Ecotoxicology and Environmental Safety最新文献

{"title":"High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics","authors":"Qiong Wu ,&nbsp;Fei Xu ,&nbsp;Yishu Yang ,&nbsp;Aogang Zhang ,&nbsp;Han Sun ,&nbsp;Lin Yang ,&nbsp;Shuaiqi Zhao ,&nbsp;Yuling Zeng ,&nbsp;Mengxin Wang ,&nbsp;Saige Shi ,&nbsp;Fengquan Zhang ,&nbsp;Zhen An ,&nbsp;Juan Li ,&nbsp;Huijun Li ,&nbsp;Hui Wu ,&nbsp;Laibao Zhuo ,&nbsp;Jie Song ,&nbsp;Wen Chen ,&nbsp;Weidong Wu","doi":"10.1016/j.ecoenv.2025.118323","DOIUrl":"10.1016/j.ecoenv.2025.118323","url":null,"abstract":"<div><div>Epidemiological studies have demonstrated associations between heat waves, ozone (O₃) pollution, and cardiovascular morbidity and mortality. High temperature (HT) and higher levels of O₃ usually co-exist in the atmosphere. However, few studies have investigated the adverse effects of HT and O₃ co-exposure on cardiovascular system. Therefore, this study aimed to examine the effects of HT and O₃ co-exposure on biomarkers of cardiovascular damage and potential mechanisms. Sixty-four healthy SPF male C57BL/6N mice, aged 8 weeks, were randomly allocated into four groups: control, O₃, HT, and co-exposure (HT+O₃). Mice inhaled filtered air or 1 ppm O₃ at 24 °C or 36 °C, respectively, 4 h/day, for 5 consecutive days. Following the exposure, the biological samples of mice were collected for examination of biomarkers of cardiovascular disorders. Exposure to HT+O₃ exacerbated cardiovascular pathological damage induced by HT or O₃ alone. Compared to the control, the co-exposure group caused significant alterations of cardiovascular biomarkers. Moreover, co-exposure enhanced reduction of <em>Lactobacillus</em> and <em>Ruminococcus</em> and increases in <em>Prevotella</em> and <em>Alistipe</em> abundances induced by either HT or O₃. Moreover, co-exposure also promoted O₃-induced plasma metabolic disorder and these metabolites were enriched in multiple metabolic pathways typified by steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, among others. Spearman correlation analysis indicated that alterations of gut microbiota were significantly correlated with biomarkers of cardiovascular damage as well as plasma metabolic disorder. Exposure to HT and O₃ leads to cardiovascular damage, which possibly implicates gut microbial dysbiosis and plasma metabolic disorder.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118323"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling DINCH – Induced hepatotoxicity mechanisms via network toxicology and molecular docking with experimental validation","authors":"Jingxin Xin ,&nbsp;Changxu Zhou ,&nbsp;Ying Wang ,&nbsp;Huiqi Chen ,&nbsp;Keling Yin ,&nbsp;Ling Gao ,&nbsp;Shanshan Shao","doi":"10.1016/j.ecoenv.2025.118305","DOIUrl":"10.1016/j.ecoenv.2025.118305","url":null,"abstract":"<div><div>Phthalates, as a class of known endocrine disruptors, have been controversial because of their potential carcinogenicity and toxicity. Diisononyl cyclohexane-1,2-dicarboxylate (DINCH) is considered to be less toxic and more prone to environmental degradation, and is widely used as a substitute for phthalate. With the increasing use of DINCH in consumer products and industrial materials, the frequency of its detection in the air and human urine has also increased, which has aroused concern about its potential toxicity in food safety. Despite the increasing popularity of DINCH, toxicological studies on this topic are still limited. This study first predicted the hepatotoxicity and carcinogenicity of DINCH via the ADMETlab 3.0 platform. Next, the potential hepatotoxic genes associated with DINCH were collected through multiple databases, and a gene network was constructed. Through protein<img>protein interaction, GO enrichment and KEGG pathway analyses, we elucidated the primary mechanism by which DINCH may induce hepatotoxicity. The expression of the selected key genes in related diseases was subsequently validated via the liver cancer database of TCGA and the NASH dataset of GEO. In addition, molecular docking technology and dynamics simulation were used to simulate the interaction and binding ability between DINCH and the core target. Cell experiments verified that DINCH increases hepatotoxicity primarily by upregulating TNF, TP53, and PPARG. In summary, this study elucidates the potential biological mechanisms of DINCH-induced hepatotoxicity, providing new scientific insights for the prevention and management of related toxicities.