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1.
Regen Med ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829095

RESUMO

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

2.
Arterioscler Thromb Vasc Biol ; 39(12): 2468-2479, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31597442

RESUMO

OBJECTIVE: A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride. CONCLUSIONS: Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.

3.
PLoS One ; 12(9): e0184256, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28961259

RESUMO

OBJECTIVE: Our previous study has found that circulating microRNA (miRNA, or miR) -122, -140-3p, -720, -2861, and -3149 are significantly elevated during early stage of acute coronary syndrome (ACS). This study was conducted to determine the origin of these elevated plasma miRNAs in ACS. METHODS: qRT-PCR was performed to detect the expression profiles of these 5 miRNAs in liver, spleen, lung, kidney, brain, skeletal muscles, and heart. To determine their origins, these miRNAs were detected in myocardium of acute myocardial infarction (AMI), and as well in platelets and peripheral blood mononuclear cells (PBMCs, including monocytes, circulating endothelial cells (CECs) and lymphocytes) of the AMI pigs and ACS patients. RESULTS: MiR-122 was specifically expressed in liver, and miR-140-3p, -720, -2861, and -3149 were highly expressed in heart. Compared with the sham pigs, miR-122 was highly expressed in the border zone of the ischemic myocardium in the AMI pigs without ventricular fibrillation (P < 0.01), miR-122 and -720 were decreased in platelets of the AMI pigs, and miR-122, -140-3p, -720, -2861, and -3149 were increased in PBMCs of the AMI pigs (all P < 0.05). Compared with the non-ACS patients, platelets miR-720 was decreased and PBMCs miR-122, -140-3p, -720, -2861, and -3149 were increased in the ACS patients (all P < 0.01). Furthermore, PBMCs miR-122, -720, and -3149 were increased in the AMI patients compared with the unstable angina (UA) patients (all P < 0.05). Further origin identification revealed that the expression levels of miR-122 in CECs and lymphocytes, miR-140-3p and -2861 in monocytes and CECs, miR-720 in monocytes, and miR-3149 in CECs were greatly up-regulated in the ACS patients compared with the non-ACS patients, and were higher as well in the AMI patients than that in the UA patients except for the miR-122 in CECs (all P < 0.05). CONCLUSION: The elevated plasma miR-122, -140-3p, -720, -2861, and -3149 in the ACS patients were mainly originated from CECs and monocytes.


Assuntos
Síndrome Coronariana Aguda/sangue , Leucócitos Mononucleares/metabolismo , MicroRNAs/sangue , Síndrome Coronariana Aguda/genética , Animais , Perfilação da Expressão Gênica , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Porco Miniatura , Distribuição Tecidual
4.
Chronic Dis Transl Med ; 2(2): 102-109, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29063030

RESUMO

OBJECTIVE: This study aims to determine the distribution of observed atherosclerotic cardiovascular disease (ASCVD) incidence in contemporary cohorts in China, and to identify cut-off points for ASCVD risk classification based on traditional criteria and new equations developed by Prediction for ASCVD Risk in China (China-PAR). METHODS: The study populations included cohorts in the China-PAR project, with 34,757 participants eligible for the current analysis. Traditional risk stratification was assessed by using Chinese guidelines on prevention of CVD and hypertension, and 5 risk groups were classified based on these guidelines after slight modification for available risk factors. Kaplan-Meier analysis was conducted to obtain the cumulative incidence of observed ASCVD events for all subjects and sub-groups. The predicted 10-year ASCVD risk was obtained using the China-PAR equations. RESULTS: A total of 1922 ASCVD events were identified during an average follow-up of 14.1 years. According to the group classification based on traditional risk stratification, the observed 10-year risks for ASCVD were 4.61% (95% confidence interval [CI]: 4.11-5.10%) in the moderate-risk group and 8.74% (95% CI: 7.82-9.66%) in the high-risk group. Based on the China-PAR equations for risk assessment of ASCVD, those with predicted risks of <5%, 5-10%, and ≥10% could be classified into categories of low-, moderate-, and high-risk for ASCVD, respectively. CONCLUSION: The findings enable development of a simple method for classification of individuals into low-, moderate-, and high-risk groups, based on the China-PAR equations. The method will be useful for self-management and prevention of ASCVD in Chinese adults.

