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.

Input: Consider Input: Context: The present study was undertaken to determine whether exposure of the sclera to prostaglandin (PG)F(2alpha) or to the PGF(2alpha) analogue latanoprost acid alters mRNA for matrix metalloproteinases.', 'Fifteen human eye bank eyes were studied. Circular pieces of sclera were either immediately preserved in a stabilization reagent or cultured in low-serum DMEM/F-12 medium. The cultures were treated for 24 hours with medium supplemented with PGF(2a), latanoprost acid, or vehicle. Total RNA was then isolated, and the expression of mRNA for matrix metalloproteinase (MMP)-1, -2, -3, -8, -9, -10, and -12 were determined by real-time PCR. All results were normalized according to the GAPDH mRNA in each sample. Altered mRNA expression after PG treatments also was evaluated with microarrays containing 19 MMP genes and 4 tissue inhibitor of matrix metalloproteinase (TIMP) genes.', 'Real-time PCR results showed that 24 hours of exposure to 100 nM PGF(2alpha) significantly increased mRNA for MMP-1 and -9 (P < 0.06 Wilcoxon test) and that exposure to 100 nM latanoprost acid significantly increased mRNA for MMP-9 (P < 0.06 Wilcoxon test). Array analysis demonstrated increases of MMP-3 and -10 mRNA after exposure to 100 nM latanoprost and further increases after exposure to 200 nM latanoprost. The array results also showed that latanoprost induced dose-dependent increases in the expression of TIMP-1, -2, and -3 mRNA in the scleral cultures.
Answer: PGF(2alpha) and latanoprost acid induce coordinated alterations of MMP gene transcription in scleral organ cultures. These results indicate that PGs can directly trigger MMP gene transcription changes within the sclera. These changes support a role for increased MMPs in the enhancement of uveoscleral outflow that occurs after topical treatment with latanoprost.

Output: Do prostaglandin FP agonists alter metalloproteinase gene expression in sclera?


Input: Consider Input: Context: 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.
Answer: CVB-D exerts anti-inflammatory effects in LPS-stimulated murine macrophages in vitro at least in part by blocking the JAK-STAT signaling pathway. The anti-inflammatory actions of CVB-D may contribute to its cardioprotection.

Output: Does cyclovirobuxinum D suppress lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway?


Input: Consider Input: Context: The FAS/FASLG system has been proposed to play a key role in germ cell apoptosis. To elucidate the role of the genetic variants of cell death pathway genes in male infertility, we genotyped the polymorphisms of FAS, FASLG and caspase-8 (CASP8) genes and evaluated their effects on sperm apoptosis and semen quality in infertile men.', 'The genotypes of FAS, FASLG and CASP8 were determined in 620 infertile men. Sperm apoptosis rates were measured by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end labelling (TUNEL) assay, and the semen quality analysis was performed using computer assisted sperm analysis.', 'We found that polymorphisms of FAS-670A/G (rs1800682: A>G) and CASP8-652 6N ins/del (rs3834129: -/CTTACT) were associated with sperm apoptosis and semen quality. Individuals with FAS-670GG showed low apoptosis rate and decreased sperm concentration, compared with the FAS-670AA genotype. Similarly, in comparison with the CASP8-652 6N ins/ins genotype, the CASP8-652 6N (ins/del+del/del) genotypes also showed significantly decreased sperm apoptosis rate and poor sperm motility. Other polymorphisms investigated did not appear to affect sperm apoptosis and semen quality.
Answer: This study showed for the first time that functional variants of FAS and CASP8 might contribute to the dysfunctional apoptotic mechanism in germ cells, which could result in poor semen quality of ejaculated sperm.


Output: Are polymorphisms in cell death pathway genes associated with altered sperm apoptosis and poor semen quality?