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1.
PLoS One ; 15(9): e0237977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915802

RESUMO

The objective of this study was to determine the radiocesium transfer rates of pigs fed haylage contaminated with low levels of cesium at different growth stages. We measured the body weight of juvenile and adult pigs during the treatment period to confirm their health status. We also performed pig blood hematologic and biochemical analyses at both growth stages. To our knowledge, this is the first study to report pig radiocesium transfer coefficient rates after 1 month of chronic oral treatment, which is the period assumed to be required for body equilibrium under a diet of radiocesium-contaminated food. The results showed higher radiocesium retention rates in the kidneys, liver, spleen, genitals, psoas major, bladder, thyroid, and urine than in the blood and bone (tibia and femur) of pigs at both growth stages. The radiocesium retention levels were generally higher in juvenile pigs than in adult pigs, with the highest transfer coefficient ratio in the kidneys (16.2%).


Assuntos
Radioisótopos de Césio/metabolismo , Contaminação Radioativa de Alimentos/análise , Administração Oral , Animais , Peso Corporal , Radioisótopos de Césio/sangue , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Suínos
2.
J Chromatogr A ; 1628: 461442, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32822981

RESUMO

An analytical method for the quantification of thirty-three perfluoroalkyl and polyfluoroalkyl substances (PFASs) in animal liver was developed applying the isotopic dilution methodology with twenty-one labelled isotopologues of native compounds. The proposed protocol involved the determination of short and long aliphatic chain PFASs (C4C18) extracting liver with acetonitrile followed by two clean-up steps. The instrumental analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. The acquisition method combined full MS/dd-MS2, t-SIM/dd-MS2 and SIM experiments with variable resolution in order to maximize in one chromatographic run accuracy, sensitivity and selectivity. An eight-level validation study was performed evaluating linearity, trueness, precision, quantification and detection limits. Trueness was from 94 to 126% with intra-laboratory reproducibility lower than 20%. Limits of quantification were in the range 2-100 pg g-1, except for 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)-propanoic acid, HFPO-DA (500 pg g-1). The analysis of a certified reference material (IRMM-427) and participation in a proficiency test scheme (FAPAS - 0687) confirmed these satisfactory performances. Finally, the application of the developed procedure to detect PFASs in sixteen liver samples of farm animals revealed that chicken was the less contaminated species.


Assuntos
Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fluorcarbonetos/análise , Fígado/química , Espectrometria de Massas em Tandem , Animais , Reprodutibilidade dos Testes
3.
Mar Pollut Bull ; 158: 111094, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32753165

RESUMO

Concentrations of Fe, Mn, Zn, and Cu in the muscle, lung, liver, and kidney tissues of 49 cetaceans, including 11 Kogia sima (Ks), 10 Lagenodelphis hosei (Lh), 14 Grampus griseus (Gg), and 14 Stenella attenuata (Sa) from 1994 to 2012 in Taiwan were measured. Ks exhibited the highest Fe, and the lowest Zn, Cu and Mn tissue concentrations. The Kogiid and Delphinid groups were significantly categorized by nMDS analysis. Fe muscle concentrations were found to be positively correlated with Ks, Lh, and Gg but not Sa body length. The different levels of Zn-, Cu-, and Mn- tissue concentrations of the two families were due to their different SOD systems. Their calves contained higher Cu liver concentrations. The four essential elements in cetaceans regulate homeostasis to meet their eco-physiological demand. The baseline levels for these four elements in these four tissues in the Delphinid group are defined.


Assuntos
Golfinhos , Oligoelementos/análise , Animais , Bovinos , Fígado/química , Taiwan , Baleias , Zinco/análise
4.
Arch Environ Contam Toxicol ; 79(2): 270-281, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32696228