5.
Chin Med J (Engl) ; 124(22): 3702-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22340227

RESUMO

BACKGROUND: Increased blood pressure and elevated total cholesterol (TC) level are the two most important modifiable risk factors of cardiovascular disease (CVD) in the world. Hypertension and hypercholesterolemia co-exist more often than would be expected and whether there is a synergistic impact on fatal CVD between elevated TC and hypertension need to be further examined in Chinese population. METHODS: We conducted a cohort study which recruited 5092 Chinese male steelworkers aged 18 - 74 years in 1974 - 1980 and followed up for an average of 20.84 years. Totally 302 fatal CVD events were documented by the year of 2001. Cox proportional hazards regression models were undertaken to adjust for baseline variables with fatal CVD events as the outcome variable. Additive interaction model was used to evaluate the interaction between elevated TC and hypertension. RESULTS: Hypercholesterolemia and hypertension were significantly associated with an increased hazard ratio (HR) of fatal CVD (1.67 (95%CI 1.18 - 2.38) and 2.91 (95%CI 2.23 - 3.80) respectively. Compared to participants with normotension and TC < 240 mg/dl, the HRs were 1.11 (95%CI 0.56 - 2.21), 2.74 (95%CI 2.07 - 3.64) for hypercholesterolemia and hypertension respectively, and 5.51 (95%CI 3.58 - 8.46) for participants with both risk factors. There was an additive interaction with a 2.65 (95%CI 0.45 - 4.85) relative excess risk (RERI) between hypercholesterolemia and hypertension on CVD. CONCLUSION: We found that the risk of fatal CVD was significantly associated with an additive interaction due to hypercholesterolemia and hypertension besides a conventional main effect derived from either of them, which highlights that the prevention and treatment of both risk factors might improve the individual risk profile thus reduce the CVD mortality.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Colesterol/sangue , Hipercolesterolemia/complicações , Hipertensão/complicações , Aço , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Humanos , Hipercolesterolemia/sangue , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Biomed Environ Sci ; 23(1): 37-41, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20486434

RESUMO

OBJECTIVE: Total cholesterol (TC) is an important risk factor for myocardial infarction (MI), but the effect of TC on MI in Chinese male hypertension population has not been well documented. We conducted a prospective cohort study to determine the incidence and relative risk for MI across a wide range of TC levels in Chinese male hypertension population. METHODS: A cohort of 5298 male employees aged 18-74 years recruited from Capital Steel and Iron Company in Beijing of China in 1974-1980 was followed up for an average of 20.84 years. A total of 122 incident MI cases were identified during the period of follow-up. RESULTS: The incidence of MI among participants with elevated TC and those with desirable TC in male non-hypertension population was 137.20 and 63.81 per 100,000 person-years, respectively; and the corresponding incidence in male hypertension population was 279.80 and 130.96 per 100,000 person-years, respectively. After adjustment for important covariables, 10.38%, 16.71%, and 23.80% of MI cases were attributable to hypertension, elevated TC, and hypertension plus elevated TC, respectively. In male hypertension population, the multivariate adjusted hazard ratios of MI were 1.21, 2.39, 3.38, and 3.95 for participants with TC level of 5.17-5.68, 5.69-6.20, 6.21-6.71, and > or = 6.72 mmol/L, compared with those with TC < 5.17 mmol/L. The corresponding population attributable risks were 2.92%, 9.20%, 8.87%, and 9.84%, respectively. CONCLUSION: Elevated TC is an important independent risk factor of MI both in male non-hypertension and hypertension populations. There is a linear association between TC level and MI incidence in Chinese male hypertension population.


Assuntos
Colesterol/sangue , Hipertensão/sangue , Hipertensão/complicações , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Adolescente , Adulto , Idoso , China/epidemiologia , Humanos , Hipertensão/epidemiologia , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto Jovem
7.
Yi Chuan ; 32(2): 97-104, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20176552

RESUMO

As a new effective strategy for researching complex diseases, genome-wide association study (GWAS) has being developed rapidly in recent years worldwide. The world genomic study has been taken into a new stage, since a series of disease related genes or variants have been identified by GWAS strategy. Coronary heart disease (CHD) is a complex disease that is caused by both environmental and genetic factors, and has become one of the leading causes of death and disability worldwide. With the application of GWAS strategy, researchers from all over the world have identified many susceptibility loci or regions of CHD that were unable to be identified by candidate gene case-control study. The present paper reviewed the important progresses worldwide attained in GWAS of CHD in recent years. Then it is also expounded the challenges we are facing nowadays in GWAS as well as the future study direction. The information outlined in this paper provides us a valuable guidance upon further exploration into genetic mechanism of CHD.


