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1.
Nanoscale ; 13(31): 13353-13367, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477741

RESUMO

Despite the significance of surface absorbed proteins in determining the biological identity of nanoparticles (NPs) entering the human body, little is known about the surface corona and factors that shape their formation on dietary particles used as food additives. In this study, food grade NPs of silica and titania and their food additive counterparts (E551 and E171) were interacted with milk proteins or with skimmed milk and the levels of protein adsorption were quantified. Characteristics of proteins correlating with their level of adsorption to NPs were determined using partial least squares regression analysis. Results from individual protein-particle interactions revealed the significance of factors such as zeta potential, hydrophobicity and hydrodynamic size of particles, and protein characteristics such as the number of beta strands, isoelectric points, the number of amino acid units (Ile, Tyr, Ala, Gly, Pro, Asp, and Arg), and phosphorylation sites on their adsorption to particles. Similar regression analysis was performed to identify the characteristics of twenty abundant and enriched proteins (identified using LC-MS/MS analysis) for their association with the surface corona of milk-interacted particles. Contrary to individual protein-particle interactions, protein characteristics such as helices, turns, protein structures, disulfide bonds, the number of amino acid units (Cys, Met, Leu, and Trp), and Fe binding sites were significant for their association with the surface corona of milk interacted particles. This difference in factors identified from individual proteins and milk interacted particles suggested possible interactions of proteins with surface adsorbed biomolecules as revealed by scanning transmission X-ray microscopy and other biochemical assays.


Assuntos
Nanopartículas , Coroa de Proteína , Adsorção , Sequência de Aminoácidos , Cromatografia Líquida , Humanos , Proteoma , Espectrometria de Massas em Tandem
2.
BMC Microbiol ; 21(1): 222, 2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332549

RESUMO

BACKGROUND: Bovine mastitis is the most common infectious disease in dairy cattle with major economic implications for the dairy industry worldwide. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from dairy farms is vital not only for animal husbandry but also for public health. METHODS: In this study, the prevalence of AMR in 113 Escherichia coli isolates from cases of bovine clinical mastitis in Canada was investigated. Kirby-Bauer disk diffusion test with 18 antibiotics and microdilution method with 3 heavy metals (copper, zinc, and silver) was performed to determine the antibiotic and heavy-metal susceptibility. Resistant strains were assessed for efflux and ß-lactamase activities besides assessing biofilm formation and hemolysis. Whole-genome sequences for each of the isolates were examined to detect the presence of genes corresponding to the observed AMR and virulence factors. RESULTS: Phenotypic analysis revealed that 32 isolates were resistant to one or more antibiotics and 107 showed resistance against at least one heavy metal. Quinolones and silver were the most efficient against the tested isolates. Among the AMR isolates, AcrAB-TolC efflux activity and ß-lactamase enzyme activities were detected in 13 and 14 isolates, respectively. All isolates produced biofilm but with different capacities, and 33 isolates showed α-hemolysin activity. A positive correlation (Pearson r = + 0.89) between efflux pump activity and quantity of biofilm was observed. Genes associated with aggregation, adhesion, cyclic di-GMP, quorum sensing were detected in the AMR isolates corroborating phenotype observations. CONCLUSIONS: This investigation showed the prevalence of AMR in E. coli isolates from bovine clinical mastitis. The results also suggest the inadequacy of antimicrobials with a single mode of action to curtail AMR bacteria with multiple mechanisms of resistance and virulence factors. Therefore, it calls for combinatorial therapy for the effective management of AMR infections in dairy farms and combats its potential transmission to the food supply chain through the milk and dairy products.

