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1.
Ecotoxicol Environ Saf ; 208: 111469, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091769

RESUMO

Coal ash spills occasionally occur due to the accidental failure of surface impoundments, and toxic metal-laden ash can pose a serious health threat to adjacent aquatic ecosystems. Here, we performed an investigation into longitudinal variations of mercury (Hg) contamination in the Dan River (North Carolina, United States) about 17 and 29 months after a February 2014 coal ash spill incident, in which the reported Hg concentrations in the spilled coal ash (210 ng/g) were 1-2 orders of magnitude higher than the river sediments (2-61 ng/g). We examined total Hg (THg) and methyl Hg (MeHg) in sediments from 0 to 65 km downstream of the spill, and found that most of the variations of THg and MeHg in surface sediments (0-16 cm) could be well accounted by the organic matter content and appeared to be not contaminated by Hg derived from coal ash. In examining MeHg bioaccumulation in invertebrates (aquatic and riparian) and fish in the Dan River and fish in a reservoir downstream of Dan River, we found no evidence of elevated MeHg bioaccumulation due to the 2014 coal ash spill. Thus, we concluded that Hg contamination from the coal ash spill is largely absent in the Dan River for both surface sediments and biota within the first three years of spill (until 2017), even though the majority of coal ash may be buried deeper in the sediment in the river channel and/or the downstream reservoir. Alternatively, the Hg associated with the coal ash is largely not bioavailable for extensive microbial Hg methylation. The findings provide useful insights into remediation strategies for this incident and other coal ash spills.


Assuntos
Vazamento de Resíduos Químicos , Cinza de Carvão/análise , Monitoramento Ambiental , Mercúrio/análise , Poluentes Químicos da Água/análise , Animais , Ecossistema , Peixes , Compostos de Metilmercúrio/análise , North Carolina , Rios , Estados Unidos , Poluentes Químicos da Água/toxicidade
2.
Environ Sci Technol ; 53(5): 2434-2440, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30727732

RESUMO

Compared to the extensive research on aquatic ecosystems, very little is known about the sources and trophic transfer of methylmercury (MeHg) in terrestrial ecosystems. In this study, we examine energy flow and trophic structure using stable carbon (δ13C) and nitrogen (δ15N) isotope ratios, respectively, and MeHg levels in basal resources and terrestrial invertebrates from four temperate forest ecosystems. We show that MeHg levels in biota increased significantly ( p < 0.01) with δ13C and δ15N at all sites, implying the importance of both microbially processed diets (with increased δ13C) and trophic level (with increased δ15N) at which organisms feed, on MeHg levels in forest floor biota. The trophic magnification slopes of MeHg (defined as the slope of log10MeHg vs δ15N) for these forest floor food webs (0.20-0.28) were not significantly different ( p > 0.05) from those observed for diverse temperate freshwater systems (0.24 ± 0.07; n = 78), demonstrating for the first time the nearly equivalent efficiencies with which MeHg moves up the food chain in these contrasting ecosystem types. Our results suggest that in situ production of MeHg within the forest floor and efficient biomagnification both elevate MeHg levels in carnivorous invertebrates in temperate forests, which can contribute to significant bioaccumulation of this neurotoxin in terrestrial apex predators.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Ecossistema , Peixes , Cadeia Alimentar , Florestas
3.
Int J Mol Sci ; 18(2)2017 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-28208579

RESUMO

Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics.


Assuntos
Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Comunicação Celular , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Metabolismo Energético , Variação Genética , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Sistema de Sinalização das MAP Quinases , Terapia de Alvo Molecular , Ligação Proteica , Fatores de Risco , Transdução de Sinais , Estresse Fisiológico , Serina-Treonina Quinases TOR/metabolismo
4.
Appl Environ Microbiol ; 81(22): 7833-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26341208

