Journal of Applied Toxicology最新文献

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Toxic Effects of CdTe Quantum Dots on Locomotor Behavior, Neurodevelopment, and Axon Growth in Zebrafish Larvae. CdTe量子点对斑马鱼幼体运动行为、神经发育和轴突生长的毒性作用。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-20 DOI: 10.1002/jat.4809
Changcun Bai, Meng Tang
{"title":"Toxic Effects of CdTe Quantum Dots on Locomotor Behavior, Neurodevelopment, and Axon Growth in Zebrafish Larvae.","authors":"Changcun Bai, Meng Tang","doi":"10.1002/jat.4809","DOIUrl":"https://doi.org/10.1002/jat.4809","url":null,"abstract":"<p><p>The nervous system is very sensitive to CdTe quantum dots (CdTe QDs), and an understanding of the effects of CdTe QDs on the nervous system is indispensable for their use in biomedical applications, especially in clinical medicine. This research explored the possible neurotoxic effects of CdTe QDs on the peripheral nervous system of zebrafish, including motor neuron damage, altered mobility and motor behavior of zebrafish larvae. The mechanism of peripheral neurotoxicity induced by CdTe QDs was also investigated by qRT-PCR in this study. The experimental results showed that 100 nM and above quantum dot exposure induced shortening of axon length of motor neurons and reduced the length and number of neurogenesis as well as motor nerve branching in 24-120-hpf zebrafish. The toxic effects of 100 nM and above CdTe QDs on motor neurons were further manifested as a decrease in the overall activity level of the 144-hpf zebrafish larvae including decreased locomotor velocity and shortened movement time. The average swimming velocity and total movement time of zebrafish in the 400-nM CdTe QDs-treated group were 24.7% and 17.1% of those of the control group, respectively. Molecular toxicology studies showed that genes related to neurogenesis (nrd) and axonal growth (mbp, gfap, and gap43) were significantly affected by CdTe QDs exposure. Their expressions all tended to decrease in zebrafish larvae at 72 hpf after exposure to 400-nM CdTe QDs. In conclusion, the present study demonstrates that exposure of zebrafish to CdTe QDs at early life stages leads to adverse neural outcomes through inhibition of neural development and motor neuron axon growth.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety of Inks Used in Tattoos. 纹身用墨水的安全性。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-19 DOI: 10.1002/jat.4810
Klaudia Kowalska, Ewa Skwarek
{"title":"Safety of Inks Used in Tattoos.","authors":"Klaudia Kowalska, Ewa Skwarek","doi":"10.1002/jat.4810","DOIUrl":"https://doi.org/10.1002/jat.4810","url":null,"abstract":"<p><p>Since 2015, the number of articles on tattoo inks has increased significantly in recent years as more and more people choose to decorate their bodies. The introductory section presents a multifaceted psychological and social perspective. Attitudes toward tattoos in different parts of the world are taken into account, as well as the approach to the topic by different social groups. It has changed over the years and depending on the wealth of a given group. The main part is an overview of tattoo ink tests, which mainly focus on the safety of the products used, direct tests and potential allergens contained in the composition. The information contained can be summed up by the great need for ongoing implementation of further regulations in order to protect people using the services of tattooists.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antitumor Cytotoxic Activity Retained in Tolerized T Cells Following Daily Dose Escalation of a T-Cell Engager in Cynomolgus Monkeys to Mitigate Cytokine Release Syndrome. 在食蟹猴中,T细胞结合物每日剂量递增以减轻细胞因子释放综合征后,耐受性T细胞保留抗肿瘤细胞毒活性。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-19 DOI: 10.1002/jat.4812
Yoshika Iwata, Tomochika Matsushita, Yuta Narushima, Asako Harada, Yuichiro Sakamoto, Akihisa Sakamoto, Hisashi Ikegami, Masayuki Mishima, Hiromi Suzuki
