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1.
In Vitro Cell Dev Biol Anim ; 56(2): 120-128, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31942725

RESUMO

Growing evidence suggests the crucial role of microRNAs (miRNAs) in regulating basic cell functions, and therefore participating in the pathologic development of diverse human diseases, including cardiac hypertrophy. Herein, we explained that miR-4458 was distinctly stimulated in Ang II-stimulated hypertrophic H9c2 cells. Intriguingly, miR-4458 inhibition led to exacerbated hypertrophic phenotypes in Ang II-treated H9c2 cells. In addition, the compensatory upregulation of miR-4458 in Ang II-treated H9c2 cells was ascribed to its transcriptional enhancement by NRF1, a transcription factor previously identified to be activated in early cardiac hypertrophy. Moreover, we discovered that miR-4458 served as a negative modulator in cardiac hypertrophy by prompting TFAM, a well-recognized myocardial protective protein. TTP, a RBP that always leads to degradation of recognized mRNAs, was predicted to interact with both miR-4458 and TFAM mRNA. Importantly, we verified that miR-4458 facilitated TFAM expression in cardiomyocytes by directly targeting TTP and releasing TTP-destabilized TFAM mRNA. On the whole, these findings demonstrated that NRF1-induced miR-4458 boosted TFAM via targeting TTP to dampen the exacerbation of cardiac hypertrophy, which indicates miR-4458 as a promising biomarker for the cardiac hypertrophy treatment.

2.
Cancer Med ; 9(5): 1790-1797, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918459

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and is a clinical, pathological, and molecular heterogeneous disease with highly variable clinical outcomes. Currently, valid prognostic biomarkers in DLBCL are still lacking. To optimize targeted therapy and improve the prognosis of DLBCL, the performance of proposed biomarkers needs to be evaluated in multiple cohorts, and new biomarkers need to be investigated in large datasets. Here, we developed a consensus Online Survival analysis web server for Diffuse Large B-Cell Lymphoma, abbreviated OSdlbcl, to assess the prognostic value of individual gene. To build OSdlbcl, we collected 1100 samples with gene expression profiles and clinical follow-up information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, DNA mutation data were also collected from the TCGA database. Overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) are important endpoints to reflect the survival rate in OSdlbcl. Moreover, clinical features were integrated into OSdlbcl to allow data stratifications according to the user's special needs. By inputting an official gene symbol and selecting desired criteria, the survival analysis results can be graphically presented by the Kaplan-Meier (KM) plot with hazard ratio (HR) and log-rank p value. As a proof-of-concept demonstration, the prognostic value of 23 previously reported survival associated biomarkers, such as transcription factors FOXP1 and BCL2, was evaluated in OSdlbcl and found to be significantly associated with survival as reported (HR = 1.73, P < .01; HR = 1.47, P = .03, respectively). In conclusion, OSdlbcl is a new web server that integrates public gene expression, gene mutation data, and clinical follow-up information to provide prognosis evaluations for biomarker development for DLBCL. The OSdlbcl web server is available at https://bioinfo.henu.edu.cn/DLBCL/DLBCLList.jsp.

3.
Mol Carcinog ; 59(3): 304-310, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31912599

RESUMO

Pancreatic carcinoma (PC) is a type of highly lethal malignant tumor that has unfavorable outcomes. One major challenge in improving clinical outcomes is to identify novel biomarkers for prognosis. In this study, we developed an online consensus survival tool for pancreatic adenocarcinoma (OSpaad), which allows researchers and clinicians to analyze the prognostic value of selected genes in PC. OSpaad contains 1319 unique PC cases that have both gene expression data and correspondent clinical data from seven individual cohorts and provides four survival terms including overall survival, disease-specific survival, disease-free interval, progression-free interval for prognosis evaluation. To meet the different research needs, OSpaad allows users to limit survival analysis in subgroups by selecting different terms of clinical confounding factors such as TNM stage, sex, smoking time, lymph invasion, and race. Moreover, we showed that 97% (116 out of 120) previously reported prognostic biomarkers, including ERBB2, TP53, EGFR and so forth, were validated and confirmed their prognostic significance in OSpaad, demonstrating the well performance of survival analysis in OSpaad. OSpaad is a user-friendly online tool with a straightforward interface allowing clinicians and basic research scientists with even a limited bioinformatics background to easily screen and evaluate the prognostic value of genes in a large PC cohort. This online tool can be accessed at http://bioinfo.henu.edu.cn/PAAD/PAADList.jsp.