RESUMO

One of the world's largest, but low-grade, sulfide nickel deposits in northeastern Finland has been exploited by a bioheapleaching technology since 2008. Bioheapleaching is a relatively new, cost-effective technology, but humid climate, e.g., in boreal temperate environments, causes challenges to the management of the water balance in the ore heaps with wide catchment area, and the mining effluents have caused substantial metal and salting contamination of the receiving waterbodies. In our study, the impacts of metal-extracting bioheapleaching mine effluents on muscle and liver element concentrations, body condition, liver and testes mass, and sperm count and motility of male perch Perca fluviatilis were analysed. Liver, testes, and carcass mass of perch in relation to their length were lower in the mining-impacted lakes than in the reference lake, which may be due to the metal contamination, food availability, and energy demand under multistressor conditions. The sperm counts of the males in the mining-impacted lakes were lower, but the endurance of their sperm motility was longer than the endurance of sperm of the reference males. These findings suggested that the condition and sperm characteristics of perch were altered in lakes receiving metal mining effluents. Measured variables seem to be useful indicators for metal mining impacts on freshwater fish but only if high natural variation in these characteristics can be controlled by multiyear monitoring scheme.


Assuntos
Metais/toxicidade , Mineração , Percas/fisiologia , Espermatozoides/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Monitoramento Ambiental , Finlândia , Humanos , Lagos , Fígado/química , Masculino , Metais/análise , Níquel , Motilidade Espermática , Poluentes Químicos da Água/análise
5.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3144-3154, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726023

RESUMO

To reveal the processing mechanism of Chrysanthemi Flos from the changes of chemical compositions after frying and its effect on the efficacy of liver protection. Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) and ultra high performance liquid chromatography(HPLC) were used for the qualitative and quantitative researches of chemical compositions before and after Chrysanthemi Flos frying. Progenesis QI and SPSS software were used for principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), variable importance projection(VIP) analysis and t-test to identify the compositions with significant changes. Pharmacodynamics experiment was used to investigate the protective effect of crude and fried Chrysanthemi Flos on CCl_4-induced acute liver injury in mice. According to mass spectrometry data, there were 28 chemical compositions in crude and fried Chrysanthemi Flos, mainly including flavonoids and organic acids. 13 compositions such as luteolin, apigenin and luteolin glycoside were increased significantly after frying, while 7 compositions such as chlorogenic acid, luteolin-7-O-glucuronide and apigenin-7-O-glucuronide were decreased significantly after frying. Through principal component analysis, crude and fried Chrysanthemi Flos products were divided into two categories, indicating that there were internal differences in quality. The results of liver injury protection experiment in mice showed that the AST, ALT and MDA contents were significantly decreased and SOD level was increased in mice with liver injury in both the high and medium dose groups. Histopathological examination showed that crude and fried Chrysanthemi Flos can protect the liver by reducing inflammatory cell infiltration, reducing steatosis, and repairing damaged liver cells. The results of this study showed that the chemical compositions had obvious changes after frying, and both crude and fried Chrysanthemis Flos had protective effects on CCl_4-induced acute liver injury in mice. In addition, in the range of high, medium and low doses, the liver protection effect of crude and fried Chrysanthemi Flos increased with the increase of dose. The experiment results provided reference for the mechanism of fried Chrysanthemi Flos and clinical selection of processed products.


Assuntos
Chrysanthemum , Animais , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Flores/química , Fígado/química , Camundongos
6.
Arch Environ Contam Toxicol ; 79(2): 258-269, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32666217

RESUMO

Phenothiazine (PTZ) is a heterocyclic thiazine compound used for industrial and medical purposes. Through environmental surveillance studies, PTZ was found being discharged into a local river in Connecticut. Phenothiazine has been shown to act similarly to endocrine disrupting chemicals. This study sought to identify sex specific hormone receptor changes in Fundulus heteroclitus in response to PTZ exposure. Fundulus heteroclitus, also known as mummichog, are small fish native to the Atlantic coast of the United States and Canada. They reside in brackish waters and can survive harsh toxic environments. This model organism is native to the polluted waters found in Connecticut. In this study, fish were exposed to PTZ concentrations of 0.5 ppm, 1.0 ppm, and 2.0 ppm for 1 week. Following exposure, brain, liver, and gonad tissues were harvested; cDNA was synthesized; and mRNA expression was assessed for 6 different hormone receptors. Compared with vehicle control (ethanol) differences in mRNA expression, levels of hormone receptors were observed in various tissues from male and female fish. Many of the tissues assessed showed changes in expression level, while only female liver and testis showed no change. These results implicate PTZ as a potential endocrine disrupting compound to mummichog at environmentally relevant concentrations.