Assuntos
Doença das Coronárias/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Genética Médica , Humanos , Polimorfismo de Nucleotídeo Único
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(10): 870-4, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20137533

RESUMO

OBJECTIVE: In individuals without cardiovascular disease, elevated body mass index (BMI) is associated with an increased risk of death. However, in patients with certain chronic diseases, including heart failure, low BMI has been associated with increased mortality. We investigated the association between BMI and prognosis in patients with systolic HF. METHOD: Follow-up was made on 540 patients (mean age 58.53 years, 84.2% men) with systolic HF (LVEF < or = 45%) and association between BMI and adverse cardiac events was analyzed. RESULTS: During a median follow-up of 24 months, 92 patients died including 87 cases of cardiac death and 92 patients were rehospitalized. Compared with patients with BMI higher than 28.0 kg/m(2), patients in lower BMI categories (BMI < or = 18.5 kg/m(2) and > or = 18.5 kg/m(2) < 24.0 kg/m(2)) had a graded increase in the all cause death rate [5.44 (1.78 - 16.66), 4.30 (1.71 - 10.82)], cardiac death rate [OR(95%CI): 5.42 (1.77 - 16.59), 4.00 (1.59 - 10.10)], HF death rate [8.94 (2.37 - 33.74), 4.97 (1.52 - 16.20)] and MACE rate [2.10 (1.09 - 4.07), 1.79 (1.14 - 2.82)]. After adjustment for age, gender, LVEF and NYHA grade using cox regression analysis, BMI categories still significantly associated with all cause death rate (OR = 0.77, P < 0.05), cardiac death rate (OR = 0.78, P < 0.05) and HF death rate (OR = 0.79, P < 0.05). CONCLUSION: In patients with systolic heart failure, lower BMI was an independent predictor of increased all cause death rate, cardiac death rate and HF death rate.


Assuntos
Índice de Massa Corporal , Insuficiência Cardíaca Sistólica/fisiopatologia , Adulto , Idoso , Causas de Morte , Seguimentos , Insuficiência Cardíaca Sistólica/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 29(8): 757-62, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19103107

RESUMO

OBJECTIVE: To study the current situation of ten types of junk food consumption (assessed by World Health Organization) among children and adolescent as well as the contributing factors in Haidian District, Beijing so as to provide evidence for developing preventive and control measures and interventions. METHODS: A questionnaire survey was conducted to investigate the consumption of ten types of junk food practices in 1019 children and adolescent aged 8-16 years in Beijing Haidian District. RESULTS: One month prior to the study, 97.50% of the children and adolescent had eaten at least one type of junk food and 15.88% of them had eaten all types of them. Rates on having eaten deep fried food, pickled food, processed meat products, biscuits, coke or alike drinks, convenience/fast food, canned food, dried or preserved fruit, cold and sweet food, barbecue food etc. appeared to be 70.43%, 60.14%, 79.72%, 64.24%, 69.63%, 78.72%, 42.16%, 51.95%, 68.13%, 60.14% respectively. The rate on eaten more than once a day of these ten types were 26.95%, 36.88%, 34.84%, 32.97%, 27.40%, 28.18%, 37.91%, 26.15%, 37.39%, 22.10% respectively. The rates for "do not like" and "dislike" these ten types junk food were 10.96%, 27.42%, 7.08%, 12.11%, 6.56%, 6.59%, 17.80%, 13.59%, 3.42%, 5.19% respectively. Most of the children and adolescent ate junk food mainly during breakfast at home. Most of the surveyed children and adolescent did not have correct idea on nutrition of junk food. They received the information of junk food mainly from sources as advertisement on TV (67.95%), mother (9.02%), newspaper or magazines (6.71%). Many factors, such as individual factors (including physiological and psychological situations), social factors, family factors and the characteristics of food contributed to the eating junk food practices of children and adolescent. CONCLUSION: Eating junk food is a popular event among children and adolescent in Beijing Haidian District. Education strategies on nutrition should be developed and launched in order to help children develop their own healthy eating behaviors.


