Environmental Toxicology最新文献

SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma. SERPING1 通过 ERK-MMP2-MMP-9 级联降低索拉非尼耐药肝细胞癌的细胞迁移率

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-10-30 DOI: 10.1002/tox.24434

Ching-Chuan Hsieh, Yuh-Harn Wu, Yi-Li Chen, Chun-I Wang, Chao-Jen Li, I-Hsiu Liu, Chen-Wei Chou, Yang-Hsiang Lin, Po-Shuan Huang, Te-Chia Huang, Cheng-Yi Chen

{"title":"SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma.","authors":"Ching-Chuan Hsieh, Yuh-Harn Wu, Yi-Li Chen, Chun-I Wang, Chao-Jen Li, I-Hsiu Liu, Chen-Wei Chou, Yang-Hsiang Lin, Po-Shuan Huang, Te-Chia Huang, Cheng-Yi Chen","doi":"10.1002/tox.24434","DOIUrl":"10.1002/tox.24434","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor, and it ranks 2nd in terms of mortality rate among all malignancies in Taiwan. Sorafenib is a multiple tyrosine kinase inhibitor that suppresses tumor cell proliferation and angiogenesis around tumors via different pathways. However, the survival outcome of advanced HCC patients treated with sorafenib is still unsatisfactory. Unfortunately, there are no clinically applicable biomarkers to predict sorafenib therapeutic efficiency in HCC thus far. We found that serpin peptidase inhibitor, clade G, member 1 (SERPING1) is highly associated with overall and recurrence-free survival rates in HCC patients and is also highly correlated with several clinical parameters. SERPING1 expression was increased with sorafenib in both the HCC cell extract and conditioned medium, which was also observed in sorafenib-resistant HepG2 and Huh7 cells. Sorafenib decreased cell viability and migration, which was similar to the effect of SERPING1 in HCC progression. Moreover, sorafenib inhibited both MMP-2 and MMP-9 activity and enhanced the expression of p-ERK in HCC cells. In summary, sorafenib reduces HCC cancer progression might through the p-ERK-MMP-2-MMP-9 cascade via upregulation of SERPING1. In the present study, the roles and molecular mechanisms of SERPING1 and its value as a marker for predicting sorafenib resistance and progression in HCC patients were examined. The results of the present study provide a deep understanding of the roles of SERPING1 in HCC sorafenib resistance, which can be applied to develop early diagnosis and prognosis evaluation methods and establish novel therapeutic targets for specifically treating HCC.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"318-327"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544454","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

Se-Methylselenocysteine Ameliorates DEHP-Induced Ferroptosis in Testicular Sertoli Cells via the Nrf2/GPX4 Axis. Se-甲基硒半胱氨酸通过Nrf2/GPX4轴改善DEHP诱导的睾丸Sertoli细胞铁突变

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-10-03 DOI: 10.1002/tox.24425

Weilin Mao, Yan Liu, Wei Gu, Wenchao Xu, Jihong Liu, Qing Ling, Jiaxin Wang

{"title":"Se-Methylselenocysteine Ameliorates DEHP-Induced Ferroptosis in Testicular Sertoli Cells via the Nrf2/GPX4 Axis.","authors":"Weilin Mao, Yan Liu, Wei Gu, Wenchao Xu, Jihong Liu, Qing Ling, Jiaxin Wang","doi":"10.1002/tox.24425","DOIUrl":"10.1002/tox.24425","url":null,"abstract":"Di (2-ethylhexyl) phthalate (DEHP) is an important plasticizer in industrial production, and its toxic effects on testes are widely recognized. Se-methylselenocysteine (SMC) is a major selenium compound found in selenium-rich plants, which possesses unique biological properties such as antioxidants. However, the effect of SMC on DEHP-induced testicular injury and the specific mechanism remains unknown. In this study, 50 mice were randomly divided into 5 groups and were given corn oil (Control), DEHP, low-dose SMC (L-SMC), moderate-dose SMC (M-SMC), or high-dose SMC (H-SMC). The sperm quality of the mice in each group was determined, and HE staining and transmission electron microscopy (TEM) were applied to observe testicular morphology, and testicular tissues were collected for the subsequent molecular biological analyses. The TM4 cell line was applied in vitro for mechanism validation. Our results showed that DEHP could lead to decreased sperm quality and blood-testis barrier damage in mice, which could be alleviated by SMC. Mitochondrial damage accompanied by accumulation of total iron content, MDA, and 4-HNE, as well as downregulation of antioxidants SOD, GSH, and GSH-Px were observed after DEHP treatment, which exhibited a typical ferroptosis feature. In vitro experiments confirmed that SMC promoted upregulation of GPX4 in TM4 cells and was able to alleviate DEHP metabolite MEHP-induced ferroptosis and promote the expression of cell junction key proteins ZO-1, Occludin, and Connexin 43, which could be inhibited by the GPX4 inhibitor RSL3 or the Nrf2 inhibitor ML385. Overall, the above results suggest that SMC ameliorates the DEHP-induced ferroptosis in testicular Sertoli cells, protects the blood-testis barrier, and prevents sperm aberrations via the Nrf2/GPX4 axis.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"191-203"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364897","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

