Ecotoxicology and Environmental Safety最新文献_第7页

Exposure to particulate matter (PM2.5) weakens corneal defense by downregulating thrombospondin-1 and tight junction proteins 暴露于颗粒物（PM2.5）会通过下调凝血酶原-1 和紧密连接蛋白来削弱角膜防御能力。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117276

Liangliang Niu , Jiamin Liu , Huan Xu , Binghui Liu , Maomao Song , Chunchun Hu , Rui Jiang , Xinghuai Sun , Yuan Lei

Background

Fine particulate matter (PM_2.5) induces ocular surface toxicity through pyroptosis, oxidative stress, autophagy, and inflammatory responses. However, the precise molecular pathways through which PM_2.5 causes corneal damage remain unclear. This study aims to investigate the underlying mechanisms by exposing human corneal epithelial cells (HCECs) to PM_2.5.

Methods

After the morphology and chemical composition analysis of the PM samples, we conducted both in vivo and in vitro experiments to investigate PM_2.5-induced corneal epithelial damage. We assessed corneal barrier function in HCECs using transepithelial electrical resistance (TEER) assays. To explore the molecular mechanisms of PM_2.5-induced corneal epithelial damage, we performed whole-transcriptome resequencing, quantitative RT-PCR, and western blotting in vitro. In addition, we analyzed mouse corneas exposed to concentrated ambient PM_2.5 through immunofluorescence staining to observe the resulting changes in corneal epithelial protein expression in vivo.

Results

Our results showed significant impairment of corneal epithelial barrier function in PM_2.5-treated HCECs, as indicated by decreased TEER values. The expression of thrombospondin-1 (THBS1) and claudin-1, both key factors for maintaining corneal epithelial barrier integrity, was markedly reduced at the gene and protein levels in both in vitro and in vivo PM_2.5 exposure models. Moreover, the levels of tight junction-associated proteins, including occludin, zonula occludens-1 (ZO-1) and ZO-2, essential components of the corneal epithelial barrier, were significantly diminished in PM_2.5-treated HCECs.

Conclusion

PM_2.5 exposure leads to corneal epithelium damage by disrupting tight junction proteins and THBS1 expression. These findings provide insight into potential pathways for PM_2.5-induced ocular toxicity and underscore the need for protective strategies against such environmental pollutants.

背景：细颗粒物（PM2.5）通过热跃迁、氧化应激、自噬和炎症反应诱发眼表毒性。然而，PM2.5 造成角膜损伤的确切分子途径仍不清楚。本研究旨在通过将人类角膜上皮细胞（HCECs）暴露于 PM2.5 来研究其潜在机制：在对可吸入颗粒物样本进行形态和化学成分分析后，我们进行了体内和体外实验来研究PM2.5诱导的角膜上皮损伤。我们使用经皮层电阻（TEER）测定法评估了HCECs的角膜屏障功能。为了探索PM2.5诱导角膜上皮损伤的分子机制，我们在体外进行了全转录组重测序、定量RT-PCR和Western印迹。此外，我们还通过免疫荧光染色分析了暴露于高浓度环境 PM2.5 的小鼠角膜，观察角膜上皮蛋白质表达在体内的变化：结果：我们的研究结果表明，PM2.5处理的HCECs角膜上皮屏障功能明显受损，表现为TEER值下降。在体外和体内PM2.5暴露模型中，维持角膜上皮屏障完整性的两个关键因子--thrombospondin-1（THBS1）和claudin-1--在基因和蛋白水平上的表达均显著降低。此外，在经 PM2.5 处理的 HCECs 中，角膜上皮屏障的重要组成部分--紧密连接相关蛋白（包括闭塞素、闭塞带-1（ZO-1）和 ZO-2）的水平显著降低：结论：PM2.5暴露会破坏紧密连接蛋白和THBS1的表达，从而导致角膜上皮损伤。这些发现深入揭示了PM2.5诱发眼毒性的潜在途径，并强调了针对此类环境污染物采取保护策略的必要性。

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引用次数: 0

Hydrochlorothiazide disrupts DNA damage response to exacerbate skin photosensitivity 氢氯噻嗪会扰乱 DNA 损伤反应，从而加剧皮肤光敏性。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117314

Lei Tao , Yujiao Xu , Yingyue Cui , Qingcheng Wei , Boyang Lin , Yu Cao , Zhen Dai , Zhi Ma , Ling Zhang , Aiping Shi , Ling Gu , Yunyao Liu

