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1.
Environ Int ; 138: 105589, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32146266

RESUMO

BACKGROUND: The concentration-response relationship between mortality and long-term exposure to fine particulate matter (PM2.5) has not been fully elucidated, especially at high levels of PM2.5 concentrations. OBJECTIVE: We aimed to evaluate chronic effects of ambient PM2.5 exposure on deaths among Chinese adults in high-exposure settings. METHODS: Participants of the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) project were included from four prospective cohorts among Chinese adults aged ≥18 years old. The overall follow-up rate of the four cohorts was 93.4% until the recent follow-up survey that ended in 2015. The average of satellite-based PM2.5 concentrations during 2000-2015 at 1-km spatial resolution was assigned to each participant according to individual residence addresses. Based on the pooled analysis of individual data from the four cohorts, a Cox proportional hazards model was used to estimate the hazard ratio (HR) and corresponding 95% confidence intervals (95% CIs) for the association of PM2.5 exposure with mortality after multivariate adjustment. RESULTS: A total of 116,821 participants were eligible in the final analysis. During a mean of 7.7 years of follow-up, 6,395 non-accidental deaths and 2,507 cardio-metabolic deaths occurred. The mean of PM2.5 concentration was 64.9 µg/m3 ranging from 31.2 µg/m3 to 97.0 µg/m3. For each 10 µg/m3 increment in PM2.5, the HR was 1.11 (95% CI: 1.08-1.14) for non-accidental mortality and 1.22 (95% CI: 1.16-1.27) for cardio-metabolic mortality. In addition, a weak exponential curve for the concentration-response association between mortality and PM2.5 was observed among Chinese adults. CONCLUSIONS: Our study provided important evidence of the long-term effects of PM2.5 exposure on deaths among Chinese adults. The findings expand our knowledge on concentration-response relationship in high-exposure environments, which is essential to address the urgent challenge of reducing the disease burden attributable to PM2.5 exposure in rapidly industrializing countries such as China.

2.
Atherosclerosis ; 286: 88-96, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31103880

RESUMO

BACKGROUND AND AIMS: The role of circular RNAs (circRNAs) in coronary artery disease (CAD) remains elusive. The aim of the present study was to profile circRNAs expression in CAD patients and assess diagnostics biomarkers for CAD. METHODS: The circRNA profiles of 24 CAD patients and 7 controls were assessed by microarray. The expression levels of candidate circRNAs were further verified by qRT-PCR in large cohorts. Logistic regression analysis and receiver operating characteristic were conducted to assess the diagnostic value. Gain-of-function approach was used to determine the functional significance of validated circRNA in THP-1-derived macrophages. RESULTS: A total of 624 circRNAs and 171 circRNAs were significantly upregulated and downregulated, respectively, in CAD patients relative to controls. Hsa_circ_0001879 and hsa_circ_0004104 were validated to be significantly upregulated in large cohorts. The receiver operating characteristics analysis of hsa_circ_0001879 and hsa_circ_0004104 in CAD patients and controls showed that the area under curve was 0.703 (95% confidence interval: 0.656-0.750; p < 0.001) and 0.700 (95% confidence interval: 0.646-0.755; p < 0.001), respectively. The combination of hsa_circ_0001879 and hsa_circ_0004104, together with CAD risk factors, had the better performance to discriminate CAD patients from healthy controls. Overexpression of hsa_circ_0004104 resulted in dysregulation of atherosclerosis-related genes in THP-1-derived macrophages. CONCLUSIONS: We offered a transcriptome-wide overview of aberrantly expressed circRNAs in CAD patients and identified two novel circRNA biomarkers to diagnose CAD. Upregulation of hsa_circ_0004104 might contribute to the pathogenesis of CAD.