3.
Nanotoxicology ; 15(4): 527-541, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33756094

RESUMO

Silver (nAg) and titanium dioxide nanoparticles (nTiO2) are common engineered nanoparticles (ENPs) added into paint for their antimicrobial and whitening properties, respectively. Weathering of outdoor painted surfaces can release such ENPs, though little is known about the potential effects of released ENPs on aquatic species. The objective of this study was to characterize the toxicity of nAg and nTiO2 released from painted panels using fish liver cells (CRL2643) and zebrafish embryos (OECD 236 embryotoxicity test). Cells and embryos were exposed to suspensions of pristine nAg or nTiO2, panels (unpainted or painted with nAg or nTiO2) or base paint, after sonication. Cell viability and gene expression were assessed using resazurin assay and qPCR, respectively, while embryo mortality and deformities were scored visually via microscopic examination. In the cell studies, both paint-released nanoparticles did not affect viability, but paint-released nAg resulted in differential expression of a few genes including gclc and ncf1. In embryos, paint-released nAg increased mortality and incidence of deformities, whereas paint-released nTiO2 resulted in differential expression of several genes including gclc, ncf1, txnrd1, gpx1b, and cyp1c1 but without major phenotypic abnormalities. Comparing the two types of exposures, paint-released exposures affected both molecular (gene expression) and apical (embryotoxicity) endpoints, while pristine exposures affected the expression of some genes but had no apical effects. The differing effects of paint-released and pristine nanoparticle exposures suggest that further research is needed to further understand how paint coatings (and the products of their weathering and aging) may influence nanoparticle toxicity to aquatic organisms.


Assuntos
Nanopartículas Metálicas , Animais , Nanopartículas Metálicas/toxicidade , Pintura/toxicidade , Prata/toxicidade , Titânio/toxicidade , Peixe-Zebra
4.
Chemosphere ; 243: 125401, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995870

RESUMO

Severe haze episodes originating from biomass burning are common in Southeast Asia. However, there is a paucity of data on the personal exposure and characteristics of Particulate Matter (PM) present in ambient air during haze and non-haze periods. Aims of this study were to monitor 24 h ambulatory exposure to PM among school children in Singapore; characterize haze and non-haze PM for their physicochemical properties, cytotoxicity and inflammatory potential, using bronchial epithelial cell culture model (BEAS-2B). Forty-six children had ambulatory PM exposure monitored using portable Aethalometer and their hourly activity recorded. The mean (±SE) PM exposure on a typical school day was 3343 (±174.4) ng/m3/min. Higher PM exposure was observed during haze periods and during commuting to and from the school. Characterization of PM collected showed a drastic increase in the proportion of ultrafine particle (UFP) in haze PM. These PM fraction showed higher level of sulphur, potassium and trace metals in comparison to those collected during non-haze periods. Dose dependent increases in abiotic reactive oxygen species generation, activation of NF-κB and cytotoxicity were observed for both haze and non-haze PM. Generally, haze PM induced significantly higher release of IL-6, IL-8 and TNFα by BEAS-2B cells in comparison to non-haze PM. In summary, this study provides experimental evidence for higher PM exposure during haze period which has the potential to elicit oxidative stress and pro-inflammatory cytokine release from airway epithelial cells.


Assuntos
Poluentes Atmosféricos/análise , Células Epiteliais/efeitos dos fármacos , Material Particulado/análise , Sistema Respiratório/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Biomassa , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Criança , Feminino , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Material Particulado/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Singapura , Oligoelementos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
5.
J Biomed Nanotechnol ; 15(11): 2216-2228, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31847936

