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.
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Question: 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.

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


Question: Context: To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community-dwelling normal population.', 'This neuropathological study used both silver staining and A beta immunohistochemistry in brain tissue microarrays, including SP coverage and NFT counts from frontal cortex and hippocampus, and APOE genotyping, and was performed on a consecutive prospective series of 603 subjects (aged between 0 and 97 years) of an unselected population living outside of institutions. Cases were subjected to autopsy following sudden or unexpected out-of-hospital death, covering 22.1% of the mortality of Tampere, Finland and its surroundings. None died of AD, although 22 (3.7%) were demented and 10 (1.7%) had memory problems.', 'Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age. Both changes had already appeared at around 30 years of age, reaching an occurrence of almost 100% in the oldest. SP were more frequent in APOE epsilon 4-carriers compared with noncarriers in every age group except the oldest (>90 years). The difference was most evident during the ages 50 to 59 years, where 40.7% of epsilon 4-carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55-27.62). The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group.
Answer: The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.

Answer: Does apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begin in middle age?


Question: Context: Periprosthetic osteolysis, involving RANK/RANKL/osteoprotegerin (OPG) and TNF-α/NFκB signaling, contributes to bone resorption and inflammation. We constructed lentivirus vectors to inhibit TNF-α and enhance OPG expression and assessed their impacts on wear debris-induced inflammation and osteoclastogenesis in an osteoclast/osteoblast coculture system.', 'We transduced mouse osteoblastic MC3T3-E1 cells with Lenti-negative control (Lenti-NC), Lenti-OPG or Lenti-siTNFα-OPG, and murine macrophage/monocyte RAW264.7 cells with Lenti-NC, Lenti-TNF-α siRNA or Lenti-siTNFα-OPG. Then, TNF-α and OPG protein levels were evaluated by enzyme-linked immunosorbent assay. We cocultured transduced MC3T3-E1 and RAW264.7 cells in transwell chambers in the presence of 0.1 mg/mL Ti particles to investigate the capacity of TNF-α inhibition to reduce wear debris-induced inflammation. We also assessed mRNA levels TNF-α, IL-1β, IL-6 and OPG by RT-PCR as well as osteoclastogenesis by tartrate-resistant acid phosphatase.', 'Lenti-siTNFα-OPG ameliorated Ti-particle-induced expression of TNF-α, IL-1β, IL-6 in MC3T3-E1/RAW264.7 cocultures, while enhancing mRNA and protein levels of OPG, and reducing the fraction of tartrate-resistant acid phosphatase (TRAP)+ cells.
Answer: Lenti-siTNFα-OPG can inhibit the wear debris-induced inflammatory responses and osteoclastogenesis in vitro, and may represent a promising therapeutic candidate for the treatment or prevention of wear particle-induced osteolysis.

Answer:
Does tNF-α suppression and osteoprotegerin overexpression inhibit wear debris-induced inflammation and osteoclastogenesis in vitro?