Assuntos
Neoplasias Pancreáticas/diagnóstico , Software , Biomarcadores Tumorais/análise , Seguimentos , Perfilação da Expressão Gênica , Humanos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Prognóstico , Análise de Sobrevida
4.
Mol Carcinog ; 59(1): 56-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31646691

RESUMO

Uveal melanoma (UM) is a rare, aggressive, but the most frequent primary intraocular malignancy in adults, and up to 50% of patients develop a tendency of liver metastases. Great efforts have been made to develop biomarkers that facilitate diagnosis, prediction of the risk, and response to treatment of UM. However, a biologically informative and highly accurate gold standard system for prognostic evaluation of UM remains to be established. To facilitate assessment of the prognosis of UM patients, we established a user-friendly Online consensus Survival tool for uveal melanoma, named OSuvm, by which users can easily estimate the prognostic values of genes of interest by the Kaplan-Meier survival plot with hazard ratio and log-rank test. OSuvm comprises four independent cohorts including 229 patients with both gene expression profiles and relevant clinical follow-up information, and it has shown great performance in evaluating the prognostic roles of previously reported biomarkers. Using OSuvm enables researchers and clinicians to rapidly and conveniently explore the prognostic value of genes of interest and develop new potential molecular biomarkers for UM. OSuvm can be accessed at http://bioinfo.henu.edu.cn/UVM/UVMList.jsp.


Assuntos
Melanoma/diagnóstico , Neoplasias Uveais/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Internet , Estimativa de Kaplan-Meier , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Prognóstico , Software , Transcriptoma , Neoplasias Uveais/genética
5.
J Cardiovasc Pharmacol ; 74(5): 474-481, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725080

RESUMO

Myocardial infarction (MI) is one of cardiovascular diseases with high incidence and mortality. MicroRNAs, as posttranscriptional regulators of genes, are involved in many diseases, including cardiovascular diseases. The aim of the present study was to determine whether miR-203 was functional in MI therapy and how it worked. Left anterior descending artery ligation and hypoxia/reoxygenation (H/R) treatment were, respectively, performed to obtain MI rats and hypoxia-injured H9c2 cells. Western blot and quantitative real-time polymerase chain reaction were used to determine protein levels and messenger RNA of relevant genes, respectively. Lentivirus-mediated overexpression of miR-203 was performed to study the miR-203 functions on left ventricular remodeling, infarct size, and cardiomyocyte apoptosis. Compared with the sham group, miR-203 levels were significantly decreased in MI and H/R groups. However, overexpressing miR-203 greatly improved the cardiac function, reduced infarct size in rats after MI and weakened infarction-induced apoptosis by increasing Bcl-2 and reducing decreasing Bax, cleaved caspase-3, and cleaved caspase-9. In addition, Protein tyrosine phosphatase 1B (PTP1B) was proved as a target of miR-203 in cardiomyocytes, and it was negatively regulated by miR-203. Further experiments indicated that PTP1B overexpression could remarkably inhibit miR-203-mediated antiapoptosis of cardiomyocytes and alleviate protective effects of miR-203 on mitochondria after H/R treatment. Altogether, miR-203 prevented infarction-induced apoptosis by regulating PTP1B, including reducing proapoptosis proteins, inactivating caspase pathway, and protecting mitochondria. In conclusion, miR-203 had abilities to alleviate MI-caused injury on myocardium tissues and reduce mitochondria-mediated apoptosis, which might be a potential target used for MI therapy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31425379

