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1.
Appl Environ Microbiol ; 86(4)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31811045

RESUMO

Recent studies have suggested that the gut microbiome is modified in space analogs and that human health can be affected during actual spaceflight. However, the relationship between the gut microbiome and dietary intake in simulator subjects and astronauts remains unclear. Bioregenerative life support systems (BLSSs) are confined and self-sufficient ecosystems that enable exploration of this issue. Here, we correlate changes in gut microbes to the nutrient types present in controlled diets within subjects cohabitating in a BLSS. A metagenome-wide association study (MWAS) was performed on 55 shotgun-sequenced fecal samples longitudinally obtained from healthy Chinese subjects (n = 4 in total, n = 2 per sex) subjected to a 60-day BLSS stay and a specialized diet. Each food item was categorized based on nutrient type according to the Chinese Food Ingredients List (https://wenku.baidu.com/view/3f2b628488eb172ded630b1c59eef8c75fbf9514.html?from=search). The physical parameters of each subject fluctuated within normal medical ranges. Sex- and individual-specific differences and a trend of individual convergence of the gut microbiome in the BLSS were observed. Depletion of bacterial taxa such as Faecalibacterium prausnitzii, Bifidobacterium longum, and Escherichia coli and functional modules such as short-chain fatty acid (SCFA) production, as well as an increase in an unidentified Lachnospiraceae and glutamate/tryptophan synthesis, were observed in the BLSS. Correlation analysis showed that these compositional and functional changes were associated with energy/nutrient intake during the BLSS stay. Our findings suggest that the gut microbiota is a useful indicator for monitoring health and that individual nutritive diets should be considered according to sex and individual differences in simulations or in spaceflight.IMPORTANCE The gut microbiome shows individual specificity and is affected by sex, environment, and diet; gut microbiome imbalance is related to cancer, cardiovascular diseases, and autoimmune diseases. Astronauts are faced with a challenging environment and limited diet in outer space. Recent studies indicate that the gut microbiome is altered in space simulators and space, but what happens to intestinal microorganisms when astronauts cohabitate in a self-sufficient ecosystem in which they plant and cook food is unclear. Bioregenerative life support systems (BLSSs) are ideal devices to investigate the above issues because they are closed and self-sufficient. Four healthy Chinese subjects cohabitated in a confined BLSS for 60 days, during which their physical parameters and energy/nutrient intake were recorded. We performed a metagenome-wide association study (MWAS) on 55 shotgun-sequenced fecal samples longitudinally obtained from the subjects. Alterations occurred in the gut microbial composition and function, and their relationships with energy/nutrient intake were explored.

2.
Chemosphere ; 240: 124933, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726611

RESUMO

The occurrence, air-sea exchange, and gas-particle partitioning of polybrominated diphenyl ethers (PBDEs) were analyzed during a 2015 research expedition from the East China Sea (ECS) to the open Northwest Pacific Ocean (NWP). The sum of 13 PBDEs (Σ13PBDEs) in air and surface seawater varied in the range of 0.54-14.5. pg m-3 and 0.60-13.5 pg L-1, respectively, with the highest concentrations observed in the ECS. The Clausius-Clapeyron approach and air mass origin analysis indicated that continued primary emissions of PBDEs, particularly BDE-209, from East Asian sources governed the spatial variability of air PBDEs over the NWP through long-range atmospheric transport (LRAT). Net air-to-seawater gas deposition of PBDEs was evidenced based on the fugacity calculation with sum fluxes of seven selected PBDEs ranging from -45 to -582 pg m-2 d-1. Following the substantial advection of aerosol phase BDE-209 over the ECS, dry particle deposition dominated the input pathway of PBDEs into the ECS, whereas in the open NWP, relatively free from the influence of the land emissions, fluxes in PBDE absorption and in dry particle deposition were comparable. This suggests an impact of continental outflow on the fate of atmospheric PBDEs over the NWP. Regarding gas-particle partitioning, PBDEs over the NWP were obviously absorbed into continental organic aerosols during atmospheric transport, except for BDE-209, which tended to remain within the steady state.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Aerossóis/análise , Ásia , Atmosfera/química , China , Extremo Oriente , Oceano Pacífico , Água do Mar
3.
FEBS J ; 286(3): 572-583, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30521142

