A lack of role for antibodies in regulating Helicobacter pylori colonization and associated gastritis.
- 作者列表："Arshad U","Sarkar S","Alipour Talesh G","Sutton P
BACKGROUND:Helicobacter pylori occupy a unique niche, located within the mucus layer lining the stomach, and attached to the apical surface of the gastric epithelium. As such, antibodies would be expected to play a major role in regulating infection and/or pathogenesis. However, experiments using antibody-deficient mice to study gastric helicobacter infection have yielded inconsistent results, although some pointed toward antibodies increasing colonization levels and decreasing gastritis severity. The variability in these studies is possibly due to their use of nonmatched wild-type controls. This current study presents the first evaluation of the role of antibodies in H pylori infection by comparing antibody-deficient mice with matched wild-type siblings. METHODS:Matched wild-type and antibody-deficient μMT mice were generated by heterozygous crossings. In two separate experiments, appropriately genotyped sibling littermates were infected with H pylori for 4 months and then sera and stomachs were collected. RESULTS:There was no difference in H pylori colonization levels between infected μMT mice and sibling wild-type controls. Similarly, there was no significant difference in the severity of gastritis between these groups of mice, although there was a trend toward less severe gastritis in μMT mice which was supported by a significantly lower IFNγ (Th1) gastric cytokine response. CONCLUSIONS:Comparing matched antibody-deficient and antibody-competent mice indicates that an antibody response does not influence H pylori colonization levels. Contrary to previous studies, these results suggest antibodies might have a minor pro-inflammatory effect by promoting gastric Th1 cytokines, although this did not translate to a significant effect on gastritis severity.
背景: 幽门螺杆菌占据了一个独特的位置，位于胃粘膜层内，并附着在胃上皮的顶端表面。因此，抗体有望在调节感染和/或发病机制中发挥主要作用。然而，使用抗体缺陷小鼠研究胃幽门螺杆菌感染的实验得出了不一致的结果，尽管一些实验指出抗体增加定植水平和降低胃炎严重程度。这些研究的变异性可能是由于它们使用了不匹配的野生型对照。本研究通过比较抗体缺陷小鼠与匹配的野生型兄弟姐妹，首次评价了抗体在 H.pylori 感染中的作用。 方法: 通过杂合交叉产生匹配的野生型和抗体缺陷型 μ mt 小鼠。在两个单独的实验中，适当基因分型的同胞同窝被 H.pylori 感染 4 个月，然后收集血清和胃。 结果: 感染 μ mt 小鼠和同胞野生型对照组的 H.pylori 定植水平无差异。同样，这些组小鼠之间胃炎的严重程度没有显著差异, 尽管 μ mt 小鼠存在轻度胃炎的趋势，但 ifn γ (Th1) 胃细胞因子反应显著降低支持了这一趋势。 结论: 比较匹配的抗体缺陷小鼠和抗体感受态小鼠表明抗体反应不影响幽门螺杆菌定植水平。与以前的研究相反，这些结果表明抗体可能通过促进胃 Th1 细胞因子产生轻微的促炎作用，尽管这并没有转化为对胃炎严重程度的显著影响。
METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
METHODS::Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.
METHODS:Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, andmetastasis of cancer cells is one of the main features of this illness. The expressionlevels of the CFL1 gene have been modulated in this pathway. Using small interferingRNA (siRNA) in the treatment of gastric cancer is considered a hopeful genetherapeutic approach. The present study reported the level of CFL1 genes betweentumor and margin and healthy tissue of gastric cancer. Also, the features of a cationicnanoparticle with a polymer coating containing polyacrylic acid and polyethylenei-mine that were used in the delivery of CFL1 siRNA, were shown. Then thecytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle wereevaluated with CFL1siRNA. Method:In this study, the CFL1 gene expression was measured in 40 gastricadenocarcinoma, marginal and 15 healthy biopsy samples by a real‐time polymerasechain reaction. Physicochemical characteristics, apoptosis, and inhibition of migrationof the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated ingastric cancer cells. Result:The CFL1 expression was remarkably increased in gastric cancer tissues incomparison with the marginal samples and normal tissues (p< .05) and the biomarkerindex for CFL1 was obtained as 0.94, then this gene can be probably used as abiomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, theCFL1 expression level of mRNA and migration in AGS cells were remarkablysuppressed after transfection. Furthermore, the amount of apoptosis increased(p< .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells caninterdict cell migration. Finally, our outcomes propose that CFL1 can function as anoncogenic gene in gastric cancer and would be considered as a potential purpose ofgene therapy for gastric cancer treatment