Assuntos
Comportamento Alimentar/psicologia , Adolescente , Criança , China , Inquéritos sobre Dietas , Humanos , Amostragem , Inquéritos e Questionários
10.
Zhonghua Xin Xue Guan Bing Za Zhi ; 36(6): 501-5, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19100060

RESUMO

OBJECTIVE: To investigate the association between the severity of coronary arteries in patients with coronary artery disease and the single nucleotide polymorphisms of MMP-3 gene. METHODS: One thousand and three hundred seventy-one patients with coronary artery disease (CAD) diagnosed by coronary angiography and six hundred and ninety-five healthy controls without CAD were enrolled in this study. The SNPs of -1612 5A/6A, -376C/G, Glu45Lys of MMP-3 were genotyped by restriction fragment length polymorphism analysis (RFLP) in all subjects. Univariate analysis was applied to measure the association of the single nucleotide polymorphisms with the severity of coronary arteries. RESULTS: The minor allele frequency of -1612 5A/6A was 0.189, 0.185, 0.183 and 0.152 (P < 0.05 vs. non-CAD control and single stenosis), the minor allele frequency of -376C/G was 0.311, 0.329, 0.326 and 0.325, and the minor allele frequency of Glu45Lys was 0.367, 0.423, 0.417 and 0.405 in non-CAD control, CAD patients with single, two and three vessels stenosis, respectively. 5A allele frequency is significant lower in the group with three vessels stenosis than in non-CAD control and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04). The 5A/5A and 5A/6A genotypes frequency is significant lower in the group with three vessels stenosis than in the non-CAD group and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04). CONCLUSIONS: The single nucleotide polymorphism of -1612 5A/6A of MMP-3 gene may be associated with the severity of coronary atherosclerosis in the Chinese Han patients with coronary artery disease, and the 5A allele might therefore, play a protective role on the progression of coronary atherosclerosis.


Assuntos
Doença da Artéria Coronariana/genética , Metaloproteinase 3 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , China , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
11.
Chin Med J (Engl) ; 121(16): 1549-53, 2008 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-18982866

RESUMO

BACKGROUND: Although the role of fibrinogen as a predictor of acute myocardial infarction (MI) has been well-established, the association of genetic polymorphisms in the fibrinogen gene with MI is still controversial. This study was conducted to elucidate the association between the genetic polymorphisms of the fibrinogen beta-chain (FGB) gene and MI in Chinese Han population. METHODS: The occurrence of 3 common polymorphisms (i.e., -455G/A, R448K and 8558C/G) in a case-control study including 508 patients with MI and 503 healthy controls was investigated. Results Analyses of single polymorphisms showed that individuals carrying the rare alleles for the 3 polymorphisms were significantly associated with a decreased risk of MI. Logistic regression analysis indicated that R448K remained independently associated with MI after adjustment for environmental risk factors (adjusted odds ratio(OR) = 0.71 for KK/RK versus RR, P = 0.023). The three polymorphisms were found to be in strong linkage disequilibrium. Haplotype analyses showed that the A-K-G haplotype (-455A, 448K, 8558G) was associated with a protective effect against MI. Compared with the common haplotype G-R-C, the adjusted OR for A-K-G was 0.68 (95% CI, 0.51-0.90; P = 0.006). CONCLUSION: These data indicate that individuals carrying the FGB 448K allele may be protective against having MI in this population.


Assuntos
Fibrinogênio/genética , Infarto do Miocárdio/genética , Adulto , Idoso , China/etnologia , Feminino , Variação Genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Polimorfismo de Nucleotídeo Único
12.
Chin Med J (Engl) ; 121(8): 716-20, 2008 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-18701025

RESUMO

BACKGROUND: Hydrogen sulfide (H(2)S) plays an important role in the smooth muscle cell relaxation and thereby participates in the development of hypertension. Cystathionine gamma-lyase is the key enzyme in the endogenous production of H(2)S. Up to now, the reports on the relationship between the polymorphisms of cystathionine gamma-lyase gene (CTH) and essential hypertension (EH) are limited. This study was designed to assess their underlying relationship. METHODS: A total of 503 hypertensive patients and 490 age-, gender- and area-matched normotensive controls were enrolled in this study. Based on the FASTSNP, a web server to identify putative functional single nucleotide polymorphisms (SNPs) of genes, we selected two SNPs, rs482843 and rs1021737, in the CTH gene for genotyping. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method (PCR-RFLP). The frequencies of the alleles and genotypes between cases and controls were compared by the chi-square test. The program Haplo. stats was used to investigate the relationship between the haplotypes and EH. RESULTS: These two SNPs were in Hardy-Weinberg Equilibrium in both cases and controls. The genotype distribution and allele frequencies of them did not significantly differ between cases and controls (all P > 0.05). In the stepwise logistic regression analysis we failed to observe their association with hypertension. In addition, none of the four estimated haplotypes or diplotypes significantly increased or decreased the risk of hypertension before or after adjustment for several known risk factors. CONCLUSIONS: The present study suggests that the SNPs rs482843 and rs1021737 of the CTH gene were not associated with essential hypertension in the Northern Chinese Han population. However, replications in other populations and further functional studies are still necessary to clarify the role of the CTH gene in the pathogenesis of EH.