RESUMO

Mycobacterium tuberculosis (Mtb) is the pathogen responsible for tuberculosis, a leading cause of illness and death worldwide. Growing evidence suggests that the proinflammatory cytokine IL-32 plays a major role in host defences against pathogens such as Mtb. IL-32 exists in six alternatively spliced isoforms, but antituberculosis effects have been reported only for some of them. In this study, we examined the effect of all six IL-32 isoforms on Mtb replication in the murine macrophage cell line RAW 264.7. Compared with cells transfected with the other isoforms, IL-32ε-transfected cells exhibited the strongest antituberculosis effect and the highest rate of Mtb-induced apoptosis. Of note, this apoptosis pathway was independent of caspase-3 activation. Instead, N-Myc interactor (NMI), an inhibitor of Wnt signalling, was a key player in IL-32ε-mediated apoptosis by inhibiting Wnt/ß-catenin signalling and thereby activating c-Myc-mediated apoptosis. Moreover, we identified two cis-acting elements that are binding sites for the transcriptional regulators paired box 6 (PAX6) and transcription factor CP2 (TFCP2) in the promoter of NMI and these elements proved essential for IL-32ε-induced upregulation of Nmi expression. Furthermore, IL-32ε-mediated activation of the mitogen-activated protein kinase p38 also contributed to NMI upregulation. In conclusion, our results demonstrate that Mtb infection-induced IL-32ε-mediated apoptosis in macrophages plays a key role in host defences against Mtb.


Assuntos
Interações Hospedeiro-Patógeno/genética , Interleucinas/genética , Mycobacterium tuberculosis/genética , Proteína Proto-Oncogênica N-Myc/genética , Processamento Alternativo , Animais , Apoptose/genética , Sítios de Ligação , Caspase 3/genética , Caspase 3/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Genes Reporter , Humanos , Interleucinas/metabolismo , Luciferases/genética , Luciferases/metabolismo , Camundongos , Mycobacterium tuberculosis/metabolismo , Proteína Proto-Oncogênica N-Myc/metabolismo , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX6/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Células RAW 264.7 , Células THP-1 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Environ Pollut ; 230: 444-452, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28675854

RESUMO

We measured 15 parent polycyclic aromatic hydrocarbons (PAHs) in atmosphere and water during a research cruise from the East China Sea (ECS) to the northwestern Pacific Ocean (NWP) in the spring of 2015 to investigate the occurrence, air-sea gas exchange, and gas-particle partitioning of PAHs with a particular focus on the influence of East Asian continental outflow. The gaseous PAH composition and identification of sources were consistent with PAHs from the upwind area, indicating that the gaseous PAHs (three-to five-ring PAHs) were influenced by upwind land pollution. In addition, air-sea exchange fluxes of gaseous PAHs were estimated to be -54.2-107.4 ng m-2 d-1, and was indicative of variations of land-based PAH inputs. The logarithmic gas-particle partition coefficient (logKp) of PAHs regressed linearly against the logarithmic subcooled liquid vapor pressure (logPL0), with a slope of -0.25. This was significantly larger than the theoretical value (-1), implying disequilibrium between the gaseous and particulate PAHs over the NWP. The non-equilibrium of PAH gas-particle partitioning was shielded from the volatilization of three-ring gaseous PAHs from seawater and lower soot concentrations in particular when the oceanic air masses prevailed. Modeling PAH absorption into organic matter and adsorption onto soot carbon revealed that the status of PAH gas-particle partitioning deviated more from the modeling Kp for oceanic air masses than those for continental air masses, which coincided with higher volatilization of three-ring PAHs and confirmed the influence of air-sea exchange. Meanwhile, significant linear regressions between logKp and logKoa (logKsa) for PAHs were observed for continental air masses, suggesting the dominant effect of East Asian continental outflow on atmospheric PAHs over the NWP during the sampling campaign.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , Adsorção , Atmosfera/química , Carbono , China , Gases , Oceano Pacífico , Estações do Ano , Fuligem , Volatilização
5.
Can J Neurol Sci ; 44(6): 718-725, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28631579

