Toxicology in Vitro最新文献

Role of CD163 in the mechanism of hydrophilic silica nanoparticle-induced pulmonary fibrosis CD163在亲水二氧化硅纳米颗粒诱导肺纤维化机制中的作用。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-05-01 Epub Date: 2026-01-24 DOI: 10.1016/j.tiv.2026.106201

Chaoya Ma, Yaotang Deng, Xiao Zhang, Qifeng Wu, Fengrong Lu, Jin Wu, Ying Zhang, Cuiju Wen

Objective

Silicosis, a progressive pulmonary fibrosis caused by silica dust exposure, remains a global occupational health threat, particularly with the rising use of nano-silica (nano-SiO₂) in industries. This study aims to explore the role of CD163 in pulmonary fibrosis induced by nano-silica (nano-SiO₂), and to evaluate its potential as a diagnostic biomarker by combining clinical analysis of patients with silicosis and in vitro validation models.

Method

Gene expression in BALF from stage I silicosis patients was analyzed by PCR. In vitro, THP-1-derived macrophages and MRC-5 fibroblasts were exposed to 100 μg/mL nano-SiO₂ (LC₅₀) in mono- and co-culture systems. CD163, CD68, and TNF-α levels were quantified via ELISA and Western blot.

Result

In patients, M2 markers (CD163/CD68) were upregulated, while M1 gene (TNF) was downregulated. In vitro, nano-SiO₂ increased macrophage CD163 by 1.7 times (P < 0.05) and decreased TNF-α by 42%. Co-culture further increased CD163 by 2.1 times (P < 0.01), indicating amplified M2 polarization via crosstalk.

Conclusion

Nano-SiO₂ drives M2 polarization (CD163↑/TNF-α↓). This finding suggests that CD163 may become one of the potential biomarkers for assessing the risk of pulmonary fibrosis induced by nano-SiO₂, providing important clues for the early warning and mechanism research of silicosis.

目的：矽肺病是一种由二氧化硅粉尘暴露引起的进行性肺纤维化，仍然是全球职业健康威胁，特别是随着纳米二氧化硅（纳米二氧化硅）在工业中的使用不断增加。本研究旨在通过对矽肺患者的临床分析和体外验证模型，探讨CD163在纳米二氧化硅（nano-SiO₂）诱导的肺纤维化中的作用，并评估其作为诊断性生物标志物的潜力。方法：采用PCR方法对ⅰ期矽肺患者BALF基因表达进行分析。在体外，thp -1来源的巨噬细胞和MRC-5成纤维细胞在单培养和共培养系统中暴露于100 μg/mL纳米sio₂（LC50）中。ELISA和Western blot检测各组小鼠CD163、CD68、TNF-α水平。结果：在患者中，M2标记物（CD163/CD68）上调，M1基因（TNF）下调。在体外，纳米sio₂使巨噬细胞CD163增加1.7倍(P 结论：纳米sio₂驱动M2极化（CD163↑/TNF-α↓）。这一发现提示CD163可能成为评估纳米sio2诱导肺纤维化风险的潜在生物标志物之一，为矽肺早期预警和机制研究提供重要线索。

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引用次数: 0

Barrier gel formulations and coated gloves to reduce skin permeation of nicotine and protect against green tobacco sickness 屏障胶配方和涂层手套，以减少皮肤对尼古丁的渗透，防止绿色烟草病。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2025-12-22 DOI: 10.1016/j.tiv.2025.106192

Abhay U. Andar , Youcheng Liu , Dana C. Hammell , David A. Sterling , Tom Klingner , Mark Tokarski , Mark Boeniger , Audra Stinchcomb

Tobacco harvesting workers may have high levels of skin exposure to nicotine that can lead to green tobacco sickness. Current exposure reduction methods are often infeasible. The purpose of this work was to develop and evaluate the effectiveness of topical barrier gel formulations as a personal protective equipment to reduce nicotine permeation through skin. Four formulations of a barrier gel developed and applied on Yucatan miniature pig skin were tested using a PermeGear flow through in vitro diffusion apparatus. Donor solutions of either L-nicotine or green tobacco leaf extract with and without the use of barrier gel formulations were analyzed over a 24 h exposure period. High pressure liquid chromatography was used to quantify the nicotine content in the receiver compartment. Gloves coated with a barrier gel formulation were also tested. The best barrier gel formulations reduced in vitro skin permeation of nicotine by 97.6 % from L-nicotine, by 64.0 % from green tobacco leaf extract, and by 86.6 % from green tobacco leaf extract for gardening gloves coated with the barrier gel. The barrier gel is effective in reducing skin permeation of nicotine in vitro and might have greater preventive capabilities at environmental exposure levels of nicotine during tobacco harvesting.

