Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

Correlation analysis between the chemical contents and bioactivity for the quality control of Alismatis Rhizoma

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed.Methodologies included HPLC–PDA, HPLC–VWD and UHPLC–MSn, combined with principal component analysis(PCA) and partial least squares regression techniques(PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated in vitro. PLSR analysis revealed significant positive correlations(R2= 0.5795) between the contents of triterpenes 10, 14, 15, 18 and 22 and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.

The kinase p38αfunctions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation

Dendritic cells(DCs)play a critical role in controlling T helper 2(Th2)cell-dependent diseases,but the signaling mechanism that triggers this function is not fully understood.We showed that p38αactivity in DCs was decreased upon HDM stimulation and dynamically regulated by both extrinsic signals and Th2-instructive cytokines.p38α-specific deletion in cDC1s but not in cDC2s or macrophages promoted Th2 responses under HDM stimulation.Further study showed that p38αin cDC1s regulated Th2-cell differentiation by modulating the MK2−c-FOS−IL-12 axis.Importantly,crosstalk between p38α-dependent DCs and Th2 cells occurred during the sensitization phase,not the effector phase,and was conserved between mice and humans.Our results identify p38αsignaling as a central pathway in DCs that integrates allergic and parasitic instructive signals with Th2-instructive cytokines from the microenvironment to regulate Th2-cell differentiation and function,and this finding may offer a novel strategy for the treatment of allergic diseases and parasitic infection.

Advances in immunopathogenesis of adult immune thrombocytopenia

Primary immune thrombocytopenia(ITP)is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production.Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP,several abnormalities involving the cellular mechanisms of immune modulation have been identified,and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction.This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.