RESUMO
BACKGROUND: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease. METHODS: Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins in the plasma, and the coagulation factor prekallikrein (PK; encoded by the KLKB1 gene) was revealed. The correlation between serum PK protein content and lipid levels in young Chinese Han people was then analyzed. To investigate the effects of PK ablation on LDLR and lipid levels in vivo, we genetically deleted Klkb1 in hamsters and heterozygous Ldlr knockout mice and knocked down Klkb1 using adeno-associated virus-mediated shRNA in rats. The additive effect of PK and proprotein convertase subtilisin/kexin 9 inhibition also was evaluated. In addition, we applied the anti-PK neutralizing antibody that blocked the PK and LDLR interaction in mice. Mice lacking both PK and apolipoprotein e (Klkb1-/-Apoe-/-) were generated to assess the role of PK in atherosclerosis. RESULTS: PK directly bound LDLR and induced its lysosomal degradation. The serum PK concentrations positively correlated with LDL cholesterol levels in 198 young Chinese Han adults. Genetic depletion of Klkb1 increased hepatic LDLR and decreased circulating cholesterol in multiple rodent models. Inhibition of proprotein convertase subtilisin/kexin 9 with evolocumab further decreased plasma LDL cholesterol levels in Klkb1-deficient hamsters. The anti-PK neutralizing antibody could similarly lower plasma lipids through upregulating hepatic LDLR. Ablation of Klkb1 slowed the progression of atherosclerosis in mice on Apoe-deficient background. CONCLUSIONS: PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol, and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat atherosclerotic cardiovascular disease.
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Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , LDL-Colesterol/metabolismo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/prevenção & controle , Pré-Calicreína/deficiência , Receptores de LDL/metabolismo , Animais , Aterosclerose/genética , LDL-Colesterol/genética , Lisossomos/genética , Lisossomos/metabolismo , Camundongos , Camundongos Knockout , Placa Aterosclerótica/genética , Pré-Calicreína/metabolismo , Proteólise , Receptores de LDL/genéticaRESUMO
BACKGROUND: HMGCR, SCAP, SREBF1, SREBF2 and TBL2 are well-known genes that are involved in the process of lipid metabolism. However, it is not known whether epigenetic changes of these genes are associated with lipid metabolism. In this study, the methylation levels of the HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes were analyzed between samples from a hyper-low-density lipoprotein cholesterolemia (hyper-LDL) group and a control group to examine the association between the methylation levels of these genes and the risk of hyper-LDL. METHODS: In this study, a case-control approach was used to explore the association between DNA methylation and hyper-LDL. The DNA methylation levels of HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes and 231 CpG sites in the promoter regions of these genes were measured in 98 hyper-LDL participants and 89 participants without hypo-LDL. RESULTS: Compared with participants without hyper-LDL, patients with hyper-LDL TBL2 gene had lower methylation levels (11.93 vs. 12.02, P = 0.004). The methylation haplotypes with significant abundance in the TBL2 gene are tcttttttttt (P = 0.034), ctttttttcct (P = 0.025), ctctttctttt (P = 0.040), ccttttttttt (P = 0.028), and tctttttttttttttt. CONCLUSION: The study demonstrates that participants with hyper-LDL have lower methylation of TBL2. The results suggest that DNA methylation of TBL2 can decrease the risk for hyper-LDL in humans.
Assuntos
Proteínas de Ligação ao GTP/metabolismo , Hipercolesterolemia/genética , Idoso , Estudos de Casos e Controles , LDL-Colesterol/sangue , Ilhas de CpG , Metilação de DNA , Feminino , Proteínas de Ligação ao GTP/genética , Predisposição Genética para Doença , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hipercolesterolemia/sangue , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genéticaRESUMO
BACKGROUND: This study was designed to investigate whether differential DNA methylationin of cholesterol absorption candidate genes can function as a biomarker for patients with coronary heart disease (CHD). METHODS: DNA methylation levels of the candidate genes FLOT1, FLOT2 and SOAT1 were measured in peripheral blood leukocytes (PBLs) from 99 patients diagnosed with CHD and 89 control subjects without CHD. A total of 110 CPG sites around promoter regions of them were examined. RESULTS: Compared with groups without CHD, patients with CHD had lower methylation levels of SOAT1 (P<0.001). When each candidate genes were divided into different target segments, patients with CHD also had lower methylation levels of SOAT1 than patients without (P = 0.005). After adjustment of other confounders, methylation levels of SOAT1 were still associated with CHD (P = 0.001, OR = 0.290, 95% CI: 0.150-0.561). CONCLUSIONS: SOAT1 methylation may be associated with development of CHD. Patients with lower methylation levels in SOAT1 may have increased risks for CHD. Further studies on the specific mechanisms of this relationship are necessary.
