RESUMO
Prostate cancer cells were transfected with plasmids [empty plasmids, wild-type pcDNA3.1-p53 (V/V), mutant type pcDNA3.1- p53 (G/G)] to analyze the effect of p53 gene polymorphisms on the proliferation, cycle, and apoptosis of prostatic cancer cells. Empty plasmids containing wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1- p53 (G/G) were used to transfect PC3 and LNCaP cells, respectively. Cell proliferation was detected at 0, 24, 48, and 72 h using the MTT method. Cells were collected at 24 and 72 h. The distribution of cell cycles in various groups was detected using flow cytometry (propidium iodide staining method) and the apoptosis rate was detected using annexin V + propidium iodide double staining. Compared with the control group, wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G) showed a significant inhibitory effect on cell proliferation (P < 0.05); the inhibitory effect of the mutant type was stronger than that of the wild-type. There was no significant difference between PC3 cells and LNCaP cells. After transfection with wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G), PC3 and LNCaP cells were arrested in the G0/G1 stage. Transfection with pcDNA3.1-p53 (G/G) showed a more significant effect than transfection with pcDNA3.1-p53 (V/V). Both the wild-type pcDNA3.1-p53 (V/V) and mutant-type pcDNA3.1-p53 (G/G) led to an increased apoptosis rate of PC3 and LNCaP cells. The p53 gene polymorphism affects the proliferation, apoptosis, and cycle of prostate cancer cells and may serve as a reliable index for the diagnosis and treatment of prostate cancer.
Assuntos
Proliferação de Células/genética , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Apoptose , Linhagem Celular Tumoral , Células Epiteliais/patologia , Citometria de Fluxo , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Masculino , Mutação , Plasmídeos/química , Plasmídeos/metabolismo , Próstata/metabolismo , Próstata/patologia , Transfecção , Proteína Supressora de Tumor p53/metabolismoRESUMO
This retrospective study aimed to observe the clinicopathological features and immunological phenotypes, and explore effective treatment and prognosis for 12 Chinese Han patients with acquired immunodeficiency syndrome-related cutaneous Kaposi's sarcoma. All 12 patients were human immunodeficiency virus-positive, and underwent the standard highly active antiretroviral therapy (HAART). Skin lesions mainly presented as purple, or rufous papules, or plaques; skin biopsy showed diffuse or flaky infiltration of spindle cells, active proliferation of slit-like vasculature, erythrocyte exudation, hemosiderin deposition, and inflammatory cell infiltration. Immunohistochemical analysis showed the expression of Ubiquitin C-terminal hydrolase L1 (+), and CD31 (+) in T-cells; factor VIII (+) and HHF-35 (+) in the proliferating vascular endothelial cells; vimentin (+) and S-100 protein (-) in the vessel wall; and CD34 (+++) in the spindle cells of 6 cases, with 1 case of negative CD34 expression. Four patients with confined lesions underwent surgery and microwave therapy, and received a favorable prognosis. Two patients with limited lesions underwent microwave therapy, and the lesions subsided. Of six patients with widely distributed sarcomas, five underwent microwave therapy and one received combined chemotherapy; five attained significant efficacy, and one died. There were no significant differences in the clinicopathological features and immunological phenotypes between the Chinese Han patients and those from other populations. Along with basal HAART, patients in early stages, with sarcomas <2 cm in diameter should undergo surgery and microwave therapy, while patients with sarcomas >2 cm in diameter should undergo chemotherapy and microwave therapy.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/radioterapia , Terapia Antirretroviral de Alta Atividade/métodos , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/radioterapia , Pele/patologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/cirurgia , Adulto , Antígenos CD34/genética , Antígenos CD34/metabolismo , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Vasos Sanguíneos/efeitos da radiação , Procedimentos Cirúrgicos Dermatológicos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Células Endoteliais/efeitos da radiação , Fator VIII/genética , Fator VIII/metabolismo , Feminino , Expressão Gênica , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Humanos , Masculino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Prognóstico , Estudos Retrospectivos , Proteínas S100/genética , Proteínas S100/metabolismo , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/cirurgia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Linfócitos T/efeitos dos fármacos , Linfócitos T/patologia , Linfócitos T/efeitos da radiação , Resultado do Tratamento , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Vimentina/genética , Vimentina/metabolismoRESUMO
