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.

Q: Context: The ADAMTS13-von Willebrand factor (vWF) axis has been suggested to play a critical role in the pathophysiology of ischemia-reperfusion injury (IRI) in the heart or brain. Therefore, we aimed to investigate whether this axis was involved in the pathophysiology of IRI-induced acute kidney injury.', 'We performed renal IRI in ADAMTS13 knockout (KO) or wild type (WT) mice. Functional and histological kidney damage, and inflammation were compared and the effect of anti-vWF antibodies in ADAMTS13 KO mice was assessed.', 'Following IRI, the blood and kidney ADAMTS13 levels were significantly decreased. vWF expression was significantly upregulated in both the medulla and cortex of injured kidneys as shown by immunohistochemistry and western blot analyses. There was also an increased level of vWF dimers after IRI. In ADAMTS13 KO mice, kidney vWF levels were further increased and this was associated with greater endothelial and epithelial injury compared to WT mice, suggesting an important role of vWF in renal IRI. In addition, the number of Gr-1
Answer: Our data show that the ADAMTS13-vWF axis is partially involved in the pathophysiology of kidney IR, suggesting that regulating ADAMTS13- and vWF-dependent mechanisms could have therapeutic potential to limit renal IRI. This article is protected by copyright. All rights reserved.

A: Is the ADAMTS13-von Willebrand factor axis involved in the pathophysiology of kidney ischemia-reperfusion injury?
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Q: Context: Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression.', 'This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein.', 'Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit.', 'Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL.
Answer: Cisplatin pretreatment enhances Ad/gTRAIL cytotoxicity in malignant cells while not affecting normal cells. The mechanisms underlying this effect might include both enhancement of the susceptibility of cisplatin-treated cells to TRAIL and cisplatin-mediated enhancement of TRAIL expression in Ad/gTRAIL infected cells. These findings provide a rationale for development of Ad/gTRAIL-based therapy for thoracic malignancies.

A: Does cisplatin enhance apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand?
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Q: Context: It is well known that cyclooxygenase-2 (COX-2) and its major derivative product prostaglandin E2 (PGE2) play key regulatory roles in the ovulation process. Animal studies have demonstrated that the inhibition of nitric oxide (NO) suppresses ovarian PGE2 production and ovulation. Although the expression of NO synthases has been detected in human granulosa cells, the effect of NO on COX-2 expression and PGE2 production in these cells remains unknown.', 'The purpose of this article was to investigate the effects of NO on COX-2 expression and PGE2 production in human granulosa cells.', 'SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with simian virus 40 large T antigen. SVOG cells were used to investigate the effects of NO on COX-2 expression and PGE2 production.', 'The study was conducted in an academic research center.', 'The levels of mRNA and protein were examined by RT-quantitative real-time PCR and Western blotting, respectively. The accumulation levels of PGE2 were measured by ELISA.', 'Treatment with the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) induced COX-2 expression and PGE2 production. In addition, the stimulatory effect of SNAP on COX-2 and PGE2 was mimicked by treatment with the cGMP analog 8-bromo-cGMP (8-Br-cGMP). Interestingly, neither SNAP nor 8-Br-cGMP affected the expression of COX-1. Moreover, our results showed that either SNAP or 8-Br-cGMP activated cAMP response element-binding protein (CREB) signaling and that the knockdown of CREB attenuated SNAP- and 8-Br-cGMP-induced COX-2 expression and PGE2 production.
Answer: CREB mediates NO and cGMP-induced COX-2 expression and PGE2 production, which subsequently contribute to NO-regulated ovulation in human granulosa cells.

A:
Do nitric oxide and cGMP induce COX-2 expression and PGE2 production in human granulosa cells through CREB signaling pathway?
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