Journal of Applied Toxicology最新文献_第4页

Allergenicity, Genotoxicity and Subchronic Toxicity Assessment of IgG Binding Protein LT Produced From Aspergillus oryzae. 米曲霉IgG结合蛋白LT的致敏性、遗传毒性和亚慢性毒性评价。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-27 DOI: 10.1002/jat.4787

Kirt R Phipps, Sachin Patel, Kevin Scaife, Toby Holmes, Alica Šoltésová, Sandra Wingaard Thrane, Louise Kristine Vigsnæs, Nigel Baldwin, Christel Jørgensen

{"title":"Allergenicity, Genotoxicity and Subchronic Toxicity Assessment of IgG Binding Protein LT Produced From Aspergillus oryzae.","authors":"Kirt R Phipps, Sachin Patel, Kevin Scaife, Toby Holmes, Alica Šoltésová, Sandra Wingaard Thrane, Louise Kristine Vigsnæs, Nigel Baldwin, Christel Jørgensen","doi":"10.1002/jat.4787","DOIUrl":"https://doi.org/10.1002/jat.4787","url":null,"abstract":"Gastrointestinal health is one of the fastest growing areas in the food and beverage industry, as its importance to overall health and well-being is becoming increasingly recognized. Immunoglobulins play a key role in protecting the gastrointestinal tract, and nonbovine sources of immunoglobulins (including camel milk, which has a long history of consumption in East Africa and Asia) are increasing in popularity in Western countries as functional foods, particularly for individuals with allergies or intolerances to cow's milk. The physiological benefits of consuming certain heavy-chain immunoglobulins from camel milk relate to the binding domains of camelid single-domain antibodies; thus, a novel binding protein termed \"immunoglobulin G (IgG) binding protein LT\" (a dimer of two camelid single-domain antibody protein sequences) has been developed for use in food and beverage products, to provide some of the physiological benefits attributed to consuming camel milk, on an industrial scale. To support the safety of IgG binding protein LT for such use, a comprehensive safety assessment (in silico allergenicity assessment, in vitro genotoxicity studies [bacterial reverse mutation test and in vitro mammalian cell micronucleus test], and a 90-day gavage toxicity study in rats) was conducted. The in silico allergenicity assessment results demonstrate that IgG binding protein LT is highly unlikely to pose a risk of allergenic cross-reactivity, and there was no evidence of genotoxicity in vitro. There were no test article-related effects in the 90-day toxicity study. These data demonstrate the safety of IgG binding protein LT for its intended uses in foods and beverages.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005594","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

Exploring Holistic Healing of Cancer: German New Medicine (GNM) and Homeopathic Treatment Beyond Traditional Therapies. 探索癌症的整体治疗：德国新药（GNM）和传统疗法之外的顺势疗法治疗。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-24 DOI: 10.1002/jat.4796

Ramalakshmi Devi Konudula, Chandra Sekhara Rao Gorantla, Ramesh Athe

{"title":"Exploring Holistic Healing of Cancer: German New Medicine (GNM) and Homeopathic Treatment Beyond Traditional Therapies.","authors":"Ramalakshmi Devi Konudula, Chandra Sekhara Rao Gorantla, Ramesh Athe","doi":"10.1002/jat.4796","DOIUrl":"https://doi.org/10.1002/jat.4796","url":null,"abstract":"The study delves into the convergence of German new medicine (GNM) and homeopathy, examining their potential to enhance treatment strategies when considered together such that GNM posits a link between emotional trauma and physical manifestations of disease, providing a specific lens through which one can examine the origins of conditions such as cancer. Homeopathy, with its holistic and individualized approach, considers a vast array of symptoms and patient aspects. The present study debates the merits of integrating the detailed emotional analyses of GNM into the wide-ranging, symptom-based approach of homeopathy. Integration efforts are aimed at augmenting the depth of patient assessments, especially concerning the emotional etiology of diseases. The study indicated that while GNM can provide valuable insights, it should supplement rather than overshadow the comprehensive methodologies of homeopathic treatment. Future research avenues are proposed to evaluate the impact of combined GNM and homeopathic practices on patient outcomes, particularly in the domain of cancer, to uphold and possibly enhance the tradition of holistic and personalized patient care.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020252","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