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Doença das Coronárias/genética , Metilação de DNA/genética , Esterol O-Aciltransferase/genética , Idoso , Ilhas de CpG/genética , Feminino , Genótipo , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fatores de RiscoRESUMO
Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1ß,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1ß and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.
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Fadiga/prevenção & controle , Ginsenosídeos/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Animais , Regulação da Expressão Gênica , Ontologia Genética , Masculino , Camundongos , Distribuição AleatóriaRESUMO
BACKGROUND: Limited information is available when it comes to the impact of genetic on Calcific Aortic Stenosis (CAS). Apolipoprotein B (apoB) is a key component in lipid metabolism and plays an important role in the dynamic equilibrium of cholesterol. We performed a case-control study to explore the association of apoB genetic polymorphisms with CAS in Chinese subjects, in Xinjiang, China. METHODS: We designed a case-control study including 314 CAS patients and 652 age- and sex-matched control subjects. Using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method, we genotyped two SNPs (rs6725189 and rs693) of apoB gene in all subjects. RESULTS: We found that the rs693 T allele was associated with a significantly elevated CAS risk [TT/CT vs. CC: adjusted odds ratio (AOR) = 1.58, 95% confidence interval (CI) = 1.82-2.10, P = 0.002] and the rs6725189 T allele was also associated with a significantly elevated CAS risk (GT vs. GG: AOR = 1.82, 95% CI = 1.14-2.92, P = 0.013). Furthermore, we also found that the TC levels were significantly higher in rs693 TT/CT genotypes than that in CC genotypes (P < 0.05). CONCLUSIONS: Both rs693 and rs6725189 of the apoB gene are associated with CAS in Chinese subjects, in Xinjiang, China.
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Estenose da Valva Aórtica/genética , Valva Aórtica/patologia , Apolipoproteína B-100/genética , Calcinose/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Lipídeos/sangue , Lipídeos/genética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. METHODS: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. RESULTS: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. CONCLUSIONS: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.
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Nicotinamida N-Metiltransferase/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Estresse Fisiológico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Técnicas de Silenciamento de Genes , Humanos , Nicotinamida N-Metiltransferase/genética , Neoplasias Pancreáticas/metabolismo , Transfecção , Regulação para Cima , Neoplasias PancreáticasRESUMO
A heterometallic cluster [Ag6Au6(ethisterone)12] of an unprecedented topology was synthesized and characterized. A sensitive and specific probe for estrogen receptor α (ERα) has been developed for the first time based on the enhancement of the Ag6Au6 luminescence.
Assuntos
Receptor alfa de Estrogênio/metabolismo , Etisterona/metabolismo , Cobre , Ouro , Humanos , LuminescênciaAssuntos
Dor Abdominal/etiologia , Cistadenoma Mucinoso/patologia , Anormalidades do Sistema Digestório/diagnóstico por imagem , Anormalidades do Sistema Digestório/etiologia , Neoplasias Ovarianas/patologia , Abdome/diagnóstico por imagem , Dor Abdominal/diagnóstico , Idoso , Antígeno Ca-125/metabolismo , Cistadenoma Mucinoso/cirurgia , Anormalidades do Sistema Digestório/patologia , Feminino , Humanos , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Pelve/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: The optimal cutoff of the waist-to-hip ratio (WHR) among Han adults in Xinjiang, which is located in the center of Asia, is unknown. We aimed to examine the relationship between different WHRs and cardiovascular risk factors among Han adults in Xinjiang, and determine the optimal cutoff of the WHR. METHODS: The Cardiovascular Risk Survey was conducted from October 2007 to March 2010. A total of 14618 representative participants were selected using a four-stage stratified sampling method. A total of 5757 Han participants were included in the study. The present statistical analysis was restricted to the 5595 Han subjects who had complete anthropometric data. The sensitivity, specificity, and distance on the receiver operating characteristic (ROC) curve in each WHR level were calculated. The shortest distance in the ROC curves was used to determine the optimal cutoff of the WHR for detecting cardiovascular risk factors. RESULTS: In women, the WHR was positively associated with systolic blood pressure, diastolic blood pressure, and serum concentrations of serum total cholesterol. The prevalence of hypertension and hypertriglyceridemia increased as the WHR increased. The same results were not observed among men. The optimal WHR cutoffs for predicting hypertension, diabetes, dyslipidemia and ≥ two of these risk factors for Han adults in Xinjiang were 0.92, 0.92, 0.91, 0.92 in men and 0.88, 0.89, 0.88, 0.89 in women, respectively. CONCLUSIONS: Higher cutoffs for the WHR are required in the identification of Han adults aged ≥ 35 years with a high risk of cardiovascular diseases in Xinjiang.
