Ecotoxicology and Environmental Safety最新文献_第2页

Hexavalent chromium induced metabolic reprogramming, carcinogenesis and tumor progression through PDK1 upregulation 六价铬通过 PDK1 上调诱导代谢重编程、致癌和肿瘤进展。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117341

Wen-Jing Liu , Lin Wang , Fan-Li Sun , Feng-Mei Zhou , Rui-Ke Zhang , Jie Liu , Min Zhao , Li-Hong Wang , Yan-Ru Qin , Yan-Qiu Zhao , Jian-Ge Qiu , Bing-Hua Jiang

Lung cancer is the leading factor of cancer-related death in the worldwide. Hexavalent chromium [Cr(VI)] is a potential carcinogen for inducing lung cancers. To understand new mechanism of Cr(VI)-induced tumorigenesis and cancer development, we identified that PDK1 expression levels were greatly increased in chromium-transformed cells (Cr-T) compared to the parental BEAS-2B (B2B) cells by proteomic profiling and Western blotting; PDK1 levels were also induced in lung cancer cell lines and in lung samples of mice exposed to Cr(VI). Cr(VI) increased Warburg effect, cell migration, proliferation and colony formation through PDK1 upregulation. To identify the mechanism of PDK1 induction, we performed miRNA-seq analysis of Cr-T and B2B cells, and found miR-493 levels was significantly suppressed by Cr(VI). PDK1 was induced by miR-493 suppression, and was a direct target of miR-493. Interestingly, we also found HIF-1α was directly targeting by miR-493 and was induced by miR-493 downregulation. HIF-1α expression levels were upregulated in lung samples of mice with Cr(VI)-exposure. PDK1 was induced by HIF-1α, showing miR-493 suppression can directly induce PDK1 as well as through HIF-1α induction. MiR-493 overexpression was sufficient to suppress tumor growth, PDK1 and HIF-1α expression in vivo. We also showed that levels of miR-493 suppression, HIF-1α and PDK1 elevations were strongly correlated with poor prognosis of lung cancer subjects. These results demonstrate both HIF-1α and PDK1 expression are induced by Cr(VI)-mediated miR-493 suppression, and MiR-493/HIF-1α/PDK1 axis is a new pathway in Cr(VI)-inducing carcinogenesis and tumor growth.

肺癌是全球癌症致死的首要因素。六价铬[Cr(VI)]是诱发肺癌的潜在致癌物质。为了了解铬（六价铬）诱导肿瘤发生和癌症发展的新机制，我们通过蛋白质组分析和 Western 印迹发现，与亲本 BEAS-2B (B2B) 细胞相比，铬转化细胞（Cr-T）中 PDK1 的表达水平大大增加；肺癌细胞系和暴露于铬（六价铬）的小鼠肺部样本中 PDK1 的水平也被诱导。六价铬通过上调 PDK1 增加了沃伯格效应、细胞迁移、增殖和集落形成。为了确定PDK1的诱导机制，我们对Cr-T和B2B细胞进行了miRNA-seq分析，发现miR-493的水平被Cr(VI)显著抑制。PDK1受到miR-493的抑制而被诱导，并且是miR-493的直接靶标。有趣的是，我们还发现 HIF-1α 也是 miR-493 的直接靶标，并被 miR-493 下调所诱导。在暴露于六价铬的小鼠肺部样本中，HIF-1α的表达水平上调。HIF-1α诱导了PDK1，表明抑制miR-493可直接诱导PDK1，也可通过HIF-1α诱导PDK1。在体内，miR-493的过表达足以抑制肿瘤生长、PDK1和HIF-1α的表达。我们还发现，miR-493的抑制水平、HIF-1α和PDK1的升高与肺癌患者的不良预后密切相关。这些结果表明，HIF-1α和PDK1的表达均受Cr（VI）介导的miR-493抑制的诱导，而MiR-493/HIF-1α/PDK1轴是Cr（VI）诱导癌变和肿瘤生长的新途径。

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引用次数: 0

Elucidating tobacco smoke-induced craniofacial deformities: Biomarker and MAPK signaling dysregulation unraveled by cross-species multi-omics analysis 阐明烟草烟雾诱发的颅面畸形：跨物种多组学分析揭示生物标志物和 MAPK 信号失调

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117343

Yuxin Lin , Hao Li , Shukai Zheng , Rui Han , Kusheng Wu , Shijie Tang , Xiaoping Zhong , Jiasheng Chen

