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目的NPRA-cGMP信号通路系统可激活cGMP依赖的蛋白激酶,活化的蛋白激酶调控离子转运蛋白和转录因子的表达,从而最终影响细胞生长、凋亡、增殖和炎症反应。本研究旨在研究NPRA基因在胃癌细胞中的甲基化状态及其对下游mRNA表达的影响。方法应用亚硫酸氢钠处理基因组DNA后PCR并测序,我们分析了6株胃癌细胞株NPRA基因的甲基化状态及去甲基化试剂对下游mRNA表达的影响。结果在胃癌细胞中发现NPRA基因启动子区存在甲基化畸变并导致下游mRNA表达减少或沉默。去甲基化试剂可逆转mRNA表达沉默。结论胃癌细胞中存在NPRA基因甲基化畸变。  相似文献   
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Background and aims

Laboratory studies on human adipose tissue and differentiated adipocytes indicate that natriuretic peptides (NPs) affect lipid metabolism and plasma cholesterol. Few previous clinical studies in non-elderly populations found associations between NPs in the physiological range and cholesterol. Aim: evaluate the association between NT-proBNP and lipid profile in very elderly hospitalized patients characterized by a wide range of NT-proBNP levels.

Methods and results

Cross-sectional study on 288 very elderly patients hospitalized for medical conditions, in which increased NT-proBNP levels are very common. NT-proBNP, total cholesterol (TC), HDL cholesterol (HDLc) and triglycerides were collected just few days before discharge. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Calculated LDL-cholesterol (LDLc) was used for the analyses. Mean age: 87.7 ± 6.2 years; female prevalence (57.3%). Median NT-proBNP: 2949 (1005–7335) pg/ml; mean TC: 145.1 ± 40.3 mg/dl; mean HDLc: 38.4 ± 18.6 mg/dl; median triglycerides: 100 (75–129) mg/dl; mean LDLc: 84.0 ± 29.5 mg/dl. We found negative correlations between NT-proBNP and both TC and LDLc (Rho = ?0.157; p = 0.008 and Rho = ?0.166; p = 0.005, respectively), while no correlations emerged between NT-proBNP and HDLc (Rho = ?0.065; p = 0.275) or triglycerides (Rho = ?0.009; p = 0.874). These associations were confirmed considering NT-proBNP tertiles. The inverse association between NT-proBNP and LDLc was maintained even after adjusting for confounding factors.

Conclusion

Our real-life clinical study supports the hypothesis that NPs play a role on cholesterol metabolism, given the association found between LDLc and NT-proBNP even in very elderly patients where NT-proBNP values are often in the pathological range.  相似文献   
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Lipofuscin accumulation is a characteristic feature of senescent postmitotic neuronal cells but estrogen may have protecting effects by inhibiting its formation. In the present ultrastructural study, lipofuscin accumulation was studied in 2 estrogen-α-receptive brainstem areas: nucleus pararetroambiguus (NPRA) and the commissural part of the solitary tract nucleus/A2 catecholaminergic group (NTScom/A2) and compared with the estrogen-insensitive medial tegmental field (mtf), in young (23 weeks) and aged (95 weeks) female hamsters. In the aged animals, extensive intracytoplasmic lipofuscin accumulation was observed. A total number of 6450 neurons were classified in 4 categories. Levels were significantly elevated in each of the brain areas studied. Lipofuscin accumulation was strongest in the mtf, less in NPRA, and remarkably less in the area of NTScom/A2. In conclusion, the observed differences in lipofuscin accumulation suggest: (1) considerable regional differences in the degree of neuronal vulnerability; and (2) a possible neuroprotective role for estrogen, because the degree of accumulation is inversely related to the density of the estrogen receptors, varying from nonreceptive (mtf) to NPRA and NTScom/A2 (most receptive).  相似文献   
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