Toxicology in Vitro最新文献_第9页

Dihydrotanshinone I induces necroptosis and cell cycle arrest in gastric cancer through the PTPN11/p38 pathway 二氢丹参酮 I 通过 PTPN11/p38 通路诱导胃癌坏死和细胞周期停滞

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-19 DOI: 10.1016/j.tiv.2024.105955

Aizhen Li, Mingjin Yang, Wenbiao Duan, Bo Wu

{"title":"Dihydrotanshinone I induces necroptosis and cell cycle arrest in gastric cancer through the PTPN11/p38 pathway","authors":"Aizhen Li, Mingjin Yang, Wenbiao Duan, Bo Wu","doi":"10.1016/j.tiv.2024.105955","DOIUrl":"10.1016/j.tiv.2024.105955","url":null,"abstract":"<div><div>In this study, MTT assays, apoptosis detection, immunofluorescence, and functional studies were used to elucidate the mechanisms underlying the effects of dihydrotanshinone I (DHT) on gastric cancer cells. Drug target prediction and analysis were conducted to identify potential targets of DHT. MTT assay revealed significant inhibition of AGS and HGC27 cells by DHT. Morphological changes, including nuclear shrinkage and the induction of necrotic cell death, were observed in DHT-treated gastric cancer cells, along with cell cycle arrest at the G2/M phase. Further analysis revealed potential targets of DHT, including PTPN11, which is highly expressed in gastric cancer cells. DHT treatment increased necrosis-related proteins (RIPK1/RIPK3/MLKL) and downregulated cell cycle-related proteins (CDC25C and CDK1) levels in gastric cancer cells. After DHT treatment, PTPN11 protein expression decreased. Furthermore, DHT significantly increased the phosphorylated p38/JNK protein level, with the phosphorylated p38 protein notably enriched in the nucleus. These functional studies indicate that PTPN11 plays a key role in mediating the effects of DHT, including cell cycle regulation and necrosis induction. In conclusion, PTPN11 is a central target through which DHT affects gastric cancer cells, regulating downstream pathways involved in necroptosis (p38/RIPK1/RIPK3/MLKL/JNK) and cell cycle arrest (p38/CDC25C/CDK1).</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105955"},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the potential of reconstructed human epithelial tissue models for safety assessment of intraoral medical devices 探索重建人体上皮组织模型在口腔内医疗器械安全评估中的潜力。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-19 DOI: 10.1016/j.tiv.2024.105956

Peter Pôbiš , Tatiana Milasová , Helena Kandárová

{"title":"Exploring the potential of reconstructed human epithelial tissue models for safety assessment of intraoral medical devices","authors":"Peter Pôbiš , Tatiana Milasová , Helena Kandárová","doi":"10.1016/j.tiv.2024.105956","DOIUrl":"10.1016/j.tiv.2024.105956","url":null,"abstract":"<div><div>Medical devices are integral to a wide array of medical interventions and are increasingly utilized in both clinical and home settings. Within the oral cavity, intraoral medical devices are employed for various applications, to improve quality of life and maintain oral health and hygiene. However, the dynamic and complex environment of the oral cavity, characterized by the influence of factors, such as saliva composition, fluctuating pH, and microbial flora presents a challenge to ensure the safety of end-users.</div><div>In this paper, we investigate the feasibility of utilization of 3D reconstructed human tissue models for the assessment of biocompatibility of intraoral medical devices. Building upon experiences drawn from the development and validation of ISO 10993-23 and from the development of a protocol for ocular irritation and photo-irritation, we suggest a new protocol for buccal mucosa irritation testing. The methodology is based on the viability assessment and analysis of cytokine release into media. By addressing intraoral medical devices biocompatibility testing, we aim to contribute to the advancement of biocompatibility assessment methodologies and increase the applicability of ISO 10993-23.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 105956"},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Go with the flow: An in vitro model of a mature endothelium for the study of the bioresponse of IV injectable nanomedicines 顺其自然：用于研究静脉注射纳米药物生物反应的成熟内皮体外模型

