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.

Input: Consider Input: Mycophenolate mofetil (MMF) is an effective immunosuppressant developed for use in organ transplantation. It specifically targets lymphocyte purine biosynthesis. However, side effects do occur. Understanding how the active metabolite of MMF, mycophenolic acid (MPA) affects the normally integrated interaction between intracellular purine and pyrimidine pathways might aid the development of improved therapeutic regimes.', 'We used a primary human T-lymphocyte model to study how preincubation with MPA (0.1-50 microM) affected normal ribonucleotide pool responses to phytohemagglutinin using radiolabeled precursors.', 'MPA not only restricted the mitogen-induced expansion of GTP pools, but actually induced a severe drop in both GTP (10% of unstimulated cells) and GDP-sugar pools, with a concomitant fall in ATP (up to 50%). These effects were concentration dependent. By contrast, uridine pools expanded whereas CTP pools remained at resting levels. These changes were confirmed by the altered incorporation of [14C]-bicarbonate and [14C]-glycine into nucleotides. Restriction of [14C]-hypoxanthine incorporation and reduction of [14C]-uridine uptake comparable to that of unstimulated cells indicated that MPA also inhibited both salvage routes of nucleotide synthesis.

Output: Does mycophenolic acid-induced GTP depletion also affect ATP and pyrimidine synthesis in mitogen-stimulated primary human T-lymphocytes?


Input: Consider Input: Lieber-DeCarli diet has been used to induce obesity and non-alcoholic steatohepatitis (NASH). As scarce anatomical and clinical-related information on this diet model exists and being exercise an advised strategy to counteract metabolic diseases, we aimed to analyze the preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect of exercise on clinical/anatomical features of rats fed with Lieber-DeCarli diet.', 'In the beginning of the protocol, Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 20), standard-diet VPA (SVPA, n = 10), high-fat diet sedentary (HS, n = 20) and high-fat diet VPA (HVPA, n = 10) groups. After 9-weeks, half (n = 10) of SS and HS groups were engaged in an ET program (8 wks/5 d/wk/60 min/day). At this time, a blood sample was collected for biochemical analysis. At the end of protocol (17-weeks) anatomic measures were assessed. Heart, liver, femur and visceral fat were weighted and blood was collected again. Liver section was used for histopathological examination.', 'At 17-weeks, high-fat diet increased visceral adiposity (HS vs. SS), which was counteracted by both exercises. However, ET was the only intervention able to diminished obesity-related measures and the histological features of NASH. Moreover, blood analysis at 9 weeks showed that high-fat diet increased ALT, AST, cholesterol and HDL while VLDL and TG levels were decreased (HS vs. SS). Notably, although these parameters were counteracted after 9-weeks of VPA, they were transitory and not observed after 17-weeks.

Output: Does physical exercise antagonize clinical and anatomical features characterizing Lieber-DeCarli diet-induced obesity and related metabolic disorders?


Input: Consider Input: Activation of the transcription factor NF-κB and expression of pro-inflammatory mediators have been considered as major events of acute pancreatitis (AP). Karyopherin alpha 2 (KPNA2), a member of the importin α family, reportedly modulates p65 subcellular localization.', 'This study aimed to investigate the expression and possible functions of KPNA2 in the AP cell and animal model, focusing on its association with NF-κB activation.', 'An AP cell model was established with the cerulein-stimulated AR42J and isolated rat pancreatic acinar cells. The AP rat model was induced by the intraperitoneal injection of cerulein. The secretion of TNF-α, IL-6, and LDH was detected by ELISA kits and the production of NO using nitric oxide kit. Expression of KPNA2 was measured by RT-PCR and Western blot. Expression levels of IKKα, phosphorylation of p65, and total p65 were detected by Western blot. Co-localization of KPNA2 with p65 was observed by immunofluorescence assay. To determine the biological functions of KPNA2 in cerulein-induced inflammatory response, RNA interference was employed to knockdown KPNA2 expression in AR42J and isolated pancreatic acini cells.', 'Cerulein stimulated KPNA2 expression and IL-6, TNF-α, NO, and LDH production in rat pancreatic acinar cells. Cerulein triggered the phosphorylation and nuclear translocation of NF-κB p65 subunit, indicating the NF-κB activation. The co-localization and nuclear accumulation of KPNA2 and p65 were detected in cerulein-treated cells. Knocking down KPNA2 hindered cerulein-induced nuclear transportation of p65 and alleviated the subsequent inflammatory response in rat pancreatic acinar cells. Additionally, KPNA2 expression was significantly up-regulated in cerulein-induced AP rat model.


Output: Does karyopherin Alpha 2 promote the Inflammatory Response in Rat Pancreatic Acinar Cells Via Facilitating NF-κB Activation?