Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation

AIM: To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.

Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P < 0.05) in the jejunum,whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and modulation of TGF-β1 signaling

AIM:To investigate whether targeting proteasome might reverse intestinal fibrosis in rats.METHODS:Chronic colitis was induced in rats by repeated administration of increasing dose of2,4,6-trinitrobenzene sulfonic acid(TNBS,15,30,45,60,60,60 mg)by rectal injection for 6 wk(from day0 to day 35),while control rats received the vehicle.TNBS+bortezomib(BTZ)rats received intraperitoneal injections of BTZ twice weekly(from day 37 to day44)at a dose of 25 mg/kg,whereas the control and TNBS groups received the same amount of the vehicle.Histologic scoring of inflammation and fibrosis was performed.Colonic production of transforming growth factor(TGF)-βwas measured by ELISA.Colon fibrosisrelated proteins such as phospho-p38,phosphoSMAD2/3,Akt and peroxisome proliferator activated receptorγ(PPARγ)were studied by western blot.Expression of the tight junction proteins,occludin and claudin-1,were assessed by Western blot.Colon proteasome activities(chymotrypsin-like and trypsinlike activities)were assessed.RESULTS:TNBS-treated rats had a higher colon weight/length ratio compared to control rats(P<0.01).Furthermore,fibrosis and inflammation scores were higher in TNBS-treated rats compared to control rats(P<0.01 for both).Colonic production of TGF-βproduction tended to be higher in TNBS-treated rats(P<0.06).Fibrosis-related proteins such as phospho-p38,phospho-SMAD2/3,and PPARγwere significantly higher in TNBS-treated rats compared to control rats(all P<0.05).TNBS rats had a higher expression of Akt compared to control rats(P<0.01).Tight junction proteins were modified by repeated TNBS challenge:colon occludin expression rose significantly(P<0.01),whereas claudin-1 expression fell(P<0.01).Bortezomib inhibition significantly decreased chymotrypsin-like activity(P<0.05),but had no significant effect on trypsin-like activity(P>0.05).In contrast,bortezomib had no effect on other studied parameters such as fibrosis score,TGF-βsignaling,or tight junction expression(P>0.05 for all).CONCLUSION:Rats with TNBS-induced chronic colitis exhibited colon fibrosis associated with higher TGF-βsignaling.Proteasome inhibition by bortezomib had no effect on fibrosis in our experimental conditions.

Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia

AIM： To quantify the intraepithelial lymphocytes （IELs） and to document the membrane expression of CD4, CD8, TCRγδ and adhesion and/or activation-associated molecules （CD103, CD28, CD44, CD69, HLA-DR, CD95/ Fas） in the duodenal mucosa of patients with functional dyspepsia （FD） in order to provide arguments for an immunological process in FD. METHODS： Twenty-six FD patients according to Rome Ⅱ criteria （20 were H pylori negative） were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS： Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRy8 and CD103, CD44, CD28, CD69 on CD3＋ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/ Fas [22 （9-65） vs 45 （19-88）, P = 0.03] and HLADR expressing CD3＋ IELs [4 （0-30） vs 13 （4-42）, P = 0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 （6.7-62.5） vs 10.8 （3-33.3）, P = 0.02] due to a higher number of CD8＋ CD3＋ IELs. CONCLUSION： In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.