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1.
Chemosphere ; 287(Pt 3): 132305, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34563770

RESUMO

BACKGROUND: Metal exposures are suspected to associate with the risk of hyperuricemia (HUA), but the current results are still conflicting. OBJECTIVE: To investigate the associations between multiple plasma metal exposures and HUA risk. METHODS: A cross-sectional study was conducted in 1406 Chinese Han adults who underwent routine physical examination in the Eighth Affiliated Hospital of Sun Yat-Sen University in Shenzhen. The plasma levels of 13 metals were measured by the inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic, linear regression models, least absolute shrinkage and selection operator (LASSO) penalized regression analysis, and restricted cubic spline (RCS) models were applied to assess the associations. RESULTS: The median plasma uric acid concentration in HUA group (434 µmol/L) was significantly higher than that in non-HUA group (305 µmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 1.62(1.08-2.43) for magnesium, 1.61(1.05-2.47) for copper, 1.62(1.06-2.49) for zinc, 1.87(1.26-2.81) for arsenic, 1.50(1.01-2.23) for selenium, and 1.70(1.16-2.49) for thallium based on the single-metal logistic regression models, comparing the highest versus the lowest quartile of metal levels. Further multi-metal logistic, linear regression models and the LASSO analysis all indicated positive associations of zinc, arsenic with HUA risk or uric acid levels. RCS model indicated an inverted V-shaped positive association between zinc levels and HUA risk (p for non-linearity = 0.048, p for overall association = 0.022), while arsenic levels showed a positive and linear dose-response relationship with HUA risk (p for non-linearity = 0.892, p for overall association<0.001). CONCLUSIONS: Higher plasma levels of zinc and arsenic might increase HUA risk and showed positive dose-response relationships. Further cohort studies in larger population are required to testify our findings.


Assuntos
Hiperuricemia , Adulto , China/epidemiologia , Estudos Transversais , Humanos , Hiperuricemia/epidemiologia , Metais , Pessoa de Meia-Idade , Ácido Úrico
2.
Diagn Microbiol Infect Dis ; 101(4): 115419, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34610496

RESUMO

Since 2016, several mobile colistin resistance (mcr) genes have been identified worldwide. It's worth noting that only mcr-1, mcr-3, mcr-8, and mcr-10 have been reported isolated directly from clinical samples which created greater risk to human health than other mcr gene types. A novel Quadruplex polymerase chain reaction (Quad-PCR) protocol was developed to detect and genotype transferable colistin-resistance genes (mcr-1, mcr-3, mcr-8, mcr-10) in Enterobacteria for clinical laboratory purposes. The protocol was validated by testing 11 clinical isolates of Escherichia coli and 3 clinical isolates of Klebsiella of human origin, each well characterized and prospectively validated. The Quad-PCR assay showed full concordance with whole-genome sequence data and displayed higher sensitivity and 100% specificity. The Quad-PCR assay achieved genotyping of mcr alleles (as singleton and mixture with double or triple gene types) described in one test.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34197932

RESUMO

OBJECTIVES: China banned the use of colistin as animal growth promoter in April 2017. Herein, we report the prevalence of mcr-1 in the intestine of healthy humans and risk factors associated with mcr-1 carriage after the implementation of the ban. METHODS: We recruited 719 healthy volunteers from Shenzhen City from 1 March 2018 to 31 December 2019 to investigate the prevalence of mcr-1 in human intestine, and undertook a case-control study to ascertain the risk factors associated with the mcr-1-positive population. A further comparative study was conducted to identify differences between genetic characteristics of mcr-1-positive and mcr-1-negative Escherichia coli. RESULTS: Overall, 56 (7.8%, 95% CI 5.9%-10.0%, n = 719) individual faecal samples were positive for mcr-1, and prevalence of mcr-1 among individuals in 2019 (2.4%, 95% CI 8.7%-15.0%, 7/294) was significantly lower than that in 2018 (11.5%, 95% CI 1.0%-4.8%, 49/425) (p < 0.0001). After the colistin ban, animal-derived food (pork and chicken meat) was no longer a risk factor for mcr-1 carriage in human intestine, whereas a higher intake of fish and seafood (>75 g/day) and whole grains (>150 g/day) was associated with higher and lower risk of mcr-1 carriage, respectively (OR 2.175, 95% CI 1.047-4.517; OR 0.045, 95% CI 0.004-0.567). Compared with mcr-1-negative E. coli, the mcr-1-positive E. coli had different patterns of resistance genes and genetic heterogeneity. CONCLUSIONS: Our study implicates aquatic food as beeing associated with mcr-1 carriage in the healthy population, even after the ban on colistin. Dietary modification (e.g. whole grains) may help to combat mcr-1-positive bacterial colonization of the gut.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34199383