The Molecular Mechanism of miRNA-195-5p Regulating ERK Involvement in Abnormal Phosphorylation of Tau Protein by Aluminum Maltol in PC12 Cells. miRNA-195-5p调控ERK参与PC12细胞中麦芽糖醇对Tau蛋白异常磷酸化的分子机制

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-24 DOI: 10.1002/jat.4795

Dan Gao, Jinzhu Yin, Yunwei Zhang, Chenyang Li, Le Zhao, Linping Wang, Jing Song, Huifang Zhang, Qiao Niu, Xiaoting Lu

{"title":"The Molecular Mechanism of miRNA-195-5p Regulating ERK Involvement in Abnormal Phosphorylation of Tau Protein by Aluminum Maltol in PC12 Cells.","authors":"Dan Gao, Jinzhu Yin, Yunwei Zhang, Chenyang Li, Le Zhao, Linping Wang, Jing Song, Huifang Zhang, Qiao Niu, Xiaoting Lu","doi":"10.1002/jat.4795","DOIUrl":"https://doi.org/10.1002/jat.4795","url":null,"abstract":"Although aluminum is ubiquitously present on Earth, it is not necessary for life. Aluminum is a metal element that can induce neurotoxicity. The neurotoxicity of aluminum is mainly caused by the aggregation of abnormally phosphorylated tau protein to form neurofibrillary tangles (NFTs). The phosphorylation of tau is regulated by both kinases and phosphatases. ERK is involved in PHF-type tau hyperphosphorylation. Recent studies have revealed that the interaction between microRNAs (miRNAs) and the ERK/MAPK cascade is related to maintaining the normal function of the nervous system. miR-195 is involved in the early development of AD with a potential impact on cognition. Therefore, we speculate that miRNA-195 may regulate ERK activity, thereby causing hyperphosphorylation of tau protein and neurotoxicity. The purpose of this study was to explore the role of miRNA-195-5p in regulating ERK in the process of aluminum maltol-induced tau hyperphosphorylation. The results showed that aluminum exposure decreased the expression level of miRNA-195-5p and increased the expression of P-ERK, abnormal phosphorylated tau. After inhibiting the activity of ERK, the expression of phosphorylation tau protein decreased. There is an interaction effect between inhibiting the activity of ERK and aluminum exposure on the expression of phosphorylated tau proteins. After the overexpression of miRNA-195-5p, the activity of ERK was inhibited. There is an interaction effect between miRNA-195-5p and aluminum exposure on the expression of phosphorylated tau. In conclusion, miRNA-195-5p regulates ERK involvement in the abnormal phosphorylation of tau protein by Al (mal)3in PC12 cells.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005598","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 Assessment of a Protein-Rich Postbiotic Derived From Methylorubrum extorquens XC23: A 90-Day Feeding Study in Rats and Associated Genotoxicity Assessment. 富蛋白后生物来源Methylorubrum exquens XC23的安全性评估：大鼠90天喂养研究及相关遗传毒性评估。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-22 DOI: 10.1002/jat.4792