RESUMO

BACKGROUND: ATP-sensitive K+ (KATP) channels couple metabolic state to cellular excitability. Activation of neuronal and astrocytic mitochondrial KATP (mitoKATP) channels regulates a variety of neuronal functions. However, less is known about the impact of mitoKATP on tonic γ-aminobutyric acid (GABA) inhibition. Tonic GABA inhibition is mediated by the binding of ambient GABA on extrasynaptic GABA A-type receptors (GABAARs) and is involved in regulating neuronal excitability. METHODS: We determined the impact of activation of KATP channels with diazoxide (DIZ) on tonic inhibition and recorded tonic current from rat cortical layer 5 pyramidal cells by patch-clamp recordings. RESULTS: We found that neonatal tonic current increased with an increase in GABA concentration, which was partially mediated by the GABA A-type receptor (GABAAR) α5, and likely the δ subunits. Activation of KATP channels resulted in decreased tonic current in newborns, but there was increased tonic current during the second postnatal week. CONCLUSIONS: These findings suggest that activation of KATP channels with DIZ regulates GABAergic transmission in neocortical pyramidal cells during development.


Assuntos
Encéfalo/efeitos dos fármacos , Canais KATP/metabolismo , Células Piramidais/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Encéfalo/metabolismo , Feminino , Canais KATP/efeitos dos fármacos , Masculino , Inibição Neural/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos Sprague-Dawley
6.
Int J Mol Med ; 40(1): 155-163, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28560440

RESUMO

Inflammation and remodeling play a role in the pathogenesis of pulmonary arterial hypertension (PAH). Nuclear factor-κB (NF-κB) and nuclear factor of activated T cells-1 (NFAT-1) participate in inflammation and remodeling in a number of diseases. As a tryptophan hydroxylase inhibitor, 4-chloro-DL-phenylalanine (PCPA) had been reported to exert anti-inflammatory and remodeling effects. Therefore, we hypothesized that PCPA may attenuate monocrotaline (MCT)-induced PAH through the NFAT-1 and NF-κB signaling pathways. In order to confirm our hypothesis, we divided 68 Sprague-Dawley male rats into 4 groups as follows: the control, MCT, MCT + P1 and MCT + P2 groups. MCT was administered at a dose of 60 mg/kg once via intraperitoneal injection. PCPA was administered via intraperitoneal injection at a dose of 50 or 100 mg/kg once daily for 21 consecutive days. We then measured the hemodynamic index and morphological analysis was carried out on the lung tissues. Western blot analysis and immunohistochemistry were used to examine the levels of NFAT-1 and NF-κB p-65. The expression levels of phosphorylated inhibitor of NF-κB kinase (p-IKK), IKK, phosphorylated extracellular signal­regulated kinase (p-ERK), ERK, intercellular adhesion molecule-1 (ICAM-1) and inter-leukin-6 (IL-6) were examined by western blot analysis. MCT was found to significantly induce PAH, with inflammation and remodeling of the lung tissues. This was associatd with an increased expression of NFAT-1, p-IKK, p-ERK and nuclear p65. PCPA significantly attenuated MCT-induced inflammation and arterial remodeling, and decreased the expression of NFAT-1, as well as that of relevant proteins of the NF-κB signaling pathway. The above-mentioned findings suggest that the inhibitory effects of PCPA on MCT-induced inflammation and arterial remodeling are related to the downregulation of the NFAT-1 and NF-κB signaling pathways in rats with PAH.


Assuntos
Fenclonina/análogos & derivados , Hipertensão Pulmonar , Monocrotalina/toxicidade , Fatores de Transcrição NFATC/metabolismo , Fator de Transcrição RelA/metabolismo , Triptofano Hidroxilase/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Fenclonina/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Triptofano Hidroxilase/metabolismo
7.
Oncotarget ; 8(67): 111642-111655, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29340081

RESUMO

The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP), right ventricle hypertrophy index (RVI) and pulmonary artery morphology were assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by western blot or immunohistochemistry. The concentration of serotonin in plasma was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial remodeling induced by MCT, and this action was associated with accelerated apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study suggests that PCPA protects against the pathogenesis of PAH by suppressing remodeling and inducing apoptosis, which are likely associated with CTGF and downstream ERK signaling pathway in rats.

