Toxicology Mechanisms and Methods最新文献_第4页

Cytotoxic potential of an indole-conjugated Oleanolic acid analogue: suppression of NSCLC proliferation through modulation of mitochondrial apoptotic dynamics. 吲哚共轭齐墩果酸类似物的细胞毒性潜力：通过调节线粒体凋亡动力学抑制非小细胞肺癌增殖。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-25 DOI: 10.1080/15376516.2025.2481915

Srividya Subramanian, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, Parthiban Anaikutti, Rukkumani Rajagopalan

{"title":"Cytotoxic potential of an indole-conjugated Oleanolic acid analogue: suppression of NSCLC proliferation through modulation of mitochondrial apoptotic dynamics.","authors":"Srividya Subramanian, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, Parthiban Anaikutti, Rukkumani Rajagopalan","doi":"10.1080/15376516.2025.2481915","DOIUrl":"10.1080/15376516.2025.2481915","url":null,"abstract":"Pre-clinical toxicological investigations are pivotal in the development of safer and more efficacious chemotherapeutic agents. Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid, has demonstrated anticancer potential but is often limited by the toxic side effects of its derivatives. In the current study, we carried out the facile synthesis of a modified OA analogue, OD2, and studied its cytotoxicity and efficacy analysis across several cell lines. Mechanistic toxicology was explored through fluorescence-based assays. Annexin-V/Propidium Iodide (A-V/PI) staining and TUNEL assays were used to confirm apoptosis. OD2 exhibited dose-dependent cytotoxicity, with a pronounced effect on A549 lung cancer cells compared to other cancerous and non-cancerous cell lines. Apoptosis was found to be the predominant mode of cell death, evidenced by Fluorescence imaging analysis of chromatin condensation and mitochondrial dysfunction. This was further validated by an increase in Annexin-V-positive and TUNEL-positive cells in treated groups. OD2 activated the intrinsic mitochondrial apoptotic pathway as evidenced by increased Bax and decreased Bcl-2 protein abundance levels. While the current study showcases the therapeutic potential of the selective toxicological activity of OD2, future studies will focus on the deconvolution of its potential polypharmacological mode of action and decoding the basis of its selective action, so as to glean important lessons that can be applied in the development of chemotherapeutic agents with favorable toxicological profiles.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Leveraging AlphaFold models to predict androgenic effects of endocrine-disrupting chemicals through zebrafish androgen receptor analysis. 利用AlphaFold模型通过斑马鱼雄激素受体分析预测内分泌干扰化学物质的雄激素效应。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-12 DOI: 10.1080/15376516.2025.2477036

Md Adnan Karim, Chang Gyun Park, Hyunki Cho, Annmariya Elayanithottathil Sebastian, Chang Seon Ryu, Juyong Yoon, Young Jun Kim

{"title":"Leveraging AlphaFold models to predict androgenic effects of endocrine-disrupting chemicals through zebrafish androgen receptor analysis.","authors":"Md Adnan Karim, Chang Gyun Park, Hyunki Cho, Annmariya Elayanithottathil Sebastian, Chang Seon Ryu, Juyong Yoon, Young Jun Kim","doi":"10.1080/15376516.2025.2477036","DOIUrl":"10.1080/15376516.2025.2477036","url":null,"abstract":"The androgen receptor (AR) activation by androgens is vital for tissue development, sexual differentiation, and reproductive attributes in zebrafish (Danio rerio). However, our understanding of the molecular mechanisms behind their activation remains limited. In this study, we employed both ab initio (AlphaFold) and homology (SWISS-MODEL) structure models of zebrafish androgen receptor ligand-binding domain (zAR-LBD) to explore the binding specificity, binding affinity, and molecular interactions of endogenous hormones (testosterone (T), 11-ketotestosterone (11-KT), and dihydrotestosterone (DHT)) in a computational simulation. Molecular docking analysis showed that both structures formed the same interactions and similar patterns of binding energy with androgens. Molecular Dynamics (MD) simulation analysis revealed that hydrogen bond occupancy aligned with in vitro findings related to androgenic effect. When comparing complexes modeled by SWISS-MODEL and AlphaFold, significant differences were observed in root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The AlphaFold structures also exhibited a clear separation between ligands in principal component analysis. Further correlation analysis between in silico features and in vitro EC50 values identified MMPBSA energies as the most significant contributors to ligand-specific variance in the in silico complexes (p < 0.05). Overall, this integrative approach offers significant insights into the molecular mechanisms underlying zebrafish AR activity.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Investigating the genomic and biochemical effects of dalapon on antioxidant systems in zebrafish, Danio rerio. 研究达拉蓬对斑马鱼抗氧化系统的基因组和生化影响。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-12 DOI: 10.1080/15376516.2025.2473525