Guangyao Lv, Di Zhang, Shiwei Wang, Qiang Min, Meijin Guo

{"title":"Safety Assessment of a Protein-Rich Postbiotic Derived From Methylorubrum extorquens XC23: A 90-Day Feeding Study in Rats and Associated Genotoxicity Assessment.","authors":"Guangyao Lv, Di Zhang, Shiwei Wang, Qiang Min, Meijin Guo","doi":"10.1002/jat.4792","DOIUrl":"https://doi.org/10.1002/jat.4792","url":null,"abstract":"Methylorubrum extorquens XC23 is amutant strain derived from Methylorubrum extorquens PA1 that has been subjected to UV irradiation. This strain primarily utilizes one-carbon compounds as its sole carbon source. It is capable of producing protein-rich biomass, making it an environmentally sustainable alternative protein source compared to conventional proteins derived from both animals and plants. A protein-rich postbiotic derived from Methylorubrum extorquens XC23 (Mea™) was used in a 90-day dietary safety study conducted on Sprague-Dawley rats. The purpose of this study was to evaluate the potential toxicity of the substance and to determine a no-observed-adverse-effect level (NOAEL). In this study, the feed was prepared containing 0%, 4%, 8%, and 16% (total crude protein provided from Mea™ expressed as a percentage of total mass of feed) Mea™, with the corresponding dietary levels of 0, 77, 154, and 308 g/kg, respectively. All animals reached their scheduled sacrifice points without any recorded mortality, and there were no incidents of moribund conditions or unscheduled sacrifices. Additionally, no toxic effects were observed, and no specific target organs were identified. Consequently, Mea™ has a NOAEL of 16.82 and 18.72 g·kg-1·day-1 for male and female rats, respectively. A series of three genotoxicity tests (bacterial reversion mutation test, mammalian erythrocyte micronucleus test, and mouse spermatocyte chromosomal aberration test) showed no evidence of point mutation and chromosome damage.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020262","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

Glyphosate Induces Anxiety-Like Behaviors in Mice via Activating NLRP3-Mediated Hippocampal Microglia Pyroptosis. 草甘膦通过激活nlrp3介导的海马小胶质细胞焦亡诱导小鼠焦虑样行为。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-20 DOI: 10.1002/jat.4793

Shuge Shu, Xinting Chen, Jiawen Ren, Xiangyu Yu, Hao Zhang, Yongquan Yu

{"title":"Glyphosate Induces Anxiety-Like Behaviors in Mice via Activating NLRP3-Mediated Hippocampal Microglia Pyroptosis.","authors":"Shuge Shu, Xinting Chen, Jiawen Ren, Xiangyu Yu, Hao Zhang, Yongquan Yu","doi":"10.1002/jat.4793","DOIUrl":"https://doi.org/10.1002/jat.4793","url":null,"abstract":"Glyphosate is reported to compromise the central nervous system and induce behavioral disorders in mammals. However, evidence is deficient with respect to the potential mechanisms involved. In this study, C57BL/6 mice were orally exposed to glyphosate at doses ranging from 0 to 200 mg/kg/day for 16 weeks. The results of behavioral tests showed that glyphosate decreased time spent and distance traveled within the central area of open field test, decreased the retention time and number of entries into the open arms, and increased the retention time and number of entries into the close arms of elevated plus maze test. The expressions of anxiety-related genes htr5, htr6, and tmem132d were also significantly upregulated by glyphosate. This behavioral phenotype was linked to the permeation of glyphosate into the brain via disrupting the functional tight junctions of blood-brain barrier (BBB). As a result, glyphosate directly compromised the morphological structure of neurons, increased the number of IBA-1 microglia, and activated the expression of NLRP3-mediated pyroptosis pathway (NLRP3, Caspase-1, GSDMD, and IL-18) in the hippocampus of mice. Moreover, the glyphosate-induced activation of NLRP3 pathway in microglia was markedly reversed by NLRP3 inhibitor MCC950. The conditional mediums from glyphosate-treated BV2 cells aggravated the cytotoxicity of HT-22 neurons, which was also rescued by MCC950. In conclusion, this work demonstrated that microglia-mediated activation of NLRP3 pyroptosis pathway plays a detrimental role in glyphosate-behavioral disorders and neuron damage. These findings provide novel evidence for glyphosate-induced neurotoxicity and support the growing association between glyphosate exposure and neurobehavioral disorders in humans.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020259","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

Impacts of Inorganic Arsenic Exposure on Genetic Stability of Human Mesenchymal Stromal Cells. 无机砷暴露对人间充质间质细胞遗传稳定性的影响。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-16 DOI: 10.1002/jat.4785