Hydrochlorothiazide (HCTZ) is a widely utilized diuretic for the treatment of hypertension. The photosensitivity of HCTZ has been recognized for six decades, with UVA being considered the primary culprit. However, the precise molecular mechanism of HCTZ sensitizing skin to UV radiation remains unknown. In this study, we demonstrate that HCTZ exacerbates UVB-induced photosensitivity in normal skin by disrupting the DNA damage response, a crucial network responsible for maintaining epidermal homeostasis. Here, we found that HCTZ aggravates UVB-induced mouse skin damage. Through transcriptomic and proteomic profiling, we have found that the cell cycle and p53 signaling pathway may contribute to the photosensitivity caused by HCTZ. In keratinocytes, HCTZ promotes the transition from G1 to S phase and inhibits the p53 signaling pathway after exposure to UV radiation. We have found that HCTZ enhances the accumulation of DNA damage induced by UVB and impairs nucleotide excision repair (NER), which is responsible for repairing UVB-induced DNA lesions, by inhibiting the expression of NER-related genes and shortening the duration of G1 phase. Furthermore, pharmacologically inducing G1 arrest eliminates HCTZ-induced accumulation of damaged DNA. These findings unveil an unknown mechanism through which HCTZ impairs NER and interferes with UVB-induced cell cycle arrest, ultimately leading to improper response towards DNA damage and increased skin sensitivity.

氢氯噻嗪（HCTZ）是一种广泛用于治疗高血压的利尿剂。人们认识到 HCTZ 的光敏性已有六十年之久，其中 UVA 被认为是罪魁祸首。然而，HCTZ 使皮肤对紫外线辐射过敏的确切分子机制仍然未知。在这项研究中，我们证明了 HCTZ 通过破坏 DNA 损伤反应加剧了正常皮肤对 UVB 诱导的光敏感性，而 DNA 损伤反应是维持表皮稳态的关键网络。在这里，我们发现 HCTZ 会加重 UVB 诱导的小鼠皮肤损伤。通过转录组和蛋白质组分析，我们发现细胞周期和 p53 信号通路可能是 HCTZ 导致光敏感的原因。在角质形成细胞中，HCTZ能促进细胞从G1期向S期过渡，并在暴露于紫外线辐射后抑制p53信号通路。我们发现，HCTZ 通过抑制 NER 相关基因的表达和缩短 G1 期的持续时间，增强了 UVB 诱导的 DNA 损伤的积累，并损害了负责修复 UVB 诱导的 DNA 损伤的核苷酸切除修复（NER）。此外，药物诱导 G1 期停滞可消除 HCTZ 诱导的受损 DNA 积累。这些发现揭示了一种未知的机制，即 HCTZ 通过这种机制损害 NER 并干扰 UVB 诱导的细胞周期停滞，最终导致对 DNA 损伤的不当反应和皮肤敏感性的增加。

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引用次数: 0

Chlorophenols in environment: Recent updates on pretreatment and analysis methods 环境中的氯酚：预处理和分析方法的最新进展。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117326

Min Qian , Qi An , Yu Bian , Meng Zhang , Xue-song Feng , Cheng Du

Chlorophenols (CPs) are widely used in industries such as petrochemicals, insecticides, pharmaceuticals, synthetic dyes and wood preservatives. However, owing to the improper discharge and disposal, they have become major contaminants that are ubiquitously distributed in water, soil, and sewage sediments, posing a significant threat to ecosystems and human health. Consequently, accurate, sensitive and effective pretreatment and analysis methods for CPs are urgently required and have been actively explored in recent years. This review encompasses the pretreatment and detection methods for CPs in environmental samples from 2010 to 2024. The pretreatment methods for CPs primarily include solid-phase extraction, liquid-liquid extraction, solid-phase microextraction, liquid-phase microextraction, and QuEChERS. These methods are evolving towards more effective and environmentally friendly technologies, such as the miniaturization and automation of equipment, the development of innovative materials (including graphene, molecularly imprinted polymers, layered double hydroxides, porous organic polymers, and porous carbon), and the use of green solvents like deep eutectic solvents. Detection methods emphasize liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, sensors, and capillary electrophoresis. Advances in chromatographic columns, novel ion sources, and high-resolution mass spectrometry have significantly improved detection performance. In addition, the pros and cons of diverse techniques, critical comments and future perspectives are elaborated.