Tobacco smoke (TS), particularly secondhand and thirdhand smoke, poses a pervasive and intractable environmental hazard that promotes teratogenesis and the progression of craniofacial malformations, although the underlying mechanisms remain elusive. Using zebrafish larvae as a model, our research demonstrated a correlation between the increasing concentration of cigarette smoke extract (CSE) and the severity of craniofacial malformations, supported by Alcian blue staining and histological assessments. Through a combined mRNA-miRNA analysis and quantitative real-time PCR, we identified miR-96–5p, miR-152, miR-125b-2–3p, and miR-181a-3–3p as pivotal biomarkers in craniofacial cartilage development. Functional analyses revealed their association with the MAPK signaling pathway, oxidative stress (OS), and cell development, highlighting MAPK as a crucial mediator. Single-cell transcriptomics further disclosed aberrant MAPK activation in mesenchymal cells. Subsequent investigations in human embryonic palatal mesenchymal (HEPM) cells confirmed similar patterns of growth inhibition, apoptosis, and OS, and emphasized the cross-species consistency of these biomarkers and the over-activation of the MAPK signaling pathway. A comprehensive tri-omics analysis of HEPM cells identified pivotal genes, proteins, and metabolites within the MAPK pathway. This groundbreaking cross-species multi-omics study unveils novel biomarkers and MAPK pathway perturbations linked to TS-induced craniofacial developmental toxicity, promoting innovative clinical prediction, diagnosis, and interventional strategies to tackle TS-induced craniofacial malformations.

烟草烟雾（TS），尤其是二手烟和三手烟，是一种普遍存在且难以解决的环境危害，会促进畸胎的形成和颅面畸形的发展，但其潜在机制仍然难以捉摸。我们的研究以斑马鱼幼体为模型，通过阿尔新蓝染色和组织学评估，证明了香烟烟雾提取物（CSE）浓度的增加与颅面畸形严重程度之间的相关性。通过mRNA-miRNA联合分析和定量实时PCR，我们发现miR-96-5p、miR-152、miR-125b-2-3p和miR-181a-3-3p是颅面软骨发育过程中的关键生物标志物。功能分析揭示了它们与 MAPK 信号通路、氧化应激（OS）和细胞发育的关系，突出了 MAPK 作为关键介质的作用。单细胞转录组学进一步揭示了间充质细胞中 MAPK 的异常激活。随后在人类胚胎腭间充质细胞（HEPM）中进行的研究证实了类似的生长抑制、细胞凋亡和OS模式，并强调了这些生物标志物的跨物种一致性以及MAPK信号通路的过度激活。通过对 HEPM 细胞进行全面的三组学分析，确定了 MAPK 通路中的关键基因、蛋白质和代谢物。这项开创性的跨物种多组学研究揭示了与TS诱导的颅面发育毒性相关的新型生物标记物和MAPK通路扰动，促进了创新性临床预测、诊断和干预策略的制定，以解决TS诱导的颅面畸形问题。

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引用次数: 0

Environmental contamination by veterinary medicinal products and their implications in the conservation of the endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus) 兽药产品对环境的污染及其对保护濒危的比利牛斯狍（Tetrao urogallus aquitanicus）的影响。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117299

Olga Nicolás de Francisco , Ana Carolina Ewbank , Ana de la Torre , Irene Sacristán , Ivan Afonso Jordana , Anna Planella , Oriol Grau , Diego Garcia Ferré , Josep Maria Olmo-Vidal , Antonio J. García-Fernández , Isabel Navas , Antoni Margalida , Carlos Sacristán

The endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus) inhabits perennial forests of the Pyrenees (Spain, France and Andorre). Feces of domestic animals (e.g., horses and cattle) are often found in this species’ habitat as evidence of land use overlapping, especially during spring and summer. As a result, pharmaceutical residues found in feces of these domestic ungulates may be absorbed by plants and insects that are part of the diet of Pyrenean Capercaillies (e.g., blueberries [Vaccinium uliginosum, Vaccinium myrtillus], red wood ants [Formica rufa]). Based on the absence of data regarding the exposure of Pyrenean Capercaillie to residues of veterinary medicinal products (VMP), we selected 71 compounds as indicators of anthropogenically-related environmental contamination, analyzed in 90 samples collected in several subalpine forests, northwestern Spain. Residues of several VMP were detected in feces (capercaillie [ciprofloxacin, enrofloxacin, tetracycline and florfenicol], horse [ciprofloxacin, enrofloxacin, tetracycline and ivermectin], and cattle [ciprofloxacin and enrofloxacin]), and in entomofauna (ciprofloxacin and ivermectin). No VMP residues were detected in blueberry plants. Herein, we present novel data about the presence of VMP residues in the Pyrenean Capercaillie’s environment, and identify potential VMP sources (i.e., livestock feces and entomofauna) and an exposure route (i.e., food chain) for Capercaillie chicks. Further studies are necessary to investigate the potential indirect or chronic effects of VMP residues in the species’ breeding success and adult fitness, which must be taken into account by managers and policy makers to improve management and conservation actions.

