Environmental Toxicology最新文献

{"title":"SRBD1 Regulates the Cell Cycle, Apoptosis, and M2 Macrophage Polarization via the RPL11-MDM2-p53 Pathway in Glioma","authors":"Hongfu Chen,&nbsp;Shuping Gao,&nbsp;Peng Wang,&nbsp;Manyi Xie,&nbsp;Hui Zhang,&nbsp;Yuechao Fan,&nbsp;Er Nie,&nbsp;Qing Lan","doi":"10.1002/tox.24396","DOIUrl":"10.1002/tox.24396","url":null,"abstract":"<div>\u0000 \u0000 <p>Low expression of certain ribosomal proteins leads to the inactivation of p53, which is mediated mainly by RPL5 or RPL11 (ribosomal protein L11). It is also unknown what mechanisms drive aberrant ribosomal proteins expression in tumor. SRBD1 (S1 RNA-binding domain 1), as a highly conserved RNA-binding protein, is lowly expressed in glioma tissues and correlated with glioma prognosis. In this study, we observed that SRBD1 was closely related to p53 signaling. The upregulation of SRBD1 elevated p53 levels, thereby activating the p53 signaling pathway. As an RNA bind protein, SRBD1 could bind to the 5′-UTR of target genes and regulate RNA translation. We further conducted RNA immunoprecipitation using anti-SRDB1 antibody and noticed 29 hub RNA, including RPL11. RPL11 could inhibit MDM2-mediated p53 ubiquitination. SRBD1 upregulation promoted RPL11 binding to MDM2 via elevating RPL11 protein levels, which in turn activated the p53 signaling. Disrupting the p53 signaling blocked SRBD1-induced glioma suppression. In mouse xenograft model, SRBD1 ectopic expression was effective in reducing the total M2 tumor-associated macrophages (TAMs) density and suppressed glioma tumor growth. In summary, these data show that SRBD1 has a critical role in inhibition of glioma tumor growth and M2 macrophage polarization, and targeting RPL11-MDM2-p53 signaling may be an effective strategy to improve therapy and survival for glioma patients.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"66-78"},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170936","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}

{"title":"Suppression of Hippocampal Neurogenesis and Oligodendrocyte Maturation Similar to Developmental Hypothyroidism by Maternal Exposure of Rats to Ammonium Perchlorate, a Gunpowder Raw Material and Known Environmental Contaminant","authors":"Yuri Sakamaki,&nbsp;Momoka Shobudani,&nbsp;Ryota Ojiro,&nbsp;Shunsuke Ozawa,&nbsp;Qian Tang,&nbsp;Xinyu Zou,&nbsp;Yuri Ebizuka,&nbsp;Ayumi Karasawa,&nbsp;Gye-Hyeong Woo,&nbsp;Toshinori Yoshida,&nbsp;Makoto Shibutani","doi":"10.1002/tox.24413","DOIUrl":"10.1002/tox.24413","url":null,"abstract":"<p>The environmental contaminant perchlorate raises concern for hypothyroidism-related brain disorders in children. This study investigated the effects of developmental perchlorate exposure on hippocampal neurogenesis and oligodendrocyte (OL) development. Pregnant Sprague–Dawley rats were administered with ammonium perchlorate (AP) in drinking water at concentrations of 0 (control), 300, and 1000 ppm from gestation day 6 until weaning [postnatal day (PND) 21]. On PND 21, offspring displayed decreased serum triiodothyronine and thyroxine concentrations at 1000 ppm and thyroid follicular epithelial cell hyperplasia at ≥300 ppm (accompanying increased proliferation activity at 1000 ppm). Hippocampal neurogenesis indicated suppressed proliferation of neurogenic cells at ≥300 ppm, causing decreases in type-1 neural stem cells (NSCs) and type-2a neural progenitor cells. In addition, an increase of SST⁺ GABAergic interneurons and decreasing trend for ARC⁺ granule cells were observed at 1000 ppm. CNPase⁺ mature OLs were decreased in number in the dentate gyrus hilus at ≥300 ppm. At PND 77, thyroid changes had disappeared; however, the decrease of type-1 NSCs and increase of SST⁺ interneurons persisted, CCK⁺ interneurons were increased, and white matter tissue area was decreased at 1000 ppm. Obtained results suggest an induction of hypothyroidism causing suppressed hippocampal neurogenesis (targeting early neurogenic processes and decreased synaptic plasticity of granule cells involving ameliorative interneuron responses) and suppressed OL maturation during the weaning period. In adulthood, suppression of neurogenesis continued, and white matter hypoplasia was evident. Observed brain changes were similar to those caused by developmental hypothyroidism, suggesting that AP-induced developmental neurotoxicity was due to hypothyroidism.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"30-53"},"PeriodicalIF":4.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153378","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}

