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“Epigenetic changes have been implicated in the pathogenesis of asthma. We sought to determine if IL13, a key cytokine in airway inflammation and

remodeling, induced epigenetic DNA methylation and miRNAs expression changes in the airways in conjunction with its transcriptional gene regulation. Inducible expression of an IL13 transgene in the airways resulted in significant changes in DNA methylation in 177 genes, most of which were associated with the IL13 transcriptional signature in the airways. A large number of MK-2206 manufacturer genes whose expression was induced by IL13 were found to have decreased methylation, including those involved in tissue remodeling (Olr1), leukocyte Ruboxistaurin influx (Cxcl3, Cxcl5, CSFr2b), and the Th2 response (C3ar1, Chi3l4). Reciprocally, some genes whose expression was suppressed were found to have increased methylation (e. g. Itga8). In addition, miRNAs were identified with targets for lung development and Wnt signaling, amongst others. These results indicate that IL13 confers an epigenetic methylation and miRNA signature that accompanies its transcriptional program in the airways, which may play a critical role in airway inflammation and remodeling.”
“It is generally known that many psychological factors, such as

stress or insomnia, cause mental fatigue. However, the detailed mechanisms underlying mental fatigue have not been clarified. We speculated that mental fatigue

may be caused by 4SC-202 nmr neuronal brain damage through the activation of N-methyl-D-aspartate (NMDA) receptors by quinolinic acid (QUIN), one of the metabolites of tryptophan in the kynurenine pathway. In the present study, we tested this hypothesis in mice using a home cage equipped with a running wheel; voluntary wheel-running reflected mental activity. In normal mice, wheel-running activity was not affected by intraperitoneal administration of QUIN, but it was significantly decreased by intracerebroventricular administration of QUIN. In restraint stress-loaded mice, whose blood-brain barriers were weakened, wheel-running activity was significantly decreased by intraperitoneal administration of QUIN, and this effect was inhibited by memantine hydrochloride (MEM), an NMDA receptor antagonist. Intraperitoneal administration of lipopolysaccharide (LPS) induced a decrease in wheel-running activity and a concomitant increase in blood and brain QUIN levels. MEM inhibited the LPS-induced decrease in wheel-running activity, but it did not affect the increase in blood and brain QUIN levels. The number of hippocampal neurons was significantly decreased by LPS treatment, and this effect was inhibited by MEM. These results suggest that QUIN, which is produced via tryptophan metabolism, decreases mental activity in mice by damaging brain neurons through the activation of NMDA receptors.