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1.
Artigo em Inglês | MEDLINE | ID: mdl-34695267

RESUMO

OBJECTIVE: Elder abuse (EA) is a critical social, health, and economic issue worldwide. To date, there is limited information on EA in certain similar culture-specific subpopulations, especially in East Asia. This study aims to summarize EA incidence in East Asia through a systematic review and meta-analysis and identify its variations and heterogeneity in the incidence estimates. METHODS/DESIGN: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. Systematic review registration number PROSPERO CRD42020197131. A systematic literature search was performed to identify relevant articles published before July 5th, 2020, from six electronic databases. Two reviewers screened for relevance of the studies against eligible criteria and assessed the bias of the included studies independently. A random-effect model was adopted to estimate the incidence of EA, followed by subgroup analyses and multi meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analysis by Stata version 15.1. RESULTS: Twelve eligible studies were included in the meta-analysis, which involved 79,395 subjects from 3 East Asian countries (China, Japan, and South Korea) ranging from 2004 to 2020. The overall incidence of EA was 78.33 per 1000 person-year (95% CI: 39.12-156.87) with high between-study variability (χ2  = 15,568, d.f. = 11, p<0.001; I2  = 99.9%). The sampling method, sample size, scope, instrument, data collection method, income classification, types of participants, and urbanity are all the sources of heterogeneity, which can explain nearly 100% of the variance between studies. CONCLUSIONS: The incidence of EA in this study is not as high as the global level. It may be furtherly underestimated in East Asia due to cultural norms. It is imperative to develop a culture-tailored EA assessment instrument to evaluate potential victims. Future studies should also identify more effective educational programs to raise the public's awareness and promote recognition ability.


Assuntos
Abuso de Idosos , Idoso , China , Ásia Oriental/epidemiologia , Humanos , Incidência , Japão
2.
Cancer Cell Int ; 21(1): 127, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608016

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer related mortality worldwide. The 5-year survival rate is rather low owing to advanced unresectable and distant metastasis. The EMT has been widely implicated in the stemness, metastatic dormancy, and chemoresistance of different solid tumors. Given the fact that activating transcription factor-3 (ATF3) is a member of the ATF/CREB family of transcription factors and its role in regulation of GC recurrence and metastasis remain poorly understood, the aim of the present study was to investigate its potential impact in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties and GC aggression. METHODS: To elucidate the potential role of ATF3 in gastric cancer, we utilized SGC-7901 and MGC-803 gastric cancer cell lines as research models and constructed stable cell lines overexpressing ATF3. We conducted a series of assays including cell proliferation, colony formation, cell migration, tumorsphere formation, and invasion to investigate the functional roles of ATF3 in stemness of gastric cancer. The possible effect of ATF3 on epithelial-mesenchymal transition (EMT) was assessed through flow cytometry and qRT-PCR. In vivo functional effect of upregulation of ATF3 on tumor growth was examined in a mouse xenograft model. RESULTS: We found that overexpression of ATF3 inhibited cell proliferation, colony formation, cell migration and invasion. In addition, up-regulation of ATF3 attenuated tumorsphere formation, cell stemness, and potentially decreased expression of EMT markers. Moreover, ATF3 overexpression inhibited tumorigenesis in mouse xenograft model. CONCLUSION: Our data suggest a suppressive role of ATF3 in gastric cancer development. Our findings will provide a potential therapeutic strategy and novel drug target for gastric cancer.

3.
Cell Physiol Biochem ; 35(6): 2181-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25896499

RESUMO

BACKGROUND: Previous researches have reported that donor lymphocyte infusion (DLI) provides a new approach for the treatment of hematological malignancies and some solid tumors. The present study was designed to discuss the antitumor effect on mice with melanoma and possible involvement of the mechanism of haploidentical DLI in CB6F1 mice→CC3HF1 mice (F1→F1) mouse model. METHODS: An F1→F1 haploidentical infusion model was established. CB6F1 mice (H-2b/d) bearing melanoma were used as recipients. CC3HF1 mice (H-2d/k) were used as donors. Changes in tumor volume and mice survival, host-derived lymphocytes proliferation, cytotoxicity, donor cell survival in vivo, histopathological examination of important organs, and the secretion Th1/Th2 cytokines were analyzed. RESULTS: Irradiated haploidentical DLI combined with low-dose cyclophosphamide (Cy) chemotherapy induced an antitumor effect on mice with melanoma using the F1→F1 infusion model. Graft-versus-host disease (GvHD) was not obvious in any DLI-treated groups. Donor lymphocytes disappeared within 5 days after infusion, while the antitumor effect continued to be observed. Moreover, the DLI-treated groups showed a significant increase in the secretion of Th1 cytokines, including IFN-γ and IL-2, and an enhanced proliferation of CD8(+) T lymphocytes and NK cells. CONCLUSIONS: Irradiated haploidentical DLI without bone marrow transplantation offers a safe, feasible, and effective approach in the treatment of melanoma.