烟草采收工人的皮肤可能高度暴露于尼古丁，从而导致绿烟病。目前减少暴露的方法往往是不可行的。这项工作的目的是开发和评估局部屏障凝胶制剂作为个人防护设备的有效性，以减少尼古丁通过皮肤的渗透。开发并应用于尤卡坦微型猪皮肤的四种屏障凝胶配方，使用pergear体外扩散装置进行了测试。在24 h的暴露时间内，对l -尼古丁或绿色烟草叶提取物的供体溶液进行了分析，其中有或没有使用屏障凝胶配方。采用高压液相色谱法定量烟碱含量。涂有屏障凝胶配方的手套也进行了测试。在涂有屏障凝胶的园艺手套中，最佳屏障凝胶配方可使l -尼古丁的体外皮肤渗透率降低97.6% %，使绿烟叶提取物的体外皮肤渗透率降低64.0 %，使绿烟叶提取物的体外皮肤渗透率降低86.6% %。屏障凝胶在体外有效地减少尼古丁的皮肤渗透，并且在烟草收获期间的尼古丁环境暴露水平下可能具有更大的预防能力。

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引用次数: 0

Using a reconstructed human vaginal epithelium model to assess irritation: A proof-of-concept study supporting regulatory qualification of the method for use with personal lubricants 使用重建的人阴道上皮来评估刺激：一项概念验证研究，支持该方法用于个人润滑剂的监管资格。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.tiv.2026.106198

Jessica Perrin , Gertrude-Emilia Costin , Seyoum Ayehunie , Helena Kandárová , Timothy Landry , Jeffrey Brown , Amy J. Clippinger

Consumers tend to think of personal lubricants as personal care products or cosmetics that are not tested using animals, but the regulatory classification and hence the testing requirements for these products vary by country. For example, in the United States, regulations and guidance classify personal lubricants as medical devices, for which manufacturers must perform a rabbit vaginal irritation (RVI) test as part of a typical safety assessment submitted to the Food and Drug Administration (FDA). This publication discusses replacing the RVI with an in vitro reconstructed human vaginal epithelium (RHVE) test method, which uses the EpiVaginal model to assess the irritation potential of personal lubricants. The proof-of-concept studies presented here indicate that this in vitro test method can rank water-based personal lubricants by vaginal irritation potential. Scientific confidence in this test method is evaluated based on an established framework that considers the method's context of use, human biological relevance, technical characterization, data integrity and transparency, and independent review. A proposed workplan aims to further develop and qualify the in vitro test method for regulatory acceptance in assessing vaginal irritation of personal lubricants, and expanding its use to other products.

消费者倾向于认为个人润滑剂是没有使用动物进行测试的个人护理产品或化妆品，但这些产品的监管分类和测试要求因国家而异。例如，在美国，法规和指南将个人润滑剂归类为医疗器械，制造商必须进行兔子阴道刺激（RVI）测试，作为提交给食品和药物管理局的典型安全评估的一部分。本文讨论了用体外重建人阴道上皮（RHVE）测试方法替代RVI，该方法使用外阴部模型来评估个人润滑剂的刺激潜力。这里提出的概念验证研究表明，这种体外测试方法可以根据阴道刺激潜力对水性个人润滑剂进行排名。该测试方法的科学可信度是基于既定框架进行评估的，该框架考虑了该方法的使用背景、人类生物学相关性、技术特征、数据完整性和透明度以及独立审查。一项拟议的工作计划旨在进一步开发和鉴定体外测试方法，以便在评估个人润滑剂对阴道的刺激时获得监管机构的认可，并将其应用于其他产品。