RESUMO

Two previously uncharacterized potential broad-spectrum mercury (Hg) resistance operons (mer) are present on the chromosome of the soil Alphaproteobacteria Xanthobacter autotrophicus Py2. These operons, mer1 and mer2, contain two features which are commonly found in mer operons in the genomes of soil and marine Alphaproteobacteria, but are not present in previously characterized mer operons: a gene for the mercuric reductase (MerA) that encodes an alkylmercury lyase domain typical of those found on the MerB protein, and the presence of an additional gene, which we are calling merK, with homology to glutathione reductase. Here, we demonstrate that Py2 is resistant to 0.2 µM inorganic mercury [Hg(II)] and 0.05 µM methylmercury (MeHg). Py2 is capable of converting MeHg and Hg(II) to elemental mercury [Hg(0)], and reduction of Hg(II) is induced by incubation in sub toxic concentrations of Hg(II). Transcription of the merA genes increased with Hg(II) treatment, and in both operons merK resides on the same polycistronic mRNA as merA. We propose the use of Py2 as a model system for studying the contribution of mer to Hg mobility in soil and marine ecosystems.


Assuntos
Proteínas de Bactérias/genética , Mercúrio/metabolismo , Compostos de Metilmercúrio/metabolismo , Poluentes do Solo/metabolismo , Xanthobacter/genética , Proteínas de Bactérias/metabolismo , Óperon , Oxirredução , Xanthobacter/metabolismo
5.
Front Microbiol ; 14: 1016872, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910172

RESUMO

The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.

6.
Sci Rep ; 10(1): 9023, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488074

RESUMO

Cardiovascular disease (CVD) is the major cause of morbidity, mortality, and health care costs in the United States, and possibly around the world. Among the various risk factors of CVD, environmental and dietary exposures to mercury (Hg), a highly toxic metal traditionally regarded as a neurotoxin, has been recently suggested as a potential contributor towards human atherosclerotic development. In this study, we investigated the toxicity, type of cell death, dose-dependent uptake, and efflux of inorganic HgII (as HgCl2) and methylmercury or MeHg (as CH3HgCl) in EA.hy926 endothelial cells, as these two forms of Hg are often reported to be present in human blood among the general populations (~20-30% as HgII and ~70-80% as MeHg). Our results showed that HgII is more toxic than MeHg to the endothelial cells, owing to the higher uptake into the cytoplasm and perhaps importantly lower efflux of HgII by the cells, thus the "net" accumulation by the endothelial cells is higher for HgII than MeHg when exposed to the same Hg levels in the media. Furthermore, both HgII and MeHg were found to induce apoptotic and necrotic cell death. This study has important implications for the contributions of these two common Hg species to the development of atherosclerosis, an important process leading to CVD.


Assuntos
Células Endoteliais/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , Compostos de Metilmercúrio/toxicidade , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Células Endoteliais/patologia , Endotélio Vascular/citologia , Humanos , Cloreto de Mercúrio/administração & dosagem , Cloreto de Mercúrio/farmacocinética , Mercúrio/farmacocinética , Compostos de Metilmercúrio/administração & dosagem , Compostos de Metilmercúrio/farmacocinética
7.
Chin Med Sci J ; 23(2): 108-12, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18686630

RESUMO

OBJECTIVE: To analyze how the infection of human papillomavirus 16 (HPV16) affects expression of DNA polymerase beta (DNA polB) with the aim of probing the mechanism of over-expression of DNA polB in human cancers. METHODS: Four fragments of human DNA polB promoter were amplified and constructed into luciferase reporter vector pGL-Basic, generating pGL-BP, pGL-BMH, pGL-BMS, and pGL-BAT constructs respectively, and co-transfected with HPV16 or HPV6 into Hep2 cells. Luciferase activity was assayed 48 hours after transfection. Semi-quantitative RT-PCR was used to measure mRNA expression of endogenous DNA polB. Immunohistochemistry and in situ hybridization were used to analyze DNA polB expression and HPV16 or HPV6 infection in 38 cases of cervical lesions respectively. RESULTS: With co-transfection of HPV16 and DNA polB promoter-driving reporters into Hep2 cells, pGL-BP reporter in full-length DNA polB promoter presented markedly elevated luciferase activities (P < 0.05). However, the other three mutant reporters: pGL-BMH, pGL-BMS, and pGL-BAT, generated no reporting activities in the presence of HPV16 (P > 0.05). On the contrary, all of polB promoter reporters were little stimulated in co-transfection of HPV6 (P > 0.05). The transfection of HPV16 could enhance the endogenous polB mRNA expression compared with that of HPV6 (3.42 vs. 0.80, P < 0.05). The DNA polB expression was found in 8 of 10 HPV16-positive cervical intraepithelial neoplasia grade III (CIN III) cases, while was only found in 3 of 11 HPV6-positive condyloma accuminatum cases, but was negative in all chronic cervicitis cases. The correlation of DNA polB expression with HPV16 infection in cervical lesions was significant (P < 0.05). CONCLUSIONS: HPV16 is able to specifically stimulate the expression of DNA polB in human epithelial cells through interaction with the core upstream regulatory sequences of DNA polB promoter. Over-expression of DNA polB might be an explanation for the molecular mechanism underlying HPV-related human cancers.


