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1.
Drug Chem Toxicol ; 45(4): 1660-1669, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33297782

RESUMO

Nano-titanium nitride (Nano-TiN) has strong resistance to wear and corrosion, good biocompatibility, and an attractive metallic luster. Nano-TiN is widely used in medical devices, such as orthopedic implants, syringe needles, coronary stents, and long-term dental implants, and also in imitation gold jewelry. Despite its widespread use, there are few reports describing safety evaluations of Nano-TiN. Here, we exposed healthy zebrafish embryos to different concentrations of Nano-TiN solution for five days, starting at about four hours post fertilization, and found that Nano-TiN caused dose- and time-dependent developmental toxicity. With increasing Nano-TiN concentration and length of exposure, mortality, and deformities gradually increased; body length shortened and hatching rate and motility were significantly reduced. We also found that exposure to Nano-TiN affected development of the heart, liver, nerves, and other organs, and led to elevated levels of reactive oxygen species and reduced antioxidant capacity. Exposure to Nano-TiN resulted in downregulation of expression of antioxidant genes, such as nrf2, gclc, gclm, ho-1, and nqo1. Our results showed that exposure to Nano-TiN caused developmental and organ toxicity in zebrafish embryos and that the toxic effects may be mediated through oxidative stress.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Antioxidantes/metabolismo , Embrião não Mamífero/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade
2.
Int J Mol Sci ; 21(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32093039

RESUMO

Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms has been documented, but the toxicity and behavioral changes of nanoplastics (NPs) in mammals are scarce. In spite of their small size, nanoplastics have an enormous surface area, which bears the potential to bind even bigger amounts of toxic compounds in comparison to microplastics. Here, we used polystyrene nanoplastics (PS-NPs) (diameter size at ~70 nm) to investigate the neurobehavioral alterations, tissue distribution, accumulation, and specific health risk of nanoplastics in adult zebrafish. The results demonstrated that PS-NPs accumulated in gonads, intestine, liver, and brain with a tissue distribution pattern that was greatly dependent on the size and shape of the NPs particle. Importantly, an analysis of multiple behavior endpoints and different biochemical biomarkers evidenced that PS-NPs exposure induced disturbance of lipid and energy metabolism as well as oxidative stress and tissue accumulation. Pronounced behavior alterations in their locomotion activity, aggressiveness, shoal formation, and predator avoidance behavior were exhibited by the high concentration of the PS-NPs group, along with the dysregulated circadian rhythm locomotion activity after its chronic exposure. Moreover, several important neurotransmitter biomarkers for neurotoxicity investigation were significantly altered after one week of PS-NPs exposure and these significant changes may indicate the potential toxicity from PS-NPs exposure. In addition, after ~1-month incubation, the fluorescence spectroscopy results revealed the accumulation and distribution of PS-NPs across zebrafish tissues, especially in gonads, which would possibly further affect fish reproductive function. Overall, our results provided new evidence for the adverse consequences of PS-NPs-induced behavioral dysregulation and changes at the molecular level that eventually reduce the survival fitness of zebrafish in the ecosystem.


Assuntos
Biomarcadores/metabolismo , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poliestirenos/toxicidade , Poluição da Água/efeitos adversos , Peixe-Zebra/metabolismo , Agressão/efeitos dos fármacos , Animais , Escala de Avaliação Comportamental , Comportamento Animal/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Ecossistema , Metabolismo Energético/efeitos dos fármacos , Gônadas/diagnóstico por imagem , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Intestinos/diagnóstico por imagem , Intestinos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/diagnóstico por imagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Microscopia Eletrônica de Transmissão , Músculos/efeitos dos fármacos , Músculos/metabolismo , Nanopartículas/química , Nanopartículas/ultraestrutura , Neurotransmissores/metabolismo , Poliestirenos/química , Medição de Risco , Espectrometria de Fluorescência , Distribuição Tecidual/efeitos dos fármacos
3.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098080

RESUMO

A T-maze test is an experimental approach that is used in congenital research. However, the food reward-based protocol for the T-maze test in fish has low efficiency and a long training period. The aim of this study is to facilitate the T-maze conditions by using a combination of the principles of passive avoidance and a spatial memory test. In our modified T-maze settings, electric shock punishment (1-2 V, 0.3-0.5 mA) is given at the left arm, with a green cue at the right arm. Also, the depth of both arms of the T-maze was increased. The parameters measured in our T-maze design were latency, freezing time, and time spent in different areas of the T-maze. We validated the utility of our modified T-maze protocol by showing the consistent finding of memory impairment in ZnCl2-treated fish, which has been previously detected with the passive avoidance test. In addition, we also tested the spatial memory performance of leptin a (lepa) mutants which displayed an obesity phenotype. The results showed that although the learning and memory performance for lepa KO fish were similar to control fish, they displayed a higher freezing behavior during the training phase. In conclusion, we have established a modified T-maze protocol that can be used to evaluate the anxiety, learning, and memory capacity of adult zebrafish within three days, for the first time.