濒危的比利牛斯秧鸡（Tetrao urogallus aquitanicus）栖息在比利牛斯山（西班牙、法国和安道尔）的多年生森林中。家畜（如马和牛）的粪便经常出现在该物种的栖息地，这也是土地使用重叠的证据，尤其是在春季和夏季。因此，这些家养有蹄类动物粪便中的药物残留可能会被比利牛斯狍的部分食物植物和昆虫（如蓝莓 [Vaccinium uliginosum, Vaccinium myrtillus]、红木蚂蚁 [Formica rufa]）吸收。由于缺乏有关比利牛斯狍接触兽药残留物（VMP）的数据，我们选择了 71 种化合物作为与人类活动相关的环境污染指标，并对在西班牙西北部几个亚高山森林采集的 90 份样本进行了分析。在粪便（狍[环丙沙星、恩诺沙星、四环素和氟苯尼考]、马[环丙沙星、恩诺沙星、四环素和伊维菌素]、牛[环丙沙星和恩诺沙星]）和内动物（环丙沙星和伊维菌素）中检测到了几种 VMP 的残留。在蓝莓植物中未检测到 VMP 残留。在此，我们提供了有关比利牛斯狍环境中存在 VMP 残留的新数据，并确定了 VMP 的潜在来源（即牲畜粪便和内动物）和狍雏鸡的接触途径（即食物链）。有必要开展进一步研究，调查 VMP 残留物对该物种繁殖成功率和成年体质的潜在间接或慢性影响，管理者和决策者必须考虑到这一点，以改进管理和保护行动。

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引用次数: 0

Macrophytes mitigate Microcystis aeruginosa-induced fish appetite suppression via intestinal metabolite regulation 营养体通过调节肠道代谢物缓解铜绿微囊藻引起的鱼类食欲抑制。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117348

Minmin Niu , Keira Harshaw , Qianqian Xiang , Yuan Zhou , Ping Xiang , Zhihao Ju , Wenyu Long , Hugh J. MacIsaac , Xuexiu Chang

Cyanobacterial blooms and aquatic macrophytes can affect the health, physiology, and behavior of freshwater fish. Changes in food intake can be a key indicator of stress in teleost fish, while changes in metabolite abundance in the gut can indicate a shift in metabolic priorities, including response to environmental stressors. Here, we exposed stone moroko (Pseudorasbora parva) to the cyanobacterium Microcystis aeruginosa and/or the macrophyte Ottelia acuminata and analyzed changes in fish health, appetite regulation, and intestinal metabolome after 96-h exposures. We found that O. acuminata treatment didn’t change the tested indicators, while exposure to M. aeruginosa increased concentrations of appetite-inhibiting factors, such as CART and GLP-1, and decreased concentrations of stimulatory factors like orexin. Exploration of the metabolome following exposure revealed that the appetite-inhibiting influence of M. aeruginosa was positively correlated with key metabolites of lipid, amino acid, and cholesterol metabolism, especially those associated with bile acid synthesis and secretion. Further, the presence of O. acuminata decreased the adverse effects of M. aeruginosa among neuro-endocrine regulatory factors, which could be explained by altered regulation of intestinal amino acid metabolites. The deeper mechanism by which O. acuminata moderates the harmful effects of M. aeruginosa remains to be identified.

蓝藻水华和水生大型藻类会影响淡水鱼的健康、生理和行为。摄食量的变化可以作为远摄性鱼类压力的一个关键指标，而肠道中代谢物丰度的变化可以表明代谢优先级的变化，包括对环境压力的反应。在这里，我们将石斑鱼（Pseudorasbora parva）暴露于蓝藻微囊藻（Microcystis aeruginosa）和/或大型藻类Ottelia acuminata，并分析了暴露96小时后鱼类健康、食欲调节和肠道代谢组的变化。我们发现，铜绿微囊藻处理没有改变测试指标，而暴露于铜绿微囊藻会增加食欲抑制因子（如 CART 和 GLP-1）的浓度，降低刺激因子（如奥曲肽）的浓度。对暴露后代谢组的研究表明，铜绿微囊藻抑制食欲的影响与脂质、氨基酸和胆固醇代谢的关键代谢物呈正相关，尤其是与胆汁酸合成和分泌相关的代谢物。此外，铜绿微囊藻的存在降低了铜绿微囊藻对神经内分泌调节因子的不利影响，这可能是由于肠道氨基酸代谢物的调节发生了改变。关于尖嘴鱼缓和铜绿假单胞菌有害影响的深层机制仍有待确定。