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118305"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal exposure to 4-hydroxy-4′-isopropoxydiphenylsulfone alters the adipogenesis in adult mice: A sex-specific study","authors":"Shengnan Zhang ,&nbsp;Jiatong Shen ,&nbsp;Kaini Hu ,&nbsp;Yitong Zhou ,&nbsp;Yumeng Wang ,&nbsp;Xin Wang ,&nbsp;Kashif Hayat ,&nbsp;Mingrong Qian","doi":"10.1016/j.ecoenv.2025.118328","DOIUrl":"10.1016/j.ecoenv.2025.118328","url":null,"abstract":"<div><div>4-hydroxy-4′-isopropoxydiphenylsulfone (BPSIP), a common alternative to bisphenol A (BPA), has been detected in breast milk and across placental barriers. However, the long-term impacts of perinatal exposure to BPSIP on adipogenesis and susceptibility to metabolic disorders later in life remain poorly understood. This study explored the effects of early-life BPSIP exposure on obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were administered with BPSIP <em>via</em> oral gavage at doses of 0.02, 0.1, and 0.5 mg/kg body weight/day from gestational day 6 to postnatal day 21. After weaning, male and female offspring from control and high dose groups were fed either a normal diet (ND) or a high-fat diet (HFD) for 6 weeks. Results showed that perinatal BPSIP exposure significantly increased serum cholesterol levels, parametrial white adipose tissue (pWAT) weight, and body weight in female offspring, whereas males exhibited the opposite trend. Gene expression analyses revealed sex-specific alterations in adipogenesis, lipid metabolism, and endocrine function within pWAT, with these effects being more pronounced in HFD-fed BPSIP-exposed offspring. These findings demonstrate that perinatal exposure to BPSIP disrupts lipid metabolism in a sex-dependent manner, underscoring the potential long-term metabolic risks associated with BPSIP exposure during critical developmental periods.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118328"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network toxicology and molecular docking to investigate the mechanism of bisphenol A toxicity in human diabetic cardiomyopathy","authors":"Bo Li ,&nbsp;Xu Zhao ,&nbsp;Yan Ding ,&nbsp;Yi Zhang","doi":"10.1016/j.ecoenv.2025.118301","DOIUrl":"10.1016/j.ecoenv.2025.118301","url":null,"abstract":"<div><div>Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is widely used in polymers, plasticizers, and food packaging, raising significant concerns for human health. Growing evidence links BPA exposure to cardiovascular diseases, including diabetic cardiomyopathy (DCM), a severe complication of diabetes characterized by myocardial dysfunction. This study employs an integrative approach combining network toxicology and molecular docking to elucidate the molecular mechanisms underlying BPA-induced DCM. Using computational tools such as ADMETlab2.0, ProTox3.0, GeneCards, OMIM, Swiss Target Prediction, and ChEMBL databases, we systematically predicted BPA's potential to induce DCM and constructed comprehensive disease and BPA target libraries. Venn diagram analysis identified 93 potential targets associated with BPA-induced DCM, and a robust BPA regulatory network was established using Cytoscape. Functional enrichment analyses revealed significant involvement of oxidative stress, insulin signaling, and metabolic pathways in BPA toxicity. Molecular docking simulations demonstrated stable binding interactions between BPA and core targets (INS, AKT1, PPARG, STAT3, PPARA, MMP9), with binding energies ranging from −5.3 to −7.5 kcal/mol. Our findings indicate that BPA may induce DCM through key genes and pathways, including cGMP−PKG signaling pathway, insulin signaling pathway, AMPK signaling pathway, and HIF−1 signaling pathway. This study provides a novel theoretical framework for understanding the molecular pathogenesis of BPA-induced DCM and highlights the potential of network toxicology in identifying toxic pathways for uncharacterized environmental compounds. These insights offer potential targets for preventive and therapeutic strategies against BPA-associated cardiovascular complications.