Mehtap Bayır, Abdulkadir Bayır, Burcu Naz Uzun, Serpil Turhan

{"title":"Investigating the genomic and biochemical effects of dalapon on antioxidant systems in zebrafish, Danio rerio.","authors":"Mehtap Bayır, Abdulkadir Bayır, Burcu Naz Uzun, Serpil Turhan","doi":"10.1080/15376516.2025.2473525","DOIUrl":"https://doi.org/10.1080/15376516.2025.2473525","url":null,"abstract":"This research explored the effects of dalapon exposure on the expression of various genes, including cat, sod1, sod2, sod3a, sod3b, gpx1a, gpx3, gpx4a, gpx4b, gpx7, gpx8, gpx9, gstr, g6pd, and gsr, along with the activities of related antioxidant enzymes (AEs), such as CAT, SOD, GPX, G6PD, GST, and GR in zebrafish. Kidney and liver tissues were analyzed to assess oxidative stress levels. Results indicated that both the concentration of dalapon (25 and 50 ppm) and the duration of exposure had a significant effect on AE activities and gene expression. RT-PCR analysis suggested that changes in gene expression among dalapon-exposed zebrafish might indicate a rapid response to pesticide-induced stress. Moreover, the activities of CAT, G6PD, and GST increased in response to dalapon exposure at the specified concentrations. In contrast, prolonged exposure exceeding 72 h led to significantly higher malondialdehyde levels in liver and kidney tissues compared to the control group. These findings enhance our understanding of the role of antioxidant enzymes in oxidative stress and provide important insights for developing aquaculture breeding programs focused on improving fish stress tolerance. Furthermore, phylogenetic analysis and conserved gene synteny analysis confirmed that the antioxidant enzyme genes in zebrafish are orthologous to those found in other model organisms, such as medaka and stickleback. Consequently, these results could be beneficial for other vertebrate species.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Exploring the impact of ambient air PM_2.5 on multiple sclerosis: an experimental dive into neuroinflammation. 探索环境空气PM2.5对多发性硬化症的影响：神经炎症的实验研究。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-11 DOI: 10.1080/15376516.2025.2468726

Shilan Mozaffari, Mohammad Sadegh Hassanvand, Maryam Baeeri, Mahdi Gholami, Zahra Bayrami, Masud Yunesian, Mohammad Ali Sahraian, Shekoufeh Nikfar, Mohammad Abdollahi

{"title":"Exploring the impact of ambient air PM2.5 on multiple sclerosis: an experimental dive into neuroinflammation.","authors":"Shilan Mozaffari, Mohammad Sadegh Hassanvand, Maryam Baeeri, Mahdi Gholami, Zahra Bayrami, Masud Yunesian, Mohammad Ali Sahraian, Shekoufeh Nikfar, Mohammad Abdollahi","doi":"10.1080/15376516.2025.2468726","DOIUrl":"https://doi.org/10.1080/15376516.2025.2468726","url":null,"abstract":"There is mounting evidence about the connection between particulate matter (PM) and neuroinflammation. This study aimed to evaluate the toxicological effects of PM2.5 associated with inflammatory factors in a mouse's multiple sclerosis (MS) model. Thirty C57BL/6 male mice were categorized into five groups: a group of healthy mice, a control cuprizone-induced MS group, and three MS-induced groups, intranasally exposed to three concentrations of ambient air PM2.5 (5, 10, and 20 mg/mL) from Tehran in a phosphate-buffered saline (PBS) solution. All mice were investigated by motor function, molecular, and histopathological assays. Moreover, the chemical content of the collected PM2.5 was assessed and reported. The cumulative exposure doses were equal to 0.025, 0.05, and 0.1 mg per gram of body weight of mice, which were approximately 3.52, 7.04, and 14.08 times higher than the human daily dose in Tehran. The PM2.5-exposed groups showed a high inflammatory response characterized by a significant increase in the mRNA expression of tumor necrosis alpha (TNF-α), NLRP3, and interleukin 18 (IL-18). In addition, the PM2.5-exposed groups exhibited a notably lower velocity level, total traveled distance (TD), and duration traveled in the central zone (DC) than the control group. The histopathological assays revealed significant pathological alterations and demyelination in the PM2.5-exposed groups compared to the control group. Identifying the risks and reducing the likelihood of exposure through preventive measures and regulations can result in financial savings and improve the quality of life for MS patients.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The effect of simvastatin induced neurotoxicity on mitochondrial function in human neuronal cells. 辛伐他汀诱导的神经毒性对人神经元细胞线粒体功能的影响。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-03 DOI: 10.1080/15376516.2025.2471807

