RESUMO
BACKGROUND/AIMS: Chronic myocardial infarction (MI) results in the formation of arrhythmogenic substrates, causing lethal ventricular arrhythmia (VA). We aimed to determine whether mesenchymal stem cells (MSCs) carrying a hepatocyte growth factor (HGF) gene modification (HGF-MSCs) decrease the levels of arrhythmogenic substrates and reduce the susceptibility to developing VA compared with unmodified MSCs and PBS in a swine infarction model. METHODS: The left descending anterior artery was balloon-occluded to establish an MI model. Four weeks later, the randomly grouped pigs were administered MSCs, PBS or HGF-MSCs via thoracotomy. After an additional four weeks, dynamic electrocardiography was performed to assess heart rate variability, and programmed electrical stimulation was conducted to evaluate the risk for VA. Then, the pigs were euthanized for morphometric, immunofluorescence and western blot analyses. RESULTS: The HGF-MSC group displayed the highest vessel density and Cx43 expression levels, and the lowest levels of apoptosis, and tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) expression. Moreover, the HGF-MSC group exhibited a decrease in the number of sympathetic nerve fibers, substantial decreases in the low frequency and the low-/high- frequency ratio and increases in the root mean square of successive differences (rMSSD) and the percentage of successive normal sinus R-R intervals longer than 50 ms (pNN50), compared with the other two groups. Finally, the HGF-MSC group displayed the lowest susceptibility to developing VA. CONCLUSION: HGF-MSCs displayed potent antiarrhythmic effects, reducing the risk for VA.
Assuntos
Arritmias Cardíacas/terapia , Células da Medula Óssea/citologia , Fator de Crescimento de Hepatócito/genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Apoptose , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Sobrevivência Celular , Estimulação Elétrica , Regulação da Expressão Gênica , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Neovascularização Fisiológica , SuínosRESUMO
Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The -174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between -174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between -174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR=4.33, 95% CI: 1.93-9.71 for CC vs. GC, OR=2.81, 95% CI: 1.39-5.68 for CC vs. GG, and OR=2.19, 95% CI: 1.32-3.64 for CC vs. GG/GC), and among Asians (OR=2.08, 95% CI: 1.07-4.06 for CC vs. GG, and OR=2.20, 95% CI: 1.02-4.74 for CC vs. GG/GC) and Africans (OR=1.61, 95% CI: 1.07-2.42 for GC vs. GG). This meta-analysis showed the evidence that the -174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, preferably prospective studies are needed to confirm this relationship.
Assuntos
Predisposição Genética para Doença/genética , Interleucina-6/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , População Negra/genética , Feminino , Humanos , Masculino , Razão de Chances , População Branca/genéticaRESUMO
Vascular endothelial growth factor (VEGF) is a major driver of physiological and pathological angiogenesis and plays important roles in the etiology and metastasis of cancers. The -460C>T polymorphism in VEGF gene region has been implicated in cancer risk and related to VEGF expression. However, published data remain conflicting. To derive a more precise estimation, a meta-analysis of 5,863 cases and 5,276 controls from 14 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. VEGF -460T represented a risk factor for cancers in Asians (OR=1.69, 95% CI: 1.09-2.62) but not in Europeans (OR=0.92, 95% CI: 0.78-1.08). Our meta-analysis showed the evidence that VEGF -460T was associated with increased cancer risk in Asians. Further prospective researches with larger numbers of worldwide participants are expected to validate this result.
Assuntos
Neoplasias/genética , Polimorfismo Genético/genética , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Etnicidade , Humanos , Neoplasias/etnologia , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the relationship between IL8-251 gene polymorphisms and gastric cancer. METHODS: Literatures were reviewed and selected based on the criteria for inclusion. The Meta-analysis software, REVMAN 4.2, was applied to check the heterogeneity across the studies and calculating the pooled OR. RESULTS: Total of 2114 cases and 2505 controls from 8 studies for IL8-251 were included. The chi(2) value was 21.48 (P = 0.003), and the pooled OR of (AA + AT) vs. TT was 1.12 (95% CI 0.90 - 1.40). Large heterogeneity was found among the studies. After the sensitivity analysis, the pooled OR of (AA + AT) vs. TT 1.21 (95% CI 1.06 - 1.39). CONCLUSION: IL8-251-A allele might be associated with higher risk of developing gastric cancer.
