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1.
Front Public Health ; 9: 637529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816422

RESUMO

This systematic review and meta-analysis aimed to evaluate the association between serum vitamin D concentration and the risk of urinary tract infection (UTI) in children. Human studies reported the serum vitamin D level in children with UTI and healthy controls were collected from PubMed, Scopus, Embase, and Cochrane databases. The strictly standardized mean difference (SSMD) and 95% confidence interval (CI) were calculated to evaluate the relationship between serum vitamin D levels and risk of UTI. The results of analysis showed that serum vitamin D levels in children with UTI were significantly lower than healthy control children (SSMD: 0.891, 95% CI: 0.707-1.075, p < 0.000; SSMD: 0.797, 95% CI: 0.500-1.094, p < 0.000, respectively). It can be concluded that there is a significant negative relationship between serum vitamin D level and risk of UTI in children.

2.
Nat Commun ; 12(1): 1275, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627666

RESUMO

Synthetic lethality is emerging as an important cancer therapeutic paradigm, while the comprehensive selective treatment opportunities for various tumors have not yet been explored. We develop the Synthetic Lethality Knowledge Graph (SLKG), presenting the tumor therapy landscape of synthetic lethality (SL) and synthetic dosage lethality (SDL). SLKG integrates the large-scale entity of different tumors, drugs and drug targets by exploring a comprehensive set of SL and SDL pairs. The overall therapy landscape is prioritized to identify the best repurposable drug candidates and drug combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, an FDA-approved multiple sclerosis treatment drug, is selected and identified as a repurposable drug for treating melanoma with CDKN2A mutation by in vitro validation, serving as a demonstrating SLKG utility example for novel tumor therapy discovery. Collectively, SLKG forms the computational basis to uncover cancer-specific susceptibilities and therapy strategies based on the principle of synthetic lethality.


Assuntos
Mutações Sintéticas Letais/genética , Linhagem Celular Tumoral , Cladribina/uso terapêutico , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Modelos Teóricos , Mutação/genética
3.
Gene ; 764: 145105, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32882333

RESUMO

Sarcoma (SARC) represents a group of highly histological and molecular heterogeneous rare malignant tumors with poor prognosis. There are few proposed classifiers for predicting patient's outcome. The Cancer Proteome Atlas (TPCA) and The Cancer Genome Atlas (TCGA) databases provide multi-omics datasets that enable a comprehensive investigation for this disease. The proteomic expression profile of SARC patients along with the clinical information was downloaded. 55 proteins were found to be associated with overall survival (OS) of patients using univariate Cox regression analysis. We developed a prognostic risk signature that comprises seven proteins (AMPKALPHA, CHK1, S6, ARID1A, RBM15, ACETYLATUBULINLYS40, and MSH6) with robust predictive performance using multivariate Cox stepwise regression analysis. Additionally, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters. Patients in high-risk group also have worse progression free intervals (PFI) than that of patients in low-risk group, but not for disease free intervals (DFI). The signature was validated using transcriptomic profile of SARC patients from TCGA. Potential mechanisms between high- and low-risk groups were identified using differentially expressed genes (DEGs) analysis. These DEGs were primarily enriched in RAS and MPAK signaling pathways. The signature protein molecules are candidate biomarkers for SARC, and the analysis of computational biology in tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinctly immune landscapes of high- and low-risk patients. Together, we constructed a prognostic signature for predicting outcomes for SARC integrating proteomic and transcriptomic profiles, this might have value in guiding clinical practice.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Testes Genéticos/métodos , Sarcoma/mortalidade , Microambiente Tumoral/imunologia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Mapeamento de Interação de Proteínas , Proteômica , Curva ROC , Sarcoma/tratamento farmacológico , Sarcoma/genética , Sarcoma/imunologia , Transcriptoma/genética , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
4.
J Rheumatol ; 47(11): 1725-1726, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33139524
5.
Front Genet ; 11: 978, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005178

RESUMO

Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. "Cytokine-cytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.

6.
Genome Med ; 11(1): 67, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666118

RESUMO

BACKGROUND: Cancer neoantigens are expressed only in cancer cells and presented on the tumor cell surface in complex with major histocompatibility complex (MHC) class I proteins for recognition by cytotoxic T cells. Accurate and rapid identification of neoantigens play a pivotal role in cancer immunotherapy. Although several in silico tools for neoantigen prediction have been presented, limitations of these tools exist. RESULTS: We developed pTuneos, a computational pipeline for prioritizing tumor neoantigens from next-generation sequencing data. We tested the performance of pTuneos on the melanoma cancer vaccine cohort data and tumor-infiltrating lymphocyte (TIL)-recognized neopeptide data. pTuneos is able to predict the MHC presentation and T cell recognition ability of the candidate neoantigens, and the actual immunogenicity of single-nucleotide variant (SNV)-based neopeptides considering their natural processing and presentation, surpassing the existing tools with a comprehensive and quantitative benchmark of their neoantigen prioritization performance and running time. pTuneos was further tested on The Cancer Genome Atlas (TCGA) cohort data as well as the melanoma and non-small cell lung cancer (NSCLC) cohort data undergoing checkpoint blockade immunotherapy. The overall neoantigen immunogenicity score proposed by pTuneos is demonstrated to be a powerful and pan-cancer marker for survival prediction compared to traditional well-established biomarkers. CONCLUSIONS: In summary, pTuneos provides the state-of-the-art one-stop and user-friendly solution for prioritizing SNV-based candidate neoepitopes, which could help to advance research on next-generation cancer immunotherapies and personalized cancer vaccines. pTuneos is available at https://github.com/bm2-lab/pTuneos , with a Docker version for quick deployment at https://cloud.docker.com/u/bm2lab/repository/docker/bm2lab/ptuneos .