{"title":"Antitumor Cytotoxic Activity Retained in Tolerized T Cells Following Daily Dose Escalation of a T-Cell Engager in Cynomolgus Monkeys to Mitigate Cytokine Release Syndrome.","authors":"Yoshika Iwata, Tomochika Matsushita, Yuta Narushima, Asako Harada, Yuichiro Sakamoto, Akihisa Sakamoto, Hisashi Ikegami, Masayuki Mishima, Hiromi Suzuki","doi":"10.1002/jat.4812","DOIUrl":"https://doi.org/10.1002/jat.4812","url":null,"abstract":"<p><p>T-cell engagers demonstrate promise in cancer immunotherapy but often cause severe cytokine release syndrome (CRS). Intrapatient dose escalation can mitigate CRS, but reduced cytokine levels may compromise therapeutic efficacy. We previously reported that a single 1000 μg/kg dose of ERY22, an anti-GPC3/CD3 monkey surrogate T-cell engager, induces life-threatening CRS in cynomolgus monkeys, but that daily dose escalation from 1 to 1000 μg/kg almost completely prevented CRS in the monkeys without premedication with immunosuppressants. This study aimed to investigate whether T cells tolerized in vivo through dose escalation maintain antitumor cytotoxicity. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from animals that were administered daily doses ranging from 1 to 1000 μg/kg and then restimulated with ERY22 ex vivo. Cytokine concentrations in supernatants and cytotoxicity against target cells were examined in ex vivo experiments. We used ATAC-seq to assess chromatin accessibility in T cells responding to daily dose escalation. Under tolerance-induced conditions, ex vivo cytokine release was almost completely inhibited, whereas approximately half of the cytotoxic activity was retained. T-cell chromatin states changed after ERY22 administration. Because the relevancy of the ex vivo cytotoxic assay to clinical effects is unknown, the impact of reduced cytotoxicity through dose escalation on actual cancer treatment efficacy remains unclear. Although this and species differences must be considered, our findings provide valuable insights into mechanisms underlying dose escalation-induced tolerance and may be useful for predicting human responses. A deeper understanding of these shared mechanisms is critical for advancing the clinical development of T-cell engagers.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of Ulinastatin Combined With High-Volume Hemofiltration on Inflammatory Response and MODS Incidence in Severe Sepsis. 乌司他丁联合大容量血液滤过对严重脓毒症患者炎症反应及MODS发生率的影响。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-12 DOI: 10.1002/jat.4804
Xuhong Wu, Shuliang Ma, Chao Wang, Zeping Xu, Nan Ma
{"title":"Effect of Ulinastatin Combined With High-Volume Hemofiltration on Inflammatory Response and MODS Incidence in Severe Sepsis.","authors":"Xuhong Wu, Shuliang Ma, Chao Wang, Zeping Xu, Nan Ma","doi":"10.1002/jat.4804","DOIUrl":"https://doi.org/10.1002/jat.4804","url":null,"abstract":"<p><p>This study evaluated the impact of ulinastatin combined with high-volume hemofiltration (HVHF) on inflammation and the development of multiple organ dysfunction syndrome (MODS) in severe sepsis. One hundred patients with severe sepsis were recruited and allocated into two groups based on treatment methods (n = 50 patients). The control group underwent HVHF, while the observation group received ulinastatin-assisted HVHF. Comparisons of general data were made in treatment efficacy (APACHE II score), MODS score, and SOFA score. Inflammatory markers and organ function indicators were also measured before and after treatment. The incidence of disseminated intravascular coagulation (DIC), MODS, and mortality rates at 28 days were also analyzed. The observation group showed significantly reduced APACHE II, MODS, and SOFA scores, along with lower levels of IL-6, IL-10, TNF-α, ALT, and Scr (p < 0.05). Additionally, the observation group had lower incidences of DIC, MODS, and mortality (p < 0.05). Furthermore, elevated CD4+ and CD4+/CD8+ ratios while reduced CD8+ levels were noted in the observation group (p < 0.05). We demonstrate that ulinastatin combined with HVHF effectively reduces inflammatory levels in patients with severe sepsis, improves organ function, lowers the incidence of MODS and mortality, and enhances immune function.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and Toxicity of Qi-Fu Yin, a Classical Traditional Chinese Medicine Prescription: A Nonclinical Research. 中药复方气附饮的安全性和毒性:一项非临床研究。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-10 DOI: 10.1002/jat.4791
Kai Chen, Xuemin Yao, Ying Yu, Junmei Sun, Yanhua Zhang, Hui Ma, Hu Zheng, Bo Qiu, Haitao Li, Wenjing Zhao, Tianbin Liu, Lingling Xu, Zhiyong Zheng, Lianshen Tang, Xiaorui Cheng