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-12 DOI: 10.1016/j.tiv.2024.105953

Niusha Nikravesh , Alexandra Rippl , Tobias Hoch , Stephanie Eitner , Amy Barton Alston , Reinaldo Digigow , Savvina Chortarea , Liliane Diener , Vanesa Ayala-Nunez , Peter Wick

{"title":"Go with the flow: An in vitro model of a mature endothelium for the study of the bioresponse of IV injectable nanomedicines","authors":"Niusha Nikravesh , Alexandra Rippl , Tobias Hoch , Stephanie Eitner , Amy Barton Alston , Reinaldo Digigow , Savvina Chortarea , Liliane Diener , Vanesa Ayala-Nunez , Peter Wick","doi":"10.1016/j.tiv.2024.105953","DOIUrl":"10.1016/j.tiv.2024.105953","url":null,"abstract":"<div><div>The first exposure of intravenously (IV) administered nanomedicines <em>in vivo</em> is to endothelial cells (ECs) lining blood vessels. While it is known that <em>in vitro</em> endothelium models to assess responses to circulating nanoparticles require shear stress, there is no consensus on when and how to include it in the experimental design. Our experimental workflow integrates shear stress by featuring a flow-induced mature endothelium (14 days) and a flow-mediated nanoparticle treatment. The mature endothelium model exhibited distinct features that indicated a structurally stable and quiescent monolayer. Upon treatment with iron sucrose under dynamic conditions, there was a lower nanoparticle uptake, lower cytotoxicity, and decreased expression of activation markers compared to the static control. This response was attributed to glycocalyx expression, predominantly observed on the mature endothelium. In conclusion, our proposed <em>in vitro</em> endothelium model can be leveraged to understand the dynamics of IV injectable nanomedicines at the initial nano-bio interface in veins immediately post-injection.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105953"},"PeriodicalIF":2.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NDMA enhances claudin-1 and -6 expression viaCYP2E1/ROS in AGS cells NDMA 通过 CYP2E1/ROS 增强 AGS 细胞中 claudin-1 和 -6 的表达。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-10 DOI: 10.1016/j.tiv.2024.105952

Carlos Abraham García-García , Alfredo Cruz-Gregorio , José Pedraza-Chaverri , Luis F. Montaño , Erika P. Rendón-Huerta

{"title":"NDMA enhances claudin-1 and -6 expression viaCYP2E1/ROS in AGS cells","authors":"Carlos Abraham García-García , Alfredo Cruz-Gregorio , José Pedraza-Chaverri , Luis F. Montaño , Erika P. Rendón-Huerta","doi":"10.1016/j.tiv.2024.105952","DOIUrl":"10.1016/j.tiv.2024.105952","url":null,"abstract":"<div><div>Carcinogenic N-nitroso compounds, especially N-nitroso dimethylamine, increase the risk of gastric cancer development. Cytochrome P450-2E1 metabolizes this compound, thus generating an oxidant microenvironment. We aimed to evaluate in gastric adenocarcinoma cells if its effect on CYP2E1 and ROS affects signaling pathways associated with gastric cancer oncogenesis. The impact of N- nitroso dimethylamine upon CYP2E1 and ROS activation/secretion was evaluated by the DCFDA assay protocol, TER measurements, Stat3, pSTAT3, ERK1/2, and pERK1/2 expression, claudins-1 and -6 expression, and finally mRNA values of IL-1β IL-6, IL-8 and TNFα. Our results showed that exposure to N- N-nitroso dimethylamine disrupts the regulation of Stat3 and Erk1/2, alters the expression of claudin-1 and claudin-6 tight junction proteins, and increases the secretion of pro-inflammatory cytokines. These alterations induce a continuous local inflammatory process, an event identified as a gastric cancer promoter. In summary, N-nitroso dimethylamine can disrupt cell mechanisms associated with gastric cancer oncogenesis.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105952"},"PeriodicalIF":2.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of curcumin on the embryotoxic effect of ethanol in a zebrafish model 姜黄素对斑马鱼模型中乙醇胚胎毒性效应的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-09 DOI: 10.1016/j.tiv.2024.105951