Assuntos
Cistationina gama-Liase/genética , Hipertensão/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
13.
Zhong Xi Yi Jie He Xue Bao ; 6(6): 595-9, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-18559237

RESUMO

OBJECTIVE: To observe the effects of Feixian Formula, a compound traditional Chinese herbal medicine for treating pulmonary fibrosis, on bleomycin-induced pulmonary fibrosis in rats, and its influence on serum transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF). METHODS: Seventy-two male Wistar rats were infused with bleomycin (1 mg/kg) through tracheal intubation to induce pulmonary fibrosis, and they were randomly divided into untreated group (n=24), prednisone-treated group (n=24) and Feixian Formula-treated group (n=24). Fifteen male Wistar rats of the sham-operated group were infused with equivalent normal saline. Twenty-four hours after operation, prednisone (5 mg/kg) and Feixian Formula (1.25 g/kg) were given to the prednisone-treated group and Feixian Formula-treated group respectively by intragastric administration once a day. Equivalent saline was administered to rats of the untreated group and sham-operated group. On the 14th, 28th and 45th day, 5 rats in the sham-operated group and 8 rats in each of the other three groups were dissected to observe pathologic changes of the lung tissues, and the levels of serum TGF-beta1 and PDGF were determined by enzyme-linked immunosorbent assay. RESULTS: At the 45th day, the degree of pulmonary interstitial fibrosis was lesser in rats of the Feixian Formula-treated group as compared with those of the untreated group and prednisone-treated group. The levels of serum TGF-beta1 and PDGF were increased, and were significantly higher than those of the sham-operated group, especially on the 45th day (P<0.05). Changes of TGF-beta1 level in the prednisone-treated group and the Feixian Formula-treated group were similar to untreated group (P>0.05), and there was no significant difference between the prednisone-treated group and the Feixian Formula-treated group (P>0.05). PDGF in the Feixian Formula-treated group reached the highest level on the 14th day, significantly higher than those of the other three groups (P<0.01). Then it decreased, and was close to that of the sham-operated group on the 45th day (P=0.792). The levels of PDGF in untreated group and prednisone-treated group were increased depending on time, and were obviously higher than that of the sham-operated group on the 45th day (P<0.01). CONCLUSION: Feixian Formula can relieve bleomycin-induced pulmonary fibrosis in rats, and the mechanism of its action may be related to down-regulating serum PDGF.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fator de Crescimento Transformador beta1/sangue , Animais , Bleomicina , Masculino , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar
14.
Zhong Xi Yi Jie He Xue Bao ; 6(1): 60-7, 2008 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-18184548

RESUMO

OBJECTIVE: To study the approach for developing a rat model of pulmonary fibrosis induced by bleomycin (BLM). METHOD: Different doses (7, 6, 5, 3.4, 2, 1 mg/kg) of bleomycin A5-saline were infused into the rats' lung in bleomycin-treated group through tracheal intubation, and rats in sham-operated group were infused with same volume of saline. The living state and lung pathology of the rats were observed. The author deeply studied the condition of the rats in 1 mg/kg bleomycin-treated group, and the changes of body weight and lung pathology were observed. Lung quotient, the content of transforming growth factor beta1(TGF-beta1) and platelet-derived growth factor (PDGF) in serum were measured on the 14th, 28th and 45th day of the experiment. RESULTS: The study demonstrated that infusing large doses of bleomycin A5 quickly through tracheal intubation had a high mortality, and infusing 1 mg/kg quickly could successfully develop an animal model of pulmonary fibrosis. Compared with the sham-operated group, fibrosis was appeared obviously in the rats' lung in 1 mg/kg bleomycin A5-treated group after 14 days of experiment, diffuse fibrosis was appeared after 28 days of experiment, and the fibrosis became more severe after 45 days of experiment. The body weight of the rats in bleomycin-treated group was declined after 3, 7 and 14 days of experiment as compared with the sham-operated group (P<0.01). Twenty-one days after the experiment, the body weight was declined too, but there was no significant difference between the bleomycin-treated group and the sham-operated group (P>0.05). Lung quotient was increased 14, 28 and 45 days after the experiment (P<0.01), the level of serum TGF-beta1 began to increase since 28 days after the experiment (P<0.05, P<0.01), and the level of serum PDGF also increased gradually 45 days after the experiment (P<0.05). And the mortality rate of 1 mg/kg bleomycin A5-treated group was lower than those of the other doses of bleomycin A5-treated groups. CONCLUSION: A rat model of pulmonary fibrosis can be duplicated successfully by infusing 1 mg/kg bleomycin A5 quickly through tracheal intubation.