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引用次数: 0

Comparative analysis of 3D and 2D in vitro models of the permanent fish liver cell line RTL-W1: Metabolic capabilities and responses to xenobiotics 永久性鱼肝细胞系 RTL-W1 的三维和二维体外模型比较分析：代谢能力和对异种生物的反应。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117327

Vanessa Holgersson , Shelby Joyce , Marianne Brookman-Amissah, Tobias Lammel

In vitro models based on permanent fish liver cell lines have proven to be versatile tools for examining chemical biotransformation and toxicity. However, their in vivo relevance remains uncertain due to their potentially de-differentiated phenotype. Here, we investigate whether a 3D cell culture environment can restore hepatocyte-like properties of the Rainbow trout liver cell line RTL-W1. Utilizing ultralow attachment (ULA) microwell plates, we achieved controlled sizing and extended culture (3 weeks) of spheroidal aggregate cultures (spheroids). RTL-W1 cells within the spheroids remained viable and metabolically active, as confirmed by the CellTiter-Glo 3D assay. Transmission electron microscopy revealed that spheroids exhibit tissue-like arrangements, such as interdigitations, cell-cell junctions, and endo- or exocytic activity at the cell-cell interface. They also displayed ultrastructural characteristics typical of metabolically active cells/hepatocytes, including abundant endoplasmic reticulum (ER), Golgi apparatus, and mitochondria. RT-qPCR analysis showed upregulation of genes involved in xenobiotic and endogenous (lipid) metabolism in 3D cultures over time. Notably, for several genes, especially cyp1a, expression levels were significantly higher in spheroids than in monolayers cultured for the same duration. This was corroborated at the enzyme level by increased Cyp1a-dependent catalytic activity (EROD). Interestingly, increased Cyp1a expression did not lead to heightened susceptibility to benzo[a]pyrene toxicity, which requires bioactivation. However, RTL-W1 3D and 2D cell cultures exhibited differential susceptibility to toxicity from other model chemicals, such as the surfactant SDS and the metal copper (Cu). These findings support the hypothesis that RTL-W1 cells can re-differentiate to a hepatocyte-like phenotype when cultured in a 3D configuration and may exhibit distinct biological responses upon exposure to xenobiotics. Overall, this study advances our understanding of the potential of cell line-derived 3D in vitro models for research and providing more physiologically relevant data for regulatory contexts.

事实证明，基于永久性鱼肝细胞系的体外模型是研究化学品生物转化和毒性的多功能工具。然而，由于其潜在的去分化表型，它们在体内的相关性仍不确定。在此，我们研究了三维细胞培养环境能否恢复虹鳟肝细胞系 RTL-W1 的肝细胞样特性。利用超低附着力（ULA）微孔板，我们实现了球状聚集培养物（球体）的大小可控和延长培养时间（3 周）。经 CellTiter-Glo 3D 检测法证实，球体内的 RTL-W1 细胞仍具有活力和代谢活性。透射电子显微镜显示，球形培养物呈现出组织样排列，如相互咬合、细胞-细胞连接以及细胞-细胞界面的内吸或外排活动。它们还显示出代谢活跃细胞/肝细胞的典型超微结构特征，包括丰富的内质网（ER）、高尔基体和线粒体。RT-qPCR 分析表明，随着时间的推移，三维培养物中涉及异生物和内源性（脂质）代谢的基因出现上调。值得注意的是，有几个基因，特别是 cyp1a，在球状培养物中的表达水平明显高于在单层培养物中相同时间的表达水平。在酶水平上，这一点通过 Cyp1a 依赖性催化活性（EROD）的增加得到了证实。有趣的是，Cyp1a 表达的增加并没有导致对苯并[a]芘毒性的敏感性增加，因为苯并[a]芘的毒性需要生物活化。然而，RTL-W1 三维和二维细胞培养物对其他模型化学物质（如表面活性剂 SDS 和金属铜）的毒性表现出不同的敏感性。这些发现支持了一种假设，即 RTL-W1 细胞在三维结构中培养时可重新分化为肝细胞样表型，并可能在暴露于异种生物时表现出不同的生物反应。总之，这项研究加深了我们对细胞系衍生三维体外模型研究潜力的理解，并为监管提供了更多生理相关数据。

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引用次数: 0

Environmental triggers and future risk of developing autoimmune diseases: Molecular mechanism and network toxicology analysis of bisphenol A 环境诱因与未来罹患自身免疫性疾病的风险：双酚 A 的分子机制和网络毒理学分析。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117352

Yanggang Hong , Deqi Wang , Yinfang Lin , Qianru Yang , Yi Wang , Yuanyuan Xie , Wanyi Shu , Sheng Gao , Chunyan Hua

