Toxicology in Vitro最新文献_第2页

Heat shock protein HSPA8 impedes hemin-induced cellular-toxicity in liver 热休克蛋白HSPA8能抑制肝脏中海明诱导的细胞毒性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-30 DOI: 10.1016/j.tiv.2024.105959

Alok Kumar Pandey, Vishal Trivedi

{"title":"Heat shock protein HSPA8 impedes hemin-induced cellular-toxicity in liver","authors":"Alok Kumar Pandey, Vishal Trivedi","doi":"10.1016/j.tiv.2024.105959","DOIUrl":"10.1016/j.tiv.2024.105959","url":null,"abstract":"<div><div>Accumulation of hemin in cells, tissues, and organs is one of the major pathological conditions linked to hemolytic diseases like malaria. Pro-oxidant hemin confers high toxicity following its accumulation. We tested the cellular toxicity of hemin on HepG2 cells by exploring modulation in various cellular characteristics. Hemin reduces the viability of HepG2 cells and brings about visible morphological changes. Hemin causes perforations on the surface of HepG2 cells observed through SEM. Hemin leads to the extracellular release of liver enzymes and reduces the wound-healing potential of HepG2 cells. Hemin leads to the fragmentation of HepG2 DNA, arrests the cell cycle progression in the S-phase and induces apoptosis in these cells. Western blot analysis revealed that hemin triggers both the extrinsic and intrinsic pathways of apoptosis in HepG2 cells. We have already shown that the cytoprotective protein HSPA8 can polymerize hemin and minimize its toxicity. Similar experiments with hemin in the presence and absence of HSPA8 showed that HSPA8 reverses all the tested toxic effects of hemin on HepG2 cells. The protection from hemin toxicity in HepG2 cells appeared to be due to the extracellular polymerization of hemin by HSPA8.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105959"},"PeriodicalIF":2.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565316","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

Food grade titanium dioxide induced endoplasmic reticulum stress in colon cells: Comparison between normal and colorectal carcinoma cells 食品级二氧化钛诱导结肠细胞内质网应激：正常细胞与结直肠癌细胞的比较

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-24 DOI: 10.1016/j.tiv.2024.105957

Alina Uribe-García , Estefany I. Medina-Reyes , Carlos A. Flores-Reyes , Alejandro A. Zagal-Salinas , Octavio Ispanixtlahuatl-Meraz , Eduardo Delgado-Armenta , Miguel Santibáñez-Andrade , Cesar M. Flores , Yesennia Sánchez-Pérez , Claudia M. García-Cuéllar , Yolanda I. Chirino

{"title":"Food grade titanium dioxide induced endoplasmic reticulum stress in colon cells: Comparison between normal and colorectal carcinoma cells","authors":"Alina Uribe-García , Estefany I. Medina-Reyes , Carlos A. Flores-Reyes , Alejandro A. Zagal-Salinas , Octavio Ispanixtlahuatl-Meraz , Eduardo Delgado-Armenta , Miguel Santibáñez-Andrade , Cesar M. Flores , Yesennia Sánchez-Pérez , Claudia M. García-Cuéllar , Yolanda I. Chirino","doi":"10.1016/j.tiv.2024.105957","DOIUrl":"10.1016/j.tiv.2024.105957","url":null,"abstract":"<div><h3>Background</h3><div>Food-grade titanium dioxide (E171) has been under scrutiny in the last decade since its possible adverse effects; however, the cellular mechanisms underlying E171 toxicity have not been thoroughly described.</div></div><div><h3>Aim</h3><div>We aimed to compare the effects of E171 on endoplasmic reticulum (ER) homeostasis in normal and cancer colon cells.</div></div><div><h3>Experimental design</h3><div>We exposed normal, carcinoma, and adenocarcinoma cells to 0.1, 1, 10, 50 and 100 μg/cm<sup>2</sup> of E171 for 24, 48 and 72 h, and we evaluated ER stress, cell viability, titanium uptake, intracellular calcium concentration, and gene expression related to unfolded protein response (UPR) and chaperone pathways.</div></div><div><h3>Results</h3><div>Cell viability decreased only after 72 h of exposure to 100 μg/cm<sup>2</sup> of E171. Adenocarcinoma cells internalized higher titanium amounts than normal and carcinoma cells, but the effects in ER distribution, intracellular calcium concentration, and gene expression were similar among the three cell lines. The expression of UPR and chaperone pathways were downregulated at the lowest concentrations but upregulated at the highest concentrations in the three cell lines.</div></div><div><h3>Conclusion</h3><div>E171 induces ER stress through alterations in ER distribution, intracellular calcium, and UPR and chaperone protein pathways.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105957"},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513029","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

Curcumin-loaded emulsome nanoparticles induces apoptosis through p53 signaling pathway in pancreatic cancer cell line PANC-1 姜黄素负载的乳化纳米粒子通过 p53 信号通路诱导胰腺癌细胞系 PANC-1 的细胞凋亡。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-10-21 DOI: 10.1016/j.tiv.2024.105958

Zuleyha Demirci , Zeynep Islek , Halime Ilhan Siginc , Fikrettin Sahin , Mehmet H. Ucisik , Zeynep Busra Bolat

{"title":"Curcumin-loaded emulsome nanoparticles induces apoptosis through p53 signaling pathway in pancreatic cancer cell line PANC-1","authors":"Zuleyha Demirci , Zeynep Islek , Halime Ilhan Siginc , Fikrettin Sahin , Mehmet H. Ucisik , Zeynep Busra Bolat","doi":"10.1016/j.tiv.2024.105958","DOIUrl":"10.1016/j.tiv.2024.105958","url":null,"abstract":"<div><div>Pancreatic cancer is a global health problem with a poor prognosis, limited treatment options and low survival rates of patients. Thus, the exploration of novel treatment approaches is crucial. Curcumin shows promise in pancreatic cancer. Curcumin has anticancer properties promoting apoptosis through the p53 pathway. However, adverse effects and low bioavailability are curcumin's main drawbacks and its delivery by nanoparticles could improve its effectiveness as a treatment option. Curcumin-loaded emulsome nanoparticles (CurEm) have shown promise in colorectal, hepatocellular, and prostate cancers. This study aims to evaluate the anticancer potential of CurEm in pancreatic cancer cell line PANC-1. The cytotoxic effects of CurEm on PANC-1 cells show cytotoxicity in dose and time-dependent manner. The selected dose 30 μM CurEm resulted spheroidal morphology in PANC-1 cells and colony forming and scratch assay conducted demonstrated significant growth inhibition and decrease in migration ability, respectively. Cell cycle analysis shows that CurEm induces G2/M arrest in PANC-1 cells. CurEm-treated PANC-1 cells showed a significant increase in p53 and Caspase 3 genes, while a significant decrease in Bcl-2 genes compared to untreated group. Western blot results showed parallel results to qPCR analysis for Bcl-2 protein levels. Interestingly, we saw low p53 protein levels in CurEm-treated PANC-1 cells. These findings shed light on the potential of CurEm as an effective and stable therapeutic approach for pancreatic cancer.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105958"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513028","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

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 Kandarova

{"title":"Exploring the potential of reconstructed human epithelial tissue models for safety assessment of intraoral medical devices.","authors":"Peter Pôbiš, Tatiana Milasová, Helena Kandarova","doi":"10.1016/j.tiv.2024.105956","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105956","url":null,"abstract":"<p><p>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. 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.</p>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":" ","pages":"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