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1.
J Oncol ; 2022: 9039110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276273

RESUMO

Retinoid-binding protein7 (RBP7) is a member of the cellular retinol-binding protein (CRBP) family, which is involved in the pathogenesis of breast cancer. The study aims to illustrate the prognostic value and the potential regulatory mechanisms of RBP7 expression in breast cancer. Bioinformatics analysis with the TCGA and CPTAC databases revealed that the mRNA and protein expression levels of RBP7 in normal were higher compared to breast cancer tissues. Survival analysis displayed that the lower expression of RBP7, the worse the prognosis in ER-positive (ER+) breast cancer patients. Genomic analysis showed that low expression of RBP7 correlates with its promoter hypermethylation in breast cancer. Functional enrichment analysis demonstrated that downregulation of RBP7 expression may exert its biological influence on breast cancer through the PPAR pathway and the PI3K/AKT pathway. In summary, we identified RBP7 as a novel biomarker that is helpful for the prognosis of ER+ breast cancer patients. Promoter methylation of RBP7 is involved in its gene silencing in breast cancer, thus regulating the occurrence and development of ER+ breast cancer through the PPAR and PI3K/AKT pathways.

2.
Dermatology ; : 1-12, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35843211

RESUMO

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS)/acne inversa is an intractable skin disease that is characterized by destructive lesions - primarily on the flexural areas. Although its etiology is unknown, genetics is considered to be a factor of its pathology - mutations in γ-secretase genes have been identified in certain familial HS patients, and follicular occlusion is widely accepted as the primary cause of HS. But, no relationship between these mutations and the components of hair follicles has been reported. Thus, we examined changes in these components in mice with a mutation in NCSTN (a γ-secretase gene). METHODS: We generated C57BL/6 mice with an NCSTN mutation and examined their expression of hair cortex cytokeratin and trichohyalin by Western blot and immunohistochemistry, in addition to nicastrin, the product of NCSTN, and NICD compared with wild-type mice. The structure of hair follicles was analyzed by hematoxylin-eosin staining and transmission electron microscopy. RESULTS: In mice with an NCSTN mutation, HS-like skin lesions appeared after age 6 months, the pathological manifestations of which were consistent with the features of human HS. The structure of hair follicles was abnormal in mice with an NCSTN mutation versus wild-type mice, and hair cortex cytokeratin, trichohyalin, nicastrin, and NICD were downregulated in these mice. CONCLUSIONS: This NCSTN mutant mouse model could be an improved model to study early lesion development aspects of human HS pathogenesis and could perhaps be a better alternative for evaluating early-acting and preventive therapeutics for HS experimentally before clinical trials in HS patients. NCSTN mutations disrupt the development of hair follicles, leading to abnormal hair follicle structures, perhaps resulting in the onset of HS.

3.
Biosci Rep ; 41(12)2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34821362

RESUMO

Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelial-mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were up-regulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Onco Targets Ther ; 14: 785-793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33574674

RESUMO

PURPOSE: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited. METHODS: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial-mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC. RESULTS: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3-14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%. CONCLUSION: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.

6.
J Exp Clin Cancer Res ; 40(1): 287, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517880

RESUMO

BACKGROUND: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown. METHODS: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo. RESULTS: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells. CONCLUSION: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients.


Assuntos
Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Transportador de Glucose Tipo 1/biossíntese , Glicólise/genética , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Gli3 com Dedos de Zinco/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Prognóstico , Proteína Gli3 com Dedos de Zinco/genética
7.
Cad Saude Publica ; 36(11): e00123719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237201

RESUMO

This study aimed to illustrate the impact of injury-related deaths on life expectancy in China in 2016 and to identify the high-risk population. Standard life tables were used to calculate life expectancy and cause-eliminated life expectancy by utilizing mortality data from the national mortality surveillance system. In 2016, the life expectancy of Chinese residents was 78.91 years. After eliminating injury-related mortality, the life expectancy of the residents increased by 1.13 years, which was higher in male and rural residents compared with female and urban residents. The life expectancy on the Eastern and Central regions increased slowly compared with the Western region. The greatest influencing factor on life expectancy was road traffic injuries, followed by falls. Falls had a greater impact on life expectancy for children under 5 years old and those aged over 65 years. This study indicates that deaths caused by injury had a noteworthy impact on life expectancy in China. More attention should be paid to road traffic injuries, and effective preventive measures should be taken to reduce deaths related to injury to increase the life expectancy of residents, especially in children under 5 years and adults over 65 years. By reducing the deaths caused by injury, the life expectancy level is likely to further improve.