8.
Ying Yong Sheng Tai Xue Bao ; 27(2): 421-8, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-27396113

RESUMO

Based on the phenophase data of Amygdalus communis and homochronous meteorological observation data at agrometeorological experimental station of Shache County during 2008-2013, the change characteristics of phenological period of A. communis and the effects of temperature and sunshine duration on them were analyzed. The results showed that before flowering, positive correlations existed among the first day of phenological phases, and after flowering, the correlations among the first day of phenological phases were mostly less. A significant positive correlation was observed between earlier bud flower swelling and the days of dormant period. and growth period, and a significant negative correlation existed between later bud flower swelling and the days of dormant period and growth period. Before fruit maturation, there was negative correlation between temperature and the interval days of phenological period, and after fruit maturation, the correlations were mostly positive. But the correlation between sunshine duration and the interval days of phenological period was positive before and after fruit maturation. The interval days from fruit maturation to the beginning date of leaf colour change had evident response to the average maximum temperature, and the interval days from the emergence of inflorescence to the ending data of flowering, and from the beginning date of leaf colour change to the ending date of leaf fall, had obvious response to sunshine duration. When the dormant period exceeded 30 days and the average daily temperature met the rang from -3.0 to -7.5 °C, A. communis would get into the flower swelling period after another 17-28 d. There were one-to-one correspondences between flower swelling, the beginning date of flowering, the beginning date of leaf colour change, the ending date of leaf fall, and the first pentad average temperature greater than or equal to 4 °C and pentad average maximum temperature greater than or equal to 12 °C, pentad average temperature greater than or equal to 14 °C and pentad average maximum temperature greater than or equal to 22 °C in spring, the first pentad temperature less than or equal to 10 °C and pentad average maximum temperature less than or equal to 18 °C in autumn the first pentad average temperature less than or equal to 1.9 °C in winter, respectively. By using partial least squares regression analysis, the first day of flowering forecast model of A. communis was established with good prediction.


Assuntos
Flores/fisiologia , Prunus dulcis/fisiologia , Tempo (Meteorologia) , China , Frutas/fisiologia , Folhas de Planta/fisiologia , Estações do Ano , Temperatura Ambiente
9.
Transl Stroke Res ; 7(2): 132-40, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26691164

RESUMO

Notch signaling is critically involved in various biological events. Notch undergoes cleavage by the γ-secretase enzyme to release Notch intracellular domain that will translocate into nucleus to result in expression of target gene. γ-Secretase inhibitors have been developed as potential treatments for neurological degenerative diseases, but its effects against ischemic injury remain relatively uncertain. In the present study, we demonstrated that N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor not only rescued the cerebral hypoperfusion or ischemia neonatal rats from death, reduced apoptosis in penumbra, but also reduced brain infarct size. Furthermore, DAPT elicited some morphologic hallmarks such as neurogenesis and angiogenesis that related to the brain repair and functional recovery after stroke: increased accumulations of newborn cells in the peri-infarct region with a higher fraction of them adopting immature neuronal and glial markers instead of microglial markers on 5 days, enhanced vascular densities in penumbra at 14 days, and evident regulations of the gene profiles associated with neurogenesis in penumbral tissues. The current results suggest that DAPT is a potential neuroprotectants against ischemic injury in immature brain, and future treatment strategies such as clinical trials using γ-secretase inhibitors would be an attractive therapy for perinatal ischemia.