Assuntos
Bleomicina , Modelos Animais de Doenças , Fibrose Pulmonar/induzido quimicamente , Animais , Bleomicina/administração & dosagem , Intubação Intratraqueal , Pulmão/patologia , Masculino , Ratos , Ratos Wistar
15.
Chin Med J (Engl) ; 120(24): 2218-23, 2007 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-18167206

RESUMO

BACKGROUND: Calpain-10 (CAPN10) has been identified as a susceptibility gene in type 2 diabetes mellitus (T2DM) and insulin resistance. The present study aimed to identify the effects of genetic variations in the CAPN10 gene on the development of type 2 diabetes and hypertension in northern Han Chinese population. METHODS: We performed a case-control study and genotyped single nucleotide polymorphism (SNP)-44, -43, -19 and -63 of CAPN10 gene in 1046 subjects from the northern China, including 493 patients with T2DM and hypertension and 553 age- and gender-matched normal healthy controls. RESULTS: Univariate analysis showed that the four polymorphisms were not independently associated with T2DM and hypertension. However, the frequency distributions of SNP-44 allele C (allele 2) (17.89% vs 9.80%, P = 0.0016) and genotype CC (22) (4.21% vs 1.01%, P = 0.0059) in obese patients (body mass index > or = 30 kg/m2) were different from those in non-obese patients. Logistic regression analyses revealed that carriers of the 1112/1221 diplotype had a significantly lower odds ratio for diabetes and hypertension (OR = 0.399, 95% CI, 0.196 - 0.814, P = 0.0115). The 1112/1121 diplotype associated with significantly increased risk of type 2 diabetes in Mexican-American was not associated with the increased risk in Chinese. CONCLUSION: These results suggested that CAPN10 gene variations might play roles in the risk of diabetes and hypertension in northern Han Chinese population.


Assuntos
Calpaína/genética , Diabetes Mellitus Tipo 2/genética , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , China/etnologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Hipertensão/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Locos de Características Quantitativas
17.
Yi Chuan Xue Bao ; 31(3): 236-40, 2004 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-15195560

RESUMO

At present, a point that cell biologists and medicine scientists focus their close attention on is the mechanisms of cell proliferation and carceration. Breast cancer, one of the frequently occurring cancers, is often been studied intensively. Centromere constitutive molecules, related to various regulatory factors, play an important role in cell proliferation check point regulation. Cell cycle engine molecules, oncogenes, anti-oncogenes and other molecules conform a cell proliferation network. The basic courses of all tumors are associated to this network. However, there are still many problems to be resolved in the analyses of cancer related genes which cause tumors and tumor gene markers. In the current study, using Northern blot, 31 samples of breast cancer tissues and their normal (not cancerous) tissues a little far away from them in the same individuals showed that, in the majority of the tests (87.1%), the mRNA of centromere protein CenpB over expressed in breast cancer tissues, and moreover, tissue in situ hybridization also revealed that all of the CenpB-over-expressed cancer tissues, having identified with Northern blot, over expressed CenpB mRNA. Analyzing the same samples by means of Western blot, the result was highly consistent to the studies in the RNA level. A conclusion was drawn that the over expression of CenpB gene probably relates to malignant cell proliferation in breast gland. It has been testified by researchers that a few of CenpB homogenous proteins are co-operative, the loss of their genes resulting in chromosomes' separating abnormally and cell growth's slowing down. Having transfected HeLa (Tet-Off) cells with anti-sense Cenp in a previous experiment, we ever got a result that cellular duplicating time was prolonged for another 32.8 h, and together with the inhibition of centromere assembly, the mitotic index dropped sharply. In another research, we drew a conclusion that CenpG may be related to cancer, and its differential expressing probably relates to malignant cell proliferation. Combined with these researches, the results obtained from the current study are beneficial to further recognition of the mechanism of cancer.


Assuntos
Autoantígenos , Neoplasias da Mama/metabolismo , Centrômero/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA , Northern Blotting , Mama/química , Mama/metabolismo , Proteína B de Centrômero , Proteínas Cromossômicas não Histona/análise , Feminino , Humanos , Hibridização In Situ , RNA Mensageiro/análise
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