RESUMO

While the wide-spectrum antimicrobial properties and stability of silver nanomaterials have been copiously utilized in many medical and consumer products, we found that Methicillin Resistant Staphylococcus aureus (MRSA) is less susceptible to silver in comparison to Methicillin Sensitive Staphylococcus aureus (MSSA). Pre-exposure of MRSA to sub-lethal concentrations of AgNO3 caused 2.5-fold increase in LD50 of silver suggesting an inducible resistance mechanism. Studies involving gene expression profiling and efflux pump blockers showed the induction of P-type efflux pumps (Cop A, Cop Z and Nor B) as the principle mechanism conferring silver resistance in MRSA. Chlorpromazine-an efflux pump blocker increased sensitivity of MRSA to silver. Leveraging on these observations, silver resistance in MRSA was circumvented by enhancing the bioavailability of silver by cationic functioning of silver nanoparticles or by co-delivering silver together with chlorpromazine. Atomic Force Microscopy showed that poly-ethylene imine (PEI) functionalized silver nanoparticles adhere to bacterial cells which was found to increase the bioavailability, membrane rupture and cell death. The strategy of co-delivery of AgNO3 and chlorpromazine using chitosan-functionalized wormhole silica nanoparticles caused 12 log reduction in bacterial count which was 1000 times higher than bacterial reduction by AgNO3 alone. In short, these studies showed that circumventing antimicrobial resistance in pathogenic bacteria is possible by designed silver nanotechnology.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Antibacterianos , Disponibilidade Biológica , Meticilina , Testes de Sensibilidade Microbiana , Nanotecnologia , Prata
6.
J Agric Food Chem ; 67(44): 12264-12272, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31613615

RESUMO

While silica particles are used extensively in food products, different grades and temperature variants of silica particles have not been compared for their physiochemical and biological properties. Different grades of silica (food-grade nanoparticles (FG-NPs), nonfood-grade nanoparticles (NFG-NPs), and food-grade micron particles (FG-MPs)) and the temperature variants generated by exposing FG-NPs to wet heating, dry heating, and refrigeration were compared for their physicochemical properties and interaction with trypsin. FG-NPs were similar to NFG-NPs and FG-MPs in their elemental composition and amorphous nature but had relatively less branched and ring siloxane groups than the latter ones. There were subtle but noticeable changes in the agglomeration behavior and relative abundance of different silica groups in FG-NPs exposed to food-handling temperatures. Secondary structure and function of trypsin were negatively impacted by FG-NPs and their temperature variants. Silica particles showed a "mixed-type inhibition" of trypsin resulting in partial digestion of bovine serum albumin. In conclusion, our studies showed differences in the surface chemistry of different grades of silica particles and temperature variants of FG-NPs and their negative impact on the structure and function of trypsin.


Assuntos
Aditivos Alimentares/química , Nanopartículas/química , Dióxido de Silício/química , Tripsina/química , Animais , Biocatálise , Bovinos , Hidrodinâmica , Tamanho da Partícula , Soroalbumina Bovina/química , Propriedades de Superfície , Temperatura
7.
Int J Biol Macromol ; 107(Pt B): 2364-2374, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29055708

RESUMO

Microbial transglutaminase (MTGase) has been currently utilized to form new food structures and matrices with high physicochemical stability. Incorporation of this multi-functional enzyme into structural composition of milk protein-based products, such as cheese and ice cream, can not only be a successful strategy to improve their nutritional and technological characteristics through intramolecular cross-linking, but also to reduce the production cost by decreasing fat and stabilizer contents. The recent research developments and promising results of MTGase application in producing functional formulations of cheese and ice cream with higher quality characteristics are reviewed. New interesting insights and future perspectives are also presented. The addition of MTGase to cheese led to significant improvements in moisture, yield, texture, rheology and sensory properties, without changes in the chemical composition. Furthermore, pH value of ice cream is not affected by the MTGase treatment. Compared to untreated ice creams, application of MTGase significantly promotes consistency, fat destabilization, overrun and organoleptic acceptance, while a substantial reduction in firmness and melting rate of samples was observed. The addition of MTGase to cheese and ice cream-milk provides reinforcement to the protein matrix and can be considered as a novel additive for improving the physicochemical and organoleptic properties of final products.