RESUMO

AIM: There is an ongoing debate as to what extent antimicrobial resistance (AMR) can be transmitted from dietary to humans via the consumption of food products. We investigated this association between dietary and global spreading carbapenem-resistant gene blaNDM Methods: We did a cross-sectional study to assess the risk factors for carrier of blaNDM in health community. Healthy adults were recruited from the residents attending Community Healthcare Service in Shenzhen City (Guangdong Province, China), through 1February 2018 to 31December 2019, and 718 pre-participants were included in this study. Questionnaire were obtained and the qualitative food frequency questionnaire (Q-FFQ) were used to assess dietary intake. qPCR was applied to confirm the carrier of blaNDM in participants'fecal samples. Multivariable logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of each outcome according to each dietary factor before and after prosperity score matching (PSM). RESULTS: we showed that a high intake of coarse grain (OR 1.003; 95% CI 1.001-1.005, p < 0.01) and root and tuber crops (OR 1.003; 95% CI 1.001-1.004, p < 0.05) were independent risk factor for blaNDM carrier in health communities, suggesting a possible transfer of AMRbetweendietary andhumans. Surprisingly, we also showed an association between a higher intake of poultry as a protective, which may be explained by the beneficial effects on the gut microbiota. CONCLUSION: Dietary factors such as intake of coarse grain, root and tuber crops and poultry were associated with blaNDM carrier in health communities. The influence of dietary factorson blaNDM carrier in the present study provides insights for the tangible dietary advice with guidelines to the routine of people with the risk of blaNDM carrier. This demonstrates the role of dietary intake in the prevention of blaNDM carrier, since prevention is the best way to control modifiable risk factors. A lower carrier rate of blaNDM is helpful to reduce the possibility of transmission and pathogenicity. Further studies on food, microbiota and antimicrobial resistance are necessary to confirm this possible association and unravel underlying mechanisms.


Assuntos
Dieta , Microbioma Gastrointestinal , Adulto , China/epidemiologia , Estudos Transversais , Humanos , Fatores de Risco
5.
Arch Microbiol ; 203(7): 4405-4417, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34125247

RESUMO

Plasmid-mediated colistin-resistance genes have been reported in human origin clinical samples worldwide which raises its threats to human infections. Notably, mcr-1, mcr-3, mcr-8, and mcr-10 have been reported isolated directly from clinical samples which creates more seriously threaten to human health than other mcr gene types. A multiplex polymerase chain reaction (Multi-PCR) protocol was developed to detect and genotype mobile colistin-resistance genes (mcr-1, mcr-3, mcr-8, mcr-10) in Enterobacteria for clinical laboratory purposes. We first designed four pairs of new primers for the amplification of mcr-1, mcr-3, mcr-8, and mcr-10 gene respectively to achieve stepwise separation of amplicons between 216 and 241 bp, and complete this Multi-PCR system with the assistance of another pair of universal primer. Among which the forward primers for mcr-8 and mcr-10 amplicons were identical. The protocol was validated by testing 11 clinical isolates of Escherichia coli and 3 clinical isolates of Klebsiella from human origin, each well characterized and prospectively validated. The Multi-PCR assay showed full concordance with whole-genome sequence data and displayed higher sensitivity and 100% specificity. The assay could detect all variants of the various mcr alleles described. The Multi-PCR assay successfully genotyped of mcr alleles described in one test.


