An improved noninfections murine skin model of organized granulomatous inflammation

Summary An improved model of granulomatous inflammation in skin was developed by second passage skin grafting of isolated, lyophilized skin granulomas, originally elicited in naive mice by inoculations of lyophilized hepatic schistosome egg granulomas. The tissue reaction is caused by a single exposure to a noninfectious, acellular granulomagenic stimulus and occurs in healthy mice free of systemic disease. The model should prove useful for isolation of granuloma initiation factor(s). Furthermore, because there is a time lag before new granuloma formation begins, a window exists for analytical dissection of the initiation process. In this study we described the responses of host cells by autoradiography, and light and electron microscopy. The activity of angiotensin-converting enzyme and proline-specific endopeptidase showed a modulation during granuloma formation. In addition we found that severe immunosuppression with high dose cyclosporine therapy did not alter granuloma formation, supporting the idea that initiation of organized granulomas is T-cell independent.     

An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis

Osteoarthritis is the most common form of human arthritis. We investigated the potential role of asporin, an extracellular matrix component expressed abundantly in the articular cartilage of individuals with osteoarthritis, in the pathogenesis of osteoarthritis. Here we report a significant association between a polymorphism in the aspartic acid (D) repeat of the gene encoding asporin (ASPN) and osteoarthritis. In two independent populations of individuals with knee osteoarthritis, the D14 allele of ASPN is over-represented relative to the common D13 allele, and its frequency increases with disease severity. The D14 allele is also over-represented in individuals with hip osteoarthritis. Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. The effect on TGF-beta activity is allele-specific, with the D14 allele resulting in greater inhibition than other alleles. In vitro binding assays showed a direct interaction between asporin and TGF-beta. Taken together, these findings provide another functional link between extracellular matrix proteins, TGF-beta activity and disease, suggesting new therapeutic strategies for osteoarthritis.     

Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.     

同步辐射技术在大气环境生物监视器中的应用研究

基于同步辐射先进光源为研究平台, 探讨了苔藓植物监视大气污染的机制. 使用同步辐射X射线显微成像技术, 观测了苔藓植物细胞超微结构的变化. 使用同步X荧光微探针对苔藓组织表面和茎干剖面进行微区扫描测定, 获取了苔藓植物叶面和茎断面Pb, Cu, Fe, Ni, Mn, Zn, Ca, K等元素的精细分布. 结果表明, 苔藓植物对环境重金属污染十分敏感且具有较强的富集能力, 环境污染会导致苔藓植物体细胞损伤、超微结构变化和生长发育滞缓等一系列影响. 在遭受污染情况下, 叶表吸附和富集了过量的Fe, Ni, Pb等金属离子, 同时抑制了植物对K, Ca, Zn等微量营养元素的正常吸收.     

A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction

Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in a member of protein kinase C (PKC) family, PRKCH, was significantly associated with lacunar infarction in two independent Japanese samples (P = 5.1 x 10(-7), crude odds ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted hazard ratio of 2.83). We also found that PKCeta was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and its expression increased as the lesion type progressed. Our results support a role for PRKCH in the pathogenesis of cerebral infarction.