RESUMO
This year, France banned the application of titanium dioxide nanoparticles as a food additive (hereafter, E171) based on the insufficient oral toxicity data. Here, we investigated the subchronic toxic responses of E171 (0, 10, 100, and 1,000 mg/kg) and tried to elucidate the possible toxic mechanism using AGS cells, a human stomach epithelial cell line. There were no dose-related changes in the Organisation for Economic Cooperation and Development test guideline-related endpoints. Meanwhile, E171 deeply penetrated cells lining the stomach tissues of rats, and the IgM and granulocyte-macrophage colony-stimulating factor levels were significantly lower in the blood from rats exposed to E171 compared with the control. The colonic antioxidant protein level decreased with increasing Ti accumulation. Additionally, after 24-h exposure, E171 located in the perinuclear region of AGS cells and affected expression of endoplasmic reticulum stress-related proteins. However, cell death was not observed up to the used maximum concentration. A gene profile analysis also showed that immune response-related microRNAs were most strongly affected by E171 exposure. Collectively, we concluded that the NOAEL of E171 for 90 days repeated oral administration is between 100 and 1,000 mg/kg for both male and female rats. Additionally, further study is needed to clarify the possible carcinogenesis following the chronic accumulation in the colon.
Assuntos
Aditivos Alimentares/toxicidade , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Administração Oral , Animais , Feminino , França , Humanos , Masculino , Nível de Efeito Adverso não Observado , Tamanho da Partícula , RatosRESUMO
It is necessary to locate microplastic particles mixed with beach sand to be able to separate them. This paper illustrates a kernel weight histogram-based analytical process to determine an appropriate neural network to perform tiny object segmentation on photos of sand with a few microplastic particles. U-net and MultiResUNet are explored as target networks. However, based on our observation of kernel weight histograms, visualized using TensorBoard, the initial encoder stages of U-net and MultiResUNet are useful for capturing small features, whereas the later encoder stages are not useful for capturing small features. Therefore, we derived reduced versions of U-net and MultiResUNet, such as Half U-net, Half MultiResUNet, and Quarter MultiResUNet. From the experiment, we observed that Half MultiResUNet displayed the best average recall-weighted F1 score (40%) and recall-weighted mIoU (26%) and Quarter MultiResUNet the second best average recall-weighted F1 score and recall-weighted mIoU for our microplastic dataset. They also require 1/5 or less floating point operations and 1/50 or a smaller number of parameters over U-net and MultiResUNet.
Assuntos
Processamento de Imagem Assistida por Computador , Microplásticos , Redes Neurais de Computação , PlásticosRESUMO
Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 µg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 µg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.
Assuntos
Betacoronavirus/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Compostos de Amônio Quaternário/toxicidade , Animais , Apoptose/efeitos dos fármacos , COVID-19 , Linhagem Celular , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Compostos de Amônio Quaternário/administração & dosagem , SARS-CoV-2RESUMO
Due to mass production and extensive use, the potential adverse health effects of amorphous silica nanoparticles (ASiNPs) have received a significant attention from the public and researchers. However, the relationship between physicochemical properties of ASiNPs and their health effects is still unclear. In this study, we manufactured two types of ASiNPs of different diameters (20 and 50â¯nm) and compared the toxic response induced in rats after intratracheal instillation (75, 150 or 300⯵g/rat). There were no dose-related differences in mortality, body weight gain or organ weight between the groups. However both types of ASiNPs significantly decreased the proportion of neutrophils in male rats, whereas the levels of hemoglobin and hematocrit were markedly reduced only in female rats instilled with 20â¯nm-ASiNPs. ASiNPs-induced lung tissue damage seemed to be more evident in the 20â¯nm ASiNP-treated group and in female rats than male rats. Similarly, expression of caveolin-1 and matrix metalloproteinase-9 seemed to be most notably enhanced in female rats treated with 20â¯nm-ASiNPs. The total number of bronchial alveolar lavage cells significantly increased in rats instilled with 20â¯nm-ASiNPs, accompanying a decrease in the proportion of macrophages and an increase in polymorphonuclear leukocytes. Moreover, secretion of inflammatory mediators clearly increased in human bronchial epithelial cells treated with 20â¯nm-ASiNPs, but not in those treated with 50â¯nm-ASiNPs. These results suggest that pulmonary effects of ASiNPs depend on particle size. Sex-dependent differences should also be carefully considered in understanding nanomaterial-induced adverse health effects.