Assuntos
Expectativa de Vida , População Rural , Adulto , Idoso , Brasil , Causas de Morte , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Tábuas de Vida , Masculino
8.
Mol Genet Genomics ; 295(2): 439-451, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31813042

RESUMO

Stroke is a complex disease with multiple etiologies. Numerous studies suggest an established association between obesity and stroke, which may partly arise from the shared genetic components between the two phenotypes. Despite genome-wide association studies (GWASs) have identified some loci associated with stroke and obesity individually, the estimated genetic variability explained by these loci is limited (especially for stroke) and the pleiotropic loci between them are largely unknown. In this study, we jointly applied the pleiotropy-informed conditional false discovery rate (cFDR) method and the genetic analysis incorporating pleiotropy and annotation (GPA) method on summary statistics of two large GWASs to detect the genetic overlap between stroke (n = 446,696) and obesity (n = 681,275). Stratified Q-Q and fold-enrichment plots showed strong pleiotropic enrichment between the two phenotypes. With cFDR < 0.05 and fdr.GPA < 0.2, we identified 24 (16 novel) stroke-associated SNPs and 12 (10 novel) of them to be potentially pleiotropic SNPs for both phenotypes. The corresponding genes were enriched in trait-associated gene ontology (GO) terms "brain development" and "negative regulation of transport". In conclusion, our study demonstrated the feasibility and effectivity of the two pleiotropic methods which successfully improved the genetic discovery by incorporating related GWAS datasets and validated the genetic intercommunity between stroke and obesity. The identification of pleiotropic loci may provide us any new insights into potential genetic and etiology mechanism between them for the further studies.


Assuntos
Pleiotropia Genética/genética , Predisposição Genética para Doença , Obesidade/genética , Acidente Vascular Cerebral/genética , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Redes Reguladoras de Genes/genética , Estudo de Associação Genômica Ampla , Humanos , Obesidade/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/patologia
9.
Cad. Saúde Pública (Online) ; 36(11): e00123719, 2020. tab, graf
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: biblio-1132843

RESUMO

Abstract: This study aimed to illustrate the impact of injury-related deaths on life expectancy in China in 2016 and to identify the high-risk population. Standard life tables were used to calculate life expectancy and cause-eliminated life expectancy by utilizing mortality data from the national mortality surveillance system. In 2016, the life expectancy of Chinese residents was 78.91 years. After eliminating injury-related mortality, the life expectancy of the residents increased by 1.13 years, which was higher in male and rural residents compared with female and urban residents. The life expectancy on the Eastern and Central regions increased slowly compared with the Western region. The greatest influencing factor on life expectancy was road traffic injuries, followed by falls. Falls had a greater impact on life expectancy for children under 5 years old and those aged over 65 years. This study indicates that deaths caused by injury had a noteworthy impact on life expectancy in China. More attention should be paid to road traffic injuries, and effective preventive measures should be taken to reduce deaths related to injury to increase the life expectancy of residents, especially in children under 5 years and adults over 65 years. By reducing the deaths caused by injury, the life expectancy level is likely to further improve.


Resumo: O estudo teve como objetivos analisar o impacto dos óbitos por causas externas na expectativa de vida na China em 2016 e identificar a população de risco. Foram utilizadas tábuas de mortalidade padronizadas para calcular a expectativa de vida e a expectativa de vida depois de eliminar as causas externas, com base nos dados de mortalidade do Sistema Nacional de Vigilância da Mortalidade. Em 2016, a expectativa de vida dos chineses era 78,91 anos. Depois de eliminar a mortalidade por causas externas, a expectativa de vida dos chineses aumentou em 1,13 anos, e o aumento foi maior nos homens e nos moradores da área rural, comparados às mulheres e aos moradores da área urbana. A expectativa de vida das regiões Leste e Central aumentou mais lentamente do que na região Oeste do país. Os acidentes de trânsito foram o fator de maior impacto sobre a expectativa de vida, seguidos de quedas. As quedas tiveram um impacto maior sobre a expectativa de vida nas crianças abaixo de 5 anos e nos idosos acima de 65 anos de idade. O estudo indica que os óbitos por causas externas tiveram um impacto relevante na expectativa de vida na China. As lesões por acidentes de trânsito merecem mais atenção, e medidas efetivas devem ser tomadas para reduzir os óbitos por causas externas para aumentar a expectativa de vida na população chinesa, principalmente nas crianças abaixo de 5 anos e nos idosos acima de 65 anos. A redução dos óbitos por causas externas deverá melhorar mais ainda o nível de expectativa de vida.