3.
Atherosclerosis ; 285: 31-39, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31003090

RESUMO

BACKGROUND AND AIMS: Long non-coding RNAs (lncRNAs) have proven to be involved in the progression of atherosclerosis and dyslipidemia. In addition, vascular smooth muscle cells (VSMCs) phenotype switching, including VSMCs-derived foam cells formation, plays a key role in the pathogenesis of atherosclerosis. LncRNA ENST00000602558.1, one of the differentially expressed lncRNAs between coronary artery disease (CAD) patients and healthy controls identified by our previous study, was located to TG and HDL susceptibility loci, but its role and underlying mechanism in the pathogenesis of atherosclerosis remain unclear. The present study aims to explore the role and underlying mechanism of ENST00000602558.1 in the regulation of cholesterol efflux from VSMCs. METHODS: ABCG1 mRNA and protein expression in VSMCs was detected using qRT-PCR and Western blot, respectively. ABCG1-mediated cholesterol efflux to HDL from VSMCs was measured by means of NBD-cholesterol fluorescence intensity. The binding of ENST00000602558.1 to p65 and p65 to ABCG1 promoter region was detected by RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively. RESULTS: Overexpression of ENST00000602558.1 downregulated ABCG1 mRNA and protein expression, while knockdown of ENST00000602558.1 upregulated ABCG1 mRNA and protein expression. Consistently, ENST00000602558.1 overexpression decreased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.38% (p < 0.001), and knockdown of ENST00000602558.1 increased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.41% (p = 0.001). In addition to cholesterol efflux, overexpression of ENST00000602558.1 increased lipid accumulation and TC/TG levels, while knockdown of ENST00000602558.1 decreased lipid accumulation and TC/TG levels in VSMCs. Furthermore, we confirmed that ENST00000602558.1 regulated ABCG1 expression and ABCG1-mediated cholesterol efflux from VSMCs through binding to p65. CONCLUSIONS: In conclusion, ENST00000602558.1 played an important role in mediating cholesterol efflux to HDL from VSMCs by regulating ABCG1 expression through binding to p65.

4.
Org Lett ; 21(5): 1278-1282, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768277

RESUMO

A highly enantioselective cobalt-catalyzed reverse prenylation of ß-ketoester with tertiary allylic carbonate to construct vicinal all-carbon quaternary carbon centers has been developed. By using the cobalt/( S, S)Ph-BPE complex generated in situ with zinc reduction, excellent branched to linear selectivity (>20:1) and up to 92% ee have been obtained.

5.
Org Biomol Chem ; 17(4): 789-793, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30627719

RESUMO

A convenient Cs2CO3-promoted cascade benzannulation reaction of allenic ketones with indoles was achieved for the synthesis of functionalized N-arylindole derivatives under transition-metal-free conditions. A series of readily available starting materials can undergo the process successfully. It represents a practical method for the construction of N-arylindole scaffolds with high atom economy.

6.
J Hum Hypertens ; 33(1): 62-68, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30181659

RESUMO

Genetic mechanisms involved in the susceptibility to salt sensitivity have not been completely clarified. This study aimed to comprehensively examine the association between genetic variants in the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG/PRKG) genes and blood pressure (BP) responses to dietary sodium intervention in a Chinese population. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive association of 213 tag single-nucleotide polymorphisms (SNPs) in two PRKG genes (PRKG1 and PRKG2) with salt sensitivity phenotypes. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing. Mean systolic BP response to low-sodium intervention significantly decreased with the number of minor T allele of marker rs10997916 in PRKG1 (P = 2.4 × 10-5). Mean systolic BP responses (95% confidence interval) among those with genotypes CC, CT, and TT were -5.6 (-6.0, -5.3), -3.7 (-4.7, -2.8), and -1.3 (-4.6, 2.0) mmHg, respectively, during the low-sodium intervention. Gene-based analyses demonstrated that PRKG1 was significantly associated with systolic BP response to low-sodium intervention (P = 1.2 × 10-3), whereas PRKG2 was nominally significantly associated with diastolic BP responses to high-sodium intervention (P = 2.6 × 10-2). The current study suggested a significant association of genetic variants in the PRKG genes with variation of BP response to dietary sodium intake in Han Chinese population. These novel findings merit further replication in future.