Assuntos
Inflamação/induzido quimicamente , Pneumopatias/induzido quimicamente , Nanopartículas/toxicidade , Tamanho da Partícula , Dióxido de Silício/toxicidade , Animais , Feminino , Masculino , Ratos , Fatores SexuaisRESUMO
In this study, we aimed to identify a toxic mechanism and the potential health effects of ambient dusts in an underground subway station. At 24 h exposure to human bronchial epithelial (BEAS-2B) cells (0, 2.5, 10, and 40 µg/mL), dusts located within autophagosome-like vacuoles, whereas a series of autophagic processes appeared to be blocked. The volume, potential and activity of mitochondria decreased in consistent with a condensed configuration, and the percentage of late apoptotic cells increased accompanying S phase arrest. While production of reactive oxygen species, expression of ferritin (heavy chain) protein, secretion of IL-6, IL-8 and matrix metalloproteinases, and the released LDH level notably increased in dust-treated cells (40 µg/mL), intracellular calcium level decreased. At day 14 after a single instillation to mice (0, 12.5, 50, and 200 µg/head), the total number of cells increased in the lungs of dust-treated mice with no significant change in cell composition. The pulmonary levels of TGF-ß, GM-CSF, IL-12 and IL-13 clearly increased following exposure to dusts, whereas that of CXCL-1 was dose-dependently inhibited. Additionally, the population of cytotoxic T cells in T lymphocytes in the spleen increased relative to that of helper T cells, and the levels of IgA and IgM in the bloodstream were significantly reduced in the dust-treated mice. Subsequently, to improve the possibility of extrapolating our findings to humans, we repeatedly instilled dusts (1 time/week, 4 weeks, 0.25 and 1.0 mg/head) to monkeys. The total number of cells, the relative portion of neutrophils, the level of TNF-α significantly increased in the lungs of dust-treated monkeys, and the expression of cytochrome C was enhanced in the lung tissues. Meanwhile, the pulmonary level of MIP-α was clearly reduced, and the expression of caveolin-1 was inhibited in the lung tissues. More importantly, inflammatory lesions, such as granuloma, were seen in both mice and monkeys instilled with dusts. Taken together, we conclude that dusts may impair the host's immune function against foreign bodies by inhibiting the capacity for production of antibodies. In addition, iron metabolism may be closely associated with dust-induced cell death and inflammatory response.
Assuntos
Poeira , Ferrovias , Animais , Morte Celular , Poeira/análise , Pulmão/química , Camundongos , Espécies Reativas de OxigênioRESUMO
Cell cycle progression requires the E3 ubiquitin ligase anaphase-promoting complex (APC/C), which uses the substrate adaptors CDC20 and CDH1 to target proteins for proteasomal degradation. The APC(CDH1) substrate cyclin A is critical for the G1/S transition and, paradoxically, accumulates even when APC(CDH1) is active. We show that the deubiquitinase USP37 binds CDH1 and removes degradative polyubiquitin from cyclin A. USP37 was induced by E2F transcription factors in G1, peaked at G1/S, and was degraded in late mitosis. Phosphorylation of USP37 by CDK2 stimulated its full activity. USP37 overexpression caused premature cyclin A accumulation in G1 and accelerated S phase entry, whereas USP37 knockdown delayed these events. USP37 was inactive in mitosis because it was no longer phosphorylated by CDK2. Indeed, it switched from an antagonist to a substrate of APC(CDH1) and was modified with degradative K11-linked polyubiquitin.