{"title":"Safety and Toxicity of Qi-Fu Yin, a Classical Traditional Chinese Medicine Prescription: A Nonclinical Research.","authors":"Kai Chen, Xuemin Yao, Ying Yu, Junmei Sun, Yanhua Zhang, Hui Ma, Hu Zheng, Bo Qiu, Haitao Li, Wenjing Zhao, Tianbin Liu, Lingling Xu, Zhiyong Zheng, Lianshen Tang, Xiaorui Cheng","doi":"10.1002/jat.4791","DOIUrl":"https://doi.org/10.1002/jat.4791","url":null,"abstract":"<p><p>Qi-Fu-Yin (QFY) is a classic prescription in traditional Chinese medicine for treating dementia, such as Alzheimer's disease, but its safety has not yet been investigated. The purpose of this study was to assess the safety pharmacology and toxicology of QFY extract powder (QFYEP) to provide guidance for clinical trials or applications of QFY and its innovative formulations. The safety pharmacology of QFYEP on the central nervous system and respiratory system and its acute toxicity and 26-week repeated-dose toxicity were evaluated in Sprague-Dawley (SD) rats. The safety pharmacology of QFYEP on the cardiovascular system was evaluated in beagle dogs. Additionally, the genotoxicity of QFYEP was assessed using the Ames test, an in vitro chromosome aberration test, and an in vivo micronucleus test. Under the experimental doses, no effects of QFYEP on the central nervous system or respiratory system were detected, no acute toxicity, long-term toxicity, or genotoxic effects of QFYEP were observed at any of the experimental doses. Specifically, the no-observed adverse-effect level (NOAEL) for the 26-week rat toxicity study was 10 g/kg/day (approximately 42 times the intended human clinical dose). The only finding of note was dose-related vomiting and elevated blood pressure in the dog safety pharmacology study at oral doses 5.2- to 10.4- times the proposed clinical dose. In conclusion, this safety package of studies supports development of QFYEP in the clinic but with monitoring for any cardiovascular changes.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toxicological Response of the BEAS-2B Cell After Acute Exposure at the Air-Liquid Interface to Ethylbenzene and m-Xylene Alone and in Binary Mixtures. 空气-液界面急性暴露于乙苯和间二甲苯及二元混合物后BEAS-2B细胞的毒理学反应
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-08 DOI: 10.1002/jat.4806
Nour Jaber, Claude Emond, Fabrice Cazier, Sylvain Billet
{"title":"Toxicological Response of the BEAS-2B Cell After Acute Exposure at the Air-Liquid Interface to Ethylbenzene and m-Xylene Alone and in Binary Mixtures.","authors":"Nour Jaber, Claude Emond, Fabrice Cazier, Sylvain Billet","doi":"10.1002/jat.4806","DOIUrl":"https://doi.org/10.1002/jat.4806","url":null,"abstract":"<p><p>Benzene, toluene, ethylbenzene, and xylenes (o-, m-, and p-xylenes) constitute a family, named BTEX, of volatile organic compounds (VOCs) known for its toxicity. This study aimed to study the acute in vitro toxicity of ethylbenzene and m-xylene on human bronchial epithelial cells exposed at the air-liquid interface (ALI). The cells were exposed to VOCs alone and in a mixture for 1 h, followed by 5, 23, and 47 h of incubation. The kinetics of the cell response was characterized, including cytotoxicity, xenobiotic biotransformation, antioxidant defense system, inflammatory response, and apoptosis. The gene expression results showed major differences between these two compounds, even though their chemical structure is very similar. Ethylbenzene did not appear to be metabolized in BEAS-2B cells, as it inhibited gene expression of xenobiotic metabolizing enzymes (XME) and did not induce antioxidant defense systems or apoptosis. However, a slight inflammatory response was observed after exposure. m-Xylene was metabolized in BEAS-2B cells, inducing several XMEs and upregulating enzymes involved in the antioxidant defense system, as well as markers of inflammation and apoptosis. Co-exposure to the binary mixture resulted in an inhibition phenomenon, resulting in the inhibition of toxic action mechanisms studied. The results provide new information on the toxicity of ethylbenzene and m-xylene and highlight the importance of conducting ALI exposures to mixtures of toxicants.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Non-Phthalate Plasticizer Bis(2-ethylhexyl) Sebacate Induces Testis-Ova Formation and Suppresses Reproduction in Japanese Medaka. 非邻苯二甲酸酯增塑剂双(2-乙基己基)癸二酸酯诱导睾丸-卵子形成并抑制日本Medaka的生殖。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-08 DOI: 10.1002/jat.4794
Yoshifumi Horie, Yusei Matsuo, Juan Manuel Ríos, Hamidreza Ahmadniaye Motlagh, Jheng-Jie Jiang