7.
J Org Chem ; 83(22): 14181-14194, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30358402

RESUMO

A novel palladium-catalyzed cascade carbopalladation/phenol dearomatization reaction has been achieved. The process provides a variety of indolone-, dihydrobenzofuran-, dihydrobenzopyran- and hydroquinoline-containing spirofused molecules bearing two quaternary centers in moderate to good yields. The potential synthetic utility of this method is demonstrated by a gram-scale experiment and further transformations.

8.
Hypertens Res ; 41(12): 1045-1053, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30323262

RESUMO

Blood pressure (BP) responses to dietary sodium intervention vary among individuals. The inwardly rectifying potassium channel (Kir) is a potassium-selective ion channel that allows potassium ions to move more easily into rather than out of the cell. We aimed to investigate the associations of Kir genes with BP responses to dietary sodium intervention. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 participants. BP measurements were obtained at baseline and during each dietary intervention. Both single-marker and gene-based analyses were performed to explore the associations between Kir gene variants and BP responses to dietary sodium interventions. The genetic risk score (GRS) was used to assess the cumulative effect of the variants on the BP response to the sodium interventions. During the low-sodium intervention, markers rs858009, rs2835904, and rs860795 in KCNJ6 were significantly associated with the systolic BP (SBP) response (P = 8.82 × 10-6, 3.32 × 10-6, and 2.39 × 10-4, respectively), whereas rs858009 and rs2835904 were significantly correlated with the mean arterial pressure (MAP) response (P = 1.64 × 10-4 and 2.72 × 10-4, respectively). Marker rs2836023 showed a significant association with the SBP response (P = 5.72 × 10-5) to the high-sodium intervention. The GRS stratified by quartile grouping or as a continuous variable was associated with the BP response to the sodium interventions. Gene-based analyses consistently revealed that KCNJ6 was significantly associated with the BP response to the sodium interventions. These findings suggest that KCNJ6 may contribute to variation of BP responses to dietary sodium interventions. Future studies are warranted to confirm these findings and to identify functional variants for salt sensitivity.


Assuntos
Pressão Sanguínea/genética , Dieta Hipossódica , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hipertensão/dietoterapia , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Adulto , Determinação da Pressão Arterial , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sódio na Dieta
9.
Atherosclerosis ; 275: 359-367, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30015300

RESUMO

BACKGROUND AND AIMS: Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be extensively explored. Thus, the present study aims to study expression patterns, biological functions, and diagnostic value of lncRNAs in CAD. METHODS: Using microarray, we performed the transcriptome-wide lncRNA and mRNAs expression profile of peripheral blood mononuclear cells (PBMCs) of 93 CAD patients and 48 healthy controls. Gene Ontology (GO) and pathway analysis for differentially expressed mRNAs were used to investigate underlying biological associations of differentially expressed lncRNAs, and path-net was created to depict interactions of significant pathways. qRT-PCR was used to validate selected lncRNAs in 412 CAD patients and 295 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether lncRNAs could be used in the diagnosis of CAD patients. Finally, the functional significance of validated lncRNAs was determined in THP-1-derived macrophages. RESULTS: We identified 1210 lncRNAs and 890 mRNAs differentially expressed from the expression profile and validated 7 lncRNAs. Two novel lncRNA biomarkers, ENST00000444488.1 and uc010yfd.1, together with CAD risk factors, had the better performance for discrimination of CAD patients from healthy controls, and ENST00000444488.1 could diagnose acute myocardial infarction (AMI) patients. The knockdown of 20 ENST00000444488.1, uc010yfd.1, ASO3973 and ENST00000602558.1 affected the expression of inflammation-related genes and their nearby genes in THP-1-derived macrophages, respectively. CONCLUSIONS: We offered a transcriptome-wide overview of aberrantly expressed lncRNAs in CAD patients, and identified two novel lncRNA biomarkers for diagnosing CAD. Loss of validated lncRNAs regulated the expression of inflammation-related genes and their nearby genes.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Perfilação da Expressão Gênica/métodos , Leucócitos Mononucleares/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/genética , Transcriptoma , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Redes Reguladoras de Genes , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Fenótipo , Valor Preditivo dos Testes , RNA Longo não Codificante/sangue , Reprodutibilidade dos Testes , Células THP-1
10.
Phys Chem Chem Phys ; 20(17): 11730-11739, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29687125

