Nanotoxicology最新文献

{"title":"Predicting the cytotoxicity of nanomaterials through explainable, extreme gradient boosting.","authors":"Allegra Conti,&nbsp;Luisa Campagnolo,&nbsp;Stefano Diciotti,&nbsp;Antonio Pietroiusti,&nbsp;Nicola Toschi","doi":"10.1080/17435390.2022.2156823","DOIUrl":"https://doi.org/10.1080/17435390.2022.2156823","url":null,"abstract":"<p><p>Nanoparticles (NPs) are a wide class of materials currently used in several industrial and biomedical applications. Due to their small size (1-100 nm), NPs can easily enter the human body, inducing tissue damage. NP toxicity depends on physical and chemical NP properties (e.g., size, charge and surface area) in ways and magnitudes that are still unknown. We assess the average as well as the individual importance of NP atomic descriptors, along with chemical properties and experimental conditions, in determining cytotoxicity endpoints for several nanomaterials. We employ a multicenter cytotoxicity nanomaterial database (12 different materials with first and second dimensions ranging between 2.70 and 81.2 nm and between 4.10 and 4048 nm, respectively). We develop a regressor model based on extreme gradient boosting with hyperparameter optimization. We employ Shapley additive explanations to obtain good cytotoxicity prediction performance. Model performances are quantified as statistically significant Spearman correlations between the true and predicted values, ranging from 0.5 to 0.7. Our results show that i) size in situ and surface areas larger than 200 nm and 50 m2/g, respectively, ii) primary particles smaller than 20 nm; iii) irregular (i.e., not spherical) shapes and iv) positive Z-potentials contribute the most to the prediction of NP cytotoxicity, especially if lactate dehydrogenase (LDH) assays are employed for short experimental times. These results were moderately stable across toxicity endpoints, although some degree of variability emerged across dose quantification methods, confirming the complexity of nano-bio interactions and the need for large, systematic experimental characterization to reach a safer-by-design approach.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"844-856"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9095093","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}

{"title":"Silver nanoparticles suppress forskolin-induced syncytialization in BeWo cells.","authors":"Yuji Sakahashi,&nbsp;Kazuma Higashisaka,&nbsp;Ryo Isaka,&nbsp;Rina Izutani,&nbsp;Jiwon Seo,&nbsp;Atsushi Furuta,&nbsp;Akemi Yamaki-Ushijima,&nbsp;Hirofumi Tsujino,&nbsp;Yuya Haga,&nbsp;Akitoshi Nakashima,&nbsp;Yasuo Tsutsumi","doi":"10.1080/17435390.2022.2162994","DOIUrl":"https://doi.org/10.1080/17435390.2022.2162994","url":null,"abstract":"<p><p>Opportunities for the exposure of pregnant women to engineered nanoparticles have been increasing with the expanding use of these materials. Therefore, there are concerns that nanoparticles could have adverse effects on the establishment and maintenance of pregnancy. The effects of nanoparticles on the mother and fetus have been evaluated from this perspective, but there is still little knowledge about the effects on placentation and function acquisition, which are essential for the successful establishment and maintenance of pregnancy. Formation of the syncytiotrophoblast is indispensable for the acquisition of placental function, and impairment of syncytialization inevitably affects pregnancy outcomes. Here, we assessed the effect of nanoparticles on placental formation by using forskolin-treated BeWo cells, a typical <i>in vitro</i> model of trophoblast syncytialization. Immunofluorescence staining analysis revealed that silver nanoparticles with a diameter of 10 nm (nAg10) (at 0.156 µg/mL) significantly decreased the proportion of syncytialized BeWo cells, but gold nanoparticles with a diameter of 10 nm did not. Consistently, only nAg10 (at 0.156 µg/mL) significantly suppressed forskolin-induced elevation of <i>CGB</i> and <i>SDC1</i> mRNA expression levels and human chorionic gonadotropin β production in a dose-dependent manner; these molecules are all markers of syncytialization. Besides, nAg10 significantly decreased the expression of <i>ERVFRD-1</i>, which encodes proteins associated with cell fusion. Moreover, nAg10 tended to suppress the expression of sFlt-1 e15a, a placental angiogenesis marker. Collectively, our data suggest that nAg10 could suppress formation of the syncytiotrophoblast and that induce placental dysfunction and the following poor pregnancy outcomes.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"883-894"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447930","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}

