In vitro modulatory effects of functionalized pyrimidines and piperidine derivatives on Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) activities

The development of biologically active molecules based on molecular recognition is an attractive and challenging task in medicinal chemistry and the molecules that can activate/deactivate certain receptors are of great medical interest. In this contribution, selected pyrimidine/piperidine derivatives were synthesized and tested for the ability to activate/deactivate Aryl hydrocarbon receptor (AhR) and Glucocorticoid receptor (GR). Tested compounds are shown to activate the receptors but to much lesser extent than positive controls, dioxin and dexamethasone for Ahr and GR, respectively. However, some of them antagonized the positive controls action. Although further in vivo studies are needed to fully characterize the bioactivities of these compounds, the reported in vitro evidences demonstrate that they might be used as the modulators of AhR and GR activities.     

The investigation of membrane binding by amphibian peptide agonists of CCK2R using 31P and 2H solid-state NMR

It has been proposed that some neuropeptides may be anchored to the cell membranes prior to attaching to the adjacent active sites of transmembrane receptors. The three amphibian skin neuropeptides signiferin 1 [RLCIPYIIPC(OH)] (smooth muscle active and immunomodulator), riparin 1.1 [[RLCIPVIFPC(OH)] (immunomodulator) and rothein 1 [SVSNIPESIGF(OH)] (immunomodulator) act via CCK2 transmembrane receptors. A combination of ³¹P and ²H solid state NMR studies of each of these three peptides in eukaryotic phospholipid models at 25 °C shows that rothein 1 does not interact with the membrane at all. In contrast, both of the cyclic disulfides signiferin 1 and riparin 1.1 interact with phospholipid head groups and partially penetrate into the upper leaflet of the model bilayer, but to different extents. These interactions are not sufficiently effective to cause disruption of the lipid bilayer since the peptides are not antimicrobial, anticancer, antifungal nor active against enveloped viruses.     

Identification of ‘cystic fibrosis protein’ as a complex of two calcium-binding proteins present in human cells of myeloid origin

Cystic fibrosis protein is a serum protein characterized by a pI close to 8.4 and present with a higher concentration in serum and plasma of cystic fibrosis carriers than in controls. This protein was found immunologically indistinguishable from the cystic fibrosis antigen isolated from granulocytes and presenting a sequence analogous to that of MRP-8, a calcium-binding protein expressed in the myeloid cell lineage. Using antibodies directed against MRP-8 and its closely associated calcium-binding protein, MRP-14, we demonstrate here that cystic fibrosis protein purified from serum is a complex of the two proteins MRP-8 and MRP-14.     

SARS病毒s1基因片段真核表达载体的构建及免疫效果

本研究根据GenBank登录的BJ01株SARS-CoV序列合成801bpS1基因片段,该片段被亚克隆至真核表达载体pcDNA3.1( )得到重组质粒pcDNA3.1( )/S1;转染Hela细胞,SDS-PAGE、Western-Blotting鉴定蛋白表达;肌注免疫BALB/c小鼠,利用ELISA法检测免疫后小鼠的抗SARS-CoVIgG及IFN-γ水平,MTT法检测T细胞增殖活性。结果显示,重组质粒pcDNA3.1( )/S1可在Hela细胞内表达S1蛋白,免疫后小鼠的T细胞增殖活性增强,抗SARS-CoVIgG与IFN-γ水平升高。本实验说明pcDNA3.1( )/S1可诱导小鼠产生一定的体液免疫和细胞免疫应答。     

遗传标记和免疫学方法在实验动物质量控制中的应用

生命科学发展迅速,实验动物级别逐渐提高,在保证生物制品实验结果可靠性前提下,完善动物由低级别向高级别过渡显得十分必要,最终目的达到实验动物标准化和动物实验规范化。对实验动物质量控制中的遗传标记和免疫学方法进行了综述。     

甲型肝炎病毒的提取及免疫学性质分析

目的建立甲型肝炎病毒(hepatitis A virus, HAV)的提取方法,了解和掌握HAV的免疫学性质。方法利用人胚肺二倍体细胞培养并收获HAV,用层析纯化等方法提取HAV,然后通过抗原检测、免疫电镜检查以及小鼠免疫试验对HAV的免疫学性质进行检测和分析。结果利用层析纯化等方法提取HAV,抗原回收率达84%以上,蛋白去除率达97%以上,电镜及免疫电镜检查可以观测到典型的HAV以及HAV+IgM抗原抗体免疫复合物和HAV+IgG抗原抗体免疫复合物,免疫小鼠抗体阳转率为100%。结论利用层析纯化等方法可以对HAV进行有效提取,提取的HAV具有良好的免疫反应性和免疫原性。     

C6／36细胞上登革2型病毒受体的免疫共沉淀

本文利用差速离心方法提纯的登革2型病毒、抗登革病毒单抗、病毒受体、耦合有G蛋白的琼脂糖珠之间特异性结合的作用,利用免疫共沉淀方法从C6／36细胞中分离鉴定出分子量约为35kDa受体蛋白;并用糖蛋白染色方法否定了此蛋白的糖基化特征。     

Conditions for pathogen elimination by immune systems

Summary A continuous harvest effort can lead a population to extinction. How an “unconscious” immune system would perpetrate such an effort in order to eliminate a self-replicating antigen (a pathogen) becomes an intriguing problem if the system responses are functions of the pathogen population: the responses cannot be a continuous effort as the pathogen vanishes. On theoretical grounds, we show some qualities an immune response must have to support pathogen elimination. Then, three specific mechanisms are addressed: a pathogen-independent positive feedback loop among the responding cells of the system (e.g., B-lymphocyte and T-helper); the persistence of antigen bound to presenting cells; and the programmed expansion/contraction of a pool of responding cells. The maintenance of responding cells due to these mechanisms is the essential feature to the effective clearance of self-replicating agents. Thus, evolutionarily, the primary function of a helper lymphocyte would be to amplify a response and the primary function of memory would be the very elimination of pathogens.     

Territorial damselflies do not show immunological priming in the wild

Adaptive immunity allows vertebrates to gain protection against repeated pathogenic infections. Analogous responses (priming) have been recently uncovered in invertebrates. However, whether such responses are widespread is not known. The present study investigated the presence of immunological priming in males of a species whose phylogenetic position places it in one of the less derived insect orders. It is hypothesized that the efficiency of such a response could be related to animal condition, as assessed by the expression of a sexually selected ornament. Hetaerina americana Fabricius (Odonata: Calopterygidae) males bear a conspicuous ornament (a red wing spot), which is evolutionarily maintained via male territorial competition. Using field‐collected animals, a group of males is challenged with bacteria before exposure to a higher dose of the same or a different bacteria, and survival is compared with that of infected males not previously challenged, as well as control groups. Gram‐positive and Gram‐negative bacteria are used. To explore how long priming may take to work, the second exposure is carried out either after 1 or 5 days. Red spot and body size are entered in the analysis as predictors of survival within and between groups. There is no difference in survival among groups, which suggests no priming effect. Overall, red spot and body size are not consistent in explaining survival.