Assuntos
Antineoplásicos/farmacologia , Linfócitos T CD8-Positivos/imunologia , Melanoma/tratamento farmacológico , Melanoma/imunologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclofosfamida/farmacologia , Modelos Animais de Doenças , Feminino , Interferon gama/imunologia , Interleucina-2/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Doadores de Tecidos
4.
Diabetes Metab Res Rev ; 30(6): 489-96, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24665054

RESUMO

BACKGROUND: Little is known about the optimal cut-off point of fasting plasma glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese women. This study investigates the relationship between gestational fasting plasma glucose and several variables: neonatal birth weight, prenatal blood pressure and dystocia rate of pregnant women. In this study, we hoped to provide a useful tool to screen gestational diabetes mellitus in pregnant Chinese women. METHODS: For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22-30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as well as dystocia conditions, were examined. We analysed the correlations between the following: gestational fasting plasma glucose and neonatal birth weight; prenatal blood pressure and gestational fasting plasma glucose as well as dystocia rate and gestational fasting plasma glucose group. RESULTS: A modest correlation was observed between gestational fasting plasma glucose and neonatal birth weight (r = 0.093, p = 0.003). The macrosomia rate was smallest when the gestational fasting plasma glucose was in the range 3.51-5.5 mmol/L. Prenatal blood pressure increased linearly with increasing gestational fasting plasma glucose (p = 0.000). There was a significant difference between the dystocia rates in different fasting plasma glucose groups (chi-squared = 13.015, p = 0.043). The results showed that the dystocia rate significantly increased when gestational fasting plasma glucose was >4.9 mmol/L; p = 0.03, OR = 2.156 (95% CI, 1.077-4.318). CONCLUSION: We suggest that the optimal range of gestational fasting plasma glucose for pregnant Chinese women is in the range 3.5-4.9 mmol/L.


Assuntos
Glicemia/análise , Diabetes Gestacional/diagnóstico , Distocia/etiologia , Retardo do Crescimento Fetal/etiologia , Macrossomia Fetal/etiologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Pré-Hipertensão/fisiopatologia , Adolescente , Adulto , Peso ao Nascer , China/epidemiologia , Diabetes Gestacional/sangue , Diabetes Gestacional/fisiopatologia , Distocia/epidemiologia , Diagnóstico Precoce , Feminino , Retardo do Crescimento Fetal/epidemiologia , Macrossomia Fetal/epidemiologia , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Pré-Hipertensão/complicações , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Kidney Blood Press Res ; 35(5): 305-13, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22377586

RESUMO

BACKGROUND: Little is known about the prevalence and cardiovascular risk factors for prehypertension and hypertension in the She ethnic minority population of Fujian province in China. METHODS AND RESULTS: Between April 2009 and September 2009, 5,523 participants of She nationality aged between 20 and 80 years participated in this survey and 5,357 were eventually enrolled in analyses. The survey was carried out to assess blood pressure and cardiovascular risk factors. The prevalence of prehypertension and hypertension was 35.87 and 38.42%, respectively, in all participants. Only 26.63% of the subjects with hypertension were aware of their diagnosis. Multivariate logistic regression showed that age, gender, overweight/obesity, dyslipidemia and alcohol use were risk factors for prehypertension, and age, overweight/obesity, dyslipidemia, alcohol use, family history of hypertension and hyperuricemia were risk factors for hypertension. The clustering of 2 and ≥ 3 risk factors was in higher proportion for subjects with hypertension and prehypertension when compared with those with prehypertension and normotension, respectively. After adjusting for other confounding factors, multivariable logistic regression showed that the greater the number of clustering cardiovascular risk factors, the greater the odds ratios for prehypertension and hypertension are. CONCLUSION: Hypertension and prehypertension were common in the She population of Fujian province. Cardiovascular risk factors cluster during prehypertension and awareness of hypertension was minimal. Early lifestyle modifications could be advocated to prevent the transition from prehypertension to hypertension and cardiovascular disease.


