Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Insulin exerts a direct action on vascular cells, thereby affecting the outcome and progression of diabetic vascular complications. However, the mechanism through which insulin signalling is impaired in the endothelium of diabetic individuals remains unclear. In this work, we have evaluated the role of the AGE precursor methylglyoxal (MGO) in generating endothelial insulin resistance both in cells and in animal models.', 'Time course experiments were performed on mouse aortic endothelial cells (MAECs) incubated with 500 mol/l MGO. The glyoxalase-1 inhibitor S-p-bromobenzylglutathione-cyclopentyl-diester (SpBrBzGSHCp2) was used to increase the endogenous levels of MGO. For the in vivo study, an MGO solution was administrated i.p. to C57BL/6 mice for 7 weeks.', 'MGO prevented the insulin-dependent activation of the IRS1/protein kinase Akt/endothelial nitric oxide synthase (eNOS) pathway, thereby blunting nitric oxide (NO) production, while extracellular signal-regulated kinase (ERK1/2) activation and endothelin-1 (ET-1) release were increased by MGO in MAECs. Similar results were obtained in MAECs treated with SpBrBzGSHCp2. In MGO- and SpBrBzGSHCp2-exposed cells, inhibition of ERK1/2 decreased IRS1 phosphorylation on S616 and rescued insulin-dependent Akt activation and NO generation, indicating that MGO inhibition of the IRS1/Akt/eNOS pathway is mediated, at least in part, by ERK1/2. Chronic administration of MGO to C57BL/6 mice impaired whole-body insulin sensitivity and induced endothelial insulin resistance.
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Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.', 'The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.', 'We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).
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Metastasis is a primary cause of colorectal cancer (CRC)-related death, and cancer stem cells (CSCs) are thought to be majorly responsible for initiating metastatic behaviors. Doublecortin-like kinase 1 (DCLK1) was recently discovered to be a marker for gastrointestinal CSCs. Here, we aimed to explore whether DCLK1 is associated with CRC metastasis through clinical and in vitro investigations.', 'The expression levels of DCLK1 mRNA and protein in human CRC tissues were analyzed through quantitative RT-PCR and immunohistochemistry staining, respectively. Human CRC cell line SW480 was selected to explore the effect of DCLK1 overexpression on cell migration and invasion. Besides, the associations between DCLK1 and epithelial-mesenchymal transition (EMT) were determined.', 'Compared to normal colorectal tissues, DCLK1 expression was significantly up-regulated in human CRC tissues and correlated well with high lymphatic metastasis and poor prognosis in patients. DCLK1 expression was inversely associated with overall survival in CRC patients. Overexpression of DCLK1 in SW480 cells markedly promoted cell migration and invasion. Furthermore, we validated that DCLK1 could facilitate EMT in cancer cells by up-regulation of the mesenchymal markers Vimentin and ZEB1 and down-regulation of the epithelial marker E-cadherin in SW480 cells.
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