Assuntos
Colistina , Enterobacteriaceae , Fezes , Genes Bacterianos , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Genes Bacterianos/genética , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética
6.
Environ Pollut ; 277: 116630, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667749

RESUMO

Bisphenol S (BPS), an industrial chemical that is a structural analogue of bisphenol A, has been widely reported to be involved in various biological processes. Epidemiological studies have demonstrated that exposure to BPS is associated with dysglycaemia-related health outcomes. The role of BPS in glucose metabolism, however, remains controversial. In this study, we aimed to investigate the effects of chronic exposure to environmentally relevant concentrations of BPS on glucose metabolism in different nutritionally conditioned mice. Our results revealed that 1-month exposure to a BPS dosage of 100 µg/kg bw slightly increased the insulin sensitivity of normal diet-fed mice, and that this effect was enhanced after 3-month exposure. It was also found that BPS exposure attenuated insulin resistance and reduced gluconeogenesis in high-fat diet-fed mice. Consequently, the concentrations of hepatic metabolites related to glucose metabolism were altered in both groups of mice. Moreover, thyroid hormone signalling was disrupted after BPS administration in both groups of mice. Taken together, our results demonstrated that chronic exposure to environmentally relevant concentrations of BPS exerted an unexpected hypoglycaemic effect in mice of different nutritional statuses, and that this was partly attributable to disrupted thyroid hormone signalling.


Assuntos
Resistência à Insulina , Animais , Compostos Benzidrílicos/toxicidade , Gluconeogênese , Hipoglicemiantes , Masculino , Camundongos , Fenóis , Sulfonas
7.
Food Microbiol ; 92: 103585, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32950169

RESUMO

Salmonella Enteritidis is a major cause of foodborne gastroenteritis and is thus a persistent threat to global public health. The acid adaptation response helps Salmonella survive exposure to gastric environment during ingestion. In a previous study we highlighted the damage caused to cell membrane and the regulation of intracellular reactive oxygen species (ROS) in S. Enteritidis. In this study, we applied both physiologic and iTRAQ analyses to explore the regulatory mechanism of acid resistance in Salmonella. It was found that after S. Enteritidis was subject to a 1 h period of acid adaptation at pH 5.5, an additional 1 h period of acid shock stress at pH 3.0 caused less Salmonella cell death than in non-acid adapted Salmonella cells. Although there were no significant differences between adapted and non-adapted cells in terms of cell membrane damage (e.g., membrane permeability or lipid peroxidation) after 30 min, intracellular ROS level in acid adapted cells was dramatically reduced compared to that in non-acid adapted cells, indicating that acid adaption promoted less ROS generation or increased the ability of ROS scavenging with little reduction in the integrity of the cell membrane. These findings were confirmed via an iTRAQ analysis. The adapted cells were shown to trigger incorporation of exogenous long-chain fatty acids into the cellular membrane, resulting in a different membrane lipid profile and promoting survival rate under acid stress. S. Enteritidis experiences oxidative damage and iron deficiency under acid stress, but after acid adaption S. Enteritidis cells were able to balance their concentrations of intracellular ROS. Specifically, SodAB consumed the free protons responsible for forming reactive oxygen intermediates (ROIs) and KatE protected cells from the toxic effects of ROIs. Additionally, acid-labile proteins released free unbound iron promoting ferroptotic metabolism, and NADH reduced GSSH to G-SH, protecting cells from acid/oxidative stress.


Assuntos
Ácidos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Salmonella enteritidis/metabolismo , Adaptação Fisiológica , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Ácidos Graxos , Proteômica , Salmonella enteritidis/química , Salmonella enteritidis/genética
8.
Environ Int ; 144: 106005, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32739516