Assuntos
Fundulidae/fisiologia , Fenotiazinas/toxicidade , Receptores de Esteroides/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Canadá , Disruptores Endócrinos/metabolismo , Monitoramento Ambiental , Feminino , Fundulidae/metabolismo , Fígado/química , Masculino , Fenotiazinas/metabolismo , Testículo/efeitos dos fármacos , Poluentes Químicos da Água/análise
7.
Chemosphere ; 258: 127311, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32540547

RESUMO

The bioaccumulation of mercury (Hg) in the food chain may pose a threat to human health. The risk of dietary Hg intake is mostly caused by the consumption of fish and seafood, therefore the knowledge on the exposure from land animal products is limited. In our article, we summarized the results of analyses of Hg in muscle tissue and liver of different livestock and game animals obtained during ten years of official monitoring that was carried out in Poland from 2009 to 2018. The majority of the results in muscle tissue were below the limits of quantification (LOQs). The mean Hg concentrations in muscle tissue ranged from 0.6 to 5.6 µg kg-1 of wet weight and the mean liver Hg concentrations were within the range of 0.8-16.4 µg kg-1 of wet weight, with lowest levels in chickens and highest in wild boars. The results revealed decreasing trends in liver Hg in cattle and cervids over the years, which was congruous with decreasing emission of Hg in Europe. Our results showed that the consumption of meat and liver of livestock and game animals in Poland may be considered to be safe for human health, which was confirmed by the low number of noncompliant samples relative to the applicable legal limits, as well as by estimated dietary exposure.


Assuntos
Monitoramento Ambiental , Poluentes Ambientais/análise , Gado , Carne/análise , Mercúrio/análise , Animais , Bovinos , Galinhas , Exposição Dietética/análise , Europa (Continente) , Peixes , Cadeia Alimentar , Humanos , Fígado/química , Músculos/química , Polônia , Alimentos Marinhos/análise
8.
Environ Sci Pollut Res Int ; 27(27): 34442-34452, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557032

RESUMO

Adverse health effects have been observed in nearby residents due to exposure to petrochemical-derived chemicals. The objective of this study was to examine associations of soluble metals with lung and liver toxicity in fine particulate matter (PM2.5) in the vicinity of a petrochemical complex. PM2.5 was collected in the vicinity of a petrochemical complex of Mailiao Township (Yunlin County, Taiwan) to investigate lung and liver toxicity in BALB/c mice. The PM2.5 concentration was 30.2 ± 11.2 µg/m3, and the PM2.5 was clustered in major local emissions (19.1 µg/m3) and minor local emissions (14.1 µg/m3) using a k-means clustering model. The PM2.5 (50 and 150 µg/kg) and PM2.5-equivalent soluble nickel (Ni), vanadium (V), and lead (Pb) concentrations were intratracheally instilled into BALB/c mice. PM2.5 and V significantly decreased the tidal volume after exposure (p < 0.05). The peak expiratory flow (PEF) and peak inspiratory flow (PIF)/PEF ratio were significantly altered by 150 µg/kg V (p < 0.05). V and Pb significantly increased total protein and lactate dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF) (p < 0.05). Interleukin (IL)-6 in BALF significantly increased after exposure to Pb (p < 0.05) accompanied by lung inflammatory infiltration. PM2.5 and Pb significantly increased levels of 8-isoprostane (p < 0.05). The level of caspase-3 activity significantly increased after exposure to Pb (p < 0.05). LDH in the liver was significantly increased by PM2.5 (p < 0.05). 8-Isoprostane in the liver was significantly increased by PM2.5 and Pb (p < 0.05). IL-6 in the liver was significantly increased by PM2.5, Ni, V, and Pb after exposure (p < 0.05), accompanied by liver inflammatory infiltration. Our results demonstrated that V in PM2.5 was associated with an increase in 8-isoprostane for all emissions and major local petrochemical emissions. In conclusion, V contributes to in vivo liver toxicity induced by PM2.5 in the vicinity of a petrochemical complex.


