Evaluation of therapeutic properties of fermented vegetables extract (OM-X®) in the model of colitis induced by Citrobacter rodentium in mice

AbstractInfection of mice with Citrobacter rodentium serves as a model to study human intestinal infections. C. rodentium infection leads to increased production of inflammatory cytokines, immune cell infiltration and damage to the gut barrier. We used this model of colitis to evaluate the therapeutic properties of OM-X®, an extract prepared by fermentation of vegetables, seaweeds, fruits and mushrooms. Administration of OM-X® to C. rodentium-infected mice reduced damage to the intestinal epithelium, lowered inflammation scores, increased IL-10 expression and maintained FoxP3 gene expression. OM-X® also partially prevented bacterial translocation, increased expression of tight junction genes and increased proliferation of epithelial cells. PCR analysis of stool samples showed that OM-X® significantly reduced the populations of bacteria harboring buk gene (mostly Clostridium species). It is suggested that alterations of microbiota composition, following OM-X® consumption, contribute to protection against infection and epithelial damage, and lead to an increased expression of anti-inflammatory cytokines

Pathological significance and prognostic implications of heme oxygenase 1 expression in non?muscle?invasive bladder cancer: Correlation with cell proliferation, angiogenesis, lymphangiogenesis and expression of VEGFs and COX?2

Heme oxygenase 1 (HO-1) is a stress-response protein and its expression is associated with malignant potential and poor prognosis in several types of cancer. The present study investigated the association between HO-1 expression levels and the pathological features, clinical outcomes and other associated factors in patients with non-muscle-invasive bladder cancer (NMIBC). HO-1 expression was evaluated using immunohistochemistry in 147 formalin-fixed tissue specimens. The proliferation index, microvessel density, lymph vessel density and expression of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and-D were also investigated. Correlations among variables were analyzed by multivariate analysis. Survival was assessed using Kaplan-Meier survival curves and multivariate statistics. HO-1 expression levels in high-grade and pT1 tumors were significantly higher compared with low-grade and pTa tumors, and were correlated with the proliferation index (P<0.001), lymph vessel density (P=0.021) and COX-2 expression levels (P=0.003). The proliferation index and COX-2 expression levels were also identified as independent contributing factors in multivariate models. Kaplan-Meier survival curves associated HO-1 expression with a poor prognosis in metastasis-free (P=0.047) and cause-specific survival (P=0.017), but not with urinary tract recurrence (P=0.231). Furthermore, HO-1 expression was identified by multivariate analysis to be a significant predictor for cause-specific survival (hazard ratio, 4.08; 95% confidence interval, 1.06-15.66; P=0.004). HO-1 has an important role in the malignant aggressiveness of NMIBC and its expression is associated with cause-specific survival. HO-1-associated activities are regulated by cancer cell proliferation, lymphangiogenesis and COX-2. The results suggest that HO-1 may be a potential therapeutic target and a useful predictive prognostic factor in patients with NMIBC