RESUMO

Cumulative research on resistomes and microbiomes from aquatic environments has revealed that both integrated freshwater and monoculture freshwater aquaculture systems can cause the development and dissemination of antibiotic resistance genes (ARGs) and associated mobile genetic elements (MGEs). However, few studies have examined differences in resistomes between the different aquaculture modes, and those that do have focused on antibiotic residues or individual resistance genes. In the current study, we collected 44 environmental samples from two monoculture freshwater aquaculture farms and four integrated farms (two duck and fish farms, two laying duck and fish farms) in Guangdong, China, in 2018. After measuring the concentrations of antibiotic residues in the samples, we characterized MGEs and ARGs and examined their association with potential bacterial hosts in the microbial communities using high-throughput sequencing-based metagenomic and network analyses. We then compared the resistome profiles of the different aquaculture models. We found that the number and total relative abundance of ARG and MGE subtypes in the integrated (fish and duck/laying duck) farm samples were significantly higher than those in samples from monoculture freshwater aquaculture farms. Specifically, both the mobile colistin resistance genes mcr variants and tigecycline resistance gene tet(X) variants in integrated farms exhibited higher total relative abundance than that in monoculture farms. Moreover, the interrelationships among ARGs and microbial taxa, ARGs and MGEs, and MGEs and microbial taxa in the integrated farm samples were also more complex than those observed in monoculture freshwater aquaculture farm samples. Meanwhile, the species of Acinetobacter and Escherichia were identified to be the possible host of tet(X) and ESBL gene blaCTX-M in aquaculture, respectively. To the best of our knowledge, this is the first metagenomic study to analyze differences in resistome profiles between integrated and monoculture ponds. Overall, integrated aquaculture systems exhibited a higher prevalence of resistance genes compared with monoculture freshwater aquaculture farms. Therefore, additional antimicrobial resistance surveillance should be focused on this type of freshwater aquaculture system.


Assuntos
Aquicultura , Genes Bacterianos , Animais , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos/genética , Metagenômica
9.
Artigo em Inglês | MEDLINE | ID: mdl-32425881

RESUMO

Metformin is a widely used biguanide drug due to its safety and low cost. It has been used for over 60 years to treat type 2 diabetes at the early stages because of its outstanding ability to decrease plasma glucose levels. Over time, different uses of metformin were discovered, and the benefits of metformin for various diseases and even aging were verified. These diseases include cancers (e.g., breast cancer, endometrial cancer, bone cancer, colorectal cancer, and melanoma), obesity, liver diseases, cardiovascular disease, and renal diseases. Metformin exerts different effects through different signaling pathways. However, the underlying mechanisms of these different benefits remain to be elucidated. The aim of this review is to provide a brief summary of the benefits of metformin and to discuss the possible underlying mechanisms.


Assuntos
Metformina/farmacologia , Envelhecimento/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
J Sep Sci ; 43(12): 2321-2329, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32198831

RESUMO

A rapid and reliable method for the detection of five carbapenems (biapenem, imipenem, doripenem, meropenem, and faropenem) in water was developed and validated. After acidification of water samples with acetic acid, carbapenems were isolated using a Bond Elut PPL cartridge. The target compounds were separated using ultra high performance liquid chromatography with a chromatographic run time of 5 min and detected on a triple quadrupole mass spectrometer operated in positive electrospray ionization and multiple reaction monitoring mode. Mean recoveries were in the range of 76.6-106.5%, with satisfactory intraday and interday relative standard deviations lower than 10.0 and 10.8%, respectively. The limits of detection and quantification were in the ranges of 0.05-0.2 µg/L and 0.1-0.5 µg/L, respectively, depending on the analyte. The proposed method was applied to the analysis of river samples and wastewater samples from swine farms, and no carbapenems were detected in the collected samples.


Assuntos
Carbapenêmicos/análise , Poluentes Químicos da Água/química , Animais , Cromatografia Líquida de Alta Pressão , Rios/química , Suínos , Espectrometria de Massas em Tandem , Águas Residuárias/química
11.
Gene ; 731: 144364, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935511

