{"title":"Intervention of a Communication Between PI3K/Akt and β-Catenin by (−)-Epigallocatechin-3-Gallate Suppresses TGF-β1-Promoted Epithelial-Mesenchymal Transition and Invasive Phenotype of NSCLC Cells","authors":"Li-Sung Hsu, Chih-Li Lin, Min-Hsiung Pan, Wei-Jen Chen","doi":"10.1002/tox.24475","DOIUrl":"10.1002/tox.24475","url":null,"abstract":"<div>\u0000 \u0000 <p>The epithelial-mesenchymal transition (EMT) assists in the acquisition of invasiveness, relapse, and resistance in non-small cell lung cancer (NSCLC) and can be caused by the signaling of transforming growth factor-β1 (TGF-β1) through Smad-mediated or Smad-independent pathways. (−)-Epigallocatechin-3-gallate (EGCG), a multifunctional cancer-preventing bioconstituent found in tea polyphenols, has been shown to repress TGF-β1-triggered EMT in the human NSCLC A549 cell line by inhibiting the activation of Smad2 and Erk1/2 or reducing the acetylation of Smad2 and Smad3. However, its impact on the Smad-independent pathway remains unclear. Here, we found that EGCG, similar to LY294002 (a specific inhibitor of phosphatidylinositol 3-kinase [PI3K]), downregulated Akt activation and restored the action of glycogen synthase kinase-3β (GSK-3β), accompanied by TGF-β1-caused changes in hallmarks of EMT such as N-cadherin, E-cadherin, vimentin, and Snail in A549 cells. EGCG inhibited β-catenin expression and its nuclear localization caused by TGF-β1, suggesting that EGCG blocks the crosstalk between the PI3K/Akt/GSK-3β route and β-catenin. Furthermore, it was shown that EGCG suppressed TGF-β1-elicited invasive phenotypes of A549 cells, including invading and migrating activities, matrix metalloproteinase-2 (MMP-2) secretion, cell adhesion, and wound healing. In summary, we suggest that EGCG inhibits the induction of EMT by TGF-β1 in NSCLC not only through a Smad-dependent pathway, but also through the regulation of the PI3K/Akt/β-catenin signaling axis.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 5","pages":"848-859"},"PeriodicalIF":4.4,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046012","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":"Fluoride Exposure Modulates Skeletal Development and Mineralization in Zebrafish Larvae","authors":"Harsheema Ottappilakkil, Ekambaram Perumal","doi":"10.1002/tox.24474","DOIUrl":"10.1002/tox.24474","url":null,"abstract":"<div>\u0000 \u0000 <p>The presence of high levels of fluoride (F) in groundwater is a major issue worldwide. Although F is essential for healthy teeth and bones, excessive exposure can cause fluorosis or F toxicity. This condition primarily affects the hard tissues due to their high F retention capacity. F accumulation alters bone formation and resorption mechanisms interfering with mineral homeostasis and eventually manifests as skeletal fluorosis. Albeit the numerous studies on skeletal fluorosis, the effect of F on developmental osteogenesis is inconclusive. In light of this, we studied the effect of F on osteogenic differentiation, bone development, and mineralization in zebrafish. Zebrafish embryos were subjected to a low (25 ppm NaF), and a moderately high (50 ppm NaF) dose, along with a control (E3 medium alone) until 7 days postfertilization (dpf). The F content in the larvae was quantified to reveal a dose-dependent increase in the exposed groups. Alizarin Red and alkaline phosphatase (ALP) staining suggested enhanced mineralization in the F-treated groups. Quantitative analyses of the ALP activity and hydroxyproline (Hyp) content revealed similar results. Alcian blue staining of pharyngeal cartilages showed that F exposure alters the morphology of the major cartilages, indicating a possible craniofacial defect. Moreover, gene expression analyses of the bone markers associated with osteogenic differentiation, early mineralization, and remodeling (<i>runx2a/b</i>, <i>bmp4</i>, <i>ocn</i>, <i>osx</i>, <i>col1a1</i>, <i>alp</i>, <i>rank</i>, <i>rankl</i>, and <i>opg</i>) showed enhanced expression in the low F group. While the 50 ppm F group showed a decline in osteogenic activity, a considerable increase in the expression of mineralization markers was observed. The expression levels of cartilage markers <i>sox9a</i> and <i>sox9b</i>, remained insignificant, indicating the effect of F toxicity on osteogenesis and mineralization. Also, F exposure interferes with bone metabolism through altered osteogenic differentiation, development, and mineralization in zebrafish larvae.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 5","pages":"835-847"},"PeriodicalIF":4.