Assuntos
Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Peixe-Zebra/fisiologia , Animais
4.
Molecules ; 25(9)2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32403340

RESUMO

Recently, magnetic nanoparticles (MNPs) have gained much attention in the field of biomedical engineering for therapeutic as well as diagnostic purposes. Carbon magnetic nanoparticles (C-MNPs) are a class of MNPs categorized as organic nanoparticles. C-MNPs have been under considerable interest in studying in various applications such as magnetic resonance imaging, photothermal therapy, and intracellular transportof drugs. Research work is still largely in progress for testing the efficacy of C-MNPs on the theranostics platform in cellular studies and animal models. In this study, we evaluated the neurobehavioral toxicity parameters on the adult zebrafish (Danio rerio) at either low (1 ppm) or high (10 ppm) concentration level of C-MNPs over a period of two weeks by waterborne exposure. The physical properties of the synthesized C-MNPs were characterized by transmission electron microscopy, Raman, and XRD spectrum characterization. Multiple behavior tests for the novel tank, mirror biting, predator avoidance, conspecific social interaction, shoaling, and analysis of biochemical markers were also conducted to elucidate the corresponding mechanism. Our data demonstrate the waterborne exposure of C-MNPs is less toxic than the uncoated MNPs since neither low nor high concentration C-MNPs elicit toxicity response in behavioral and biochemical tests in adult zebrafish. The approach combining biochemical and neurobehavioral approaches would be helpful for understanding C-MNPs association affecting the bioavailability, biosafety, interaction, and uptake of these C-MNPs in the living organism.


Assuntos
Encéfalo/efeitos dos fármacos , Carbono/química , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/metabolismo , Animais , Escala de Avaliação Comportamental , Encéfalo/metabolismo , Catecolaminas/metabolismo , Análise por Conglomerados , Feminino , Hidrocortisona/metabolismo , Imageamento por Ressonância Magnética , Magnetismo , Nanopartículas de Magnetita/ultraestrutura , Masculino , Metalotioneína/metabolismo , Microscopia Eletrônica de Transmissão , Neurotransmissores/metabolismo , Análise de Componente Principal , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Difração de Raios X , Peixe-Zebra/fisiologia
5.
Molecules ; 25(18)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937928

RESUMO

Antrodia cinnamomea (AC) has been shown to have anti-inflammatory, anti-tumor, and immunomodulation activities. It is estimated that hundreds of metric tons of AC extraction waste (ACEW) are produced per year in Taiwan. This study aims to assess the feasibility of applying ACEW as feed supplement in the aquaculture industry. ACEW significantly inhibited the growth of microorganisms in the water tank, by around 39.4% reduction on the fifth day with feed supplemented of 10% ACEW. The feed conversion efficiency of zebrafish with 10% ACEW supplementation for 30 days was 1.22-fold compared to that of the control. ACEW dramatically improved the tolerances of zebrafish under the heat and cold stresses. When at water temperature extremes of 38 °C or 11 °C, compared to the 100% mortality rate in the control group, the 10% ACEW diet group still had 91.7% and 83.3% survival rates, respectively. In a caudal fin amputation test, the fin recovery of zebrafish was increased from 68.4% to 93% with 10% ACEW diet after 3-week regeneration. ACEW effectively down-regulated the gene expression of TNF-α, IL-1ß, IL-6, and IL-10, and up-regulated the gene expression of IL-4/13A. Additionally, the supplement of ACEW in the feed can maintain and prevent the fish's body weight from dropping too much under enteritis. Taken together, ACEW has beneficial potential in aquaculture.