RESUMO

Apolipoprotein C2 (ApoC2) is an important member of the apolipoprotein C family and functions as a major activator of lipoprotein lipase (LPL). In cardiovascular and cerebrovascular systems, the lipolytic activity of the LPL-ApoC2 complex is critical for the metabolism of triglyceride-rich lipoproteins and contributes to the pathogenesis of ischemic stroke (IS). However, the regulation of ApoC2 in IS development remains unclear. In this study, we first explored potential ApoC2-targeting microRNAs (miRNAs) by bioinformatics tool and compared the miRNA expression profiles in the blood cells of 25 IS patients and 25 control subjects by miRNA microarray. miR-1275 was predicted to bind with the 3' untranslated region of ApoC2, and a significant reduction of blood miR-1275 levels was observed in IS patients. Dual-luciferase reporter assay and quantitative RT-PCR confirmed the regulation of ApoC2 by miR-1275 in THP-1 derived macrophages. miR-1275 also inhibited cellular uptake of ox-LDL and suppressed formation of macrophage foam cell. Furthermore, the whole blood miR-1275 levels were validated in 279 IS patients and 279 control subjects by TaqMan assay. miR-1275 levels were significantly lower in IS cases and logistic regression analysis showed that miR-1275 level was negatively associated with the occurrence of IS (adjusted OR, 0.76; 95% CI, 0.69-0.85; p < 0.001). Addition of miR-1275 to traditional risk factors showed an additive prediction value for IS. Our study shows that blood miR-1275 levels were negatively associated with the occurrence of IS, and miR-1275 might exert an athero-protective role against the development of IS by targeting ApoC2 and blocking the formation of macrophage foam cells.


Assuntos
Apolipoproteína C-II/genética , Células Espumosas/patologia , MicroRNAs/sangue , Acidente Vascular Cerebral/genética , Apolipoproteína C-II/metabolismo , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Células Espumosas/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Macrófagos/patologia , Macrófagos/fisiologia , Masculino , MicroRNAs/fisiologia , Fatores de Risco , Acidente Vascular Cerebral/sangue , Células THP-1
12.
Int J Antimicrob Agents ; 55(1): 105856, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770630

RESUMO

Two novel phosphoethanolamine transferase genes, eptAv7 and eptAv3, were identified in the chromosome of an Aeromonas jandaei isolate from retail fish. The variants showed 79.9% and 80.0% amino acid identity to MCR-7.1 and MCR-3.1, respectively, and increased colistin resistance 128- to 256-fold in Aeromonas salmonicida. The two variants with no mobile genetic element in the flanking regions were also observed in other Aeromonas species. This finding supports the view that Aeromonas is a reservoir for MCR-3 and MCR-7 mobile colistin resistance.


Assuntos
Aeromonas/enzimologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Colistina/farmacologia , Etanolaminofosfotransferase/genética , Doenças dos Peixes/microbiologia , Aeromonas/efeitos dos fármacos , Aeromonas/genética , Animais , Aquicultura , Farmacorresistência Bacteriana , Etanolaminas/metabolismo , Peixes , Humanos , Filogenia , Sequenciamento Completo do Genoma
13.
Chemosphere ; 244: 125498, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31812049

RESUMO

BACKGROUND: Heavy metal exposure induces oxidative stress, which is critical for adverse male reproductive health. OBJECTIVE: To explore the mediating effect of oxidative stress on the relationship of heavy metal exposure with semen quality. METHODS: Urinary levels of three oxidative stress markers, semen quality, and urinary arsenic, cadmium and lead were examined among 1020 men. Multivariate linear regression was applied to explore cross-sectional associations, and the role of oxidative stress as mediators was investigated. RESULTS: Quartiles of metals showed significant dose-dependent relationships with increasing levels of 8-hydroxy-2deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA). Significant or suggestive associations were also found between urinary 8-OHdG levels and the percentage of normal sperm morphology (ptrend < 0.001), between urinary 8-isoPGF2α levels and total motility (ptrend = 0.052), progressive motility (ptrend = 0.050) respectively. The mediation analysis showed that about 14.59%, 18.06%, 15.35% or 16.49% of the association between arsenic/cadmium exposure and the decreased total motility/progressive motility was mediated by 8-isoPGF2α, respectively. In addition, about 16.47% of the relationship between lead exposure and the decreased percentage of normal sperm morphology was mediated by 8-OHdG. CONCLUSIONS: Our findings suggest that higher urinary arsenic, cadmium and lead levels were associated with increased oxidative stress markers, which also related with altered semen quality. 8-isoPGF2α and 8-OHdG might be the possible mediators of the associations between urinary heavy metals and total motility, progressive motility or the proportion of normal sperm morphology.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Sêmen/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Biomarcadores/urina , Cádmio , Estudos Transversais , Humanos , Chumbo/toxicidade , Masculino , Estresse Oxidativo , Reprodução , Análise do Sêmen
14.
Environ Int ; 130: 104708, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31202027