Assuntos
DNA Polimerase beta/metabolismo , Regulação Enzimológica da Expressão Gênica , Papillomavirus Humano 16/metabolismo , Linhagem Celular , DNA Polimerase beta/genética , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/metabolismo , Humanos , Infecções por Papillomavirus , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 35(4): 382-5, 2003 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12947553

RESUMO

OBJECTIVE: To investigate the promoter methylation status of gene p16INK4a and RB and their expressions at protein level in gastric carcinomas, and their correlation with clinical and pathological parmeters. METHODS: A series of 81 gastric carcinomas and 10 normal gastric tissues was examined for the promoter methylation of p16INK4a or RB by methylation-specific PCR method. The expression of p16INK4a and pRb was detected by immunohistochemistry. RESULTS: Methylation of p16INK4a and RB was found in 37% (30/81) and 42% (34/81) of gastric carcinomas, respectively, and positive immunostaining for p16INK4a and pRb was detected in 54% (44/81) and 90% (73/81) of the tumors, respectively. In addition, promoter methylation of p16INK4a was significantly associated with negative immunostaining of p16INK4a (P < 0.001), but was not associated with differentiation status, lymph node metastasis, sex and age. RB methylation was not correlated with pRb expression, differentiation status, sex and age, but was associated with lymph node metastasis. CONCLUSION: Methylation of p16INK4a or RB is a common event in gastric carcinomas and may play a role in the development of gastric carcinomas. Methylation of RB is correlated with lymph node metastasis, suggesting that RB methylation may predict lymph node metastasis. Promoter methylation of p16INK4a is an important mechanism for its inactivation.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Proteína do Retinoblastoma/genética , Neoplasias Gástricas/genética , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas
9.
Int J Syst Evol Microbiol ; 59(Pt 12): 2987-90, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19643907

RESUMO

A taxonomic study was performed on strain QM42(T), which was isolated from coastal seawater from an aquaculture site near Qingdao, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain QM42(T) was a member of the class Gammaproteobacteria. Cells of strain QM42(T) were Gram-negative, yellow, aerobic and rod-shaped. The strain formed a distinct phyletic line with less than 91 % 16S rRNA gene sequence similarity to its closest relatives with validly published names within the class Gammaproteobacteria. The genomic DNA G+C content was 51.9 mol%. The major fatty acids were C(16 : 1)omega7c/iso-C(15 : 0) 2-OH, C(18 : 1)omega7c and C(16 : 0). Based on data from a polyphasic chemotaxonomic, physiological and biochemical study, strain QM42(T) is considered to represent a novel genus and species, for which the name Gilvimarinus chinensis gen. nov., sp. nov., is proposed. The type strain is QM42(T) (=CGMCC 1.7008(T)=DSM 19667(T)).


Assuntos
Ágar/metabolismo , Gammaproteobacteria/classificação , Gammaproteobacteria/isolamento & purificação , Água do Mar/microbiologia , Composição de Bases , China , DNA Bacteriano/genética , DNA Ribossômico/genética , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Gammaproteobacteria/genética , Gammaproteobacteria/metabolismo , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética
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