Resumen: El objetivo de este estudio fue ilustrar el impacto de los fallecimientos relacionados con lesiones y la esperanza de vida en China en 2016, así como identificar a la población de alto riesgo. Las tablas de estándar de vida se utilizaron para calcular la esperanza de vida y la causa de la supresión de esperanza de vida se calculó utilizando datos de mortalidad del sistema de vigilancia de la mortalidad. En 2016, la esperanza de vida de los chinos residentes era 78,91 años. Tras eliminar la mortalidad relacionada con lesiones, la esperanza de vida de los residentes se incrementó en 1,13 años, que fue mayor en hombres, residentes en áreas rurales, comparada con las mujeres, residentes en áreas urbanas. La esperanza de vida en las regiones orientales y centrales se incrementó lentamente, comparada con la región occidental. El factor de mayor influencia en la esperanza de vida fue las lesiones en accidentes de tráfico, seguidas de las caídas. Las caídas tuvieron un impacto mayor en la esperanza de vida para los niños menores de 5 años, así como los ancianos con una edad por encima de los 65 años. Este estudio indica que las muertes causadas por lesiones tuvieron un impacto notorio en la esperanza de vida en China. Se debe prestar más atención a las lesiones por accidente de tráfico, y se deberían tomar medidas preventivas efectivas para reducir las muertes relacionadas con las lesiones para incrementar la esperanza de vida de los residentes, especialmente en niños menores de 5 años y personas mayores con más de 65 años. Si se reducen las muertes causadas por lesiones, cabe esperar que mejore el nivel de esperanza de vida.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adulto , Idoso , População Rural , Expectativa de Vida , Brasil , China/epidemiologia , Causas de Morte , Tábuas de Vida
10.
J Glob Health ; 9(2): 020601, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788232

RESUMO

BACKGROUND: Various hypertension predictive models have been developed worldwide; however, there is no existing predictive model for hypertension among Chinese rural populations. METHODS: This is a 6-year population-based prospective cohort in rural areas of China. Data was collected in 2007-2008 (baseline survey) and 2013-2014 (follow-up survey) from 8319 participants ranging in age from 35 to 74 years old. Specified gender hypertension predictive models were established based on multivariate Cox regression, Artificial Neural Network (ANN), Naive Bayes Classifier (NBC), and Classification and Regression Tree (CART) in the training set. External validation was conducted in the testing set. The estimated models were assessed by discrimination and calibration, respectively. RESULTS: During the follow-up period, 432 men and 604 women developed hypertension in the training set. Assessment for established models in men suggested men office-based model (M1) was better than others. C-index of M1 model in the testing set was 0.771 (95% confidence Interval (CI) = 0.750, 0.791), and calibration χ2 = 6.3057 (P = 0.7090). In women, women office-based model (W1) and ANN were better than the other models assessed. The C-indexes for the W1 model and the ANN model in the testing set were 0.765 (95% CI = 0.746, 0.783) and 0.756 (95% CI = 0.737, 0.775) and the calibrations χ2 were 6.7832 (P = 0.1478) and 4.7447 (P = 0.3145), respectively. CONCLUSIONS: Not all machine-learning models performed better than the traditional Cox regression models. The W1 and ANN models for women and M1 model for men have better predictive performance which could potentially be recommended for predicting hypertension risk among rural populations.