Lauren Millichap, Nadia Turton, Razan Alomosh, Robert A Heaton, Amy Bateman, Nasser Al-Shanti, Adam P Lightfoot, Elisabetta Damiani, Fabio Marcheggiani, Patrick Orlando, Sonia Silvestri, Luca Tiano, Iain P Hargreaves

{"title":"The effect of simvastatin induced neurotoxicity on mitochondrial function in human neuronal cells.","authors":"Lauren Millichap, Nadia Turton, Razan Alomosh, Robert A Heaton, Amy Bateman, Nasser Al-Shanti, Adam P Lightfoot, Elisabetta Damiani, Fabio Marcheggiani, Patrick Orlando, Sonia Silvestri, Luca Tiano, Iain P Hargreaves","doi":"10.1080/15376516.2025.2471807","DOIUrl":"https://doi.org/10.1080/15376516.2025.2471807","url":null,"abstract":"3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) inhibitors, commonly known as statins, are drugs frequently used in the treatment of hypercholesterolemia and hyperlipidemia. However, the current study has demonstrated that simvastatin induces neurotoxicity and is associated with cellular coenzyme Q10 (CoQ10) depletion. CoQ10 has a significant role in the mitochondrial electron transport chain (ETC), in addition to being a fundamental lipid-soluble antioxidant. Depletion of CoQ10 is frequently associated with impaired mitochondrial function and increased oxidative stress. The aim of this study was to investigate the potential mechanisms of simvastatin-induced neurotoxicity assessing mitochondrial function and evidence of oxidative stress in an in vitro SH-SY5Y human neuronal cell line. Fluorescence studies assessed via flow cytometry determined significant increases in intracellular and mitochondrial reactive oxygen species production following SH-SY5Y treatment with simvastatin compared to control cells. Additionally, spectrophotometric enzyme studies determined a significant (p < 0.0001) inhibition of ETC complex I and II-III activities which accompanied a significant decrease in neuronal CoQ10 content (p < 0.005) and cell viability (p < 0.0001). The results of the present study have indicated evidence of mitochondrial dysfunction and increased oxidative stress, resulting in increased loss of neuronal viability following simvastatin treatment. Thus, these results demonstrate evidence of neurotoxicity associated with statin therapy.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

From historical drugs to present perils: UHPLC-QqQ-MS/MS determination of methaqualone and its designer analogs (NPS) with comprehensive fragmentation pathways study (QTOF). 从历史上的毒品到现在的危险：利用综合碎片途径研究（QTOF）测定甲喹酮及其设计类似物（NPS）的超高效液相色谱-QqQ-MS/MS。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-11-15 DOI: 10.1080/15376516.2024.2426582