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引用次数: 0

Alternatives to animal testing in cosmetic products: A patent applications review and future perspectives 化妆品动物试验的替代方案：专利申请审查和未来展望。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2025-12-03 DOI: 10.1016/j.tiv.2025.106187

Carine Cassimiro Cedrola, Clara Cassimiro Cedrola, Ana Cláudia Chagas de Paula, Juliana de Carvalho da Costa, Fernanda Maria Pinto Vilela

Ethical concerns, high costs, and scientific limitations associated with animal testing have accelerated the search for alternative methods to evaluate the safety and efficacy of topical cosmetic formulations. This study provides a comprehensive analysis of the global patent landscape related to non-animal testing approaches for skin care products, focusing on filings from January 2015 to March 2025, indexed in the Espacenet database. From 470 patent applications initially screened, 23 met the predefined inclusion and exclusion criteria and were selected for in-depth analysis. Key innovations include 3D epidermal models featuring melanocytes, hair follicles, and sebaceous glands; advanced microfluidic chips, and enzyme-based chemical toxicity assays. Although supported by regulatory frameworks, challenges persist regarding standardization, reproducibility, and the ethical sourcing of human tissue. This patent application review reveals a clear shift toward advanced 3D models and organ-on-a-chip technologies that better replicate the complexity of human skin physiology. The trends observed indicate that alternative methods to animal testing are not only an ethical necessity but are also becoming a technological reality, offering more predictive, reliable, and efficient strategies for safety assessment.

与动物试验相关的伦理问题、高成本和科学限制加速了对替代方法的探索，以评估局部化妆品配方的安全性和有效性。本研究对全球护肤品非动物试验方法专利格局进行了全面分析，重点关注2015年1月至2025年3月的申请，并在Espacenet数据库中检索。从最初筛选的470项专利申请中，有23项符合预定义的纳入和排除标准，并被选中进行深入分析。主要创新包括以黑色素细胞、毛囊和皮脂腺为特征的3D表皮模型；先进的微流控芯片，以及基于酶的化学毒性分析。尽管得到了监管框架的支持，但在人体组织的标准化、可重复性和道德来源方面仍然存在挑战。这项专利申请审查揭示了向先进的3D模型和器官芯片技术的明显转变，这些技术可以更好地复制人类皮肤生理学的复杂性。观察到的趋势表明，动物试验的替代方法不仅在伦理上是必要的，而且正在成为一种技术现实，为安全性评估提供更有预测性、更可靠和更有效的策略。

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引用次数: 0

Interactions of neocryptotanshinone and human cytochrome P450 in silico and in vitro 新隐丹参酮与人细胞色素P450的相互作用。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2025-12-17 DOI: 10.1016/j.tiv.2025.106191

Xiu Chen , Xiaoyi Pan , Jieping Zhao , Huihui Jin , Hengbin Zhang , Yongbiao Song , Hui Zhou , Jianbiao Yao , Huidi Jiang

Neocryptotanshinone (NCTS), an ingredient of Salviae Miltiorrhizae Radix et Rhizoma, is a promising compound for development since it exhibits various pharmacological effects including hypoglycemic and anti-inflammatory activities. In this study, we aimed to elucidate the interactions between NCTS and cytochrome P450s (CYPs), including the CYP-mediated NCTS metabolism and NCTS-induced CYP regulation. The results revealed that NCTS was mainly metabolized by CYPs in human liver microsomes (HLMs), and CYP2C8 and 2C9 were identified as the main CYPs involved; the relative contributions of CYP2C8 and 2C9 were 35 % and 65 %, respectively, after normalization of individual CYP abundance in the human liver. Meanwhile, NCTS weakly inhibited CYP1A2, 2C8, and 2C9, with IC₅₀ > 30 μM. In addition, NCTS induced CYP2B6 and CYP3A4 expression in human primary hepatocytes, and the underlying mechanism was found by the activation of the pregnane X receptor (PXR) vis reporter gene assay. Molecular docking of NCTS and CYPs, PXR confirmed these results. Our study sheds light on the interactions of NCTS with CYPs and provides useful information for predicting potential drug-drug interactions for NCTS, which will be helpful for NCTS development and clinical utilization of drugs containing NCTS.

