TASK DEFINITION: Given a passage with a context and an answer, 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: Context: Cilostazol, a potent type 3 phosphodiesterase inhibitor, is found to reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC) proliferation. The aim of this study is to investigate whether the inhibitory effect of cilostazol on VSMC proliferation is operated via heme oxygenase-1 (HO-1).', 'In rat carotid arteries, cilostazol up-regulated HO-1 in the neointima of balloon-injured arteries. Treatment of human VSMCs with cilostazol enhanced the expression of HO-1, which was mainly regulated at the transcriptional level. Small interfering RNA knock-down of HO-1 attenuated the inhibitory effect of cilostazol on VSMC proliferation, suggesting the critical role of HO-1 in cilostazol effect. The transcriptional responsiveness of HO-1 to cilostazol was inversely correlated with the length of GT-repeat in human HO-1 promoter. Deletion and mutational analysis of HO-1 promoter along with chromatin immunoprecipitation showed that cyclic AMP response element (CRE)-binding protein (CREB) participated in cilostazol-induced HO-1 transcription. Furthermore, cilostazol triggered a linkage between the CRE and GT-repeat regions in the HO-1 promoter. The promoting effect of cilostazol on HO-1 expression, proliferation inhibition, and chromatin conformation in the HO-1 promoter was greater in VSMCs from subjects with shorter GT-repeat alleles than those with longer alleles.
Answer: Cilostazol inhibits VSMC proliferation involving an association between CREB and HO-1. The length polymorphism of GT-repeat in human HO-1 promoter determines the effect of cilostazol.

SOLUTION: Does gT-repeat length polymorphism in heme oxygenase-1 promoter determine the effect of cilostazol on vascular smooth muscle cells?

PROBLEM: Context: This study had investigated the anti-inflammatory activity of a seed lectin (LAL) isolated from Lonchocarpus araripensis.', 'LAL was purified by affinity chromatography (chitin column) and ion exchange chromatography (DEAE-Sephacel). In vitro LAL was tested for hemagglutinating activity against rabbit erythrocytes. In vivo LAL was assessed for the anti-inflammatory activity via intravenous injection (i.v.) in Swiss mice (25-30 g; n = 6/group) in models of paw edema and peritonitis.', 'ANOVA (p < 0.05).', 'LAL revealed two bands of 30 and 60 kDa (SDS-PAGE) and exhibited hemagglutinating activity. LAL (10 mg/kg) inhibited the paw edema (77%) and vascular permeability (26%) induced by carrageenan, and the paw edema induced by serotonin (80%), bradykinin (49%), sodium nitroprusside (83%), TNF-α (75%) and PGE2 (64%). LAL also inhibited the neutrophil migration induced by fMLP (70%) or carrageenan (69%). The intravital microscopy showed that LAL inhibited rolling (83%) and adhesion (70%) of leukocytes. LAL anti-inflammatory effect was reversed by its association with N-acetyl-glucosamine. The nine-daily treatment with LAL (10 mg/kg; i.v.) showed no toxicity.
Answer: The novel N-acetyl-D-glucosamine-binding lectin isolated from L. araripensis seeds presents anti-inflammatory effect involving the lectin domain and the inhibition of 5-HT, BK, PGE2, NO, TNF-α and leukocyte rolling and adhesion.

SOLUTION: Does a novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuate acute cellular inflammation in mice?

PROBLEM: Context: Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway.', 'The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively.', 'The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell.
Answer: This study demonstrated that APS-treated could inhibit proliferation and promote cell apoptosis, at least partially, through suppressing the expression of notch1 and notch3 and up-regulating the expression of tumor suppressors in H460 NSCLC cell lines.

SOLUTION:
Are notch1/3 and p53/p21 a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines?