RESUMO
OBJECTIVE: Our purpose was to detect the molecular mechanism of F-box and WD repeat domain containing 7 (FBXW7) in regulating cell growth and metastasis of oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were applied to calculate the messenger ribonucleic acid (mRNA) and protein levels of genes and miR-27a. The proliferation and invasive abilities were measured by methyl thiazolyl tetrazolium (MTT) and transwell assays. The. Kaplan-Meier method was conducted to evaluate the 5-year overall survival of oral squamous cell carcinoma patients. RESULTS: FBXW7 was downregulated while miR-27a was upregulated in OSCC tissues and cells compared with the corresponding adjacent tissues. Downregulation of FBXW7 or upregulation of miR-27a in OSCC tissues predicted poor outcome of OSCC patients. FBXW7 suppressed the growth through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway in OSCC cell line HSC3. FBXW7 inhibited the invasion-mediated epithelial-mesenchymal transition (EMT) in HSC3 cells. The expression of FBXW7 was mediated by miR-27a by directly binding to the 3'-untranslated region (3'-UTR) of FBXW7 in HSC3 cells. MiR-27a reversed partial roles of FBXW7 on the proliferation and invasion in OSCC cells. CONCLUSIONS: FBXW7 was mediated by miR-27a and could inhibit the proliferation through the PI3K/AKT pathway and invasion-mediated EMT in OSCC cell line. The newly identified miR-27a/FBXW7/PI3K/AKT axis provides novel insights into the pathogenesis of osCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Transição Epitelial-Mesenquimal , Proteína 7 com Repetições F-Box-WD/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Células Cultivadas , Proteína 7 com Repetições F-Box-WD/genética , Humanos , MicroRNAs/genética , Neoplasias Bucais/patologia , Transdução de SinaisRESUMO
OBJECTIVE: This study aimed to examine the prognostic value of miR-421 in terms of overall survival (OS) and recurrence free survival (RFS) in ESAD and its potential regulatory network. PATIENTS AND METHODS: An in-silico analysis was conducted using data from large databases, including The Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA), Starbase 3.0 and GeneMANIA. RESULTS: Both esophageal adenocarcinoma (ESAD) and esophageal squamous cell carcinoma (ESCC) tissues had significantly upregulate miR-421 expression, compared with adjacent normal tissues. Upregulated miR-421 expression was associated with shorter OS, but not RFS in ESAD. In patients with ESCC, no difference in miR-421 expression was observed regards to OS or RFS status. Univariate and multivariate analysis showed that high miR-421 expression was independently associated with shorter OS (HR: 2.77, 95%CI: 1.41-5.46, p<0.01), after adjustment of histological grade and pathological stages. The predicted regulatory network of miR-421 in ESAD includes both tumor suppressors and oncogenes, which makes the role of miR-421 quite mysterious in this cancer. CONCLUSIONS: MiR-421 expression might serve as a valuable prognostic biomarker in patients with ESAD. But future molecular studies are required to explore the exact regulatory effect of it.
Assuntos
Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , MicroRNAs/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Esôfago/metabolismo , Esôfago/patologia , Feminino , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Regulação para CimaRESUMO
OBJECTIVE: Growth hormone deficiency (GHD) is the most common cause for childhood dwarfism. Currently, the significance of insulin-like growth factor-1 (IGF-1) in diagnosis of GHD is still debatable. Due to the possible correlation between leptin (LEP) and GHD pathogenesis, this study investigated the gene polymorphism of LEP and its receptor (LEPR) genes, along with serum IGF-1 and LEP levels in GHD patients. This study attempted to illustrate the correlation between gene polymorphism and GHD pathogenesis. PATIENTS AND METHODS: A case-control study was performed using 180 GHD children in addition to 160 healthy controls. PCR-DNA sequencing method was employed for genotyping various polymorphism loci of LEP and LEPR genes in both GHD and healthy individuals. Serum IGF-1 and LEP levels were also determined. RESULTS: Results revealed a statistically significant difference between the levels of IGF-1 and LEP in the serum samples collected from patients in the GHD and the control groups. Both IGF-1 and LEP levels were found to be correlated with polymorphism at rs7799039 loci of LEP gene, in which GG and GA genotypes carriers had higher serum IGF-1 levels when compared to AA genotype carriers. CONCLUSIONS: GHD pathogenesis is well correlated with the LEP and IGF-1 levels in the both of which were mediated by the gene polymorphism at rs7799039 loci of LEP gene.