新crypto丹参酮（NCTS）是丹参的一种成分，具有降血糖、抗炎等多种药理作用，是一种很有开发前景的化合物。在本研究中，我们旨在阐明NCTS与细胞色素p450 （CYPs）之间的相互作用，包括CYPs介导的NCTS代谢和NCTS诱导的CYP调控。结果表明，NCTS主要被人肝微粒体（HLMs）中的CYPs代谢，其中CYP2C8和2C9是主要参与代谢的CYPs；在人肝脏个体CYP丰度归一化后，CYP2C8和2C9的相对贡献分别为35 %和65 %。NCTS对CYP1A2、2C8、2C9的抑制作用较弱，IC50 > 30 μM。此外，NCTS在人原代肝细胞中诱导CYP2B6和CYP3A4的表达，并通过激活妊娠X受体（PXR）报告基因实验发现其潜在机制。NCTS与CYPs的分子对接，PXR证实了这些结果。本研究揭示了NCTS与CYPs的相互作用，为预测NCTS的潜在药物相互作用提供了有用的信息，这将有助于NCTS的开发和含NCTS药物的临床应用。

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引用次数: 0

Effects of cyanobacterial metabolites and their mixtures on biomarkers of oxidative stress in RTgill-W1 cells 蓝藻代谢产物及其混合物对RTgill-W1细胞氧化应激生物标志物的影响

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tiv.2026.106195

Adam Bownik, Barbara Pawlik-Skowrońska

The aim of our investigation was to determine the effects of seven cyanobacterial metabolites microcystin-LR (MC-LR), anabaenopeptin-A (ANA-A), cylindrospermopsin (CYL), anabaenopeptin-B (ANA-B) aeruginosin 98 A (AER-A), aeruginosin 98B (AER-B), microginin-FR1 (MG-FR1) and their mixtures on common indicators of oxidative stress in RTgill-W1cells. The cells were exposed to the metabolites at various concentrations and the following parameters were determined after 48 h: catalase (CAT) activity, lipid peroxidation (LPO), total nitric oxide (NO) level and superoxide (SOD) dismutase activity. Data were analyzed with the use of one-way ANOVA (N = 3) and Dunnett's test. We found that all single tested metabolites increased but CYL decreased CAT activity. Mixtures had stimulatory effect, however antagonistic interactions were found in the binary and ternary mixtures. No lipid peroxidation occurred in the cells exposed to any of the tested variant. Only AER-A increased NO level, however the rest of both single metabolites at highest concentrations (1004 nM) and mixtures reduced the level of this parameter. Only ANA-B inhibited SOD activity at the highest concentration, however no alterations were found in the cells exposed to binary or ternary mixtures. The study showed that cyanobacterial metabolites may induce oxidative stress in fish gill cells, however effects are dependent on type of a metabolite and concentration of a component in mixtures. On the basis of antagonistic interactions in ternary mixture it may be hypothesized that during natural exposure components of mixtures may reciprocally mitigate their effects.

本研究旨在探讨7种蓝藻代谢产物微囊藻毒素- lr （MC-LR）、鸭绿霉素-A （ANA-A）、柱状精子素（CYL）、鸭绿霉素- b （ANA-B）、绿脓杆菌蛋白98 A （AER-A）、绿脓杆菌蛋白98B （AER-B）、微球蛋白- fr1 （MG-FR1）及其混合物对rtgill - w1细胞氧化应激指标的影响。将细胞暴露于不同浓度的代谢物中，48 h后测定过氧化氢酶（CAT）活性、脂质过氧化（LPO）、总一氧化氮（NO）水平和超氧化物歧化酶（SOD）活性。数据分析采用单因素方差分析（N = 3）和Dunnett检验。我们发现所有单一测试的代谢物都增加了，但CYL降低了CAT活性。混合物具有刺激作用，但在二元和三元混合物中发现拮抗相互作用。暴露于任何测试变体的细胞中均未发生脂质过氧化。只有AER-A增加了NO水平，而最高浓度（1004 nM）和混合浓度下的其他单代谢物均降低了该参数的水平。只有ANA-B在最高浓度下抑制SOD活性，但在二元或三元混合物中未发现任何变化。研究表明，蓝藻代谢物可能诱导鱼鳃细胞氧化应激，但影响取决于代谢物的类型和混合物中成分的浓度。根据三元混合物中的拮抗相互作用，可以假设在自然暴露期间，混合物的组分可以相互减轻其作用。

