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1.
JAMA Netw Open ; 2(5): e193348, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31050781

RESUMO

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

2.
Obes Facts ; 12(2): 190-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30928977

RESUMO

OBJECTIVES: This study was undertaken to compare gut hormone secretion between high-fat-fed and control rats, and to examine the corresponding changes in the expression of sweet taste receptors and glucose transporters in the small intestine and hypothalamus. METHODS: Four-week-old male Sprague Dawley rats were fed a standard or high-fat diet for 8 weeks (10 in each group), followed by an oral glucose tolerance test (50% glucose solution, 2 g/kg). Blood was sampled for glucose, insulin, glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) assays. One week later, small intestinal and hypothalamic tissue were analyzed for sweet taste receptor and glucose transporter expression by real-time PCR. RESULTS: After oral glucose, plasma GLP-1 concentrations were higher in high-fat-fed than standard-fat-fed rats (group × time interaction, p < 0.01) with significant differences at t = 15 min (p < 0.01) and 30 min (p < 0.05). Plasma PYY concentrations were lower in high-fat-fed than control rats at t = 0, 15 min (p < 0.05, respectively) and 120 min (p < 0.01). There were no differences in the expression of sweet taste receptors or glucose transporters between high-fat-fed and control rats in the duodenum, ileum, or hypothalamus. CONCLUSIONS: Changes in GLP-1 and PYY secretion after a high-fat diet appear unrelated to any changes in the expression of sweet taste receptors or glucose transporters. Impaired PYY secretion with high-fat feeding suggests that PYY analogues may provide a potential therapy in the treatment of obesity.

3.
Anal Chem ; 91(3): 2120-2127, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30585725

RESUMO

MicroRNAs (miRNAs) are important biomarker candidates for cancer screening and early detection research. Generally, miRNAs undergo synergistic adjustments in tumor cells. Herein, a mass-spectrometric method based on a duplex-specific-nuclease (DSN)-enzyme-assisted signal-amplification technique was proposed for label-free and multiplexed detection of multiple miRNAs, and applied to the quantification of three miRNAs (i.e., miRNA-141, miRNA-21, and let-7a) in samples of HeLa and MDA-MB231 cell extracts. Experimental results showed that the digestion modes of DSN against three different DNAs complementary to miRNA-141, miRNA-21, and let-7a in their DNA-miRNA heteroduplexes were quite different, verifying the multiplexed-detection capability of the proposed method. Moreover, an advanced calibration model was derived for the quantitative analysis of the complex mass-spectral data measured during the label-free and multiplexed detection of miRNA-141, miRNA-21, and let-7a by the proposed mass-spectrometric method. With the aid of the advanced calibration model, the proposed mass-spectrometric method achieved quite reliable quantitative results for miRNA-141, miRNA-21, and let-7a in samples of HeLa and MDA-MB231 cell extracts, with recovery rates within the range of 89.2 to 111.6%. The limits of detection (LODs) of the proposed mass-spectrometric method for miRNA-141, miRNA-21, and let-7a in standard samples were estimated to be 42, 41, and 95 pM, respectively. Therefore, it is reasonable to expect that the proposed mass-spectrometric method can be a competitive alternative for the label-free and multiplexed detection of multiple miRNAs in clinical diagnosis.

4.
Clin Endocrinol (Oxf) ; 89(6): 840-848, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30176063

RESUMO

OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst  < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined  = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined  = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

6.
EBioMedicine ; 2(11): 1718-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26870797

RESUMO

Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in A(y)/a and db/db mice. Furthermore, the expression of interleukin (IL)-1ß and IL-6 was up-regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1ß and IL-6 expression in the hypothalamus.


Assuntos
Tecido Adiposo/metabolismo , Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Leptina/metabolismo , Transdução de Sinais , Animais , Peso Corporal , Ingestão de Alimentos , Humanos , Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leptina/genética , Camundongos , Camundongos Knockout , Microglia/metabolismo , Ratos
7.
Oncol Rep ; 22(5): 1057-61, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19787221

RESUMO

Mimecan mRNA was present in a limited number of mouse and human tissues, however, abundant mimecan mRNA was observed in the lung tissue. Therefore, we hypothesize that mimecan could serve as a biomarker for differentiating various histological types of lung cancers. In humans, the mimecan mRNA was found most abundant in ovary and less abundant in lung by using Northern blot analysis. Moreover, the mimecan was expressed strongly in the epithelial cells of the bronchial wall and weaker in the epithelial cells of the alveolar sacs by in situ hybridization and immunohistochemical analysis. Furthermore, the mimecan immunoreactivity was found in 103 (97.2%) of 106 non-small cell lung cancers (NSCLCs). Nevertheless, a large majority of small cell lung cancers (SCLCs) (50/56, 89.3%) showed negative immunoreactivity to mimecan polyclonal antibody. A significant difference of mimecan immunoreactivity was found between NSCLC and SCLC (P<0.00001). This is the first study showing that mimecan could serve as an excellent pathological biomarker to distinguish NSCLCs from SCLCs.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Northern Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Casos e Controles , Diagnóstico Diferencial , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Prognóstico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo
8.
J Mol Endocrinol ; 42(1): 67-74, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18974228