Assuntos
Hormônio do Crescimento/deficiência , Fator de Crescimento Insulin-Like I/genética , Leptina/sangue , Receptores para Leptina/genética , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Hormônio do Crescimento Humano , Humanos , MasculinoRESUMO
BACKGROUND: Soluble CD40 ligand (sCD40L) is associated with inflammation. This study aimed to assess the prognostic value of sCD40L for clinical outcomes of acute intracerebral hemorrhage (ICH) patients. MATERIALS AND METHODS: The serum sCD40L levels of 110 patients and 110 age- and gender-matched healthy controls were measured using sandwich immunoassays. The relationships between serum sCD40L levels and 1-week mortality, 6-month mortality, 6-month overall survival, 6-month unfavorable outcome (modified Rankin Scale score >2), and ICH severity including hematoma volume and National Institutes of Health Stroke Scale (NIHSS) score were assessed using multivariate analysis. RESULTS: Compared with healthy controls, ICH patients had higher serum sCD40L levels. Serum sCD40L levels were correlated positively with hematoma volumes and NIHSS scores using a multivariate linear regression. Multivariate analysis results indicated that sCD40L was identified an independent predictor of 1-week mortality, 6-month mortality, 6-month unfavorable outcome and 6-month overall survival. sCD40L also showed high predictive performances for 1-week mortality, 6-month mortality and 6-month unfavorable outcome based on receiver operating characteristic curve. CONCLUSIONS: Elevated serum sCD40L levels are independently associated with ICH severity and clinical outcomes. And sCD40L has potential to be a good prognostic biomarker of ICH.
Assuntos
Ligante de CD40/sangue , Hemorragia Cerebral/sangue , Adulto , Idoso , Hemorragia dos Gânglios da Base/sangue , Hemorragia dos Gânglios da Base/mortalidade , Biomarcadores/sangue , Hemorragia Cerebral/mortalidade , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Análise de Sobrevida , Resultado do TratamentoRESUMO
Model for end-stage liver disease (MELD) scoring was initiated using traditional statistical technique by assuming a linear relationship between clinical features, but most phenomena in a clinical situation are not linearly related. The aim of this study was to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure (ACHBLF) on an individual patient level using an artificial neural network (ANN) system. The ANN model was built using data from 402 consecutive patients with ACHBLF. It was trained to predict 3-month mortality by the data of 280 patients and validated by the remaining 122 patients. The area under the curve of receiver operating characteristic (AUROC) was calculated for ANN and MELD-based scoring systems. The following variables age (P < 0.001), prothrombin activity (P < 0.001), serum sodium (P < 0.001), total bilirubin (P = 0.015), hepatitis B e antigen positivity rate (P < 0.001) and haemoglobin (P < 0.001) were significantly related to the prognosis of ACHBLF and were selected to build the ANN. The ANN performed significantly better than MELD-based scoring systems both in the training cohort (AUROC = 0.869 vs 0.667, 0.591, 0.643, 0.571 and 0.577; P < 0.001, respectively) and in the validation cohort (AUROC = 0.765 vs 0.599, 0.563, 0.601, 0.521 and 0.540; P ≤ 0.006, respectively). Thus, the ANN model was shown to be more accurate in predicting 3-month mortality of ACHBLF than MELD-based scoring systems.
Assuntos
Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Falência Hepática/mortalidade , Falência Hepática/patologia , Modelos Estatísticos , Redes Neurais de Computação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Tumour necrosis factor-α (TNF-α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF-α genes. However, there have been conflicting results reported in previous studies on TNF-α-238 and TNF-α-863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966-August, 2010) and China Biological Medicine Database (January, 1978-August, 2010) and carried out a meta-analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta-analysis did not suggest significant associations of TNF-α-238 and TNF-α-863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF-α-238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07-4.58, P = 0.032; OR = 4.46, 95% CI: 1.75-11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF-α-238A allele may increase the risk of chronic HBV infection in European populations.
Assuntos
Predisposição Genética para Doença , Hepatite B Crônica/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Europa (Continente) , Frequência do Gene , Hepatite B Crônica/imunologia , Humanos , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/imunologia , População BrancaRESUMO
Tumour necrosis factor-α (TNF-α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF-α-857 polymorphism and chronic HBV infection have reported conflicting results. So a meta-analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966-March, 2011) and the China Biological Medicine Database (January, 1978-March, 2011) were searched using the keywords TNF-α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta-analysis. All fourteen studies focussed on an Asian population. The overall meta-analysis suggested that TNF-α-857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71-0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy-Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68-0.98, P = 0.043; OR = 0.77, 95% CI: 0.68-0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70-0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF-α-857T allele reduces the risk of chronic HBV infection in this Asian population.
Assuntos
Resistência à Doença , Predisposição Genética para Doença , Hepatite B Crônica/genética , Fator de Necrose Tumoral alfa/genética , Povo Asiático , Estudos de Casos e Controles , Frequência do Gene , Hepatite B Crônica/imunologia , Humanos , Polimorfismo Genético , Fator de Necrose Tumoral alfa/imunologiaRESUMO
We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S-ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4(IL-4). The DCs were transfected the novel construct, and the impact of the expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S-ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA-DR) and proinflammatory cytokines (IL-12). The DCs modified with HBV S-ecdCD40L are able to stimulate enhanced allogeneic T-cell proliferation in vitro. Thus, the fusion gene HBV S-ecdCD40L can promote DC's activation and enhance its function and may prove to be the foundation for a new type of hepatitis B vaccine.