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引用次数: 0

Cisplatin adducts at DNA or RNA do not affect their cellular isolation efficiencies using column-based kits or manual Trizol-based purification methods DNA或RNA上的顺铂加合物使用柱基试剂盒或手动trizol基纯化方法不影响其细胞分离效率。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2025-12-06 DOI: 10.1016/j.tiv.2025.106188

Ketaki Sandu, Dirk Theile

In experimental toxicology, evaluating cisplatin adducts at DNA or RNA is often required but can be complicated by methodological aspects. For instance, the cross-linking might affect the nucleic acid isolation efficiencies, which in turn can be influenced by the purification approach. Two cancer cell lines were cisplatin treated and DNA/RNA were isolated using manual Trizol-based protocols or column-based kits. Platinum levels at DNA/RNA were evaluated by atomic absorption spectroscopy.

For RNA, the manual purification yielded higher concentrations than the kit for both cisplatin-treated and non-treated samples. RNA platination was identical for both isolation approaches. For DNA, the manual method can yield lower concentrations from cisplatin-treated cells, likely reflecting diminished solubility of cross-linked DNA. DNA platination levels again were identical with both isolation methods.

Because DNA isolation is less efficient than RNA isolation, platinum-DNA adduct quantification is difficult when DNA yields are low or cells were exposed to low cisplatin concentrations. However, DNA platination can be estimated by the platination degree of RNA because platination of both nucleic acids agreed well and RNA was always isolated very efficiently.

In summary: First, manual purification and column-based kits can yield unequal nucleic acid concentrations, and RNA is more efficiently purified than DNA. Second, column-based kits remain practical because platination does not affect isolation efficiency. Third, when DNA platination is not quantifiable (low yield, small sample volumes), RNA platination is a good proxy.

在实验毒理学中，通常需要评估DNA或RNA上的顺铂加合物，但可能因方法学方面而复杂化。例如，交联可能会影响核酸分离效率，而核酸分离效率又会受到纯化方法的影响。顺铂处理两种癌细胞系，使用手动trizol协议或柱基试剂盒分离DNA/RNA。用原子吸收光谱法测定DNA/RNA中的铂含量。对于RNA，无论是顺铂处理的样本还是未处理的样本，人工纯化的RNA浓度都高于试剂盒。两种分离方法的RNA镀化是相同的。对于DNA，手工方法可以从顺铂处理的细胞中产生较低的浓度，可能反映了交联DNA的溶解度降低。DNA铂化水平再次与两种分离方法相同。由于DNA分离比RNA分离效率低，当DNA产量低或细胞暴露于低顺铂浓度时，铂-DNA加合物的定量是困难的。而DNA的铂化程度可以通过RNA的铂化程度来判断，因为两种核酸的铂化程度一致，RNA的分离效率很高。综上所述：首先，人工纯化和柱式试剂盒可能产生不相等的核酸浓度，RNA的纯化效率高于DNA。其次，基于柱的试剂盒仍然是实用的，因为镀化不会影响分离效率。第三，当DNA铂化无法量化（产量低、样品体积小）时，RNA铂化是一个很好的替代方法。

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引用次数: 0

Quercetin mitigates pro-inflammatory effects of polyvinylpyrrolidone-coated silver nanoparticles on human intestinal epithelial cells 槲皮素减轻聚乙烯吡咯烷酮包被银纳米颗粒对人肠上皮细胞的促炎作用。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2025-11-22 DOI: 10.1016/j.tiv.2025.106176

Adelaide Sousa , Inês Santos , Rui Fernandes , Sofia Pacheco , Félix Carvalho , Eduarda Fernandes , Marisa Freitas