{"title":"Photocatalytic activity of nanoparticles: the development of the standardized measurement for physiological conditions.","authors":"Vytas Reipa,&nbsp;Nam Wong Song,&nbsp;Minjeong Kwak,&nbsp;Min Beom Heo,&nbsp;Tae Geol Lee,&nbsp;Paul Westerhoff,&nbsp;Yuqiang Bi,&nbsp;Blaza Toman,&nbsp;Vincent A Hackley,&nbsp;Haruhisa Kato,&nbsp;Yosuke Tabei,&nbsp;Kanokwan Nontapot,&nbsp;Yonghyun Choi,&nbsp;Jonghoon Choi","doi":"10.1080/17435390.2022.2159558","DOIUrl":"https://doi.org/10.1080/17435390.2022.2159558","url":null,"abstract":"<p><p>Recently a new International Standard for testing nanomaterial photocatalytic activity under physiological conditions was issued by Technical Committee 229 (Nanotechnologies) of the International Organization for Standardization (ISO 20814:2019 Nanotechnologies-Testing the photocatalytic activity of nanoparticles for NADH oxidation). The document offers a robust, high throughput photocatalytic assay using a bio-compatible indicator nicotinamide amide dinucleotide (NAD) and provides a screening tool to gauge nanomaterial potency for phototoxicity. This paper describes the measurement principles behind this assay, the scope of the standard and its validation through an interlaboratory comparison study using a traceable standard reference material (SRM 1898).</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"857-866"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10773622","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}

{"title":"Biomarkers of oxidative stress in urine and plasma of operators at six Singapore printing centers and their association with several metrics of printer-emitted nanoparticle exposures.","authors":"Dhimiter Bello,&nbsp;Lucia Chanetsa,&nbsp;Costas A Christophi,&nbsp;Dilpreet Singh,&nbsp;Magdiel Inggrid Setyawati,&nbsp;David C Christiani,&nbsp;Sanjay H Chotirmall,&nbsp;Kee Woei Ng,&nbsp;Philip Demokritou","doi":"10.1080/17435390.2023.2175735","DOIUrl":"https://doi.org/10.1080/17435390.2023.2175735","url":null,"abstract":"<p><p>Inhalation of nanoparticles emitted from toner-based printing equipment (TPE), such as laser printers and photocopiers, also known as PEPs, has been associated with systemic inflammation, hypertension, cardiovascular disease, respiratory disorders, and genotoxicity. Global serum metabolomics analysis in 19 healthy TPE operators found 52 dysregulated biomolecules involved in upregulation of inflammation, immune, and antioxidant responses and downregulation of cellular energetics and cell proliferation. Here, we build on the metabolomics study by investigating the association of a panel of nine urinary OS biomarkers reflecting DNA/RNA damage (8OHdG, 8OHG, and 5OHMeU), protein/amino acid oxidation (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine), and lipid oxidation (8-isoprostane, 4-hydroxy nonenal, and malondialdehyde [MDA]), as well as plasma total MDA and total protein carbonyl (TPC), with several nanoparticle exposure metrics in the same 19 healthy TPE operators. Plasma total MDA, urinary 5OHMeU, 3-chlorotyrosine, and 3-nitrotyrosine were positively, whereas o-tyrosine inversely and statistically significantly associated with PEPs exposure in multivariate models, after adjusting for age and urinary creatinine. Urinary 8OHdG, 8OHG, 5OHMeU, and total MDA in urine and plasma had group mean values higher than expected in healthy controls without PEPs exposure and comparable to those of workers experiencing low to moderate levels of oxidative stress (OS). The highest exposure group had OS biomarker values, most notably 8OHdG, 8OHG, and total MDA, that compared to workers exposed to welding fumes and titanium dioxide. Particle number concentration was the most sensitive and robust exposure metric. A combination of nanoparticle number concentration and OS potential of fresh aerosols is recommended for larger scale future studies.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"913-934"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097058","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}

