Induction of CD69 expression by cag PAI-positive Helicobacter pylori infection

AIM: To investigate and elucidate the molecular mechanism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori ) infection. METHODS: The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononuclear cells (PBMCs), and CD4 + T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori-induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island (cag PAI) and virD4 were used to elucidate the role of cag PAI-encoding type Ⅳ secretion system and CagA in CD69 expression.RESULTS: CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of pa- tients with H. pylori-positive gastritis. Although cag PAI- positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cag-PAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4 + T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori-induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori-induced CD69 mRNA expression. CONCLUSION: The results suggest that H. pylori induces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori-induced gastritis.

Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection

AIM:To evaluate the effects of fucoidan,a complex sulfated polysaccharide extract from marine seaweed,on hepatitis C virus(HCV) RNA load both in vitro and in vivo.METHODS:HCV-1b replicon-expressing cells were cultured in the presence of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in Okinawa,Japan,and quantified the level of HCV replication.In an open-label uncontrolled study,15 patients with chronic hepatitis C,and HCV-related cirrhosis and hepatocellular carcinoma were treated with fucoidan(0.83 g/d) for 12 mo.The clinical symptoms,biochemical tests,and HCV RNA levels were assessed before,during,and after treatment.RESULTS:Fucoidan dose-dependently inhibited the expression of HCV replicon.At 8-10 mo of treatment with fucoidan,HCV RNA levels were significantly lower relative to the baseline.The same treatment also tended to lower serum alanine aminotransferase levels,and the latter correlated with HCV RNA levels.However,the improved laboratory tests did not translate into significant clinical improvement.Fucoidan had no serious adverse effects.CONCLUSION:Our findings suggest that fucoidan is safe and useful in the treatment of patients with HCVrelated chronic liver diseases.Further controlled clinical trials are needed to confirm the present findings.

Comparison of High-Dose Dexamethasone and Prednisone for Initial Treatment of Adult Primary Immune Thrombocytopenia

Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.

Do predators prefer toxic animals?A case of chemical discrimination by an Asian snake that sequesters firefly toxins

Several Asian natricine snakes of the genus Rhabdophis feed on toads and sequester steroidal cardiac toxins known as bufadienolides(BDs)from them.A recent study revealed that species of the Rhabdophis nuchalis Group ingest lampyrine fireflies to sequester BDs.Although several species of fireflies are distributed in the habitat of the R.nuchalis Group,only lampyrine fireflies,which have BDs,are included in the diet of these snakes.Thus,we hypothesized that the R.nuchalis Group chemically distinguishes fireflies that have BDs from those that do not have BDs.We also predicted that the R.nuchalis Group detects BDs as the chemical cue of toxin source.To test these predictions,we conducted 3 behavioral experiments using Rhabdophis chiwen,which belongs to the R.nuchalis Group.In the first experiment,R.chiwen showed a moderate tongue flicking response to cinobufagin,a compound of BDs.On the other hand,the snake showed a higher response to the chemical stimuli of lampyrine fireflies(BD fireflies)than those of lucioline fireflies(non-BD fireflies).In the second experiment,in which we provided live BD and non-BD fireflies,the snake voluntarily consumed only the former.In the third,a Y-maze experiment,the snake tended to select the chemical trail of BD fireflies more frequently than that of non-BD fireflies.These results demonstrated that R.chiwen discriminates BD fireflies from non-BD fireflies,but the prediction that BDs are involved in this discrimination was not fully supported.To identify the proximate mechanisms of the recognition of novel toxic prey in the R.nuchalis Group,further investigation is necessary.