RESUMO

A combined theoretical and experimental approach has been used to investigate the binding energy of a ruthenium metalloporphyrin ligated with CO, ruthenium tetraphenylporphyrin [RuII TPP], in the RuII oxidation degree. Measurements performed with VUV ionization using the DESIRS beamline at Synchrotron SOLEIL led to adiabatic ionization energies of [RuII TPP] and its complex with CO, [RuII TPP-CO], of 6.48 ± 0.03 eV and 6.60 ± 0.03 eV, respectively, while the ion dissociation threshold of [RuII TPP-CO]+ is measured to be 8.36 ± 0.03 eV using the ground-state neutral complex. These experimental data are used to derive the binding energies of the CO ligand in neutral and cationic complexes (1.88 ± 0.06 eV and 1.76 ± 0.06 eV, respectively) using a Born-Haber cycle. Density functional theory calculations, in very satisfactory agreement with the experimental results, help to get insights into the metal-ligand bond. Notably, the high ligation energies can be rationalized in terms of the ruthenium orbital structure, which is singular compared to that of the iron atom. Thus, beyond indications of a strengthening of the Ru-CO bond due to the decrease in the CO vibrational frequency in the complex as compared to the Fe-CO bond, high-level calculations are essential to accurately describe the metal ligand (CO) bond and show that the Ru-CO bond energy is strongly affected by the splitting of triplet and singlet spin states in uncomplexed [Ru TPP].

11.
Org Lett ; 20(6): 1538-1541, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29509014

RESUMO

A novel palladium-catalyzed domino cyclization/alkylation of terminal alkynes was achieved for the synthesis of alkynyl-functionalized 3,3-disubstituted azaindoline derivatives under air atmosphere conditions. Various types of terminal alkynes, including aromatic alkynes, aliphatic alkynes, and ferrocene acetylene, can undergo the process successfully. The protocol provides a range of alkynyl-functionalized azaindoline scaffolds bearing a quarternary carbon center.

12.
J Hum Hypertens ; 32(4): 287-293, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29463833

RESUMO

Previous studies have indicated that reactive oxygen species produced by NADPH oxidase (Nox) are important risk factors of hypertension. The current study aims to examine the associations of Nox-related genes with longitudinal blood pressure (BP) changes and the risk of incident hypertension in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study. A total of 1,768 participants from 633 families were included in our analysis. Nine BP measurements were obtained in the morning at baseline and during two follow-up visits. The mixed-effect models were used to investigate the associations of 52 tagged single-nucleotide polymorphisms in 11 Nox-related genes with BP changes and incident hypertension. Gene-based analyses were performed by truncated product method (TPM) and Versatile Gene-based Association Study (VEGAS). Over the 7.2 years of follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and 32.1% (512) of participants developed hypertension. SNPs rs12094228, rs16861188 and rs12066019 in NCF2 were significantly associated with longitudinal change in SBP (Pinteraction = 1.1 × 10-3, 2.8 × 10-3 and 1.2 × 10-3, respectively). Gene-based analyses revealed that NCF2 was significantly associated with SBP (PTPM = 1.00 × 10-6, PVEGAS = 1.26 × 10-4) and DBP changes (PTPM = 5.84 × 10-4, PVEGAS = 1.04 × 10-3). These findings suggested that NCF2 may play an important role in BP changes over time in the Han Chinese population.


