Chemical Research in Toxicology最新文献

Quantification of Flavors, Volatile Organic Compounds, Tobacco Markers, and Tobacco-Specific Nitrosamines in Heated Tobacco Products and Their Mainstream Aerosol.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-20 DOI: 10.1021/acs.chemrestox.5c00005

Saria Hoshino, Kazushi Noro, Takashi Amagai

{"title":"Quantification of Flavors, Volatile Organic Compounds, Tobacco Markers, and Tobacco-Specific Nitrosamines in Heated Tobacco Products and Their Mainstream Aerosol.","authors":"Saria Hoshino, Kazushi Noro, Takashi Amagai","doi":"10.1021/acs.chemrestox.5c00005","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00005","url":null,"abstract":"As an alternative to cigarettes, the sales of heated tobacco products (HTPs) have increased in the Japanese market. This may contribute to improving a smoker's health because the levels of most toxic compounds─such as tobacco-specific nitrosamines (TSNAs) and volatile organic compounds (VOCs)─in the mainstream of HTPs are lower than those in cigarettes. However, the risks associated with the flavors that provide attractive tastes to HTPs remain unknown. We demonstrated that compared with cigarettes, HTPs reduce the health risks associated with VOCs and TSNAs while achieving comparable nicotine and flavor levels. The VOC and TSNA concentrations in the mainstream aerosol of HTPs were 0.0039 (benzene)-0.53 (acetaldehyde) times lower than those in cigarettes. Using HTPs may still pose adverse noncarcinogenic and carcinogenic effects on human health, as indicated by hazard quotients >1 for acrolein and acetaldehyde, margins of exposure <100 for (R)-(+)-limonene, and cancer risks >1.0 × 10-6 for acetaldehyde. Additionally, the exhalation of mainstream aerosol may increase the indoor acrolein concentration to 0.069 μg m-3, exceeding the reference concentration for acrolein (0.02 μg m-3). Therefore, reducing acrolein concentrations is an effective measure for improving the safety of HTP use.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nanoparticle-Mediated Embryotoxicity: Mechanisms of Chemical Toxicity and Implications for Biological Development.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-19 DOI: 10.1021/acs.chemrestox.4c00472

Biswajeet Acharya, Amulyaratna Behera, Srikanta Moharana, Bhupendra G Prajapati, Suchismeeta Behera

{"title":"Nanoparticle-Mediated Embryotoxicity: Mechanisms of Chemical Toxicity and Implications for Biological Development.","authors":"Biswajeet Acharya, Amulyaratna Behera, Srikanta Moharana, Bhupendra G Prajapati, Suchismeeta Behera","doi":"10.1021/acs.chemrestox.4c00472","DOIUrl":"10.1021/acs.chemrestox.4c00472","url":null,"abstract":"Nanoparticles, defined by their nanoscale dimensions and unique physicochemical properties, are widely utilized in healthcare, electronics, environmental sciences, and consumer products. However, increasing evidence of their potential embryotoxic effects during pregnancy underscores the need for a molecular-level understanding of their interactions during embryonic development. Nanoparticles such as titanium dioxide, silver, cerium oxide, copper oxide, and quantum dots can cross the placental barrier and interfere with crucial developmental processes. At the molecular level, they disrupt signaling pathways like Wnt and Hedgehog, induce oxidative stress and inflammation, and cause genotoxic effects, all critical during sensitive phases, such as organogenesis. Furthermore, these nanoparticles interact directly with cellular components, including DNA, proteins, and lipids, impairing cellular function and viability. Innovative strategies to mitigate nanoparticle toxicity, such as surface modifications and incorporation of biocompatible coatings, are discussed as potential solutions to reduce adverse molecular interactions. Various laboratory animal models used to investigate nanoparticle-induced embryotoxicity are evaluated for their efficacy and limitations, providing insights into their applicability for understanding these effects. This Account examines the molecular mechanisms by which nanoparticles compromise embryonic development and emphasizes the importance of designing safer nanoparticles to minimize maternal-fetal exposure risks, particularly in biomedical applications.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Systematic Investigation of CYP3A4 Using Side-by-Side Comparisons of Apo, Active Site, and Allosteric-Bound States.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-19 DOI: 10.1021/acs.chemrestox.4c00387

