Association of MCP-1 promoter polymorphism with susceptibility to nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is prevalent among populations from southern China and is influenced by both genetic and environmental risk factors. The monocyte chemoattractant protein-1 (MCP-1), a member of cysteine-cysteine chemokine family, plays critical roles in cancers. A polymorphism within the MCP-1 promoter, rs1024611, has been shown to be significantly associated with the risk of several cancers. Our purpose was to assess the role of rs1024611 in NPC susceptibility. By polymerase chain reaction-restriction fragment length polymorphism method, we genotyped rs1024611 in 593 patients with NPC (cases) and 480 cancer-free subjects (controls) among Guangxi population from southern China. We observed that the G allele of rs1024611 was significantly associated with the increased risk of NPC in an additive model and dominant model, respectively (P = 0.018 and 0.010, odds ratio = 1.25 and 1.41, respectively). No appreciable variation of the effects was found across the subgroups stratified by age, sex, nationality, smoking and drinking status, and smoking level. In addition, significantly higher messenger RNA (mRNA) expression level of MCP-1 was observed in NPC tissues than that in normal nasopharyngeal tissues, and the G allele of rs1024611 was significantly associated with elevated mRNA expression level of MCP-1 in Epstein-Barr virus-transformed lymphocytes. In conclusion, our findings suggested that rs1024611 at the MCP-1 promoter may be a risk factor for NPC. Further studies with larger sample size are necessary to confirm these findings.     

Identification of differential proteins in nasopharyngeal carcinoma cells with p53 silence by proteome analysis

Although mutation of p53 tumor-suppressor gene is rare in nasopharyngeal carcinoma (NPC), NPC has a high frequency of overexpression of p53 protein. There seem to be complex mechanisms of inactivation and stabilization of p53 in NPC. To detect proteins associated with the function of p53 in high throughout screening, we succeeded in establishing p53 knockdown human NPC CNE2 cell line (CNE2sip53) using stable RNA interference, and compared the proteomic changes between CNE2sip53 and control cell line CNE2/pSUPER using two-dimensional gel electrophoresis. Twenty-two differentially expressed proteins between the two cell lines were identified by both matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization tandem mass spectrometry, some of which are known to be associated with the p53 function (HSP27, hnRNP K, 14-3-3sigma, etc.), and others may be novel proteins associated with p53 function (eIF4B, TPT1, hnRNP H3, SFRS1 etc.). Furthermore, several differential proteins including HSP27, HSP70, GRP75 and GRP78 were verified as p53 interacting proteins in NPC by immunoprecipitation and Western blot analysis, and the suppression of HSP27 expression by HSP27 antisense oligonucleotides could decrease the p53 protein level. Our data suggest that these differential proteins may be associated with the function of p53 in NPC, and provide new clues to elucidate the mechanisms of inactivation and stabilization of p53 in NPC.     

Circulating (cell-free) nucleic acids--a promising, non-invasive tool for early detection of several human diseases

Circulating nucleic acids (CNA) are present in small amounts in the plasma of healthy individuals. However, increased levels of plasma CNA have been reported in a number of clinical disorders like cancer, stroke, trauma, myocardial infarction, autoimmune disorders, and pregnancy-associated complications. CNA has received special attention because of its potential application as a non-invasive, rapid and sensitive tool for molecular diagnosis and monitoring of acute pathologies and the prenatal diagnosis of fetal genetic diseases. This review throws light on the current status of blood CNA as a diagnostic marker and its potential as a powerful tool in the future.     

What can Caenorhabditis elegans tell us about the nuclear envelope?

The nuclear envelope (NE) of the eukaryotic cell provides an essential barrier that separates the nuclear compartment from the cytoplasm. In addition, the NE is involved in essential functions such as nuclear stability, regulation of gene expression, centrosome separation and nuclear migration and positioning. In metazoa the NE breaks down and re-assembles around the segregated chromatids during each cell division. In this review we discuss the molecular constituents of the Caenorhabditis elegans NE and describe their role in post-mitotic NE re-formation, as well as the usefulness of C. elegans as an in vivo system for analyzing NE dynamics.     