氯酚（CPs）广泛应用于石油化工、杀虫剂、制药、合成染料和木材防腐剂等行业。然而，由于排放和处理不当，它们已成为主要污染物，广泛分布于水、土壤和污水沉积物中，对生态系统和人类健康构成严重威胁。因此，准确、灵敏、有效的氯化石蜡预处理和分析方法已成为当务之急，近年来人们一直在积极探索这种方法。本综述涵盖了 2010 年至 2024 年环境样本中氯化石蜡的预处理和检测方法。氯化石蜡的预处理方法主要包括固相萃取、液液萃取、固相微萃取、液相微萃取和 QuEChERS。这些方法正朝着更有效、更环保的技术方向发展，例如设备的微型化和自动化、创新材料的开发（包括石墨烯、分子印迹聚合物、层状双氢氧化物、多孔有机聚合物和多孔碳）以及绿色溶剂（如深共晶溶剂）的使用。检测方法主要包括液相色谱-质谱法、气相色谱-质谱法、传感器和毛细管电泳。色谱柱、新型离子源和高分辨率质谱技术的进步大大提高了检测性能。此外，还阐述了各种技术的优缺点、批评意见和未来展望。

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引用次数: 0

Ambient PMs pollution, blood pressure, potential mediation by short-chain fatty acids: A prospective panel study of young adults in China 环境可吸入颗粒物污染、血压、短链脂肪酸的潜在中介作用：一项针对中国年轻成年人的前瞻性小组研究。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117316

Xin Chou , Miao Fang , Yue Shen , Cunzhong Jiang , Lin Miao , Liyan Yang , Zexi Wu , Xiangyu Yao , Kunpeng Ma , Kun Qiao , Zhijing Lin

Background

The concurrent effects of particulate matter (PM) on both blood pressure (BP) and short-chain fatty acids (SCFAs) are insufficiently explored, with limited research on the potential mediating roles of SCFAs.

Methods

In this prospective panel study with 4 follow-ups, we recruited 40 college students in Hefei, China, to assess the impacts of short-term exposure to PM (aerodynamic diameter ≤10 μm (PM₁₀), ≤2.5 μm (PM_2.5), and ≤1 μm (PM₁)) on BP and SCFAs, along with potential mechanisms. Real-time PM data, urinary SCFAs levels, and BP indicators were systematically collected. Linear mixed-effects models assessed the relationships between PM, SCFAs, and BP. Mediation analyses explored SCFAs’ mediating role in the PM-BP association.

Results

PM exposure was positively linked to BP and negatively associated with SCFAs. For a 10 μg/m³ rise in PM₁₀ at lag 0–72 h, there were notable reductions of 0.0019 % (95 %CI: −0.0028, −0.0010) in Acetic acid, 0.0262 % (-0.0369, −0.0155) in Propionic acid, and 0.0702 % (-0.1025, −0.0378) in Butyric acid. Systolic BP, diastolic BP, and mean arterial pressure (MAP) increased by 2.60 mmHg (0.96, 4.25), 2.24 mmHg (1.18, 3.31), and 2.36 mmHg (1.20, 3.53), respectively, per 10-μg/m³ rise in PM₁ at lag 0–24 h. Decreased SCFAs levels explained significant portions (24.69–31.80 %) of the elevated MAP due to PM₁₀. Stronger associations were found in females and individuals with abnormal BMI.

Conclusions

Our study shows that PM exposure decreases urinary SCFAs levels, which partially mediate the impact of PM on elevated BP. These findings enhance our comprehension of the pathways linking PM exposure to BP changes.

背景：颗粒物（PM）对血压（BP）和短链脂肪酸（SCFAs）同时产生的影响尚未得到充分探讨，而关于SCFAs潜在中介作用的研究也很有限：在这项为期4次随访的前瞻性小组研究中，我们在中国合肥招募了40名大学生，以评估短期暴露于可吸入颗粒物（空气动力学直径≤10 μm（PM10）、≤2.5 μm（PM2.5）和≤1 μm（PM1））对血压和SCFAs的影响及其潜在机制。研究人员系统地收集了可吸入颗粒物的实时数据、尿液中 SCFAs 的水平以及血压指标。线性混合效应模型评估了 PM、SCFAs 和 BP 之间的关系。中介分析探讨了 SCFAs 在 PM-BP 关联中的中介作用：结果： PM暴露与血压呈正相关，而与SCFAs呈负相关。在滞后 0-72 小时内，PM10 上升 10 μg/m3 时，乙酸显著减少 0.0019 %（95 %CI：-0.0028，-0.0010），丙酸减少 0.0262 %（-0.0369，-0.0155），丁酸减少 0.0702 %（-0.1025，-0.0378）。在滞后 0-24 小时内，PM1 每上升 10μg/m3 ，收缩压、舒张压和平均动脉压（MAP）分别上升 2.60 mmHg (0.96, 4.25)、2.24 mmHg (1.18, 3.31) 和 2.36 mmHg (1.20, 3.53)。SCFAs 含量的降低可以解释 PM10 导致的 MAP 升高的很大一部分原因（24.69%-31.80%）。女性和体重指数（BMI）异常者的相关性更强：我们的研究表明，暴露于可吸入颗粒物会降低尿液中 SCFAs 的水平，而 SCFAs 的水平在一定程度上介导了可吸入颗粒物对血压升高的影响。这些发现加深了我们对 PM 暴露与血压变化之间关联途径的理解。