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/imunologia , Melanoma/imunologia , Software , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/genética , Vacinas Anticâncer/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Coortes , Genoma , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Linfócitos T Citotóxicos
7.
Aging (Albany NY) ; 11(22): 10557-10580, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740623

RESUMO

The tumor microenvironment (TME) has a strong influence on the progression, therapeutic response, and clinical outcome of acute myeloid leukemia (AML), one of the most common hematopoietic malignancies in adults. In this study, we identified TME-related genes associated with AML prognosis. Gene expression profiles from AML patients were downloaded from TCGA database, and immune and stromal scores were calculated using the ESTIMATE algorithm. Immune scores were correlated with clinical features such as FAB subtypes and patient's age. After categorizing AML cases into high and low score groups, an association between several differentially expressed genes (DEGs) and overall survival was identified. Functional enrichment analysis of the DEGs showed that they were primarily enriched in the immune response, inflammatory response, and cytokine activity, and were involved in signaling processes related to hematopoietic cell lineage, B cell receptor, and chemokine pathways. Two significant modules, dominated respectively by CCR5 and ITGAM nodes, were identified from the PPI network, and 20 hub genes were extracted. A total of 112 DEGs correlated with poor overall survival of AML patients, and 11 of those genes were validated in a separate TARGET-AML cohort. By identifying TME-associated genes, our findings may lead to improved prognoses and therapies for AML.


Assuntos
Leucemia Mieloide Aguda/genética , Microambiente Tumoral/genética , Humanos , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Transcriptoma
8.
Plant Physiol Biochem ; 70: 354-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23816928

RESUMO

Drought stress can severely affect plant growth and substantially diminish crop yields. We previously isolated Arachis hypogaea NAC3 (AhNAC3), a dehydration-induced NAM/ATAF/CUC (NAC) gene from peanut. In this study, to examine the role of AhNAC3 in stress tolerance, we constructed transgenic tobacco lines overexpressing AhNAC3. The transgenic plants showed hyper-resistance to dehydration and drought stresses and accumulated more proline and less superoxide anion (O2(-)) than wild type under dehydration and drought conditions. Moreover, the transgenic plants showed upregulation of four functional genes, superoxide dismutase (SOD), pyrroline-5-carboxylate synthetase (P5SC), late embryogenic abundant proteins (LEA), and early response to drought 10 (ERD10C). Protein localization and transactivation analysis suggested that AhNAC3 activates its specific targets in the nucleus. These results suggest that AhNAC3 is a dehydration-induced transcription factor that improves water stress tolerance by increasing superoxide scavenging and promoting the accumulation of various protective molecules.


Assuntos
Adaptação Fisiológica/genética , Arachis/genética , Secas , Proteínas de Plantas/metabolismo , Superóxidos/metabolismo , Tabaco/metabolismo , Fatores de Transcrição/metabolismo , Núcleo Celular , Desidratação/genética , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Prolina/genética , Prolina/metabolismo , Estresse Fisiológico/genética , Tabaco/genética , Fatores de Transcrição/genética , Regulação para Cima , Água
9.
Clin Chim Acta ; 412(23-24): 2046-51, 2011 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-21266169

RESUMO

BACKGROUND: ELISA and CMIA are commonly used for detection of HBsAg. However, few investigations have been performed to evaluate their value in clinical practice, especially when jointly used. A reasonable and economic HBsAg testing algorithm is in great need. METHODS: A total of 161,426 specimens in China were tested for 5 serum HBV markers with commonly used ELISA kits. 498 of these specimens were further tested for HBsAg by another ELISA kit, a CMIA kit and an HBsAg confirmatory assay. RESULTS: The sensitivities of the 2 ELISA kits were 76.21% and 88.42%, respectively. However, when using "gray-zones", the sensitivities were significantly improved to 97.43% and 96.43%. Furthermore, the combined use of the 2 ELISA kits and their "gray-zones" improved the sensitivity to 99.04%. Nevertheless, 2.91% of the samples with S/CO values below the lower "gray-zone" limits were reactive by the CMIA kit and then confirmed as HBsAg positive. However, 71.43% of the samples with HBsAg values within 0.05 and 0.10 IU/ml detected by the CMIA kit could not be confirmed. CONCLUSIONS: As a rational and economic strategy, combined use of "gray-zones" in ELISA and several different detection assays can significantly increase the efficiency of HBsAg detection.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/diagnóstico , Portador Sadio , Hepatite B/sangue , Humanos , Sensibilidade e Especificidade
10.
Zhongguo Zhong Yao Za Zhi ; 35(4): 485-8, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20450049

