EBV感染上皮细胞机制的研究进展

近年来发现 EBV与多种上皮细胞恶性肿瘤的发生密切相关 ,探讨 EBV感染上皮细胞的机制对预防和治疗 EBV相关疾病有重要意义。本文就 EBV感染上皮细胞的可能机制作一综述。

志贺菌侵袭上皮细胞机制的研究进展

志贺菌主要的致病特点是侵入肠粘膜上皮细胞。同上皮细胞的接触激活了志贺菌Ⅲ型分泌器,分泌一套Ipas蛋白,通过复杂的信号过程引起宿主细胞骨架重排,促使细菌侵入,其中IpaB、IpaC、VirA、IcsA及IcsB与溶泡及胞内的运动、胞间的扩散密切相关。

EB病毒感染上皮细胞机制的研究进展

Epstein －Barr 病毒（EBV）为疱疹病毒科嗜淋巴细胞属的成员，是单核细胞增多症的病原体，并与多种人类恶性肿瘤如 Burkitt 淋巴瘤、鼻咽癌及免疫缺陷患者的 B 淋巴细胞瘤等发生密切相关。 EBV 在超过90％的人群中存在着潜伏感染［1］，但它一般仅存在于淋巴细胞内，仅有极少数侵入上皮细胞中并参与恶性肿瘤的发生发展。 EBV 侵犯上皮细胞是细胞恶性转化的表现，该观点也越来越受到学者们的认可。目前，学者们对 EBV 感染 B 淋巴细胞的机制了解较多，然而对 EBV 是如何感染上皮细胞的却是知之甚少，EBV 感染上皮细胞的机制也逐渐成为近年来的研究热点。本文就EBV 感染上皮细胞的4种可能的主要途径作一综述。

乙型肝炎病毒损伤肾小管上皮细胞机制的研究进展

乙型肝炎病毒（HBV）感染除了导致急慢性肝炎、肝硬化、肝癌以外，还可能引起多种肝外损害。乙肝病毒相关性肾炎（HBV—GN）是HBV感染最常见的肝外损伤之一，其发病机制至今尚未完全阐明。目前的研究显示，HBV对肾小管上皮细胞有着多方面的影响，可以通过多种途径引起肾小管上皮细胞的凋亡，且能导致肾小管上皮细胞的固有免疫及适应性免疫功能紊乱。本文旨在总结HBV对肾小管上皮细胞的影响及其可能机制。

Helicobacter pylori infection and micronutrient deficiencies

It is known that deficiencies of micronutrients due to infections increase morbidity and mortality.This phenomenon depicts itself conspicuously in developing countries. Deficiencies of iron,vitamins A,E,C,B12,etc are widely prevalent among populations living in the third world countries.Helicobacter pylori(H pylori)infection has a high prevalence throughout the world.Deficiencies of several micronutrients due to H pylori infection may be concomitantly present and vary from subtle sub-clinical states to severe clinical disorders.These essential trace elements/ micronutrients are involved in host defense mechanisms, maintaining epithelial cell integrity,glycoprotein synthesis, transport mechanisms,myocardial contractility,brain development,cholesterol and glucose metabolism.In this paper H pylori infection in associaed with various micronutrients deficiencies is briefly reviewed.

BRCA1 affects global DNA methylation through regulation of DNMT1

Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1. BRCA1 binds to the promoter of the DNMT1 gene through a potential OCT1 site and the binding is required for maintaining a transcriptional active configuration of the promoter in both mouse and human cells. We further demonstrated that impaired function of BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an open chromatin configuration in several types of tissues examined in a BRCA1 mutant mouse model at premaligant stages. BRCA1 deficiency is also associated with significantly increased expression levels of several protooncogenes, including c-Fos, Ha-Ras, and c-Myc, with a higher expression in tumors, while premalignant mammary epithelial cells displayed an intermediate state between tumors and controls. In human clinical samples, reduced expression of BRCA1 correlates with decreased levels of DNMT1, and reduced methylation of CpG islands. Thus, BRCA1 prevents global DNA hypomethylation through positively regulating DNMT1 expression, and this provides one of mechanisms for BRCAl-associated breast cancer formation.

Different cytokine response of primary colonic epithelial cells to commensal bacteria

AIM: To determine if primary murine colonic epithelial cells (CEC) respond to commensal bacteria and discriminate between different types of bacteria. METHODS: A novel CEC: bacteria co-culture system was used to compare the ability of the colonic commensal bacteria, Bacteroides ovatus, E coli(SLF) and Lactobacillus rhamnosus (LGG) to modulate production of different cytokines (n = 15) by primary CEC. Antibody staining and flow cytometry were used to investigate Toll-like receptor (TLR) expression by CEC directly ex vivo and TLR responsiveness was determined by examining the ability of TLR ligands to influence CEC cytokine production. RESULTS: Primary CEC constitutively expressed functional TLR2 and TLR4. Cultured in complete medium alone, CEC secreted IL-6, MCP-1 and IP-10 the levels of which were significantly increased upon addition of the TLR ligands peptidoglycan (PGN) and lipopolysaccharide (LPS). Exposure to the commensal bacteria induced or up-regulated different patterns of cytokine production and secretion.E coli induced production of MIP-1α/β and p defensin3 whereas B. ovatus and L. rhamnosus exclusively induced MCP-1 and MIP-2α expression, respectively. TNFa, RANTES and MEC were induced or up-regulated in response to some but not all of the bacteria whereas ENA78 and IP-10 were up-regulated in response to all bacteria. Evidence of bacterial interference and suppression of cytokine production was obtained from mixed bacterial: CEC co-cultures. Probiotic LGG suppressed E coli- and B. ovatus-induced cytokine mRNA accumulation and protein secretion. CONCLUSION: These observations demonstrate the ability of primary CEC to respond to and discriminate between different strains of commensal bacteria and identify a mechanism by which probiotic bacteria (LGG) may exert anti-inflammatory effects in vivo.

Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma

AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma.METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues.CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.

Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis

Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.

Juvenile polyposis syndrome

Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer.The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34.Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes.Clinically,juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum,juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis.In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found.Both genes play a role in the BMP/TGF-beta signalling pathway.It has been suggested that cancer in juvenile polyposis may develop through the socalled "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma.Recognition of this rare disorder is important for patients and their families with regard to treatment,follow-up and screening of at risk individuals.Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome.In addition,juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer.This review discusses clinical manifestations,genetics,pathogenesis and management of juvenile polyposis syndrome.

Expression of the novel gene NM23-H1B in ovarian cancer

Objective:To study the expression of the human novel gene NM23-H1B in ovarian cancer. Methods: Totally 24 samples from patients with epithelial ovarian tumor at different clinical stages and 4 from normal ovaries were examined for NM23-H1B mRNA expression by RT-PCR and Northern blot. Results: All samples expressed NM23-H1B mRNA through RT-PCR, while the level of expression in ovarian tumor was higher than that of normal ovary. The results of Northern blot showed that NM23-H1B was overexpressed in ovarian cancer while lowexpressed in normal ovary or low malignant potential (LMP). The level of expression at early stage cancer(stageⅠand Ⅱ) was higher than those in advanced cancer(stage Ⅲ and Ⅳ). In early stage carcinoma, the expression level was involved in the differentiation of tumor cell, and well-differentiated cancer expressed NM23-H1B mRNA in comparatively higher level. Conclusion: The novel gene NM23-N1B is closely correlated with the ovarian cancer.