Background Chronic airway inflammation and airway remodeling are important features of bronchial asthma. IL-11 is one of the important mediators involved in the process of airway inflammation and ...remodeling. Cysteinyl leukotrienes (cysLTs) play roles in recruitment of inflammatory cells, airway smooth muscle contraction, vascular leakage, increased mucus secretion, decreased mucociliary clearance, and airway fibrosis. Objective An aim of the present study was to determine the effect of the cysLTs on the regulation of IL-11 expression. Methods We used a C57BL/6 mouse model of allergic airway disease and murine tracheal epithelial cells to examine the effects of cysLTs on the regulation of IL-11 expression. Results Our present study with an ovalbumin-induced murine model of allergic airway disease revealed that levels of leukotriene C4 (LTC4 ) in bronchoalveolar lavage fluids were increased and that administration of montelukast or pranlukast reduced the increased levels of LTC4 ; the increased expression of IL-11 protein and mRNA in lung tissues; airway inflammation, bronchial hyperresponsiveness; the increased levels of TGF-β1 , IL-4, and IL-13 in bronchoalveolar lavage fluids and lung tissues; and airway fibrosis. In addition, LTC4 stimulates epithelial cells to produce IL-11. Our results also showed that cysLT type 1 receptor antagonists downregulated the activity of a transcription factor, nuclear factor κB, and BAY 11-7085 substantially reduced the increased levels of IL-11 after ovalbumin inhalation. Conclusion These results suggest that cysLTs regulate the IL-11 expression in allergic airway disease. Clinical implications These findings provide one of the molecular mechanisms for the effects of cysLTs on airway inflammation and fibrosis in allergic airway diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This paper presents a salient clock deskewing method with a mixed-mode delay-locked loop (MDLL) for high-speed synchronous DRAM applications. The presented method not only solves the resolution ...problem of conventional digital deskewing circuits, but also improves the jitter performance to the level of well-designed analog deskewing circuits, while keeping the power consumption and locking speed of digital deskewing circuits. The whole deskewing circuit is fabricated in a 3.3-V 0.6-/spl mu/m triple-metal CMOS process and occupies a die area of 0.45 mm/sup 2/. Measured rms jitter is 6.38 ps. The power consumption of the entire chip, including I/O peripherals, is 33 mW at 200 MHz with a 3.3-V supply.
LL-37 is a human cathelicidin antimicrobial peptide that is released in the skin after injury and acts to defend against infection and modulate the local cellular immune response. We observed in ...human dermal keloids that fibrosis was inversely related to the expression of cathelicidin and sought to determine how LL-37 influenced expression of types I and III collagen genes in dermal fibroblasts. At nano-molar concentrations, LL-37 inhibited baseline and transforming growth factor-β-induced collagen expression. At these concentrations, LL-37 also induced phosphorylation of extracellular signal-regulated kinase (ERK) within 30 minutes. Activation of ERK, and the activation of a G-protein-dependent pathway, was essential for inhibition of collagen expression as pertussis toxin or an inhibitor of ERK blocked the inhibitory effects of LL-37. c-Jun N-terminal kinase and p38 mitogen-activated protein kinase inhibitors did not alter the effects of cathelicidin. Silencing of the Ets-1 reversed inhibitory effects of LL-37. Taken together, these findings show that LL-37 can directly act on dermal fibroblasts and may have antifibrotic action during the wound repair process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground ...Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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