MDOC and atorvastatin have potential antiinflammatory effects in vascular endothelium of apoE-/- mouse model of atherosclerosis

Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM- 1), strongly participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherogenesis. The aim of this study was to detect and quantify the changes of endothelial expression of VCAM-1, and ICAM-1 in the vessel wall after the short-term administration of simvastatin, atorvastatin, and micro dispersed derivatives of oxidised cellulose (MDOC™) in apolipoprotein-E-deficient (apoE^−/−) mice atherosclerotic model. Hyperlipidemic apoE^−/− mice (n = 32) received normal chow diet or diet containing simvastatin or atorvastatin 10 mg/kg/day or MDOC™ 50 mg/kg/day. Total cholesterol, VLDL, LDL, HDL and TAG were measured and the endothelial expression of VCAM-1 and ICAM-1 was visualized and quantified by means of immunohistochemistry and stereology, respectively. Total cholesterol levels was insignificantly lowered only in MDOC™ treated mice but not in mice treated with statins. ICAM-1 endothelial expression was not affected by neither simvastatin nor MDOC™ treatment. However, significant diminution of VCAM-1 endothelial expression was observed in both atorvastatin and MDOC™ treated mice. These results provide new information of potential hypolipidemic substance MDOC™ and its potential anti-inflammatory effects. Furthermore, we have confirmed anti-inflammatory effects of atorvastatin independent of plasma cholesterol lowering. Thus, the results of this study show potential benefit of both MDOC™ and atorvastatin treatment in apoE^−/− mouse model of atherosclerosis suggesting their possible combination might be of interest.     

Circulating adhesion molecules in apoE-deficient mouse strains with different atherosclerosis susceptibility

Recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in development of atherosclerosis. Apolipoprotein E-deficient (apoE(-/-)) mice have spontaneous hyperlipidemia and develop all phases of atherosclerotic lesions. We sought to examine plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and sP-selectin in two apoE(-/-) strains C57BL/6 (B6) and BALB/c with early or advanced lesions. Mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. On either diet, BALB/c.apoE(-/-) mice developed much smaller atherosclerotic lesions and displayed significantly lower levels of sVCAM-1 and sP-selectin than B6.apoE(-/-) mice. The Western diet significantly elevated sVCAM-1 levels in both strains and sP-selectin levels in B6.apoE(-/-) mice. BALB/c.apoE(-/-) mice exhibited 2-fold higher HDL cholesterol levels on the chow diet and 15-fold higher HDL levels on the Western diet than B6.apoE(-/-) mice, although the two strains had comparable levels of total cholesterol and triglyceride. Thus, increased atherosclerosis is accompanied by increases in circulating VCAM-1 and P-selectin levels in the two apoE(-/-) mouse strains, and the high HDL level may protect against atherosclerosis by inhibiting the expression of adhesion molecules in BALB/c.apoE(-/-) mice.     

Cranial nerve growth in birds is preceded by cholinesterase expression during neural crest cell migration and the formation of an HNK-1 scaffold

Summary The expression of the neural crest cell (NCC) markers acetylcholinesterase (AChE) and the HNK-1-epitope is compared from the emigration of cephalic NCC until the formation of the cranial nerves V-X in chicken and quail hindbrain. We show that NCC transiently express acetylcholinesterase (AChE) activity during their emigration; NCC migrate into butyrylcholinesterase (BChE)-positive areas of the cranial mesenchyme. Along these migratory tracks that foreshadow the course of later projecting cranial nerves, BChE increases strongly in cells that may represent immature Schwann cells. Both AChE and BChE, but not HNK-1, are expressed in the ectodermal placodes. In NCC, HNK-1 is expressed strongly only when they approach their destination sites. Their intense expression of HNK-1 then leads to the establishment of tunnel-shaped HNK-1 matrices, within which G4-positive cranial neurites begin to extend. We conclude that AChE and HNK-1 expression in cephalic NCC serve different functions, since AChE is related to their migration, and HNK-1 to their aggregation and the formation of an extracellular neurite scaffold.     