Assuntos
Hipertensão/epidemiologia , Modelos Estatísticos , População Rural/estatística & dados numéricos , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco
11.
Sci Rep ; 9(1): 10340, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316127

RESUMO

Plenty of genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and blood pressure (BP). However, these SNPs only explain a small proportion of the heritability of two traits/diseases. Although high BP is a major risk factor for CAD, the genetic intercommunity between them remain largely unknown. To recognize novel loci associated with CAD and BP, a genetic-pleiotropy-informed conditional false discovery rate (cFDR) method was applied on two summary statistics of CAD and BP from existing GWASs. Stratified Q-Q and fold enrichment plots showed a high pleiotropic enrichment of SNPs associated with two traits. Adopting a cFDR of 0.05 as a threshold, 55 CAD-associated loci (25 variants being novel) and 47 BP loci (18 variants being novel) were identified, 25 of which were pleiotropic loci (13 variants being novel) for both traits. Among the 32 genes these 25 SNPs were annotated to, 20 genes were newly detected compared to previous GWASs. This study showed the cFDR approach could improve gene discovery by incorporating GWAS datasets of two related traits. These findings may provide novel understanding of etiology relationships between CAD and BP.


Assuntos
Pressão Sanguínea/genética , Doença da Artéria Coronariana/genética , Pleiotropia Genética , Bioestatística , Estudos de Casos e Controles , Bases de Dados Genéticas/estatística & dados numéricos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único
12.
Kardiol Pol ; 75(9): 850-858, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28612911

RESUMO

BACKGROUND AND AIM: This study aimed to investigate the efficacy and safety of dual and triple antiplatelet therapy (DAPT and TAPT) in patients with diabetes and acute ST segment elevation myocardial infarction (D-STEMI), who had undergone primary percutaneous coronary intervention (PCI). METHODS: We designed a phase IV, single-centre, randomised, double-blind, placebo-controlled study. The D-STEMI patients (n = 258) were randomly divided into three groups. Control group A (85 patients), was treated with aspirin and clopidogrel; group B (87 patients) received aspirin, clopidogrel, and tirofiban; and group C (86 patients) were treated with aspirin, ticagrelor, and tirofiban. Patients in all three groups received oral DAPT, and patients in groups B and C received intravenous tirofiban when primary PCI was performed. RESULTS: Compared to the findings in group A, the post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow in groups B and C increased significantly (TIMI grade 3 in groups A, B, C: 74%, 91%, and 98%, respectively; TIMI myocardial perfusion grade [TMPG] grade 3 in groups A, B, C: 59%, 86%, and 97%, respectively), and the incidence of major adverse cardiac events (MACE) decreased significantly (p < 0.05). Compared to the findings in group B, the rate of TMPG 3 in group C was significantly higher (p < 0.05) and the incidence of MACE was significantly lower (p < 0.05). Patients in group B exhibited minor bleeding; however, the incidence of mild to moderate bleeding in group C increased significantly (p < 0.05). CONCLUSIONS: TAPT effectively improved the TIMI blood flow and TMPG and reduced the occurrence of MACE. Ticagrelor was more effective than clopidogrel in TAPT; however, when using the combination of aspirin, ticagrelor, and tirofiban, close monitoring is required for possible bleeding complications.


Assuntos
Cardiomiopatias Diabéticas , Segurança do Paciente , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Adenosina/efeitos adversos , Adenosina/análogos & derivados , Adenosina/farmacologia , Adenosina/uso terapêutico , Idoso , Aspirina/efeitos adversos , Aspirina/farmacologia , Aspirina/uso terapêutico , Clopidogrel , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Ticagrelor , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Tirofibana , Resultado do Tratamento , Tirosina/efeitos adversos , Tirosina/análogos & derivados , Tirosina/farmacologia , Tirosina/uso terapêutico
13.
Saudi J Biol Sci ; 24(3): 466-476, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28386169

RESUMO

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

14.
Saudi J Biol Sci ; 24(8): 1781-1786, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29551923

RESUMO

Objective: to establish regulatory network of colorectal cancer involving p42.3 protein and to provide theoretical evidence for deep functional exploration of p42.3 protein in the onset and development of colorectal cancer. Methods: with protein similarity algorithm, reference protein set of p42.3 cell apoptosis was built according to structural features of p42.3. GO and KEGG databases were used to establish regulatory network of tumor cell apoptosis involving p42.3; meanwhile, the largest possible working pathway that involves p42.3 protein was screened out based on Bayesian network theory. Besides, GO and KEGG were used to build regulatory network on early diagnosis gene markers for colorectal cancer including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, at the same time, a regulatory network of colorectal cancer cell apoptosis which involves p42.3 was established. Results: cell apoptotic regulatory network that p42.3 participates in primarily consists of Bcl-2 family genes and the largest possible pathway is p42.3 → FKBP → Bcl-2 centered as FKBP protein. Combined with colorectal cancer regulatory network that involves early diagnosis gene markers, it can be predicted that p42.3 is most likely to regulate the colorectal cancer cell apoptosis through FKBP → Bcl-2 → Bax → caspase-9 → caspase-3 pathway. Conclusion: the colorectal cancer apoptosis network based on p42.3 established in the study provides theoretical evidence for deep exploration of p42.3 regulatory mechanism and molecular targeting treatment of colorectal cancer.