Assuntos
Povo Asiático , Doenças Cardiovasculares/etnologia , Obesidade/diagnóstico , Obesidade/etnologia , Razão Cintura-Estatura , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Pressão Sanguínea , China/epidemiologia , Feminino , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/etnologia , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/etnologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Fatores SexuaisRESUMO
To accelerate the discovery of high-affinity aptamers, a magnetically activated continuous deflection (MACD) chip was designed. The MACD chip could achieve dynamic selection in a continuous flow, which meant that the binding and separation were carried out consecutively. Dynamic selection could make selection efficient. Low-affinity sequences could be eluted in time and high-affinity sequences could be enriched via dynamic selection. The stringency of the conditions could be further increased by lowering the target concentration in the dynamic selection. Finally, a C.al3 aptamer with high-affinity and high-specificity for Candida albicans (C. albicans) was obtained through six rounds of selection. Its dissociation constant (Kd) was 7.9 nM. This demonstrated that dynamic selection using a MACD chip was an effective method for high-affinity aptamer selection.
Assuntos
Aptâmeros de Nucleotídeos , Microfluídica , Microfluídica/métodos , Técnica de Seleção de Aptâmeros/métodos , Análise de Sequência com Séries de OligonucleotídeosRESUMO
OBJECTIVE: To survey the clinical epidemiology and correlations between pathology and clinical features of major groups of kidney diseases in a rural area of China. METHODS: From January 1996 to December 2010, histologic diagnosis of renal disease was made on samples collected from 919 patients from a single center in the midland rural area of China. Demographic data were obtained from all patients, and clinical profiles were analyzed in 917 patients. RESULTS: The mean age of the whole group was 33.13 (14.13) years (range 16-72 years). Men accounted for 55.28% (n = 508) and women made up 45.72% (n = 408). Patients aged 16 to 50 years comprised 83.75% of the sample (n = 770). Lupus nephritis was the predominant diagnosis in women; renal diseases were predominant in men. In patients with nephrotic syndrome, mesangial proliferative glomerulonephritis was the most frequent pathologic pattern (39.46%), followed by IgA nephropathy (18.39%), whereas in patients with nephritic syndrome, IgA nephropathy (39.64%) was the most frequent pathologic pattern, followed by mesangial proliferative glomerulonephritis (32.38%). The most common pathologic pattern in patients with secondary glomerulonephritis was Henoch-SchoËnlein purpura nephritis, followed by lupus nephritis. CONCLUSIONS: Mesangial proliferative glomerulonephritis was the most common renal pathologic pattern. Male adolescents were predominant in this group of patients. The most common clinical syndrome was nephrotic syndrome.
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This study is purposed to investigate the effects of praeruptorin A (PA) and praeruptorin C (PC) on UGT1A1 in HepG2 cells through hCAR pathway. PA and PC were incubated with HepG2 cells for 24 h and 48 h, mRNA and protein expressions of UGT1A1 were determined by real-time PCR and Western blotting assays. Additionally, effects of PA and PC on UGT1A1 mRNA and protein expressions were also measured after transient transfection of a specific CAR siRNA for 72 h in HepG2 cells. UGT1A1 mRNA and protein expression levels were significantly increased by PA and PC after incubation for 48 h. Moreover, the mRNA and protein up-regulations of UGT1A1 were attenuated by transient transfection of a specific CAR siRNA, suggesting the induction was mediated by CAR. The results suggest that PA and PC can significantly up-regulate UGT1A1 expression partially via the CAR-mediated pathway.
