A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.     

Participation of miR-200 in pulmonary fibrosis

Excessive extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF). Epithelial-mesenchymal transition, involving transition of alveolar epithelial cells (AECs) to pulmonary fibroblasts, appears to be an important contributory process to lung fibrosis. Although aberrant expression of microRNAs (miRs) is involved in a variety of pathophysiologic processes, the role of miRs in fibrotic lung diseases is less well understood. In the present study, we found that miR-200a, miR-200b, and miR-200c are significantly down-regulated in the lungs of mice with experimental lung fibrosis. Levels of miR-200a and miR-200c were reduced in the lungs of patients with IPF. miR-200 had greater expression in AECs than in lung fibroblasts, and AECs from mice with experimental pulmonary fibrosis had diminished expression of miR-200. We found that the miR-200 family members inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition of AECs. miR-200 family members can reverse the fibrogenic activity of pulmonary fibroblasts from mice with experimental pulmonary fibrosis and from patients with IPF. Indeed, the introduction of miR-200c diminishes experimental pulmonary fibrosis in mice. Thus, the miR-200 family members participate importantly in fibrotic lung diseases and suggest that restoring miR-200 expression in the lungs may represent a novel therapeutic approach in treating pulmonary fibrotic diseases.     

Validation of diffusion tensor MRI in the central nervous system using light microscopy: quantitative comparison of fiber properties

Diffusion tensor imaging (DTI) provides an indirect measure of tissue structure on a microscopic scale. To date, DTI is the only imaging method that provides such information in vivo, and has proven to be a valuable tool in both research and clinical settings. In this study, we investigated the relationship between white matter structure and diffusion parameters measured by DTI. We used micrographs from light microscopy of fixed, myelin‐stained brain sections as a gold standard for direct comparison with data from DTI. Relationships between microscopic tissue properties observed with light microscopy (fiber orientation, density and coherence) and fiber properties observed by DTI (tensor orientation, diffusivities and fractional anisotropy) were investigated. Agreement between the major eigenvector of the tensor and myelinated fibers was excellent in voxels with high fiber coherence. In addition, increased fiber spread was strongly associated with increased radial diffusivity (p = 6 × 10^–6) and decreased fractional anisotropy (p = 5 × 10^–8), and was weakly associated with decreased axial diffusivity (p = 0.07). Increased fiber density was associated with increased fractional anisotropy (p = 0.03), and weakly associated with decreased radial diffusivity (p < 0.06), but not with axial diffusivity (p = 0.97). The mean diffusivity was largely independent of fiber spread (p = 0.24) and fiber density (p = 0.34). Copyright © 2012 John Wiley & Sons, Ltd.     

Lack of association of polymorphism in miRNA-196a2 with Parkinson's disease risk in a Chinese population

MicroRNAs (miRNAs) are a new class of non-protein coding RNA molecules, which participate in diverse biological pathways. We hypothesized that miRNA-196a2 polymorphism is associated with the risk of Parkinson's disease (PD) in a Chinese population. In a case-control study of 549 PD patients and 736 control subjects frequency matched by age and gender, we genotyped the single-nucleotide polymorphism (SNP) rs11614913 (T>C) in miRNA-196a2, whose target mRNA was alpha-synuclein, and assessed its association with risk of PD by TaqMan Genotyping method. No association was found for the miR-196a2 rs11614913 CT/CC genotype (odds ratio (OR), 0.879, 95% confidence interval (CI), 0.681-1.135 for CT genotype; OR, 1.085, 95% CI, 0.793-1.484 for CC genotype) with risk of PD, compared with the TT genotype. These results suggest that SNP rs11614913 in miRNA-196a2 may not contribute to the susceptibility to PD.     

单核细胞趋化蛋白1与神经干细胞的体外迁移

背景：研究表明趋化因子基质细胞衍生因子1及血管内皮生长因子参与神经干细胞的迁移。 目的：观察趋化因子单核细胞趋化蛋白1及其受体CCR2对神经干细胞体外迁移的作用。 方法：分离培养胎鼠海马组织神经干细胞,体外传代扩增及鉴定;通过细胞免疫荧光及RT-PCR检测其受体CCR2表达情况;通过琼脂糖下细胞迁移实验观察50,100,200,300,500 μg/L 单核细胞趋化蛋白1对神经干细胞的体外趋化作用。 结果与结论：细胞免疫荧光及RT-PCR检测证实胎鼠海马来源神经干细胞表达趋化因子受体CCR2;琼脂糖下细胞迁移实验显示,体外条件下单核细胞趋化蛋白1可趋化神经干细胞迁移,且趋化迁移作用随质量浓度增加而增强,抗CCR2多克隆抗体可对抗其趋化迁移作用。     