Assuntos
Diaminas/farmacologia , Diaminas/uso terapêutico , Neurogênese/efeitos dos fármacos , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Animais , Animais Recém-Nascidos , Infarto Encefálico/etiologia , Infarto Encefálico/prevenção & controle , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia
10.
PLoS One ; 10(4): e0121255, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25849351

RESUMO

BACKGROUND: Previous studies suggested that dietary fatty acids could affect blood lipids by interacting with genetic variations in fatty acid desaturase 1 (FADS1). However, little is known about their direct effects on coronary artery disease (CAD). The aim of this study was to evaluate whether dietary n-3 long-chain polyunsaturated fatty acids (LCPUFAs)-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could modulate the effect of FADS1 rs174547 polymorphism on CAD. METHODS: FADS1 single-nucleotide polymorphisms rs174547 genotypes were measured in 440 CAD patients and 838 healthy controls. Dietary EPA and DHA intakes were assessed with a validated quantitative frequency food questionnaire. The association between FADS1 rs174547 and CAD was estimated using logistic regression under both dominant and additive genetic models. The interactions between rs174547 polymorphism and LCPUFAs were analyzed by using multiple logistic regression and the "genotype × n-3 LCPUFAs" interaction term was included into the model. RESULTS: We found that the minor T allele of FADS1 rs174547 increased CAD risk (OR = 1.36, 95%CIs 1.03-1.80), and observed significant interaction between rs174547 and dietary EPA intakes on CAD (P-interaction = 0.028). The T-allele was only associated with higher CAD risk among individuals with lower dietary EPA intakes, but not in those with higher EPA intakes. Similarly, significant interaction was also observed between rs174547 and dietary DHA intakes on CAD (P-interaction = 0.020). CONCLUSIONS: Dietary n-3 LCPUFA intakes could modulate the association between FADS1 rs174547 polymorphism and CAD. High dietary n-3 LCPUFA intakes could negate the unfavorable effect of genetic variation in FADS1 on CAD in middle-aged and elderly Chinese population.


Assuntos
Doença da Artéria Coronariana , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Ácidos Graxos Dessaturases/genética , Polimorfismo de Nucleotídeo Único , Idoso , Grupo com Ancestrais do Continente Asiático , China , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacocinética , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
PLoS One ; 10(3): e0120633, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25786118

RESUMO

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1 with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors. METHODS: MCP-1 was measured at baseline in 1411 CAD patients who were 40-85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk. RESULTS: During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89-2.58), 1.00, and 2.11 (95% CI 1.31-3.40) for all-cause mortality, and 1.50 (95% CI 0.80-2.81), 1.00, and 2.21 (95% CI 1.27-3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method. CONCLUSIONS: Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.


Assuntos
Quimiocina CCL2/sangue , Doença da Artéria Coronariana/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Quimiocina CCL2/genética , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
12.
Biomed Res Int ; 2014: 709756, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24982904

RESUMO

The proatherogenic effect of low-density lipoprotein cholesterol (LDL-C) and antiatherogenic effect of high-density lipoprotein cholesterol (HDL-C) have been confirmed in general population. But controversy arises among coronary artery disease (CAD) patients. The goal of this study was to identify the association of different lipid measurements with CAD prognosis. The study cohort included 1916 CAD patients who were 40-85 years of age. Cox proportional hazards regression models were used to estimate the association of baseline 6 lipid factors and 3 ratios with all-cause and cardiovascular (CVD) mortality. During a median follow-up of 3.1 years, 147 deaths were recorded, 113 of which were due to CVD. When lipid factors were categorized, HDL-C showed a U-shape association with all-cause and CVD mortality after adjustment for major CVD risk factors. Serum LDL-C, apoB, LDL/HDL ratio, and apoB/apoA-I ratio were positively, and apoA-I level was inversely associated with the risk of CVD mortality. After further pairwise comparison of lipid-related risk, LDL/HDL ratio and LDL-C had stronger association with all-cause and CVD mortality than other proatherogenic measurements among Chinese CAD patients.


Assuntos
Apolipoproteínas/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Resultado do Tratamento
13.
Heart ; 100(20): 1597-605, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24957531