Assuntos
Povo Asiático/estatística & dados numéricos , Hipertensão/etnologia , Pré-Hipertensão/etnologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , China/epidemiologia , Análise por Conglomerados , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
6.
Front Neuroanat ; 16: 893953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847828

RESUMO

Purpose: To investigate the application value of 3D arterial spin labeling (3D-ASL) for evaluating distal limb ischemic preconditioning to improve acute ischemic stroke (AIS) perfusion. Materials and Methods: A total of 40 patients with AISs treated in our hospital from January 2020 to December 2020 were recruited, and 15 healthy individuals who were examined in our hospital during the same period were included as the control group; all of these participants were scored on the National Institutes of Health Stroke Scale (NIHSS) and examined by MRI. Sequences included conventional sequences, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA), and 3D-ASL, and cerebral infarct volume and cerebral blood flow (CBF) in the area of the infarct lesion were measured. After 3 months of treatment, patients with AIS were scored on the modified Rankin Scale (mRS) and divided into good prognosis and poor prognosis groups. In total, 55 adult male Sprague-Dawley rats were divided randomly into three groups: 20 in the middle cerebral artery occlusion (MCAO) group, 20 in the MCAO + limb remote ischemic preconditioning (LRP) group, and 15 in the sham group. In total, 48 h after the procedures, conventional MRI, DWI, and 3D-ASL sequence data were collected, and 2,3,5-trphenyltetrazolium chloride monohydrate (TTC) staining and behavioral scoring were performed. CBF was recorded in the infarct lesion area and the corresponding contralateral area, and the affected/contralateral relative values (rCBF) were calculated to compare the differences in rCBF between different groups. The pathological changes in brain tissues were observed by HE staining, and the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in brain tissues was detected by immunofluorescence and real-time quantitative polymerase chain reaction (RT-qPCR). The protein expression of VEGF was detected by western blotting. Results: Hypertension and internal carotid atherosclerosis are high-risk factors for ischemic stroke, and CBF values in the infarct area are significantly lower than those in the corresponding areas on the contralateral side. NIHSS and mRS scores and CBF values have higher specificity and sensitivity for the prognosis of patients with AIS. LRP significantly reduces the infarct area, improves behavioral deficits in rats with cerebral ischemia, reduces neurological injury and histological damage, protects vascular structures, and promotes neovascularization. In addition, 3D-ASL showed a significant increase in brain tissue perfusion in the ischemic area after LRP, and the expression of VEGF and CD31 showed a significant positive correlation with CBF values. Conclusion: Three dimensional (3D) ASL can be used to evaluate LRP to improve stroke perfusion, and its protective effect may be closely related to LRP-induced vascular regeneration.

7.
Kidney Blood Press Res ; 34(2): 69-74, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21212687

RESUMO

OBJECTIVES: The aim of this study was to investigate the prevalence and epidemiological characteristics of hypertension in the Chinese She ethnic minority in Fujian province of China. After analyzing relevant risk factors of hypertension, we wanted to provide information for prevention and control of hypertension in this ethnic minority. METHODS: Using the stratified and cluster methods, we randomly selected 5,350 She subjects for a questionnaire survey. Their weight, height and blood pressure were measured. Hypertension was defined as a mean systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg, or use of antihypertensive medication. SPSS 13.0 software was used for database building and the χ(2) test for statistical analysis. RESULTS: The number of patients with hypertension was 1,931 (prevalence 36.09%) and 71.15% of them (1,374 patients) were undiagnosed. The prevalence of hypertension increased with age and was associated with education levels, occupation, body mass index, smoking, salt intake levels and a lack of health concepts. CONCLUSIONS: The prevalence of hypertension in the She has grown rapidly, which is closely correlated with lifestyle and lack of health education of hypertension. The prevention and control of hypertension in the She is imperative, and the promotion of health education on hypertension can be improved to enhance awareness, prevention, and control of hypertension.