Assuntos
Caderinas/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Endopeptidases/metabolismo , Fase S , Antígenos CD , Ciclina A/metabolismo , Fatores de Transcrição E2F/metabolismo , Células HEK293 , Humanos , Mitose , Fosforilação , Poliubiquitina/metabolismo , Regulação para CimaRESUMO
Nanoparticles (NPs) have recently emerged as an inhalable pollutant, owing to their applications, aluminum-based NPs (Al-NPs) have been prioritized for toxicity testing. In the current study, we compared the pulmonary biopersistence and subsequent toxicity of four different types of Al-NPs (two rod-type aluminum oxide NPs [AlONPs] with different aspect ratios [short (S)- and long (L)-AlONPs], spherical aluminum cerium oxide NPs [AlCeO3 , AlCeONPs] and spherical γ-aluminum oxide hydroxide nanoparticles [AlOOHNPs]) 13weeks after a single intratracheal instillation, considering the importance of their properties in their toxicity. We found that the pulmonary biopersistence of Al-NPs was strengthened by a high aspect ratio in the rod-type AlONPs and by the presence of hydroxyl groups in the spherical-type Al-NPs. The highest toxicity was observed in the mice treated with AlOOHNPs, which showed low biostability. More importantly, we identified that the commercially available AlCeONPs were Al2 O3 -coated CeO2 NPs, but not AlCeO3 NPs, although they have been sold under the trade name of AlCeONPs. In conclusion, the aspect ratio and biostability may be important factors in the determination of the biopersistence of NPs and the subsequent biological response. In addition, the physicochemical properties of NPs should be examined in detail before their release into the market to prevent unexpected adverse health effects.
Assuntos
Alumínio/toxicidade , Nanopartículas Metálicas/toxicidade , Alumínio/administração & dosagem , Animais , Basófilos/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Ensaio de Imunoadsorção Enzimática , Eosinófilos/efeitos dos fármacos , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos ICR , Neutrófilos/efeitos dos fármacosRESUMO
The tissue distribution and toxicity of nanoparticles (NPs) depend on their physical and chemical properties both in the manufactured condition and within the biological system. We characterized three types of commercially available aluminum-based NPs (Al-NPs), two rod-type aluminum oxide NPs (Al2 O3 , AlONPs), with different aspect ratios (short [S]- and long [L]-AlONPs), and spherical aluminum cerium oxide NPs (AlCeO3 , AlCeONPs). The surface area was in order of the S-AlONPs > L-AlONPs > AlCeONPs. Very importantly, we found that AlCeONPs is Al2 O3 -coated CeO2 NPs, but not AlCeO3 NPs, and that the Al level in AlCeONPs is approximately 20% of those in S- and L-AlONPs. All three types of Al-NPs were slightly ionized in gastric fluid and rapidly particlized in the intestinal fluid. There were no significant differences in the body weight gain following 28 days of repeated oral administration of the three different types of Al-NPs. All Al-NPs elevated Al level in the heart, spleen, kidney and blood at 24 hours after the final dose, accompanied by the altered tissue level of redox reaction-related trace elements. Subsequently, in four types of cells derived from the organs which Al-NPs are accumulated, H9C2 (heart), HEK-293 (kidney), splenocytes and RAW264.7 (blood), S-AlONPs showed a very low uptake level and did not exert significant cytotoxicity. Meanwhile, cytotoxicity and uptake level were the most remarkable in cells treated with AlCeONPs. In conclusion, we suggest that the physicochemical properties of NPs should be examined in detail before the release into the market to prevent unexpected adverse health effects.
