Toxicology Mechanisms and Methods最新文献

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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 <i>in vivo</i>? 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":"<p><p>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 <i>via</i> 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 <i>in vivo</i>. 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.</p>","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
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":"<p><p>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-<i>d<sub>7</sub></i> 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.</p>","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
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":"<i>In silico</i> aquatic toxicity prediction of chemicals toward <i>Daphnia magna</i> 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":"<p><p>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. <i>Daphnia magna</i> and <i>Fathead minnow</i> 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 <i>Daphnia magna</i> and <i>Fathead minnow</i>. 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, TF<sub>1</sub>, TF<sub>2</sub>, and TF<sub>3</sub> 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 TF<sub>3</sub> demonstrate the best statistical quality with <i>R</i><sup>2</sup> values ranging from 0.9467 to 0.9607, <i>Q</i><sup>2</sup> 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.</p>","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":"<p><p>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.</p>","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":"<p><p>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.</p>","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
Mechanistic paradigms of immunotoxicity, triggered by nanoparticles - a review. 纳米粒子引发免疫毒性的机理范例--综述。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-12-05 DOI: 10.1080/15376516.2024.2431687
S V S Rana
{"title":"Mechanistic paradigms of immunotoxicity, triggered by nanoparticles - a review.","authors":"S V S Rana","doi":"10.1080/15376516.2024.2431687","DOIUrl":"10.1080/15376516.2024.2431687","url":null,"abstract":"<p><p>Nanoparticles (NPs) possess the ability to penetrate cells and elicit a rapid and targeted immune response, influenced by their distinct physicochemical properties. These particles can engage with both micro and macromolecules, thereby impacting various downstream signaling pathways that may lead to cell death. This review provides a comprehensive overview of the primary mechanisms contributing to the immunotoxicity of both organic and inorganic nanoparticles. The effects of carbon-based nanomaterials (CNMs), including single-walled carbon nanotubes, multi-walled carbon nanotubes, graphene, and metal oxide nanoparticles, on various immune cell types such as macrophages, neutrophils, monocytes, dendritic cells (DCs), antigen-presenting cells (APCs), and RAW 264.7 cells are examined. The immune responses discussed encompass inflammation, oxidative stress, autophagy, and apoptosis. Additionally, the roles of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ, along with JAK/STAT signaling pathways, are highlighted. The interaction of NPs with oxidative stress pathways, including MAPK signaling and Nrf2/ARE signaling, is also explored. Furthermore, the mechanisms by which nanoparticles induce damage to organelles such as lysosomes, the endoplasmic reticulum, exosomes, and Golgi bodies within the immune system are addressed. The review also emphasizes the genotoxic and epigenetic mechanisms associated with the immunotoxicity of NPs. Recent advancements regarding the immunotherapeutic potential of engineered NPs are reported. The roles of autophagy and apoptosis in the immunotoxicity of NPs merit further investigation. In conclusion, understanding how engineered nanoparticles modulate immune responses may facilitate the prevention and treatment of human diseases, including cancer and autoimmune disorders.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"262-278"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711129","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
Disposable electronic cigarettes - chemical composition and health effects of their use. A systematic review. 一次性电子香烟--化学成分及其使用对健康的影响。系统综述。
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-03-01 Epub Date: 2024-11-08 DOI: 10.1080/15376516.2024.2423927
Paulina Natalia Kopa-Stojak, Rafal Pawliczak