The objectives of the present study were to identify additional genes that may play important roles in the regulation of skeletal muscle growth and development, and to provide fundamental information for understanding the underlying molecular mechanisms. Eighteen cDNA libraries were constructed from the longissimus muscle of Polled Dorset (PD) and Small-tailed Han (SH) fetuses. To reveal the differences between the two species, we analyzed the differences in gene expression in 60-, 90- and 120-day fetal skeletal muscle by applying Agilent ovine genome-wide microarray. In this study, we obtained 17,704 genes using a chip containing 39,242 probes. There were 88 differentially expressed genes in the 60-day group (P < 0.05), 128 genes in the 90-day group (P < 0.05), and 340 genes in the 120-day group (P < 0.05) between the two breeds. The differentially expressed genes were grouped in different GO categories and signaling pathways. These results suggested that there are many genetic differences in the muscle growth and development transcriptomes between these two breeds. This study laid the foundation for future genomic research in sheep.
Assuntos
Perfilação da Expressão Gênica , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Transcriptoma/genética , Animais , Feto , Regulação da Expressão Gênica no Desenvolvimento , Músculo Esquelético/crescimento & desenvolvimento , Ovinos/genética , Carneiro Doméstico/genéticaRESUMO
The amyloid C-terminal fragment (ßCTF) of the amyloid precursor protein (APP) is the cleaved component of APP by beta secretase-1 (BACE1), which shows similar neurotoxicity as amyloid beta (Aß) in many ways. Evidence suggested that in addition to Aß, ßCTF might also participate in the pathogenesis of Alzheimer's disease (AD). In recent years, the relationship between ßCTF processing and hyperphosphorylated tau has attracted increasing research attention. In this study, we established an animal model of tau hyperphosphorylation with okadaic acid (OA) treatment, and analyzed ßCTF processing in vivo. The ßCTF level was found to increase in neurons, which was most likely caused by the induction of OA and BACE1 overexpression. Furthermore, these results provide the first evidence that ßCTF can predominately accumulate in the axons of neurons in a hyperphosphorylated tau state in vivo, and suggested that the redistribution of ßCTF is involved in the pathogenesis of AD. These results indicate that BACE1 could be a therapeutic target of AD by affecting the processing of ßCTF.
Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Neurônios/metabolismo , Inibidores de Proteases/farmacologia , Tauopatias/genética , Proteínas tau/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/genética , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ácido Okadáico , Fosforilação , Ratos , Ratos Sprague-Dawley , Técnicas Estereotáxicas , Tauopatias/induzido quimicamente , Tauopatias/tratamento farmacológico , Tauopatias/patologia , Proteínas tau/genéticaRESUMO
Insulin-like growth factor binding protein-3 (IGFBP-3) exerts anti-proliferative or pro-apoptotic effects through IGF-dependent as well as IGF-independent mechanisms in vitro. The purpose of this study was to examine the association between genetic variants in IGFBP-3 (rs2270628) and the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. Five hundred ESCC cases and 500 cancer-free controls of the Chinese Han population were involved in this study. The IGFBP-3 single-nucleotide polymorphism (SNP) rs2270628 was genotyped and the estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for its association with the risk of ESCC were determined using unconditional logistic regression analysis. Compared with the rs2270628 CC genotype, TT genotype was associated with a significantly increased ESCC risk with OR (95%CI) of 2.07 (1.05-4.09), but CT genotype was not (OR = 1.25, 95%CI =0.94-1.66). IGFBP-3 SNP rs2270628 may contribute to the risk of ESCC in the Chinese Han population.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Idoso , Povo Asiático , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Increased disease resistance through improved general immune capacity would be beneficial for the welfare and productivity of farm animals. Classical swine fever (CSF) is a contagious disease in farm animals. The immunoglobulin G (IgG) blocking percentage of CSF virus (CSFV) in serum is an essential diagnostic parameter in veterinary practice. In addition, lysozymes are a part of the innate immune system. To identify quantitative trait loci (QTL) for IgG blocking percentage of CSFV and lysozyme concentration, IgG blocking percentage and lysozyme concentration in serum were measured in a composite pig population before and after challenge with modified live CSF vaccine. Through genome-wide mapping by MQREML analysis and the SOLAR software, several QTL for the lysozyme concentration and the IgG blocking percentage of CSFV were identified, respectively. Within these QTL regions, some known genes were revealed, and some of them may serve as candidate genes in the pig.
