic impact, emphasizing its role in modulating the phosphorylation landscape, which influences crucial cellular processes. The results underscore OA's multifaceted effects on the liver, particularly through PP2A inhibition, impacting xenobiotic metabolism, cytoskeletal dynamics, and energy homeostasis. These insights enhance our comprehension of OA's biological significance and potential health risks.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy. 开发并验证预测丙戊酸治疗癫痫患者转氨酶异常升高的自动机器学习模型。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-06-16 DOI: 10.1007/s00204-024-03803-5
Hongying Ma, Sihui Huang, Fengxin Li, Zicheng Pang, Jian Luo, Danfeng Sun, Junsong Liu, Zhuoming Chen, Jian Qu, Qiang Qu
{"title":"Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy.","authors":"Hongying Ma, Sihui Huang, Fengxin Li, Zicheng Pang, Jian Luo, Danfeng Sun, Junsong Liu, Zhuoming Chen, Jian Qu, Qiang Qu","doi":"10.1007/s00204-024-03803-5","DOIUrl":"10.1007/s00204-024-03803-5","url":null,"abstract":"<p><p>Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using \"H2O\" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does climate change increase the risk of marine toxins? Insights from changing seawater conditions. 气候变化会增加海洋毒素的风险吗?海水条件变化带来的启示。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-09-01 Epub Date: 2024-05-25 DOI: 10.1007/s00204-024-03784-5
Ruiyang Meng, Xingde Du, Kangfeng Ge, Chunrui Wu, Zongxin Zhang, Xiao Liang, Jun Yang, Huizhen Zhang
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