Bisphenol A (BPA), a chemical compound in plastics and resins, widely exist in people's production and life which have great potential to damage human and animal health. It has been proved that BPA could affect human immune function and promote the occurrence and development of autoimmune diseases (ADs). However, the mechanism and pathophysiology remain unknown. Therefore, this study aims to advance network toxicology strategies to efficiently investigate the putative toxicity and underlying molecular mechanisms of environmental pollutants, focusing on ADs induced by BPA exposure. Leveraging databases including ChEMBL, STITCH, SwissTargetPrediction, GeneCards, and OMIM, we identified potential targets associated with BPA exposure and ADs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), Hashimoto's thyroiditis (HT), inflammatory bowel disease (IBD), and type 1 diabetes (T1D). Subsequent refinement using STRING and Cytoscape software highlighted core targets respectively, and Metascape was utilized for enrichment analysis. Gene expression data from the GEO database revealed the upregulation or downregulation of these targets across these ADs. Molecular docking performed with Autodock confirmed robust binding between BPA and core targets, notably PPARG, CTNNB1, ESR1, EGFR, SRC, and CCND1. These findings suggest that BPA exposure may serve as an environmental trigger in the development of autoimmunity, underscoring potential environmental risk factors for the onset of autoimmune conditions.

双酚 A（BPA）是塑料和树脂中的一种化合物，广泛存在于人们的生产和生活中，对人类和动物的健康具有极大的潜在危害。事实证明，双酚 A 会影响人体免疫功能，促进自身免疫性疾病（ADs）的发生和发展。然而，其机理和病理生理学仍然未知。因此，本研究旨在推进网络毒理学策略，以有效研究环境污染物的推定毒性和潜在分子机制，重点关注双酚A暴露诱发的自身免疫性疾病。利用 ChEMBL、STITCH、SwissTargetPrediction、GeneCards 和 OMIM 等数据库，我们确定了与双酚 A 暴露和 ADs 相关的潜在靶点，包括类风湿性关节炎 (RA)、系统性红斑狼疮 (SLE)、多发性硬化症 (MS)、桥本氏甲状腺炎 (HT)、炎症性肠病 (IBD) 和 1 型糖尿病 (T1D)。随后，利用 STRING 和 Cytoscape 软件分别对核心靶标进行了细化，并利用 Metascape 进行了富集分析。来自 GEO 数据库的基因表达数据显示了这些靶点在这些 ADs 中的上调或下调情况。使用 Autodock 进行的分子对接证实了双酚 A 与核心靶点之间的紧密结合，尤其是 PPARG、CTNNB1、ESR1、表皮生长因子受体、SRC 和 CCND1。这些研究结果表明，暴露于双酚 A 可能是诱发自身免疫病的环境因素之一，并强调了自身免疫病发病的潜在环境风险因素。

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引用次数: 0

Endosulfan promotes cell growth, migration and invasion via CCL5/CCR5 axis in MCF-7 cells 硫丹通过 CCL5/CCR5 轴促进 MCF-7 细胞的生长、迁移和侵袭。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117344

Zeming Liu , Xiaolin Ding , Boxiang Zhang , Yue Pang , Yuhui Wang , Dan Xu , Hailong Wang

Endosulfan, recognized as an endocrine disruptor, has emerged as an important risk factor for human breast cancer. The chemokine ligand 5 (CCL5) and its receptor CCR5 constitute a biological axis, that is implicated in tumorigenesis and cancer progression. However, the role of the CCL5/CCR5 axis in breast cancer when exposure to endosulfan remains unclear. The present study aimed to determine the significance of the CCL5/CCR5 axis in the carcinogenic effects of endosulfan in human breast cancer MCF-7 cells. The results showed that endosulfan significantly promoted cell proliferation, increased the rate of colony formation, and enhanced cell migration ability in a dose-dependent manner by activating the PI3K/AKT signaling pathway, which were rescued by the specific inhibitor (LY-294002) for PI3K/AKT signaling pathway. We utilized Cytoscape software to construct protein-protein interaction (PPI) network when exposure to endosulfan, and identified 47 highly connected genes in the network diagram centered on CCL5. Endosulfan significantly increased the secretion of CCL5 and the expression levels of CCL5/CCR5, which were reversed by CCR5 inhibitor (HY-13004). HY-13004 significantly counteracted the effects of endosulfan on colony formation, cell migration and the activation of PI3K/AKT signaling pathway. Endosulfan markedly altered the expression levels of epithelial-mesenchymal transition (EMT) biomarkers and enhanced transwell migration and invasion capabilities of MCF-7 cells, which were inhibited by HY-13004, similar to the effects observed with LY-294002. Collectively, our findings suggest that endosulfan activates the PI3K/AKT signaling pathway to promote cell growth, and induces EMT, thereby enhancing cell migration and invasion via the CCL5/CCR5 axis in MCF-7 cells.