{"title":"Non-Phthalate Plasticizer Bis(2-ethylhexyl) Sebacate Induces Testis-Ova Formation and Suppresses Reproduction in Japanese Medaka.","authors":"Yoshifumi Horie, Yusei Matsuo, Juan Manuel Ríos, Hamidreza Ahmadniaye Motlagh, Jheng-Jie Jiang","doi":"10.1002/jat.4794","DOIUrl":"https://doi.org/10.1002/jat.4794","url":null,"abstract":"<p><p>Bis(2-ethylhexyl) sebacate (DEHS), a commonly used non-phthalate plasticizer considered relatively safe relative to phthalates, has been reported to disrupt the endocrine system, affect reproduction-related genes, and potentially induce thyroid hormone-disrupting and estrogenic effects on Japanese medaka (Oryzias latipes). However, the long-term effects of DEHS exposure on aquatic organisms remain unclear; further, data on residual DEHS concentrations in rivers are extremely limited. Here, the effects of DEHS on the reproductive performance and gonadal sex differentiation of Japanese medaka were determined. Japanese medaka embryos and larvae were exposed to varying DEHS concentrations that have been reported to induce thyroid hormone-disrupting effects. The residual concentrations of DEHS in the Sumiyoshi River were measured weekly from May to July in 2024. The formation of testis-ova was induced in XY medaka exposed to varying DEHS concentrations. DEHS exposure was shown to significantly reduce the number of eggs laid but did not affect fertilization rates. The DEHS levels in the Sumiyoshi River were either undetected or below the method quantification limit. Although significant changes in reproductive capacity and testis-ova were not observed at environmentally relevant residual concentrations, this study highlights the potentially harmful effects of a chemical that was previously considered environmentally friendly.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Respiratory Exposure to Agriculture Dust Extract Alters Gut Commensal Species and Key Metabolites in Mice. 呼吸暴露于农业粉尘提取物改变小鼠肠道共生物种和关键代谢物。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-08 DOI: 10.1002/jat.4808
Meli'sa S Crawford, Arzu Ulu, Briana M Ramirez, Alina N Santos, Pritha Chatterjee, Vinicius Canale, Salomon Manz, Hillmin Lei, Sarah Mae Soriano, Tara M Nordgren, Declan F McCole
{"title":"Respiratory Exposure to Agriculture Dust Extract Alters Gut Commensal Species and Key Metabolites in Mice.","authors":"Meli'sa S Crawford, Arzu Ulu, Briana M Ramirez, Alina N Santos, Pritha Chatterjee, Vinicius Canale, Salomon Manz, Hillmin Lei, Sarah Mae Soriano, Tara M Nordgren, Declan F McCole","doi":"10.1002/jat.4808","DOIUrl":"https://doi.org/10.1002/jat.4808","url":null,"abstract":"<p><p>Exposure to agricultural dust containing antimicrobial-resistant pathogens poses significant health risks for workers in animal agriculture production. Beyond causing severe airway inflammation, pollutants are linked to intestinal diseases. Swine farm dust is rich in ultrafine particles, gram-positive and gram-negative bacteria, and bacterial components such as lipopolysaccharides (LPS; endotoxins). In our previous study, we demonstrated that intranasal exposure of male and female C57BL/6J mice to 12.5% hog dust extract (HDE, containing 22.1-91.1 EU/mL) for 3 weeks resulted in elevated total cell and neutrophil counts in bronchoalveolar lavage fluid and increased intestinal permeability compared to saline controls. Now, we report that 16S and metagenomic analyses of Week 3 stool samples from HDE-treated mice indicate a reduced abundance of the beneficial species Akkermansia muciniphila and Clostridium sp. ASF356 and Lachnospiraceae bacterium. Bacterial alpha diversity showed increased species evenness in fecal samples from HDE-treated mice (Pielou's evenness, p = 0.047, n = 5-6/group). Metabolomic analysis also indicated significant reductions in key metabolites involved in energy metabolism, including riboflavin (p = 0.027, n = 11) and nicotinic acid (p = 0.049, n = 11), as well as essential amino acids, such as inosine (p = 0.043, n = 11) and leucine (p = 0.018, n = 11). While HDE exposure does not robustly alter overall microbial abundance or community structure, it leads to specific reductions in beneficial bacterial species and critical metabolites necessary for maintaining intestinal homeostasis by supporting energy metabolism, gut barrier function, microbiota balance, and immune regulation. The results of this study underscore the potential risks for gut health posed by inhalation of agricultural dust.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