RESUMO

OBJECTIVE: Epidemiological evidence suggests that different lengths of carbon chains might predict cardiovascular disease (CVD) events differently. However, little data exist concerning the effects of specific types of monounsaturated fatty acids (MUFAs) stratified by chain length. Therefore, the study aimed to explore whether the associations of long-chain MUFAs (LC-MUFAs: 16:1n-7 and 18:1n-9) and very long-chain MUFAs (VLC-MUFAs: 20:1n-9, 22:1n-9 and 24:1n-9) with mortality were different among patients with coronary artery disease (CAD). METHODS: Erythrocyte membrane fatty acids were measured at baseline in 1320 Chinese patients with CAD (56.2% were newly diagnosed) in the Guangdong Coronary Artery Cohort from 2008 to 2011. Cox proportional hazards models were used to estimate the association of each MUFA with risk of all-cause mortality and CVD mortality. RESULTS: During 4229 person-years of follow-up, 104 deaths occurred, 80 of which were due to CVD. There were no statistically significant associations between overall MUFAs and all-cause mortality and CVD mortality. When we stratified MUFAs, comparing with the lowest quartile, multivariable-adjusted HRs in the top quartile of LC-MUFAs were 0.40 (95% CI 0.21 to 0.75) for all-cause mortality and 0.41 (95% CI 0.20 to 0.85) for CVD mortality, whereas multivariable-adjusted HRs in the highest quartile of VLC-MUFAs were 2.72 (95% CI 1.47 to 5.01) for all-cause mortality and 2.58 (95% CI 1.30 to 5.10) for CVD mortality. CONCLUSIONS: This study showed an inverse association between LC-MUFAs and mortality and a positive association between VLC-MUFAs and mortality among patients with CAD. These findings may help explain some of the reported controversial effects of MUFAs.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Ácidos Graxos Monoinsaturados/análise , Ácidos Graxos Monoinsaturados/química , Membrana Eritrocítica/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Sci Rep ; 4: 4240, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24577484

RESUMO

PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.


Assuntos
Fibroblastos/fisiologia , Engenharia Genética/métodos , Recombinases/genética , Transfecção/métodos , Transgenes/genética , Animais , Sítios de Ligação , Bovinos , Células Cultivadas , Técnicas de Transferência de Genes , Marcadores Genéticos/genética , Vetores Genéticos/genética
15.
Mol Cell Probes ; 28(4): 163-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24556376

RESUMO

DNA methylation has been implicated in the regulation of gene expression, genome imprinting, and chromatin remodeling in eukaryotes. In this study, we analyzed possible alterations in levels and patterns of cytosine methylation in male and female spinach plants after treatment with demethylation agent 5-azacytidine (5-azaC) using two methods: (1) direct determination of 5-methylcytidine (5 mC) amounts in genomic DNA by high-performance liquid chromatography (HPLC) separation and quantification of nucleosides and (2) methylation-sensitive inter-simple sequence repeat (MS-ISSR) technique. HPLC analysis revealed that the DNA methylation events in male and female spinach leaves markedly decreased upon 30 µM 5-azaC treatment, and the methylation level gradually decreased with the increase in 5-azaC concentration. To study the altered DNA methylation patterns in spinach after 5-azaC treatment, untreated and 500 µM 5-azaC-treated samples were analyzed by MS-ISSR assay. A total of 385 informative profiles were resolved using 35 ISSR primer sets. MS-ISSR analysis showed various altered methylation patterns between untreated and 5-azaC-treated spinach plants. These alterations were mainly demethylation events, which were largely consistent with the HPLC results. Both HPLC and MS-ISSR analyses showed that the changes in DNA methylation levels and patterns were similar in male and female spinach leaves, which implies that sex was not the main factor influencing DNA methylation levels and patterns in the vegetative organs of spinach. This study could provide a molecular basis of the altered DNA methylation induced by 5-azaC, and lay a foundation for further investigation of the relationship between methylation and sex determination and development in this dioecious plant spinach.


Assuntos
Azacitidina/administração & dosagem , Metilação de DNA/efeitos dos fármacos , Genoma de Planta , Spinacia oleracea/efeitos dos fármacos , Azacitidina/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica de Plantas , Genoma de Planta/efeitos dos fármacos , Nucleosídeos/análise , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Spinacia oleracea/genética
16.
Diabetes Care ; 37(2): 546-54, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24089546