Co-Administration of a Plantain-Based Diet and Quercetin Modulates Atrazine-Induced Testicular Dysfunction in Rats via Testicular Steroidogenesis and Redox-Inflammatory Processes. 通过睾丸类固醇生成和氧化还原-炎症过程同时服用车前草和槲皮素可调节阿特拉津诱导的大鼠睾丸功能障碍

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-20 DOI: 10.1002/tox.24431

Damilare Emmanuel Rotimi, Olusola Olalekan Elekofehinti, Olarewaju Michael Oluba, Oluyomi Stephen Adeyemi

{"title":"Co-Administration of a Plantain-Based Diet and Quercetin Modulates Atrazine-Induced Testicular Dysfunction in Rats via Testicular Steroidogenesis and Redox-Inflammatory Processes.","authors":"Damilare Emmanuel Rotimi, Olusola Olalekan Elekofehinti, Olarewaju Michael Oluba, Oluyomi Stephen Adeyemi","doi":"10.1002/tox.24431","DOIUrl":"10.1002/tox.24431","url":null,"abstract":"Plantain has been reported to enhance testicular function indices, however, the mechanism remains unknown. The present study investigated the action mechanisms of a plantain-based diet in the treatment of rat testicular dysfunction caused by exposure to atrazine (ATZ). The rats were grouped into 10 groups (5 rats each); control group, 50% plantain-based diet (50% PBD), 25% PBD, 12.5% PBD, quercetin (QUE), ATZ only, 50% PBD + ATZ, 25% PBD + ATZ, 12.5% PBD + ATZ, and QUE + ATZ for 21 days. Results revealed that ATZ treatments in rats lowered gonadal hormone levels and the semen quality (sperm concentration, motility, count, and viability), damaged testicular morphology and functions, and impaired redox-inflammatory balance as well as cholinergic and purinergic activities. However, treatment with PBD and QUE ameliorated the testicular toxicity induced by ATZ, although the treatment did not improve the rat semen quality. In addition, the ATZ + QUE and QUE groups showed mild to moderate atrophic degenerative changes, with reduced spermatogenic activity. Together, the results are evidence that 21 days of exposure to ATZ impaired testicular function. However, co-administration of atrazine and PBD improves rat gonadal hormones, redox state, inflammatory indices, cholinergic, and purinergic activities, as well as histoarchitecture of the testes.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"291-305"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675244","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

MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway. MCM4 通过激活 PI3K/AKT 通路促进恶性黑色素瘤的进展

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-06 DOI: 10.1002/tox.24433

Xuewei Zhang, Mingming Dong, Guoxing Zheng, Meng Sun, Chuzhao Zhang, Zibin Zhou, Shijie Tang

{"title":"MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway.","authors":"Xuewei Zhang, Mingming Dong, Guoxing Zheng, Meng Sun, Chuzhao Zhang, Zibin Zhou, Shijie Tang","doi":"10.1002/tox.24433","DOIUrl":"10.1002/tox.24433","url":null,"abstract":"This study aims to elucidate the role of minichromosome maintenance protein 4 (MCM4) in malignant melanoma (MM) and explore the underlying mechanism. Initially, data from The Cancer Genome Atlas (TCGA) database and the Molecular Signature Database (MSigDB) were used to investigate the biological impact of MCM4 on MM. Further, a prognostic model using Cox regression analysis was developed to predict the overall survival (OS) rate in the MM patients. The effects of MCM4 on the proliferation, migration, and invasion abilities of MM (B16F0 and A375) cells were demonstrated using the CCK-8, colony formation, EDU, wound scratch, and Transwell assays. In subcutaneous tumor models in C57BL/6 mice in vivo, the expression levels of MCM4 in MM cells and tumors were detected using Western blot and immunofluorescence approaches. The bioinformatics analysis indicated that MCM4 was expressed higher in MM tissues than in the normal tissues (p < 0.05). The established OS prediction model could significantly contribute to devising follow-up strategies and treating MM patients. MCM4 knockdown resulted in reduced proliferation, migration, and invasion abilities of MM cells, which were reversed by MCM4 overexpression (p < 0.05). Moreover, MCM4 could activate the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway in MM cells. The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway in vivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"306-317"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582557","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