Assuntos
Queijo , Tecnologia de Alimentos/tendências , Sorvetes , Transglutaminases/química , Animais , Reagentes para Ligações Cruzadas/química , Estabilidade Enzimática , Manipulação de Alimentos , Humanos , Proteínas do Leite/química , Proteínas do Soro do Leite/química
8.
Nanotechnol Sci Appl ; 10: 147-162, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29238173

RESUMO

This article presents a simple, one-step, in situ generation of silver nanoparticle-functionalized fabrics with antibacterial properties, circumventing the conventional, multistep, time-consuming methods. Silver nanoparticle formation was studied with a library of capping agents (branched polyethylenimine [BPEI] of molecular weight [Mw] 10,000 and 25,000, polyvinylpyrrolidone, polyethylene glycol, polyvinylalcohol and citrate) mixed with silver nitrate. The mixture was then exposed to an assortment of light wavelengths (ultraviolet, infrared and simulated solar light) for studying the light-assisted synthesis of nanoparticles. The formation of nanoparticles corresponded with the reducing capabilities of the polymers wherein BPEI gave the best response. Notably, the irradiation wavelengths had little effect on the formation of the nanoparticle when the total irradiation energy was kept constant. The feasibility of utilizing this method for in situ nanoparticle synthesis on textile fabrics (towel [100% cotton], gauze [100% cotton], rayon, felt [100% polyester] and microfiber [15% nylon, 85% polyester]) was verified by exposing the fabrics soaked in an aqueous solution of 1% (w/v) AgNO3 and 1% (w/v) BPEI (Mw 25,000) to light. The formation of nanoparticles on fabrics and their retention after washing was verified using scanning electron microscopy and quantified by inductively coupled plasma optical emission spectrometry. The functional property of the fabric as an antibacterial surface was successfully demonstrated using model bacteria such as Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. The successful generation of silver nanoparticle-functionalized textile fabrics without the use of caustic chemicals, solvents and excessive heating presents a major step towards realizing a scalable green chemistry for industrial generation of functionalized fabrics for a wide range of applications.

9.
Aquat Toxicol ; 193: 60-71, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29040830

RESUMO

While, Aflatoxin B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEN) are the most prevalent mycotoxins co-existing in grain products and animal feeds, little is known about their combinatorial toxicities on aquatic life-forms. We studied the individual and combined effects of these mycotoxins in a fish cell line (BF-2) and zebrafish larvae (wild-type and transgenic). The types of interactions in mycotoxins combinations on cell viability were determined by using Chou-Talalay model. Induction of oxidative stress pathway in mycotoxins-exposed BF-2 cells was assessed using high content screening (HCS). Mycotoxin-exposed wild-type zebrafish larvae were examined for mortality and morphological abnormalities and transgenic zebrafish larvae (expressing DsRed in the liver) were imaged using HCS and examined for liver abnormalities. Results showed that the cytotoxicity of mycotoxins in a decreasing order was AFB1>DON>ZEN, however, the highest mortality rate and liver damage in zebrafish were observed for AFB1 followed by ZEN. AFB1+DON and AFB1+ZEN synergistically enhanced the toxic effects on BF-2 cells and zebrafish while DON+ZEN showed antagonism. Interestingly, in the tertiary combination, the synergism seen at lower individual concentrations of mycotoxins progressively turned to an overall antagonism at higher doses. The results provide a scientific basis for the necessity to consider co-exposure when formulating risk-management strategies.


Assuntos
Aflatoxina B1/toxicidade , Tricotecenos/toxicidade , Poluentes Químicos da Água/toxicidade , Zearalenona/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Ração Animal , Animais , Animais Geneticamente Modificados , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/genética , Larva/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
10.
Food Chem Toxicol ; 103: 18-27, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28223122