Assuntos
Cumarínicos/farmacologia , Glucuronosiltransferase/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Apiaceae/química , Receptor Constitutivo de Androstano , Cumarínicos/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glucuronosiltransferase/genética , Células Hep G2 , Humanos , Raízes de Plantas/química , Plantas Medicinais/química , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais , TransfecçãoRESUMO
Objective: The human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China. Methods: A total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies. Results: We found that in the Uygur population studied, for both rs2255280 and rs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CC vs. CA + AA) between T2DM patients and the controls (P < 0.05). After adjusting for confounders, the recessive model (CC vs. CA + AA) of both rs2255280 and rs2855512 remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to -22.755], P = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to -21.013], P = 0.033). The genotypes (AA/CA/CC) and recessive models (CC vs. CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all P < 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (all P > 0.05). Conclusions: The present study suggests that the variation of the Dab2 gene loci rs2255280 and rs2855512 is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Diabetes Mellitus Tipo 2 , Humanos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , População do Leste Asiático , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genéticaRESUMO
BACKGROUND: Long-term outcomes for patients with adult idiopathic nephrotic syndrome correlate closely with steroid responsiveness. The aim of this prospective study was to evaluate the difference in serum proteomes between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) patients and identify potential biomarkers for the prediction of SRNS. METHODS: We performed a gel-based proteomic study of serum obtained from SRNS and SSNS patients and healthy controls at the time of presentation (n = 6 for each group). Proteins from the serum samples were separated using 2-D electrophoresis, digested in-gel and subjected to MALDI-TOF-MS/MS analysis. Further validation was performed utilizing Western blot and ELISA. The sensitivities and specificities of the candidate proteins for predicting SRNS were determined using receiver operating characteristic curves. RESULTS: Thirteen differentially expressed proteins were identified as haptoglobin (Hp) with different isoelectric points and molecular weights. Western blot and ELISA analysis of samples from 146 subjects (healthy controls = 52, SSNS = 54, SRNS = 40) showed a markedly increased level of Hp in the serum, but not urine, of SRNS compared to SSNS patients. The optimal serum cutoff level of Hp was set at ≥1,279 µg/ml using the receiver operating characteristic curve. The sensitivity and specificity for predicting SRNS were 85.0 and 96.3%, respectively. CONCLUSIONS: This study provides a novel overview of the difference in serum proteomes of SSNS and SRNS patients. Serum Hp may be a useful predictive biomarker for steroid therapy efficacy in the treatment of idiopathic nephrotic syndrome.
Assuntos
Haptoglobinas/metabolismo , Síndrome Nefrótica/congênito , Proteômica/métodos , Adolescente , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Colesterol/sangue , Creatinina/sangue , Eletroforese em Gel Bidimensional , Ensaio de Imunoadsorção Enzimática , Feminino , Haptoglobinas/urina , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/sangue , Síndrome Nefrótica/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto JovemRESUMO
The secondary structure of the mushroom polyphenoloxidase treated by the high hydrostatic pressure (HHP) was analyzed by the synchrotron radiation circular dichroism (SRCD) and Fourier transform infrared spectroscopy (FTIR). The alpha-helix content of mushroom PPO was decreased after HHP treatment, which indicated that the secondary structure of PPO was changed. There was a discrepancy of the result of the secondary structure content between untreated or HHP-treated mushroom PPO analyzed by SRCD and FTIR spectra, and this discrepancy may be due to the different determination temperature, the concentration of the PPO solution and the spectra analysis method etc. The fluorescence spectra showed that the fluorescence intensity of the mushroom PPO was decreased after HHP treatment, and a red shift was observed after HHP treatment, which indicated that the tertiary structure of the enzyme molecule has been modified.
Assuntos
Agaricales , Catecol Oxidase , Dicroísmo Circular , Fluorescência , Pressão Hidrostática , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , SíncrotronsRESUMO
Background: Coronary heart disease has become the leading cause of death in developed countries, and dyslipidemia is closely associated with the risk of cardiovascular disease. Dyslipidemia is caused by the abnormal regulation of several genes and signaling pathways, and dyslipidemia is influenced mainly by genetic variation. AMFR, FBXW7, INSIG1, INSIG2, and MBTPS1 genes are associated with lipid metabolism. In a recent GWAS study, the GRINA gene has been reported to be associated with dyslipidemia, but its molecular mechanism has not been thoroughly investigated. The correlation between the DNA methylation of these genes and lipid metabolism has not been studied. This study aimed to examine the relationship between the DNA methylation of these genes and the risk of dyslipidemia by comparing the methylation levels of dyslipidemia and control samples. Methods: A case-control research method was used in this study. The patient's blood samples were collected at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. In the Xinjiang Han population, 100 cases of hyperlipidemia and 80 cases of the control group were selected. The two groups were age and gender-matched. Quantitative methylation analysis of CpG sites in the gene promoter regions of six genes was performed by Solexa high-throughput sequencing. Results: The DNA methylation levels of 23 CpG sites in six genes were shown to be associated with hyperlipidemia, and a total of 20 DNA methylation haplotypes showed statistically significant differences between the two groups. When compared with the control group, the dyslipidemia group had significantly higher levels of methylation in the GRINA gene (2.68 vs 2.36, P = 0.04). Additionally, we also discovered a significant methylation haplotype of GRINA (P = 0.017). Conclusion: The findings of this study reveal that the DNA methylation of GRINA increases the risk for dyslipidemia in humans.