15.
J Cancer Res Ther ; 12(2): 650-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27461626

RESUMO

AIMS: This purpose of the study was to optimize the regulatory mechanism of p42.3 novel protein molecule in gastric cancer and also verified it by the use of intelligent algorithms. SUBJECTS AND METHODS: Threading method was employed to analyze structural domain characteristics of p42.3 protein. Referential proteins were gathered and formed by domain homology and function similarity. Afterwards, the possible regulatory network of p42.3 was established by analyzing the acting pathways of the referential proteins. Spherical polar coordinates stratification and stratified multi-parameter weight were used for calculation of the similarity between the referential proteins and p42.3 protein, the result of which was taken as the prior probability of the initial node in Bayes network, thus the probability of occurrence of each pathway was figured out by using conditional probability formula, and the one with the biggest probability was considered as the possible pathway of p42.3. At last, molecular biological experiments were conducted to verify it. RESULTS: The acting pathway with the maximum probability predicted by Bayesian probability optimizing calculation was "S100A11" - RAGE - P38 - MAPK - Microtubule-associated protein - Spindle protein-Centromere protein - Cell proliferation" which was the most likely acting pathway participated by p42.3, and has been validated by biological experiments. CONCLUSIONS: By the theoretical analysis and experimental verification, this study confirmed that assumptions that p42.3 protein was related to the occurrence and development of gastric carcinoma, predicted and verified the acting pathways of p42.3, which will provide a new research direction of the relationship between p42.3 and gastric cancer, as well as the target therapy of gastric cancer. The algorithm in predicting the acting pathway of the protein also offers a new thought in studying new functional proteins.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Neoplasias Gástricas/etiologia , Algoritmos , Teorema de Bayes , Proteínas de Ciclo Celular/química , Fatores Quimiotáticos/análise , Humanos , Proteínas Nucleares , Domínios Proteicos , Proteínas S100/análise
17.
Comput Math Methods Med ; 2015: 683679, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26106439

RESUMO

AIMS: To optimize and verify the regulatory pathway of p42.3 in the pathogenesis of gastric carcinoma (GC) by intelligent algorithm. METHODS: Bioinformatics methods were used to analyze the features of structural domain in p42.3 protein. Proteins with the same domains and similar functions to p42.3 were screened out for reference. The possible regulatory pathway of p42.3 was established by integrating the acting pathways of these proteins. Then, the similarity between the reference proteins and p42.3 protein was figured out by multiparameter weighted summation method. The calculation result was taken as the prior probability of the initial node in Bayesian network. Besides, the probability of occurrence in different pathways was calculated by conditional probability formula, and the one with the maximum probability was regarded as the most possible pathway of p42.3. Finally, molecular biological experiments were conducted to prove it. RESULTS: In Bayesian network of p42.3, probability of the acting pathway "S100A11→RAGE→P38→MAPK→Microtubule-associated protein→Spindle protein→Centromere protein→Cell proliferation" was the biggest, and it was also validated by biological experiments. CONCLUSIONS: The possibly important role of p42.3 in the occurrence of gastric carcinoma was verified by theoretical analysis and preliminary test, helping in studying the relationship between p42.3 and gastric carcinoma.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/fisiopatologia , Algoritmos , Teorema de Bayes , Sítios de Ligação , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Ligantes , Modelos Teóricos , Proteínas Nucleares , Probabilidade , Estrutura Terciária de Proteína
18.
BMC Cancer ; 15: 168, 2015 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-25885227