Assuntos
Hipertensão/epidemiologia , China/epidemiologia , Educação em Saúde , Humanos , Hipertensão/etnologia , Hipertensão/prevenção & controle , Estilo de Vida , Prevalência , Fatores de Risco , Inquéritos e Questionários
8.
Front Mol Biosci ; 8: 781307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004851

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. The tumor microenvironment (TME) plays a vital role in HCC progression. Thus, this research was designed to analyze the correlation between the TME and the prognosis of HCC patients and to construct a TME-related long noncoding RNA (lncRNA) signature to determine HCC patients' prognosis and response to immunotherapy. Methods: We assessed the stromal-immune-estimate scores within the HCC microenvironment using the ESTIMATE (Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data) algorithm based on The Cancer Genome Atlas database, and their associations with survival and clinicopathological parameters were also analyzed. Thereafter, differentially expressed lncRNAs were filtered out according to the immune and stromal scores. Cox regression analysis was performed to build a TME-related lncRNA risk signature. Kaplan-Meier analysis was used to explore the prognostic value of the risk signature. Furthermore, we explored the biological functions and immune microenvironment features in the high- and low-risk groups. Lastly, we probed the association of the risk model with treatment responses to immune checkpoint inhibitors (ICIs) in HCC. Results: The stromal, immune, and estimate scores were obtained utilizing the ESTIMATE algorithm for patients with HCC. Kaplan-Meier analysis showed that high scores were significantly correlated with better prognosis in HCC patients. Six TME-related lncRNAs were screened to construct the prognostic model. The Kaplan-Meier curves suggested that HCC patients with low risk had better prognosis than those with high risk. Receiver operating characteristic (ROC) curve and Cox regression analyses indicated that the risk model could predict HCC survival exactly and independently. Functional enrichment analysis revealed that some tumor- and immune-related pathways were activated in the high-risk group. We also revealed that some immune cells, which were important in enhancing immune responses toward cancer, were significantly increased in the low-risk group. In addition, there was a close correlation between ICIs and the risk signature, which can be used to predict the treatment responses of HCC patients. Conclusion: We analyzed the influence of the stromal, immune, and estimate scores on the prognosis of HCC patients. A novel TME-related lncRNA risk model was established, which could be effectively applied as an independent prognostic biomarker and predictor of ICIs for HCC patients.

9.
Ther Adv Endocrinol Metab ; 12: 20420188211054690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733468

RESUMO

PURPOSE: To investigate the effect of subclinical hypothyroidism on pregnancy outcomes of women early in their pregnancy with different thyroid-stimulating hormone levels and thyroid peroxidase antibody-negative status and to explore reasonable thyroid-stimulating hormone levels for subclinical hypothyroidism in early pregnancy. METHODS: A total of 2378 women early in their pregnancy were studied retrospectively. The baseline characteristics were collected from medical records. Pregnancy outcomes were compared between the euthyroidism and subclinical hypothyroidism groups that were diagnosed by 2011 or 2017 American Thyroid Association guidelines. In addition, the effect of different maternal thyroid-stimulating hormone levels on adverse pregnancy outcomes was analyzed using binary logistic regression. RESULTS: According to the 2011 American Thyroid Association diagnostic criteria of subclinical hypothyroidism, the prevalence of pregnancy outcomes was not significantly higher in the subclinical hypothyroidism group than in the euthyroidism group. However, pregnant women with subclinical hypothyroidism identified by the 2017 American Thyroid Association criteria had a higher risk of premature delivery (odds ratio = 3.93; 95% confidence interval = 1.22-12.64), gestational diabetes mellitus (odds ratio = 2.69; 95% confidence interval = 1.36-5.32), and gestational anemia (odds ratio = 3.28; 95% confidence interval = 1.60-6.75). Moreover, no differences in the prevalence of adverse pregnancy outcomes were observed between the mildly elevated thyroid-stimulating hormone group (2.5 < thyroid-stimulating hormone ⩽4.0 mIU/l) and the normal thyroid-stimulating hormone group (0.27 < thyroid-stimulating hormone ⩽2.5 mIU/l). The significantly elevated thyroid-stimulating hormone group (4.0 < thyroid-stimulating hormone < 10.0 mIU/l) had a higher prevalence of premature delivery, gestational diabetes mellitus, and gestational anemia than the normal thyroid-stimulating hormone group, even after controlling for potential confounding factors. CONCLUSION: A mildly elevated thyroid-stimulating hormone level or maternal subclinical hypothyroidism diagnosed by 2011 American Thyroid Association guidelines during early pregnancy in thyroid peroxidase antibody-negative women was not associated with adverse pregnancy outcomes. However, maternal subclinical hypothyroidism identified by the 2017 American Thyroid Association guidelines increased the risks of several adverse pregnancy outcomes in women untreated with levothyroxine. The 2017 American Thyroid Association guidelines could be more reasonable for the diagnosis of subclinical hypothyroidism in southern China.