硫丹被认为是一种内分泌干扰物，已成为人类乳腺癌的一个重要风险因素。趋化因子配体 5（CCL5）及其受体 CCR5 构成了一个生物轴，与肿瘤发生和癌症进展有关。然而，当暴露于硫丹时，CCL5/CCR5 轴在乳腺癌中的作用仍不清楚。本研究旨在确定 CCL5/CCR5 轴在人乳腺癌 MCF-7 细胞硫丹致癌效应中的重要作用。结果表明，硫丹通过激活PI3K/AKT信号通路，以剂量依赖性方式显著促进细胞增殖、提高集落形成率和增强细胞迁移能力，而PI3K/AKT信号通路的特异性抑制剂（LY-294002）可挽救这些效应。我们利用Cytoscape软件构建了暴露于硫丹时的蛋白质-蛋白质相互作用（PPI）网络，并在网络图中发现了以CCL5为中心的47个高度关联的基因。硫丹能明显增加CCL5的分泌和CCL5/CCR5的表达水平，而CCR5抑制剂（HY-13004）能逆转这些变化。HY-13004能明显抵消硫丹对集落形成、细胞迁移和PI3K/AKT信号通路激活的影响。硫丹明显改变了上皮-间质转化（EMT）生物标志物的表达水平，增强了MCF-7细胞的经孔迁移和侵袭能力，而HY-13004抑制了这些作用，这与LY-294002观察到的效果相似。总之，我们的研究结果表明，硫丹可激活PI3K/AKT信号通路以促进细胞生长，并诱导EMT，从而通过CCL5/CCR5轴增强MCF-7细胞的迁移和侵袭能力。

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引用次数: 0

The correlation between heavy metal chelation and transcriptional potential of GRAS genes in Broussonetia papyrifera 重金属螯合与 Broussonetia papyrifera 中 GRAS 基因转录潜能之间的相关性。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117342

Dapei Li , Chenhao Li , Shen Yang , Ying Lu , Yan Tang , Zhenggang Xu , Shaobing Peng , Guiyan Yang

In order to understand the adaptation mechanism of Broussonetia papyrifera to heavy metal stress and then promote its remediation and utilization, in this study, a total of 24 GRAS transcription factors were identified from B. papyrifera transcriptomes. Their complete ORFs were 597–2250 bp in length with encoding proteins 22.40–84.13 kDa. The 24 BpGRASs were distributed across nine chromosomes and two scaffolds. Their promoters contained numerous cis-acting elements involving in plant development, environmental stimuli, and hormonal regulation. These BpGRAS genes were predominantly transcribed in flowers and fruits. The most prominent genes were BpSCL21b and BpDELLA1, whose expression levels in flowers were 4.11- and 4.56-fold higher than the minimal one in leaves. All BpGRASs were apparently induced by ABA and at least one treatment of Cd, Cu, Mn, and Zn. The expression of some BpGRAS genes (including BpSCL1d, BpSCL7, BpSCL27, BpSCL34, etc.) was significantly correlated with HM chelation and the non-protein thiols (NPT) accumulation, which was regarded as barriers to resist HM stress, under Cd, Cu, Mn, and Zn stress. Moreover, BpSCL15 and BpSCL21b transgenic yeast displayed significantly enhanced growth and viability (1.23-–2.71-fold, 1.30-–1.96-fold of control OD₆₀₀, accordingly) and metal accumulation (1.81-–3.58-fold, 1.91-–3.17-fold of control, accordingly). These results suggested that BpGRASs, especial BpSCL15, BpSCL21b, and BpSCL34, are essential for B. papyrifera response to HM stress depending on ABA signaling. It’s the first time to investigate the correlation of BpGRASs’ expression with HM and NPT accumulation, which may benefit for revealing the HM adaptation mechanism of B. papyrifera and provide candidate genes for HM resistance breeding in woody plants.