RESUMO

Although circulating ghrelin levels correlate inversely with adiposity at baseline, little is known about the effect of percent visceral adipose tissue value (PVATV) on ghrelin expression and secretion in response to fasting. Our study demonstrated that ghrelin increased with 24-h fasting in rats with the lowest PVATV (less than 6%), after 3 days in rats with intermediate PVATV (6-9%) and 5 days in rats with the highest PVATV (greater than 9%). Ghrelin mRNA in the stomach was increased after 3 days in low-PVATV (5.8+/-0.9%) rats but not in high-PVATV (14+/-1.6%) rats. Therefore, both ghrelin secretion and mRNA were delayed in response to fasting in rats with increased visceral fat. In rats matched for PVATV, but with different body weights, the fasting induced similar levels of increased ghrelin while in rats with different PVATV ghrelin secretion was different in response to fasting, even when body weights were matched in two groups. These data suggested that the initial PVATV, not lean mass, was related to the pattern of plasma ghrelin in response to fasting in rats.


Assuntos
Adiposidade , Composição Corporal , Jejum , Grelina/metabolismo , Gordura Intra-Abdominal/metabolismo , Animais , Peso Corporal , Gorduras na Dieta , Grelina/sangue , Grelina/genética , Humanos , Leptina/sangue , Masculino , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estômago/anatomia & histologia , Estômago/fisiologia
9.
Aust N Z J Psychiatry ; 37(4): 452-7, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12873330

RESUMO

OBJECTIVE: To assess the characteristics and factors affecting course of schizophrenia in a Chinese rural area. METHOD: An epidemiological investigation was conducted to identify all the patients with schizophrenia among 149 231 people in Xinjin County, Chengdu. RESULTS: The total prevalence of schizophrenia was 4.13 per 1000 population. Males had an earlier mean age of onset (29.6 years) than females (32.3 years). Duration of illness before treatment and the total duration of illness were found to be significantly associated with level of remission. The status of treatment, family economy, housing, and families' care of patients had a significant effect on the clinical course of the illness. CONCLUSIONS: Duration of illness before treatment may be an important predictor of course in schizophrenia. Early treatment for the patients may produce higher level of improvement in prognosis. Education intervention and community-based service are urgent priorities for these patients.


Assuntos
População Rural/estatística & dados numéricos , Esquizofrenia/epidemiologia , Esquizofrenia/terapia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Indução de Remissão , Psicologia do Esquizofrênico , Índice de Gravidade de Doença , Distribuição por Sexo , Resultado do Tratamento
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 24(12): 1104-7, 2003 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-14761625

RESUMO

OBJECTIVE: To study the prevalence of mild cognitive impairment (MCI) in the urban and the rural areas in Chengdu, Southwest China. METHODS: Residents aged 55 or over were selected by stratified random cluster sampling from 19 districts, cities, and counties of Chengdu area in Sichuan province. A two-stage survey was carried out. In the first stage, CMMSE, CES-D were used as screening instruments. In the second stage, Diagnostic questionnaires of dementia and CDR were used as diagnostic instruments. The diagnostic criteria of mild cognitive impairment adopted from Petersen's were: (1) memory complaint; (2) normal activities of daily living; (3) normal general cognitive function; (4) memory impairment incompatible with age; (5) not demented; (6) CDR = 0.5 and (7) exclusion of the reversible cognitive impairment caused by other factors (i.e. depression). RESULTS: Three thousand, nine hundred and ten subjects were examined. The prevalence rates of MCI was 2.4%. The MCI prevalence rates in the urban and the rural areas were 1.5%, 2.5% respectively, without significant difference. The MCI prevalence in males and females were 1.8%, 2.9% respectively. Prevalence rate in female was higher than in males with significant difference. Prevalence of illiteracy (4.0%) was the highest among different educational levels. The accumulated prevalence increased with age. CONCLUSION: The prevalence of MCI (2.4%) was slightly higher than the prevalence of AD (2.05%) in the same areas of Chengdu. MCI seemed to be a high risk factor for AD which should to be followed up. Early intervention in MCI might be helpful in the prevention of AD.


Assuntos
Transtornos Cognitivos/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição Aleatória , Características de Residência/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Classe Social
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