Homocysteine induces vascular inflammatory response via SMAD7 hypermethylation in human umbilical vein smooth muscle cells.

Homocysteine (Hcy) can induce atherosclerosis through the inflammatory response and DNA methylation disorder. Our recent study has reported a novel epigenetic modified gene related to atherosclerosis -SMAD7. To further understand the pathogenesis of atherosclerosis, the current study was designed to investigate an inflammatory role of Hcy in human umbilical vein smooth muscle cells (HUVSMCs) through interfering with SMAD7 methylation. Using MALDI-TOF MS, we found that Hcy increased DNA methylation levels of SMAD7 promoter in a dose and time-dependent manner in HUVSMCs. Meanwhile, both SMAD7 mRNA and protein levels were decreased along with the increase of Hcy concentrations and treating time. Decreased SMAD7 levels led to up regulation of pro-inflammatory cytokines (TNF-α and IL-1ß) expression in HUVSMCs. Furthermore, we found that activation of NF-κB pathway was the mechanism by which reduced Smad7 levels enhanced vascular inflammation. Thus, Hcy is able to activate NF-κB-mediated vascular inflammatory response via inducing hypermethylation of SMAD7 promoter in HUVSMCs. The in vitro findings supplement our recent clinical study that SMAD7 methylation as a novel marker in atherosclerosis and further elucidate the role of Hcy in atherogenesis.

[Tree species identification of wooden funeral utensil from Qing Dynasty's tombs and its potential of ecological and environmental indicator in Shenyang, Northeast China]. / æ²ˆé˜³æ¸ å¢“æœ¨è´¨è‘¬å ·çš„æ ‘ç§é‰´å®šåŠç”Ÿæ€çŽ¯å¢ƒçš„æŒ‡ç¤ºæ½œåŠ›.

The wood used for funeral utensil in ancient tomb is a kind of valuable materials and important for understanding vegetation, climate and society conditions in the history. Here, we identified the tree species and dated the time of wooden utensils for funeral excavated from tombs in Shuijia Village, Shenyang, using wood anatomy methods and dendrochronological techniques. The results showed that 7 out of the 16 wood samples were identified as Pinus tabuliformis from Pinaceae, 8 were Larix sp. from Pinaceae and most likely Larix olgensis, and the rest one was Acer sp. from Aceraceae. Currently, these tree species are still widely distributed in Liaoning Province, indicating that forest structure (tree species composition) is relatively stable and that the climate at that time was quite similar to that at present. The timbers used for wooden utensils of funeral for civilian tombs had regional biogeographic characteristics and reflected regional social productivity development level in Mukden (now Shenyang) in Qing Dynasty: most of them were native tree species with low cost and high availability; the main timber trees were conifer species, and a few of them were broadleaved trees. These timbers were likely from the forest in Shenyang or mountainous areas in Eastern Liaoning, with Hunhe River waterway being an important transport way for timbers to Shenyang. Some P. tabuliformis and Larix sp. timbers could be cross-dated well, and the growth period of the trees was determined to be 1680s-1770s (early to mid-Qing Dynasty). The variations of tree-ring width of these timbers had good consistency and high climate sensitivity, reflecting the consistency of regional climate and environment. These timbers have the potential to indicate the climate condition of the early to mid-Qing Dynasty.