Association of Four Genetic Polymorphisms of AGER and Its Circulating Forms with Coronary Artery Disease: A Meta-Analysis

Background

Considerable efforts have been devoted to evaluating the association of the receptor for advanced glycation end-products (gene AGER and protein: RAGE) genetic variants to coronary artery disease (CAD); the results, however, are often irreproducible. To generate more information, we sought to explore four common polymorphisms of AGER and its circulating forms associated with the risk of CAD via a meta-analysis.

Methodology/Principal Findings

Articles were identified by searching PubMed, EMBASE, Wanfang and CNKI databases before March 2013. Qualified articles had case-control designs and investigated AGER four polymorphisms (T-429C, T-374A, Gly82Ser, G1704A) or circulating soluble RAGE (sRAGE) or endogenous secretory RAGE (esRAGE) levels associated with CAD. Twenty-seven articles involving 39 independent groups fulfilled the predefined criteria. Overall, no significance was observed for all examined polymorphisms under allelic and dominant models. When restricting groups to CAD patients with diabetes mellitus or renal disease, deviations of risk estimates from the unity were stronger than overall estimates for all polymorphisms except for G1704A due to limited available studies. For example, under dominant model, having -429C allele increased the odds of developing CAD in diabetic patients by 1.22-fold (95% confidence interval (95% CI) 0.99–1.51; P = 0.06; I ² = 6.7%) compared with that of overall estimate of 1.15-fold (95% CI: 0.97–1.36; P = 0.111; I ² = 18.0%). Circulating sRAGE levels were non-significantly lower in CAD patients than in controls, whereas this reduction was totally and significantly reversed in CAD patients with diabetes mellitus (weighted mean difference: 185.71 pg/ml; 95% CI: 106.82 to 264.61 pg/ml). Circulating esRAGE levels were remarkably lower in CAD patients, as well as in subgroups with or without diabetes mellitus and without renal disease.

Conclusions

Our findings demonstrated that association of AGER genetic polymorphisms with CAD was potentiated in patients with diabetes mellitus or renal disease. Practically, circulating esRAGE might be a powerful negative predictor for the development of CAD.     

The Role of Metal Components in the Cardiovascular Effects of PM2.5

Exposure to ambient fine particulate matter (PM_2.5) increases risks for cardiovascular disorders (CVD). However, the mechanisms and components responsible for the effects are poorly understood. Based on our previous murine exposure studies, a translational pilot study was conducted in female residents of Jinchang and Zhangye, China, to test the hypothesis that specific chemical component of PM_2.5 is responsible for PM_2.5 associated CVD. Daily ambient and personal exposures to PM_2.5 and 35 elements were measured in the two cities. A total of 60 healthy nonsmoking adult women residents were recruited for measurements of inflammation biomarkers. In addition, circulating endothelial progenitor cells (CEPCs) were also measured in 20 subjects. The ambient levels of PM_2.5 were comparable between Jinchang and Zhangye (47.4 and 54.5µg/m³, respectively). However, the levels of nickel, copper, arsenic, and selenium in Jinchang were 82, 26, 12, and 6 fold higher than Zhangye, respectively. The levels of C-reactive protein (3.44±3.46 vs. 1.55±1.13), interleukin-6 (1.65±1.17 vs. 1.09±0.60), and vascular endothelial growth factor (117.6±217.0 vs. 22.7±21.3) were significantly higher in Jinchang. Furthermore, all phenotypes of CEPCs were significantly lower in subjects recruited from Jinchang than those from Zhangye. These results suggest that specific metals may be important components responsible for PM_2.5-induced cardiovascular effects and that the reduced capacity of endothelial repair may play a critical role.     