RESUMO

Myocardial infarction (MI) is one of cardiovascular diseases with high incidence and mortality. MicroRNAs (miRNAs), as post-transcriptional regulators of genes, are involved in many diseases, including cardiovascular diseases. The aim of present study was to determine whether miR-203 was functional in MI therapy and how it worked. Left anterior descending artery ligation and hypoxia/reoxygenation (H/R) treatment were respectively performed to obtain MI rats and hypoxia-injured H9c2 cells. Western blot and qRT-PCR were used to determine protein levels and mRNA of relevant genes, respectively. Lentivirus-mediated over-expression of miR-203 was performed to study the miR-203 functions on left ventricular remodeling, infarct size and cardiomyocyte apoptosis. Compared with the sham group, miR-203 levels were significantly decreased in MI and H/R groups. However, over-expressing miR-203 greatly improved the cardiac function, reduced infarct size in rats after MI, as well as weakened infarction-induced apoptosis by increasing Bcl-2 and reducing decreasing Bax, cleaved caspase-3 and cleaved caspase-9. In addition, PTP1B was proved as a target of miR-203 in cardiomyocytes, and it was negatively regulated by miR-203. Further experiments indicated that PTP1B over-expression could remarkably inhibit miR-203-mediated anti-apoptosis of cardiomyocytes, and alleviate protective effects of miR-203 on mitochondria after H/R treatment. Altogether, miR-203 prevented infarction-induced apoptosis by regulating PTP1B, including reducing pro-apoptosis proteins, inactivating caspase pathway and protecting mitochondria. In conclusion, miR-203 had abilities to alleviate MI-caused injury on myocardium tissues and reduce mitochondria-mediated apoptosis, which might be a potential target used for MI therapy.

7.
Medicine (Baltimore) ; 98(32): e16462, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393350

RESUMO

The outcome of patients with acute type B aortic dissection (BAAD) is largely dictated by whether or not the case is "complicated." The purpose of this study was to investigate the risk factors leading to in-hospital death among patients with BAAD and then to develop a predictive model to estimate individual risk of in-hospital death.A total of 188 patients with BAAD were enrolled. Risk factors for in-hospital death were investigated with univariate and multivariable logistic regression analysis. Significant risk factors were used to develop a predictive model.The in-hospital mortality rate was 9% (17 of 188 patients). Univariate analysis revealed 7 risk factors to be statistically significant predictors of in-hospital death (P < .1). In multivariable analysis, the following variables at admission were independently associated with increased in-hospital mortality: hypotension (odds ratio [OR], 4.85; 95% confidence interval [CI], 1.12-18.90; P = .04), ischemic complications (OR, 8.24; 95% CI, 1.25-33.85; P < .001), renal dysfunction (OR, 12.32; 95% CI, 10.63-76.66; P < .001), and neutrophil percentage ≥80% (OR, 5.76; 95% CI, 2.58-12.56; P = .03). Based on these multivariable results, a reliable and simple prediction model was developed, a total score of 4 offered the best point value.Independent risk factors associated with in-hospital death can be predicted in BAAD patients. The prediction model could be used to identify the prognosis for BAAD patients and assist physicians in their choice of management.


Assuntos
Aneurisma Dissecante/mortalidade , Aneurisma da Aorta Torácica/mortalidade , Mortalidade Hospitalar , Adulto , Idoso , Aneurisma Dissecante/classificação , Aneurisma Dissecante/terapia , Aneurisma da Aorta Torácica/classificação , Aneurisma da Aorta Torácica/terapia , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Razão de Chances , Fatores de Risco
8.
Front Oncol ; 9: 466, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275847

