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1.
Biomed Pharmacother ; 88: 507-514, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28126676

RESUMO

Chemotherapy resistance is the major obstacle to the effective therapy of cancer. While the mechanism of chemotherapy resistance is still not fully understood. Increasing evidences demonstrated that microRNAs (miRNAs) may have a crucial function in chemotherapy resistance through modulating intracellular pathways. MiR-199a has been shown to be involved in multiple malignancy-related processes, although the precise mechanism is unclear at present. In this study, we found that the expression level of miR-199a-3p was lower in cisplatin (DDP) resistant breast cancer MDA-MB-231/DDP cells compared with parental DDP-sensitive cells. Inhibition of miR-199a-3p in MDA-MB-231 cells significantly attenuated DDP-induced apoptosis and anti-proliferative effects, while overexpression of miR-199a-3p in MDA-MB-231/DDP cells increased the sensitivity to DDP. Moreover, expression levels of mitochondrial transcription factor A (TFAM) were modulated by miR-199a-3p. The luciferase reporter assay indicated that TFAM may be the target gene of miR-199a. Knocking down of TFAM could partially reverse DDP resistance in MDA-MB-231 cells induced by miR-199a-3p inhibition, while TFAM overexpression could partially restore miR-199a-3p-induced chemo-sensitivity of MDA-MB-231/DDP cells to DDP. These results show that miR-199a-3p is able to attenuate cisplatin resistance in breast cancer cells through inhibiting TFAM expression.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Cisplatino/uso terapêutico , Proteínas de Ligação a DNA/genética , Regulação para Baixo , MicroRNAs/metabolismo , Proteínas Mitocondriais/genética , Fatores de Transcrição/genética , Sequência de Bases , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , DNA Mitocondrial/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/genética , Proteínas Mitocondriais/metabolismo , Fatores de Transcrição/metabolismo
2.
PLoS One ; 10(3): e0119651, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25799347

RESUMO

The formation of new genes is a primary driving force of evolution in all organisms. The de novo evolution of new genes from non-protein-coding genomic regions is emerging as an important additional mechanism for novel gene creation. Y chromosomes underlie sex determination in mammals and contain genes that are required for male-specific functions. In this study, a search was undertaken for Y chromosome de novo genes derived from non-protein-coding sequences. The Y chromosome orphan gene variable charge, Y-linked (VCY)2, is an autosome-derived gene that has sequence similarity to large autosomal fragments but lacks an autosomal protein-coding homolog. VCY2 locates in the amplicon containing long DNA fragments that were transposed from autosomes to the Y chromosome before the ape-monkey split. We confirmed that VCY2 cannot be encoded by autosomes due to the presence of multiple disablers that disrupt the open reading frame, such as the absence of start or stop codons and the presence of premature stop codons. Similar observations have been made for homologs in the autosomes of the chimpanzee, gorilla, rhesus macaque, baboon and out-group marmoset, which suggests that there was a non-protein-coding ancestral VCY2 that was common to apes and monkeys that predated the transposition event. Furthermore, while protein-coding orthologs are absent, a putative non-protein-coding VCY2 with conserved disablers was identified in the rhesus macaque Y chromosome male-specific region. This finding implies that VCY2 might have not acquired its protein-coding ability before the ape-monkey split. VCY2 encodes a testis-specific expressed protein and is involved in the pathologic process of male infertility, and the acquisition of this gene might improve male fertility. This is the first evidence that de novo genes can be generated from transposed autosomal non-protein-coding segments, and this evidence provides novel insights into the evolutionary history of the Y chromosome.


Assuntos
Evolução Molecular , Proteínas/genética , Testículo/metabolismo , Cromossomo Y/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Humanos , Macaca mulatta , Masculino , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Pan troglodytes , Filogenia , Homologia de Sequência do Ácido Nucleico
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 46(4): 359-63, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22800638

RESUMO

OBJECTIVE: To evaluate the relationship between peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala polymorphism and type 2 diabetes mellitus (T2DM) in Chinese Han population. METHODS: PubMed, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang database were searched for all relevant articles investigating the association between PPARγ2 Pro12Ala polymorphism and T2DM that were available from January, 1990 to June, 2011. A total of 29 relevant articles were selected. A Meta-analysis was performed to estimate heterogeneity and the pooled odds ratio (OR) to evaluate the relationship between PPARγ2 Pro12Ala polymorphism and T2DM. The sensitivity analysis was also assessed. RESULTS: A total of 21 qualified articles including 3870 patients with T2DM and 3333 healthy controls were analyzed in the study. The frequencies of the allele Ala12 in T2DM and control groups were 4.13% (320/7740) and 4.56% (304/6666), respectively. There were not heterogeneity (χ(2) = 25.96, P = 0.17) among the 21 qualified articles. The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP calculated by fixed effects model was 0.96 (0.81 - 1.14) (P = 0.64). There was not heterogeneity among the remaining articles after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 respectively (χ(2) values were 24.23, 16.87 respectively, both P values > 0.05). The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP of the remaining articles were 1.01 (0.84 - 1.21) and 1.07 (0.89 - 1.28) after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 (both P values > 0.05). CONCLUSION: PPARγ2 Pro12Ala polymorphism was not associated with type 2 diabetes mellitus in Chinese Han population.