Extended oral intake of silver nanoparticles (AgNP) may result in significant exposure of intestinal cells, which could trigger intestinal inflammation, an effect that requires deep comprehension and the development of mitigation measures. This study aimed to investigate the potential pro-inflammatory effects of polyvinylpyrrolidone (PVP)-coated AgNP with two different sizes (5 and 50 nm) on human intestinal epithelial C2BBe1 cells, as well as the potential mitigation effects of quercetin, a flavonoid with acknowledged antioxidant and anti-inflammatory potential. The pro-inflammatory effects of PVP-AgNP on several proteins related to the intestinal inflammatory response, as well as on ^●NO production and cytokine production, were investigated. PVP-AgNP exposure caused cellular stress and damage, as evidenced by a reduction in cellular metabolic activity, ultrastructural changes, and loss of viability. The present study also found that 5 nm PVP-AgNP triggered inflammation through the p65-induced NF-κB pathway and reduced p-Nrf2 expression, while 50 nm PVP-AgNP activated the IκBα-induced NF-κB pathway and elevated COX-2 levels. Both sizes induced an increase of PGE₂ levels and IL-8 production, with only 5 nm PVP-AgNP increasing IL-6. The harmful effects of PVP-AgNP were effectively mitigated by quercetin, which highlights the potential of this flavonoid to modulate the respective potential damage at the intestinal level.

长期口服银纳米颗粒（AgNP）可能导致肠细胞大量暴露，从而引发肠道炎症，这一影响需要深入了解并制定缓解措施。本研究旨在探讨聚乙烯吡咯烷酮（PVP）包被两种不同尺寸（5和50 nm）的AgNP对肠上皮C2BBe1细胞的潜在促炎作用，以及槲皮素（一种公认具有抗氧化和抗炎潜力的类黄酮）的潜在缓解作用。研究了PVP-AgNP对肠道炎症反应相关蛋白的促炎作用，以及对NO生成和细胞因子生成的影响。PVP-AgNP暴露导致细胞应激和损伤，如细胞代谢活性降低、超微结构改变和活力丧失。本研究还发现，5 nm的PVP-AgNP通过p65诱导的NF-κB通路引发炎症，降低p-Nrf2的表达，而50 nm的PVP-AgNP激活i -κB α-诱导的NF-κB通路，升高COX-2水平。两种大小的PVP-AgNP均能增加PGE2水平和IL-8的产生，只有50 nm的PVP-AgNP能增加IL-6。槲皮素有效地减轻了PVP-AgNP的有害作用，这突出了这种类黄酮在肠道水平上调节各自潜在损伤的潜力。

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引用次数: 0

Dual effects of metformin and resveratrol on compromising viability of endometrial cancer cells 二甲双胍和白藜芦醇对子宫内膜癌细胞生存能力的双重影响

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tiv.2026.106194

Henrique Leal de Oliveira , Sara Hartke , Victória Borgmann A. de Souza , Carolina Vaccari Batista , Gabriela Pasqualim , Vânia Marisia Santos Fortes dos Reis , Edison Capp , Leo Anderson Meira Martins , Ilma Simoni Brum

Raising of mitogenic and anti-apoptotic agents – such as insulin, insulin-like growth factor type 1, and estrogen – during obesity and diabetes mellitus (types 1 and 2) favors the endometrial cancer (EC) development. Metformin, commonly used for treating type 2 diabetes, and resveratrol, a natural polyphenol, can both decrease cancer cell proliferation by modulating the PI3K/Akt/mTOR pathway. We evaluate the effects of metformin and/or resveratrol in an in vitro model of human type 1 endometrioid EC. Ishikawa cells were treated with 0.1 to 50 mM of metformin and/or 0.1 to 75 μM of resveratrol from 24 h to 72 h. Analyses assessed cell viability, cytotoxicity, caspases activation, mitochondrial function, cellular death, cell cycle, and the PI3K/Akt/mTOR pathway gene expression. In-silico analysis was conducted using Cytoscape. Metformin induced mitochondrial swelling, caspase-mediated apoptosis, and cell cycle arrest. Resveratrol decreased mitochondrial mass, cytotoxicity, and induced cell cycle arrest. Combined treatment with the highest concentrations reduced mitochondrial activity, cytotoxicity, and caspase activation while maintaining apoptotic features and cell cycle arrest. Resveratrol attenuated the toxic effects of metformin but it could be inducing a caspase-independent cell death in co-treated cells. Although in-silico analysis suggested potential molecular targets and interconnected mechanisms, lower concentrations did not alter PI3K/Akt/mTOR gene expression.