Anna Małkowska , Katerina Makarowa , Katarzyna Zawada , Maksymilian Grzelak , Aleksandra Zmysłowska

{"title":"Effect of curcumin on the embryotoxic effect of ethanol in a zebrafish model","authors":"Anna Małkowska , Katerina Makarowa , Katarzyna Zawada , Maksymilian Grzelak , Aleksandra Zmysłowska","doi":"10.1016/j.tiv.2024.105951","DOIUrl":"10.1016/j.tiv.2024.105951","url":null,"abstract":"<div><div>Curcumin, a natural polyphenol found in the turmeric plant, has been shown to have anti-inflammatory and antioxidant properties. It has been widely studied for its potential protective effect against various health conditions, including ethanol-induced malformation.</div><div>Ethanol exposure during pregnancy can lead to various developmental abnormalities, known as fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD). Due to the high prevalence of FASD and FAS and no effective treatment, it is essential to develop preventive strategies. Recent studies have investigated the potential protective effect of curcumin against ethanol-induced malformation in animal models.</div><div>This study aimed to examine whether curcumin can reduce the toxic effects of ethanol in zebrafish embryos. The present study showed that pure curcumin applied together with 1.5 % ethanol (<em>v</em>/v) did not lead to a protective effect on ethanol-induced malformations such as disturbances of body length and width or pericardia oedema in growing zebrafish embryos. Moreover, curcumin extract showed a pro-oxidant effect in the Fenton reaction in the presence of ethanol.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105951"},"PeriodicalIF":2.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation 丹参酮 IIA 在减轻 HMGB1 或 TNF-α 介导的微神经胶质细胞活化引起的神经元损伤方面的干预机制

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-30 DOI: 10.1016/j.tiv.2024.105950

Yan-Zhu Quan , Jing-He Wang , Si-Hui Zhang , Guang-Nan Jin , Jing-Mei Lu , Yi-Ming Liu , Hong-Yan Gao , Jin-Yi Zhou , Bing-Zhe Wang , Yan Xin , Yue-Xian Cui , Xiang Xu , Lian-Xun Piao

{"title":"The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation","authors":"Yan-Zhu Quan , Jing-He Wang , Si-Hui Zhang , Guang-Nan Jin , Jing-Mei Lu , Yi-Ming Liu , Hong-Yan Gao , Jin-Yi Zhou , Bing-Zhe Wang , Yan Xin , Yue-Xian Cui , Xiang Xu , Lian-Xun Piao","doi":"10.1016/j.tiv.2024.105950","DOIUrl":"10.1016/j.tiv.2024.105950","url":null,"abstract":"<div><div>Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from <em>Salvia miltiorrhiza</em>, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105950"},"PeriodicalIF":2.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A high throughput screening assay for human Thyroperoxidase inhibitors 人甲状腺过氧化物酶抑制剂的高通量筛选试验。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-28 DOI: 10.1016/j.tiv.2024.105946

Hongyan Dong , Katie Paul Friedman , Alain Filiatreault , Errol M. Thomson , Michael G. Wade