Assuntos
Poluentes Atmosféricos/análise , Material Particulado/farmacologia , Animais , Fígado/química , Pulmão/efeitos dos fármacos , Metais/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Taiwan
9.
Environ Sci Pollut Res Int ; 27(24): 30789-30799, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474784

RESUMO

Enzymatic biomarkers, especially oxidative-stress enzymes, are useful for assessing the status of aquatic environments. The present study used biochemical markers determined in nervous, gill, and liver tissues of Sciades herzbergii, concomitantly with analyses of trace metals in the tissues and bottom sediment, to evaluate environmental quality in Amazon estuaries. The study was conducted from March 2014 to February 2016 in two areas: Caeté estuary in Bragança, state of Pará, which is relatively unimpacted; and São Marcos Bay, next to a harbor in São Luís, state of Maranhão. In the laboratory, the fish were weighed (g) and measured (cm). Fragments of the gills, the brain, and the liver were biochemically analyzed, and the metal contents in the brain, the liver, and the muscle tissues were determined. Turbidity was significantly higher (p < 0.05) in São Marcos than in Bragança. Specimens of S. herzbergii were smaller in São Marcos, and aluminum, iron, nickel, copper, cadmium, and mercury levels were higher in bottom sediment (p < 0.05) collected at this location. Fish from São Marcos contained significantly higher (p < 0.05) concentrations of aluminum, iron, and cadmium in the muscle tissue than fish from Bragança. In addition, fish from São Marcos had significantly higher concentrations of nickel in both the nervous and hepatic tissues. Only fish from São Marcos contained measurable concentrations of mercury in the liver and muscle. Fish from Bragança had copper concentrations in the liver significantly different from those captured at São Marcos (p < 0.05). The activities of gill glutathione S-transferases (GSTs) (F = 6.62; df = 1, 16; p < 0.05) and liver CAT (F = 10.22; df = 1, 16; p < 0.05) were higher in fish from São Marcos. However, ChE in brain tissues and lipid peroxidation (LPO) in the gills and liver did not differ significantly between fish from both areas. The physico-chemical conditions of the water and the concentrations of metals found in sediment and biological tissues, together with the biochemical responses of S. herzbergii in the study areas, indicate that this species is still tolerant to adverse environmental conditions, but the presence of metals is a risk to the health of fish, mainly to fish from São Marcos, especially if chronically exposed.


Assuntos
Peixes-Gato , Poluentes Químicos da Água/análise , Animais , Biomarcadores , Monitoramento Ambiental , Estuários , Brânquias/química , Fígado/química , Metais
10.
Food Chem ; 331: 127369, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32590262

RESUMO

To make better use of chicken liver, a byproduct of meat processing with rich proteins, the influence of ultrasound pretreatment on the extent of Maillard reaction (MR) and the properties of MR products (MRPs) of chicken liver protein (CLP) and its hydrolysate (CLPH) were investigated. The extent of MR of sonicated CLPH (SCLPHMs) was significantly higher than that of the other two MRPs. The decreased fluorescence intensity (FI) of the SCLPHMs indicated adequate reaction of d-xylose with sonicated CLPH (SCLPH). The particle size of the three MRPs was significantly larger than that of CLP, CLPH, and SCLPH, respectively. Ultrasound treatment increased the utilization of amino acids and enriched the variety of volatile compounds in all groups. Furfural was the main heterocyclic compound in the MRPs. Therefore, ultrasound pretreatment and enzymolysis of chicken liver may be a foundation for high-value development in flavors for the food industry.


Assuntos
Galinhas , Indústria de Processamento de Alimentos/métodos , Fígado/química , Reação de Maillard , Proteínas de Aves Domésticas/química , Compostos Orgânicos Voláteis/química , Aminoácidos/análise , Aminoácidos/química , Animais , Aromatizantes/química , Produtos Finais de Glicação Avançada/química , Produtos Avícolas , Hidrolisados de Proteína/química , Paladar , Ultrassom , Compostos Orgânicos Voláteis/análise , Xilose/química
11.
Sci Total Environ ; 735: 139505, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32480153