为了解纸浆草属植物对重金属胁迫的适应机制，进而促进其修复和利用，本研究从纸浆草属植物转录组中鉴定出24个GRAS转录因子。它们的完整ORFs长度为597-2250 bp，编码蛋白为22.40-84.13 kDa。这 24 个 BpGRASs 分布在 9 条染色体和 2 个支架上。它们的启动子包含许多顺式作用元件，涉及植物发育、环境刺激和激素调控。这些 BpGRAS 基因主要在花和果实中转录。最显著的基因是 BpSCL21b 和 BpDELLA1，它们在花中的表达水平分别是叶中最低表达水平的 4.11 倍和 4.56 倍。所有 BpGRAS 都明显受到 ABA 和至少一种 Cd、Cu、Mn 和 Zn 处理的诱导。在镉、铜、锰和锌胁迫下，一些 BpGRAS 基因（包括 BpSCL1d、BpSCL7、BpSCL27、BpSCL34 等）的表达与 HM 螯合和非蛋白质硫醇（NPT）积累显著相关，NPT 被认为是抵抗 HM 胁迫的屏障。此外，BpSCL15和BpSCL21b转基因酵母的生长和活力（OD600分别是对照的1.23--2.71倍和1.30--1.96倍）以及金属积累（分别是对照的1.81--3.58倍和1.91--3.17倍）均显著增强。这些结果表明，BpGRASs，特别是BpSCL15、BpSCL21b和BpSCL34，对于纸莎草对HM胁迫的响应是必不可少的，这取决于ABA信号转导。这是首次研究BpGRASs的表达与HM和NPT积累的相关性，有助于揭示纸莎草对HM的适应机制，为木本植物抗HM育种提供候选基因。

{"title":"The correlation between heavy metal chelation and transcriptional potential of GRAS genes in Broussonetia papyrifera","authors":"Dapei Li , Chenhao Li , Shen Yang , Ying Lu , Yan Tang , Zhenggang Xu , Shaobing Peng , Guiyan Yang","doi":"10.1016/j.ecoenv.2024.117342","DOIUrl":"10.1016/j.ecoenv.2024.117342","url":null,"abstract":"<div><div>In order to understand the adaptation mechanism of <em>Broussonetia papyrifera</em> to heavy metal stress and then promote its remediation and utilization, in this study, a total of 24 GRAS transcription factors were identified from <em>B. papyrifera</em> transcriptomes. Their complete ORFs were 597–2250 bp in length with encoding proteins 22.40–84.13 kDa. The 24 <em>BpGRAS</em>s were distributed across nine chromosomes and two scaffolds. Their promoters contained numerous <em>cis</em>-acting elements involving in plant development, environmental stimuli, and hormonal regulation. These <em>BpGRAS</em> genes were predominantly transcribed in flowers and fruits. The most prominent genes were <em>BpSCL21b</em> and <em>BpDELLA1</em>, whose expression levels in flowers were 4.11- and 4.56-fold higher than the minimal one in leaves. All <em>BpGRAS</em>s were apparently induced by ABA and at least one treatment of Cd, Cu, Mn, and Zn. The expression of some <em>BpGRAS</em> genes (including <em>BpSCL1d</em>, <em>BpSCL7</em>, <em>BpSCL27</em>, <em>BpSCL34</em>, etc.) was significantly correlated with HM chelation and the non-protein thiols (NPT) accumulation, which was regarded as barriers to resist HM stress, under Cd, Cu, Mn, and Zn stress. Moreover, <em>BpSCL15</em> and <em>BpSCL21b</em> transgenic yeast displayed significantly enhanced growth and viability (1.23-–2.71-fold, 1.30-–1.96-fold of control OD<sub>600</sub>, accordingly) and metal accumulation (1.81-–3.58-fold, 1.91-–3.17-fold of control, accordingly). These results suggested that <em>BpGRAS</em>s, especial <em>BpSCL15</em>, <em>BpSCL21b</em>, and <em>BpSCL34</em>, are essential for <em>B. papyrifera</em> response to HM stress depending on ABA signaling. It’s the first time to investigate the correlation of <em>BpGRAS</em>s’ expression with HM and NPT accumulation, which may benefit for revealing the HM adaptation mechanism of <em>B. papyrifera</em> and provide candidate genes for HM resistance breeding in woody plants.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"288 ","pages":"Article 117342"},"PeriodicalIF":6.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomics integrated with metabolomics reveals the effect of benzo[a]pyrene exposure on acute lung injury 转录组学与代谢组学结合揭示苯并[a]芘暴露对急性肺损伤的影响

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117323

Yuting Lin , Haibo Xu , Kaitao Wang , Xinye Wang , Xinyu Wu , Zhiyi Tang , Yuxi Lin , Chengshui Chen , Beibei Wang

Benzo[a]pyrene (BaP), a major harmful component in PM2.5, is widely present in automobile emissions and atmospheric pollution. BaP exposure directly targets the lungs, often resulting in acute lung injury (ALI). However, comprehensive metabolic and transcriptomic profiles related to BaP-induced ALI remain unexplored. To simulate BaP-induced lung injury, we performed intratracheal instillation of BaP. To investigate how BaP exposure affects lung transcriptome and metabolic profiles, we used RNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). We aimed to understand the underlying mechanisms of BaP-induced lung damage. Metabolomics analyses indicated that in BaP-exposed animals, most fatty acids, carbohydrates, and steroids were significantly reduced, whereas most amino acids and organic acids remained unchanged. Analysis of transcriptomics data showed that fatty acid synthesis decreased and fatty acid oxidation increased, suggesting that lipid breakdown occurs after BaP exposure. Additionally, there were increases in oxidative stress system activity and decreases in immune system function. Finally, BaP altered mitochondrial, lipid, immune system, and fatty acid pathways, as indicated by pathway enrichment analyses. These results show that BaP substantially affects metabolic and inflammatory responses, enhancing the broader understanding of the underlying mechanisms of ALI after BaP exposure.