RESUMO

To understand the combinatorial toxicity of mycotoxins, we measured the effects of individual, binary and tertiary combinations of Aflatoxin B1 (AFB1), Deoxynivalenol (DON) and Zearalenone (ZEN) on the cell viability and cellular perturbations of HepG2 and RAW 264.7 cells. The nature of mycotoxins interactions was assessed using mathematical modeling (Chou-Talalay). Mechanisms of cytotoxicity were studied using high content screening (HCS) that probed cytotoxicity responses, such as changes in intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), intracellular calcium ([Ca2+]i) flux, and cell membrane damage. Our results showed that individual cytotoxicity of mycotoxins in a decreasing order was DON>AFB1>ZEN. Varying combinations of mycotoxins at differing concentrations showed different types of interactions. Most of the mixtures showed increasing toxic effects-synergism and/or addition while antagonistic effects were observed with combination of AFB1+ZEN. Generally, combination of mycotoxins showed significantly increased intracellular ROS production and [Ca2+]i flux, and decreased MMP in both cell lines, showing that the synergistic and additive effects of mycotoxin combination originate from perturbations of multiple cellular functions. Additionally, this study demonstrated the applicability of HCS for gaining mechanistic understanding on the toxicity of individual as well as combinatorial mycotoxins, and also provided scientific bases for formulating regulatory policies.


Assuntos
Aflatoxina B1/toxicidade , Testes de Toxicidade/métodos , Tricotecenos/toxicidade , Zearalenona/toxicidade , Aflatoxina B1/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Células Hep G2/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Micotoxinas/administração & dosagem , Micotoxinas/toxicidade , Células RAW 264.7/efeitos dos fármacos , Tricotecenos/administração & dosagem , Zearalenona/administração & dosagem
11.
Toxicol Lett ; 238(3): 20-9, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26253280

RESUMO

Although building constructions are a recurring part of urbanization, the health risk of particulate matters (PM) originating from such activities have seldom been subjected to detailed studies. We sought to characterize the relative risk of air borne PM collected from different heights (ground and top floor) of a building adjacent to a building under early phase of construction. We determined the physico-chemical properties such as size and shape, elemental composition and surface charge of the PM. The oxidative stress dependent cytotoxic and pro-inflammatory responses were assessed in BEAS-2B and RAW 264.7 cell lines using high-content-screening platforms. In comparison to top floor, the total mass of PM collected from ground floor was two-three folds higher and the mass fraction was dominated by PM20-35. Elemental analysis showed abundance of Si, Al, K, Ca and Fe in bigger PM while for PM0.25-0.5 it was mostly constituted by C and crystals rich in S and K. PM caused NFκB activation, secretion of pro-inflammatory cytokines and cytotoxicity wherein PM0.25-0.5 was the most potent among the tested PM. Estimated exposure level and lung burden together with the data on hazard potential were used for developing a MATLAB based risk-assessment model which suggested that the potential for health risk is relatively higher at the ground floor. Our studies demonstrated differences in, relative abundance of PM, their physicochemical and biological properties collected from different heights adjacent to a construction site and showed that relative health risk is higher at the ground floor.


Assuntos
Poluentes Atmosféricos/química , Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/toxicidade , Animais , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Varredura , NF-kappa B/genética , NF-kappa B/metabolismo , Medição de Risco
12.
Nanotoxicology ; 9(3): 404-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25976321

RESUMO

An international symposium for nanosafety was held recently at the Nanyang Technological University in Singapore. Topics relating to understanding nanomaterial properties, tools, and infrastructure required for predicting hazardous outcomes, measuring nanomaterial exposure levels, systems approach for risk assessment and public's perception of nanotechnology were covered. The need for a multidisciplinary approach, across both natural and social sciences, for developing sustainable nanotechnology solutions was heavily emphasized. This commentary highlights the major issues discussed and the commitment of the nanosafety research community in Singapore to contribute collectively to realise the vision of sustainable nanotechnology.