RESUMO

The effects of the rupture of a mining tailings dam were investigated using the gills and liver of Astyanax lacustris as a proxy for environmental quality. The fish were exposed for seven days to water sampled forming four groups: upstream of the dam rupture (P1), and 22 km (P2); 48 km (P3); and 70 km (P4) downstream from the dam rupture in the Doce River basin. The control group received dechlorinated tap water. The dissolved concentrations of metals were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). We evaluated the histology of the gills and liver, as well as, immunohistochemistry for HSP70 and Na+/K+ ATPase (NKA) in the gills, and for P-gp in liver. In all sites we observed a mix of metals, with higher concentrations of Mn, Cd, As, and Cu/Cr in P1, P2, P3, and P4, respectively. All treatments groups showed histological changes in gills and liver, with the highest amount of these alterations found in the P2 group. Disorganization of the secondary lamellae, epithelial lifting, and mitochondria-rich cells (MRC) were observed in the gills. The parenchyma of the liver was rather disorganized, and hepatocytes and nuclei showed hypertrophy, vacuolization and cytoplasmic degeneration. A higher immunoreaction of HSP70 in P2 when compared with the other groups and lower labeling of HSP70 in the P4 was registered. In P2 and P3, NKA-positive cells were observed with hypertrophy and disorganization. Morphometric analyses of the liver revealed that all treatment groups presented a lower immunolabeling of P-gp when compared with the control group. Thus, the experimental approach revealed that the water from Doce basin can promote histological alterations in fish's liver and gills, as well as modulation of disruption of ionic balance, cellular responses to stress, and cell detoxification pathways.


Assuntos
Brânquias/química , Poluentes Químicos da Água/análise , Animais , Brasil , Fígado/química , Água
12.
Chemosphere ; 257: 127183, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32497841

RESUMO

Here, we evaluate maternal offloading of 16 trace elements (Essential: Co, Cr, Cu, Fe, Mn, Ni, Se and Zn; Nonessential: Al, As, Ba, Cd, Hg, Pb, Tl and U) and determine mother-offspring isotopic fractionation of δ13C and δ15N in muscle and liver tissue of four pregnant Mustelus higmani and 18 associated embryos sampled from the Amazon Coast of Brazil. Embryo muscle tissue had significantly higher concentrations of most trace elements when compared to mothers, with the exception of Hg. Embryo liver accumulated more nonessential elements than muscle (n = 7 vs. 0, respectively), while the Se:Hg molar ratio was >1 in liver and muscle of both mothers and embryos. Livers of embryos were moderately enriched in δ13C and δ15N when compared to that of their mother. Negative correlations were observed between embryo body length and δ13C and trace elements concentrations. We conclude that mothers offload a large portion of all essential elements and Al, As and Pb to their young and that the isotopic fractionation of embryos reflects maternal diet and habitat occupied, with δ13C diluted with embryonic growth. We also show that muscle and liver accumulate trace elements at different rates relative to the body length of embryos. The Se:Hg molar ratio suggests that Se could play a protective role against Hg toxicity during early stages of M. higmani embryonic development.


Assuntos
Monitoramento Ambiental , Músculos/metabolismo , Tubarões/metabolismo , Oligoelementos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Brasil , Ecossistema , Feminino , Isótopos , Fígado/química , Mercúrio , Músculos/química , Gravidez , Oligoelementos/análise
13.
PLoS One ; 15(5): e0232886, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396553

RESUMO

There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available pool of donated livers. This study demonstrates the ability to improve the function of steatotic rat livers using a combination of ex situ machine perfusion and a "defatting" drug cocktail. After 6 hours of perfusion, defatted livers demonstrated lower perfusate lactate levels and improved bile quality as demonstrated by higher bile bicarbonate and lower bile lactate. Furthermore, defatting was associated with decreased gene expression of pro-inflammatory cytokines and increased expression of enzymes involved in mitochondrial fatty acid oxidation. Rehabilitation of marginal or discarded steatotic livers using machine perfusion and tailored drug therapy can significantly increase the supply of donor livers for transplantation.