{"title":"Exposure to Polypropylene Microplastics Causes Cardiomyocyte Apoptosis Through Oxidative Stress and Activation of the MAPK-Nrf2 Signaling Pathway","authors":"Tao Lu,&nbsp;Xiaoqing Yuan,&nbsp;Changbai Sui,&nbsp;Chen Yang,&nbsp;Desheng Li,&nbsp;Huan Liu,&nbsp;Guanqing Zhang,&nbsp;Guozhi Li,&nbsp;Song Li,&nbsp;Jiayu Zhang,&nbsp;Ling Zhou,&nbsp;Maolei Xu","doi":"10.1002/tox.24411","DOIUrl":"10.1002/tox.24411","url":null,"abstract":"<div>\u0000 \u0000 <p>Microplastics are a growing concern as pollutants that impact both public health and the environment. However, the toxic effects of polypropylene microplastics (PP-MPs) are not well understood. This study aimed to investigate the effects of PP-MPs on cardiotoxicity and its underlying mechanisms. The cardiotoxicity of exposure to different amounts of PP-MPs were investigated in both ICR mice and H9C2 cells. Our results demonstrated that sub-chronic exposure to 5 and 50 mg/L PP-MPs led to myocardial structural damage, apoptosis, and fibrosis in mice cardiomyocytes. Flow cytometry analysis revealed that PP-MPs could decrease mitochondrial membrane potential and induce apoptosis in H9C2 cells. Western blotting revealed decreased expression of Bcl-2, poly(ADP-ribose) polymerase (PARP) and caspase 3 and increased expression of Bax, cleaved-PARP, and cleaved-caspase 3 in PP-MPs-treated cardiac tissue and H9C2 cells. These results confirmed the apoptotic effects induced by PP-MPs. Moreover, PP-MPs treatment triggered oxidative stress, as evidenced by the increased levels of malondialdehyde; reduction in glutathione peroxidase, superoxide dismutase, and catalase activities in mice cardiac tissues; and increased reactive oxygen species levels in H9C2 cells. Finally, western blotting demonstrated that exposure to PP-MPs significantly reduced the expression levels of Nrf2 and p-ERK proteins associated with MAPK-Nrf2 pathway in both cardiac tissue and H9C2 cells. Overall, our findings indicate that PP-MPs can induce cardiomyocyte apoptosis through MAPK-Nrf2 signaling pathway, which is triggered by oxidative stress. This study provides a foundation for determining the effects of PP-MPs on cardiotoxicity and their underlying mechanisms.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5371-5381"},"PeriodicalIF":4.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153376","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}

{"title":"In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Phthalates Alters Hypothalamic Gene Expression and Sexual Preference in Rats","authors":"Tatiana Zauer Curi,&nbsp;Marcella Tapias Passoni,&nbsp;Sara Emilia Lima Tolouei,&nbsp;Anderson Tadeu de Araújo Ramos,&nbsp;Samara Christina França de Almeida,&nbsp;Renata Marino Romano,&nbsp;Jeane Maria de Oliveira,&nbsp;Paulo Roberto Dalsenter,&nbsp;Anderson Joel Martino-Andrade","doi":"10.1002/tox.24414","DOIUrl":"10.1002/tox.24414","url":null,"abstract":"<div>\u0000 \u0000 <p>Several phthalates, mainly used as plasticizers, are known for their adverse effects on the male genital system. Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500 mg PMix/kg/day) were established starting from the extrapolated human dose (0.1 mg/kg/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating-related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased <i>Esr2</i> expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased <i>Kiss1</i> transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"54-65"},"PeriodicalIF":4.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153377","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}

{"title":"Correction to “LINC00365 Inhibited Lung Adenocarcinoma Progression and Glycolysis via Sponging miR-429/KCTD12 Axis”","authors":"","doi":"10.1002/tox.24410","DOIUrl":"10.1002/tox.24410","url":null,"abstract":"<p>C. W. Zhang, B. Zhou, Y. C. Liu, L. W. Su, J. Meng, S. L. Li, and X. L. Wang, “LINC00365 Inhibited Lung Adenocarcinoma Progression and Glycolysis via Sponging miR-429/KCTD12 Axis,” <i>Environmental Toxicology</i> 37, no. 8 (2022): 1853–1866.</p><p>After carefully re-checking the manuscript and raw data, we regret that the Figures 2D,E and 5E,F were misused during figure assembly when we were preparing for manuscript submission. We repeated every experiment for 3 times and took multiple photos each time. As a result, we did not pay attention to the repeated area when assemble figures. We have meticulously reviewed our data and have prepared revised figures, utilizing our original experimental images. These revised figures align with and support the results and conclusions we initially reported. We trust that these adjustments accurately convey our findings and uphold the integrity of our scientific endeavors.</p><p>We apologize for this error.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"156-158"},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139665","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}