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035017","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":"Effects of Environmentally Relevant Concentrations of Roundup on Oxidative-Nitrative Stress, Cellular Apoptosis, Prooxidant-Antioxidant Homeostasis, Renin and CYP1A Expressions in Goldfish: Molecular Mechanisms Underlying Kidney Damage During Roundup Exposure","authors":"Md Imran Noor, Md Saydur Rahman","doi":"10.1002/tox.24471","DOIUrl":"10.1002/tox.24471","url":null,"abstract":"<div>\u0000 \u0000 <p>Roundup is one of the most widely used glyphosate-based harmful herbicides in the United States as well as globally, which poses a severe risk for terrestrial and aquatic organisms. In order to identify the detrimental effects of Roundup exposure in aquatic organisms, we investigated the environmentally relevant concentrations of Roundup exposure (low dose: 0.5 μg/L and high dose: 5.0 μg/L for 2 weeks) on renin expression, oxidative-nitrative stress biomarkers (e.g., 2,4-dinitrophenol, DNP; and 3-nitrotyrosine protein, NTP), prooxidant-antioxidant enzymes expressions (e.g., superoxide dismutase, SOD; and catalase, CAT), cellular apoptosis, and cytochrome P450 1A (CYP1A) mRNA levels in the kidneys of goldfish (\u0000 <i>Carassius auratus</i>\u0000 ). Histopathological and in situ TUNEL analyses showed widespread tissue disruption (e.g., bowman's capsule shrinkage, melanin pigment formation, etc.) and induced apoptotic nuclei in the kidneys of goldfish. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses showed a significant (<i>p</i> < 0.05) increase in the expression of renin, DNP, NTP, SOD, and CAT, as well as CYP1A mRNA levels in the kidneys of fish exposed to Roundup. These results suggest that environmentally relevant concentrations of Roundup disrupt kidney architecture by inducing oxidative-nitrative stress, cellular apoptosis, and change in osmoregulatory enzymes (i.e., renin) and prooxidant-antioxidant systems in the kidneys of teleost fishes.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 5","pages":"817-834"},"PeriodicalIF":4.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030839","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":"RETRACTION: Poly (Lactic-Co-Glycolic Acid)-Encapsulated Endostar-Loaded Calcium Phosphate Cement as Anti-Tumor Bone Cement for the Treatment of Bone Metastasis in Lung Cancer","authors":"","doi":"10.1002/tox.24482","DOIUrl":"10.1002/tox.24482","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION:</b> <span>Q. H. Tian</span>, <span>C. Tian</span>, <span>Y. Y. Lu</span>, <span>B. C. Yan</span>, <span>K. Zhang</span>, and <span>C. G. Wu</span>, “ <span>Poly (Lactic-Co-Glycolic Acid)-Encapsulated Endostar-Loaded Calcium Phosphate Cement as Anti-Tumor Bone Cement for the Treatment of Bone Metastasis in Lung Cancer</span>,” <i>Environmental Toxicology</i> (EarlyView): https://doi.org/10.1002/tox.24166.\u0000 </p><p>The above article, published online on 23 February 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 3","pages":"502"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030740","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":"RETRACTION: The Role of PKP1 in Tumor Progression in Melanoma: Analysis of a Cell Adhesion-Related Model","authors":"","doi":"10.1002/tox.24483","DOIUrl":"10.1002/tox.24483","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION:</b> <span>C. Yue</span>, <span>W. Lian</span>, <span>Z. Fan</span>, <span>H. Li</span>, <span>M. Duan</span>, <span>L. Qin</span>, <span>X. Cao</span>, and <span>J. Peng</span>, “ <span>The Role of PKP1 in Tumor Progression in Melanoma: Analysis of a Cell Adhesion-Related Model</span>,” <i>Environmental Toxicology</i> <span>39</span>, no. <span>2</span> (<span>2024</span>): <span>915</span>\u0000 <b>–</b>\u0000 <span>926</span>, https://doi.org/10.1002/tox.24017.\u0000 </p><p>The above article, published online on 15 November 2023, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted. The authors agree with this decision.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 4","pages":"712"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030838","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":"RETRACTION: Calcitriol Suppresses Gastric Cancer Progression and Cisplatin Resistance by Inhibiting Glycolysis and M2 Macrophage Polarization Through Inhibition of mTOR Activation","authors":"","doi":"10.1002/tox.24484","DOIUrl":"10.1002/tox.24484","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION:</b> <span>L. Jie</span>, <span>W. Hengyue</span>, and <span>H. Ting</span>, <b>“</b>\u0000 <span>Calcitriol Suppresses Gastric Cancer Progression and Cisplatin Resistance by Inhibiting Glycolysis and M2 Macrophage Polarization Through Inhibition of mTOR Activation</span>,<b>”</b> <i>Environmental Toxicology</i> <span>39</span>, no. <span>2</span> (<span>2024</span>): <span>830</span>\u0000 <b>–</b>\u0000 <span>839</span>, https://doi.org/10.1002/tox.23975\u0000 \u0000 </p><p>The above article, published online on 4 October 2023, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 4","pages":"713"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030837","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":"RETRACTION: DNMT1-Mediated Regulating on FBXO32 Promotes the Progression of Glioma Cells Through the Regulation of SKP1 Activity","authors":"","doi":"10.1002/tox.24485","DOIUrl":"10.1002/tox.24485","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION:</b> <span>J. Quan</span> and <span>C. Ma</span>, “ <span>DNMT1-Mediated Regulating on FBXO32 Promotes the Progression of Glioma Cells Through the Regulation of SKP1 Activity</span>,” <i>Environmental Toxicology</i> <span>39</span>, no. <span>2</span> (<span>2024</span>): <span>783</span>–<span>793</span>, https://doi.org/10.1002/tox.23976.