Assuntos
Aquicultura , Resíduos Industriais , Polyporales/química , Regeneração/efeitos dos fármacos , Amputação Cirúrgica , Ração Animal , Animais , Anti-Infecciosos/química , Anti-Inflamatórios/química , Peso Corporal/efeitos dos fármacos , Temperatura Baixa , Suplementos Nutricionais , Feminino , Temperatura Alta , Concentração de Íons de Hidrogênio , Inflamação/tratamento farmacológico , Masculino , Polissacarídeos/química , Triterpenos/química , Água/análise , Peixe-Zebra/fisiologia
6.
Int J Mol Sci ; 20(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344827

RESUMO

Notch signaling is one of the evolutionarily conserved signaling pathways in multicellular organisms. It plays an important role in embryonic development. During skeletal development of vertebrates, it regulates bone homeostasis by manipulating both osteoblastogenesis and osteoclastogenesis through different mechanisms. However, due to the different nature of Notch signaling in mesenchymal stem cell and osteoblast, regulation of Notch signaling in bone-related diseases remains unsettled. Previous studies by cell culture and mouse models showed contradictory results regarding the role of Notch signaling in bone homeostasis. To clarify the role of Notch signaling in osteogenesis, we established a zebrafish model, in which Notch1a intracellular domain (N1aICD) was specifically expressed in the osteoblasts. We found that overexpression of N1aICD in osteoblasts caused hyperosteogeny in the column region of zebrafish with the morphology of narrowed neural/hemal canals. Moreover, increased metabolic activity of osteoblasts instead of augmenting osteoblast number led to hyperosteogeny in N1aICD-overexpressed zebrafish. In summary, we successfully established a transgenic zebrafish line overexpressing N1aICD to clarify the in-vivo function of Notch signaling during osteoblastogenesis. In the future, this fish line can serve as a valuable tool to test the therapeutic drugs for hyperosteogeny.


Assuntos
Desenvolvimento Embrionário/genética , Proteínas de Homeodomínio/genética , Proteínas do Tecido Nervoso/genética , Osteogênese/genética , Receptor Notch1/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Doenças Ósseas/genética , Doenças Ósseas/patologia , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteoblastos/metabolismo , Receptores Notch/genética , Transdução de Sinais/genética , Peixe-Zebra/crescimento & desenvolvimento
7.
Int J Mol Sci ; 20(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752171

RESUMO

There is an imperative need to develop efficient whole-animal-based testing assays to determine the potential toxicity of engineered nanomaterials. While previous studies have demonstrated toxicity in lung and skin cells after C70 nanoparticles (NPs) exposure, the potential detrimental role of C70 NPs in neurobehavior is largely unaddressed. Here, we evaluated the chronic effects of C70 NPs exposure on behavior and alterations in biochemical responses in adult zebrafish. Two different exposure doses were used for this experiment: low dose (0.5 ppm) and high dose (1.5 ppm). Behavioral tests were performed after two weeks of exposure of C70 NPs. We found decreased locomotion, exploration, mirror biting, social interaction, and shoaling activities, as well as anxiety elevation and circadian rhythm locomotor activity impairment after ~2 weeks in the C70 NP-exposed fish. The results of biochemical assays reveal that following exposure of zebrafish to 1.5 ppm of C70 NPs, the activity of superoxide dismutase (SOD) in the brain and muscle tissues increased significantly. In addition, the concentration of reactive oxygen species (ROS) also increased from 2.95 ± 0.12 U/ug to 8.46 ± 0.25 U/ug and from 0.90 ± 0.03 U/ug to 3.53 ± 0.64 U/ug in the muscle and brain tissues, respectively. Furthermore, an increased level of cortisol was also observed in muscle and brain tissues, ranging from 17.95 ± 0.90 pg/ug to 23.95 ± 0.66 pg/ug and from 3.47 ± 0.13 pg/ug to 4.91 ± 0.51 pg/ug, respectively. Increment of Hif1-α level was also observed in both tissues. The elevation was ranging from 11.65 ± 0.54 pg/ug to 18.45 ± 1.00 pg/ug in the muscle tissue and from 4.26 ± 0.11 pg/ug to 6.86 ± 0.37 pg/ug in the brain tissue. Moreover, the content of DNA damage and inflammatory markers such as ssDNA, TNF-α, and IL-1ß were also increased substantially in the brain tissues. Significant changes in several biomarker levels, including catalase and malondialdehyde (MDA), were also observed in the gill tissues. Finally, we used a neurophenomic approach with a particular focus on environmental influences, which can also be easily adapted for other aquatic fish species, to assess the toxicity of metal and carbon-based nanoparticles. In summary, this is the first study to illustrate the adult zebrafish toxicity and the alterations in several neurobehavior parameters after zebrafish exposure to environmentally relevant amounts of C70 NPs.