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118301"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-driven nanoparticle toxicity","authors":"Zied Hosni ,&nbsp;Sofiene Achour ,&nbsp;Fatma Saadi ,&nbsp;Yangfan Chen ,&nbsp;Mohammed Al Qaraghuli","doi":"10.1016/j.ecoenv.2025.118340","DOIUrl":"10.1016/j.ecoenv.2025.118340","url":null,"abstract":"<div><div>This study presents a comprehensive machine learning-driven analysis to understand and predict the toxicity of nanoparticles (NPs), a crucial aspect in ensuring the safe application of nanotechnology in medicine, pharmaceuticals, biotechnology, and various other industries. By using a robust dataset, we deployed Random Forest (RF) and Light Gradient Boosting Machine (LightGBM) algorithms to identify key NP features that significantly influence cellular toxicity. The integration of Shapley Additive exPlanations (SHAP) values provided an interpretative insight into the predictive models, allowing for a quantitative assessment of feature impact. Our findings highlighted the inverse relationship between NP concentration and cell viability and the heightened toxicity of smaller NPs due to their larger surface-to-volume ratios. Notably, the LightGBM model's sensitivity to zeta potential elucidates the nuanced impact of surface charge on cytotoxic effects. The results from this investigation can guide the synthesis of safer NPs, emphasized the need to consider these critical features to mitigate toxicity while maintaining functional integrity. The study underlines the complexity of NP toxicity modeling and the necessity for advanced analytical methods to capture the multifaceted nature of nanomaterial interactions with biological systems. This work lays the groundwork for future research aimed at refining NP design for safer biomedical applications and consumer products, marking a significant step towards responsible nanotechnology development.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118340"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of polystyrene nanoplastics on zebrafish gut microbiota and mechanistic insights","authors":"Abdul Rehman ,&nbsp;Théogène Habumugisha ,&nbsp;Fuyi Huang ,&nbsp;Zixing Zhang ,&nbsp;Claude Kiki ,&nbsp;Mamun Abdullah Al ,&nbsp;Changzhou Yan ,&nbsp;Uzma Shaheen ,&nbsp;Xian Zhang","doi":"10.1016/j.ecoenv.2025.118332","DOIUrl":"10.1016/j.ecoenv.2025.118332","url":null,"abstract":"<div><div>Aquatic environments are frequently contaminated with nanoplastics (NPs) ranging from 1–100 nm generated by plastic aging, but their bio-enrichment and toxicological impacts remain poorly understood. This study investigates how chronic exposure to carboxylated polystyrene nanoplastics (PNPs) alters gut microbiota composition and function in zebrafish (<em>Danio rerio</em>). Adult zebrafish were exposed to 50 nm PNPs at concentrations of 0.1, 1.0, and 10 mg/L for 14 and 28 days, followed by gut microbiota analysis using 16S rRNA gene sequencing. PNP exposure altered gut microbiota composition, including an increase in Proteobacteria abundance and a decrease in Firmicutes, Bacteroidetes, and the inflammation-related genus <em>Alistipes</em>. Beneficial probiotics such as <em>Faecalibacterium</em>, <em>Streptococcus</em>, <em>Bifidobacterium</em>, and <em>Lachnospira</em> were diminished, while pathogenic bacteria proliferated. TEM imaging revealed the internalization of PNP particles within intestinal tissues resulted in vacuolation, suggesting potential epithelial damage. Co-occurrence network patterns of gut microbiota greatly decreased during treatment with NPs. The neutral community model showed that among PNP treatments, 0.1 mg/L led to a less predictable (stochastic assembly process). PNP exposure led to increased predicted microbial functions (<em>via</em> PICRUSt2) related to xenobiotic metabolism, infection pathways, and lipopolysaccharide (LPS) production, while RNA transport and N-glycan biosynthesis were decreased. However, pathways related to microbial antioxidants exhibited significant variation across different PNP levels. These results provide critical insights into the toxicological impacts of chronic PNP exposure on fish gut health, highlighting the potential risks to aquatic ecosystems and human health.