Assuntos
Anticorpos Antivirais/genética , Vírus da Febre Suína Clássica/imunologia , Imunoglobulina G/genética , Muramidase/genética , Locos de Características Quantitativas , Imunidade Adaptativa/genética , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Mapeamento Cromossômico , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Muramidase/sangue , SuínosRESUMO
ATP-sensitive potassium channels play an important role in myocardial electrical activity. Genetic disruption of these channels predisposes the myocardium to cardiac diseases. Herein we investigated whether two polymorphisms, E23K and I337V, located in the Kir6.2 subunit of ATP-sensitive potassium channels are associated with dilated cardiomyopathy (DCM) in a Chinese population. Blood was collected from DCM patients and controls. DNA was extracted for polymerase chain reaction, which was followed by DNA sequencing. The 2 polymorphisms were present in both DCM patients and normal controls. The frequencies of both the E23K and the I337V polymorphisms were not significantly different between DCM patients and normal controls. However, in DCM patients carrying the E23K polymorphism, the left ventricular end diastolic dimension (LVEDD) and the left atrial dimension (LAD) were significantly greater than those in DCM patients without the E23K polymorphism. Moreover, the occurrence of ventricular arrhythmias in DCM patients was also slightly increased in the presence of the E23K polymorphism (P < 0.05). We failed to identify an association between the I337V polymorphism and LVEDD, LAD, or ventricular arrhythmias in patients with DCM. The Kir6.2 E23K polymorphism in DCM patients of Han ethnicity may increase the risk of negative outcomes such as congestive heart failure and sudden cardiac death by affecting LVEDD and LAD.
Assuntos
Cardiomiopatia Dilatada/genética , Polimorfismo de Nucleotídeo Único , Canais de Potássio Corretores do Fluxo de Internalização/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Subunidades Proteicas/genética , Análise de Sequência de DNARESUMO
Ischemic stroke (IS) is a multifactorial disorder, and genetic factors act as important contributors to its onset and progression. Inflammation is a key event that is closely associated with the pathophysiology of IS. The association of genetic polymorphisms of inflammatory cytokines with IS remains poorly understood. We investigated the relationship between the variable number of tandem repeats (VNTR) for IL-4, which is an important biomarker of inflammation, and the risk of IS. To assess the nature of the VNTR polymorphism in IL-4 and identify any links with IS, we recruited 200 subjects from a unique population that has 60% European and 40% East Asian ancestry. The subjects comprised 100 IS patients diagnosed using magnetic resonance imaging within 24 h of symptom onset and 100 age-, gender- and ethnicity-matched normal healthy controls. VNTR was identified using high-performance capillary electrophoresis with specially designed tailed primers. The IL-4 VNTR polymorphism was significantly associated with IS after adjustment for cardiovascular risk factors (OR = 0.571, 95%CI = 0.330-0.949, P < 0.05). Our data indicate that IL-4 VNTR polymorphism may affect susceptibility to IS in the Chinese Uyghur population. Moreover, total cholesterol, fasting blood glucose, waist-to-hip ratio, hypertension, history of heart diseases, and negative events may increase the risk of IS, with a trend for HDL to be a protective factor for IS in the Uyghur population.