Assuntos
Nanoestruturas/toxicidade , Nanotecnologia , Segurança
13.
Indian J Microbiol ; 55(2): 184-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25805905

RESUMO

Coenzyme Q10 (CoQ10) is a blockbuster nutraceutical molecule which is often used as an oral supplement in the supportive therapy for cardiovascular diseases, cancer and neurodegenerative diseases. It is commercially produced by fermentation process, hence constructing the high yielding CoQ10 producing strains is a pre-requisite for cost effective production. Paracoccus denitrificans ATCC 19367, a biochemically versatile organism was selected to carry out the studies on CoQ10 yield improvement. The wild type strain was subjected to iterative rounds of mutagenesis using gamma rays and NTG, followed by selection on various inhibitors like CoQ10 structural analogues and antibiotics. The screening of mutants were carried out using cane molasses based optimized medium with feeding strategies at shake flask level. In the course of study, the mutant P-87 having marked resistance to gentamicin showed 1.25-fold improvements in specific CoQ10 content which was highest among all tested mutant strains. P-87 was phenotypically differentiated from the wild type strain on the basis of carbohydrate assimilation and FAME profile. Molecular differentiation technique based on AFLP profile showed intra specific polymorphism between wild type strain and P-87. This study demonstrated the beneficial outcome of induced mutations leading to gentamicin resistance for improvement of CoQ10 production in P. denitrificans mutant strain P-87. To investigate the cause of gentamicin resistance, rpIF gene from P-87 and wild type was sequenced. No mutations were detected on the rpIF partial sequence of P-87; hence gentamicin resistance in P-87 could not be conferred with rpIF gene. However, detecting the mutations responsible for gentamicin resistance in P-87 and correlating its role in CoQ10 overproduction is essential. Although only 1.25-fold improvement in specific CoQ10 content was achieved through mutant P-87, this mutant showed very interesting characteristic, differentiating it from its wild type parent strain P. denitrificans ATCC 19367, which are presented in this paper.

14.
Indian J Microbiol ; 54(3): 343-57, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24891743

RESUMO

Coenzyme Q10 (CoQ10) is an industrially important molecule having nutraceutical and cosmeceutical applications. CoQ10 is mainly produced by microbial fermentation and the process demands the use of strains with high productivity and yields of CoQ10. During strain improvement program consisting of sequential induced mutagenesis, rational selection and screening process, a mutant strain UF16 was generated from Sporidiobolus johnsonii ATCC 20490 with 2.3-fold improvements in CoQ10 content. EMS and UV rays were used as mutagenic agents for generating UF16 and it was rationally selected based on atorvastatin resistance as well as survival at free radicals exposure. We investigated the genotypic and phenotypic changes in UF16 in order to differentiate it from wild type strain. Morphologically it was distinct due to reduced pigmentation of colony, reduced cell size and significant reduction in mycelial growth forms with abundance of yeast forms. At molecular level, UF16 was differentiated based on PCR fingerprinting method of RAPD as well as large and small-subunit rRNA gene sequences. Rapid molecular technique of RAPD analysis using six primers showed 34 % polymorphic fragments with mean genetic distance of 0.235. The partial sequences of rRNA-gene revealed few mutation sites on nucleotide base pairs. However, the mutations detected on rRNA gene of UF16 were less than 1 % of total base pairs and its sequence showed 99 % homology with the wild type strain. These mutations in UF16 could not be linked to phenotypic or genotypic changes on CoQ10 biosynthetic pathway that resulted in improved yield. Hence, investigating the mutations responsible for deregulation of CoQ10 pathway is essential to understand the cause of overproduction in UF16. Phylogenetic analysis based on RAPD bands and rRNA gene sequences coupled with morphological variations, exhibited the novelty of mutant UF16 having potential for improved CoQ10 production.

