TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: An abnormal ratio of vasohibin-2/vasohibin-1 may be involved in the abnormal angiogenesis and vascular remodeling during pulmonary arterial hypertension (PAH).', 'To evaluate the pharmacological actions of Ponatinib (AP) in experimental model of PAH, the effects of AP on TGF-β1-mediated endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMEC), and the hypoxic human pulmonary artery smooth muscle cells (HPASMC) proliferation and HPMEC in vitro, and on bleomycin (BLM)-induced PAH in vivo were investigated.', 'AP treatment resulted in a reduction of EndoMT in HPMECs with a decrease of vimentin, whereas an increase of VE-cadherin, reduction of fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF) and vasohibin-2 (VASH-2), whereas an increase of vasohibin-1 (VASH-1) in the hypoxic HPMEC, a reduction of the HPASMC proliferation with decreases of wnt5a, β-catenin and cyclin D1 expression. AP ameliorated BLM-induced PAH in rats with reductions of FGF-2, VEGF, von Willebrand factor (vWF) and VASH-2 expression, whereas an increase of VASH-1 expression. AP ameliorated BLM-induced PAH in rats with reductions of the pathological score and the collagen deposition. In addition, AP ameliorated hemodynamics and right ventricular hypertrophy.

SOLUTION: Does ponatinib attenuate experimental pulmonary arterial hypertension by modulating Wnt signaling and vasohibin-2/vasohibin-1?

PROBLEM: Two-dimensional speckle tracking echocardiography (2DSTE) has been used widely in research, but rarely in clinical practice because data acquisition and analysis are time-consuming. By reducing the acquisition and analysis time, 3-dimensional STE may improve clinical impact. We investigated the feasibility of 3DSTE myocardial deformation, with comparison to 2DSTE.', 'Transthoracic 3DSTE and 2DSTE were performed in 230 adults (138 men, 51 ± 14 years, and 142 hypertension, 10 heart failure and 78 normotensive subjects). The variables of LV deformation were analyzed using EchoPAC software.', 'The 3D LV longitudinal (LS) analysis was feasible in 84.9% of the study subjects, which was lower than the 2D analysis (97.2%). The success rates for circumferential strain (CS) and radial strain (RS) were similar between the 2D and 3D techniques. All magnitude of strains measured by 2DSTE and 3DSTE were significantly correlated. The magnitude of 3D LS and CS was lower, but the 3D RS is higher than that of 2DSTE (-18.5 ± 2.8 vs. -21.2 ± 3.5; 20.8 ± 4.1 vs. 21.7; and 50.0 ± 11.2 vs. 37.7 ± 12.6, respectively). Strains measured by 3DSTE exhibited stronger correlation with LV ejection fraction (EF) than that by 2DSTE. In inter- and intra-observer reproducibility for 3D LS, CS, RS and AS were acceptable. The mean time of analysis for LV volume, EF and strains was 116s by 3DSTE, which was significantly shorter than that by 2DSTE (5 min, P<0.0001).

SOLUTION: Is three-dimensional speckle strain echocardiography more accurate and efficient than 2D strain in the evaluation of left ventricular function?

PROBLEM: Extracellular vesicles (EVs), including circulating microvesicles (MVs) or mi- croparticles (MPs) and exosomes, derived from cells or platelets are present in the peripheral blood and are important elements involved in the activation of the coagulation system, transport of macromolecules and intercellular communication. In patients with vascular complications (including diabetes), the number of EVs is significantly increased during the acute phase of the disease. However, less is known about EVs release in the chronic state of diabetes.', 'To analyse the profile of inflammatory cytokines and angiogenic factors in EVs in diabetic patients with ocular and vascular complications.', 'The study included patients with diabetes and varying degrees of ocular complications including retinopathy (n = 48) and the control group (n = 13). EV-enriched and EV-depleted fractions were obtained from platelet-poor plasma by means of the centrifugation method (16 000 g, for 90 min). In screening, the profile of cytokines with pro-angiogenic effects was preliminary assessed using the protein microarray technology for controlled diabetic patients - CD, uncontrolled diabetic patients - UD and for the control group. In all patients, concentrations of cytokines: RANTES (Regulated on Activation, Normal T-cell Expressed and secreted) and Ang-2 (angiopoietin-2) were assayed using the ELISA method. Common blood and biochemical tests were performed.', 'In patients with diabetes, analysis of supernatant revealed significantly increased concentrations of basic fibroblast growth factor (bFGF) and soluble receptor for vascular endothelial growth factor 2 (V-EGFR2) when compared to the control group: 49 (10.5-122) vs. 24 (2-72.5) SD (p = 0.03) and 260 (195.5-351) vs. 360 (256-461.5) SD (p = 0.01). In UD patients, concentrations of RANTES, angiostatin, tumor necrosis factor-α (TNF), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP1 and TIMP2) were relatively higher in the EV-enriched fraction when compared to the EV-depleted fraction. Post hoc analysis revealed significant differences between UC patients and the control group in RANTES (16.73 (14.41-18.93) vs. 14.62 (12.37-15.28) mg/ml; p = 0.0235) and Ang-2 (2.76 (2.23-4.64) ng/ml vs. 1.74 (1.54-1.93); p = 0.0316) concentrations. These analyses did not reveal any significant differences in RANTES and Ang-2 concentrations between CD patients and the control group.

SOLUTION:
Do extracellular vesicles participate in the transport of cytokines and angiogenic factors in diabetic patients with ocular complications?