在肥胖和糖尿病（1型和2型）期间，有丝分裂和抗凋亡因子如胰岛素、胰岛素样生长因子1型和雌激素的升高有利于子宫内膜癌（EC）的发展。通常用于治疗2型糖尿病的二甲双胍和天然多酚白藜芦醇都可以通过调节PI3K/Akt/mTOR通路来抑制癌细胞增殖。我们评估二甲双胍和/或白藜芦醇对人类1型子宫内膜样EC体外模型的影响。石川细胞用0.1至50 mM的二甲双胍和/或0.1至75 μM的白藜芦醇处理24至72小时。分析评估细胞活力、细胞毒性、半胱天冬酶激活、线粒体功能、细胞死亡、细胞周期和PI3K/Akt/mTOR通路基因表达。使用Cytoscape进行了硅内分析。二甲双胍诱导线粒体肿胀、caspase介导的细胞凋亡和细胞周期阻滞。白藜芦醇减少线粒体质量、细胞毒性和诱导细胞周期阻滞。最高浓度的联合治疗降低了线粒体活性、细胞毒性和半胱天冬酶活性，同时维持了凋亡特征和细胞周期停滞。白藜芦醇减轻了二甲双胍的毒性作用，但它可能在共处理的细胞中诱导caspase非依赖性细胞死亡。尽管计算机分析提示了潜在的分子靶点和相互关联的机制，但较低的浓度并未改变PI3K/Akt/mTOR基因的表达。

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引用次数: 0

Diesel exhaust nanoparticles: Cellular adaptation in lung epithelial and fibroblast cells – An in vitro study 柴油废气纳米颗粒：肺上皮细胞和成纤维细胞的细胞适应性-体外研究。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2026-04-01 Epub Date: 2026-01-03 DOI: 10.1016/j.tiv.2026.106193

Gabriel Martínez-Razo , Ruth Angélica Lezama , Armando Vega-López , María Lilia Domínguez-López

Diesel exhaust particles (DEnP) represent a major urban air pollutant with known adverse effects on human health, yet detailed cellular interactions at the nanoscale are poorly understood. This study aims to elucidate the cellular responses and adaptation mechanisms of human lung epithelial and fibroblast-like cell lines exposed to Mexican diesel exhaust nanoparticles. Exhaust samples from cold and warm engine emissions were analyzed for polyaromatic hydrocarbons, organic matter, and elemental composition using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Additionally, the DEnP nanostructure was scrutinized using 3D topographical image analysis. In vitro assays assessed cell proliferation, adhesion molecule expression (ICAM-1, VCAM-1), and proteins related to endocytosis (clathrin and dynamin) in response to DEnP exposure. SEM and TEM analyses revealed distinct nanoparticle forms and compositions, with significant increases in cell proliferation, endocytosis, and adhesion molecule expression observed, suggesting robust cellular adaptation mechanisms to counteract DEnP-induced stress. The study confirms significant cellular adaptations in response to DEnP, underscoring the need for preventive strategies to mitigate the impacts of exposure. These findings provide a foundation for further investigation into long-term cellular adaptations and their implications for pulmonary health.

柴油废气颗粒（DEnP）是一种主要的城市空气污染物，已知对人类健康有不利影响，但在纳米尺度上详细的细胞相互作用知之甚少。本研究旨在阐明墨西哥柴油机尾气纳米颗粒对人肺上皮细胞和成纤维细胞样细胞系的细胞反应和适应机制。利用扫描电子显微镜（SEM）和透射电子显微镜（TEM）对冷热发动机排放的废气样品进行了多芳烃、有机物和元素组成的分析。此外，使用三维地形图像分析仔细检查了DEnP纳米结构。体外实验评估了DEnP暴露后的细胞增殖、粘附分子表达（ICAM-1、VCAM-1）和与内吞作用相关的蛋白质（网格蛋白和动力蛋白）。扫描电镜和透射电镜分析揭示了不同的纳米颗粒形式和组成，观察到细胞增殖、内吞作用和粘附分子表达显著增加，表明细胞适应机制可以抵抗denp诱导的应激。该研究证实了对DEnP的显著细胞适应，强调了采取预防策略以减轻暴露影响的必要性。这些发现为进一步研究长期细胞适应及其对肺部健康的影响提供了基础。

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