Pranchal Shrivastava, Somnath Mondal, Shivani Thakur, Anu Manhas, Rukmankesh Mehra

{"title":"Systematic Investigation of CYP3A4 Using Side-by-Side Comparisons of Apo, Active Site, and Allosteric-Bound States.","authors":"Pranchal Shrivastava, Somnath Mondal, Shivani Thakur, Anu Manhas, Rukmankesh Mehra","doi":"10.1021/acs.chemrestox.4c00387","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00387","url":null,"abstract":"Cytochrome P450 (CYP) 3A4 (CYP3A4) is a complex enzyme that metabolizes diverse substrates. It contains a large binding site accommodating diverse ligands, binding to active or allosteric sites. CYP3A4 does not always follow Michaelis-Menten kinetics. While Km reflects substrate affinity, it does not necessarily determine the enzyme's activity, though it is often considered indicative of substrate binding characteristics. The mechanism may be highly sophisticated and driven by multiple factors. This suggests that the ligand binding affinity alone may not explain the differential behavior of the enzyme conformational stability. Here, we analyzed sequence conserveness of 57 CYPs, followed by a detailed molecular dynamics simulation study (9 μs) on CYP3A4. We studied three CYP3A4 enzyme states (apo-state, active-site, and allosteric-site ligand-bound states) collected from the same experimental setup to reduce the systematic error. We found that the enzyme conformational stability followed a consistent trend of allosteric > active > apo states, which was inconsistent with the enzyme-ligand (active/allosteric) binding affinity and the ligand conformational stability. However, the heme group showed a significant protein affinity and stability pattern directly related to the enzyme stability, suggesting that the active/allosteric binding may work by influencing the heme-CYP3A4 binding affinity, and the allosteric ligand appeared to form the most stable enzyme state of the three studied states.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Dr. Nathaniel Snyder, 2024 Young Investigator Award Recipient, American Chemical Society Division of Chemical Toxicology.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 Epub Date: 2025-02-12 DOI: 10.1021/acs.chemrestox.4c00474

Don Pivithuru Liyanarachchi

引用次数: 0

Electronic Cigarette-Derived Metals: Exposure and Health Risks in Vapers.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 DOI: 10.1021/acs.chemrestox.4c00520

Ahmad Besaratinia

{"title":"Electronic Cigarette-Derived Metals: Exposure and Health Risks in Vapers.","authors":"Ahmad Besaratinia","doi":"10.1021/acs.chemrestox.4c00520","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00520","url":null,"abstract":"Despite the popularity of electronic cigarettes (e-cigs) among adolescent and youth never-smokers and adult smokers seeking a less harmful substitute for tobacco cigarettes, the long-term health impact of vaping is largely unknown. Biochemical, molecular, and toxicological analyses of biospecimens from e-cig users as well as assays in relevant in vitro models and in silico studies can identify chemical constituents of e-cig emissions that may contribute to the disease-causing potential of vaping. E-cig aerosol contains a wide range of toxic and carcinogenic compounds, of which metals are of particular concern. This is due to the known or suspected role of various metals in the pathogenesis of numerous diseases. Many metals and metalloids (herein referred to as \"metals\") have been detected in e-cig liquid (e-liquid) and aerosol and/or in cells, tissues, biofluids, or other specimens from e-cig users. Metals can contaminate the ingredients of e-liquid or corrode from the internal components of the e-cig device. Metals may also be directly aerosolized from the surface of the heating element or other parts of the device. Inhalation of e-cig metal emissions in habitual vapers and nonusers through secondary exposure may increase the body burden of toxic and carcinogenic chemicals. This review summarizes the state of research on e-cig-derived metals and their contributions to the estimated health risks of vaping. Highlighting the chemical composition of e-cig liquid and aerosol, it focuses on the metal contents of the inhaled aerosol and the health risks associated with this exposure. Emphasis is placed on adolescents and youth who are vulnerable populations and bear a disproportionate burden of risk and harm from tobacco products. The gaps in knowledge, methodological challenges, and opportunities ahead are discussed. The importance of translating research findings into actionable information that can be used for the regulation of the manufacturing of tobacco products is underscored.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Correction to "Oxymatrine Inhibits Liver Cancer Progression by Regulating SIRT1/YY1/GPX4 Axis-Mediated Ferroptosis".

