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“The importance of Ca2+ influx via store-operated calcium channels (SOCs) leading to mast cell degranulation is well known in allergic disease. However, the underlying mechanisms are not fully understood. With food-allergic rat model, the morphology of degranulated mast cell was analysed by toluidine blue stain and electron microscope. Ca2+ influx via SOCs was checked by Ca2+ imaging confocal microscope. Furthermore, the mRNA
and protein expression of SOCs subunits were investigated using qPCR and Western blot. We found that ovalbumin (OVA) challenge significantly increased the levels of Th2 cytokines and OVA-specific IgE in allergic animals. Parallel to mast cell activation, the levels of histamine in serum and supernatant of rat AG-881 purchase peritoneal lavage solution were remarkably increased after OVA treatment. Moreover, the Ca2+ entry through SOCs evoked by thapsigargin was increased in OVA-challenged group. The mRNA and protein expressions of SOC subunits, stromal interaction molecule 1 (STIM1) and Orail (calcium-release-activated calcium channel protein 1), were dramatically CA4P elevated under food-allergic condition. Administration of Ebselen,
a scavenger of reactive oxygen species (ROS), significantly attenuated OVA sensitization-induced intracellular Ca2+ rise and upregulation of SOCs subunit expressions. Intriguingly, pretreatment with PI3K-specific inhibitor (Wortmannin) partially abolished the production of ROS and subsequent elevation of SOCs activity and their subunit expressions.
Taken together, these results imply that enhancement of SOC-mediated Ca2+ influx induces mast cell activation, contributing to the pathogenesis of OVA-stimulated food allergy. PI3K-dependent ROS generation involves in MDV3100 chemical structure modulating the activity of SOCs by increasing the expressions of their subunit.”
“Two types of three-dimensional (3D) hybrid organic-inorganic frameworks [Ln(2)(H(2)pda)(SO(4))(3)(H(2)O)(4)](n) [I, Ln = La(3+) (1), Pr(3+) (2), Nd(3+) (3), Sm(3+) (4) and Eu(3+) (5)] and {[Ln(2)(H(2)pda)(SO(4))(3)(H(2)O)(2)]center dot 2H(2)O)(n) [II, Ln = Gd(3+) (6) and Dy(3+) (7)], where H(2)pda is 1,4-piperazinediacetic acid, have been obtained by the reactions of H(2)pda, lanthanide oxides and H(2)SO(4) under similar hydrothermal conditions. All the frameworks are constructed by two-dimensional inorganic lanthanide(III) sulfate layers and organic H(2)pda pillars. The lanthanide(III) sulfate layers in both types I and II consist of the similar lanthanide(III) sulfate chains, which are built from lanthanide(III) ions and eta(3),mu(3)-sulfates, and the different sulfate bridges. The coordination modes of sulfate bridges in I and II are eta(2),mu(3)-bidentate and eta(4),mu(2)-tetradentate, respectively. Each organic H(2)pda pillar in two types is connected with four Ln(3+) ions in a bis-bidentate syn-anti mode. Compounds 1 and 6 are thermally stable below 180 and 300 degrees C, respectively.