Assuntos
Fígado Gorduroso/terapia , Fígado/fisiopatologia , Preservação de Órgãos/instrumentação , Animais , Bicarbonatos/análise , Citocinas/genética , Modelos Animais de Doenças , Fígado Gorduroso/genética , Fígado Gorduroso/fisiopatologia , Regulação da Expressão Gênica , Ácido Láctico/análise , Fígado/química , Transplante de Fígado , Masculino , Preservação de Órgãos/métodos , Perfusão , Ratos , Doadores de Tecidos
14.
Nat Protoc ; 15(6): 2024-2040, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32433625

RESUMO

Preservation of human organs at subzero temperatures has been an elusive goal for decades. The major complication hindering successful subzero preservation is the formation of ice at temperatures below freezing. Supercooling, or subzero non-freezing, preservation completely avoids ice formation at subzero temperatures. We previously showed that rat livers can be viably preserved three times longer by supercooling as compared to hypothermic preservation at +4 °C. Scalability of supercooling preservation to human organs was intrinsically limited because of volume-dependent stochastic ice formation at subzero temperatures. However, we recently adapted the rat preservation approach so it could be applied to larger organs. Here, we describe a supercooling protocol that averts freezing of human livers by minimizing air-liquid interfaces as favorable sites of ice nucleation and uses preconditioning with cryoprotective agents to depress the freezing point of the liver tissue. Human livers are homogeneously preconditioned during multiple machine perfusion stages at different temperatures. Including preparation, the protocol takes 31 h to complete. Using this protocol, human livers can be stored free of ice at -4 °C, which substantially extends the ex vivo life of the organ. To our knowledge, this is the first detailed protocol describing how to perform subzero preservation of human organs.


Assuntos
Fígado/fisiologia , Preservação de Órgãos/métodos , Temperatura Baixa , Crioprotetores/química , Desenho de Equipamento , Congelamento , Humanos , Gelo/análise , Fígado/química , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Perfusão/métodos
15.
PLoS Genet ; 16(5): e1008770, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453730

RESUMO

Hormone-dependent activation of enhancers includes histone hyperacetylation and mediator recruitment. Histone hyperacetylation is mostly explained by a bimodal switch model, where histone deacetylases (HDACs) disassociate from chromatin, and histone acetyl transferases (HATs) are recruited. This model builds on decades of research on steroid receptor regulation of transcription. Yet, the general concept of the bimodal switch model has not been rigorously tested genome wide. We have used a genomics approach to study enhancer hyperacetylation by the thyroid hormone receptor (TR), described to operate as a bimodal switch. H3 acetylation, HAT and HDAC ChIP-seq analyses of livers from hypo- and hyperthyroid wildtype, TR deficient and NCOR1 disrupted mice reveal three types of thyroid hormone (T3)-regulated enhancers. One subset of enhancers is bound by HDAC3-NCOR1 in the absence of hormone and constitutively occupy TR and HATs irrespective of T3 levels, suggesting a poised enhancer state in absence of hormone. In presence of T3, HDAC3-NCOR1 dissociates from these enhancers leading to histone hyperacetylation, suggesting a histone acetylation rheostat function of HDACs at poised enhancers. Another subset of enhancers, not occupied by HDACs, is hyperacetylated in a T3-dependent manner, where TR is recruited to chromatin together with HATs. Lastly, a subset of enhancers, is not occupied directly by TR yet requires TR for histone hyperacetylation. This indirect enhancer activation involves co-association with TR bound enhancers within super-enhancers or topological associated domains. Collectively, this demonstrates various mechanisms controlling hormone-dependent transcription and adds significant details to the otherwise simple bimodal switch model.


Assuntos
Elementos Facilitadores Genéticos/efeitos dos fármacos , Histona Acetiltransferases/metabolismo , Histonas/metabolismo , Receptores dos Hormônios Tireóideos/genética , Hormônios Tireóideos/farmacologia , Acetilação , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilases/metabolismo , Fígado/química , Masculino , Camundongos , Correpressor 1 de Receptor Nuclear/genética , Correpressor 1 de Receptor Nuclear/metabolismo
16.
J Food Sci ; 85(6): 1681-1688, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32418205

RESUMO

Valnemulin (VAL) and tiamulin (TIA) are pleuromutilin antibiotics used primarily for treating bacterial infections in swine or other food animals. Furthermore, VAL and TIA are also employed as feed additives to promote animal growth. However, the illegal use of VAL and TIA could cause a series of hazards to consumers. Here, VAL was designed to be conjugated with bovine serum protein to prepare immunogen. A highly sensitive monoclonal antibody that recognized both VAL and TIA has been successfully produced. Moreover, an immunochromatographic strip assay for rapidly screening VAL and TIA in porcine liver was established with visual detection limits (cutoff values) of 50 and 25 ng/g, respectively. The IC50 values calculated from the equation of the standard curve were 6.06 and 3.45 ng/g and the limits of detection were 0.96 and 0.29 ng/g for VAL and TIA. According to the recovery experiment results, the test strip exhibited acceptable accuracy and precision. Generally, the proposed strip provided a practical tool for the detection of VAL and TIA. PRACTICAL APPLICATION: We produced a highly sensitive monoclonal antibody and developed an immunoassay strip for simultaneously monitoring TIA and VAL. Additionally it was preliminarily confirmed that the rapid detection tool was suitable for screening TIA and VAL in porcine liver.


