34 research outputs found

    Transfection of IL-10 expression vectors into endothelial cultures attenuates α4β7-dependent lymphocyte adhesion mediated by MAdCAM-1

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    BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression vector into endothelial cultures to reduce responses to a proinflammatory cytokine, TNF-α METHODS: A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-α induced lymphocyte adhesion to lymphatic endothelial cells and TNF-α induced expression of MAdCAM-1 and compared these responses to control monolayers. RESULTS: Transfection of the IL-10 vector into endothelial cultures significantly reduced TNF-α induced, MAdCAM-1 dependent lymphocyte adhesion (compared to non-transfected cells). IL-10 transfected endothelial cells expressed less than half (46 ± 6.6%) of the MAdCAM-1 induced by TNF-α (set as 100%) in non-transfected (control) cells. CONCLUSION: Our results suggest that gene therapy of the gut microvasculature with IL-10 vectors may be useful in the clinical treatment of IBD

    American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR

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    <p>Abstract</p> <p>Background</p> <p>Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth.</p> <p>Methods</p> <p>Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA.</p> <p>Results</p> <p>Ginseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth.</p> <p>Conclusions</p> <p>Ginseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis.</p

    Bio-inspired piezoelectric artificial hair cell Bio-inspired piezoelectric artificial hair cell molding

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    A piezoelectric artificial hair cell sensor was fabricated by the powder injection molding process in order to make an acoustic vector hydrophone. The entire process of powder injection molding was developed and optimized for PMN-PZT ceramic powder. The artificial hair cell sensor, which consists of high aspect ratio hair cell and three rectangular mechanoreceptors, was precisely fabricated through the developed powder injection molding process. The density and the dielectric property of the fabricated sensor shows 98% of the theoretical density and 85% of reference dielectric property of PMN-PZT ceramic powder. With regard to homogeneity, three rectangular mechanoreceptors have the same dimensions, with 3 mu m of tolerance with 8% of deviation of dielectric property. Packaged vector hydrophones measure the underwater acoustic signals from 500 to 800 Hz with - 212 dB of sensitivity. Directivity of vector hydrophone was acquired at 600 Hz as analyzing phase differences of electric signals.113sciescopu

    Study of sintering behavior of PAN–PZT using dilatometry and co-relation with piezoelectric properties

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    The sintering behavior of Pb(Al0.5Nb0.5)O-3-Pb(Zr0.52Ti0.48)O-3 (PAN-PZT) ceramics was investigated. The sintering process of PAN-PZT was divided into four stages based on the amount of in-situ linear shrinkage: (Stage 1) initial stage at sintering temperature RT 1265 degrees C. During stage 1, heating of PAN-PZT compact did not cause structural changes except the thermal expansion. During stage 2, the PZT-perovskite structure was formed by rearrangement of crystals. During stage 3, the specimen was rapidly densified with two peaks of strain rate. During stage 4, Pb was volatilized and this loss resulted in sudden increase of shrinkage. On analyzing the sintering stages, the optimized sintering conditions were considered as 1250 degrees C just before of Pb-loss stage. The effects of T-s on the crystal structure, microstructure and the piezoelectric performance were analyzed and documented. (C) 2015 Elsevier Ltd and Techna Group S.r.l. All rights reserved.X1175sciescopu
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