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: SUMO-specific protease 1 (SENP1) removes SUMO from proteins and plays important roles in the regulation of multiple cellular signalling pathways. However, little is known about the role of SENP1 in coronary heart disease. In this study, we tested the hypothesis that SENP1 protects against myocardial ischaemia/reperfusion (I/R) injury and investigated the underlying molecular mechanisms involved.', 'First, we found that SENP1 levels increased after I/R in human and mouse myocardium in vivo and in rat cardiomyocytes in vitro. We then performed coronary artery ligation to induce I/R injury in wild-type (WT) and heterozygous SENP1-knockdown (SENP1(+/-)) mice. Compared with WT mice, SENP1(+/-) mice had normal cardiac function at baseline but lower systolic function after I/R. Post-I/R myocardial infarction sizes were larger in SENP1(+/-) mice. Furthermore, we demonstrated that SENP1 regulates the expression of hypoxia-inducible factor 1 α (HIF1α), a critical protective factor during I/R, in vivo and in vitro. Overexpression of HIF1α reversed the deteriorating effect of SENP1 knockdown on cellular death.

SOLUTION: 1

PROBLEM: Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the mechanism remains unclear. In the present study, we used in vitro methods to investigate the effects of Dex on rat TSC differentiation and the molecular mechanisms underlying this process.', 'First, we used qPCR and Western blotting to detect the expression of the adipogenic differentiation markers aP2 and C/EBPα after treating the TSCs with Dex. Oil red staining was used to confirm that high concentration Dex promoted adipogenic differentiation of rat TSCs. Next, we used qPCR and Western blotting to detect the effect of a high concentration of dexamethasone on molecules related to the canonical WNT/β-catenin pathway in TSCs.', 'Treating rat TSCs with Dex promoted the synthesis of the inhibitory molecule dickkopf1 (DKK1) at the mRNA and protein levels. Western blotting results further showed that Dex downregulated the cellular signaling molecule phosphorylated glycogen synthase kinase-3β (P-GSK-3 β (ser9)), upregulated P-GSK-3β (tyr216), and downregulated the pivotal signaling molecule β-catenin. Furthermore, DKK1 knockdown attenuated Dex-induced inhibition of the canonical WNT/β-catenin pathway and of the adipogenic differentiation of TSCs. Lithium chloride (LiCl, a GSK-3β inhibitor) reduced Dex-induced inhibition of the classical WNT/β-catenin pathway in TSCs and of the differentiation of TSCs to adipocytes.

SOLUTION: 1

PROBLEM: Marinobufagenin (MBG) promotes natriuresis via inhibition of renotubular Na/K-ATPase (NKA) and causes vasoconstriction via inhibition of vascular NKA. Atrial natriuretic peptide (ANP), via cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)-dependent mechanism, sensitizes renal NKA to MBG but reduces MBG-induced inhibition of vascular NKA. As aging is associated with a downregulation of cGMP/PKG signaling, we hypothesized that in older rats, ANP would not potentiate renal effects of MBG and would not oppose vascular effects of MBG.', 'In younger (3-month-old) and older (12-month-old) Sprague-Dawley rats, we compared SBP, natriuresis, activity of NKA in aorta and renal medulla, and levels of MBG and α-ANP at baseline and following acute NaCl loading (20%, 2.5\u200aml/kg, intraperitoneally), and studied modulation of MBG-induced NKA inhibition by α-ANP in vitro.', 'As compared with younger rats, NaCl-loaded older rats exhibited a greater MBG response, greater SBP elevation (25 vs. 10\u200ammHg, P\u200a<\u200a0.01) and greater inhibition of NKA in aorta (39 vs. 7%, P\u200a<\u200a0.01), 30% less natriuresis, and less inhibition of renal NKA (25 vs. 42%, P\u200a<\u200a0.05) in the presence of comparable responses of α-ANP and cGMP. In aorta and kidney of older rats, the levels of PKG were reduced, the levels of phosphodiesterase-5 were increased compared with that in young rats, and α-ANP failed to modulate MBG-induced NKA inhibition.

SOLUTION:
0