Assuntos
Antibacterianos/análise , Anticorpos Monoclonais/análise , Imunoensaio/métodos , Fígado/química , Animais , Bovinos , Diterpenos/análise , Contaminação de Alimentos/análise , Limite de Detecção , Suínos
17.
PLoS One ; 15(5): e0233373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453743

RESUMO

Targeted gene integration via precise homologous recombination (HR)-based gene editing has the potential to correct genetic diseases. AAV (adeno-associated virus) can mediate nuclease-free gene integration at a disease-causing locus. Therapeutic application of AAV gene integration requires quantitative molecular characterization of the edited sequence that overcome technical obstacles such as excess episomal vector genomes and lengthy homology arms. Here we describe a novel molecular methodology that utilizes quantitative next-generation sequencing to characterize AAV-mediated targeted insertion and detects the presence of unintended mutations. The methods described here quantify targeted insertion and query the entirety of the target locus for the presence of insertions, deletions, single nucleotide variants (SNVs) and integration of viral components such as inverted terminal repeats (ITR). Using a humanized liver murine model, we demonstrate that hematopoietic stem-cell derived AAVHSC15 mediates in vivo targeted gene integration into human chromosome 12 at the PAH (phenylalanine hydroxylase) locus at 6% frequency, with no sign of co-incident random mutations at or above a lower limit of detection of 0.5% and no ITR sequences at the integration sites. Furthermore, analysis of heterozygous variants across the targeted locus using the methods described shows a pattern of strand cross-over, supportive of an HR mechanism of gene integration with similar efficiencies across two different haplotypes. Rapid advances in the application of AAV-mediated nuclease-free target integration, or gene editing, as a new therapeutic modality requires precise understanding of the efficiency and the nature of the changes being introduced to the target genome at the molecular level. This work provides a framework to be applied to homologous recombination gene editing platforms for assessment of introduced and natural sequence variation across a target site.


Assuntos
Dependovirus/fisiologia , Edição de Genes/métodos , Fígado/química , Fenilalanina Hidroxilase/genética , Animais , Vetores Genéticos/administração & dosagem , Células HEK293 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Modelos Animais , Mutação , Análise de Sequência de DNA , Integração Viral
18.
Chemosphere ; 252: 126583, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32443269

RESUMO

Birds are bioindicators for research on the relationship between environmental heavy metal concentration levels and accumulation levels in bird tissues. We use roadkill samples, collected by citizen science participants, to investigate the accumulation levels and associations of seven heavy metals in internal organs (heart, liver, and kidney), feathers (primary and breast), and bones (sternum and femur) of two focal species, Amaurornis phoenicurus and Gallinula chloropus. We found that heavy metal accumulation varied by target tissue, and that variables are associated with bird species and heavy metal type. Although Zn and Cu were highest by concentration among both species, Cu was mostly accumulated in internal organs, As in feathers, and Pb in bones. Concentrations of As, Ni, and Pb in feathers of both focal species were lower than those reported in literature, whereas Cd and Cr were above toxic levels. The results also showed that spatial correlation for heavy metal concentration among bird tissues were weaker than non-spatial correlation, suggesting low spatial autocorrelations and variability. In addition, multiple regression analysis revealed significant correlation for Cr, As, and Pb estimations in A. phoenicurus heart, sternum, and kidney, respectively; and potentially Cr in G. chloropus femur by using feathers. These results support the feasibility of using feathers as indicators of As, Cr, and Pb heavy metal contamination to enhance our understanding of heavy metal accumulation in birds, although caution is required for feather-based estimations of Cd, Cu, and Ni concentration.