苯并[a]芘（BaP）是 PM2.5 中的主要有害成分，广泛存在于汽车排放物和大气污染中。暴露于 BaP 会直接损伤肺部，通常会导致急性肺损伤（ALI）。然而，与BaP诱导的急性肺损伤相关的全面代谢和转录组图谱仍未得到探索。为了模拟 BaP 诱导的肺损伤，我们对 BaP 进行了气管内灌注。为了研究BaP暴露如何影响肺转录组和代谢谱，我们使用了RNA测序和超高效液相色谱-质谱联用仪（UPLC-MS）。我们的目的是了解 BaP 诱导肺损伤的潜在机制。代谢组学分析表明，在暴露于 BaP 的动物中，大多数脂肪酸、碳水化合物和类固醇显著减少，而大多数氨基酸和有机酸保持不变。转录组学数据分析显示，脂肪酸合成减少，脂肪酸氧化增加，这表明接触 BaP 后会发生脂质分解。此外，氧化应激系统活性增加，免疫系统功能下降。最后，如通路富集分析所示，BaP 改变了线粒体、脂质、免疫系统和脂肪酸通路。这些结果表明，BaP 对新陈代谢和炎症反应产生了重大影响，从而加深了人们对暴露于 BaP 后发生 ALI 的潜在机制的广泛了解。

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引用次数: 0

Phytotoxic response of ryegrass (Lolium multiflorum L.) to extreme exposure to two anionic surfactants 黑麦草（Lolium multiflorum L.）极端暴露于两种阴离子表面活性剂的植物毒性反应。

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-16 DOI: 10.1016/j.ecoenv.2024.117320

Emmeline D’Incau, Antoine Spaudo, Sonia Henry, Stéphanie Ouvrard

Bioremediation is an effective and environment-friendly treatment used to clean up hydrocarbon-contaminated soil. However, the effectiveness of this treatment is often limited by the low bioavailability of the target contaminants. Surfactants addition thus appears as a way to increase solubility of these hydrophobic molecules and consequently improve their bioavailability. The use of biological surfactants is often favoured over synthetic ones because they are claimed to be non-toxic to the environment though few studies have addressed this issue. The present work evaluated the effects of a synthetic surfactant, sodium dodecyl sulphate (SDS) and a biosurfactant (rhamnolipids) on germination and growth of ryegrass over a wide range of concentrations, between one up to ten times their respective critical micellar concentration (CMC). Experimental results showed that SDS inhibited seed germination of Lolium multiflorum at high concentrations (10 × CMC), unlike rhamnolipids, which did not induce any toxicity symptom at germination stage. At the growth stage, high rhamnolipid concentrations induced chronic phytotoxicity by significantly reducing root length, decreasing biomass production and disrupting the enzymatic defence system. Thus, biosurfactants are less toxic than synthetic ones but their application at high doses in bioremediation treatments might still induce phytotoxicity symptoms and thus negatively affect the environment.

生物修复是一种有效且环保的处理方法，用于清理受碳氢化合物污染的土壤。然而，由于目标污染物的生物利用率较低，这种处理方法的有效性往往受到限制。因此，添加表面活性剂似乎是增加这些疏水分子的溶解度，从而提高其生物利用率的一种方法。生物表面活性剂通常比合成表面活性剂更受青睐，因为据称生物表面活性剂对环境无毒，但很少有研究涉及这一问题。本研究评估了合成表面活性剂十二烷基硫酸钠（SDS）和生物表面活性剂鼠李糖脂（rhamnolipids）对黑麦草发芽和生长的影响，浓度范围很广，从 1 倍到 10 倍临界胶束浓度（CMC）不等。实验结果表明，高浓度（10 × CMC）的 SDS 会抑制多花甘蓝种子的萌发，而鼠李糖脂则不同，在萌发阶段不会引起任何毒性症状。在生长阶段，高浓度鼠李糖脂会诱发慢性植物毒性，显著降低根长、减少生物量的产生并破坏酶防御系统。因此，生物表面活性剂的毒性低于合成表面活性剂，但在生物修复处理中使用高剂量的生物表面活性剂仍可能诱发植物毒性症状，从而对环境造成负面影响。

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引用次数: 0