Kaja Tusiewicz, Olga Wachełko, Paweł Szpot, Marcin Zawadzki

{"title":"From historical drugs to present perils: UHPLC-QqQ-MS/MS determination of methaqualone and its designer analogs (NPS) with comprehensive fragmentation pathways study (QTOF).","authors":"Kaja Tusiewicz, Olga Wachełko, Paweł Szpot, Marcin Zawadzki","doi":"10.1080/15376516.2024.2426582","DOIUrl":"10.1080/15376516.2024.2426582","url":null,"abstract":"Methaqualone, introduced in the 1960s as a sedative-hypnotic alternative to barbiturates, was withdrawn from the market due to its side effects and growing recreational use. Despite this, interest in methaqualone and its analogs remains high, raising concerns about potential abuse in the future. An ultra-high-performance liquid chromatography method coupled with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) was developed to determine nine methaqualone-related compounds simultaneously. Biological samples were prepared using liquid-liquid extraction with ethyl acetate at pH9; quantification was performed in blood using multiple reaction monitoring (MRM) mode. Methaqualone-d7 served as an internal standard. The limit of quantification (LOQ) ranged from 0.1 to 0.2 ng/mL, with precision and accuracy within 20%. Recovery ranged from 84.2% to 113.7%. The developed method allowed chromatographic separation of all compounds tested, including two structural isomers: methylmethaqualone and etaqualone. The mass spectra acquired from quadrupole time-of-flight mass spectrometer allowed for the elucidation of comprehensive fragmentation study of methaqualone derivatives. The described situation poses a significant problem from the analytical point of view, as well as interpretation and forensic toxicological expertise. The developed method will contribute to increased analytical capabilities and enhanced detection of compounds from the methaqualone group that may appear on the illicit market.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"318-328"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 waterpipe smoke induce genotoxicity (DNA damage) in mammalian cells in vivo? A systematic review. 水烟是否会诱发哺乳动物体内细胞的遗传毒性（DNA 损伤）？系统综述。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-10-06 DOI: 10.1080/15376516.2024.2411381

Thiago Guedes Pinto, Fernando Augusto Cintra Magalhães, Ana Claudia Muniz Renno, Daniel Araki Ribeiro

{"title":"Does waterpipe smoke induce genotoxicity (DNA damage) in mammalian cells in vivo? A systematic review.","authors":"Thiago Guedes Pinto, Fernando Augusto Cintra Magalhães, Ana Claudia Muniz Renno, Daniel Araki Ribeiro","doi":"10.1080/15376516.2024.2411381","DOIUrl":"10.1080/15376516.2024.2411381","url":null,"abstract":"The waterpipe works by placing tobacco in a bowl with holes at the bottom, which is connected to a tube leading to a water-filled container. Upon heating the tobacco product with hot charcoal placed atop it, the emanating smoke is inhaled by the user via a hose linked to the water receptacle. The aim of this literature review is to evaluate whether the use of waterpipes can indeed induce genotoxicity in mammalian cells in vivo. Additionally, the study aims to assess the quality of the included research articles on this topic to ensure the reliability of the findings. We performed comprehensive searches in PubMed, SCOPUS, and Web of Science to identify relevant articles published until July 2024. The findings confirmed that waterpipe smoke induces genetic damage. This assertion is supported by the fact that 11 studies (out of 15) received a Strong or Moderate assessment categorization, suggesting that the majority of studies adhered to most technical standards, thereby enhancing the reliability of the research findings. Regarding the types of DNA damage reported, DNA strand breaks, chromosome damage and oxidative DNA damage were found in this review. Taken together, this study holds significant importance in assessing the efficacy of genotoxicity assays in detecting DNA damage due to waterpipe smoke and the comet and micronucleus assays are suitable biomarkers for biomonitoring people who use waterpipe.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"240-249"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

In silico aquatic toxicity prediction of chemicals toward Daphnia magna and fathead minnow using Monte Carlo approaches. 使用蒙特卡洛方法对大型蚤和黑头鲦的化学物质水生毒性进行硅学预测。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-10-29 DOI: 10.1080/15376516.2024.2416226

Shahram Lotfi, Shahin Ahmadi, Ali Azimi, Parvin Kumar

{"title":"In silico aquatic toxicity prediction of chemicals toward Daphnia magna and fathead minnow using Monte Carlo approaches.","authors":"Shahram Lotfi, Shahin Ahmadi, Ali Azimi, Parvin Kumar","doi":"10.1080/15376516.2024.2416226","DOIUrl":"10.1080/15376516.2024.2416226","url":null,"abstract":"The fast-increasing use of chemicals led to large numbers of chemical compounds entering the aquatic environment, raising concerns about their potential effects on ecosystems. Therefore, assessment of the ecotoxicological features of organic compounds on aquatic organisms is very important. Daphnia magna and Fathead minnow are two aquatic species that are commonly tested as standard test organisms for aquatic risk assessment and are typically chosen as the biological model for the ecotoxicology investigations of chemical pollutants. Herein, global quantitative structure-toxicity relationship (QSTR) models have been developed to predict the toxicity (pEC(LC)50) of a large dataset comprising 2106 chemicals toward Daphnia magna and Fathead minnow. The optimal descriptor of correlation weights (DCWs) is calculated using the notation of simplified molecular input line entry system (SMILES) and is used to construct QSTR models. Three target functions, TF1, TF2, and TF3 are utilized to generate 12 QSTR models from four splits, and their statistical characteristics are also compared. The designed QSTR models are validated using both internal and external validation criteria and are found to be reliable, robust, and excellently predictive. Among the models, those generated using the TF3 demonstrate the best statistical quality with R2 values ranging from 0.9467 to 0.9607, Q2 values ranging from 0.9462 to 0.9603 and RMSE values ranging from 0.3764 to 0.4413 for the validation set. The applicability domain and the mechanistic interpretations of generated models were also discussed.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"305-317"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Decoding the possible mechanism of action of Paeoniflorigenone in combating Aflatoxin B1-induced liver cancer: an investigation using network pharmacology and bioinformatics analysis. 解码芍药甙元酮对抗黄曲霉毒素 B1 诱导的肝癌的可能作用机制：利用网络药理学和生物信息学分析进行的研究。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-11-06 DOI: 10.1080/15376516.2024.2411621