RESUMO

BACKGROUND: Since its discovery in 2015, the mobile colistin resistance gene mcr-1 has been reported in bacteria from >50 countries. Although aquaculture-associated bacteria may act as a significant reservoir for colistin resistance, systematic investigations of mcr-1 in the aquaculture supply chain are scarce. OBJECTIVES: We investigated the presence of colistin resistance determinants in the aquaculture supply chain in south China and determined their characteristics and relationships. METHODS: A total of 250 samples were collected from a duck-fish integrated fishery, slaughter house, and market in Guangdong Province, China, in July 2017. Colistin-resistant bacteria were isolated on colistin-supplemented CHROMagar Orientation plates, and the species were identified by matrix-assisted laser desorption/ionization time-of-flight assay. The presence of mcr genes was confirmed by polymerase chain reaction analysis. We examined the minimum inhibitory concentrations (MICs) of 16 antimicrobial agents against the isolates using agar diffusion and broth microdilution methods. Whole-genome sequencing (WGS) was used to explore the molecular characteristics and relationships of mcr-1-positive Escherichia coli (MCRPEC). RESULTS: Overall, 143 (57.2%) colistin-resistant bacteria were isolated, of which, 56 (22.4%, including 54 Escherichia coli and two Klebsiella pneumoniae) and four Aeromonas species were positive for mcr-1 and mcr-3, respectively. The animal-derived MCRPEC were significantly more prevalent in integrated fishery samples (40.0%) than those in market (4.8%, P<0.01) samples but not in slaughter house (28.0%, P=0.164). All MCRPEC were highly resistant to ampicillin, tetracycline, and compound sulfamethoxazole (>90%) but were susceptible to carbapenems and tigecycline. WGS analysis suggested that mcr-1 was mainly contained on plasmids, including IncHI2 (29.6%), IncI2 (27.8%), IncX4 (14.8%), and IncP (11.1%). Genomic analysis suggested mcr-1 transmission via the aquatic food chain. CONCLUSIONS: MCRPEC were highly prevalent in the aquaculture supply chain, with the isolates showing resistance to most antibiotics. The data suggested mcr-1 could be transferred to humans via the aquatic food chain. Taking the "One Health" perspective, aquaculture should be incorporated into systematic surveillance programs with animal, human, and environmental monitoring.


Assuntos
Aquicultura , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma
15.
Artigo em Inglês | MEDLINE | ID: mdl-31085517

RESUMO

The rapid dissemination of the macrolide resistance gene erm(B) will likely compromise the efficacy of macrolides as the treatment of choice for campylobacteriosis. More importantly, erm(B) is always associated with several multidrug resistance genomic islands (MDRGIs), which confer resistance to multiple other antimicrobials. Continuous monitoring of the emergence of erm(B) and analysis of its associated genetic environments are crucial for our understanding of macrolide resistance in Campylobacter In this study, 290 Campylobacter isolates (216 Campylobacter coli isolates and 74 Campylobacter jejuni isolates) were obtained from 1,039 fecal samples collected in 2016 from pigs and chickens from three regions of China (344 samples from Guangdong, 335 samples from Shanghai, and 360 samples from Shandong). Overall, 74 isolates (72 C. coli isolates and 2 C. jejuni isolates) were PCR positive for erm(B). Combined with data from previous years, we observed a trend of increasing prevalence of erm(B) in C. coli Pulsed-field gel electrophoresis analyses suggested that both clonal expansion and horizontal transmission were involved in the dissemination of erm(B) in C. coli, and three novel types of erm(B)-associated MDRGIs were identified among the isolates. Furthermore, 2 erm(B)-harboring C. jejuni isolates also contained an aminoglycoside resistance genomic island and a multidrug-resistance-enhancing efflux pump, encoded by RE-cmeABC Antimicrobial susceptibility testing showed that most of the isolates were resistant to all clinically important antimicrobial agents used for the treatment of campylobacteriosis. These findings suggest that the increasing prevalence of erm(B)-associated MDRGIs might further limit treatment options for campylobacteriosis.