Assuntos
Comportamento Animal/efeitos dos fármacos , Fulerenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Exposição Ambiental/efeitos adversos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hidrocortisona/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Nanopartículas Metálicas , Músculos/efeitos dos fármacos , Músculos/metabolismo , Testes de Toxicidade Crônica , Peixe-Zebra/metabolismo
8.
Int J Mol Sci ; 20(2)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669336

RESUMO

Atherosclerosis is the pathological process in arteries due to the plaque formation that is responsible for several diseases like heart disease, stroke and peripheral arterial disease. In this study, we performed in vitro and in vivo assays to evaluate the potential anti-atherosclerosis activity of peach kernel oil. For the in vitro assay, we incubated human umbilical vein endothelial cells (HUVEC) with tumor necrosis factor-α (TNF-α) to induce tissue factors (TF, an essential mediator of hemostasis and trigger of thrombosis) elevation. We found that TNF-α-induced TF elevation was suppressed by peach kernel oil in a dose-dependent manner at both mRNA and protein levels. Peach kernel oil can significantly improve HUVEC viability, protect the endothelial cells, which achieved the goal of prevention of thrombotic diseases. For the in vivo assay, we investigated the effect and mechanism of peach kernel oil on preventing atherosclerotic lesion formation in ApoE knockout mice. Results show that peach kernel oil could reduce total cholesterol, triglyceride, low-density lipoprotein cholesterol levels, elevate the high-density lipoprotein cholesterol level in serum, and reduce the area of the aortic atherosclerotic lesions in high-fat diet fed ApoE knockout mice. Moreover, peach kernel oil treatment can significantly down regulate the expression of TF protein to inhibit the formation of atherosclerotic plaque. In conclusion, peach kernel oil may be a potential health food to prevent atherosclerosis in cardiovascular diseases.


Assuntos
Aterosclerose/etiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Óleos de Plantas/farmacologia , Prunus persica/química , Tromboplastina/genética , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Graxos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Camundongos Knockout para ApoE , Modelos Biológicos , Compostos Fitoquímicos/química , Óleos de Plantas/química , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , RNA Mensageiro/genética , Tromboplastina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Int J Mol Sci ; 19(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513951

RESUMO

There is a growing concern for the potential toxicity of engineered nanomaterials that have made their way into virtually all novel applications in the electronics, healthcare, cosmetics, technology, and engineering industries, and in particular, biomedical products. However, the potential toxicity of carbon 60 (C60) at the behavioral level has not been properly evaluated. In this study, we used idTracker, a multitracking algorithm to quantitatively assess behavioral toxicity induced by C60 nanoparticles (C60 NPs) in adult zebrafish. We demonstrated that locomotion, novel tank exploration, aggression, shoaling, and color preference activities of the C60 NPs-treated fish was significantly reduced. In addition, the C60 NPs-treated fish also displayed dysregulation of the circadian rhythm by showing lower locomotion activities in both day and night cycles. The biochemical results showed that C60 NPs exposure at low concentration induced oxidative stress and DNA damage, reduced anti-oxidative capacity and ATP (adenosine triphosphate) levels, and induced stress-associated hormones, hypoxia, as well as inflammation marker upregulation in muscle and gill tissues. Together, this work, for the first time, provide direct evidence showing that the chronic exposure of C60 NPs induced multiple behavioral abnormalities in adult zebrafish. Our findings suggest that the ecotoxicity of C60 NPs towards aquatic vertebrates should be carefully evaluated.


Assuntos
Comportamento Animal/efeitos dos fármacos , Exposição Ambiental/análise , Fulerenos/toxicidade , Nanopartículas/toxicidade , Testes de Toxicidade , Peixe-Zebra/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Comportamento de Escolha/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Cor , Determinação de Ponto Final , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hipóxia/patologia , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Comportamento Predatório/efeitos dos fármacos , Comportamento Social
10.
Int J Mol Sci ; 19(12)2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30551684

