RESUMO
Recent genome-wide association studies identified 11 risk loci in different populations of familial and sporadic Parkinson's disease (PD) patients. Few loci have been verified in different European and Asian populations. We also validated 2 new single-nucleotide polymorphisms, rs947211 and rs823144, in PARK16 to explore their association with susceptibility to PD in the Xinjiang Uygur and Han populations. This case-control study included 312 PD patients (130 Uygur and 182 Han) and 359 control subjects (179 Uygur and 180 Han). Polymerase chain reaction-restriction fragment length polymorphism analysis and DNA sequencing were used to detect the rs947211 and rs823144 polymorphism in the PARK16 gene between the Xinjiang Uygur and Han populations. Frequencies of the A allele and AA genotype (42.1 and 15.7%, respectively) of rs947211 in PD patients were significantly lower than those in the control group (54.7 and 28.7%, respectively, P < 0.01). A allele and AA genotype frequencies of rs823144 were 56.8 and 31.8% in the PD patients group and were 54.1 and 29.3% in the control group; no significant difference was found (P > 0.05). In both the Han and Uygur groups, the rs947211 polymorphism was associated with PD. Haplotype analysis also indicated that the A-A and G-A haplotypes were associated with PD. We found that the rs947211 polymorphism may be a susceptibility marker for PD in the Chinese population; the A-A and G-A haplotypes may be a protective factor and a risk factor, respectively, for PD in the Chinese population.
Assuntos
Doença de Parkinson/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China , Etnicidade/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The specific role of Toll-like receptor 4 (TLR4) in bleomycin-induced lung fibrosis of mice, a model of human idiopathic pulmonary fibrosis, has not been characterized. We injected bleomycin intratracheally into TLR4 knockout (TLR4(-/-)) and wild-type (WT) mice. Twenty-one days after injection, mice were sacrificed and their lungs were harvested for pathological, hydroxyproline, mRNA expression, and collagen I analyses. Body weight changes and mortality were observed. Light microscopy showed that lung fibrosis was minimal in TLR4(-/-) compared to that in WT mice on day 21 after bleomycin instillation. The Ashcroft score was significantly lower in TLR4(-/-) than in WT mice (3.667 ± 0.730 vs 4.945 ± 0.880, P < 0.05). Hydroxyproline content was significantly lower in TLR4(-/-) than in WT mice on day 21 after bleomycin injection (0.281 ± 0.022 vs 0.371 ± 0.047, P < 0.05). Compared to WT mice, bleomycin-treated TLR4(-/-) mice expressed significantly lower type I collagen mRNA levels (mesenchymal marker; 11.069 ± 2.627 vs 4.589 ± 1.440, P < 0.05). Collagen I was significantly lower in TLR4(-/-) than in WT mice (0.838 ± 0.352 vs 2.427 ± 0.551, P < 0.05). Bleomycin-treated TLR4(-/-) mice had a significantly lower mortality rate on day 21 than WT mice (33 vs 75%, P < 0.05). Body weight reduction was lower in TLR4(-/-) mice than in WT mice; this difference was not statistically significant (-3.735 ± 5.276 vs -6.698 ± 3.218, P > 0.05). Thus, bleomycin-induced pulmonary fibrosis is TLR4-dependent and TLR4 promoted fibrosis in bleomycin-challenged mice.
Assuntos
Fibrose/genética , Lesão Pulmonar/genética , Receptor 4 Toll-Like/genética , Animais , Bleomicina/toxicidade , Colágeno Tipo I/biossíntese , Fibrose/induzido quimicamente , Fibrose/patologia , Humanos , Lesão Pulmonar/patologia , Camundongos , Camundongos Knockout , RNA Mensageiro/biossínteseRESUMO
Bone morphogenetic proteins (BMPs) are the key factors in maintaining cell growth and differentiation in ovaries. BMPs initiate signaling by assembling BMP receptors and activating Smads, which in turn alter the expression of target genes. However, little is known about the effect of the deletion of the Bone morphogenetic protein receptor type IB (BMPRIB) on porcine granulosa cell (GCs). The objective of this study was to determine the effects of BMPRIB gene silencing, by small interfering RNA (siRNA), on the apoptosis and steroidogenesis of porcine GCs, and the expression of cell cycle-related and apoptosis-related genes. Results indicate that the BMPRIB siRNA caused specific inhibition of BMPRIB mRNA expression after transfection. Knockdown of the BMPRIB gene significantly inhibited porcine GCs proliferation and estradiol production, while inducing apoptosis of porcine GCs. Additionally, the declined expression of the BMPRIB gene changed the expressions of CylinD2, Cdk2, Bcl-2, and Cyp19a1. These findings provide an important role of BMPRIB in the regulation of apoptosis and steroidogenesis of porcine GCs.