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118332"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATF4 participates in perfluorooctane sulfonate-induced neurotoxicity by regulating ferroptosis","authors":"Fangling Zhu ,&nbsp;Nan Wang ,&nbsp;Yichao Xu ,&nbsp;Xiaohua Su ,&nbsp;Ziliang Deng ,&nbsp;Yongdui Ruan ,&nbsp;Daifan Lin ,&nbsp;Yun Chen ,&nbsp;Zhuoni Kuang ,&nbsp;Guanlin Chen ,&nbsp;Chengcheng Yu ,&nbsp;Xiaoxuan Ling ,&nbsp;Linhua Liu","doi":"10.1016/j.ecoenv.2025.118303","DOIUrl":"10.1016/j.ecoenv.2025.118303","url":null,"abstract":"<div><div>Evidence from animal and human research suggests that perfluorooctane sulfonate (PFOS), a prevalent persistent organic pollutant (POP), exerts neurotoxic effects, but the precise mechanisms remain unclear. Additionally, the function of activating transcription factor 4 (ATF4), a crucial modulator of cellular metabolism, redox balance, and survival, in PFOS-induced neurotoxicity has not been fully elucidated. In vitro metabolomics studies revealed that PFOS elevated the intracellular concentration of reactive oxygen species (ROS) and lowered the levels of reduced L-glutathione (GSH). Significant alterations in the mRNA and protein expression levels of ferroptosis-related biomarkers, including ferroptosis-related genes [NRF2, nuclear receptor coactivator 4 (NCOA4), KEAP1, xCT/SLC7A11, GPX4, and FTH1], cellular iron, and lipid peroxidation were observed. Moreover, erastin (Ers) exacerbated lipid peroxidation, which was alleviated by ferrostatin-1 (Fer-1) and N-acetyl-L-cysteine (NAC). In mice, PFOS exposure damaged the structure and function of the hippocampus, including decreasing the number of neurons and impairing spatial learning and memory capacity. Importantly, ferroptosis was also observed in vivo, concomitant with the inhibition of ATF4, which was also observed in vitro. ATF4 silencing further increased ROS levels, lipid peroxidation, and ferroptosis induced by PFOS, whereas NAC and Fer-1 abrogated the effects of ATF4 silencing. Treatment with E235, an ATF4 activator, alleviated PFOS-induced ferroptosis. In conclusion, this study revealed that ATF4-mediated ferroptosis is involved in PFOS-induced neurotoxicity, offering novel mechanistic insights into the neurotoxic effects of PFOS and potentially paving the way for new therapeutic strategies.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118303"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The toxicity comparison of metformin and its degradant guanylurea through multi-routes exposure experiments using algae and rotifer","authors":"Fan Gao ,&nbsp;Lingyun Zhu ,&nbsp;Fan Zhang ,&nbsp;Meng Li ,&nbsp;Hairong Lian ,&nbsp;Sen Feng ,&nbsp;Xinfeng Cheng ,&nbsp;Xianling Xiang","doi":"10.1016/j.ecoenv.2025.118351","DOIUrl":"10.1016/j.ecoenv.2025.118351","url":null,"abstract":"<div><div>Metformin (MET) and its metabolite guanylurea (GUA) are prevalent in aquatic environments, raising concerns about their potential risks to aquatic organisms. However, the toxicity of these compounds through different exposure routes has not been reported. This study evaluated the effects of MET and GUA on the growth of the green algae <em>Tetradesmus obliquus</em> and on life table parameters of the freshwater rotifer <em>Brachionus calyciflorus</em> through various exposure routes, including waterborne, foodborne, and combined waterborne + foodborne. Our results indicated that both MET and GUA, at concentrations of 1 mg/L and 100 mg/L, inhibited algae growth, with GUA causing greater stress than MET. Additionally, compared to waterborne exposure, foodborne and combined waterborne + foodborne exposures of MET and GUA at these concentrations significantly decreased the net reproductive rate (R₀), intrinsic rate of population increase (r_m), and life expectancy (e₀) of <em>B. calyciflorus</em>. Notably, the impact of exposure routes on the life table parameters of <em>B. calyciflorus</em> was generally greater than the impact of exposure concentrations. Therefore, previous studies focusing solely on waterborne exposure may have underestimated the toxicity of MET and GUA.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"299 ","pages":"Article 118351"},"PeriodicalIF":6.