RESUMO

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. The discovery of prognostic biomarkers is still one of the major challenges to improve clinical treatment of BC patients. In order to assist biologists and clinicians in easily evaluating the prognostic potency of genes in BC patients, we developed a user-friendly Online consensus Survival tool for bladder cancer (OSblca), to analyze the prognostic value of genes. The OSblca includes gene expression profiles of 1,075 BC patients and their respective clinical follow-up information. The clinical follow-up data include overall survival (OS), disease specific survival (DSS), disease free interval (DFI), and progression free interval (PFI). To analyze the prognostic value of a gene, users only need to input the official gene symbol and then click the "Kaplan-Meier plot" button, and Kaplan-Meier curve with the hazard ratio, 95% confidence intervals and log-rank P-value are generated and graphically displayed on the website using default options. For advanced analysis, users could limit their analysis by confounding factors including data source, survival type, TNM stage, histological type, smoking history, gender, lymph invasion, and race, which are set up as optional parameters to meet the specific needs of different researchers. To test the performance of the web server, we have tested and validated its reliability using previously reported prognostic biomarkers, including KPNA2, TP53, and MYC etc., which had their prognostic values validated as reported in OSblca. In conclusion, OSblca is a useful tool to evaluate and discover novel prognostic biomarkers in BC. The web server can be accessed at http://bioinfo.henu.edu.cn/BLCA/BLCAList.jsp.

9.
Ecotoxicol Environ Saf ; 179: 249-256, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054378

RESUMO

The functional role of 1,25-vitamin D3 in cooking oil fumes (COFs)-derived PM2.5-induced cell damage is largely unexplored. The present study investigated the protective role of 1,25-vitamin D3 against cell injury by possible involvement of JAK/STAT and NF-κB signaling pathways in cardiomyocytes. Cell viability was measured using CCK-8 assay, and cell apoptosis was analyzed by flow cytometry, qRT-PCR and Western blot in cultured rat neonatal cardiomyocytes treated with 1,25-vitamin D3 and COFs-derived PM2.5. Expressions of JAK/STAT and NF-κB signaling pathway were measured by Western blot. The results suggested that treatment with COFs-derived PM2.5 significantly decreased cell viability and increased apoptosis and oxidative stress in cultured rat neonatal cardiomyocytes. 1,25-vitamin D3 pretreatment alleviated the cell injury by increasing cell viability and decreasing apoptosis in the cardiomyocytes. 1,25-vitamin D3 pretreatment also decreased the ROS level and inflammation in the cardiomyocytes. Furthermore, 1,25-vitamin D3 pretreatment alleviated COFs-derived PM2.5-evoked elevation of JAK/STAT and NF-κB signaling pathways. Our study showed that 1,25-vitamin D3 pretreatment protected cardiomyocytes from COFs-derived PM2.5-induced injury by decreasing ROS, apoptosis and inflammation level via activations of the JAK/STAT and NF-κB signaling pathways.


Assuntos
Poluentes Atmosféricos/toxicidade , Anti-Inflamatórios/farmacologia , Colecalciferol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Culinária/métodos , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos , Transdução de Sinais/efeitos dos fármacos
10.
Environ Sci Pollut Res Int ; 23(1): 793-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26341332

RESUMO

The water quality improvement of landfill leachate after sequencing batch reactor (SBR) activated sludge process were evaluated by chemical oxygen demand (COD), dissolved organic matter (DOM) fractions, and three-dimensional excitation-emission matrix (EEM), from which the new understanding was obtained. The results indicated that less than 14% COD was removed by SBR. The EEM of leachate and SBR effluent showed that HPO-A and TPI-A were appeared in the peak C, while the HPI, HPO-N, and TPI-N could not be found due to dilution. Although humic acid appeared in peak C, not all the organic materials in peak C are humic acid. And because landfill leachate is a kind of complicated wastewater, therefore, only EEM cannot efficiently reflect the water quality.


Assuntos
Recuperação e Remediação Ambiental , Poluentes Químicos da Água , Qualidade da Água , Análise da Demanda Biológica de Oxigênio , Substâncias Húmicas/análise , Esgotos , Espectrometria de Fluorescência , Poluentes Químicos da Água/análise
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