{"title":"RB1 Mutations Induce Smoking-Related Bladder Cancer by Modulating the Cytochrome P450 Pathway","authors":"Zhenguang Mao,&nbsp;Fang Gao,&nbsp;Tuo Sun,&nbsp;Yi Xiao,&nbsp;Jiajin Wu,&nbsp;Yanping Xiao,&nbsp;Haiyan Chu,&nbsp;Dongmei Wu,&nbsp;Mulong Du,&nbsp;Rui Zheng,&nbsp;Zhengdong Zhang","doi":"10.1002/tox.24409","DOIUrl":"10.1002/tox.24409","url":null,"abstract":"<div>\u0000 \u0000 <p>Cigarette smoking causes multiple cancers by directly influencing mutation burden of driver mutations. However, the mechanism between somatic mutation caused by cigarette smoking and bladder tumorigenesis remains elusive. Smoking-related mutation profile of bladder cancer was characterized by The Cancer Genome Atlas cohort. Integraticve OncoGenomics database was utilized to detect the smoking-related driver genes, and its biological mechanism predictions were interpreted based on bulk transcriptome and single-cell transcriptome, as well as cell experiments. Cigarette smoking was associated with an increased tumor mutational burden under 65 years old (<i>p</i> = 0.031), and generated specific mutational signatures in smokers. <i>RB1</i> was identified as a differentially mutated driver gene between smokers and nonsmokers, and the mutation rate of <i>RB1</i> increased twofold after smoking (<i>p</i> = 0.008). <i>RB1</i> mutations and the 4-aminobiphenyl interference could significantly decrease the <i>RB1</i> expression level and thus promote the proliferation, invasion, and migration ability of bladder cancer cells. Enrichment analysis and real-time quantitative PCR (RT-qPCR) data showed that <i>RB1</i> mutations inhibited cytochrome P450 pathway by reducing expression levels of <i>UGT1A6</i> and <i>AKR1C2</i>. In addition, we also observed that the component of immunological cells was regulated by <i>RB1</i> mutations through the stronger cell-to-cell interactions between epithelial scissor⁺ cells and immune cells in smokers. This study highlighted that <i>RB1</i> mutations could drive smoking-related bladder tumorigenesis through inhibiting cytochrome P450 pathway and regulating tumor immune microenvironment.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5357-5370"},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139615","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}

{"title":"Correction to “Overexpressed Hsp70 Alleviated Formaldehyde-Induced Apoptosis Partly via PI3K/Akt Signaling Pathway in Human Bronchial Epithelial Cells”","authors":"","doi":"10.1002/tox.24401","DOIUrl":"10.1002/tox.24401","url":null,"abstract":"<p>L. Liu, Y. Huang, X. Feng, J. Chen, and Y. Duan, “Overexpressed Hsp70 Alleviated Formaldehyde-Induced Apoptosis Partly via PI3K/Akt Signaling Pathway in Human Bronchial Epithelial Cells,” <i>Environmental Toxicology</i> 34, no. 4 (2019): 495–504, https://doi.org/10.1002/tox.22703.</p><p>FIGURE 2The protein expression level of Hsp70 in HBE-Hsp70 and HBE-NC exposed to formaldehyde. The results were expressed as mean ± SD from three independent experiments, *<i>p</i> &lt; 0.05, compared with the control group; #<i>p</i> &lt; 0.05, compared with HBE-NC treated with the same concentration of formaldehyde.</p><p>FIGURE 5Effect of LY 294002 on formaldehyde-induced apoptosis in HBE-NC and HBE-Hsp70 cells. (A) Graphs obtained by flow cytometry after Annexin V-APC/7AAD dual straining. (B) Apoptosis rates were expressed as mean ± SD (<i>n</i> = 3), *<i>p</i> &lt; 0.05, **<i>p</i> &lt; 0.01, compared with the control group (0 μmol/L formaldehyde); #<i>p</i> &lt; 0.05, ##<i>p</i> &lt; 0.01, compared with HBE-NC + DMSO treated with the same concentration of formaldehyde; +<i>p</i> &lt; 0.05, ++<i>p</i> &lt; 0.01, compared with HBE-Hsp70 + LY294002 treated with the same concentration of formaldehyde.</p><p>We apologize for this error.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"154-155"},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132138","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}