Assuntos
Diabetes Mellitus Tipo 2/genética , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Alelos , Povo Asiático/genética , China , Frequência do Gene , Genótipo , Humanos
4.
Sheng Wu Gong Cheng Xue Bao ; 28(12): 1414-22, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23593865

RESUMO

Human carboxylesterase 1 (HCE1), belonging to a multigene serine hydrolase family, is a major liver carboxylesterase responsible for the hydrolysis and metabolism of various xenobiotics. It also plays an important role in the transportation and metabolism of endogenous cholesterol ester and free fatty acid, and is closely associated with the pathogenesis of hepatocellular carcinoma. This review describes current developments in the molecular structure, the roles in drug, toxins and lipid metabolism, and the early diagnosis for hepatocellular carcinoma of human carboxylesterase 1.


Assuntos
Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/fisiologia , Ésteres do Colesterol/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Xenobióticos/metabolismo
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 27(8): 685-9, 2006 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17175588

RESUMO

OBJECTIVE: To study the effect of Oncomelania hupensis hupensis of niclosamide, and exploring the main influencing factors. METHODS: The samples of Oncomelania hupensis hupensis were collected from 37 sampling sites in 33 counties of 10 provinces by means of stratified random sampling methods in accordance with the categories of Oncomelania hupensis hupensis habitats. Samples were randomly located into study group and control group. Oncomelania hupensis hupensis of the study group was marinated in different concentration liquor of niclosamide which was confected with water for 24 hours or 48 hours, then LC50 of niclosamide by which Oncomelania hupensis hupensis was killed and amount calculated. The influencing factors of the mortality of Oncomelania hupensis hupensis in the study group was statistically analyzed by 2 test and by multiple logistic regression using SPSS 13.0 statistical software. RESULTS: The mortality of Oncomelania hupensis hupensis of the two test groups which were marinated in 0.5 mg/L liquor for 48 hours and 1.0 mg/L liquor for 24 hours was 100%. The effect of Oncomelania hupensis hupensis killed by niclosamide was markedly reduced along with the reduction of drug concentration. The average LC50 rates of niclosamide liquor by which Oncomelania hupensis hupensis killed for the 24 hours and 48 hours in the study group, were 0.0939 mg/L and 0.0625 mg/L, respectively. There was significant difference between the two test groups (chi(2) = 5.001, P <0.01) . In determinate range of concentration, the mortality of Oncomelania hupensis hupensis showed significant difference among the geographic types of habitat ( chi(2) = 4.264, P < 0.05). By means of multiple logistic regression using SPSS 13.0 statistical software, the estimate value of coefficient of regression on the influence factors, drug concentration, test time and the geographic types of habitat were 2. 047 ( OR = 5. 573), 0.263 ( OR = 2.924) and 0. 187- 0.210 ( OR = 1.969- 2. 560), respectively. CONCLUSION: Niclosamide could kill Oncomelania hupensis hupensis effectively. The main influencing factors on the efficacy of niclosamide by which Oncomelania hupensis hupensis was killed, appeared to be drug concentration, time of testing and the geographic types of habitat.


Assuntos
Moluscocidas/toxicidade , Niclosamida/toxicidade , Caramujos/efeitos dos fármacos , Animais , China , Ecossistema
6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 30(6): 711-3, 2005 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-16708817

RESUMO

OBJECTIVE: To explore the effect of nutrient support on severe infant pneumonia. METHODS: Prospective study was conducted on the outcome of 567 inpatients suffering from severe pneumonia in 13 hospitals randomly selected in Hunan. Twelve factors were surveyed and data analyzed by multiple logistic regression. RESULTS: Malnnutrition, anemia and rickets were risk factors in severe pneumonia, and nutrient support had protective effect on severe pneumonia. CONCLUSION: Nutrient support contributes to the positive outcome of severe infant pneumonia.


Assuntos
Apoio Nutricional , Nutrição Parenteral , Pneumonia/terapia , gama-Globulinas/uso terapêutico , Pré-Escolar , Nutrição Enteral , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pneumonia/dietoterapia , Estudos Prospectivos , Resultado do Tratamento
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