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引用次数: 0

Selenium protects mouse spermatogonia against ivermectin-induced apoptosis by alleviating endoplasmic reticulum stress in vitro 硒通过减轻体外内质网应激，保护小鼠精原细胞免受伊维菌素诱导的细胞凋亡。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117307

Daniel Chavez Varias, Sung-Hwan Moon, Seung Hee Shin, Buom-Yong Ryu

Ivermectin (IVM) is a widely used anthelmintic in human and veterinary medicine. However, the increasing use of IVM raises concerns about its potential harm against non-targeted organisms. This study demonstrates a novel mechanism where IVM triggers apoptosis via endoplasmic reticulum (ER) stress in GC-1 spg in vitro. The inhibitory effects of selenium (Se) against the toxicological mechanism were also explored. IVM dose-dependently induces oxidative stress, dysregulated Ca²⁺ levels, and intracellular protein aggregation. Increased mitochondria-associated ER membrane (MAM) activity through Glucose-regulated Protein 75 (Grp75) overloads the mitochondria with Ca²⁺, causing mitochondrial dysfunction. These simultaneous stressors lead to unfolded protein response and apoptosis. Se reverses all these subcellular events by promoting the expression of selenoprotein-encoding genes to maintain the ER and redox homeostasis. The testis-enriched Glutathione Peroxidase 4 (Gpx4) and the testis-specific Selenoprotein V (Selenov) are only upregulated in the IVM and Se co-treatment group, suggesting their potential role in stress response. These findings confirm that toxic doses of IVM lead to programmed cell death in type B spermatogonia through redox imbalance-associated ER stress. This study provides valuable insights into refining male reproductive toxicity evaluation, targeting of ER stress to protect male germ cells, and maintaining male fertility from IVM-induced toxicity.

伊维菌素（IVM）是一种广泛用于人类和兽医的驱虫药。然而，随着伊维菌素使用量的不断增加，人们开始担心它对非靶标生物的潜在危害。本研究展示了一种新的机制，即 IVM 通过内质网（ER）应激引发体外 GC-1 spg 的细胞凋亡。研究还探讨了硒（Se）对该毒理机制的抑制作用。IVM剂量依赖性地诱导氧化应激、Ca2+水平失调和细胞内蛋白质聚集。通过葡萄糖调控蛋白 75（Grp75）增加线粒体相关 ER 膜（MAM）的活性，使线粒体的 Ca2+ 超载，导致线粒体功能障碍。这些同时出现的压力导致未折叠蛋白反应和细胞凋亡。硒通过促进硒蛋白编码基因的表达来维持ER和氧化还原平衡，从而逆转所有这些亚细胞事件。睾丸富集的谷胱甘肽过氧化物酶 4（Gpx4）和睾丸特异性硒蛋白 V（Selenov）仅在 IVM 和 Se 联合治疗组中上调，这表明它们在应激反应中的潜在作用。这些发现证实，毒性剂量的IVM会通过氧化还原失衡相关的ER应激导致B型精原细胞的程序性细胞死亡。这项研究为完善男性生殖毒性评估、针对ER应激保护男性生殖细胞以及维持男性生育能力免受IVM诱导的毒性影响提供了宝贵的见解。

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引用次数: 0

MANF inhibits NLRP3 inflammasome activation by competitively binding to DDX3X in paraquat-stimulated alveolar macrophages MANF 通过与百草枯刺激的肺泡巨噬细胞中的 DDX3X 竞争性结合，抑制 NLRP3 炎症小体的激活。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117331