Assuntos
Doença das Coronárias , Dislipidemias , Humanos , Metilação de DNA/genética , Estudos de Casos e Controles , Doença das Coronárias/genética , Haplótipos/genética , Dislipidemias/genéticaRESUMO
The title compound, C(34)H(40)N(2)O(4)·2C(3)H(7)NO, was synthesized by the Mannich condensation of ethane-diamine, formaldehyde and p-cresol. In the crystal, the tetra-phenol mol-ecule is arranged around an inversion center. The mol-ecule and the dimethyl-formamide solvate are linked through an O-Hâ¯O hydrogen bond. An intra-molecular O-Hâ¯N hydrogen bond occurs in the tetra-phenol mol-ecule, which may influence the mol-ecular confomation. Futhermore, C-Hâ¯O and π-π stacking inter-actions [centroid-centroid distance = 3.7081â (14)â Å] stabilize the crystal packing, building a three-dimensional network.
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Dyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.
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Biomarcadores , Variação Genética , Lipídeos/sangue , Grupos Minoritários , Ubiquitina-Proteína Ligases/genética , Adulto , Alelos , China/epidemiologia , China/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Vigilância em Saúde PúblicaRESUMO
IN THE CRYSTAL STRUCTURE OF THE TITLE COMPOUND [SYSTEMATIC NAME: 1-(2-hy-droxy-eth-yl)-2-methyl-5-nitro-1H-imidazol-3-ium perchlorate], C(6)H(10)N(3)O(3) (+)·ClO(4) (-), the cations are linked by inter-molecular N-Hâ¯O hydrogen bonds into zigzag chains along the c axis. The cations and anions are connected by O-Hâ¯O and C-Hâ¯O hydrogen bonds. A weak intra-molecular C-Hâ¯O hydrogen bond is also observed.
RESUMO
An important tributary in the middle stream of the Yellow River, the Yiluo River consists of the Luohe River and Yihe River, which converge at Yanshi City. Mining activities were widely distributed in the upstream of the Yiluo River Basin (YRB), while residential areas concentrated in the downstream were coupled with extensively industrial and agricultural activities. To illustrate the influences of variable anthropogenic activities on the hydro-chemical composition of river water of the YRB, water samples from the main stream and tributaries were collected in the flood season (August) and normal season (December), respectively. The hydrogen and oxygen isotope values coupled with cation and anion content were analyzed. Temporal and spatial variations of hydrogen and oxygen isotopes and ion content were utilized to elucidate the sources and factors controlling the hydro-chemical composition of the river water, and to illustrate the pathways of human effects. The results demonstrated that:â Average hydrogen and oxygen isotope values (δD and δ18O) of Luo River water were -56 and -7.9, and -55 and -8.1 in the flood season and normal season, respectively. Mean δD and δ18O values of Yi River water were -49 and -6.9, and -53 and -7.8 in the flood season and normal season, respectively. These temporal variations indicated that river water was mainly recharged by local atmospheric precipitation. â¡ The dominant water hydro-chemical type was HCO3-SO4-Ca-Mg in the main stream of the YRB, and the ratios of Ca2+ and HCO3- molar equivalent concentrations in the flood season were lower than those in the normal season, while the ratios of SO42- molar equivalent concentrations were higher than those in the normal season, indicating more sulfate dissolved in the river water in the flood season. ⢠Carbonic acid and sulfuric acid simultaneously reacted with carbonate and silicate rocks, and in the Luo River more carbonate rocks were weathered, while in the Yi River more silicate rocks were weathered. ⣠Human effects on river water were mainly concentrated in the upstream where wastewater input was derived from mining activities, while in the downstream pollution of the river was due to industrial wastewater and sewage input. ⤠Spatial variations of sulfate sulfur isotope values were mostly due to differences between anthropogenic activities in the upstream and downstream of the Yiluo River. Negative sulfur isotope values in the upstream river water confirmed dissolved sulfate from sulfide mineral oxidation, which also indirectly verified the rock chemical weathering by sulfuric acid in this area. Positive sulfur isotope values in downstream river water were connected with industrial wastewater and sewage.