Background & Aims-The generation of oxidative stress and TGF-β1 production play important roles in liver fibrogenesis. We have previously shown that HCV increases hepatocyte TGF-β1 expression. However, the mechanisms by which this induction occurs have not been well studied. We explored the possibility that HCV infection regulates TGF-β1 expression through generation of reactive oxygen species (ROS), which act through one or more of the p38 MAPK, ERK, JNK, and NFκB signaling pathways to induce TGF-β1 expression.

No abstract

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1␤ and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1␤ cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR ‫؍‬ 2.2; 95% CI ‫؍‬ 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR ‫؍‬ 3.4; 95% CI ‫؍‬ 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1␤ levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1␤ production contributed to the development of intestinal-type GC in this Korean population.

Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid, shown to have chemopreventive and/or anticancer properties in a variety of human cancer cells. The involvement of autophagy in apigenin-induced apoptotic cell death of HCT116 human colon cancer cells was investigated. Apigenin induced suppression of cell growth in a concentration-dependent manner in HCT116 cells. Flow cytometric analyses indicated that apigenin resulted in G2/M phase arrest. This flavone also suppressed the expression of both cyclin B1 and its activating partners, Cdc2 and Cdc25c, whereas the expression of cell cycle inhibitors, such as p53 and p53-dependent p21(CIP1/WAF1), was increased after apigenin treatment. Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles by flow cytometry. Furthermore, the results of the western blot analysis revealed that the levels of LC3-II, the processed form of LC3-I, was increased by apigenin. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the levels of PARP cleavage. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in HCT116 colon cancer cells. Autophagy plays a cytoprotective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for colon cancer control.

Despite the remarkable progress recently made to enhance the resolution of white-light endoscopy, detection, and diagnosis of premalignant lesions, such as adenomas and subtle early-stage cancers, remains a great challenge. As for example, although chromoendoscopy, such as endoscopy using indigo carmine, is useful for the early diagnosis of subtle lesions, the technique presents various disadvantages ranging from the time required for spray application of the dye and suctioning of excess dye to the increased difficulty in identifying lesions in the presence of severe inflammation and obstruction of visual field due to the pooling of solution in depressed-type lesions. To overcome these diagnostic problems associated with chromoendoscopy, research has focused on the development of endoscopes based on new optical technologies. Several types of image-enhanced endoscopy methods have recently been presented. In particular, image-enhanced endoscopy has emerged as a new paradigm for the diagnosis of gastrointestinal disorders. Image-enhanced endoscopes provide high-contrast images of lesions by means of optical or electronic technologies, including the contrast enhancement of the mucosal surface and of blood vessels. Chromoendoscopy, narrow-band imaging, i-SCAN, and flexible spectral imaging color enhancement are representative examples of image-enhanced endoscopy discussed in this paper.

Cyperi rhizoma, the rhizome of Cyperus rotundus L. (Family Cyperaceae), is a well-known functional food and traditional herbal medicine in Korea. It has been reported that Cyperi rhizoma has antioxidant and free radical scavenging activities that play a major role in protection of neurodegenerative disorders, such as Parkinson's disease (PD). In the present study, the neuroprotective effects of a water extract of Cyperi rhizoma (CRE) against 6-hydroxydopamine (6-OHDA)-induced neuronal damage were evaluated in an experimental model of PD. In PC12 cells, CRE showed a significant protective effect on cell viability at 50 and 100 microg/mL. CRE inhibited generation of reactive oxygen species and nitric oxide, reduction of mitochondrial membrane potential, and caspase-3 activity, which were induced by 6-OHDA. CRE also showed a significant protective effect against damage to dopaminergic neurons in primary mesencephalic culture. These results suggest that CRE has neuroprotective effects against 6-OHDA-induced toxicity through antioxidant and anti-apoptotic activities in an in vitro PD model.

Canine atopic dermatitis (CAD) is a ubiquitous, chronic inflammatory skin disorder prevalent in dogs, which results in production of abnormal levels of IgE antibodies in reciprocation to an allergen challenge. In this study, administration of the probiotic strain Lactobacillus sakei probio-65 for 2 months significantly reduced the disease severity index in experimental dogs diagnosed with CAD. In addition, one month pre-medication of L. sakei probio-65 revealed significant difference in the PVAS score in experimental dogs for both probio-65 and placebo groups. However, post 2 months treatment resulted in a significant decrease in the CASESI score values in the probio-65-treated group (p < .0.06).

Clarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.