Assuntos
Apoptose/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Inativação Gênica , Células da Granulosa/metabolismo , RNA Interferente Pequeno/metabolismo , Esteroides/biossíntese , Animais , Tamanho Corporal , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Feminino , Células da Granulosa/citologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteína Smad4/genética , Proteína Smad4/metabolismo , Sus scrofa , TransfecçãoRESUMO
In this study, we aimed to explore the curative effect and safety of neural stem cell intrathecal transplantation for the treatment of cerebral hemorrhage. We transplanted 4.0 x 10(8) neural stem cells per procedure into the subarachnoid space by lumbar puncture 7 days after cerebral hemorrhage, twice a week, a total of 4 times. NIHSS scores and brain CT scans were conducted to assess neural functions and the volume of perihematoma lesions in patients on days 1, 7, 14, 21, and 28. We found that the NIHSS scores and the volume of the perihematoma lesions were significantly reduced after day 14. The differences before and after treatment were highly significant in intra- and between-group comparisons (P < 0.05). There were no adverse reactions, except for transient fever and shivering in a few patients. Our data suggest that the use of neural stem cells in intrathecal transplantation for the treatment of cerebral hemorrhage is safe and effective.
Assuntos
Hemorragia Cerebral/terapia , Células-Tronco Neurais/citologia , Transplante de Células-Tronco , Adulto , Idoso , Terapia Baseada em Transplante de Células e Tecidos , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
We performed a meta-analysis for systematic evaluation of the status quo of catheter thrombolysis for the treatment of acute lower limb deep vein thrombosis in China. We searched the China Biomedical bibliographic database (CBM), China National Knowledge Infrastructure (CNKI), Weipu full-text electronic journals, Wanfang full-text database, and Medline (1990 through June 2011) for clinical randomized controlled trials of catheter-directed thrombolysis and superficial venous thrombolysis to compare their efficacies for the treatment of acute deep vein thrombosis. The results were analyzed by using the Cochrane-recommended RevMan 4.2 software package, and the odds ratio (OR) was used as the combined measure of efficacy. The search retrieved 8 randomized controlled trials, and meta-analysis using the total rate of effective treatment as the clinical observation index found that the combined OR for the catheter thrombolysis group versus the superficial venous thrombolysis group was significant (P < 0.01; OR = 11.78; 95% confidence interval = 6.99-19.87). In conclusion, the meta-analysis indicated that catheter thrombolysis was more effective than superficial venous thrombolysis for the treatment of acute deep vein thrombosis in the lower limb in Chinese individuals. However, the included trials were only of medium quality, so more rational and scientific clinical trials are needed to validate this conclusion.
Assuntos
Cateterismo Periférico/métodos , Fibrinolíticos/uso terapêutico , Trombose Venosa/terapia , Doença Aguda , Povo Asiático , Humanos , Perna (Membro)/irrigação sanguínea , Perna (Membro)/patologia , Perna (Membro)/cirurgia , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Trombose Venosa/etnologia , Trombose Venosa/patologia , Trombose Venosa/cirurgiaRESUMO
Toll-like receptor 3 (TLR3) variants in mainland northern Chinese patients with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) were investigated. The complete genes of TLR3, including all exons and the promoter region, were assessed using direct sequencing technology of 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients, and 96 controls. Six single nucleotide polymorphisms were identified: rs5743303, rs5743305, rs5743312, rs3775291, rs3775290, and rs6830345. The distribution of TLR3 genotypes for nAMD and PCV was not significantly different compared with normal controls. This study indicates that the TLR3 gene polymorphism is not associated with nAMD and PCV in northern Chinese patients.
Assuntos
Doenças da Coroide/genética , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Idoso , Estudos de Casos e Controles , China , Éxons , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
We investigated the association between the LOC387715/ARMS2 polymorphism (rs10490924 G>T) and susceptibility to polypoidal choroidal vasculopathy (PCV) through a meta-analysis of 1446 cases and 3255 controls from eight case-control studies. The genetic effect of the LOC387715/ARMS2 rs10490924 G>T polymorphism on PCV was assessed by calculating pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). We found that elevated PCV risk was significantly associated with the GG genotype (GG vs TT, OR = 4.23, 95%CI = 3.53-5.06), and heterozygous genotype TG appeared to have a minor effect on PCV risk (TG vs TT, OR = 1.47, 95%CI = 1.26-1.71). Patients with the T allele were 2.09 times more likely to have PCV than those with the G allele (95%CI = 1.906-2.288). A further subgroup analysis by ages also showed that the genetic effect of the LOC387715/ARMS2 rs10490924 G>T polymorphism on PCV is stronger among patients with mean age <73 years. Our meta-analysis strengthened the evidence that the LOC387715/ARMS2 rs10490924 G>T polymorphism plays an important role in PCV susceptibility.