RESUMO

OBJECTIVE: Known diabetes is an independent predictor for mortality in coronary artery disease (CAD) patients; however, whether other glucose abnormalities are associated with death risk in CAD patients is unclear. The goal of this study was to examine the association between different glucose states and the risks of all-cause and cardiovascular disease (CVD) mortality among CAD patients. RESEARCH DESIGN AND METHODS: The study cohort included 1,726 CAD patients who were 40-85 years of age in the Guangdong Coronary Artery Disease Cohort. Cox proportional hazards regression models were used to estimate the association of baseline glucose status with risk of mortality. RESULTS: During a median follow-up of 3.1 years, 129 deaths were recorded, 109 of which were due to CVD. The multivariable-adjusted (age; sex; education; marriage; leisure-time physical activity; smoking; alcohol drinking; BMI; systolic blood pressure; total and HDL cholesterol; glomerular filtration rate; type, severity, duration, and treatment of CAD; history of heart failure; and use of antihypertensive, cholesterol-lowering, and antiplatelet drugs) hazard ratios in normoglycemia, impaired glucose regulation (IGR), newly diagnosed diabetes, and known diabetes were 1.00, 1.58 (95% CI 0.90-2.77), 2.41 (1.42-4.11), and 2.29 (1.36-3.84) for all-cause mortality and 1.00, 1.89 (1.01-3.54), 2.74 (1.50-5.01), and 2.73 (1.52-4.91) for CVD mortality. Assessing fasting plasma glucose only, impaired fasting glucose and newly diagnosed and known diabetes were also associated with increased risks of all-cause and CVD mortality compared with normoglycemia. CONCLUSIONS: CAD patients with IGR, newly diagnosed diabetes, and known diabetes have increased risk of CVD mortality.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Hiperglicemia/complicações , Idoso , Glicemia/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Behav Brain Res ; 260: 74-82, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24304720

RESUMO

Postnatal maternal separation (PMS) has been shown to be associated with an increased vulnerability to psychiatric illnesses in adulthood. However, the underlying neurological mechanisms are not well understood. Here we evaluated its effects on neurogenesis and tonic GABA currents of cortical layer 5 (L5) pyramidal neurons. PMS not only increased cell proliferation in the subventricular zone, cortical layer 1 and hippocampal dentate gyrus in the adult brain, but also promoted the newly generated cells to differentiate into GABAergic neurons, and PMS adult brain maintained higher ratios of GABAergic neurons in the survival of newly generated cells within 5 days immediately post PMS. Additionally, PMS increased the tonic currents at P7-10 and P30-35 in cortical L5 pyramidal cells. Our results suggest that the newly generated GABAergic neurons and the low GABA concentration-activated tonic currents may be involved in the development of psychiatric disorders after PMS.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Neurônios GABAérgicos/fisiologia , Privação Materna , Neurogênese/fisiologia , Células Piramidais/fisiologia , Animais , Ansiedade/fisiopatologia , Encéfalo/citologia , Proliferação de Células , Sobrevivência Celular/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Giro Denteado/citologia , Giro Denteado/crescimento & desenvolvimento , Giro Denteado/fisiologia , Emoções/fisiologia , Feminino , Neurônios GABAérgicos/citologia , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Técnicas In Vitro , Masculino , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Células Piramidais/citologia , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/metabolismo
18.
ScientificWorldJournal ; 2013: 416192, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24222736

RESUMO

BACKGROUND: Cardiometabolic risk factors significantly accelerate the progression of coronary artery disease (CAD); however, whether CAD patients in South China are aware of the prevalence of these risk factors is not clear yet. METHODS: The study consisted of 2312 in-admission CAD patients from 2008 to 2011 in South China. Disease history including hypertension, dyslipidemia, and diabetes was relied on patients' self-reported records. Physical and clinical examinations were tested to assess the real prevalence of the cardiometabolic risk factors. RESULTS: 57.9% of CAD patients had more than 3 cardiometabolic risk factors in terms of the metabolic syndrome. The self-known and real prevalence of hypertension, diabetes, and dyslipidemia were 56.6%, 28.3%, and 25.1% and 91.3%, 40.9%, and 92.0%, respectively. The awareness rates were 64.4%, 66.3%, and 28.5% for hypertension, diabetes, and dyslipidemia. The prevalence of cardiometabolic risk factors was significantly different among gender and among disease status. CONCLUSIONS: Most CAD patients in South China had more than three cardiometabolic risk factors. However, the awareness rate of cardiometabolic diseases was low, especially for dyslipidemia. Strategies of routine physical examination programs are needed for the early detection and treatment of cardiometabolic risk factors in order to prevent CAD progression and prognosis.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Síndrome Metabólica/epidemiologia , Idoso , China/epidemiologia , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco
19.
Food Funct ; 4(10): 1535-42, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24056314