{"title":"Iron oxide nanoparticles cause surface coating- and core chemistry-dependent endothelial cell ferroptosis.","authors":"Xue Zhang,&nbsp;Fei Kong,&nbsp;Tian Wang,&nbsp;Xin Huang,&nbsp;Wanqing Li,&nbsp;Meichen Zhang,&nbsp;Tao Wen,&nbsp;Jian Liu,&nbsp;Yu Zhang,&nbsp;Jie Meng,&nbsp;Haiyan Xu","doi":"10.1080/17435390.2022.2154176","DOIUrl":"https://doi.org/10.1080/17435390.2022.2154176","url":null,"abstract":"<p><p>Iron oxide nanoparticles (IONPs) are mostly intended to be administrated intravenously, understanding the interaction of IONPs with vascular endothelial cells is extremely crucial for developing safe application regimes of IONPs. In this work, interactions of three kinds of IONPs to endothelial cells were investigated both in human umbilical vein endothelial cells (HUVECs) and in healthy mice. Both meso-2,3-dimercaptosuccinic acid (DMSA) coated Fe₃O₄ NPs (DMSA-Fe₃O₄ NPs) and DMSA-Fe₂O₃ NPs induced cell growth inhibition, while polyglucose sorbitol carboxymethyether coated Fe₂O₃ NPs(PSC-Fe₂O₃ NPs) did not. The PSC coating inhibited the cellular uptake of the IONPs. Both DMSA-Fe₃O₄ and DMSA-Fe₂O₃ NPs induced ferroptosis of HUVEC through upregulating phospholipid peroxides, which could be inhibited by typical ferroptosis inhibitors ferrostatin-1, Trolox and deferoxamine. Moreover, transforming growth factor beta 1 (TGFβ1) was upregulated by DMSA-Fe₃O₄ NPs at protein and gene level. The inhibitor of TGFβ1 receptor LY210 could reduce the effect. When being intravenously injected in mice, DMSA-Fe₃O₄ NPs were observed locating in the liver, increased the levels of lipid peroxidation (4-hydroxynonenal), acyl-CoA synthetase long-chain family member 4(ACSL4) and TGFβ1, indicating ferroptosis occurrence <i>in vivo</i>. The ferroptosis of vascular endothelial cells in exposure with IONPs depended on the surface coating and core chemistry of the NPs. Both DMSA-Fe₃O₄ NPs and DMSA-Fe₂O₃ NPs could induce the ferroptosis of endothelial cells, while PSC-Fe₂O₃ NPs did not induce ferroptosis and apoptosis possibly due to the very low cellular uptake. DMSA-Fe₃O₄ NPs and TGFβ1 formed feedforward loop to induce ferroptosis.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"829-843"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097637","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}

{"title":"Comparison of toxicity and cellular responses following pulmonary exposure to different types of nanofibers.","authors":"Min-Sung Kang,&nbsp;Gwang-Hee Lee,&nbsp;Mi-Jin Yang,&nbsp;Myeong-Chang Sung,&nbsp;Hyoung-Yun Han,&nbsp;Byoung-Seok Lee,&nbsp;Bosung Baek,&nbsp;Dong-Wan Kim,&nbsp;Eun-Jung Park","doi":"10.1080/17435390.2023.2177205","DOIUrl":"https://doi.org/10.1080/17435390.2023.2177205","url":null,"abstract":"<p><p>Pulmonary effects of inhaled microfibers are an emerging public health concern. In this study, we investigated toxicity following pulmonary exposure to synthetic polyethylene oxide fibroin (PEONF) and silk fibroin (SFNF) nanofibers and the cellular responses. When instilled intratracheally weekly for four weeks, body weight gain was significantly reduced in female mice exposed to the higher dose of SFNF when compared with the control group. The total number of cells in the lungs was more significant in all treated groups than in the control, whereas the relative portion of neutrophils and eosinophils increased significantly only in female mice exposed to SFNF. Both types of nanofibers induced notable pathological changes and increased pulmonary expression of MCP-1α, CXCL1, and TGF-β. More importantly, blood calcium, creatinine kinase, sodium, and chloride concentration were affected significantly, showing sex- and material-dependent differences. The relative portion of eosinophils increased only in SFNF-treated mice. In addition, both types of nanofibers induced necrotic and late apoptotic cell death in alveolar macrophages after 24 h of exposure, with accompanying oxidative stress, increased NO production, cell membrane rupture, intracellular organelle damage, and intracellular calcium accumulation. Additionally, multinucleated giant cells were formed in cells exposed to PEONF or SFNF. Taken together, the findings indicate that inhaled PEONF and SFNF may cause systemic adverse health effects with lung tissue damage, showing differences by sex- and material. Furthermore, PEONF- and SFNF-induced inflammatory response may be partly due to the low clearance of dead (or damaged) pulmonary cells and the excellent durability of PEONF and SFNF.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"935-954"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465389","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}