Yi Pu , Siying Han , Jie Chen , Zhenning Liu

NLRP3 inflammasome activation in macrophages is involved in paraquat-induced acute lung injury (ALI). MANF exerts an inhibitory effect against inflammation and cell death. The aim of this study was to investigate the role of MANF in paraquat-stimulated alveolar macrophages and the potential mechanism. Paraquat-induced ALI mouse model was established by intraperitoneally injection of 30 mg/kg of paraquat. The lung pathological changes were observed by hematoxylin and eosin staining. The expression of MANF/DDX3X/NLRP3/Caspase-1 in mice lung macrophages was evaluated by double immunofluorescence staining and western blot. NLRP3 inflammasome activation and pro-inflammatory cytokines (IL-1β and IL-18) in paraquat-stimulated macrophage transfected with MANF overexpression plasmid (pcDNA3.1-MANF) or siRNA-MANF were measured by Western blot. The protein–protein interaction of MANF/DDX3X/NLRP3 was verified by Co-immunoprecipitation. As a result, MANF/DDX3X/NLRP3/Caspase-1 were upregulated in alveolar macrophages of paraquat-induced ALI in mice. In paraquat-stimulated alveolar macrophages, upregulation of MANF and DDX3X were also observed, accompanied by NLRP3 inflammasome activation. In addition, overexpression of MANF inhibited NLRP3 inflammasome activation in paraquat-stimulated alveolar macrophages. In contrast, knockdown of MANF aggravated NLRP3 inflammasome activation. Co-immunoprecipitation results revealed that DDX3X could bind to MANF and NLRP3, but MANF could not bind to NLRP3 in paraquat-stimulated alveolar macrophages. Furthermore, Co-immunoprecipitation of truncated three fragments of DDX3X confirmed MANF can interact with the helicase core of DDX3X which is the binding site for NLRP3. Taken together, MANF exerted a protective effect against paraquat-induced cytotoxicity by inhibiting the NLRP3 inflammasome activation in macrophages via competitive binding to the helicase core of DDX3X.

巨噬细胞中NLRP3炎性体的激活参与了百草枯诱导的急性肺损伤（ALI）。MANF具有抑制炎症和细胞死亡的作用。本研究旨在探讨MANF在百草枯刺激的肺泡巨噬细胞中的作用及其潜在机制。通过腹腔注射30毫克/千克百草枯，建立了百草枯诱导的ALI小鼠模型。苏木精和伊红染色观察肺部病理变化。小鼠肺巨噬细胞中 MANF/DDX3X/NLRP3/Caspase-1 的表达通过双重免疫荧光染色和 Western 印迹进行评估。Western印迹法测定了转染MANF过表达质粒（pcDNA3.1-MANF）或siRNA-MANF的百草枯刺激巨噬细胞的NLRP3炎性体活化和促炎细胞因子（IL-1β和IL-18）。共免疫沉淀法验证了MANF/DDX3X/NLRP3的蛋白相互作用。结果表明，MANF/DDX3X/NLRP3/Caspase-1在百草枯诱导的小鼠ALI的肺泡巨噬细胞中上调。在百草枯刺激的肺泡巨噬细胞中，也观察到 MANF 和 DDX3X 的上调，并伴随着 NLRP3 炎性体的激活。此外，在百草枯刺激的肺泡巨噬细胞中，过表达 MANF 可抑制 NLRP3 炎性体的激活。相反，敲除MANF会加剧NLRP3炎症小体的激活。共免疫沉淀结果显示，在百草枯刺激的肺泡巨噬细胞中，DDX3X能与MANF和NLRP3结合，但MANF不能与NLRP3结合。此外，DDX3X三个截短片段的共免疫沉淀证实，MANF能与DDX3X的螺旋酶核心相互作用，而该核心正是NLRP3的结合位点。综上所述，MANF通过与DDX3X的螺旋酶核心竞争性结合，抑制巨噬细胞中NLRP3炎性体的激活，从而对百草枯诱导的细胞毒性起到保护作用。

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引用次数: 0

Nicotine exposure is associated with targeted impairments in primordial follicle phenotype in cultured neonatal mouse ovaries 尼古丁暴露与培养的新生小鼠卵巢中原始卵泡表型的定向损伤有关。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117302