Assuntos
Aves/metabolismo , Monitoramento Ambiental/métodos , Metais Pesados/metabolismo , Animais , Crowdsourcing , Biomarcadores Ambientais , Plumas/química , Rim/química , Fígado/química , Metais Pesados/análise
19.
Environ Pollut ; 264: 114642, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32408079

RESUMO

This work aimed at predicting the toxic effects of phenolic compounds in Ba River on the health of female sharpbelly (Hemiculter lucidus) by the de novo transcriptomic analysis of the liver. Sharpbelly, a native fish living in freshwater ecosystem of East Asia, were sampled upstream, near, and downstream of a wastewater discharge to the Ba river. Based on the occurrence of bisphenol A (BPA), nonylphenol (NP), and 4-tert-octylphenol (4-t-OP) in the water and fish sampled from each site, up-, mid-, and down-stream were interpreted as control, high, and low treatment groups, respectively. In the mid-stream group the Fulton's condition factor (CF) and body weight were remarkably increased by approximate 20%; the gonado-somatic index (GSI) and hepatosomatic index (HSI) in mid-stream fish showed a similar increasing trend but lacking of statistical difference. Exposure to wastewater effluent caused 160 and 162 differentially expressed genes (DEGs) in up-mid and down-mid stream groups, respectively. Two sets of DEGs were primarily enriched in the signaling pathways of drug metabolism, endocrine system, cellular process, and lipid metabolism in the mid-stream sharpbelly, which may alter the fish behavior, disrupt the reproductive function, and lead to hypothyroidism, hepatic steatosis, etc. Taken together, our results linked the disrupted signaling pathways with activities of phenolic compounds to predict the potential effects of wastewater effluent on the health of wild fish.


Assuntos
Disruptores Endócrinos/análise , Poluentes Químicos da Água/análise , Animais , Compostos Benzidrílicos/análise , Ecossistema , Monitoramento Ambiental , Extremo Oriente , Feminino , Fígado/química , Transcriptoma
20.
Hum Pathol ; 100: 1-9, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32330484

RESUMO

Three types of intracytoplasmic inclusions immunoreactive to fibrinogen are collectively diagnosed as hepatic fibrinogen storage disease. This study aimed to better characterize ground glass (type II) and globular (type III) fibrinogen inclusions by the pathological examination of 3 cases and a literature review. Three adults (age: 32-64 years; male/female = 2:1) were unexpectedly found to have fibrinogen-positive ground glass changes (type II inclusions) by liver needle biopsy, against a background of acute hepatitis E, resolving acute cholangitis, or severe lobular hepatitis of unknown etiology. One patient also had fibrinogen-positive intracytoplasmic globules (type III inclusions) in the first biopsy, but they were not present in a second biopsy. None had coagulation abnormalities or hypofibrinogenemia. On immunostaining, both inclusions were strongly positive for not only fibrinogen but also C-reactive protein and C4d. Ultrastructurally, ground glass changes corresponded to membrane-bound cytoplasmic inclusions containing amorphous, granular material. The pathological features of type II fibrinogen inclusions were identical to those of pale bodies in hepatocellular carcinoma. The literature review suggested that type I fibrinogen inclusions characterized by a polygonal appearance are strongly associated with mutations in fibrinogen genes, coagulopathy, and family history, whereas type II/III inclusions are immunoreactive to multiple proteins and typically develop in cases of other unrelated liver diseases. In conclusion, type II and III fibrinogen inclusions do not represent a true hereditary storage disease but instead the collective retention of multiple proteins. Given the lack of clinical significance, a less specific name (e.g., pale body) may be more appropriate for those inclusions.


Assuntos
Fibrinogênio/análise , Corpos de Inclusão/química , Hepatopatias/metabolismo , Fígado/química , Erros Inatos do Metabolismo/metabolismo , Adulto , Biomarcadores/análise , Biópsia , Proteína C-Reativa/análise , Complemento C4b/análise , Feminino , Fibrinogênio/genética , Humanos , Imuno-Histoquímica , Corpos de Inclusão/genética , Corpos de Inclusão/ultraestrutura , Fígado/ultraestrutura , Hepatopatias/classificação , Hepatopatias/genética , Hepatopatias/patologia , Masculino , Erros Inatos do Metabolismo/classificação , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/patologia , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Terminologia como Assunto
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