{"title":"Comparison of tyrosine-modified low molecular weight branched and linear polyethylenimines for siRNA delivery.","authors":"Małgorzata Kubczak,&nbsp;Sylwia Michlewska,&nbsp;Michael Karimov,&nbsp;Alexander Ewe,&nbsp;Achim Aigner,&nbsp;Maria Bryszewska,&nbsp;Maksim Ionov","doi":"10.1080/17435390.2022.2159891","DOIUrl":"https://doi.org/10.1080/17435390.2022.2159891","url":null,"abstract":"<p><p>Polyethylenimines (PEIs) have been previously introduced for siRNA delivery. In particular, in the case of higher molecular weight PEIs, this is associated with toxicity, while low molecular weight PEIs are often insufficient for siRNA complexation. The tyrosine-modification of PEIs has been shown to enhance PEI efficacy and biocompatibility. This paper evaluates a set of tyrosine-modified low molecular weight linear or branched polyethylenimines as efficient carriers of siRNA. Complexation efficacies and biophysical complex properties were analyzed by zeta potential, dynamic light scattering and circular dichroism measurements as well as gel electrophoresis. Biological knockdown was studied in 2 D cell culture and 3 D <i>ex vivo</i> tissue slice air-liquid interface culture. The results demonstrate that siRNAs were able to form stable complexes with all tested polymers. Complexation was able to protect siRNA from degradation by RNase and to mediate target gene knockdown, as determined on the mRNA level and in PC3-Luc3/EGFP and HCT116-Luc3/EGFP expressing reporter cells on the protein level, using flow cytometry and confocal microscopy. The direct comparison of the studied polymers revealed differences in biological efficacies. Moreover, the tyrosine-modified PEIs showed high biocompatibility, as determined by LDH release and mitochondria integrity (J-aggregate assay) as well as caspase 3/7 (apoptosis) and H₂O₂ levels (ROS). In 3 D tissue slices, complexes based on LP10Y proved to be most efficient, by combining tissue penetration with efficient gene expression knockdown.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 9-10","pages":"867-882"},"PeriodicalIF":5.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097650","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}

{"title":"Developmental neurotoxicity of silver nanoparticles: the current state of knowledge and future directions.","authors":"Lidia Strużyńska, Beata Dąbrowska-Bouta, Grzegorz Sulkowski","doi":"10.1080/17435390.2022.2105172","DOIUrl":"10.1080/17435390.2022.2105172","url":null,"abstract":"<p><p>The increasing production and use of silver nanoparticles (AgNPs) as an antimicrobial agent in an array of medical and commercial products, including those designed for infants and children, poses a substantial risk of exposure during the developmental period. This review summarizes current knowledge on developmental neurotoxicity of AgNPs in both pre- and post-natal stages with a focus on the biological specificity of immature organisms that predisposes them to neurotoxic insults as well as the molecular mechanisms underlying AgNP-induced neurotoxicity. The current review revealed that AgNPs increase the permeability of the blood-brain barrier (BBB) and selectively damage neurons in the brain of immature rats exposed pre and postnatally. Among the AgNP-induced molecular mechanisms underlying toxic insult is cellular stress, which can consequently lead to cell death. Glutamatergic neurons and NMDAR-mediated neurotransmission also appear to be a target for AgNPs during the postnatal period of exposure. Collected data indicate also that our current knowledge of the impact of AgNPs on the developing nervous system remains insufficient and further studies are required during different stages of development with investigation of environmentally-relevant doses of exposure.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"1-26"},"PeriodicalIF":5.0,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40666203","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}