METTL3 Mediates Wnt/β-Catenin Pathway in Epithelial-Mesenchymal Transition of 16HBE Cells Induced by Beryllium Sulphate. METTL3介导Wnt/β-Catenin通路在硫酸铍诱导的16HBE细胞上皮-间质转化中的作用
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-08 DOI: 10.1002/jat.4807
Chenxi Yan, Guilan Li, Lian Huang, Zhaohui Zhang
{"title":"METTL3 Mediates Wnt/β-Catenin Pathway in Epithelial-Mesenchymal Transition of 16HBE Cells Induced by Beryllium Sulphate.","authors":"Chenxi Yan, Guilan Li, Lian Huang, Zhaohui Zhang","doi":"10.1002/jat.4807","DOIUrl":"https://doi.org/10.1002/jat.4807","url":null,"abstract":"<p><p>Beryllium (Be) is a recognised environmental toxicant associated with pulmonary fibrosis. Epithelial-mesenchymal transition (EMT), a critical process in cell phenotype conversion, plays a key role in its pathophysiology. Methyltransferase-like 3 (METTL3), a major N6-methyladenosine methyltransferase, regulates gene expression and cellular functions. However, its role in Be-induced EMT remains unclear. In this study, human bronchial epithelial cell line (16HBE cells) were exposed to varying concentrations of beryllium sulphate (BeSO<sub>4</sub>) to assess changes in METTL3 expression. METTL3 overexpression vectors were constructed, and quantitative reverse transcription-polymerase chain reaction, western blotting and immunofluorescence were used to detect METTL3, EMT markers and Wingless/Integrated (Wnt)/β-catenin pathway proteins. The Wnt/β-catenin pathway inhibitor ICG-001 was also employed to explore the role of the Wnt/β-catenin pathway in BeSO<sub>4</sub>-induced EMT. The study demonstrated that BeSO<sub>4</sub> suppressed METTL3 expression, induced EMT and activated the Wnt/β-catenin pathway in 16HBE cells. Both METTL3 overexpression and ICG-001 pretreatment mitigated BeSO<sub>4</sub>-induced EMT and Wnt/β-catenin pathway activation. These findings suggest that METTL3 inhibits BeSO<sub>4</sub>-induced EMT by suppressing the Wnt/β-catenin pathway, offering novel mechanistic insights into beryllium toxicity and a potential therapeutic target for Be-related pulmonary fibrosis.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating the Genotoxicity and Mutagenicity of Food Contaminants: Acrylamide, Penitrem A, and 3-Acetyldeoxynivalenol in Individual and Combined Exposure In Vitro. 评估食品污染物的遗传毒性和致突变性:丙烯酰胺、苯甲醚A和3-乙酰脱氧雪腐镰梨醇在单独和体外联合暴露中的作用。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2025-05-06 DOI: 10.1002/jat.4805
Luna Bridgeman, Cristina Juan, Houda Berrada, Isabelle Severin, Ana Juan-García
{"title":"Evaluating the Genotoxicity and Mutagenicity of Food Contaminants: Acrylamide, Penitrem A, and 3-Acetyldeoxynivalenol in Individual and Combined Exposure In Vitro.","authors":"Luna Bridgeman, Cristina Juan, Houda Berrada, Isabelle Severin, Ana Juan-García","doi":"10.1002/jat.4805","DOIUrl":"https://doi.org/10.1002/jat.4805","url":null,"abstract":"<p><p>This study aimed to evaluate the genotoxic effects of food contaminants exposure in human neuroblastoma SH-SY5Y cells using the micronucleus (MN) assay and Ames test. Acrylamide (AA), penitrem A (PEN A), and 3-acetyldeoxynivalenol (3-ADON) were tested both individually and in combination. Since humans are likely to be exposed to these substances simultaneously through diet, it is crucial to investigate their combined effects of the compounds rather than just their individual toxicities. The results demonstrated significant increases in MN frequency for all individual treatments and in a dose-dependent manner for AA and 3-ADON. Combined treatments also resulted in higher MN frequencies, particularly for AA + 3-ADON and PEN A + 3-ADON respect to the control. However, the Ames test revealed no mutagenic potential for any of the individual or combined treatments, consistent with previous studies. These findings suggest that while food contaminants induce chromosomal damage (MN induction), they do not cause gene mutations. Nonetheless, the lack of single mutations activity does not exclude the potential health risks of combined mycotoxin exposure, especially given the observed genotoxicity due to the DNA damage through chromosomal aberrations. Future studies focused on the mechanism of action should investigate the combined effects of food contaminants in more detail to better assess their potential health risks.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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