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 Epub Date: 2025-03-05 DOI: 10.1021/acs.chemrestox.5c00086

Jing Hu, Fuyi Zhang, Xiaoshan Qin, Xinlei Nong, Xiaoyan Shi, Xihan Zhou, Yueqiu Qin

引用次数: 0

Elevating Research and Careers in the Development of Safer Drugs through Artificial Intelligence.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 Epub Date: 2025-02-17 DOI: 10.1021/acs.chemrestox.4c00423

Alaa Marwan-Abu-Taha

引用次数: 0

A Promising Resveratrol Analogue Suppresses CSCs in Non-Small-Cell Lung Cancer via Inhibition of the ErbB2 Signaling Pathway.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 Epub Date: 2025-02-25 DOI: 10.1021/acs.chemrestox.4c00436

Tanapon Soonthonsrima, Ismail Dwi Putra, Preeyaphan Phookphan, Zin Zin Ei, Masashi Yokoya, Pithi Chanvorachote

{"title":"A Promising Resveratrol Analogue Suppresses CSCs in Non-Small-Cell Lung Cancer via Inhibition of the ErbB2 Signaling Pathway.","authors":"Tanapon Soonthonsrima, Ismail Dwi Putra, Preeyaphan Phookphan, Zin Zin Ei, Masashi Yokoya, Pithi Chanvorachote","doi":"10.1021/acs.chemrestox.4c00436","DOIUrl":"10.1021/acs.chemrestox.4c00436","url":null,"abstract":"The ErbB2 signaling pathway plays a crucial role in cancer stem cells (CSCs), governing cancer aggressiveness and proliferation. Targeting ErbB2 holds promise for advancing cancer therapeutics. Resveratrol (RES) and its derivatives have been noted for their ability to target proteins that are involved in CSCs. In this investigation, we synthesize novel derivatives of RES, aim at elucidating structure-activity relationships (SARs) that could enhance the anticancer properties of the RES analogues, and explore their capacities to suppress CSCs. YI-12, an O-benzyl-substituted 1,3-diphenylpropane, demonstrated the most potent anticancer activity against lung cancer cells (A549 and H460), showing high potential inhibiting cancer colony formation. Interestingly, not only does YI-12 suppress CSCs-related proteins, indicated by decreased expression of CSC-enhancing molecules such as CD133-, OCT4-, and CSC-related protein β-catenin, but it also induces apoptosis in CSC-rich spheroids after treatment. Additionally, molecular docking and bioinformatic analysis suggest ErbB2 as a potential target of the compound with a strong binding affinity (-6.709 kcal/mol) compared to the reference compound TAK-285 (-5.563 kcal/mol). YI-12's capability to bind and inhibit ErbB2 leads to the suppression of PI3K and AKT. In conclusion, we highlight the novel resveratrol derivative YI-12 for its ability to inhibit CSCs through the ErbB2 signaling pathway. This compound represents a promising structure that should be further developed for potential use in anticancer therapy.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"415-432"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Consensus Modeling for Predicting Chemical Binding to Transthyretin as the Winning Solution of the Tox24 Challenge.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 Epub Date: 2025-02-19 DOI: 10.1021/acs.chemrestox.4c00421