Assuntos
Compostos de Alumínio , Cério/química , Nanopartículas Metálicas , Administração Oral , Compostos de Alumínio/química , Compostos de Alumínio/farmacocinética , Compostos de Alumínio/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos Endogâmicos ICR , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Especificidade de Órgãos , Oxirredução , Tamanho da Partícula , Ratos , Propriedades de Superfície , Distribuição TecidualRESUMO
Accumulated evidence suggests that chronic pulmonary accumulation of harmful particles cause adverse pulmonary and systemic health effects. In our previous study, most of the graphene nanoplatelet (GNP) remained in the lung until 28 days after a single instillation. In this study, we sought to evaluate the local and systemic health effect after a long pulmonary persistence of GNP. As expected, GNP remained in the lung on day 90 after a single intratracheal instillation (1.25, 2.5 and 5 mg kg-1 ). In the lung exposed at the highest dose, the total number of cells and the percentage of lymphocytes significantly increased in the BAL fluid with an increase in both the number of GNP-engulfed macrophages and the percentage of apoptotic cells. A Th1-shifted immune response, the elevated chemokine secretion and the enhanced expression of cytoskeletal-related genes were observed. Additionally, the expression of natriuretic-related genes was noteworthy altered in the lungs. Moreover, the number of white blood cells (WBC) and the percentage of macrophages and neutrophils clearly increased in the blood of mice exposed to a 5-mg kg-1 dose, whereas total protein, BUN and potassium levels significantly decreased. In conclusion, we suggest that the long persistence of GNP in the lung may cause adverse health effects by disturbing immunological- and physiological-homeostasis of our body. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Grafite/toxicidade , Homeostase/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nanoestruturas/toxicidade , Equilíbrio Th1-Th2/efeitos dos fármacos , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Ciclo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Grafite/metabolismo , Homeostase/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos ICRRESUMO
The health effects of silica may depend on the inherent properties of crystalline silica or on external factors affecting the biological activity or distribution of its polymorphs. Inhaled crystalline silica is classified as a Group I carcinogen, however, information on the health effects of amorphous silica is still insufficient. Considering that alveolar macrophages play a key role in both innate and adaptive immune responses for removal of foreign bodies that enter via the respiratory system, we treated sheet-like glass particles (SGPs), a type of noncrystalline amorphous silica, to MH-S cells, an alveolar macrophage cell line. SGPs reduced the generation of ROS and NO and induced cell death via multiple pathways. Although the expression of CD80, CD86, and CD40, increased by exposure to SGPs, the expression of MHC class II molecules had not notably changed. Additionally, expression of ICAM-1 tended to decrease. In mice, SGPs were distributed in the interstitial region of the lung without notable pathological lesion on day 14 after a single intratracheal instillation. Pulmonary total cell number increased significantly with the highest dose, but the levels of all measured inflammatory cytokines and chemokines, except IL-1, were lower in BAL fluid from SGP-treated mice compared to control. More interestingly, the expression of antigen presentation-related proteins was enhanced in the lungs of SGP-exposed mice concomitant with an increase in the number of mature dendritic cells, whereas the expression of ICAM-1, an important adhesion molecule for helper T cell recruitment, was suppressed. Taken together, we suggest that SGPs may induce adverse health effects by down-regulating function of immune cells in the lungs. Furthermore, ICAM-1 may play a key role in immune response to remove pulmonary SGPs.
Assuntos
Citocinas/metabolismo , Vidro , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Dióxido de Silício/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Relação Dose-Resposta a Droga , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neutrófilos/citologia , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Propriedades de SuperfícieRESUMO
Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO2 and -V2O5 NPs and synthetic (S)-VO2, -V2O3, and -V2O5 NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125-170nm. The S- and C-V2O5 NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210µg/mouse, approximately 2 and 6mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V2O5 and S-V2O3 NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na(+), K(+), and Ca(2+)) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V2O5 and S-V2O3 NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies are needed to clarify effects of VO NPs on functions of the heart and the immune system.
Assuntos
Nanopartículas Metálicas/toxicidade , Vanádio/toxicidade , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxidos/farmacocinética , Óxidos/toxicidade , Organismos Livres de Patógenos Específicos , Distribuição Tecidual , Vanádio/farmacocinéticaRESUMO
With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ- and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg(-1)). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs.
