TASK DEFINITION: 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.
PROBLEM: Context: FGF receptor (FGFR) family can be activated by FGFs and play important roles in regulating cell growth, differentiation, migration and angiogenesis. Recent studies suggested that FGFR4 could regulate several processes including tumor progression. Nasopharyngeal carcinoma (NPC) is a malignancy with a high occurrence in Southeast Asia and Southern China. However, the molecule mechanism and the potential roles of FGFR4 in NPC remain unknown Methods: Immunohistochemistry and western blot were used to investigate the expression of FGFR4 in NPC samples. Then we used statistical analysis to evaluate the diagnostic value and the associations of FGFR4 expression with clinical parameters. In vitro studies, the effects of FGFR4 on proliferation and migration of NPC cell line CNE2 were measured by the starvation-refeeding experiment, CCK8 assay, wounding healing assay and transwell migration assay. The changes of the epithelial-mesenchymal transition (EMT) markers in CNE2 cells after knocking down the expression of FGFR4 were measured by Western blot and immunofluorescence analysis.', 'FGFR4 was overexpressed in NPC as compared with the inflammatory tissues. High expression of FGFR4 was correlated with Ki67 expression, clinical stages and prognosis in NPC patients (P<0.05).While in vitro, the upregulation of FGFR4 was accompanied with CNE2 cells released from serum starvation. Moreover, it could increase cell proliferation and migration by regulating EMT markers in CNE2 cells.
Answer: Our data suggested that FGFR4 might induce NPC progression and act as a potential therapeutic target in NPC.

SOLUTION: Does high Expression of FGFR4 enhance Tumor Growth and Metastasis in Nasopharyngeal Carcinoma?

PROBLEM: Context: Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear.', 'The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs.', 'After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs.', 'BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation.
Answer: Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs.

SOLUTION: Do bone Marrow Stromal Cells Inhibit the Activation of Liver Cirrhotic Fat-Storing Cells via Adrenomedullin Secretion?

PROBLEM: Context: Thrombin influences the biological behavior of periodontal ligament cells and plays multiple roles in the early stages of bone healing. Osteoprotegerin (OPG) is one of the key molecules that regulate bone homeostasis and prevent osteoclastogenesis. The purpose of this study was to evaluate the biological effects of thrombin on OPG synthesis in human periodontal ligament (HPDL) cells in vitro.', 'Cells were treated with various concentrations (0.001, 0.01 and 0.1 U/mL) of thrombin. The mRNA expression and protein synthesis of OPG, as well as of receptor activator of nuclear factor kappaB ligand (RANKL), were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The influence of thrombin on OPG synthesis and its signaling pathway were investigated using inhibitors.', "Thrombin profoundly induces protein synthesis of OPG at 0.1 U/mL. The inductive effect was inhibited by cycloheximide, but not by indomethacin. The phosphatidylinositol 3'-kinase (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exerted an inhibitory effect on the thrombin-induced OPG synthesis. In addition, the effect was inhibited by protease-activated receptor (PAR)-1 antagonist. Activation of phospho-Akt (p-Akt) was observed and the effect was abolished by LY294002.
Answer: Thrombin induces OPG synthesis in HPDL cells post-transcriptionally, possibly through PAR-1. The regulation was through the PI3K/Akt and mTOR pathway. This finding suggests that thrombin may play a significant role in alveolar bone repair and homeostasis of periodontal tissue, partly through the OPG/RANKL system.

SOLUTION:
Does thrombin induce osteoprotegerin synthesis via phosphatidylinositol 3'-kinase/mammalian target of rapamycin pathway in human periodontal ligament cells?