RESUMO

Leptin, a hormone secreted by peripheral adipose tissues, regulates the appetite in animals. Recently, evidence has shown that leptin also plays roles in behavioral response in addition to controlling appetite. In this study, we examined the potential function of leptin on non-appetite behaviors in zebrafish model. By using genome editing tool of Transcription activator-like effector nuclease (TALEN), we successfully knocked out leptin a (lepa) gene by deleting 4 bp within coding region to create a premature-translation stop. Morphological and appetite analysis showed the lepa KO fish display a phenotype with obese, good appetite and elevation of Agouti-related peptide (AgRP) and Ghrelin hormones, consistent with the canonical function of leptin in controlling food intake. By multiple behavior endpoint analyses, including novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm, and color preference assay, we found the lepa KO fish display an anxiogenic phenotype showing hyperactivity with rapid swimming, less freezing time, less fear to predator, loose shoaling area forming, and circadian rhythm and color preference dysregulations. Using biochemical assays, melatonin, norepinephrine, acetylcholine and serotonin levels in the brain were found to be significantly reduced in lepa KO fish, while the levels of dopamine, glycine and cortisol in the brain were significantly elevated. In addition, the brain ROS level was elevated, and the anti-oxidative enzyme catalase level was reduced. Taken together, by performing loss-of-function multiple behavior endpoint testing and biochemical analysis, we provide strong evidence for a critical role of lepa gene in modulating anxiety, aggression, fear, and circadian rhythm behaviors in zebrafish for the first time.


Assuntos
Leptina/genética , Obesidade/genética , Deleção de Sequência , Estresse Psicológico/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Agressão , Animais , Ansiedade/genética , Ansiedade/metabolismo , Apetite , Biomarcadores/metabolismo , Química Encefálica , Ritmo Circadiano , Modelos Animais de Doenças , Medo , Feminino , Edição de Genes , Masculino , Obesidade/metabolismo , Estresse Psicológico/metabolismo
11.
Molecules ; 22(12)2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29186901

RESUMO

Currently, drug screening relies on cell-based experiments or on animal models to confirm biological effects. The mammalian system is considered too time-consuming, expensive and complex to perform high-throughput drug screening. There is a gap between in vitro cell-based models and the in vivo mammalian models. The zebrafish is an ideal model that could link preclinical toxicity screening with the drug development pipeline. Taking advantage of a highly conservative genomic, rapid development, large number of offspring, low cost and easy manipulation, zebrafish has been considered an excellent animal model for disease-based drug screening. In this study, zebrafish embryos were incubated with small molecular compounds that potentially affected bone mineralization in microplates. Two compounds of alendronate and dorsomorphin were used as positive and negative controls, respectively. The level of osteogenic mineralization was measured and quantified by using ImageJ software with fluorescent calcein-staining images. Among twenty-four tested compounds from the kinase inhibitor library, we identified two compounds, pentamidine and BML-267, which showed increased embryonic mineralization; while six compounds, RWJ-60475, levamisole HCL, tetramisole HCL, fenvalerate, NSC-663284, and BML-267ester, were inhibitory to bone mineralization. In addition, real time quantitative PCR (RT-qPCR) was performed to evaluate the biological pathways involved in bone metabolism at the molecular level. We confirmed that alendronate enhanced the level of bone mineralization by inhibiting osteoclast-related genes. In summary, our research established a simple method to screen potential bone metabolic drugs and to perform mechanism analysis for bone mineralization in vivo.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Coloração e Rotulagem/métodos , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Embrião não Mamífero , Corantes Fluorescentes/química , Levamisol/química , Levamisol/farmacologia , Osteogênese/efeitos dos fármacos , Pentamidina/química , Pentamidina/farmacologia , Inibidores de Proteínas Quinases/química , Quinolonas/química , Quinolonas/farmacologia , Quinonas/química , Quinonas/farmacologia , Transdução de Sinais , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Peixe-Zebra
12.
Appl Environ Microbiol ; 82(6): 1889-1897, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26773082

RESUMO

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli sequence type ST131 has emerged as the leading cause of community-acquired urinary tract infections and bacteremia worldwide. Whether environmental water is a potential reservoir of these strains remains unclear. River water samples were collected from 40 stations in southern Taiwan from February to August 2014. PCR assay and multilocus sequence typing (MLST) analysis were conducted to determine the CTX-M group and sequence type, respectively. In addition, we identified the seasonal frequency of ESBL-producing E. coli strains and their geographical relationship with runoffs from livestock and poultry farms between February and August 2014. ESBL-producing E. coli accounted for 30% of the 621 E. coli strains isolated from river water in southern Taiwan. ESBL-producing E. coli ST131 was not detected among the isolates. The most commonly detected strain was E. coli CTX-M group 9. Among the 92 isolates selected for MLST analysis, the most common ESBL-producing clonal complexes were ST10 and ST58. The proportion of ESBL-producing E. coli was significantly higher in areas with a lower river pollution index (P = 0.025) and regions with a large number of chickens being raised (P = 0.013). ESBL-producing E. coli strains were commonly isolated from river waters in southern Taiwan. The most commonly isolated ESBL-producing clonal complexes were ST10 and ST58, which were geographically related to chicken farms. ESBL-producing E. coli ST131, the major clone causing community-acquired infections in Taiwan and worldwide, was not detected in river waters.