Xiaocong Liang, Huiling Yang, Pengrong Hu, Ziyan Gan, Shunqin Long, Sumei Wang, Xiaobing Yang

{"title":"Decoding the possible mechanism of action of Paeoniflorigenone in combating Aflatoxin B1-induced liver cancer: an investigation using network pharmacology and bioinformatics analysis.","authors":"Xiaocong Liang, Huiling Yang, Pengrong Hu, Ziyan Gan, Shunqin Long, Sumei Wang, Xiaobing Yang","doi":"10.1080/15376516.2024.2411621","DOIUrl":"10.1080/15376516.2024.2411621","url":null,"abstract":"Moutan cortex has demonstrated antitumor properties attributed to its bioactive compound Paeoniflorigenone (PA). Nevertheless, there is limited research on the efficacy of PA in the prevention and treatment of hepatocellular carcinoma (HCC). We aimed to investigate the potential pharmacological mechanisms of PA in the treatment of Aflatoxin B1 (AFB1)-induced hepatocarcinogenesis using network pharmacology and bioinformatics analysis approaches. Through various databases and bioinformatics analysis approaches, 34 shared targets were identified as potential candidate genes for PA in fighting liver cancer caused by AFB1. Pathway analysis revealed involvement in cell cycle, HIF-1, and Rap1 pathways. A risk assessment model was developed using LASSO regression, showing an association between the identified genes and the tumor immune microenvironment. The genes within the risk model were found to be linked to the immune response in liver cancer. Molecular docking studies indicated that PA interacts with its targets through hydrogen bonding and hydrophobic interactions. This study provides insights into the possible mechanisms of PA in liver cancer treatment and offers a predictive model for assessing the risk level of individuals with liver cancer. These findings have significant implications for the therapeutic strategies in managing liver cancer patients.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"292-304"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Do professional painters comprise a high risk group for genotoxicity? A systematic review. 职业油漆工是遗传毒性的高危人群吗？系统综述。

IF 3.2 4区医学

Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-10-09 DOI: 10.1080/15376516.2024.2411060

Thiago Guedes Pinto, Thayza Aires Dias, Daniel Araki Ribeiro

{"title":"Do professional painters comprise a high risk group for genotoxicity? A systematic review.","authors":"Thiago Guedes Pinto, Thayza Aires Dias, Daniel Araki Ribeiro","doi":"10.1080/15376516.2024.2411060","DOIUrl":"10.1080/15376516.2024.2411060","url":null,"abstract":"Professional painters represent an occupational population group that deserves attention for study in the field of occupational toxicology due to the wide range of complex chemical mixtures they are exposed to. It is imperative to underscore that the International Agency for Research on Cancer has classified commercial painting as a high-risk occupation for the development of cancer. Given this context, the primary objective of the present study was to conduct a systematic review aimed at addressing the following question: are car painters at occupational risk regarding potential genotoxicity? To address this question, a selection process was undertaken, with three reviewers carefully selecting, reading, and analyzing full manuscripts from 26 studies included in this review. The technical rigor of these studies underwent meticulous scrutiny, culminating in the classification of six studies as Strong, eight as Moderate, and 12 as Weak, predicated on the extent of confounders considered. Taken together, the findings suggest that chemical substances from paints may indeed pose a risk of genotoxicity for professionals in this field, as all studies indicated genotoxicity among professional painters through various tests.","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"230-239"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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