10.
Front Oncol ; 11: 720261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631548

RESUMO

Multiple myeloma (MM) is a malignant cancer with an increasing in incidence that can be alleviated through bortezomib (BTZ) treatment. Activating transcription factor 3 (ATF3) plays a major role in cancer development. Moreover, microRNAs (miRNAs) regulate carcinogenic pathways, apoptosis, and programmed necrotic cell death. However, the detailed mechanism by which ATF3 modulates BTZ drug sensitivity/resistance remains elusive. In the current study, expression of ATF3 was significantly increased under BTZ treatment in a dose-dependent manner in MM cell lines. In addition, ATF3 could regulate cell apoptosis under BTZ treatment. The effect of ATF3 was negatively regulated by its binding miRNA, miR-135a-5p. When either ATF3 was silenced or miR-135a-5p mimics were added to MM cells, they partially lost sensitivity to BTZ treatment. This was accompanied by low levels of Noxa, CHOP, and DR5, and a decrease in mitochondrial membrane potential. These results revealed the combinatorial regulatory patterns of ATF3 and miR-135a-5p in the regulatory protein interactome, which indicated a clinical significance of the miR-135a-5p-ATF3 protein interaction network in BTZ therapy. This study provides potential evidence for further investigation into BTZ resistance.

11.
Cancer Manag Res ; 11: 6855-6869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440083

RESUMO

BACKGROUND: Inhibitor of DNA binding 1 (Id1) is upregulated in multiple cancers, and Id1overexpression correlates with cancer aggressiveness and poor clinical outcomes in cancer patients. However, its roles in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) are still elusive. PURPOSE: This study aimed to examine the role of Id1 on the mediation of CRC stemness and explore the underlying mechanisms. METHODS: Id1 and CD133 expression was detected by qPCR assay and immunohistochemistry (IHC) in normal mucosal and primary colorectal cancer (CRC) specimens. Id1 was stably knocked down (KD) in human CRC cell lines. Spheres forming assay and tumorigenic assay were performed to evaluate self-renewal capacity and tumor initiation. Expression of CSC- and EMT-related markers and TCF/LEF activity were assessed in HCT116 cells after Id1 KD. RESULTS: qPCR assay showed higher Id1 and CD133 expression in CRC specimens than in normal mucosal specimens (P<0.05). IHC detected high cytoplasmic Id1 expression in 35 CRC specimens (46.7%), and high CD133 expression in 22 CRC specimens (29.3%) and negative expression in 18 normal mucosal specimens. High Id1 expression positively correlated with poor differentiation (P=0.034), and CD133 expression correlated with T category in CRC patients (P=0.002). Spearman correlation analysis revealed a positive correlation between Id1 and CD133 expression in CRC patients (P<0.05). Id1 KD resulted in suppression of proliferation, cell-colony formation, self-renewal capability and CSC-like features in HCT116 cells, and impaired the tumor-initiating capability in CRC cells. In addition, Id1 maintained the stemness of CRC cells via the Id1-c-Myc-PLAC8 axis through activating the Wnt/ß-catenin and Shh signaling pathways. CONCLUSIONS: Id1 expression significantly correlates with CD133 expression in CRC patients, and Id1 KD impairs CSC-like capacity and reverses EMT traits, partially via the Wnt/ß-catenin signaling. Id1 may be a promising therapeutic target against colon CSCs.

12.
Oncol Rep ; 32(1): 79-88, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24804700

RESUMO

Inhibitor of DNA-binding protein 1 (ID1) is commonly abnormally overexpressed in colorectal cancer (CRC); yet, the functional significance of ID1 in the growth and invasive properties of CRC cells remains largely unclear. The present study investigated the effects of ID1 downregulation on the cell growth and metastatic features of CRC. Using lentiviral shRNA infection, stable ID1-knockdown (KD) HCT116 and SW620 cells, human metastatic CRC cell lines, were created. In vitro, the migration/invasion capacity of the ID1-KD CRC cells was assessed by a wound healing assay. The activities of MMP2 and MMP-9 were measured by gelatin zymography. The expression of CXC chemokine receptor 4 (CXCR4), PCNA and survivin were determined by immunoblot analysis and qRT-PCR. The effects of ID1 knockdown on tumor growth and hepatic metastasis were demonstrated by a xenograft study in mice. The results showed evident decreases in proliferation, migration and invasion and an increased apoptosis rate in the ID1-KD CRC cells. Similarly, ID1 knockdown significantly decreased mRNA and protein levels of PCNA, survivin, CXCR4, MMP2 and MMP9. Overexpression of CXCR4 antagonized the negative effect on the migration and invasion abilities of the ID1-KD cells. As compared with the control, ID1 knockdown prevented tumor growth and profoundly suppressed hepatic metastasis in vivo. The present study demonstrated the significance of ID1 in colon cancer progression, and its effect on tumor invasiveness and metastatic properties may be partly dependent on CXCR4.


