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: Cyclovirobuxinum D (CVB-D), an alkaloid isolated from the Chinese medicinal plant Buxus microphylla, has been found to be effective to treat cardiac insufficiency, arrhythmias and coronary heart disease. In the present study, we investigated the effects of CVB-D on the inflammatory responses in lipopolysaccharide (LPS)-stimulated murine macrophages in vitro and the underlying mechanisms.', 'Murine macrophage cell line RAW264.7 cells were incubated in the presence of LPS (0.1 g/mL) for 24 h. The cell viability was measured using MTT assay. The release of NO and cytokines were detected using the Griess test and ELISA, respectively. The mRNA and protein levels were determined using RT-PCR and Western blot, respectively. Reporter gene assays were used to analyze the transcriptional activity of NF-B.', 'Treatment of RAW264.7 cells with CVB-D (25-300 mol/L) did not affect the cell viability. Pretreatment with CVB-D (50, 100 and 200 mol/L) concentration-dependently decreased NO release and iNOS expression in LPS-treated RAW264.7 cells (its IC50 value in inhibition of NO production was 144 mol/L). CVB-D also concentration-dependently inhibited the secretion and mRNA expression of IL-1 and IL-6 in LPS-treated RAW264.7 cells. Furthermore, CVB-D remarkably inhibited the phosphorylation of STAT1 and STAT3, as well as JAK2 in LPS-treated RAW264.7 cells, but did not affect the activation of NF-B and MAPKs pathways. Pretreatment with the JAK2 specific inhibitor AG490 (30 mol/L) produced similar effects on NO release and iNOS expression in LPS-treated RAW264.7 cells.

SOLUTION: Does cyclovirobuxinum D suppress lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway?

PROBLEM: To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration.', 'We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial.', 'Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P < 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 vs. 0.8 cm(2), P < 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70-94), whereas in those who failed to heal, the percent change in wound area was 25% (15-35; P < 0.001).

SOLUTION: Is percent change in wound area of diabetic foot ulcers over a 4-week period a robust predictor of complete healing in a 12-week prospective trial?

PROBLEM: Hypercholesterolemia is associated with abnormal endothelium-dependent vasorelaxation due to decreased nitric oxide bioavailability. Our aim was to examine the effect of adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) to the hypercholesterolemic rabbit carotid artery in vivo. In addition, we examined whether adenovirus-mediated gene transfer was associated with vascular dysfunction.', 'Rabbits were fed a 1% cholesterol diet for 4 weeks followed by a 0.5% cholesterol diet for 6 weeks. Vascular reactivity was assessed in nontransduced carotid arteries from chow- and cholesterol-fed animals. In addition, carotid arteries were surgically isolated, and 2 separate doses of adenoviral vectors encoding eNOS or beta-galactosidase (AdbetaGal) on the contralateral side were delivered to the lumen (1x10(10) and 5x10(10) pfu/mL).', 'Abnormal acetylcholine-mediated endothelium-dependent vasorelaxation was detected in the carotid artery from cholesterol-fed animals, whereas responses to calcium ionophore A23187 and diethylamine NONOate were normal. Vascular reactivity was similar in nontransduced and AdbetaGal-transduced hypercholesterolemic vessels. In vessels transduced with eNOS, transgene expression was demonstrated by immunostaining in both the endothelium and the adventitia and by Western blot analysis. High-dose but not low-dose eNOS gene transfer enhanced endothelium-dependent relaxation in vessels from cholesterol-fed rabbits.

SOLUTION:
Does in vivo gene transfer of endothelial nitric oxide synthase to carotid arteries from hypercholesterolemic rabbits enhance endothelium-dependent relaxations?