Assuntos
Hidróxido de Alumínio/toxicidade , Óxido de Alumínio/toxicidade , Nanopartículas Metálicas/toxicidade , Trifosfato de Adenosina/metabolismo , Administração Oral , Hidróxido de Alumínio/metabolismo , Óxido de Alumínio/metabolismo , Animais , Bioensaio , Biomarcadores/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Interleucina-8/sangue , Rim/efeitos dos fármacos , Rim/ultraestrutura , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/ultraestrutura , Masculino , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Tamanho da Partícula , Ratos , Medição de Risco , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/ultraestrutura , Propriedades de Superfície , Fatores de Tempo , Distribuição TecidualRESUMO
Aluminum oxide nanoparticles are listed among 14 high-priority nanomaterials published by the Organization for Economic Co-operation and Development, but limited information is available on their potential hazards. In this study, we compared the toxicity of two different aluminum oxide nanorods (AlNRs) commercially available in vivo and in vitro. Considering aspect ratio, one was 6.2 ± 0.6 (long-AlNRs) and the other was 2.1 ± 0.4 (short-AlNRs). In mice, long-AlNRs induced longer and stronger inflammatory responses than short-AlNRs, and the degree reached the maximum on day 7 for both types and decreased with time. In addition, in vitro tests were performed on six cell lines derived from potential target organs for AlNPs, HEK-293 (kidney), HACAT (skin), Chang (liver), BEAS-2B (lung), T98G (brain), and H9C2 (heart), using MTT assay, ATP assay, LDH release, and xCELLigence system. Long-AlNRs generally produced stronger toxicity than short-AlNRs, and HEK-293 cells were the most sensitive for both AlNRs, followed by BEAS-2B cells, although results from 4 kinds of toxicity tests conflicted among the cell lines. Based on these results, we suggest that toxicity of AlNRs may be related to aspect ratio (and resultant surface area). Furthermore, novel in vitro toxicity testing methods are needed to resolve questionable results caused by the unique properties of nanoparticles.
Assuntos
Óxido de Alumínio/toxicidade , Inflamação/induzido quimicamente , Nanotubos/química , Óxido de Alumínio/administração & dosagem , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Humanos , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ratos , Testes de Toxicidade/métodosRESUMO
With the development of nanotechnology, myriad types of novel materials have been discovered at the nanoscale, among which the most interesting material is graphene. However, the toxicity data available on graphene are extremely limited. In this study, we explored toxic response of commercially available graphene nanoplatelets (GNPs) in vivo and in vitro. The GNPs used in this study had a high surface area and feature considerably few defects. In mice, GNPs (2.5 and 5 mg/kg) remained in the lung until 28 days after a single instillation, and the secretion of inflammatory cytokines reached the maximal level at Day 14 and then decreased over time. In vitro study using BEAS-2B cells, a human bronchial epithelial cell line, GNPs located within autophagosome-like vacuoles 24 h after exposure. The GNPs (2.5, 5, 10, and 20 µg/mL) also dose-dependently reduced cell viability, which was accompanied by an increase in the portion of cells in the subG1 and S phases. Moreover, the GNPs down-regulated the generation of reactive oxygen species, suppressed ATP production, caused mitochondria damage, and elevated the levels of autophagy-related proteins. Based on these results, we suggest that GNPs provoked a subchronic inflammatory response in mice and that GNPs induced autophagy accompanying apoptosis via mitochondria damage in vitro.