Marc A Beal, Melanie Coughlan, Andrée Nunnikhoven, Reena Corbane, Cathy Cummings-Lorbetskie, Andrea Rowan-Carroll, Tanvi Sharma, Andrew Williams, Jessie R Lavoie, Andrew Stalker, Asish Mohapatra, Matthew J Meier

{"title":"Impacts of Inorganic Arsenic Exposure on Genetic Stability of Human Mesenchymal Stromal Cells.","authors":"Marc A Beal, Melanie Coughlan, Andrée Nunnikhoven, Reena Corbane, Cathy Cummings-Lorbetskie, Andrea Rowan-Carroll, Tanvi Sharma, Andrew Williams, Jessie R Lavoie, Andrew Stalker, Asish Mohapatra, Matthew J Meier","doi":"10.1002/jat.4785","DOIUrl":"https://doi.org/10.1002/jat.4785","url":null,"abstract":"Human mesenchymal stem/stromal cells (hMSCs) can differentiate into mesoderm-type cells, making them suitable candidates for tissue repair therapies. However, their relatively low frequency in adult tissue necessitates ex vivo expansion prior to regenerative medicine applications, and therefore, long-term hMSC genetic stability during expansion should be studied. hMSC applications in regenerative medicine ensure commercial availability of normal karyotype human primary cells for toxicity assessment and hMSCs could serve as alternatives to immortalized human cell models. In this work, we evaluated the potential of hMSCs in toxicity testing using inorganic arsenic (iAs) as a case study. hMSCs were exposed to iAs at different durations to track cellular aging and study long-term genetic stability. iAs exposures (48 h) resulted in micronuclei induction. hMSCs were also exposed to iAs for 6 days to determine if hMSCs would become more susceptible to chromosomal damage following exposure to the model genotoxicant, mitomycin C (MMC). The culture duration and iAs exposure did not alter MMC potency, indicating that the hMSC susceptibility to chromosomal damage remained unchanged. We also used gene expression analysis to investigate the molecular impacts of iAs on hMSCs over the course of short (3 days total) and long (30 days total) experiments. Both iAs exposures activated biomarkers associated with oxidative stress, but not biomarkers for direct DNA damage, providing support for an indirect mode of action for iAs genotoxicity. Overall, this study establishes the utility of hMSCs as a new model for toxicity screening and provides mechanistic information underlying iAs toxicity.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020273","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

Predator-Prey Model for Simulating the Genetic Carcinogenicity of Aggressive Toxicant-Related Cancer. 模拟侵袭性毒物相关癌症遗传致癌性的捕食者-猎物模型。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-15 DOI: 10.1002/jat.4790

Mauricio Fernández-González, Ricardo Armisen, Mario I Fernández

{"title":"Predator-Prey Model for Simulating the Genetic Carcinogenicity of Aggressive Toxicant-Related Cancer.","authors":"Mauricio Fernández-González, Ricardo Armisen, Mario I Fernández","doi":"10.1002/jat.4790","DOIUrl":"https://doi.org/10.1002/jat.4790","url":null,"abstract":"The mechanism of how toxicant exposure leads to aggressive tumors remains unresolved. A genetic-based hypothesis predicts that under stress, the transcription of growth-related genes will be inhibited by the activation of mitogenic pathways, redirecting energy toward stress response and increasing survival. This hypothesis fails to explain why epidemiological data suggest that growth and stress response are activated, as patients exposed to toxicants exhibit more aggressive growth than nonexposed individuals. This co-occurrence requires increased energy availability to prevent the activation of mitogenic pathways, as seen in the Warburg effect. We hypothesize that if pollutant effects cease, it might drive aggressive cancer, as excess energy that is no longer used for stress response can fuel rapid growth. We model this allocation between growth and stress response as a trophic competition using the Lotka-Volterra equations and using as input RNA-Seq data from growth- and stress-related genes obtained from cancer cells exposed to copper, cadmium, and carboplatin. Our findings suggest that the energy allocation to growth and its rate of allocation is higher in exposed than nonexposed tumors and results in overgrowth in unexposed cells. This study helps to understand how certain scenarios, such as partial or total cessation of exposure, in toxicant-related cancer can drive cancer aggressiveness.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009042","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