{"title":"Disposable electronic cigarettes - chemical composition and health effects of their use. A systematic review.","authors":"Paulina Natalia Kopa-Stojak, Rafal Pawliczak","doi":"10.1080/15376516.2024.2423927","DOIUrl":"10.1080/15376516.2024.2423927","url":null,"abstract":"<p><strong>Objective: </strong>Despite the rising popularity of disposable e-cigarettes, little is known about their chemical characteristics, or their impact on users' health. This work attempts to summarize current knowledge about chemical composition and known health effects of disposable e-cigarettes.</p><p><strong>Methods: </strong>The literature search was performed in February and March 2024 in Pub Med and Science Direct databases (no time range) by the terms 'disposable electronic cigarette', 'disposable e-cigarette', 'disposable e-cigs', 'cig-a-like e-cigarette', 'cig-a-like electronic cigarette'.</p><p><strong>Results: </strong>Disposable e-cigarettes contain: nicotine, humectants (propylene glycol, glycerin), flavoring agents (diacetyl, acetoin, triacetin, p-menthone, triethyl citrate, ethyl maltol, 3-hexen-1-ol, methyl anthranilate, α-terpineol, perillartine, benzyl alcohol, vanillin, melonal, methyl dihydrojasmonate, and γ-decalactone), cooling agents (WS-3, WS-23, menthol), carbonyl compounds (acetaldehyde, formaldehyde, propionaldehyde, acetone, acrolein) volatile organic compounds (VOCs) (benzene, ethanol, methanol, styrene, acetylpirazine and 2,3,5-trimethylpyrazine), metals and inorganic compounds (chromium, nickel, manganese, lead, aluminum, and zinc) and reactive oxygen species. Furthermore, there was some evidence of nicotine dependence, risk of cancer and adverse respiratory effects of using disposable e-cigarettes.</p><p><strong>Conclusions: </strong>Despite the fact that disposable e-cigarettes contain significantly less toxins compared to combustible cigarettes, they include compounds that are absent in such products that may provide health risk in prolonged usage. In addition, there is a limited number of data on the health effect of disposable e-cigarettes, especially in long time period, for never-smokers. Therefore, due to growing popularity of disposable e-cigarettes among young people, who choose them when initiating nicotine use, further research on their long-term impact of on the users' health is necessary.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"250-261"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606116","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
Quantitative methods for the risk assessment of drinking water contact chemicals following the NSF/ANSI/CAN 600 standard - part I: general methods.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-02-28 DOI: 10.1080/15376516.2025.2463487
Bradley J Lampe, Shannon Cousineau, J Caroline English, Shannon Ethridge, Lynne T Haber, Kristin Kerstens, Craig Rowlands, Kelly A Magurany
{"title":"Quantitative methods for the risk assessment of drinking water contact chemicals following the NSF/ANSI/CAN 600 standard - part I: general methods.","authors":"Bradley J Lampe, Shannon Cousineau, J Caroline English, Shannon Ethridge, Lynne T Haber, Kristin Kerstens, Craig Rowlands, Kelly A Magurany","doi":"10.1080/15376516.2025.2463487","DOIUrl":"https://doi.org/10.1080/15376516.2025.2463487","url":null,"abstract":"<p><p>Health-based criteria have been developed using quantitative methods for over 370 unregulated chemicals that have been detected in extraction testing of products certified or undergoing certification to public health-based drinking water standards. These criteria are derived in accordance with the requirements of NSF/ANSI/CAN 600, <i>Health Effects Evaluation and Criteria for Chemicals in Drinking Water</i> and undergo external peer review by an independent Health Advisory Board. However, a complete and unified description of how these criteria are derived is not available in the scientific literature. This is the first part of a two-part publication that describes the core concepts involved in deriving these criteria. In this first part, general approaches that are consistently applied to the derivation of health-based criteria are discussed, including methods related to the literature search, evaluation of study quality, derivation of the reference dose, selection of uncertainty factors, and identification of the appropriate drinking water intake rate.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524524","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
Molecular heterogeneity in pediatric sepsis: identification of oxidative stress-related subtypes and diagnostic biomarkers through integrated bioinformatics analysis.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-02-28 DOI: 10.1080/15376516.2025.2466577
Ding Ding, Min Zhang, Zhen Li, Zhengxiang Liu, Nian Liu