RESUMO

Not only is iron deficiency an abnormal iron status, but iron overload is also harmful for human health. It has been reported that overloaded iron stores are positively associated with increased coronary artery disease (CAD) risk, which is called the "iron-heart hypothesis". Previous studies evaluating the relationships between fatty acids (FAs) and body iron status only focused on participants with iron deficiency. However, whether FA composition is related to overloaded iron remains unclear. Therefore, this study was designed to investigate the relationships between erythrocyte membrane FA (Ery-FA) composition and overloaded body iron status as measured by plasma ferritin levels in Chinese CAD patients. A total of 446 subjects with angiographically identified CAD (mean age 63.1 years, 76.9% males) were recruited in a hospital between 2009 and 2010. Ery-FAs were measured by gas chromatography and the activities of FA desaturases, which are involved in the de novo synthesis of unsaturated FAs, were evaluated by using FA product-to-precursor ratios. Results showed that the average iron status was a bit overloaded in the population (median ferritin levels of 234.1 ng mL(-1) and 40.4% males of overload). Moreover, in males, saturated FAs (SFAs) were positively correlated (22 : 0, r = 0.182, p = 0.001; 24 : 0, r = 0.214, p < 0.001), whereas monounsaturated FAs (MUFAs) and n-6 polyunsaturated FAs (PUFAs) were negatively correlated (18 : 1n-9, r = -0.120, p = 0.028; 18 : 2n-6, r = -0.216, p < 0.001) with plasma ferritin levels. A negative correlation (r < 0, p < 0.05) between stearoyl-CoA desaturase (SCD) activity and ferritin levels was also found in males. However, all the significant associations above were not observed in females. In conclusion, the Ery-FA composition was related to overloaded plasma ferritin levels only in Chinese males with angiographic CAD, which might be linked to the change of SCD activity. The results may contribute to the understanding of the mechanism of the iron-heart hypothesis.


Assuntos
Doença da Artéria Coronariana/sangue , Membrana Eritrocítica/metabolismo , Ácidos Graxos/química , Ferritinas/sangue , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Eritrócitos/química , Eritrócitos/metabolismo , Ácidos Graxos/metabolismo , Feminino , Ferritinas/análise , Humanos , Masculino , Pessoa de Meia-Idade
20.
Mediators Inflamm ; 2013: 726178, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23818744

RESUMO

OBJECTIVES: To evaluate whether serum interleukin-6 (IL-6) is associated with increased risk of mortality in coronary artery disease (CAD) patients. METHODS: We performed a prospective cohort study of 718 CAD patients from the Guangzhou Cardiovascular Disease Cohort (GCDC) study. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 with all-cause and cardiovascular mortality. RESULTS: During the 1663 person-years of followup, the cumulative all-cause mortality and cardiovascular mortality were 6.5% (n = 47) and 3.3% (n = 24), respectively. The mean length of followup was 2.32 ± 0.81 years. In the multivariable analyses, a one-SD increment in log-transformed serum IL-6 was positively associated with an increased risk of all-cause and cardiovascular mortality, with hazard ratios (HR) of 2.93 (95% CI, 2.11-4.08) and 2.04 (95% CI, 1.34-3.68) within the patients combined and 2.98 (95% CI, 2.12-4.18) and 3.10 (95% CI, 1.98-4.85) within males, respectively. Patients in the highest serum IL-6 tertile versus the lowest tertile were at higher risk of all-cause and cardiovascular mortality, with HR of 17.12 (95% CI 3.11-71.76) and 8.68 (95% CI, 1.88-37.51), respectively. CONCLUSIONS: In hospitalized patients with CAD, serum IL-6 is significantly associated with all-cause and cardiovascular mortality.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Interleucina-6/sangue , Animais , Humanos , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
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