{"title":"A follow-up study on workers involved in the graphene production process after the introduction of exposure mitigation measures: evaluation of genotoxic and oxidative effects.","authors":"Delia Cavallo,&nbsp;Cinzia Lucia Ursini,&nbsp;Anna Maria Fresegna,&nbsp;Aureliano Ciervo,&nbsp;Fabio Boccuni,&nbsp;Riccardo Ferrante,&nbsp;Francesca Tombolini,&nbsp;Raffaele Maiello,&nbsp;Pieranna Chiarella,&nbsp;Giuliana Buresti,&nbsp;Valentina Del Frate,&nbsp;Diana Poli,&nbsp;Roberta Andreoli,&nbsp;Luisana Di Cristo,&nbsp;Stefania Sabella,&nbsp;Sergio Iavicoli","doi":"10.1080/17435390.2022.2149359","DOIUrl":"https://doi.org/10.1080/17435390.2022.2149359","url":null,"abstract":"<p><p>During nanomaterial (NM) production, workers could be exposed, particularly by inhalation, to NMs and other chemicals used in the synthesis process, so it is important to have suitable biomarkers to monitor potential toxic effects. Aim of this study was to evaluate the effectiveness of the introduction of exposure mitigation measures on workers unintentionally exposed to graphene co-pollutants during production process monitoring the presumable reduction of workplace NM contamination and of early genotoxic and oxidative effects previously found on these workers. We used Buccal Micronucleus Cytome (BMCyt) assay and Fpg-comet test, resulted the most sensitive biomarkers on our first biomonitoring work, to measure the genotoxic effects. We also detected urinary oxidized nucleic acid bases 8-oxoGua, 8-oxoGuo and 8-oxodGuo to evaluate oxidative damage. The genotoxic and oxidative effects were assessed on the same graphene workers (<i>N</i> = 6) previously studied, comparing the results with those found in the first biomonitoring and with the control group (<i>N</i> = 11). This was achieved 6 months after the installation of a special filter hood (where to perform the phases at higher risk of NM emission) and the improvement of environmental and personal protective equipment. Particle number concentration decreased after the mitigation measures. We observed reduction of Micronucleus (MN) frequency and oxidative DNA damage and increase of 8-oxodGuo excretion compared to the first biomonitoring. These results, although limited by the small subject number, showed the efficacy of adopted exposure mitigation measures and the suitability of used sensitive and noninvasive biomarkers to bio-monitor over time workers involved in graphene production process.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 6-8","pages":"776-790"},"PeriodicalIF":5.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10766666","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}

{"title":"Nickel nanoparticles induce epithelial-mesenchymal transition in human bronchial epithelial cells via the HIF-1α/HDAC3 pathway.","authors":"Jiali Yuan,&nbsp;Yiqun Mo,&nbsp;Yuanbao Zhang,&nbsp;Yue Zhang,&nbsp;Qunwei Zhang","doi":"10.1080/17435390.2022.2142169","DOIUrl":"10.1080/17435390.2022.2142169","url":null,"abstract":"<p><p>We and others have previously demonstrated that exposure to nickel nanoparticles (Nano-Ni) caused fibrogenic and carcinogenic effects; however, the underlying mechanisms are still not fully understood. This study aimed to investigate the effects of Nano-Ni on epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (BEAS-2B) and its underlying mechanisms since EMT is involved in both cancer pathogenesis and tissue fibrosis. Our results showed that exposure to Nano-Ni, compared to the control Nano-TiO₂, caused a remarkable decrease in the expression of E-cadherin and an increase in the expression of vimentin and α-SMA, indicating an inducible role of Nano-Ni in EMT development in human bronchial epithelial cells. HIF-1α nuclear accumulation, HDAC3 upregulation, and decreased histone acetylation were also observed in the cells exposed to Nano-Ni, but not in those exposed to Nano-TiO₂. Pretreatment of the cells with a specific HIF-1α inhibitor, CAY10585, or HIF-1α-specific siRNA transfection prior to Nano-Ni exposure resulted in the restoration of E-cadherin and abolished Nano-Ni-induced upregulation of vimentin and α-SMA, suggesting a crucial role of HIF-1α in Nano-Ni-induced EMT development. CAY10585 pretreatment also attenuated the HDAC3 upregulation and increased histone acetylation. Inhibition of HDAC3 with specific siRNA significantly restrained Nano-Ni-induced reduction in histone acetylation and restored EMT-related protein expression to near control levels. In summary, our findings suggest that exposure to Nano-Ni promotes the development of EMT in human bronchial epithelial cells by decreasing histone acetylation through HIF-1α-mediated HDAC3 upregulation. Our findings may provide information for further understanding of the molecular mechanisms of Nano-Ni-induced fibrosis and carcinogenesis.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"16 6-8","pages":"695-712"},"PeriodicalIF":5.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10749962","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}