载盐酸四环素壳聚糖缓释膜的制备

背景：壳聚糖具有良好的生物相容性、生物可降解性及较好的抗菌活性。 目的：使用流延法制备载有不同盐酸四环素的壳聚糖载药纳米纤维膜,观察其缓释性能和抑菌性能。 方法：采用流延法制备厚度为0.03 mm的载有不同含量(0,3%,5%,10%,20%)盐酸四环素的壳聚糖载药缓释膜,测定载药率,绘制盐酸四环素缓释曲线。分别用液体培养和固体培养检测载药缓释膜的体外抑菌性能,用磷酸盐缓冲液观察载药缓释膜的降解性能。 结果与结论：随盐酸四环素含量的增加,缓释膜载药率降低,突释量增大。载药壳聚糖膜可有效抑制金黄色葡萄球菌的生长,并随盐酸四环素含量的增加,抑菌效果提高,当盐酸四环素含量超过10%时,载药壳聚糖膜抑菌率的变化不明显。盐酸四环素的加入加快了壳聚糖膜降解,并随着盐酸四环素含量的增加,降解速率增大,当盐酸四环素载药量超过10%时,降解可在8 d内完成。相比较得出,盐酸四环素含量在10%时,在疗效和性价比上是较好的选择。     

CT三维重建在全膝关节置换中的应用

背景：下肢X射线测量及CT三维重建的应用,以及计算机辅助技术都有助于人工全膝关节置换术者更精确地安放假体。 目的：探讨全膝关节置换前CT三维重建确定股骨髓内定位杆置入点对置换后关节功能的影响。 方法：32例全膝关节置换患者,其中置换前进行CT三维重建确定股骨髓内定位杆置入点的18个病例(CT三维重建组),其余病例术前未进行CT三维重建(对照组),在置换后3个月、1年、2年定期随访。 结果与结论：置换后3个月、1年、2年随访与对照组比较,CT三维重建组膝关节功能评分总体功能和单纯膝关节功能评分显著增高(P均 < 0.05)。提示全膝关节置换前行膝关节CT三维重建确定股骨髓内定位杆进入点有助于在置换中正确插入股骨髓内定位杆,更准确地进行股骨端的截骨以及膝关节假体的安放,能够更好地恢复下肢力线和膝关节的功能。     

贵金属烤瓷合金与高糖对细胞外液炎性因子的影响

背景：前期研究中发现高糖与烤瓷合金浸提液对小鼠成纤维细胞L-929的增殖存在交互效应。 目的：观察3种贵金属烤瓷合金与高糖对小鼠成纤维细胞L-929中白细胞介素6水平的影响。 方法：采用两因素析因设计实验研究不同糖浓度(11.1,22.2,33.3 mmol/L)下,89%金合金、74%金合金及银钯合金贵金属烤瓷合金浸提液,分别与小鼠成纤维细胞L-929体外共培养24h后,细胞外液中白细胞介素6水平的变化,并设未加入合金材料的空白对照为阴性对照组。 结果与结论：两因素析因设计分析结果表明,贵金属烤瓷合金浸提液的主效应有统计学意义(P=0.001),其中74%金合金与银钯合金白细胞介素6水平低于阴性对照组(P=0.004,0);糖浓度的主效应也有统计学意义(P=0.005), 33.3 mmol/L糖浓度组白细胞介素6水平低于11.1 mmol/L(正常)糖浓度组(P=0.001)。但贵金属烤瓷合金浸提液与糖浓度两因素对小鼠成纤维细胞L-929细胞外液中白细胞介素6水平的影响无交互作用(P=0.33)。     

Chitooligosaccharides protect cultured hippocampal neurons against glutamate-induced neurotoxicity

Chitooligosaccharides (COSs), the biodegradation product of chitosan, have demonstrated a diverse array of biological activities. Here we report the protective effect of COSs (M.W. 800) against glutamate-induced neurotoxicity in cultured hippocampal neurons. The cell viability assessments, together with Hoechst 33342 staining and flow cytometry for cell apoptosis analysis, indicated that glutamate (125 μM)-induced cell apoptosis in cultured hippocampal neurons was attenuated in a concentration-dependent manner by COSs pretreatment. After measurement with Fluo 4-AM, COSs were found to depress glutamate-induced elevation in intracellular calcium concentration ([Ca²⁺]_c). The enzymatic assay indicated that COSs antagonized glutamate-evoked activation of caspase-3. These results collectively suggest that COSs prevent cultured hippocampal neurons from glutamate-induced cell damage by interfering with an increase in [Ca²⁺]_c and inhibiting caspase-3 activity.