Enantioselective Liquid–Liquid Extraction of Zopiclone With Mandelic Acid Ester Derivatives

Enantioselective liquid–liquid extraction of zopiclone was conducted by employing a series of (R)‐mandelic acid esters as chiral extractants. The effects of concentration of extractant, concentration of zopiclone, type of organic solvent, pH value, and temperature on the extraction efficiency were investigated. (R)‐o‐chloromandelic acid propyl ester was demonstrated to be an efficient chiral extractant for zopiclone resolution with a maximum enantioselectivity of 1.6. Chirality 25:952–956, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis and biological evaluation of nonsymmetrical aromatic disulfides as novel inhibitors of acetohydroxyacid synthase

46 Novel nonsymmetrical aromatic disulfides containing [1,3,4]thiadiazole or [1,3,4]oxadiazole groups were synthesized and their biological activities were evaluated as inhibitors of acetohydroxyacid synthase (AHAS, EC 2.2.1.6). Besides their strong in vitro inhibition against plant AHAS, compounds 3e and 3f also display 80–100% post-emergence herbicidal activities in greenhouse bioassay at 1500 g/ha dosage. The assay of exogenous branched-chain amino acids supplementation on rape root growth of 3e suggests that the herbicidal activity has relationship with AHAS inhibition.     

Argostemma bachmaense (Rubiaceae,Rubioideae, Argostemmateae), a new species from central Vietnam

Argostemma bachmaense, a new species from central Vietnam, is described and illustrated here. The new species is most similar to A. laoticum and A. vietnamicum but can be distinguished from the latter two by having a well-developed internode with leaf pairs separately arranged along stem, isophyllous or slightly anisophyllous leaves, an oblanceolate to spatulate lamina with attenuate base and lateral veins with 4–5 pairs prominent on abaxially, a terminal, solitary flower, an absent bract, narrowly ovate or broadly lanceolate, 8.5–10.5 × 2.8–4.2 mm petals, 6.5–7.5 mm long stamen with yellow anther, a 8.5–9.5 mm long, exerted style and a globose stigma. Information on ecology, phenology and preliminary conservation assessment of the proposed new species are provided. In addition, we also provide an identification key to the nine Argostemma species found in Vietnam.     

Correction to: NaCl-induced stress: physiological responses of six halophyte species in in vitro and in vivo culture

Plant Cell, Tissue and Organ Culture (PCTOC) - In the original article, some of the values in the fifth column of Table 2 and in the fifth and eighth columns of Table 4 are incorrect. The corrected...     

Atherosclerosis-associated endothelial cell apoptosis by miRNA let7-b-mediated downregulation of HAS-2

MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of human diseases including atherosclerosis. Increasing numbers of miRNAs have been identified to be important regulators in the progression of atherosclerosis by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in atherosclerosis need fully elucidation. In the present study, the function of miRNA let-7b was investigated in human aortic endothelial cells (HAECs). The results showed that downregulation of let-7b in the high-fat diet mice and HAECs was inversely correlated with the expression level of HAS-2. upregulation of let-7b significantly reduced apoptosis of HAECs. The results also revealed that HAS-2 was a target gene of let-7b and HAS-2 reduction reversed the antiapoptotic effect of let-7b through regulation of the P13K/Akt pathway. These results together suggest the potential of regulating the let-7b expression and endothelial apoptosis against development and progression of atherosclerosis.     

拟南芥黏连蛋白RAD21对增强UV-B辐射后细胞分裂的响应

UV-B辐射对植物的影响体现在多个水平, 其会引起植物DNA损伤, 造成有丝分裂异常, 最终影响植物的生长发育及生理生化过程。RAD21.3是黏连蛋白复合物的一个亚基, 参与有丝分裂中染色体的分离。该研究以哥伦比亚生态型拟南芥(Arabidopsis thaliana)和atrad21.3突变体为材料, 设置对照(CK)及UV-B处理组, 对野生型(WT)、atrad21.3及过表达株系的根长、株高、抽薹时间和生理生化指标进行统计分析。利用碱性品红染色观察拟南芥根尖的有丝分裂现象, 并统计畸变率。SPSS分析结果表明, UV-B处理后, WT UV-B和atrad21.3 CK的抽薹时间、株高及各项生理生化指标与WT CK相比无显著差异, 但atrad21.3 UV-B与之相比差异显著。通过烟草(Nicotiana benthamiana)的瞬时表达和亚细胞定位观察, 发现RAD21.3集中在细胞核; 进一步观察分裂期细胞发现落后染色体、染色体桥和游离染色体等异常现象。统计结果表明, 与WT CK相比, WT UV-B和atrad21.3 CK的畸变率较高, 但atrad21.3 UV-B的畸变率更高, 表明RAD21.3可能响应UV-B辐射诱导的异常有丝分裂。