Assuntos
Pressão Sanguínea/genética , Hipertensão/genética , NADPH Oxidases/genética , Adulto , China/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/enzimologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade
13.
Am J Hypertens ; 31(5): 582-589, 2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29385399

RESUMO

BACKGROUND: To explore how central hemodynamics respond to dietary sodium and potassium interventions, and whether the responses are associated with metabolic traits. METHODS: We conducted a dietary intervention study including a 7-day low-sodium (51.3 mmol sodium/day) intervention, a 7-day high-sodium (307.8 mmol sodium/day) intervention, and a 7-day high-sodium with potassium supplementation (60.0 mmol potassium/day) intervention among 99 northern Chinese subjects aged 18-60 years. Five metabolic traits included abdominal obesity, high triglycerides, low HDL cholesterol, raised blood pressure (BP), and high glucose. Central hemodynamics were measured at baseline and during each intervention. RESULTS: Central systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and augmentation index (AIx@75) significantly decreased during low-sodium intervention, increased during high-sodium intervention, and then decreased during potassium supplementation. We observed potential linear trends toward significance of central SBP and PP responses to low-sodium intervention, and significant linear trends of responses to high-sodium intervention as the number of metabolic traits grows. For example, among participants with 0 or 1, 2 or 3, and 4 or 5 metabolic traits, central SBP responses to high-sodium intervention were 8.8 [95% confidence interval (5.8, 11.8)], 9.3 (7.1, 11.6), and 14.0 (11.6, 16.3) mmHg, respectively (P for trend = 0.009). Significant linear trends of central SBP and DBP responses to potassium supplementation were also observed. CONCLUSIONS: Central BP and AIx@75 were lowered by sodium reduction and potassium supplementation, and elevated by sodium-loading. The responses of central BP were pronounced among individuals with metabolic traits clustering. CLINICAL TRIALS REGISTRATION: Trial Number NCT00721721 (The current study is registered on ClinicalTrials.gov; https://clinicaltrials.gov).


Assuntos
Pressão Sanguínea/fisiologia , Potássio na Dieta/administração & dosagem , Sódio na Dieta/administração & dosagem , Adulto , Dieta Hipossódica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Nat Commun ; 8(1): 1533, 2017 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-29142225

RESUMO

Esophageal squamous cell carcinoma is a major histological type of esophageal cancer, with distinct incidence and survival patterns among races. Although previous studies have characterized somatic mutations in this disease, a rigorous comparison between different patient populations has not been conducted. Here we sequence the samples of 316 Chinese patients, combine them with those from The Cancer Genome Atlas, and perform a comparative analysis between Asian and Caucasian patients. We find that mutated CSMD3 is associated with better prognosis in Asian patients. Applying a robust computational strategy that adjusts for both technical and biological confounding factors, we find that TP53, EP300, and NFE2L2 show higher mutational frequencies in Asian patients. Moreover, NFE2L2 mutations correlate with the allele status of a nearby high-Fst SNP, suggesting their potential interaction. Our study provides insights into the molecular basis underlying the striking racial disparities of this disease, and represents a general computational framework for such a cross-population comparison.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença/genética , Genômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma de Células Escamosas/etnologia , China , Neoplasias Esofágicas/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
15.
Nat Genet ; 49(12): 1722-1730, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29083407

RESUMO

Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.


Assuntos
Doença da Artéria Coronariana/genética , Exoma/genética , Predisposição Genética para Doença/genética , Variação Genética , Metabolismo dos Lipídeos/genética , Grupo com Ancestrais do Continente Asiático/genética , Doença da Artéria Coronariana/etnologia , Europa (Continente) , Grupo com Ancestrais do Continente Europeu/genética , Extremo Oriente , Frequência do Gene , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Lipídeos/análise
16.
J Phys Chem A ; 121(37): 6942-6948, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28841318