Assuntos
Escherichia coli/classificação , Escherichia coli/isolamento & purificação , Genótipo , Rios/microbiologia , beta-Lactamases/metabolismo , Criação de Animais Domésticos , Animais , Animais Domésticos , Galinhas , Escherichia coli/enzimologia , Escherichia coli/genética , Tipagem de Sequências Multilocus , Filogeografia , Reação em Cadeia da Polimerase , Estações do Ano , Taiwan , beta-Lactamases/genética
13.
Pediatr Nephrol ; 31(8): 1305-12, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26975387

RESUMO

BACKGROUND: Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management. METHODS: A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n = 111) and a rural hospital (n = 48) in southern Taiwan from 2009 to 2012. RESULTS: Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p < 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations. CONCLUSIONS: The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.


Assuntos
Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções Urinárias/microbiologia , Resistência beta-Lactâmica , Estudos Transversais , Escherichia coli , Feminino , Hospitais Rurais , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Estudos Retrospectivos , Saúde da População Rural , Saúde da População Urbana , Infecções Urinárias/epidemiologia
14.
Antibiotics (Basel) ; 10(5)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065381

RESUMO

This study aimed to investigate the effects of multi-drug-resistant organism (MDRO) infection and other factors on the length of hospital stay (LOS) of patients in the respiratory care ward (RCW) of a regional hospital in Taiwan. In this retrospective study, we collected cases from MDRO-infected patients in the RCW from January 2016 to March 2020. The RCW comprises 13 beds in total. There were 106 infected patients, of which 42 were in the case group (infected with MDROs) and 64 were in the control group (not infected with MDROs). Clinical specimens were inoculated in a selective medium to isolate the pathogenic bacteria by standard procedures. The results showed the main factors affecting the LOS were: patients with MDRO infection, patients discharged from the RCW, and patients who underwent catheterization. The LOS of patients infected with MDROs was significantly longer than that of patients without MDRO infection (ß = 0.55, 95% CI = 0.02-1.09), with the case group and the control group being 479.8 ± 546.5 and 307.3 ± 436.2 days, respectively. Infection with carbapenem-resistant Pseudomonas aeruginosa (CRPA) was associated with a longer LOS than other MDRO strains. These findings have important implications for infection control in RCW and in better tracking the health of patients.

15.
Oxid Med Cell Longev ; 2021: 7995223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336114

RESUMO

Fullerene molecules are composed of carbon in the form of a hollow sphere, tube, or ellipsoid. Since their discovery in 1985, they have gained a lot of attention in many science fields. The unique carbon cage structure of fullerene provides immense scope for derivatization, rendering potential for various industrial applications. Thus, the prospective applications of fullerenes have led to assorted fullerene derivatives. In addition, their unique chemical structure also eases them to be synthesized through various kinds of conjugating techniques, where fullerene can be located either on the backbone or the branch chain. In this review, we have compiled the toxicity and biosafety aspects of fullerene in aquatic organisms since the frequent use of fullerene is likely to come in contact and interact with the aquatic environment and aquatic organisms. According to the current understanding, waterborne exposure to fullerene-based nanomaterials indeed triggers toxicities at cellular, organic, molecular, and neurobehavioral levels.