Sara M. Idrees, Sarah L. Waite, Sofia Granados Aparici , Mark A. Fenwick

The ovarian reserve consists of a limited supply of primordial follicles (PFs), each containing an oocyte surrounded by a layer of granulosa cells (GCs). PFs are relatively quiescent and must remain viable for a long period, thereby making them susceptible to environmental and lifestyle influences. Given the widespread prevalence of e-cigarette use, this study aimed to investigate the effects of nicotine and its metabolite cotinine in a mouse model and to elucidate the mechanisms by which nicotine influences the ovarian reserve. Neonatal ovaries were cultured for 7-days in nicotine or cotinine reflective of concentrations in plasma of e-cigarette users. From histological evaluation, nicotine or cotinine had no impact on the number of PFs or early growing follicles; however, the medium (15 ng/ml) and high (45 ng/ml) concentrations of nicotine (but not cotinine) caused a small reduction in oocyte and GC size within PFs relative to controls (0 ng/ml; both P<0.01). These morphological effects were not associated with changes in immunofluorescent markers of apoptosis (active caspase-3) or proliferation (Pcna), but were associated with increased gH2AX in PF oocytes, indicative of DNA damage and repair. RNA-sequencing of cultured ovaries exposed to nicotine (45 ng/ml) relative to control (0 ng/ml), revealed a suite of differentially expressed candidates, as well as numerous gene ontology biological processes associated with increased DNA damage, metabolism, respiration and immune function, alongside suppression of meiosis, cell adhesion, differentiation and morphogenesis. Findings from this study indicate that direct nicotine exposure has a limited effect on the quantity of PFs, but importantly highlights a range of processes that could impinge on the quality of the ovarian reserve.

卵巢储备由数量有限的原始卵泡（PFs）组成，每个原始卵泡含有一个卵母细胞，周围有一层颗粒细胞（GCs）。原始卵泡处于相对静止状态，必须长期保持活力，因此很容易受到环境和生活方式的影响。鉴于电子烟的广泛使用，本研究旨在研究尼古丁及其代谢物可替宁对小鼠模型的影响，并阐明尼古丁影响卵巢储备功能的机制。新生卵巢在尼古丁或可替宁中培养了7天，尼古丁或可替宁的浓度反映了电子烟使用者血浆中的浓度。从组织学评估来看，尼古丁或可替宁对 PFs 或早期生长卵泡的数量没有影响；但是，相对于对照组（0 ng/ml；P 均为 0），中等浓度（15 ng/ml）和高浓度（45 ng/ml）的尼古丁（而非可替宁）会导致 PFs 中卵母细胞和 GC 大小的小幅减少。

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引用次数: 0

Acetylation of FOXO1 is involved in cadmium-induced rat kidney injury via mediating autophagosome-lysosome fusion blockade and autophagy inhibition FOXO1的乙酰化通过介导自噬体-溶酶体融合阻断和自噬抑制参与了镉诱导的大鼠肾损伤。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117253

Yingxin Ruan , Yang Xue , Pengyu Zhang , Junya Jia

Cadmium (Cd), a potentially toxic elements, has the potential to cause harm to the kidneys. Studies has demonstrated that autophagosome-lysosome fusion blockade and consequent autophagy inhibition is related to Cd-induced kidney injury. Studies indicate that acetylation of forkhead box protein O1 (FOXO1) as a transcriptional factor of lysosomal and autophagy genes, but its roles in Cd-exposed kidney tissues remains unclear till now. Therefore, the present study was conducted to elucidate this issue. Data found that Cd enhances the acetylation level of FOXO1 and inhibits the expression level of silent information regulator 1 (Sirt1, deacetylase of FOXO1). Pharmacological activation of Sirt1 (SRT2104 treatment) decreases Cd-increased acetylation level of FOXO1, enhances Cd-inhibited transcription level of Ras-related protein 7 (Rab7), restores Cd-blocked fusion of autophagosome and lysosome, and alleviates Cd-induced autophagy inhibition. Moreover, data corroborated that inhibiting the acetylation level of FOXO1 is conductive to mitigating Cd-induced kidney injury. Collectively, these results demonstrate that acetylation of FOXO1 mediates the autophagosome-lysosome fusion blockade and autophagy inhibition during Cd-induced kidney injury, while regulating the acetylation level of FOXO1 may be a potential mechanism of treating nephrotoxicity after Cd exposure.

