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.
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Question: Vascular endothelial growth factor (VEGF) has been well documented to stimulate cell proliferation and differentiation; however, we have observed that copper (Cu)-induced regression of heart hypertrophy was VEGF-dependent. The present study was undertaken to test the hypothesis that Cu causes alterations in the distribution of VEGF receptors (VEGFRs) in hypertrophic cardiomyocytes so that it switches the signalling pathway from stimulation of cell growth to reversal of cell hypertrophy.', 'Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cardiomyocytes were exposed to copper sulfate at a final concentration of 5 microM in cultures for 24 h with a concomitant presence of PE. Flow cytometry, gene silencing, and ELISA procedures were used to analyse the changes in VEGFRs and their relationship with regression of cardiomyocyte hypertrophy. Cu did not change the concentration of VEGF in culture media, but increased the ratio of VEGFR-1 to VEGFR-2 two-fold. Gene silencing of VEGFR-2, in the absence of Cu addition, reversed PE-induced cardiomyocyte hypertrophy, which was suppressed by an anti-VEGF antibody. Gene silencing of VEGFR-1 blocked Cu-induced regression of cell hypertrophy and decreased the activity of cGMP-dependent protein kinase-1 (PKG-1). A PKG-1 antagonist, Rp-8-pCPT-cGMPS, blocked both Cu- and VEGFR-2 gene silencing-induced regression of cardiomyocyte hypertrophy.

Answer: Is copper-induced regression of cardiomyocyte hypertrophy associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway?


Question: Previous studies have shown that Fructus Ligustri Lucide (FLL) can be used to anti-cancer. However, the mechanism by which FLL mediate this effect is unclear. In the present study, aqueous extracts of FLL induced cell apoptosis in human gastric carcinoma cell was investigated.', 'The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining and hoechst 33342 staining. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting.', 'Treatment of human gastric carcinoma cells with FLL induced cell death in a dose- and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of the early and terminal phase of apoptosis cells had gained after FLL treatment as compared to untreated group. Moreover, human gastric carcinoma cells were exposed to the aqueous extracts of FLL for 48 h, which resulted in an accumulation of cells in G2/M phase. Apoptotic bodies were clearly observed in human gastric carcinoma that had been treated with FLL for 48 h and then stained with Hochest 33342. Treatment of gastric carcinoma cells with increasing doses of FLL and increasing durations significantly increased the protein expression of Bax and Caspase3, decreased the anti-apoptotic Bcl-2 level. The expression of CDC2 and cdc25C were downregulated upon FLL treatment in human gastric carcinoma. In contrast, p53 and p21 were obviously upregulated by FLL treatment in a concentration-dependent manner.

Answer: Do aqueous extracts of Fructus Ligustri Lucide induce gastric carcinoma cell apoptosis and G2/M cycle arrest?


Question: Analyses of the pattern of p53 mutations have been essential for epidemiologic studies linking carcinogen exposure and cancer. We were concerned by the inclusion of dubious reports in the p53 databases that could lead to controversial analysis prejudicial to the scientific community.', 'We used the universal mutation database p53 database (21,717 mutations) combined with a new p53 mutant activity database (2,300 mutants) to perform functional analysis of 1,992 publications reporting p53 alterations. This analysis was done using a statistical approach similar to that of clinical meta-analyses.', 'This analysis reveals that some reports of infrequent mutations are associated with almost normal activities of p53 proteins. These particular mutations are frequently found in studies reporting multiple mutations in one tumor, silent mutations, or lacking mutation hotspots. These reports are often associated with particular methodologies, such as nested PCR, for which key controls are not satisfactory.

Answer:
Does meta-analysis of the p53 mutation database for mutant p53 biological activity reveal a methodologic bias in mutation detection?