RESUMO

To study the anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1 and its related molecular mechanism which has not been elucidated. In the present study,we showed that curcumin inhibited proliferation of Sk-hep-1 cells in a dose-dependent manner through MTF assay. The effect of curcumin on apoptosis in Sk-hep-1 cells was investigated by DAPI staining and the various apoptosis was observed in hepatocarcinoma cell lines Sk-hep-1, HepG2 and Hep3B, but not in normal liver cell line Chang's liver with curcumin treatment. Cell cycle analysis results showed that curcumin treatment resulted in dramatic accumulation of Sk-hep-1 cells at the G0/G1 or G2/M phase. The effect of curcumin on the expression of anti-apoptosis genes (Survivin and BCl-xL) and drug resistance genes (DRG2 and MDR1) was studied by reverse transcription-polymerase chain reaction (RT-PCR). The expression of MDR1 mRNA was significantly decreased in Sk-hep-1 cells treated with curcumin, while no alterations in the amount of DRG2 and anti-apoptosis genes' mRNA levels were found. These results indicate that curcumin is able to inhibit proliferation and induce apoptosis in Sk-hep-1 cells and it may cause by down-regulating the expression of MDR1 mRNA.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/fisiopatologia , Curcumina/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos
11.
Biosci Biotechnol Biochem ; 73(9): 2103-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19734653

RESUMO

We cloned the promoter of the 9-cis-epoxycarotenoid dioxygenase gene from Arachis hypogaea L. beta-Glucuronidase (GUS) histochemical staining and GUS activity assay indicated that the activity of the promoter was exhibited predominantly in the leaves and enhanced by water and NaCl stresses, and by application of abscisic acid (ABA) and salicylic acid (SA) in transgenic Arabidopsis. Moreover, two novel ABRE-like (abscisic acid response element) elements were identified in the promoter region.


Assuntos
Arachis/enzimologia , Oxigenases/genética , Regiões Promotoras Genéticas , Sequência de Bases , Clonagem Molecular , Primers do DNA , DNA de Plantas , Dioxigenases , Glucuronidase/genética , Dados de Sequência Molecular , Proteínas de Plantas , Reação em Cadeia da Polimerase
12.
Yao Xue Xue Bao ; 44(12): 1434-9, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21351482

RESUMO

The effect of curcumin on JAK-STAT signaling pathway was investigated in hepatoma cell lines Huh7 and Hep3B. Curcumin inhibited cell proliferation and induced apoptosis of both cell lines, but Huh7 cells were more sensitive to curcumin than Hep3B cells. Curcumin (50 micromol x L(-1)) significantly increased phosphorylations of p38 (T180/Y182) and STAT-1 (S727) in Huh7 and Hep3B cells, and caused relocalization of phosphorylated-STAT-1 (Y701) from cytoplasm to nucleus in Hep3B cells. In addition, curcumin (25 and 50 micromol x L(-1)) dramatically suppressed the phosphorylation level of STAT-1 (Y701) and resulted in a significant reduction of nuclear phosphorylated-STAT-1 (Y701) in Huh7 cells.


Assuntos
Carcinoma Hepatocelular/patologia , Curcumina/farmacologia , Janus Quinases/metabolismo , Neoplasias Hepáticas/patologia , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Curcuma/química , Curcumina/isolamento & purificação , Humanos , Neoplasias Hepáticas/metabolismo , Fosforilação , Plantas Medicinais/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Yao Xue Xue Bao ; 44(10): 1102-6, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20055131

RESUMO

In the present study, shRNA plasmid of pSi-p21 targeting p21 mRNA was constructed and the effect of p21 shRNA on curcumin-induced apoptosis of human hepatoma Huh7 cells was investigated. The effect of curcumin on the expression of p21 mRNA and protein and the silence efficiency of pSi-p21 were detected with RT-PCR and Western blotting. The effect of pSi-p21 on curcumin-induced apoptosis of Huh7 cells was evaluated with DAPI staining. The results showed that curcumin significantly upregulated p21 mRNA and protein expression, which was knocked down by pSi-p21 of Huh7 cells. DAPI staining results showed that pSi-p21 significantly decreased curcumin-induced apoptosis of Huh7 cells. The data suggested that curcumin induced apoptosis of Huh7 cells via upregulation of p21 expression.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Curcumina/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Hepáticas/patologia , RNA Interferente Pequeno/genética , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Plasmídeos , RNA Mensageiro/metabolismo , Transfecção , Regulação para Cima
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