Assuntos
Antibacterianos/farmacologia , Campylobacter/genética , Ilhas Genômicas/genética , Macrolídeos/farmacologia , Campylobacter/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma
16.
Nat Microbiol ; 4(9): 1450-1456, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31133751

RESUMO

Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet(X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline1,2. Here, we report two unique mobile tigecycline-resistance genes, tet(X3) and tet(X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet(X3) and tet(X4) increase (by 64-128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. In addition, both Tet(X3) (A. baumannii) and Tet(X4) (E. coli) significantly compromise tigecycline in in vivo infection models. Both tet(X3) and tet(X4) are adjacent to insertion sequence ISVsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet(X3) and tet(X4) are globally present in clinical bacteria-even in the same bacteria as blaNDM-1, resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet(X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention.


Assuntos
Bactérias , Proteínas de Bactérias/genética , Oxigenases de Função Mista/genética , Plasmídeos/genética , Resistência a Tetraciclina/genética , Tigeciclina/farmacologia , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Proteínas de Bactérias/metabolismo , Elementos de DNA Transponíveis , Humanos , Carne/microbiologia , Testes de Sensibilidade Microbiana , Oxigenases de Função Mista/metabolismo , Resistência a Tetraciclina/efeitos dos fármacos , Tigeciclina/metabolismo
17.
Ecotoxicol Environ Saf ; 176: 1-10, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30903973

RESUMO

Wide use of titanium dioxide nanoparticles (TiO2 NPs) as white pigments induces unintentionally release in environment which increases concerns about their adverse health effects on respiratory system. So it is crucial to get a deep understanding of the disease process and molecular mechanism. Epigenetic mechanisms, such as DNA methylation, have been found to play a role in the development of lung diseases by affecting expression of key genes. In addition, there could be potential different toxic effects of TiO2 NPs between young and adult. Thus, the comparative toxicity of TiO2 NPs in 5-week (young) and 10-week (adult) old NIH mice is investigated in this study following nasal inhalation of TiO2 NPs at dose of 20 mg/kg (body weight)/day for 30 days. Global DNA methylation and hydroxymethylation in lung were measured. Promoter methylation of inflammatory genes (IFN-γ and TNF-α) and tissue fibrosis gene (Thy-1) were determined. Additional, RNA-sequencing runs were performed on the pulmonic libraries. We found the induced pulmonary inflammation and fibrosis were more severe in young mice. Decreased global methylation and hydroxymethylation were only found in the young group. The altered methylation in promoter of TNF-α and Thy-1 were found to play a role in the inflammatory response and fibration. RNA-sequencing showed that in pathways in cancer expression of 197 genes was up-regulated in the young mice more that in the adult mice. All these results suggested that the young ages are more sensitive to TiO2 NP exposure and the potential of abnormal DNA methylation might be used as biomarkers of both exposure and disease development.


Assuntos
Metilação de DNA , Exposição por Inalação , Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Pneumonia/patologia , Titânio/toxicidade , Animais , Biomarcadores/metabolismo , Fibrose/genética , Pulmão/patologia , Nanopartículas Metálicas/toxicidade , Camundongos , Pneumonia/genética , Regiões Promotoras Genéticas , Análise de Sequência de RNA , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
18.
Environ Int ; 125: 125-134, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716572

RESUMO

BACKGROUND: Ischemic stroke (IS) is a major cause of morbidity and mortality globally. Environmental exposure to metals may be linked to the risk of IS, but the association remains uncertain in Chinese populations. OBJECTIVES: The present study aimed to examine the associations between the concentrations of 11 metals (aluminum, arsenic, cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, thallium, and zinc) in plasma and the risk of IS in a Chinese population. METHODS: A total of 1277 pairs of newly diagnosed IS patients and controls matched on age (±3 years) and sex were recruited in our study. Plasma metal concentrations were measured using inductively coupled plasma mass spectrometry. Multivariable conditional logistic regression models were conducted to investigate the impacts of single and multiple metals, respectively. RESULTS: In the single-metal model, exposure to seven metals (aluminum, arsenic, cadmium, cobalt, iron, manganese and selenium) was individually associated with the risk of IS based on the trend test. Further stepwise regression analyses with the multiple-metal model revealed increasing trends in the risk of IS associated with aluminum, arsenic, and cadmium quartiles and decreasing trends with iron and selenium quartiles (p-trend < 0.01). Compared to the lowest quartiles, the odds ratios (95% confidence intervals) for the highest quartiles of these five metals were 4.23 (2.63, 6.79), 1.88 (1.25, 2.81), 5.02 (3.30, 7.63), 0.59 (0.40, 0.89), and 0.10 (0.06, 0.17), respectively. CONCLUSIONS: Our study suggested that higher plasma concentrations of aluminum, arsenic, and cadmium, and lower concentrations of iron and selenium may increase the risk of IS. Further prospective studies in larger populations are warranted to confirm our findings.