Assuntos
Fulerenos/química , Nanoestruturas/química , Animais
16.
Toxins (Basel) ; 13(4)2021 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916832

RESUMO

Arecoline is one of the nicotinic acid-based alkaloids, which is found in the betel nut. In addition to its function as a muscarinic agonist, arecoline exhibits several adverse effects, such as inducing growth retardation and causing developmental defects in animal embryos, including zebrafish, chicken, and mice. In this study, we aimed to study the potential adverse effects of waterborne arecoline exposure on zebrafish larvae locomotor activity and investigate the possible mechanism of the arecoline effects in zebrafish behavior. The zebrafish behavior analysis, together with molecular docking and the antagonist co-exposure experiment using muscarinic acetylcholine receptor antagonists were conducted. Zebrafish larvae aged 96 h post-fertilization (hpf) were exposed to different concentrations (0.001, 0.01, 0.1, and 1 ppm) of arecoline for 30 min and 24 h, respectively, to find out the effect of arecoline in different time exposures. Locomotor activities were measured and quantified at 120 hpf. The results showed that arecoline caused zebrafish larvae locomotor hyperactivities, even at a very low concentration. For the mechanistic study, we conducted a structure-based molecular docking simulation and antagonist co-exposure experiment to explore the potential interactions between arecoline and eight subtypes, namely, M1a, M2a, M2b, M3a, M3b, M4a, M5a, and M5b, of zebrafish endogenous muscarinic acetylcholine receptors (mAChRs). Arecoline was predicted to show a strong binding affinity to most of the subtypes. We also discovered that the locomotion hyperactivity phenotypes triggered by arecoline could be rescued by co-incubating it with M1 to M4 mAChR antagonists. Taken together, by a pharmacological approach, we demonstrated that arecoline functions as a highly potent hyperactivity-stimulating compound in zebrafish that is mediated by multiple muscarinic acetylcholine receptors.


Assuntos
Arecolina/toxicidade , Comportamento Animal/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Agonistas Muscarínicos/toxicidade , Receptores Muscarínicos/efeitos dos fármacos , Animais , Arecolina/metabolismo , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Agonistas Muscarínicos/metabolismo , Antagonistas Muscarínicos/farmacologia , Fotoperíodo , Ligação Proteica , Receptores Muscarínicos/metabolismo , Transdução de Sinais , Fatores de Tempo , Peixe-Zebra/embriologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-31816426

RESUMO

The effects of endocrine disruption with respect to potential human toxicities have been extensively evaluated to date. However, the standard testing methods used have not always taken the most pertinent approach. In this study, we used juvenile male tilapia (Oreochromis niloticus) as an animal model to test for endocrine disruption by chemicals. We measured 17ß-estradiol (E2) concentrations, and the mRNA relative expression ratio (RER; treatment/control) of vitellogenin (vtg2) and estrogen receptors (ERs) to assess whether the effluent concentration of selected plasticizers disrupt E2 function in fish. We found that the vtg2 RER was significantly increased after exposure to 2.52 nM E2 for 5 days, 0.438 µM of bisphenol A (BPA) for 7 days, or 2.865 µM Cd2+ for 7 days. These data support vtg2 transcript level as a sensitive biomarker to evaluate contamination of water by endocrine disrupting chemicals (EDCs). However, vtg2 expression did not respond to fluctuations of E2 concentrations in the tilapia juveniles exposed to selected plasticizers. However, the RER of three types of ERs appeared to change dramatically upon exposure to plasticizers. ERα significantly increased, but ERß2 decreased with 3.6 µM DEP exposure. Both ERα and ERß2 decreased significantly after 1.44 µM DIBP exposure. We suggest that changes of vtg2 mRNA RER, E2 levels and ERs mRNA expression should be taken into consideration at the same time to determine if chemical contaminants in the water are endocrine disrupters.


Assuntos
Ciclídeos/metabolismo , Disruptores Endócrinos/toxicidade , Larva/metabolismo , Receptores de Estrogênio/metabolismo , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Compostos Benzidrílicos/toxicidade , Biomarcadores/metabolismo , Cádmio/toxicidade , Estradiol/toxicidade , Masculino , Modelos Animais , Fenóis/toxicidade , Plastificantes/toxicidade , Poluição Química da Água
18.
Environ Pollut ; 266(Pt 1): 115239, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32795887