Hypoxia-Associated GPNMB+ Macrophages Promote Malignant Progression of Colorectal Cancer and Its Related Risk Signature Are Powerful Predictive Tool for the Treatment of Colorectal Cancer Patients. 缺氧相关 GPNMB+ 巨噬细胞促进结直肠癌恶性进展及其相关风险特征是治疗结直肠癌患者的有力预测工具

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-10-04 DOI: 10.1002/tox.24426

Junli Zhang, Shangshang Hu, Xinxin Jin, Yiwen Zheng, Lianchen Yu, Junrao Ma, Biao Gu, Fen Wang, Wenjuan Wu

{"title":"Hypoxia-Associated GPNMB+ Macrophages Promote Malignant Progression of Colorectal Cancer and Its Related Risk Signature Are Powerful Predictive Tool for the Treatment of Colorectal Cancer Patients.","authors":"Junli Zhang, Shangshang Hu, Xinxin Jin, Yiwen Zheng, Lianchen Yu, Junrao Ma, Biao Gu, Fen Wang, Wenjuan Wu","doi":"10.1002/tox.24426","DOIUrl":"10.1002/tox.24426","url":null,"abstract":"Colorectal cancer (CRC) is a highly malignant tumor with hypoxia being a crucial feature during its progression. This study utilized multiple independent CRC cohorts for bioinformatics analysis and in vitro experiments to investigate the role of hypoxia-related subgroups in CRC. Machine learning was employed to construct risk features associated with this subgroup and further explore its therapeutic value in CRC. The study identified the GPNMB+ Macrophage (GPNMB+ Macr) subgroup as most relevant to hypoxia. GPNMB+ Macr showed significantly higher infiltration in tumor tissues compared to non-tumor tissues, increasing with CRC stage. High infiltration of GPNMB+ Macr was associated with poor prognosis in terms of overall and recurrence-free survival in CRC patients. GPNMB+ Macrophages exhibit M2-like characteristics and have the ability to promote 5-FU resistance, proliferation, and metastasis of CRC cells. The study developed the Hypoxia-Related Macrophage Risk Score (HMRS), which not only served as an independent prognostic factor for CRC patients but also demonstrated robust prognostic performance compared to 84 previously published prognostic features. Patients with low HMRS were sensitive to fluorouracil, oxaliplatin (FOLFOX), and anti-PD-1 immunotherapy, while those with high HMRS showed resistance. Additionally, HMRS was identified as an independent prognostic factor in other digestive tract tumors (hepatocellular carcinoma, pancreatic cancer, esophageal cancer, and gastric cancer), indicating potential extrapolation to other tumor types. In conclusion, GPNMB+ Macr promotes the malignant progression of CRC, and HMRS serves as a powerful predictive tool for prognosis, chemotherapy, and immunotherapy in CRC patients, aiding in improving the quality of survival.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"204-221"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375192","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 "Inflammatory Response and Endothelial Dysfunction in the Hearts of Mice Co-Exposed to SO2, NO2, and PM2.5". 更正 "共同暴露于二氧化硫、二氧化氮和 PM2.5 的小鼠心脏的炎症反应和内皮功能障碍"。

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-10-29 DOI: 10.1002/tox.24432

引用次数: 0

Nimbolide Induces Cell Apoptosis via Mediating ER Stress-Regulated Apoptotic Signaling in Human Oral Squamous Cell Carcinoma. Nimbolide 通过介导 ER 应激调节的人口腔鳞状细胞癌细胞凋亡信号诱导细胞凋亡

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-02-01 Epub Date: 2024-10-27 DOI: 10.1002/tox.24436

Bou-Yue Peng, Chia-Yu Wu, Chia-Jung Lee, Tsung-Ming Chang, Ya-Ting Tsao, Ju-Fang Liu