15.
Environ Sci Technol ; 48(11): 6374-82, 2014 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-24811346

RESUMO

The increasing use of silver (Ag) and titanium dioxide (TiO2) nanoparticles (NPs) in consumer products and their inevitable seepage into the environment prompted us to investigate their potential toxicity to a fish cell line (BF-2) and zebrafish embryos under dark and Simulated Solar Light (SSL) exposure conditions. Using high throughput screening (HTS) platforms, we showed that the oxidative stress-dependent cytotoxicity and embryonic toxicity of NPs were significantly increased upon exposure to SSL. While, the toxicity of TiO2 NPs under SSL exposure could be explained by hydroxyl radical generation, the enhanced toxicity of Ag NPs under SSL exposure was due to surface oxidation and physicochemical modification of Ag NPs and shedding of Ag+, leading to an increased bioavailability of silver. Our observations that solar light could induce physicochemical transformation of TiO2 and Ag NPs and enhance their toxic potential emphasizes the need for conducting future toxicity studies under environmentally relevant exposure conditions to guide decision making on the safe handling of NPs.


Assuntos
Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Prata/toxicidade , Luz Solar , Titânio/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Embrião não Mamífero , Nanopartículas Metálicas/efeitos da radiação , Prata/farmacocinética , Prata/efeitos da radiação , Titânio/farmacocinética , Titânio/efeitos da radiação , Peixe-Zebra
16.
Analyst ; 139(5): 943-53, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24260774

RESUMO

Relationships among fourteen different biological responses (including ten signaling pathway activities and four cytotoxicity effects) of murine macrophage (RAW264.7) and bronchial epithelial (BEAS-2B) cells exposed to six metal and metal oxide nanoparticles (NPs) were analyzed using both statistical and data mining approaches. Both the pathway activities and cytotoxicity effects were assessed using high-throughput screening (HTS) over an exposure period of up to 24 h and concentration range of 0.39-200 mg L(-1). HTS data were processed by outlier removal, normalization, and hit-identification (for significantly regulated cellular responses) to arrive at reliable multiparametric bioactivity profiles for the NPs. Association rule mining was then applied to the bioactivity profiles followed by a pruning process to remove redundant rules. The non-redundant association rules indicated that "significant regulation" of one or more cellular responses implies regulation of other (associated) cellular response types. Pairwise correlation analysis (via Pearson's χ(2) test) and self-organizing map clustering of the different cellular response types indicated consistency with the identified non-redundant association rules. Furthermore, in order to explore the potential use of association rules as a tool for data-driven hypothesis generation, specific pathway activity experiments were carried out for ZnO NPs. The experimental results confirmed the association rule identified for the p53 pathway and mitochondrial superoxide levels (via MitoSox reagent) and further revealed that blocking of the transcriptional activity of p53 lowered the MitoSox signal. The present approach of using association rule mining for data-driven hypothesis generation has important implications for streamlining multi-parameter HTS assays, improving the understanding of NP toxicity mechanisms, and selection of endpoints for the development of nanomaterial structure-activity relationships.


Assuntos
Ensaios de Triagem em Larga Escala/métodos , Nanopartículas Metálicas/toxicidade , Óxidos/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Camundongos
17.
J Agric Biol Environ Stat ; 18(2): 159-177, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24839387

RESUMO

The development of high throughput screening (HTS) assays in the field of nanotoxicology provide new opportunities for the hazard assessment and ranking of engineered nanomaterials (ENMs). It is often necessary to rank lists of materials based on multiple risk assessment parameters, often aggregated across several measures of toxicity and possibly spanning an array of experimental platforms. Bayesian models coupled with the optimization of loss functions have been shown to provide an effective framework for conducting inference on ranks. In this article we present various loss-function-based ranking approaches for comparing ENM within experiments and toxicity parameters. Additionally, we propose a framework for the aggregation of ranks across different sources of evidence while allowing for differential weighting of this evidence based on its reliability and importance in risk ranking. We apply these methods to high throughput toxicity data on two human cell-lines, exposed to eight different nanomaterials, and measured in relation to four cytotoxicity outcomes. This article has supplementary material online.