Assuntos
Células Epiteliais/efeitos dos fármacos , Grafite/toxicidade , Inflamação/induzido quimicamente , Nanopartículas/toxicidade , Animais , Autofagia/efeitos dos fármacos , Brônquios/citologia , Brônquios/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/patologia , Grafite/administração & dosagem , Humanos , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Nanopartículas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Fatores de TempoRESUMO
It is predicted that the toxicity of nanoparticles may be different depending on the properties of the nanoparticles and biological system being tested. However, the factors that influence the toxicity of nanoparticles have not been adequately investigated. In this study, we characterized two types of TiO2 nanorods, anatase (ATO) and brookite (BTO), and compared their toxicity in vivo and in vitro. ATO and BTO differed from each other most notably in their surface areas. Treatment with the two TiO2 nanorods (10 µg ml(-1) ) produced similar effects on the cell cycle in eight cell lines which are derived from potential target organs of nanoparticles, with the BTO eliciting stronger responses than ATO in all cell lines, among the cell lines, H9C2 showed the maximal change. Similarly, when mice were exposed to two TiO2 nanorods (1 mg kg(-1) ), BTO induced clearer histopathological lesions and triggered a more robust secretion of inflammatory cytokines than ATO. Furthermore, we compared the cellular response of both TiO2 nanorods using BEAS-2B cells, the human bronchial epithelial cell line. Both nanorods induced cell death by increasing the formation of autophagosome-like vacuoles. The mitochondrial calcium concentration decreased by exposure of both types, but the distribution of lysosome and endoplasmic reticulum (ER) showed a clear difference between the two nanorods. Thus, we conclude that the surface area acts as an important factor which depends on toxicity of nanorod type-TiO2 nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the type of cells tested, and that the assembly of autophagosome-like vacuoles is a critical part of the cellular response to nanoparticle exposure.
Assuntos
Pulmão/efeitos dos fármacos , Nanotubos/química , Titânio/química , Titânio/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Ratos , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Propriedades de Superfície , Testes de Toxicidade/métodosRESUMO
A complete understanding of the interaction between nanoparticles and biological systems, including nanoparticle uptake and distribution and the biological responses, could guide the design of safer and more effective nanoparticles than those currently available. In this study, we compared the distribution in mice over time of two rod-type titanium dioxide nanoparticles (TiNPs) that feature distinct phases, anatase (ATO) and brookite (BTO). Surface areas of BTO and ATO were estimated to be 102 and 268 m(2) g(-1) , respectively, and negative charge on the surface of ATO was higher than that of BTO in deionized water. Both TiNPs were rapidly distributed into tissues after injection. At 4 weeks after injection, both TiNPs were maximally accumulated in the spleen, followed by the liver, but the total accumulation of ATO in tissues measured in this study was more than that of BTO. Moreover, the cellular antioxidant function was similar although the levels of Ti measured in tissues were distinct between the two TiNPs. Based on these results, we suggest that the fate of TiNPs in the body may differ according to the size and surface charge of the TiNPs even when their shape is the same.
Assuntos
Nanopartículas Metálicas/análise , Titânio/farmacocinética , Animais , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Baço/efeitos dos fármacos , Baço/metabolismoRESUMO
Doping and hybridization with other semiconductors are highly effective ways to address the limitations, including their weak response to visible light and significant recombination of photogenerated carriers. In addition, the assisted carbon on the catalyst surface and the structural design have the advantage of being catalytically active. Herein, visible-light-active N-doped C/Na2Ti6O13/TiO2 hollow spheres (denoted as N-C/NTO/TiO2 HS) were successfully prepared using a facile two-step method and evaluated for methylene blue (MB) aqueous solution degradation under visible-light irradiation. The as-obtained N-C/NTO/TiO2 HS demonstrated improved photocatalytic efficiency (94 %) and pseudo-first-order kinetic degradation rate (0.023 min-1). Moreover, after three cycles of testing, N-C/NTO/TiO2 HS showed a 91 % degradation rate in its photostability. The enhanced photocatalytic performance was attributed to the combined effects of N-doping, carbon species on the surface, and the coupling of TiO2 and Na2Ti6O13 using morphology engineering. Finally, based on the experimental results, a possible photocatalytic mechanism was proposed. This study provides a rational approach toward the development of high-performance titanate-based photocatalysts for solar energy-assisted wastewater treatment.