Differential gene expression in the developing human macula: microarray analysis using rare tissue samples

The macula is a unique and important region in the primate retina that achieves high resolution and color vision in the central visual field. We recently reported data obtained from microarray analysis of gene expression in the macula of the human fetal retina (Kozulin et al., Mol Vis 15:45–59, 1). In this paper, we describe the preliminary analyses undertaken to visualize differences and verify comparability of the replicates used in that study, report the differential expression of other gene families obtained from the analysis, and show the reproducibility of our findings in several gene families by quantitative real-time PCR.     

Regulation of interleukin-21 receptor expression and its signal transduction by WSB-2

Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain (γc) receptor subunit. We identified novel IL-21R-binding molecule, WD-40 repeats containing SOCS-box-2, WSB-2. WSB-2 associated with the membrane-proximal intracytoplasmic region of IL-21R, including box1 and box2. Overexpression study of WSB-2 showed the reduction of IL-21R expression and IL-21-induced signal transduction. On the other hand, small interfering RNA for WSB-2 enhanced the expression level of IL-21R and IL-21-induced STAT3 activation, indicating that WSB-2 negatively controls the receptor expression. This report provides the first evidence that WSB-2 is a regulator of IL-21R expression and IL-21-induced signal transduction.     

Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents

The interactions of the T cell receptor (TCR) with cognate MHC-peptide and co-stimulatory molecules expressed at surface of antigen presenting cells (APC) leads to activation or tolerance of T cells. The development of molecular biological tools allowed for the preparation of soluble MHC-peptide molecules as surrogate for the APC. A decade ago a monomeric class II MHC molecule in which the peptide was covalently linked to β-chain of class II molecule was generated. This type of molecule had a low-binding affinity and did not cause the multimerization of TCR. The requirement of multimerization of TCR led to development of a new class of reagents, chimeric peptides covalently linked to MHC that was dimerized via Fc fragment of an immunoglobulin and linked to 3' end of the β-chain of MHC class II molecule. These soluble dimerized MHC-peptide chimeric molecules display high affinity for the TCR and caused multimerization of TCR without processing by an APC. Because dimeric molecules are devoid of co-stimulatory molecules interacting with CD28, a second signal, they induce anergy rather the activation of T cells. In this review, we compare the human and murine dimerized MHC class II-peptides and their effect on CD4(+) T cells, particularly the generation of T regulatory cells, which make these chimeric molecules an appealing approach for the treatment of autoimmune diseases.     

Attenuation of DNA damage and mRNA gene expression in hypoxic rats using natural antioxidants

This study aimed to explore the efficiency of carnosine (Cs) and/or l ‐arginine (Agn) in the downregulation of apoptotic and inflammatory molecule expression and DNA damage caused hepatic injury in response to sodium nitrite (Sd)‐induced hypoxia in rats. Rats were injected with Sd; Agn or/and Cs were administrated prior to Sd intoxication. Sd significantly decreased hemoglobin concentration and Bcl‐2 mRNA expression, while increased expressions of apoptotic markers (Bax and caspase), tumor necrosis factor‐α, nuclear factor kappa B, and C‐reactive protein and the oxidative DNA damage in hepatic tissue. Moreover, administration of Agn or/and Cs exhibited a modulation of the previous parameters. However, concurrent treatment with the forementioned antioxidants modulated these levels. It was concluded that the treatment with the combination of Agn and Cs was the most effective regimen in ameliorating Sd toxicity accompanied by hypoxic stress.     

菜粉蝶颗粒体病毒分子与银表面间相互作用的SERS谱研究

通过对菜粉蝶颗粒体病毒粒子（样品）遥表面增强拉曼散射（ＳＥＲＳ）光谱的分析,得出样品分子在ＳＥＲＳ中与银表面相互作用的一些特征。样品分子主要通过闳基和氨基与银表面键联。相应谱带的拉曼增强效果与分子基因处于银表面的几何状态有关。分子与银表面产生化学吸附芳香族氨基酸侧链的π－电子得合物和分子基因的α－复合物的存在,使增强具有短程特性,其增强机制主要为分子增强。