{"title":"Nimbolide Induces Cell Apoptosis via Mediating ER Stress-Regulated Apoptotic Signaling in Human Oral Squamous Cell Carcinoma.","authors":"Bou-Yue Peng, Chia-Yu Wu, Chia-Jung Lee, Tsung-Ming Chang, Ya-Ting Tsao, Ju-Fang Liu","doi":"10.1002/tox.24436","DOIUrl":"10.1002/tox.24436","url":null,"abstract":"Human oral squamous cell carcinoma (OSCC) poses a significant health challenge in Asia, with current therapeutic strategies failing to improve the survival rates for OSCC patients sufficiently. To elucidate the effects of Nimbolide on OSCC cell proliferation and apoptosis, we performed a series of experiments, including cell proliferation assays, annexin V/PI assays, and cell cycle analysis. We further investigated nimbolide's role in modulating endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) production, and mitochondrial dysfunction using flow cytometry. Additionally, Western blotting was used to detect apoptosis-related protein expression. Our findings reveal that nimbolide exerts its anti-proliferative effects on OSCC cells by inducing apoptosis. The nimbolide increased intracellular ROS levels and acceleration of cellular calcium accumulation, respectively promoting endoplasmic reticulum stress and cancer cell apoptosis. Furthermore, nimbolide activates the caspase cascade by altering the mitochondrial membrane potential and apoptotic protein expression, thereby inhibiting the viability of tumor cells. Our data show that Nimbolide suppresses tumor growth through the induction of ROS production, ER stress, and mitochondrial dysfunction, resulting in apoptosis in OSCC cells. Overall, our study highlights nimbolide as a potential natural compound for OSCC therapy.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"347-356"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497363","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

Revolutionizing prognosis: Introducing cell death index (CDI) as a powerful prognostic tool for CSCC patients.

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-01-31 DOI: 10.1002/tox.24265

Rongjun Tang, Qing Yao, Ke Zhang, Qingqing Yu, Jun Lou, Lingdi Li

{"title":"Revolutionizing prognosis: Introducing cell death index (CDI) as a powerful prognostic tool for CSCC patients.","authors":"Rongjun Tang, Qing Yao, Ke Zhang, Qingqing Yu, Jun Lou, Lingdi Li","doi":"10.1002/tox.24265","DOIUrl":"https://doi.org/10.1002/tox.24265","url":null,"abstract":"Background: Cervical squamous cell carcinoma (CSCC) threatens the body health of women worldwide. This study aimed to foster a new concept of prognostic indicator named cell death index (CDI).Methods: RNA-seq and scRNA-seq datasets were downloaded from the GEO and TCGA database as the training and validation cohorts. Programmed cell death (PCD)-related gene signatures were obtained from published research. The construction of prognostic model was performed based on CDI value. Patients with CSCC were divided into high- and low-CDI groups. We explored the differences in overall survival time, immune infiltration, mutation status, and drug sensitivity between high and low CDI groups by R software.Results: We constructed prognostic model to calculate the CDI value with 23 genes. Patients with high CDI have shorter survival time than those with low CDI. CDI was considered a risk factor compared to other characteristics. The nomogram model estimated overall survival (OS) at 1, 3, and 6 years, with age, Stage, and CDI, indicating the accuracy of the model in predicting 1-, 3-, and 6-year survival rates. CDI values were negatively correlated with most immune checkpoint genes. We measured the significant drug sensitivity of Mitoxantrone, Sabutoclax, Sepantronium bromide, Topotecan, BI-2536, and BMS-754807 between high- and low-CDI groups with significant correlation.Conclusion: This investigation constructed a novel effective prognostic indicator of CDI in patients with CSCC and identified potential genes associated with cell death that could be targeted for prognosis and treatment of CSCC.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064578","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

The role and mechanism of hepatocyte nuclear factor 1β in the occurrence and development of different human tumors: A pan-cancer analysis.