镉（Cd）是一种潜在的有毒元素，有可能对肾脏造成伤害。研究表明，自噬体-溶酶体融合受阻以及随之而来的自噬抑制与镉诱发的肾损伤有关。研究表明，叉头盒蛋白 O1（FOXO1）的乙酰化是溶酶体和自噬基因的转录因子，但其在 Cd 暴露肾组织中的作用至今仍不清楚。因此，本研究旨在阐明这一问题。数据发现，镉能提高 FOXO1 的乙酰化水平，抑制沉默信息调节因子 1（Sirt1，FOXO1 的去乙酰化酶）的表达水平。药理激活 Sirt1（SRT2104 处理）可降低 Cd 增加的 FOXO1 乙酰化水平，提高 Cd 抑制的 Ras 相关蛋白 7（Rab7）转录水平，恢复 Cd 阻断的自噬体和溶酶体融合，缓解 Cd 诱导的自噬抑制。此外，数据还证实，抑制 FOXO1 的乙酰化水平有利于减轻 Cd 引起的肾损伤。总之，这些结果表明，FOXO1的乙酰化介导了镉诱导的肾损伤过程中自噬体-溶酶体融合受阻和自噬抑制，而调节FOXO1的乙酰化水平可能是治疗镉暴露后肾毒性的一种潜在机制。

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引用次数: 0

Benzophenone-3 exposure induced apoptosis via impairing mitochondrial function in human chondrocytes 接触二苯甲酮-3会损害人软骨细胞的线粒体功能，从而诱导细胞凋亡。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117286

Ye Yang , Rui Gao , Zhenyu Zhu, Wenfeng Xiao, Jing Wang, Wenxia Zhao, Yingjun Li

Osteoarthritis (OA) is a chronic joint disease affecting millions of adults worldwide, characterized by degeneration of articular cartilage. Many environmental risk factors contribute to OA development. Benzophenone-3 (BP-3), a commonly used ultraviolet filter in personal care products, has been positively associated with OA risk. However, it remains unclear whether and how BP-3 induces toxic effects on articular chondrocytes and promote OA development. This study aims to investigate the damage of BP-3 at environmentally relevant concentrations to human chondrocytes, as well as potential mechanisms linking BP-3 with injury of chondrocytes. Notably, BP-3 significantly inhibited cell viability, induced apoptosis, and up-regulated matrix metalloproteinase (MMP) 1 and 13 which mediated cartilage degradation in C28/I2 human normal chondrocytes. Moreover, the function of mitochondria was impaired and oxidative stress occurred in BP-3 exposure groups, evidenced by elevation of reactive oxygen species (ROS) generation, reduction of mitochondrial membrane potential, decrease of ATP production and inhibition of mitochondrial respiratory chain complex I, II, III and IV. Meanwhile, BP-3 caused mitochondrial cristae vague and formation of autophagosomes. PTEN induced putative kinase 1/E3 ubiquitin protein ligase (PINK1/Parkin) pathway was also activated by BP-3. Addition of autophagy inhibitor, 3-Methyladenine (3-MA), suppressed PINK1/Parkin-mediated mitophagy, but increased BP-3-induced expression of MMP1 and 13, as well as exacerbated BP-3-induced apoptosis, suggesting mitophagy may exert a chondroprotective effect and partially alleviate apoptosis induced by this compound. In brief, BP-3 exposure may increase OA risk via inducing apoptosis and increasing breakdown of extracellular matrix in chondrocytes, and mitochondrial dysfunction and mitophagy may play a crucial role in the mechanisms of BP-3-induced toxicity to articular chondrocytes.

骨关节炎（OA）是一种影响全球数百万成年人的慢性关节疾病，以关节软骨退化为特征。许多环境风险因素都会导致 OA 的发生。个人护理产品中常用的紫外线过滤器二苯甲酮-3（BP-3）与 OA 风险呈正相关。然而，BP-3 是否以及如何对关节软骨细胞产生毒性作用并促进 OA 的发生仍不清楚。本研究旨在探讨环境相关浓度的 BP-3 对人体软骨细胞的损伤，以及 BP-3 与软骨细胞损伤之间的潜在关联机制。值得注意的是，BP-3 能显著抑制 C28/I2 人正常软骨细胞的细胞活力，诱导细胞凋亡，并上调基质金属蛋白酶（MMP）1 和 13，从而介导软骨降解。此外，BP-3 暴露组的线粒体功能受损并出现氧化应激，表现为活性氧（ROS）生成增加、线粒体膜电位降低、ATP 生成减少以及线粒体呼吸链复合物 I、II、III 和 IV 受抑制。同时，BP-3 会导致线粒体嵴模糊和自噬体的形成。PTEN 诱导的推定激酶 1/E3 泛素蛋白连接酶（PINK1/Parkin）通路也被 BP-3 激活。加入自噬抑制剂 3-甲基腺嘌呤（3-MA）可抑制 PINK1/Parkin 介导的有丝分裂，但会增加 BP-3 诱导的 MMP1 和 13 的表达，并加剧 BP-3 诱导的细胞凋亡，这表明有丝分裂可发挥软骨保护作用，并部分缓解该化合物诱导的细胞凋亡。简而言之，暴露于BP-3可能会通过诱导软骨细胞凋亡和增加细胞外基质的破坏而增加OA风险，线粒体功能障碍和有丝分裂可能在BP-3诱导的对关节软骨细胞的毒性机制中起着至关重要的作用。