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin K2 prevents postoperative cognitive impairments, anxiety-like behavior, and motor dysfunction induced by nanoplastics in young adult mice","authors":"Yu Hou ,&nbsp;Shuai Li ,&nbsp;Jian Yu ,&nbsp;Qi Hou ,&nbsp;Runjia Wang ,&nbsp;Xueran Xu ,&nbsp;Xiyuan Xu ,&nbsp;Zhichao Li ,&nbsp;Linhui Ma ,&nbsp;Qidong Liu ,&nbsp;Yuan Shen ,&nbsp;Guotao Peng ,&nbsp;Hui Zheng","doi":"10.1016/j.ecoenv.2025.118318","DOIUrl":"10.1016/j.ecoenv.2025.118318","url":null,"abstract":"<div><div>Nanoplastics (NPs) pollution poses serious health risks and worsens various diseases. However, its role in postoperative complications, particularly perioperative neurocognitive disorders (PNDs), remains unclear. While PNDs are common in the elderly and rare in young adults, lifelong and cumulative exposure to NPs may increase the susceptibility of young individuals to PNDs. Herein, surgery alone caused no neurobehavioral impairments in young adult male and female mice and exposed to NPs alone exhibited anxiety-like behavior. However, young adult male and female mice exposed to NPs for 30 days, with surgery on day 31, exhibited postoperative cognitive impairment and anxiety-like behavior associated with PNDs, along with motor dysfunction. Vitamin K2 (VK2) pretreatment mitigated the behavioral impairments induced by nanoplastics and surgery (NS) exposure. RNA sequencing and bioinformatics analysis of male mice revealed that NS activated inflammatory and cell death pathways in the hippocampus (HIP), with upregulation of key genes such as Selp, Timp1, and Emp3. In the medial prefrontal cortex (mPFC), NS exposure upregulated pathways associated with neuronal apoptosis, reactive oxygen species (ROS) processes, and cell death, accompanied by dysregulated expression of genes such as Tert, Adam8, Esr2, and Emp3. VK2 pretreatment rescued these molecular alterations by normalizing the expression of key genes. Additionally, VK2 reduced levels of IL-1β, TNF-α, IL-6, ROS and MDA, while attenuating brain cell apoptosis and microglial activation in the HIP and mPFC of male mice. This study demonstrates that NS exposure increases the susceptibility of young adults to PNDs and highlights VK2 as a promising preventive strategy. Moreover, it elucidates critical molecular pathways and genes, providing a solid foundation for future research.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"298 ","pages":"Article 118318"},"PeriodicalIF":6.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organelles Ca2+ redistribution contributes to cadmium-induced EMT of renal cancer cells through p-cPLA2-mediated arachidonic acid release","authors":"Jie Gu ,&nbsp;Jiacheng Ruan ,&nbsp;Chuanzhi Guo ,&nbsp;Zehua Li ,&nbsp;Huilin Fu ,&nbsp;Yimin Xie ,&nbsp;Hebing Xie ,&nbsp;Xun Gong ,&nbsp;Haifeng Shi","doi":"10.1016/j.ecoenv.2025.118317","DOIUrl":"10.1016/j.ecoenv.2025.118317","url":null,"abstract":"<div><div>Cadmium ion (Cd²⁺) is a non-essential metal that can increase cancer risk, including potentially renal cell carcinoma (RCC), though this link is not definitive. Cd²⁺ exposure impairs fatty acid metabolism in the kidneys, particularly affecting arachidonic acid (AA) levels, which are crucial for health. Previous studies have suggested that Cd²⁺-altered the AA metabolism associates with renal dysfunction. However, the role and mechanism of Cd²⁺-regulated AA source in promoting RCC progression are still unclear. This study aims to investigate how Cd²⁺ exposure affects AA levels in renal cancer cells and its role in promoting cell migration. Cd²⁺ exposure increases AA levels through cPLA₂-mediated release. It also induces calcium ion (Ca²⁺) redistribution from the endoplasmic reticulum (ER) to mitochondria, activating the p38 MAPK/cPLA₂ signaling pathway, and epithelial-mesenchymal transition (EMT) of Caki-1 cells. Cd²⁺-induced ER Ca²⁺ release, p38 MAPK/cPLA₂ signaling activation, AA levels, and EMT of Caki-1 cells were effectively reversed by siRNA knockdown of IP3R. Both exogenous AA treatments and Cd²⁺-induced AA metabolite PGD2 promoted EMT and cell migration of Caki-1 cells. This study highlights Cd^2+’s impact on fatty acid metabolism and organelle function in renal cancer cells, identifying potential therapeutic targets for RCC.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"298 ","pages":"Article 118317"},"PeriodicalIF":6.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}