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-01-31 DOI: 10.1002/tox.24254

Liang Li, Haikun Li, Ke Zhang, Chunchun Zhao, Fei Wang, Jian Sun, Jianqing Wang

{"title":"The role and mechanism of hepatocyte nuclear factor 1β in the occurrence and development of different human tumors: A pan-cancer analysis.","authors":"Liang Li, Haikun Li, Ke Zhang, Chunchun Zhao, Fei Wang, Jian Sun, Jianqing Wang","doi":"10.1002/tox.24254","DOIUrl":"https://doi.org/10.1002/tox.24254","url":null,"abstract":"Carcinomatosis is one of the leading threats to human public fitness. HNF1B is a critical transcription element in vertebrate proliferation and oncogenesis, which has been shown to play roles in reactive oxygen species (ROS) metabolism. Our previous results have identified HNF1B as a tumor suppressor that could inhibit the malignant progression of prostate cancer. Yet there is no pan-carcinomatosis analysis of HNF1B, which could help us better understand common and unique underlying mechanisms in mankind knubs to enhance novel and competent treatment. Here, in our research, we evaluated the utterance pattern and explored the function of HNF1B in 33 knub categories using the data from the Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO), and CLNICAL PROTEOMICTUMOR ANALYSIS CONSORTIUM (CPTAC) dataset. We found different HNF1B roles in various cancer types. HNF1B was upregulated in CHOL, STAD, KIRP, and THCA, and was downregulated in GBM, KICH, COAD, KIRC, LUSC, SARC, PAAD, and TGCT. Prognostic analyses indicated that higher HNF1B displayed better illness outcomes in BLCA, READ, and PRAD, while poorer outcomes in LUSC and THYM. HNF1B mutation was most frequent in endometrial cancer but was not associated with disease prognosis. It was discovered that HNF1B utterance relevant to endothelial cell penetration status in BLCA, ESCA, LUAD, LUSC, and TGCT, and carcinomatosis-associated fibroblast infiltration was observed in ESCA, KIRC, LIHC, and TGCT. Moreover, functional enrichment analysis disclosed that metabolism-related functions were implicated in the function of HNF1B. Taken together, our pan- carcinomatosis analysis showed the complicated roles of HNF1B in a variety of carcinomatoses, being able to improve the extensive comprehension of HNF1B's role in tumorigenesis.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064584","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

Screening for Endocrine Bioactivity Potential of Tobacco Product Chemicals Including Flavor Chemicals.

IF 4.4 3区医学

Environmental Toxicology Pub Date : 2025-01-30 DOI: 10.1002/tox.24472

Theresa Joseph-Thekkudan, Jueichuan Connie Kang, Maria M Kaltcheva, P Dilip Venugopal

{"title":"Screening for Endocrine Bioactivity Potential of Tobacco Product Chemicals Including Flavor Chemicals.","authors":"Theresa Joseph-Thekkudan, Jueichuan Connie Kang, Maria M Kaltcheva, P Dilip Venugopal","doi":"10.1002/tox.24472","DOIUrl":"https://doi.org/10.1002/tox.24472","url":null,"abstract":"Adolescence and pregnancy involve elevated levels of hormones (e.g., estrogen, androgen) during which exposure to endocrine disruptors could have long-term developmental and reproductive toxicity (DART) effects. Therefore, the use prevalence and abuse liability of electronic nicotine delivery systems (ENDS) among adolescents and youth, and during pregnancy, raises concerns about possible exposure to endocrine disruptors. In addition, endocrine disruptors have adverse effects on wildlife and environmental health. While many studies focus on carcinogenicity and mutagenicity of tobacco products, research efforts screening chemicals in tobacco products for endocrine disruption potential are few. In this study, we curated 5179 chemicals in tobacco and tobacco smoke, 2803 flavor chemicals, and 156 e-liquid chemicals from literature or openly available databases. We screened the chemicals for endocrine bioactivity using new approach methodologies (NAMs) developed through US Environmental Protection Agency's Endocrine Disruptor Screening Program. The specific NAMs, estrogenic and androgenic pathway models, identified 137 tobacco chemicals, 34 flavor chemicals, and three e-liquid chemicals (Veratraldehyde, (2E)-3-Phenylprop-2-enal, and 2'-Acetonaphthone) as \"active,\" indicating potential endocrine bioactivity. Further, among the tobacco chemicals with endocrine bioactivity potential, 48 were environmentally persistent, 29 bioaccumulative, and 19 both persistent and bioaccumulative. Our findings document many chemicals in tobacco products with potential endocrine bioactivity, which raises concerns for both human and environmental health. These results also underscore the importance of DART potential of tobacco products and flavors. Overall, our study characterizes the endocrine bioactivity potential of tobacco and flavor chemicals and provides a list of chemicals to consider in future ecological and health risk assessments.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064580","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