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.

Q: 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 μg/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-κB.', 'Treatment of RAW264.7 cells with CVB-D (25-300 μmol/L) did not affect the cell viability. Pretreatment with CVB-D (50, 100 and 200 μmol/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 μmol/L). CVB-D also concentration-dependently inhibited the secretion and mRNA expression of IL-1β 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-κB and MAPKs pathways. Pretreatment with the JAK2 specific inhibitor AG490 (30 μmol/L) produced similar effects on NO release and iNOS expression in LPS-treated RAW264.7 cells.

A: Does cyclovirobuxinum D suppress lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway?
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Q: Development of novel strategies in the treatment of advanced thyroid cancer are needed. Our laboratory has previously identified a role for nuclear factor κB (NF-κB) signaling in human thyroid cancer cell growth, survival, and invasion.', 'Our goal was to establish the role of NF-κB signaling on thyroid cancer growth and metastases in vivo and to begin to dissect mechanisms regulating this effect.', 'We examined tumor formation of five thyroid cancer cell lines in an in vivo model of thyroid cancer and observed tumor establishment in two of the cell lines (8505C and BCPAP).', 'Inhibition of NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα) significantly inhibited thyroid tumor growth in tumors derived from both cell lines. Further studies in an experimental metastasis model demonstrated that NF-κB inhibition impaired growth of tumor metastasis and prolonged mouse survival. Proliferation (mitotic index) was decreased in 8505C tumors, but not in BCPAP tumors, while in vitro angiogenesis and in vivo tumor vascularity were significantly inhibited by mIkBα only in the BCPAP cells. Cytokine antibody array analysis demonstrated that IL-8 secretion was blocked by mIκBα expression. Interestingly, basal NF-κB activity and IL-8 levels were significantly higher in the two tumorigenic cell lines compared with the nontumorigenic lines. Furthermore, IL-8 transcript levels were elevated in high-risk human tumors, suggesting that NF-κB and IL-8 are associated with more aggressive tumor behavior.

A: Is nuclear factor κB-dependent regulation of angiogenesis , and metastasis in an in vivo model of thyroid cancer associated with secreted interleukin-8?
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Q: To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively.', 'Retrospective study with Cox regression analysis to control for possible preoperative, intraoperative and postoperative confounders.', 'University hospital-based single-center study.', 'All patients who underwent coronary artery bypass grafting ± valve surgery during 2012.', 'None.', 'Acute surgery within 24 hours of coronary angiography, previous nephrectomy, preoperative sCr >2.26 mg/dL and selective cerebral perfusion during cardiopulmonary bypass were used as exclusion criteria. Acute kidney injury was defined, using the Acute Kidney Injury Network (AKIN) criteria. Six hundred eight patients were included in the study. Mean age was 68.2 ± 9.7 years, and 81% were males. Acute kidney injury was seen in 28.1% of the patients. Overall mortality at one year was 7% and 3% in the no-AKI group. At one year, mortality was 15% in patients with AKIN stage 1 and AKIN stage 2 compared to 70% in AKIN stage 3. A hazard ratio of 2.34 (95% CI: 1.21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), p<0.0001) were found for AKIN stage 1 and 2/3 combined, respectively.

A:
Is acute kidney injury independently associated with higher mortality after cardiac surgery?
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