{"title":"Jing-Si Herbal Tea Suppresses H2O2-Instigated Inflammation and Apoptosis by Inhibiting Bax and Mitochondrial Cytochrome C Release in HIG-82 Synoviocytes","authors":"Shih-Wen Kao,&nbsp;Yu-Chun Chang,&nbsp;Feng-Huei Lin,&nbsp;Tai-Lung Huang,&nbsp;Tung-Sheng Chen,&nbsp;Shinn-Zong Lin,&nbsp;Kuan-Ho Lin,&nbsp;Wei-Wen Kuo,&nbsp;Tsung-Jung Ho,&nbsp;Chih-Yang Huang","doi":"10.1002/tox.24406","DOIUrl":"10.1002/tox.24406","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans; however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H₂O₂-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at &lt;188 μg/mL; however, a cytotoxic effect was observed at 188–1883 μg/mL concentrations tested. We found that expressions of inflammation associated extracellular matrix (ECM)-degrading proteases MMP-13, ADAMTS-2, -8, and -17 were abnormally enhanced under H₂O₂-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H₂O₂-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, ADAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H₂O₂, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H₂O₂-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5347-5356"},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132139","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}

{"title":"Integrative analysis of bulk and single-cell RNA sequencing reveals sphingolipid metabolism and immune landscape in clear cell renal cell carcinoma","authors":"Dongdong Xie,&nbsp;Zhitao Han,&nbsp;Yu Wang,&nbsp;Haoyu Shi,&nbsp;Xiang Wu,&nbsp;Jiaqing Wu,&nbsp;Yingbo Dai","doi":"10.1002/tox.24319","DOIUrl":"10.1002/tox.24319","url":null,"abstract":"<div>\u0000 \u0000 <p>Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive behavior and complex molecular heterogeneity, posing significant challenges for treatment and prognostication. This study offers a comprehensive analysis of ccRCC by leveraging both bulk and single-cell RNA sequencing data, with a specific aim to unravel the complexities of sphingolipid metabolism and the intricate dynamics within the tumor microenvironment (TME). By examining ccRCC samples sourced from public databases, our investigation delves deep into the genetic and transcriptomic landscape of this cancer type. Employing advanced analytical techniques, we have identified pivotal patterns in gene expression and cellular heterogeneity, with a special focus on the roles and interactions of various immune cells within the TME. Significantly, our research has unearthed insights into the dynamics of sphingolipid metabolism in ccRCC, shedding light on its potential implications for tumor progression and strategies for immune evasion. A novel aspect of this study is the development of a risk score model designed to enhance prognostic predictions for ccRCC patients, which is currently pending external validation to ascertain its clinical utility. Despite its contributions, the study is mindful of its limitations, including a reliance on observational data from public sources and a primary focus on RNA sequencing data, which may constrain the depth and generalizability of the findings. The study does not encompass critical aspects, such as protein expression, posttranslational modifications, and comprehensive metabolic profiles. Moreover, its retrospective design underscores the necessity for future prospective studies to solidify these preliminary conclusions. Our findings illuminate the intricate interplay between genetic alterations, sphingolipid metabolism, and immune responses in ccRCC. This research not only enhances our understanding of the molecular foundations of ccRCC but also paves the way for the development of targeted therapies and personalized treatment modalities. The study underlines the importance of cautious interpretation of results and champions ongoing research using diverse methodologies to thoroughly comprehend and effectively combat this formidable cancer type.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5391-5404"},"PeriodicalIF":4.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125167","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}

{"title":"Resveratrol Alleviated T-2 Toxin-Induced Liver Injury via Preservation of Nrf2 Pathway and GSH Synthesis","authors":"Hong Jin,&nbsp;Jun He,&nbsp;Min Wu,&nbsp;Xiaohan Wang,&nbsp;Li Jia,&nbsp;Li Zhang,&nbsp;Jiabin Guo","doi":"10.1002/tox.24412","DOIUrl":"10.1002/tox.24412","url":null,"abstract":"<div>\u0000 \u0000 <p>T-2 toxin is a trichothecene mycotoxin and is considered as an extremely inevitable pollutant with potent hepatotoxicity. However, the approach to alleviation of T-2 toxin-triggered hepatotoxicity has been recognized as a serious challenge. Resveratrol (Res) is a polyphenol natural product isolated from various plant species, but its protective effect against T-2 toxin hepatotoxicity and detailed mechanism remains obscure. In the present study, the effect of Res against the hepatotoxicity was evaluated, and the underlying mechanisms were further revealed in mice. Functionally, Res inhibited liver injury, oxidative damage, and mitochondrial dysfunction induced by T-2 toxin. Mechanistically, Res modulated Nrf2-mediated antioxidant pathway and glutathione synthesis inhibition. Collectively, our findings first showed beyond doubt that Res ameliorated T-2 toxin-triggered liver injury by regulating Nrf2 pathways in mice.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"19-29"},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119273","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}