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 resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity.', 'To determine if a common, functional polymorphism in the UCP2 gene promoter region (the -866 G/A polymorphism) contributes to the risk of hyperglycaemia in severe sepsis.', 'In the prospective group 120 non-diabetic patients who were carriers of the G allele had significantly higher maximum blood glucose recordings than non-carriers (mean (SD) AA 8.5 (2.2) mmol/l; GA 8.5 (2.4) mmol/l; GG 10.1 (3.1) mmol/l; p = 0.0042) and required significantly more insulin to maintain target blood glucose (p = 0.0007). In the retrospective study 103 non-diabetic patients showed a similar relationship between maximum glucose and UCP genotype (AA 6.8 (2.3) mmol/l; GA 7.8 (2.2) mmol/l; GG 9.2 (2.9) mmol/l; p = 0.0078).
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Liver ischemia reperfusion (I/R) injury is a common pathophysiological process in many clinical settings. Carvacrol, a food additive commonly used in essential oils, has displayed antimicrobials, antitumor and antidepressant-like activities. In the present study, we investigated the protective effects of carvacrol on I/R injury in the Wistar rat livers and an in vitro hypoxia/restoration (H/R) model.', 'The hepatoportal vein, hepatic arterial and hepatic duct of Wistar rats were isolated and clamped for 30 min, followed by a 2 h reperfusion. Buffalo rat liver (BRL) cells were incubated under hypoxia for 4 h, followed normoxic conditions for 10 h to establish the H/R model in vitro. Liver injury was evaluated by measuring serum levels of alanine aminotransferase (ALT) and aspatate aminotransferase (AST), and hepatic levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondiadehyde (MDA), and hepatic histology and TUNEL staining. MTT assay, flow cytometric analysis and Hoechst 33258 staining were used to evaluate the proliferation and apoptosis of BRL cells in vitro. Protein expression was examined by Western Blot analysis.', 'Carvacrol protected against I/R-induced liver damage, evidenced by significantly reducing the serum levels of ALT and AST, histological alterations and apoptosis of liver cells in I/R rats. Carvacrol exhibited anti-oxidative activity in the I/R rats, reflected by significantly reducing the activity of SOD and the content of MDA, and restoring the activity of CAT and the content of GSH, in I/R rats. In the in vitro assays, carvacrol restored the viability and inhibited the apoptosis of BRL cells, which were subjected to a mimic I/R injury induced by hypoxia. In the investigation on molecular mechanisms, carvacrol downregulated the expression of Bax and upregulated the expression of Bcl-2, thus inhibited the activation of caspase-3. Carvacrol was also shown to enhance the phosphorylation of Akt.
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Despite new therapeutic approaches, metastatic melanomas still have a poor prognosis. Statins reduce low-density lipoprotein cholesterol and exert anti-inflammatory and anti-proliferative actions. We have recently shown that simvastatin triggers an apoptotic burst in human metastatic melanoma cells by the synthesis of an autocrine factor.', 'The current in vitro study was performed in human metastatic melanoma cell lines (A375, 518a2) and primary human melanocytes and melanoma cells. The secretome of simvastatin-stressed cells was analysed with two-dimensional difference gel electrophoresis and MS. The signalling pathways involved were analysed at the protein and mRNA level using pharmacological approaches and siRNA technology.', 'Simvastatin was shown to activate a stress cascade, leading to the synthesis of 15-deoxy-12,14-PGJ2 (15d-PGJ2 ), in a p38- and COX-2-dependent manner. Significant concentrations of 15d-PGJ2 were reached in the medium of melanoma cells, which were sufficient to activate caspase 8 and the mitochondrial pathway of apoptosis. Inhibition of lipocalin-type PGD synthase, a key enzyme for 15d-PGJ2 synthesis, abolished the apoptotic effect of simvastatin. Moreover, 15d-PGJ2 was shown to bind to the fatty acid-binding protein 5 (FABP5), which was up-regulated and predominantly detected in the secretome of simvastatin-stressed cells. Knockdown of FABP5 abolished simvastatin-induced activation of PPAR-γ and amplified the apoptotic response.

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