Acetyl L-Carnitine Protects Zebrafish Embryos From Verapamil and Inorganic Arsenic-Induced Cardiotoxicity and Developmental Toxicity With No Effect on Supernumerary Motor Neuron Development. 乙酰左旋肉碱保护斑马鱼胚胎免受维拉帕米和无机砷诱导的心脏毒性和发育毒性，但对多余运动神经元的发育没有影响。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-15 DOI: 10.1002/jat.4788

Nathan C Twaddle, Camila S Silva, Frederick A Beland, Jyotshna Kanungo

{"title":"Acetyl L-Carnitine Protects Zebrafish Embryos From Verapamil and Inorganic Arsenic-Induced Cardiotoxicity and Developmental Toxicity With No Effect on Supernumerary Motor Neuron Development.","authors":"Nathan C Twaddle, Camila S Silva, Frederick A Beland, Jyotshna Kanungo","doi":"10.1002/jat.4788","DOIUrl":"https://doi.org/10.1002/jat.4788","url":null,"abstract":"Verapamil (a P-glycoprotein inhibitor) and inorganic arsenic cotreatment has been shown to be toxic in chick cardiomyocytes. Previously, we have shown that sodium arsenite at 200 mg/L did not cause developmental toxicity or cardiotoxicity in zebrafish embryos. Here, we investigated the effect of verapamil and sodium arsenite cotreatment on the zebrafish embryos. Embryos at 5 h post-fertilization (hpf) were exposed to sodium arsenite (100-400 mg/L; 0.77-3.08 mM) in the presence or absence of 20 μM verapamil for 67 h. At 72 hpf, all the embryos treated with sodium arsenite or verapamil alone were alive, while only ~23% and ~17% survived in the groups cotreated with 20 μM verapamil and 100 mg/L or 200 mg/L arsenite, respectively. However, 10 μM of verapamil and 200 mg/L sodium arsenite cotreatment resulted in 100% embryo survival. Inductively coupled plasma mass spectrometry analysis showed that in the verapamil and sodium arsenite cotreated group, the internal arsenic concentration was significantly higher than in the group treated with only sodium arsenite, suggesting that verapamil inhibited arsenic efflux. Surprisingly, verapamil, a calcium channel blocker, reduced sodium arsenite-induced apoptosis but caused developmental toxicity and cardiotoxicity in the sodium arsenite cotreated embryos, without affecting arsenite-induced supernumerary motor neuron development. Furthermore, acetyl L-carnitine (ALCAR) completely abolished both developmental toxicity and cardiotoxicity induced by sodium arsenite and verapamil cotreatment. We show for the first time that ALCAR prevents toxicities induced by arsenic and verapamil cotreatment in zebrafish embryos, a vertebrate model for investigating chemical toxicity.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003147","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

Synergistic Effect of ROS and p38 MAPK in Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles. 活性氧和p38 MAPK在二氧化钛纳米颗粒诱导的TM4细胞凋亡中的协同作用