The maximal size of protein to diffuse through the nuclear pore is larger than 60kDa

It has generally been believed that the diffusion limit set by the nuclear pore for protein is 60kDa. We here studied the cellular localization of several artificial proteins and found that the diffusion limit set by the nuclear pore is not as small as previously thought. The results indicate that the maximal size of protein to diffuse through the nuclear pore complex could be quite larger than 60kDa, thus greatly extending the diffusion limit that the nuclear pore can accommodate.     

鼻咽癌患者EB病毒潜伏膜蛋白（LMP1）的特异性细胞免疫研究

建立了检测ＥＢ病毒伏膜蛋持异性杀伤性Ｔ细胞功能的一步法,并用于检测鼻咽癌患者外周血中ＬＭＰ１特异性ＣＴＬ功能,发现鼻咽癌患者外周血中ＬＭＰ１特异性ＣＴＬ功能显著低于正常人群,这可能与鼻咽癌的发病有关。研究还ＬＭＰ１鼻咽癌的疫苗抗原。为研究鼻咽癌的特异性细胞免疫预防与治疗提供了实验依据。     

Epstein-Barr病毒和鼻咽癌血清学诊断

EB病毒与鼻咽癌关系密切。 EB病毒抗原可用于鼻咽癌早期诊断以提高鼻咽癌病人存活率。本文对 EB病毒生活周期及其抗原系统 ,EB病毒与鼻咽癌之间关系及应用 EB病毒抗原进行鼻咽癌血清学诊断的进展作一概括介绍     

进入细胞核之门：核移位机制研究进展

细胞中DNA复制和RNA生物形成发生在细胞核,而蛋白质的合成场所位于细胞质,这些生命活动的整合依赖于功能蛋白等在两个亚空间尺度的选择性穿梭.这是一个信号介导的过程,需要能量和可溶性因子如穿梭载体的参与.通过介绍功能蛋白受控核移位机制研究进展,拓宽了其潜在的医学应用,该领域的深入研究,将有力推动抗病毒治疗和基因治疗载体的设计研究.     

The Ran GTPase cycle is required for yeast nuclear pore complex assembly

Here, we report the first evidence that the Ran GTPase cycle is required for nuclear pore complex (NPC) assembly. Using a genetic approach, factors required for NPC assembly were identified in Saccharomyces cerevisiae. Four mutant complementation groups were characterized that correspond to respective mutations in genes encoding Ran (gsp1), and essential Ran regulatory factors Ran GTPase-activating protein (rna1), Ran guanine nucleotide exchange factor (prp20), and the RanGDP import factor (ntf2). All the mutants showed temperature-dependent mislocalization of green fluorescence protein (GFP)-tagged nucleoporins (nups) and the pore-membrane protein Pom152. A decrease in GFP fluorescence associated with the nuclear envelope was observed along with an increase in the diffuse, cytoplasmic signal with GFP foci. The defects did not affect the stability of existing NPCs, and nup mislocalization was dependent on de novo protein synthesis and continued cell growth. Electron microscopy analysis revealed striking membrane perturbations and the accumulation of vesicles in arrested mutants. Using both biochemical fractionation and immunoelectron microscopy methods, these vesicles were shown to contain nups. We propose a model wherein a Ran-mediated vesicular fusion step is required for NPC assembly into intact nuclear envelopes.     

Ezetimibe enhances macrophage reverse cholesterol transport in hamsters: Contribution of hepato–biliary pathway

Reverse cholesterol transport (RCT) is pivotal in the return of excess cholesterol from peripheral tissues to the liver for excretion in bile and eventually feces. RCT from macrophages is a critical anti-atherogenicity mechanism of HDL. As the cholesterol absorption inhibitor ezetimibe promoted RCT in mice, which lack cholesterol ester transfer protein (CETP), we investigated its effects in hamsters, which have CETP.