{"title":"Molecular heterogeneity in pediatric sepsis: identification of oxidative stress-related subtypes and diagnostic biomarkers through integrated bioinformatics analysis.","authors":"Ding Ding, Min Zhang, Zhen Li, Zhengxiang Liu, Nian Liu","doi":"10.1080/15376516.2025.2466577","DOIUrl":"10.1080/15376516.2025.2466577","url":null,"abstract":"<p><strong>Background: </strong>Pediatric sepsis is a life-threatening condition characterized by a dysregulated immune response to infection, often involving heightened oxidative stress. Understanding the molecular heterogeneity of sepsis can provide insights into potential therapeutic targets and diagnostic biomarkers.</p><p><strong>Methods: </strong>Machine learning approaches were employed to identify diagnostic biomarkers. Unsupervised clustering was performed to identify distinct sepsis subtypes. We conducted an integrative analysis combining Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), differential gene expression, and functional enrichment to study oxidative stress-related subgroups in sepsis patients. Immune cell infiltration and immune-related pathway activities were analyzed using the ssGSEA algorithm. GSVA and GSEA indicated significant enrichment of oxidative stress-related pathways in sepsis patients compared to controls.</p><p><strong>Results: </strong>Differential expression analysis identified 371 upregulated and 304 downregulated genes in sepsis, with 34 genes linked to oxidative stress. LASSO and Random Forest analyses highlighted key diagnostic genes (GBA and MGST1), validated in independent datasets (GSE13904) with high diagnostic accuracy (AUC: GBA = 0.924, MGST1 = 0.857). Unsupervised clustering revealed two distinct sepsis subtypes with differential immune cell infiltration and pathway activities: Subtype 1 showed higher T cell and TFH infiltration, while Subtype 2 exhibited increased macrophage infiltration. Functional enrichment and GSEA identified key metabolic, oxidative stress, and immune pathways that were enriched in Subtype 2.</p><p><strong>Conclusion: </strong>Our comprehensive bioinformatics analysis unveils significant oxidative stress-related molecular heterogeneity in sepsis, identifying potential diagnostic biomarkers and therapeutic targets. Personalized medicine approaches targeting specific oxidative stress pathways and immune responses could enhance sepsis management and patient outcomes.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415343","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
Network toxicology analysis reveals molecular mechanisms associated with noise exposure to multiple diseases.
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2025-02-13 DOI: 10.1080/15376516.2025.2460591
Maria Taboada-Alquerque, Jesus Olivero-Verbel
{"title":"Network toxicology analysis reveals molecular mechanisms associated with noise exposure to multiple diseases.","authors":"Maria Taboada-Alquerque, Jesus Olivero-Verbel","doi":"10.1080/15376516.2025.2460591","DOIUrl":"10.1080/15376516.2025.2460591","url":null,"abstract":"<p><p>Noise pollution is recognized as an environmental stressor that affects various biological processes beyond auditory functions, mainly through stress hormones release. This work explored the biological processes, diseases attributable to noise-regulated targets, and the main targets involved in each disease, employing a network toxicology approach. Through various databases and bioinformatics analysis, a total of 577 targets were identified as potential candidates implicated in diseases related to noise exposure, 10 from the GEO database and the rest from other databases. Noise pollution was found to regulate processes such as hormone response, cellular response to cytokines, and circulatory system functions, contributing to the development of the pathological manifestations related to the diseases like hypertension, ischemia, atherosclerosis, and cirrhosis. Hub targets for ischemia included IL-6, CASP3, AKT1, and TNF-α, while NOS3 was related to hypertension, and NOS3, TNF-α, AGT, and IL-1B to atherosclerosis. The targets were found to be linked to vascular regulation and inflammation in cardiovascular and cerebrovascular diseases. Molecular docking studies indicated stress hormones released by noise exposure regulates these diseases through signaling pathways, without implicating its direct binding to hub targets. The results indicate that individuals with vascular diseases are more vulnerable to the effects of prolonged noise exposure.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081143","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
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