01)The

01).The Ruxolitinib price expression of Toll like receptor-4 and cyclooxygenase-2 in sporadic colorectal cancer were correlated with the infiltration depth, TNM stage and lymph node metastasis(P < 0.05), but not with age, sex, position and histology grade(P > 0.05). Conclusion: Increased expression of the Toll like receptor-4 and cyclooxygenase-2 in colorectal carcinoma may play an important role in the development and carcinogenesis of sporadic colorectal cancer and can be used as marker to estimate the development of colorectal carcinoma. Toll like receptor-4 may promote sporadic colorectal

cancer progression via upregulating the expression of cyclooxygenase-2. Key Word(s): 1. colorectal cancer; 2. Toll like receptor-4; 3. Cyclooxygenase-2; 4. Microenviroment; Presenting Author: YUN WANG Additional Authors: LIN LIN, QINGE WANG Corresponding Author: YUN WANG Affiliations: The First Affiliated Hospital of Nanjing Medical Universiy Objective: Excessive production of advanced glycation end products (AGEs) implicate in pathogenesis

of diabetic complications. Smooth muscle pathology is involved in diabetic-associated colonic motility dysfunction. The aim of present study was to investigate whether AGEs contribute to diabetic colon myopathy. Methods: Streptozotocin-induced diabetic or nondiabetic Sprague Dawley rats were followed for 16 weeks, with groups randomized to no treatment or the AGEs formation inhibitor aminoguanidine (AG). At 16 week, colonic motility function (distal colon transit find more time and circular smooth muscle strips contractility) and histopathologic changes in colonic muscle layer were measured. Plasma levels of Nε-carboxymethyl lysine (CML) and smooth muscle contractile protein including myosin heavy chain (MHC) and smooth muscle α-actin (SM α-actin) expression levels were studied. Complementary in vitro studies were performed in which primary rat colonic smooth muscle cells (SMCs), in the presence and absence of AGEs,

were treated with MAPK inhibitors. Results: Circulating CML levels, the major AGEs compound, in diabetes rats were decreased by AG administration. AG attenuated diabetic colon motility 上海皓元 dysfunction and weakness of circular smooth muscle strips contractility. However, morphological study demonstrated that the length of colon, the thickness of both of circular and longitudinal muscle layer and sizes of SMCs were increased significantly in diabetic rats, and these changes were associated with an increase expression of contractile protein (MHC and SMα-actin), while AG administration reversed these changes. In cultured SMCs, AGEs induced contractile protein expression in a concentration and time-dependent manner. Finally, AGEs treatment activated phosphorylation of JNK and p38 MAPK in SMCs, but only p38 MAPK inhibitor SB239063 blocked the effects of AGEs on contractile protein expression.

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