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1.
Acta Cardiol ; 73(2): 131-140, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28786773

RESUMO

BACKGROUND: Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population. METHODS: Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay. RESULTS: Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile. CONCLUSIONS: Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.


Assuntos
Doenças Cardiovasculares/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , MicroRNAs/genética , RNA/genética , Adulto , Idoso , Alelos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Egito/epidemiologia , Feminino , Humanos , Incidência , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos
2.
Mol Med ; 22: 653-663, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27623812

RESUMO

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profile of three pluripotency-associated genes (OCT4, NANOG, and SOX2), G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand (CXCL2), and alpha feto-protein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC, and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction was performed for relative quantification of the 6 target genes using LIVAC method. In silico network analysis was also executed to explore the pluripotency and tumorigenic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly up-regulated in HCC patients with late clinical stage. In contrast, SOX2 and CXCL2 were markedly over-expressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high-expression with late HCC, could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have a potential application in HCC prognosis and treatment.

3.
Diagn Pathol ; 8: 11, 2013 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-23343214

RESUMO

BACKGROUND: Human epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases. METHODS: CA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively. RESULTS: Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively. CONCLUSION: Measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759.


Assuntos
Adenocarcinoma Mucinoso/sangue , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Endometrioide/sangue , Proteínas de Membrana/sangue , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Ovarianas/sangue , Proteínas/análise , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Análise de Variância , Área Sob a Curva , Carcinoma Endometrioide/terapia , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Endometriose/sangue , Feminino , Humanos , Leiomioma/sangue , Modelos Lineares , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Doença Inflamatória Pélvica/sangue , Valor Preditivo dos Testes , Curva ROC , Resultado do Tratamento , Regulação para Cima , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Adulto Jovem
4.
Egypt J Immunol ; 20(2): 1-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24617042

RESUMO

Many cellular, preclinical and observational studies support a role of vitamin D in pathogenesis of type-1 diabetes mellitus (DM). The vitamin D receptor (VDR) locus has been studied in different populations for association with susceptibility to immune-mediated diseases, but with inconsistent findings in type-1 DM. This study aimed to investigate vitamin D status in patients with type-1 DM. We examined the frequency of VDR Fokl (rs10735810) gene polymorphism, and its association with serum 25-hydroxyvitamin D (25(OH) D) level in Egyptian patients with type-1 DM. 132 children with type-1 DM and 40 age and sex matched healthy control subjects were studied. VDR Fokl polymorphism was assessed using polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis. Diabetic children demonstrated lower circulating levels of 25(OH) D than the controls (13.4 +/- 7.6 vs 32.1 +/- 3.8ng/ml) (P < 0.01). Patients with deficient 25(OH) D showed lower calcium levels and higher HbA1c% than those with sufficient levels (8.1 +/- 2.1 versus 9.1 +/- 1.6 mg/dl & 9.9 +/- 2.5 versus 8.1 +/- 1.4%, respectively (P < 0.05). There was no significant difference in the genotype distribution or the allele frequencies of VDR Fokl between patients and controls. The odds ratio (OR) was 1.08 (P = 0.76), and the 95% confidence interval (CI) ranged from 0.64-1.85. The diabetic carriers of the ff genotype showed low serum levels of 25(OH) D and calcium when compared with the carriers of the F allele (9.1 +/- 4.4 vs 13.1 +/- 7 and 13.9 +/- 6.09 ng/ml & 8.1 +/- 2.1 vs 9.1 +/- 1.1 and 9.3 +/- 1.2 mg/dl, respectively) (P < 0.05). In conclusion, 84.8% of children with type-1 DM have low circulating levels of 25(OH) D. These patients have poor glycemic control (56.06%) than those with sufficient levels of 25(OH) D. Fokl polymorphism of VDR gene is associated with vitamin D deficiency but has no significant role in susceptibility to type-1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina D/análogos & derivados , Adolescente , Criança , Pré-Escolar , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Diabetes Mellitus Tipo 1/sangue , Egito , Feminino , Genótipo , Humanos , Masculino , Vitamina D/sangue
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