Assuntos
Neoplasias Colorretais/patologia , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo , Neoplasias Hepáticas/secundário , Receptores CXCR4/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Neoplasias Experimentais , Receptores CXCR4/genética
13.
J Diabetes ; 5(2): 136-45, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23298195

RESUMO

BACKGROUND: Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes-related genes/loci, T2DM and diabetic complications in Chinese She subjects. METHODS: A comprehensive gene-based association study was conducted using 17 single nucleotide polymorphisms in Chinese She subjects with normal glucose tolerance (n = 1119), impaired glucose regulation (n = 1767), and T2DM (n = 443). We applied major abnormal Minnesota Code findings to predict cardiovascular risk and estimated glomerular filtration rate to assess kidney function. RESULTS: Nine variants in FTO rs8050136, WFS1 rs10010131, CDKN2A/B rs10811661, KCNJ11 rs5219, CDC123/CAMK1D rs12779790, JAZF1 rs864745, SLC30A8 rs13266634, CDKAL1 rs10946398, and HHEX/IDE rs5015480 were significantly associated with T2DM (P < 0.05). Single nucleotide polymorphisms in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMK1D rs12779790, JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were associated with T2DM and impaired glucose regulation. Risk alleles in WFS1 rs10010131, IGF2BP2 rs4402960, CDKAL1 rs10946398, FTO rs8050136, KCNQ1 rs2237897, and ADAMTS9 rs4607103 were significantly associated with decreased homeostatic model assessment (HOMA)-ß (P < 0.05). After adjusting for age, gender and body mass index, genetic variants JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were significantly related to reduced estimated glomerular filtration rate (P < 0.05). Genetic variants in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMID rs12779790, JAZF1 rs864745, FTO rs80501360, CDKAL1 rs10946398, and HHEX/IDE rs5015480 correlated with abnormal major Minnesota Code findings (P < 0.05). CONCLUSION: Variants in WFS1, CDKN2A/B, KCNJ11, CDC123/CAMK1D, JAZF1, SLC30A8, FTO, CDKAL1, and HHEX/IDE genes are significantly associated with T2DM in She Chinese subjects. JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with diabetic nephropathy. WFS1, CDKN2A/B, CDC123/CAMK1D, JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with cardiovascular risk.


Assuntos
Povo Asiático , Doenças Cardiovasculares/genética , Nefropatias Diabéticas/genética , Loci Gênicos , Variação Genética , Alelos , Doenças Cardiovasculares/etnologia , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/etnologia , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
14.
Diabetes Technol Ther ; 14(5): 430-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22304539

