instruction:
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.
question:
Context: To investigate the effects of quercetin, an herbal flavonoid, on LPS-induced delay in spontaneous apoptosis, adhesion molecules (CD62L, CD11b/CD18) expression of neutrophils, and superoxide (O(2)(-)) generation by LPS-primed fMLP-induced human neutrophils.', 'Neutrophils were incubated in the presence or absence of lipopolysaccharide (LPS) at a final concentration of 1 microg/ml for 24 hours. Some wells with neutrophils were pre-treated with quecetin at the final concentration ranging from 0-100 microM for 30 min and then 1 microg/ml LPS was added into the cultures for 24 hours. The apoptosis of neutrophils was evaluated by flowcytometry analysis of propidum iodide (PI)-staining of the nuclei and annexin V staining of phosphatidylserine (PS) in the cell membrane. Agarose gel electrophoresis of low molecular weight DNA was performed to analyze DNA fragmentation. The effects of quercetin on adhesion molecules were detected by using flowcytometry analysis. The generation of O(2) (-) by LPS-primed fMLP-induced neutrophils was determined by reduced cytochrome c assay.', 'LPS markedly inhibited the spontaneous apoptosis of neutrophils, but the inhibitory effect was abrogated after the pre-treatment of neutrophils with quercetin (approximately 40 microM) for 30 min. Quercetin (40 microM) also prevented LPS-induced down-regulation of CD62L expression, up-regulation of CD11b/CD18 expression, and O(2) (-) generation by fMLP-induced neutrophils.
Answer: As one of the pro-inflammatory factors, LPS aggravates inflammation through priming neutrophils to synthesize/release cytotoxic contents and prolonging functional lifespan of neutrophils by delaying the spontaneous apoptosis. Thus, our data suggest to us that quercetin might decrease the susceptibility of neutrophils to pro-inflammatory factors (e. g. LPS), which could partially explain the anti-inflammatory mechanisms of quercetin.
answer:
Does quercetin inhibit LPS-induced delay in spontaneous apoptosis and activation of neutrophils?


question:
Context: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of growth factors that have been implicated in skin patho-physiology. Although endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) appear to be involved in mitogenesis and chemotaxis in epidermal keratinocytes, the activation of eNOS and VEGF production induced by HB-EGF and its signaling mechanism remains undefined.', 'We examined possible signal transduction pathways by which HB-EGF leads to eNOS activation and VEGF production in human epidermal keratinocyte cell line (HaCaT cells).', 'The phosphorylation of epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK; p42/p44 MAPK), Akt and eNOS were examined by Western blotting analysis. VEGF production was determined by enzyme-linked immunosorbent assay. Various inhibitors were utilized to investigate the signaling mechanisms of eNOS activation and VEGF production.', 'HB-EGF-induced phosphorylation of EGFR with maximum phosphorylation at 1h. HB-EGF-induced phosphorylation of p42/p44 MAPK in a few minutes. It activated Akt with maximum phosphorylation at 1h and eNOS with maximum phosphorylation at 3h. The HB-EGF-induced eNOS activation was significantly blocked by the p42/p44 MAPK inhibitor U0126 and the phosphatidylinositol 3-kinase (P13K) inhibitor LY294002. HB-EGF increased VEGF production. The HB-EGF-induced VEGF production was blocked by U0126 and LY294002. Finally, the HB-EGF-induced activation of Akt and eNOS was suppressed by VEGF competitive antagonist, CBO-P11.
Answer: These results demonstrate that HB-EGF-induced eNOS activation depends on p42/p44 MAPK, PI3K/Akt pathways and endogenous VEGF in HaCaT cells.
answer:
Do hB-EGF-induced VEGF production and eNOS activation depend on both PI3 kinase and MAP kinase in HaCaT cells?


question:
Context: A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood.', 'The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia.', 'Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using χ(2) tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a χ(2) test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate.', 'Mean age (SD) at imaging was 59.5 (±4.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m(2) (expressed as median [25th-75th percentile], 29.8 [25.9-33.7] vs 25.3 [23.1-32.0], P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval [CI], 1.39-9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95-7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21-8.49).
Answer: In this first prospective cohort study with confirmation of preeclampsia by medical record review, a history of preeclampsia is associated with an increased risk of CAC >30 years after affected pregnancies, even after controlling individually for traditional risk factors. A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women. Among women with histories of preeclampsia, the presence of CAC may be able to identify those at a particularly high cardiovascular risk, and should be the subject of future studies.
answer:

Is a history of preeclampsia associated with a risk for coronary artery calcification 3 decades later?