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jat.4789

Pengfei Li, Xiaojia Meng, Tianjiao Lu, Chenhao Sun, Guanling Song

{"title":"Synergistic Effect of ROS and p38 MAPK in Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.","authors":"Pengfei Li, Xiaojia Meng, Tianjiao Lu, Chenhao Sun, Guanling Song","doi":"10.1002/jat.4789","DOIUrl":"https://doi.org/10.1002/jat.4789","url":null,"abstract":"The adverse effects of titanium dioxide nanoparticles (TiO2 NPs) on the integrity of the blood-testis barrier (BTB) are widely recognized. However, the underlying mechanisms remain incompletely understood. The integrity of the BTB is imperative for the preservation of male reproductive health. TM4 cells, which are major component of the BTB, play a critical role in its integrity. The apoptosis of TM4 cells is closely associated with the disruption of the BTB. Therefore, we selected TM4 cells as experimental models to investigate the apoptosis induced by TiO2 NPs and the underlying mechanisms. Cell viability, excessive production of reactive oxygen species (ROS), activation of p38 mitogen-activated protein kinase (MAPK) pathway, and apoptosis-related protein expression levels were determined under various concentrations (50, 100, 150, and 200 μg/mL) of TiO2 NPs exposure. The results indicate that TiO2 NPs induced the overproduction of ROS and activated the p38 MAPK signaling pathway, which subsequently led to apoptosis. The ROS scavenger N-acetylcysteine (NAC) was able to suppress the activation of p38 MAPK pathway induced by TiO2 NPs, while the p38 MAPK inhibitor SB203580 mitigated TiO2 NPs-induced ROS overproduction and subsequent apoptosis, suggesting an interplay between ROS overproduction and p38 MAPK pathway activation. In summary, TiO2 NPs induced mitochondrial apoptosis via the ROS-p38 MAPK axis. A positive feedback regulatory mechanism exists between the two processes, promoting apoptosis in TM4 cells through a synergistic effect.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019850","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

Development of a New Reporter Gene Assay for Detecting Juvenile Hormone Agonists Using Yeast Expressing Methoprene-Tolerant of the Freshwater Cladoceran Daphnia magna. 一种新的报告基因检测方法的建立，用于用酵母表达淡水毛藻大水蚤耐甲氧苯乙酯的幼鱼激素激动剂。

IF 2.7 4区医学

Journal of Applied Toxicology Pub Date : 2025-04-13 DOI: 10.1002/jat.4784

Sayoko Ito-Harashima, Erika Sano, Eiji Takada, Mayuko Nakashima, Masanobu Kawanishi, Takashi Yagi

{"title":"Development of a New Reporter Gene Assay for Detecting Juvenile Hormone Agonists Using Yeast Expressing Methoprene-Tolerant of the Freshwater Cladoceran Daphnia magna.","authors":"Sayoko Ito-Harashima, Erika Sano, Eiji Takada, Mayuko Nakashima, Masanobu Kawanishi, Takashi Yagi","doi":"10.1002/jat.4784","DOIUrl":"https://doi.org/10.1002/jat.4784","url":null,"abstract":"Juvenile hormones (JHs) play crucial roles in regulating growth, metamorphosis, and reproduction in arthropods. Synthetic JH agonists (JHAs), categorized as insect growth regulators, have been widely employed as insecticides. Natural JHs and synthetic JHAs both exert their physiological effects by binding to the JH receptor methoprene-tolerant (Met), forming a functional heterodimer complex with steroid receptor coactivators (SRCs). These juvenoids induce male offspring production in various daphnids, including Daphnia magna, highlighting the significance of the Met-mediated signaling in environmental sex determination. As a representative invertebrate model for assessing aquatic endocrine-disrupting chemicals, D. magna is incorporated in the test guidelines of the Organization for Economic Corporation and Development. We herein introduced a newly developed yeast-based reporter gene assay (RGA) for easy and rapid screening of JH-like ligands for D. magna Met (Dapma-Met). Dapma-Met was expressed alongside the SRC of D. magna (Dapma-SRC) in yeast cells carrying the lacZ reporter plasmid with a JH-responsive element derived from the Bombyx mori Krüppel homolog 1 gene. The yeast RGA system for Dapma-Met revealed a dose-dependent response to various juvenoids. The rank order of the ligand potencies of natural JHs and synthetic JHAs examined in yeast RGA strongly correlated with those previously observed in RGAs for Daphnia Met proteins established in Chinese hamster ovary cells and positively correlated with the male neonate-inducing activity in vivo. Our novel yeast RGA offers a rapid, easy-to-handle, and cost-effective solution that will be valuable for discriminating Dapma-Met ligands among chemicals with male offspring-inducing activity.","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026360","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