RESUMO

Common solvents are frequently used as carriers to dissolve chemicals with a hydrophobic property that is extensively applied in the industrial and biomedical fields. In this study, we aimed to systematically study the sub-chronic effect of ten common solvents at low concentration exposure in adult zebrafish and perform neurobehavioral assessments for mechanistic exploration. After exposed to ten common solvents, including methanol, ethanol (EtOH), dimethyl sulfoxide (DMSO), isopropanol, acetone, polyethylene glycol-400 (PEG-400), glycerol, butanol, pentane, and tetrahydrofuran for continuous 10 day at 0.1% concentration level, adult zebrafish were subjected to perform a serial of behavioral tests, such as novel tank, mirror biting, predator avoidance, social interaction and shoaling. Later, 20 behavioral endpoints obtained from these five tests were transformed into a scoring matrix. Principal component analysis (PCA) and hierarchy clustering were performed to evaluate and compare the zebrafish behavior profiling. By using this phenomic approach, we were able to systematically evaluate the toxicity of the common solvents in zebrafish at a neurobehavioral level for the first time and found each common solvent-induced unique behavioral alteration to produce fingerprint-like patterns in hierarchy clustering and heatmap analysis. Among all tested common solvents, acetone and PEG-400 displayed better biocompatibility and less toxicity since they triggered less behavioral and biochemical alterations while methanol and DMSO caused severe behavior alterations in zebrafish after chronic exposure of these solvents. We conclude the behavioral phenomic approach conducted in this study providing a powerful tool to a systematical exploration of the common solvent toxicity at the whole organism level.


Assuntos
Fenômica , Peixe-Zebra , Acetona , Animais , Dimetil Sulfóxido , Solventes
19.
Biomolecules ; 10(9)2020 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-32842481

RESUMO

Pesticides are widely used to eradicate insects, weed species, and fungi in agriculture. The half-lives of some pesticides are relatively long and may have the dire potential to induce adverse effects when released into the soil, terrestrial and aquatic systems. To assess the potential adverse effects of pesticide pollution in the aquatic environment, zebrafish (Danio rerio) and Daphnia magna are two excellent animal models because of their transparent bodies, relatively short development processes, and well-established genetic information. Moreover, they are also suitable for performing high-throughput toxicity assays. In this study, we used both zebrafish larvae and water flea daphnia neonates as a model system to explore and compare the potential toxicity by monitoring locomotor activity. Tested animals were exposed to 12 various types of pesticides (three fungicides and 9 insecticides) for 24 h and their corresponding locomotor activities, in terms of distance traveled, burst movement, and rotation were quantified. By adapting principal component analysis (PCA) and hierarchical clustering analysis, we were able to minimize data complexity and compare pesticide toxicity based on locomotor activity for zebrafish and daphnia. Results showed distinct locomotor activity alteration patterns between zebrafish and daphnia towards pesticide exposure. The majority of pesticides tested in this study induced locomotor hypo-activity in daphnia neonates but triggered locomotor hyper-activity in zebrafish larvae. According to our PCA and clustering results, the toxicity for 12 pesticides was grouped into two major groups based on all locomotor activity endpoints collected from both zebrafish and daphnia. In conclusion, all pesticides resulted in swimming alterations in both animal models by either producing hypo-activity, hyperactivity, or other changes in swimming patterns. In addition, zebrafish and daphnia displayed distinct sensitivity and response against different pesticides, and the combinational analysis approach by using a phenomic approach to combine data collected from zebrafish and daphnia provided better resolution for toxicological assessment.


Assuntos
Daphnia/efeitos dos fármacos , Praguicidas/toxicidade , Peixe-Zebra/fisiologia , Animais , Análise por Conglomerados , Daphnia/crescimento & desenvolvimento , Daphnia/fisiologia , Fungicidas Industriais/toxicidade , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Larva/fisiologia , Locomoção/efeitos dos fármacos , Modelos Animais , Análise de Componente Principal , Natação/fisiologia , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento
20.
Biomedicines ; 8(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756400

RESUMO

The zebrafish has a tetrachromatic vision that is able to distinguish ultraviolet (UV) and visible wavelengths. Recently, zebrafish color preferences have gained much attention because of the easy setup of the instrument and its usefulness to screen behavior-linked stimuli. However, several published papers dealing with zebrafish color preferences have contradicting results that underscore the importance of method standardization in this field. Different laboratories may report different results because of variations in light source, color intensity, and other parameters such as age, gender, container size, and strain of fish. In this study, we aim to standardize the color preference test in zebrafish by measuring light source position, light intensity, gender, age, animal size to space ratio, and animal strain. Our results showed that color preferences for zebrafish are affected by light position, age, strain, and social interaction of the fish, but not affected by fish gender. We validated that ethanol can significantly induce color preference alteration in zebrafish which may be related to anxiety and depression. We also explored the potential use of the optimized method to examine color preference ranking and index differences in various zebrafish strains and species, such as the tiger barb and glass catfish. In conclusion, zebrafish color preference screening is a powerful tool for high-throughput neuropharmacological applications and the standardized protocol established in this study provides a useful reference for the zebrafish research community.

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