TASK DEFINITION: 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.
PROBLEM: 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 μmol/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.

SOLUTION: 1

PROBLEM: Defects in phagocytic nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) function cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by dysfunctional microbicidal activity and chronic inflammation.', 'We sought to study the effect of chronic inflammation on the hematopoietic compartment in patients and mice with X-linked chronic granulomatous disease (X-CGD).', 'We used immunostaining and functional analyses to study the hematopoietic compartment in patients with CGD.', 'An analysis of bone marrow cells from patients and mice with X-CGD revealed a dysregulated hematopoiesis characterized by increased numbers of hematopoietic progenitor cells (HPCs) at the expense of repopulating hematopoietic stem cells (HSCs). In patients with X-CGD, there was a clear reduction in the proportion of HSCs in bone marrow and peripheral blood, and they were also more rapidly exhausted after in vitro culture. In mice with X-CGD, increased cycling of HSCs, expansion of HPCs, and impaired long-term engraftment capacity were found to be associated with high concentrations of proinflammatory cytokines, including IL-1β. Treatment of wild-type mice with IL-1β induced enhanced cell-cycle entry of HSCs, expansion of HPCs, and defects in long-term engraftment, mimicking the effects observed in mice with X-CGD. Inhibition of cytokine signaling in mice with X-CGD reduced HPC numbers but had only minor effects on the repopulating ability of HSCs.

SOLUTION: 1

PROBLEM: MicroRNA-622 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, its role in esophageal squamous cell carcinoma (ESCC) is still unclear. The aim of this study was to explore the expression and function of miR-622 in ESCC.', 'Using quantitative RT-PCR, we detected miR-622 expression in ESCC cell lines and primary tumor tissues. The association of miR-622 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-622 on the biological behavior of ESCC cells were investigated. At last, the potential regulatory function of miR-622 on E2F1 expression was confirmed.', 'miR-622 was found to be down-regulated in ESCC tissues and cell lines. Decreased miR-622 expression was closely correlated with aggressive clinicopathological features and poor overall survival. Multivariate regression analysis corroborated that low level of miR-622 expression was an independent unfavourable prognostic factor for patients with ESCC. Up-regulation of miR-622 could significantly reduce ESCC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while down-regulation of miR-622 showed opposite effects. Further, E2F1 was confirmed as a direct target of miR-622 by using Luciferase Reporter Assay.

SOLUTION:

Show your work and conclude with the exact phrasing "Therefore, the final answer is [answer]." where [answer] is just the final number or expression that solves the problem.
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