Dmitriy M Makarov, Alexander A Ksenofontov, Yury A Budkov

{"title":"Consensus Modeling for Predicting Chemical Binding to Transthyretin as the Winning Solution of the Tox24 Challenge.","authors":"Dmitriy M Makarov, Alexander A Ksenofontov, Yury A Budkov","doi":"10.1021/acs.chemrestox.4c00421","DOIUrl":"10.1021/acs.chemrestox.4c00421","url":null,"abstract":"The utilization of predictive methodologies for the assessment of toxicological properties represents an alternative approach that facilitates the identification of safe compounds while concurrently reducing the financial costs associated with the process. The objective of the Tox24 Challenge was to assess the progress in computational methods for predicting the activity of chemical binding to transthyretin (TTR). In order to fulfill the requirements of this task, the data set, measured by the Environmental Protection Agency, consisted of 1512 chemical substances of diverse nature. This paper describes the model that won the Tox24 Challenge and the steps taken for its further improvement. The Transformer convolutional neural network (CNN) model achieved the best performance as a standalone solution. Meanwhile, a multitask model built on a graph CNN, trained using 11 additional acute systemic toxicity data sets with increased weighting on the TTR binding activity, showed comparable results on the blind test set. The winning solution was a consensus model consisting of two catBoost models with OEstate and Mold2 descriptor sets, as well as two transformer-based models. The improvement of this solution involved adding a fifth model based on multitask learning using the graph CNN method, which led to a reduction in RMSE on the blind test set to 20.3%. The winning model was developed using the OCHEM web platform and is available online at https://ochem.eu/article/162082.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"392-399"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nicotine Dosimetry in Evaluating Electronic Cigarettes Compared to Cigarette Smoking: Implications for Tobacco Regulatory Science.

IF 3.7 3区医学

Chemical Research in Toxicology Pub Date : 2025-03-17 DOI: 10.1021/acs.chemrestox.4c00462

Neal L Benowitz, Hao-Yuan Yang, Peyton Jacob, Gideon St Helen

{"title":"Nicotine Dosimetry in Evaluating Electronic Cigarettes Compared to Cigarette Smoking: Implications for Tobacco Regulatory Science.","authors":"Neal L Benowitz, Hao-Yuan Yang, Peyton Jacob, Gideon St Helen","doi":"10.1021/acs.chemrestox.4c00462","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00462","url":null,"abstract":"The delivery and systemic absorption of nicotine are important for assessing the potential safety and efficacy of novel inhaled nicotine delivery devices. We describe an experimental approach for examining systemic nicotine intake, looking at individual variability, comparing JUUL electronic cigarettes and cigarette smoking, and comparing standardized puffing and ad libitum use. Fourteen cigarette smokers who were infrequent e-cigarette users vaped JUUL or smoked cigarettes, both in a standardized session (ten 3.5 s puffs over 5 min) and in a 4 h ad libitum use session. Plasma nicotine concentrations were measured, and using sex and body weight-based population nicotine clearance predictions, systemic nicotine dose was estimated in each session. The pharmacokinetically (PK)-estimated nicotine dose in the standardized session averaged 0.55 mg (range 0.16-0.82) for JUUL and 1.15 mg (range 0.35-4.56) for cigarette smoking. The PK-estimated dose with ad libitum use averaged 4.1 mg (range 0.4-9.5) for JUUL and 5.0 mg (range 1.5-15) for smoking (average 3.4 cigarettes). Within individual correlations, comparing PK-estimated dose for JUUL use with standardized vs ad libitum session was weak (r = 0.45, NS) but was much stronger for cigarette smoking (r = 0.82, p < 0.001). Data from ad libitum use predicted that consumption of the liquid contained in a JUUL pod would correspond to smoking 15 cigarettes, which is similar to that observed in real world studies. We conclude that standardized vaping sessions do not predict usual nicotine self-administration behavior with ad libitum use. With ad libitum use, nicotine intake is much more similar to vaping and smoking and provides a much better predictor of product delivery in the real world. This approach is recommended for screening of novel inhaled nicotine devices and to aid FDA regulatory decision making.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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