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BACKGROUND: The faithful determination of the concentration and viability of yeast cells is important for biological research as well as industry. To this end, it is important to develop an automated cell counting algorithm that can provide not only fast but also accurate and precise measurement of yeast cells. RESULTS: With the proposed method, we measured the precision of yeast cell measurements by using 0%, 25%, 50%, 75% and 100% viability samples. As a result, the actual viability measured with the proposed yeast cell counting algorithm is significantly correlated to the theoretical viability (R2 = 0.9991). Furthermore, we evaluated the performance of our algorithm in various computing platforms. The results showed that the proposed algorithm could be feasible to use with low-end computing platforms without loss of its performance. CONCLUSIONS: Our yeast cell counting algorithm can rapidly provide the total number and the viability of yeast cells with exceptional accuracy and precision. Therefore, we believe that our method can become beneficial for a wide variety of academic field and industries such as biotechnology, pharmaceutical and alcohol production.
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In this study, we compared their toxicity in vivo and in vitro based on the physicochemical properties of three different types of TiO2 nanowires, H2Ti3O7 nanowires (1HTO), hydrothermal treatment (2HTO), and calcination (3HTO) of 1HTO. The surface of 1HTO was smooth, and the surface of 2HTO was much rougher. The negative charge on the surface increased in the order of 2HTO, 3HTO, and 1HTO, whereas the surface area increased in the order of 3HTO, 1HTO, and 2HTO. The lung is a main exposure route of nanoparticles. On day 28 after a single instillation (1 mg/kg), three nanowires induced a Th2-type inflammatory response together with the relative increase in CD4⺠T cells, especially by 2HTO. In vitro, three TiO2 nanowires (10 µg/ml) commonly induced the generation of cell debris in eight cell lines which may be the potential target organ of nanoparticles, especially by 2HTO. It seemed that the generation of cell debris coincides with the increase in autophagosome-like vacuoles in the cytosol. In further study using BEAS-2B cells originated from the lung, the protein amount from cells exposed to 2HTO decreased more clearly although the generation of reactive oxygen species (ROS) was less compared to 1HTO and 3HTO. Based on these results, we suggest that surface area may act as an important factor depends on the biological response by TiO2 nanowires. Furthermore, the increase in autophagosome-like vacuoles may be an important cause of cell death by nanoparticles with ROS.
Assuntos
Pulmão/efeitos dos fármacos , Nanofios/toxicidade , Pneumonia/induzido quimicamente , Linfócitos T/efeitos dos fármacos , Titânio/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Células HEK293 , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Linfócitos T/imunologia , Fatores de TempoRESUMO
Feline hypertrophic cardiomyopathy (HCM) is a common heart disease affecting 10-15% of all cats. Cats with HCM exhibit breathing difficulties, lethargy, and heart murmur; furthermore, feline HCM can also result in sudden death. Among various methods and indices, radiography and ultrasound are the gold standards in the diagnosis of feline HCM. However, only 75% accuracy has been achieved using radiography alone. Therefore, we trained five residual architectures (ResNet50V2, ResNet152, InceptionResNetV2, MobileNetV2, and Xception) using 231 ventrodorsal radiographic images of cats (143 HCM and 88 normal) and investigated the optimal architecture for diagnosing feline HCM through radiography. To ensure the generalizability of the data, the x-ray images were obtained from 5 independent institutions. In addition, 42 images were used in the test. The test data were divided into two; 22 radiographic images were used in prediction analysis and 20 radiographic images of cats were used in the evaluation of the peeking phenomenon and the voting strategy. As a result, all models showed > 90% accuracy; Resnet50V2: 95.45%; Resnet152: 95.45; InceptionResNetV2: 95.45%; MobileNetV2: 95.45% and Xception: 95.45. In addition, two voting strategies were applied to the five CNN models; softmax and majority voting. As a result, the softmax voting strategy achieved 95% accuracy in combined test data. Our findings demonstrate that an automated deep-learning system using a residual architecture can assist veterinary radiologists in screening HCM.