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引用次数: 0

Relationships between bisphenol A and paraben exposure, oxidative stress, and the activity of outer hair cells in the cochlea in children with hearing loss 听力损失儿童耳蜗中双酚 A 和对羟基苯甲酸酯暴露、氧化应激和外毛细胞活性之间的关系。

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

Ecotoxicology and Environmental Safety

Pub Date : 2024-11-15 DOI: 10.1016/j.ecoenv.2024.117310

Chia-Huang Chang , Chun-Ting Lu , Tai-Ling Chen , Hsin-Chang Chen , Wen-Chi Pan , Chen-Wei Chang , Yu-Chun Chen , Yu-Lin Yu

This study aimed to determine the associations of childhood exposure to bisphenol A (BPA) and parabens (PBs) with oxidative stress and the activity of outer hair cells (OHCs) in the cochlea of children with hearing loss (HL). A total of 641 children were enrolled in this cross-sectional study. Urinary concentrations of BPA and four PBs including methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), and butyl paraben (BP) were quantified by using liquid chromatography–tandem mass spectrometry (LC/MSMS). Four urinary biomarkers of oxidative stress, 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO₂Gua), 4-hydroxynonenal mercapturic acid (HNE-MA), and 8-isoprostaglandin F2α (8-iso-PGF_2α), were measured using high-performance liquid chromatography-electrospray ionization mass spectrometry. Hearing tests were conducted by an audiologist in the audiometric test room, and the results were confirmed by an otolaryngologist. The activity of OHCs in the cochlea was measured by distortion product otoacoustic emissions (DPOAEs). The associations of BPA/PB exposure and oxidative stress with the activity of OHCs at different frequencies were evaluated in the multivariable linear regression models. There were 91 children with HL, for an incidence of approximately 14.2 %. There was a significant negative association between the presence of EP (1.5 K Hz, 3 K Hz) or PP (2 K Hz) or 8-OHdG (1 K Hz, 1.5 K Hz, 2 K Hz) and the activity of OHCs in the left ear. Significant results were also observed for BPA (2 K Hz), MP (1 K Hz, 1.5 K Hz, 2 K Hz), EP (3 K Hz), and 8-OHdG (2 K Hz) in the right ear. This study revealed that exposure to BPA/PBs reduces the activity of OHCs, especially at middle frequencies, in children.

本研究旨在确定儿童时期接触双酚 A（BPA）和对羟基苯甲酸酯（PB）与听力损失（HL）儿童耳蜗中氧化应激和外毛细胞（OHC）活性的关系。共有 641 名儿童参加了这项横断面研究。采用液相色谱-串联质谱法（LC/MS）对尿液中的双酚A和四种对羟基苯甲酸酯（PB）（包括对羟基苯甲酸甲酯（MP）、对羟基苯甲酸乙酯（EP）、对羟基苯甲酸丙酯（PP）和对羟基苯甲酸丁酯（BP））进行了定量分析。使用高效液相色谱-电喷雾质谱法测量了四种尿液氧化应激生物标志物，即 8-羟基-2'-脱氧鸟苷（8-OHdG）、8-硝基鸟嘌呤（8-NO2Gua）、4-羟基壬烯醛巯基酸（HNE-MA）和 8-异前列腺素 F2α（8-iso-PGF2α）。听力测试由听力学家在听力测试室进行，结果由耳鼻喉科医生确认。耳蜗中 OHCs 的活性通过畸变产物耳声发射（DPOAEs）进行测量。在多变量线性回归模型中评估了双酚A/PB暴露和氧化应激与不同频率OHCs活性的关系。共有 91 名儿童患有 HL，发病率约为 14.2%。左耳中 EP（1.5 K Hz、3 K Hz）或 PP（2 K Hz）或 8-OHdG（1 K Hz、1.5 K Hz、2 K Hz）的存在与 OHCs 的活性之间存在明显的负相关。在右耳，双酚 A（2 K Hz）、MP（1 K Hz、1.5 K Hz、2 K Hz）、EP（3 K Hz）和 8-OHdG （2 K Hz）也有显著结果。这项研究表明，暴露于双酚 A/PBs 会降低儿童耳部听觉器官的活性，尤其是在中频。

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引用次数: 0