{"title":"A high throughput screening assay for human Thyroperoxidase inhibitors","authors":"Hongyan Dong , Katie Paul Friedman , Alain Filiatreault , Errol M. Thomson , Michael G. Wade","doi":"10.1016/j.tiv.2024.105946","DOIUrl":"10.1016/j.tiv.2024.105946","url":null,"abstract":"<div><div>Rapid, human relevant assays are needed to assess potential hazards of the many chemicals in commerce. An assay of thyroid peroxidase (TPO) inhibition, using the substrate Amplex Ultra Red, was recently adapted for human TPO (AUR-hTPO). We tested a large number (788) of chemicals through this AUR-hTPO assay and compared performance with published results from an assay using enzyme from rat thyroid microsomes (AUR-rTPO). Coded chemicals, from the US EPA ToxCast Inventory, were tested in a tiered approach: 1) Initial screening at a single concentration; 2) Potency estimation for active chemicals with multiple concentrations; 3) Screening active chemicals for the non-specific activity. The assay gave consistent results for positive chemical methimazole and several positive and negative reference chemicals. hTPO inhibition was observed for 190 chemicals reported as positive in rTPO. Of these, 158 showed no confounding activity (interference due to fluorescence or non-specific protein inhibition). Comparison of all result with rTPO data and with evidence of TPO inhibition found in the literature suggest that the current assay has a higher rate of false negative but a much lower rate of false positive compared with the rTPO screen. These findings underscore the effectiveness of the AUR assay, using hTPO enzyme from engineered cell lines, to identify moderate to strong inhibitors but some improvements may be needed to detect weak TPO inhibitors.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105946"},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intragenic antimicrobial peptide Hs02 toxicity against leukemia cell lines is associated with increased expression of select pyroptotic components 基因内抗菌肽 Hs02 对白血病细胞株的毒性与特定热解成分的表达增加有关。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-27 DOI: 10.1016/j.tiv.2024.105945

Isabella de Souza Mota , Miguel Cardoso , João Bueno , Ingrid Gracielle Martins da Silva , João Gonçalves , Sonia N. Bao , Brenno A.D. Neto , Guilherme Brand , José Raimundo Corrêa , José Roberto S.A. Leite , Felipe Saldanha-Araujo

{"title":"Intragenic antimicrobial peptide Hs02 toxicity against leukemia cell lines is associated with increased expression of select pyroptotic components","authors":"Isabella de Souza Mota , Miguel Cardoso , João Bueno , Ingrid Gracielle Martins da Silva , João Gonçalves , Sonia N. Bao , Brenno A.D. Neto , Guilherme Brand , José Raimundo Corrêa , José Roberto S.A. Leite , Felipe Saldanha-Araujo","doi":"10.1016/j.tiv.2024.105945","DOIUrl":"10.1016/j.tiv.2024.105945","url":null,"abstract":"<div><div>The anticancer potential of some antimicrobial peptides has been reported. Hs02 is a recently characterized Intragenic Antimicrobial Peptide (IAP), which was able to exhibit potent antimicrobial and anti-inflammatory action. In this study, we evaluate for the first time the antineoplastic potential of the Hs02 IAP using cell lines representing the main types of leukemia as cancer models. Interestingly, this peptide decreased the viability of several leukemic cell lines, without compromising the viability of PBMCs in the same concentration. In the HL-60 line, treatment with Hs02 controlled cell division, leading to cell arrest in the G1 phase of the cell cycle. More importantly, HL-60 cells treated with Hs02 undergo cell death, with the formation of pores in the plasma membrane and the release of LDH. Accordingly, Hs02 treatment stimulated the expression of components involved in pyroptosis, such as <em>NLRP1</em>, <em>CASP-1</em>, <em>GSDME</em>, and <em>IL-1β</em>. Taken together, our data characterize the antineoplastic potential of Hs02 and open an opportunity for both evaluating the peptide's antineoplastic potential in other cancer models and using this molecule as a template for new peptides with therapeutic potential against cancer.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105945"},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intradermal and transdermal absorption of beta-naphthylamine and N-Phenyl-beta-naphthylamine in a viable human skin model 活体人体皮肤模型对 beta-萘胺和 n-苯基-beta-萘胺的皮内吸收和透皮吸收。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-27 DOI: 10.1016/j.tiv.2024.105947

Suvarna Mini Vijayan , Moritz Baierl , Thomas Göen , Raymund E. Horch , Ingo Ludolph , Hans Drexler , Sonja Kilo