RESUMO

The electronic and spectral properties of p-tert-butylthiacalix[4]arene (TCA) and its Cu2+ complexes (CuTCA and Cu2TCA) were characterized by time-dependent density functional theory (TD-DFT). Geometries of TCA, CuTCA, and Cu2TCA were optimized at the CAM-B3LYP/6-31+G(d,p) level of theory in water using the conductor-like polarizable continuum model. The absorption spectra of TCA, CuTCA, and Cu2TCA were demonstrated by TD-DFT method. The quenching mechanism of perylene as the fluorophore of a chemosensor based on thiacalix[4]arene was discussed. The addition of Cu2+ to TCA introduced a series of low-lying excited states involving copper d orbitals. The overlap between absorption of TCA complexes and emission of perylene indicated that the quenching of perylene fluorescence is due to fluorescence resonance energy transfer.

17.
Org Biomol Chem ; 15(35): 7282-7285, 2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28850141

RESUMO

An efficient and concise CuCl-catalyzed C2-alkenylation reaction of benzoxazoles with allyl halides has been established. The distinctive features of this protocol include the use of an inexpensive copper salt as a catalyst, simple and readily available starting materials, and ligand-free conditions. An important application of this method to the synthesis of 1,3-diene substituted benzoxazoles has also been achieved.

18.
Am J Hypertens ; 30(4): 427-434, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28200110

RESUMO

BACKGROUND: The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population. METHODS: We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses. RESULTS: Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4). CONCLUSIONS: These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Pressão Sanguínea/genética , Dieta Hipossódica/métodos , Hipertensão/dietoterapia , Proteínas Adaptadoras de Transporte Vesicular/genética , Adulto , China , Feminino , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 1/genética , NADPH Oxidase 2/genética , NADPH Oxidase 4/genética , NADPH Oxidase 5/genética , NADPH Oxidases/genética , Polimorfismo de Nucleotídeo Único , Cloreto de Sódio na Dieta , Resultado do Tratamento , Proteínas rac de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/genética
19.
Am J Hypertens ; 30(1): 95-101, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27664953

RESUMO

BACKGROUND: Single-marker and novel gene-based methods were employed to examine the associations of the serum/glucocorticoid regulated kinases (SGK) gene family with longitudinal blood pressure (BP) changes and hypertension incidence in a family-based cohort study. METHODS: Totally, 1,768 Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current analyses. Nine BP measures were obtained at each of 3 visits during the GenSalt follow-up study. Mixed-model and Gene-based analyses were used to examine the associations of the SGK gene family with longitudinal BP phenotypes. Bonferroni correction was applied to account for multiple testing. RESULTS: After an average 7.2-year follow-up, 32.2% (513) of participants free of hypertension at baseline developed hypertension. Four novel SNPs in the SGK1 gene were predictive of the longitudinal BP phenotypes. The major alleles of SGK1 rs1763498 and rs114414980 conferred 2.9- and 2.5-fold increased risks of hypertension development, respectively (P = 1.0×10-4 and 6.0×10-4, respectively). In addition, the major allele of SGK1 rs229133 was significantly associated with 0.4mm Hg larger annual increases in systolic BP (P = 4.2×10-4), while the major allele of rs6924468 was significantly associated with 0.2mm Hg smaller annual increases in diastolic BP (P = 4.2×10-4). Gene-based analyses revealed an association of the SGK1 gene with risk of hypertension development (P = 7.4×10-3). No evidence for the SGK2 and SGK3 genes was found. CONCLUSIONS: The findings of the current study suggest that the SGK1 gene may play a role in long-term BP regulation and hypertension incidence.


Assuntos
Pressão Sanguínea/genética , Hipertensão/genética , Proteínas Imediatamente Precoces/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Família Multigênica
20.
J Org Chem ; 81(23): 11987-11993, 2016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27813413

RESUMO

An efficient and concise Cu(OTf)2-catalyzed Friedel-Crafts alkylation/annulation cascade reaction of substituted indoles with 1,2-dicarbonyl-3-enes has been established. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of diverse 9H-pyrrolo[1,2-a]indoles bearing a carbonyl group.

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