Assuntos
Isquemia Encefálica/induzido quimicamente , Metais/sangue , Metais/toxicidade , Acidente Vascular Cerebral/induzido quimicamente , Idoso , Grupo com Ancestrais do Continente Asiático , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Acidente Vascular Cerebral/sangue
19.
J Cell Mol Med ; 23(1): 167-176, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30499219

RESUMO

Spleen tyrosine kinase (SYK) gene has been identified as novel susceptibility locus for ischaemic stroke (IS) previously. However, regulation of SYK gene remains unknown in IS. In this study, we aimed to identify miRNAs that might be involved in the development of IS by targeting SYK gene. miRNAs were firstly screened by bioinformatics predicting tool. The expression levels of SYK gene were detected by qRT-PCR and western blotting, respectively, after miRNA transfection. Luciferase reporter assay was applied to investigate the direct binding between miRNAs and target gene. miRNA levels were detected by miRNA TaqMan assays in the blood cells of 270 IS patients and 270 control volunteers. Results suggest that SYK gene might be a direct target of miR-129-2-3p. The blood level of miR-129-2-3p was significantly lower in IS patients (P < 0.05), and negatively associated with the risk of IS (adjusted OR: 0.88; 95% CI: 0.80-0.98; P = 0.021) by multivariable logistic regression analysis. The blood levels of SYK gene were significantly higher in IS patients, and miR-129-2-3p expression was negatively correlated with mean platelet volume. In summary, our study suggests that miR-129-2-3p might be involved in the pathogenesis of IS through interrupting SYK expression and the platelet function, and further investigation is needed to explore the underlying mechanism.


Assuntos
Isquemia Encefálica/genética , MicroRNAs/genética , Acidente Vascular Cerebral/genética , Quinase Syk/genética , Regiões 3' não Traduzidas , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , Quinase Syk/sangue
20.
Oxid Med Cell Longev ; 2018: 3295807, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30327711

RESUMO

Curcumin has several therapeutic properties such as anti-inflammatory effect. Heme oxygenase-1 (HO-1) has been showed to have cytoprotective effects in some pathological conditions. However, the role of HO-1 in anti-inflammatory effect of curcumin is unknown. In this study, we investigate whether the anti-inflammatory effect of curcumin in vascular may be involved in the activation of HO-1. New Zealand white rabbits were fed regular control diet or control diet added with 0.3% curcumin (wt/wt) for four weeks. Acute vascular inflammation of rabbits was induced by putting a collar on the left common carotid artery for 24 hours. HO-1 inhibitor and siRNA were used to investigate the role of HO-1 in the anti-inflammatory effect of curcumin in collared vascular. We also explored the mechanism of curcumin-induced activation of HO-1 in vitro. The serum bilirubin and vascular, liver, and spleen HO-1 mRNA levels were significantly increased in curcumin-treated rabbits. The vascular inflammation was significantly decreased in the curcumin-treated animals compared with the control. Treatment of the rabbits with an inhibitor of HO or HO-1 siRNA to knock down the carotid artery HO-1 abolished the ability of curcumin to inhibit vascular inflammation. Treatment of cultured human artery endothelial cells with curcumin induced the HO-1 expression through the activation of nuclear factor-E2-related factor 2 (Nrf2) and an antioxidant responsive element via the p38 MAPK signalling pathway. In conclusion, curcumin inhibits vascular inflammation in vivo and in vitro through the activation of HO-1.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Animais , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/metabolismo , Endotélio Vascular/metabolismo , Ativação Enzimática/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Coelhos
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