{"title":"Intradermal and transdermal absorption of beta-naphthylamine and N-Phenyl-beta-naphthylamine in a viable human skin model","authors":"Suvarna Mini Vijayan , Moritz Baierl , Thomas Göen , Raymund E. Horch , Ingo Ludolph , Hans Drexler , Sonja Kilo","doi":"10.1016/j.tiv.2024.105947","DOIUrl":"10.1016/j.tiv.2024.105947","url":null,"abstract":"<div><div>Technical products containing N-Phenyl-beta-naphthylamine (PBNA) are contaminated with beta-naphthylamine (BNA), a known carcinogen. Both amines penetrate the skin to different degrees, but little is known about their dermal-depot formation. This study investigated the dermal penetration of PBNA and its degradation product BNA using a viable human-skin model. PBNA (259 μg) or BNA (0.52 μg) in <em>n</em>-hexane and industrial grease were applied to freshly excised human skin (<em>n</em> = 6, 0.64 cm<sup>2</sup>) for 2-72 h. After temporary/continuous and single/repeated exposure, samples were taken (stratum corneum, epidermis/dermis, receptor fluid) and analyzed for their amine content by GC–MS. Continuous exposure led to a PBNA dermal depot of ∼47 μg/cm<sup>2</sup> over 72 h. Temporary applications also resulted in lower but consistent PBNA dermal depots. A single 2-h application resulted in a dermal depot of ∼16 μg/cm<sup>2</sup> after 72 h, while this was ∼25 μg/0.64 cm<sup>2</sup> with repeated applications. BNA behaved differently; with repeated 2-h applications, intradermally retained BNA initially increased 3–6 fold, then dropped to ∼200–250 ng/cm<sup>2</sup>. This incomplete decline upon repeated short-term exposure to PBNA suggests that a BNA dermal depot is formed either due to contamination of PBNA with BNA or to enzymatic conversion of PBNA to BNA. Additionally, PBNA dermal depots were saturable under the given conditions. These findings highlight the importance of understanding the dermal-exposure dynamics of potential carcinogenic compounds in industrial settings.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105947"},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cigarette smoke extract decreases human bone marrow mesenchymal stromal cell adipogenic differentiation 香烟烟雾提取物会降低人骨髓间充质基质细胞的成脂分化。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-09-27 DOI: 10.1016/j.tiv.2024.105949

Janne Heikkinen , Sanna Palosaari , Petri Lehenkari

{"title":"Cigarette smoke extract decreases human bone marrow mesenchymal stromal cell adipogenic differentiation","authors":"Janne Heikkinen , Sanna Palosaari , Petri Lehenkari","doi":"10.1016/j.tiv.2024.105949","DOIUrl":"10.1016/j.tiv.2024.105949","url":null,"abstract":"<div><h3>Background</h3><div>Smoking and nicotine impose detrimental health effects including adipose tissue dysfunction. Despite extensive physiological evidence, the cellular mechanisms remain poorly understood, with few studies examining the effects of cigarette smoke extract (CSE) or nicotine on adipocyte differentiation.</div></div><div><h3>Methods</h3><div>Primary human bone marrow-derived mesenchymal stromal cells (MSCs) were exposed to CSE or nicotine (50–500 ng/ml) during adipogenic differentiation. Cell viability and metabolic activity were assessed <em>via</em> MTT assay. Lipid droplet accumulation was evaluated using Sudan III staining and quantitative image analysis. Adiponectin, IL6, and IL8 concentrations were measured after 35 days using ELISA.</div></div><div><h3>Results</h3><div>At these doses, CSE and nicotine do not immediately affect cell viability but inhibit undifferentiated cell proliferation. Notably, both agents at 50 ng/ml significantly increased lipid accumulation during adipogenesis, while higher CSE doses nearly completely inhibited this process. Additionally, CSE dose-dependently decreased adiponectin secretion and increased IL6 and IL8, indicating a shift towards an inflammatory state. Nicotine alone primarily increased IL6 secretion with less pronounced effects.</div></div><div><h3>Conclusion</h3><div>The study highlights the complex impact of CSE and nicotine on adipocyte function during early differentiation from MSCs. Dose-dependent changes in lipid accumulation, cytokine, and adiponectin secretion induced by CSE and nicotine can partly explain smoking-related adipose tissue dysfunction.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"101 ","pages":"Article 105949"},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0