18.
Small ; 9(9-10): 1504-20, 2013 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-23019115

RESUMO

The rising production of nanomaterial-based consumer products has raised safety concerns. Testing these with animal and other direct models is neither ethically nor economically viable, nor quick enough. This review aims to discuss the strength of in vitro testing, including the use of 2D and 3D cultures, stem cells, and tissue constructs, etc., which would give fast and repeatable answers of a highly specific nature, while remaining relevant to in vivo outcomes. These results can then be combined and the overall toxicity predicted with relative accuracy. Such in vitro models can screen potentially toxic nanomaterials which, if required, can undergo further stringent studies in animals. The cyto- and phototoxicity of some high-volume production nanomaterials, using in vitro models, is also reviewed.


Assuntos
Exposição Ambiental , Nanoestruturas , Humanos , Células-Tronco/efeitos dos fármacos , Engenharia Tecidual , Testes de Toxicidade
19.
Arch Toxicol ; 87(1): 99-109, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22885792

RESUMO

To uncover the size influence of TiO(2) nanoparticles on their potential toxicity, the cytotoxicity of different-sized TiO(2) nanoparticles with and without photoactivation was tested. It was demonstrated that without photoactivation, TiO(2) nanoparticles were inert up to 100 µg/ml. On the contrary, with photoactivation, the toxicity of TiO(2) nanoparticles significantly increased, which correlated well with the specific surface area of the particles. Our results also suggest that the generation of hydroxyl radicals and reactive oxygen species (ROS)-mediated damage to the surface-adsorbed biomolecules could be the two major reasons for the cytotoxicity of TiO(2) nanoparticles after photoactivation. Higher ROS generation from smaller particles was detected under both biotic and abiotic conditions. Smaller particles could adsorb more proteins, which was confirmed by thermogravimetric analysis. To further investigate the influence of the generation of hydroxyl radicals and adsorption of protein, poly (ethylene-alt-maleic anhydride) (PEMA) and chitosan were used to coat TiO(2) nanoparticles. The results confirmed that surface coating of TiO(2) nanoparticles could reduce such toxicity after photoactivation, by hindering adsorption of biomolecules and generation of hydroxyl radical (·OH) during photoactivation.


Assuntos
Dermatite Fototóxica , Nanopartículas Metálicas/toxicidade , Tamanho da Partícula , Adsorção , Animais , Linhagem Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/toxicidade , Radical Hidroxila/metabolismo , Maleatos/química , Maleatos/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Microscopia Eletrônica de Varredura , Polietilenos/química , Polietilenos/farmacologia , Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade/métodos , Raios Ultravioleta
20.
Arch Toxicol ; 87(6): 1075-86, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22983807

RESUMO

The aim of this study is to uncover the size influence of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles on their potential cytotoxicity. PLGA and TiO(2) nanoparticles of three different sizes were thoroughly characterized before in vitro cytotoxic tests which included viability, generation of reactive oxygen species (ROS), mitochondrial depolarization, integrity of plasma membrane, intracellular calcium influx and cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7 cells and BEAS-2B cells after cells were incubated with PLGA or TiO(2) nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly lethal toxicity up to a concentration of 300 µg/ml, the TNF-α release after the stimulation of PLGA nanoparticles should not be ignored especially in clinical applications. Relatively more toxic TiO(2) nanoparticles triggered cell death, ROS generation, mitochondrial depolarization, plasma membrane damage, intracellular calcium concentration increase and size-dependent TNF-α release, especially at a concentration higher than 100 µg/ml. These cytotoxic effects could be due to the size-dependent interaction between nanoparticles and biomolecules, as smaller particles tend to adsorb more biomolecules. In summary, we demonstrated that the ability of protein adsorption could be an important paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for low toxic nanomaterials such as PLGA and TiO(2) nanoparticles.


Assuntos
Células Epiteliais/efeitos dos fármacos , Ácido Láctico/toxicidade , Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Ácido Poliglicólico/toxicidade , Titânio/toxicidade , Adsorção , Animais , Sinalização do Cálcio/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/patologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mediadores da Inflamação/metabolismo , Ácido Láctico/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/metabolismo , Fatores de Tempo , Titânio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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