\u0000 </p><p>The above article, published online on 2 October 2023, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 4","pages":"714"},"PeriodicalIF":4.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030836","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":"RETRACTION: Refining Molecular Subtypes and Risk Stratification of Ovarian Cancer Through Multi-Omics Consensus Portfolio and Machine Learning","authors":"","doi":"10.1002/tox.24479","DOIUrl":"10.1002/tox.24479","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION</b>: <span>J. Zhang</span>, <span>S. He</span>, and <span>H. Ying</span>, “ <span>Refining Molecular Subtypes and Risk Stratification of Ovarian Cancer Through Multi-Omics Consensus Portfolio and Machine Learning</span>,” <i>Environmental Toxicology</i> (EarlyView): https://doi.org/10.1002/tox.24222.\u0000 </p><p>The above article, published online on 13 March 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 3","pages":"501"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002376","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":"RETRACTION: Integrated RNA Expression and Alternative Polyadenylation Analysis Identified CPSF1-CCDC137 Oncogenic Axis in Lung Adenocarcinoma","authors":"","doi":"10.1002/tox.24478","DOIUrl":"10.1002/tox.24478","url":null,"abstract":"<p>\u0000 \u0000 <b>RETRACTION:</b> <span>X. Xudong</span>, <span>L. Heng</span>, <span>C. Benchao</span>, <span>C. Wenjie</span>, <span>L. Bao</span>, and <span>L. Gaofeng</span>, “ <span>Integrated RNA Expression and Alternative Polyadenylation Analysis Identified CPSF1-CCDC137 Oncogenic Axis in Lung Adenocarcinoma</span>,” <i>Environmental Toxicology</i> <span>39</span>, no. <span>4</span> (<span>2024</span>): <span>2405</span>–<span>2416</span>, https://doi.org/10.1002/tox.24105.\u0000 </p><p>The above article, published online on 4 January 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 4","pages":"711"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002426","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}
Chen-Si Li, Jie Liu, Qiangqiang Zhang, Xue-Rui Tang, Yuan-Yuan Liu, Aoneng Cao, Haifang Wang
{"title":"Combined Effect of Nanoparticles of Silver and Silica to HeLa Cells: Synergistic Internalization and Toxicity","authors":"Chen-Si Li, Jie Liu, Qiangqiang Zhang, Xue-Rui Tang, Yuan-Yuan Liu, Aoneng Cao, Haifang Wang","doi":"10.1002/tox.24480","DOIUrl":"10.1002/tox.24480","url":null,"abstract":"<div>\u0000 \u0000 <p>The wide range of applications and the enormous production of nanomaterials have raised the possibility that humans may simultaneously contact with various nanomaterials through multiple routes. Although numerous toxicity studies have been conducted on the toxicity of nanomaterials, knowledge of the combined toxicity of nanomaterials remains limited. Herein, the combined toxic effects of the two types of the most widely used nanomaterials, silver and silica, were studied on HeLa cells. In addition, considering there may have possible interplay between nanoparticles of different sizes, two different-sized silica nanoparticles (SNPs) were used. The results indicate that compared with individual exposure, the combined exposure to 35 nm silver nanoparticles (Ag35) and 40 nm or 120 nm SNPs (SNP40 or SNP120) at individual non-toxic concentrations causes more severe cytotoxicity, manifested by the ROS overgeneration, decreased mitochondrial membrane potential and ATP level, and increased apoptosis/necrosis. The internalized Ag35 and its dissolved Ag ions that are delivered into cells by adsorbing on SNPs are identified as the primary contributors to the combined toxicity. Although the cytotoxicity of the mixed Ag35 and SNP40 is comparable to that of the mixed Ag35 and SNP120, there are noticeable differences in their intracellular contents and their subcellular locations due to size effects. This study provides in-depth insights into the combined toxicity of inorganic nanoparticles and highlights the importance of the size effect of nanoparticles in their nanotoxicity assessment.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 5","pages":"802-816"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002259","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}