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome. They have important regulatory functions in chromatin remodeling and gene expression. Dysregulated lncRNAs have been studied in cancers, but their role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We have conducted lncRNA expression screening and a genome-wide analysis of lncRNA and coding gene expression on primary tumor and adjacent normal tissue from four ESCC patients, tend to understand the functionality of lncRNAs in carcinogenesis of esopheagus in combination with experimental and bioinformatics approach. METHODS: LncRNA array was used for coding and non-coding RNA expression. R program and Bioconductor packages (limma and RedeR) were used for differential expression and co-expression network analysis, followed by independent confirmation and functional studies of inferred onco-lncRNA ESCCAL-1 using quantitative real time polymerase chain reaction, small interfering RNA-mediated knockdown, apoptosis and invasion assays in vitro. RESULTS: The global coding and lncRNA gene expression pattern is able to distinguish ESCC from adjacent normal tissue. The co-expression network from differentially expressed coding and lncRNA genes in ESCC was constructed, and the lncRNA function may be inferred from the co-expression network. LncRNA ESCCAL-1 is such an example as a predicted novel onco-lncRNA, and it is overexpressed in 65% of an independent ESCC patient cohort (n = 26). More over, knockdown of ESCCAL-1 expression increases esophageal cancer cell apoptosis and reduces the invasion in vitro. CONCLUSION: Our study uncovered the landscape of ESCC-associated lncRNAs. The systematic analysis of coding and lncRNAs co-expression network increases our understanding of lncRNAs in biological network. ESCCAL-1 is a novel putative onco-lncRNA in esophageal cancer development.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , RNA Longo não Codificante/genética , Idoso , Carcinoma de Células Escamosas do Esôfago , Humanos , Masculino , Valor Preditivo dos Testes
19.
Cancer Lett ; 354(2): 220-6, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25168479

RESUMO

Chemotherapy is the mainstay of treatment in mid-advanced tumors. Considering their toxicity on hematopoietic cells, chemotherapeutics are often considered as immunosuppressive inducers. However, recently accumulating data indicate that some chemotherapeutic agents with specific administration schedules also display some positive immunological effect to contribute to tumor elimination. For instance, metronomic chemotherapy could promote tumor eradication not only by inhibiting tumor angiogenesis but also by selectively eliminating immunosuppressive cells and improving anti-tumor immune responses. In this review, we summarize what is currently known regarding metronomic chemotherapy-induced immunoregulation. Understanding of the molecular mechanisms of metronomic chemotherapy-induced immunoregulation may yield invaluable information for the optimal design of immunochemotherapies.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Administração Metronômica , Animais , Humanos , Imunomodulação/efeitos dos fármacos , Imunomodulação/imunologia
20.
PLoS One ; 9(8): e104673, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25157814

RESUMO

OBJECTIVE: To determine the impact factors of latent tuberculosis infection (LTBI) and the knowledge of TB prevention and treatment policy among health care workers (HCWs) in different types of hospitals and explore the strategies for improving TB prevention and control in medical institutions in China. METHODS: A cross-sectional study was carried out to evaluate the risk of TB infection and personnel occupational protection among HCWs who directly engage in medical duties in one of two public hospitals. Each potential participant completed a structured questionnaire and performed a tuberculin skin test (TST). Factors associated with LTBI were identified by logistic regression analysis. RESULTS: Seven hundred twelve HCWs completed questionnaires and 74.3% (n = 529) took the TST or had previous positive results. The TST-positive prevalence was 58.0% (n = 127) in the infectious disease hospital and 33.9% (n = 105) in the non-TB hospital. The duration of employment in the healthcare profession (6-10 years vs. ≤5 years [OR = 1.89; 95% CI = 1.10, 3.25] and >10 vs. ≤5 [OR = 1.80; 95% CI = 1.20, 2.68]), type of hospital (OR = 2.40; 95% CI = 1.59, 3.62), and ever-employment in a HIV clinic or ward (OR = 1.87; 95% CI = 1.08, 3.26) were significantly associated with LTBI. The main reasons for an unwillingness to accept TST were previous positive TST results (70.2%) and concerns about skin reaction (31.9%). CONCLUSION: A high prevalence of TB infections was observed among HCWs working in high-risk settings and with long professional experiences in Henan Province in China. Comprehensive guidelines should be developed for different types of medical institutions to reduce TB transmission and ensure the health of HCWs.


Assuntos
Tuberculose Latente/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Hospitais Públicos , Humanos , Tuberculose Latente/diagnóstico , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Doenças Profissionais/diagnóstico , Exposição Ocupacional/análise , Recursos Humanos em Hospital , Teste Tuberculínico
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