TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity.', 'The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age-matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro-inflammatory cytokines (interleukin (IL)-1β and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects.', 'Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-γ, IL-12β, IL-1β, CCL2, CCL5, IL-6 and TNFα) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1β and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months.\Question: Are upregulation of inflammasome activity and increased gut permeability associated with obesity in children and adolescents?

SOLUTION: In children and adolescents, obesity is characterized by the activation of the inflammasome and by an alteration of gut permeability. Successful lifestyle modification is effective in reducing inflammation, suggesting that inhibition of the inflammasome may be a potential therapeutic strategy in obesity.

PROBLEM: Context: Crohn's disease is a heterogeneous inflammatory bowel disease. The impact of age at diagnosis on the clinical course of patients varies widely as reported in the Western literature. Using the Vienna Classification, we seek to determine whether young Crohn's disease patients in an Asian population followed a different clinical course than old patients.", "The case records of 100 Crohn's disease patients who were treated at the Inflammatory Bowel Disease Center, Singapore General Hospital, were studied retrospectively. The age group and location of disease and behavior according to the Vienna classification were determined at diagnosis.", 'A1 group (age <40 years) defined as "young" and A2 group (age > or =40) defined as "old" contained 65 and 35 patients, respectively. Median age for the young group was 27.4 years and that for the old group was 52.6 years. Of the young patients, 66.7% flared at least once compared with 28.6% of the old patients, odds ratio of 5.0 (P < 0.001). Young patients were more likely to be steroid dependent (20.0% of A1 versus 8.6% of A2, P = 0.14), received azathioprine (38.5% of A1 versus 5.7% of A2, P < 0.001) and experienced complications (31% of A1 versus 20% of A2, P = 0.25)-numerically higher rates that did not reach statistical significance. There was no significant difference between the age groups for the location and behavior of disease as well as requirement for surgery.\Question: Does crohn 's disease run a more aggressive course in young Asian patients?

SOLUTION: In this first Asian study looking specifically at the impact of age at diagnosis of Crohn's disease, we found that young patients underwent a more aggressive clinical course.

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

SOLUTION:
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.