RESUMO

OBJECTIVE: According to recent reports, the development of type 2 diabetes in China has soared at an alarming rate. However, most of the investigations were based on Han people, who account for the majority of people in China. Little is known about the prevalence of diabetes its chronic complications in the She people, who have their own traditional lifestyle and hereditable background, different from other Asian population. The present study investigated the prevalence of type 2 diabetes and associated risk factors in the adult population of She nationals. SUBJECTS AND METHODS: A total of 5,385 participants entered into the analysis eventually, including 2,308 men and 3,077 women. An oral glucose tolerance test was performed in subjects without diagnosed diabetes. Liver function, cardiovascular risk (brachial-ankle pulse wave velocity, estimated glomerular filtration rate, and abnormal Minnesota codes findings), uric acid, and neuropathy were tested to assess the profiles of associated risks. RESULTS: In general, the self-reported diabetes rate was 9.5%. After age and sex standardization, the prevalence of diabetes was 6.1% (6.7% for men and 5.7% for women) in She Chinese people. In logistic regression models, age, family history of diabetes, alcohol use, total cholesterol, and triglycerides were all significantly associated with the risk of diabetes in this cross-sectional study (all P<0.05). In all, 47.4% had cardiovascular risks, 19.4% had liver dysfunction, and 6.2% had hyperuricemia. For women, compared with the first quartile, log-transformed homeostasis model assessment for insulin resistance of the fourth quartile was significantly higher (P<0.05), and log-transformed homeostasis model assessment for ß cells was also higher in the second, third, and fourth quartiles (all P<0.05). The prevalences of polyneuropathy in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT, and diabetes mellitus (DM) were 16.1%, 13.1%, 18.6%, and 28.4% separately, which was higher than that in normal glucose tolerance. The prevalences of polyneuropathy in IFG/IGT and DM were higher than that in IGT. CONCLUSIONS: The present study revealed that a total of 6.1% She people suffered from type 2 diabetes, which was lower than the average level of China, but the standardized prevalence of prediabetes was higher, 20.6%. Early peripheral neuropathy screening should be performed in the prediabetes population. The Toronto Clinical Neuropathy Scoring System is convenient to assess diabetic polyneuropathy in clinical practice and should be tested regularly for people in prediabetes. Liver dysfunction, headache, and insomnia, appearing before type 2 diabetes, should be assessed regularly to avoid deterioration.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Neuropatias Diabéticas/epidemiologia , Estado Pré-Diabético/epidemiologia , Glicemia , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/prevenção & controle , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/etnologia , Neuropatias Diabéticas/prevenção & controle , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/etnologia , Estado Pré-Diabético/prevenção & controle , Prevalência , Fatores de Risco , Distribuição por Sexo
15.
Atherosclerosis ; 219(2): 709-14, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21963141

RESUMO

OBJECTIVES: Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China. METHODS: The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model. RESULTS: As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP (ß = -1.17, P = 0.002 and ß = -0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP (ß = -0.56, P=0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65-0.97) and 1.19 (1.01-1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4. CONCLUSIONS: We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension.


Assuntos
Povo Asiático/genética , Pressão Sanguínea/genética , Canais de Cálcio Tipo L/genética , Proteínas de Transporte/genética , Hipertensão/genética , Grupos Minoritários , Polimorfismo de Nucleotídeo Único , Pré-Hipertensão/genética , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Análise de Variância , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Hipertensão/enzimologia , Hipertensão/etnologia , Hipertensão/fisiopatologia , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Pré-Hipertensão/enzimologia , Pré-Hipertensão/etnologia , Pré-Hipertensão/fisiopatologia , Medição de Risco , Fatores de Risco
16.
Atherosclerosis ; 217(1): 279-85, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21501840

RESUMO

OBJECTIVE: To explore the cardiovascular disease (CVD) risk in prehypertensive subjects and evaluate whether high blood pressure (BP) is associated with insulin resistance (IR) and ß-cell dysfunction. METHODS: A total of 2949 people aged 20-94 years old were selected in Fujian province of China. We assessed CVD risk using Minnesota code-indicated major abnormal electrocardiography (MA-ECG) and presence of microalbuminuria in all population. IR/sensitivity and ß-cell function indices were derived from an oral glucose tolerance test. RESULTS: Prehypertensives with systolic/diastolic BP (SBP/DBP) 130-139/85-89 mm Hg had significant higher risk of MA-ECG and presence of microalbuminuria compared with normotensives (odds ratio [OR]: 1.483, 95% confidence interval [CI]: 1.016-2.165 and OR: 1.613, 95% CI: 1.142-2.277, respectively). In non-diabetic subjects, we found that prehypertensives and hypertensives had significant higher HOMA-IR and lower Matsuda's insulin sensitivity index compared with normotensives. There was a slightly decreased trend in ß-cell function assessed by disposition index (DIo) across the BP categories, when adjusted with age and BMI. The slight decline of DIo remained between hypertension and normotension, after additional adjustments were made, but the reduction of DIo lost statistic significance between prehypertension and normotension. CONCLUSIONS: Prehypertensives with SBP/DBP 130-139/85-89 mm Hg have higher CVD risk than normotensives. Prehypertension and hypertension are both in IR condition, however, what is more important is that early ß-cell dysfunction may exists in hypertension to some extent, while for prehypertension the compensation of ß-cell function may be appropriate.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Resistência à Insulina , Células Secretoras de Insulina/citologia , Pré-Hipertensão/sangue , Pré-Hipertensão/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/análise , Pressão Sanguínea , China , Eletrocardiografia/métodos , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Risco
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