Matrine Inhibits CNS Autoimmunity Through an IFN-ß-Dependent Mechanism.

Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-ß, one of the first-line MS therapies. Indeed, while low levels of IFN-ß production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly increased after MAT treatment. Increased numbers of CD11b+IFN-ß+ microglia/infiltrating macrophages were observed in the CNS of MAT-treated mice. The key role of IFN-ß induction in the suppressive effect of MAT on EAE was further verified by administration of anti-IFN-ß neutralizing antibody, which largely reversed the therapeutic effect of MAT. Further, we found that, while MAT treatment induced production of IL-27 and IL-10 by CNS microglia/macrophages, this effect was significantly reduced by IFN-ß neutralizing antibody. Finally, the role of IFN-ß in MAT-induced IL-27 and IL-10 production was further confirmed in human monocytes in vitro. Together, our study demonstrates that MAT exerts its therapeutic effect in EAE through an IFN-ß/IL-27/IL-10 pathway, and is likely a novel, safe, low-cost, and effective therapy as an alternative to exogenous IFN-ß for MS.

Vitamin D suppress the production of vascular endothelial growth factor in mast cell by inhibiting PI3K/Akt/p38 MAPK/HIF-1α pathway in chronic spontaneous urticaria.

Mast cells play a significant role in urticaria pathogenesis. It's evidenced that vitamin D has positive impact in chronic spontaneous urticaria (CSU) recently, but underlying mechanisms remain unclear. In this study, isobaric tag for relative and absolute quantification-liquid chromatography-mass spectrometer/mass spectrometer was used to detect the expression of proteins in sera of CSU patients and healthy subjects. Thirty-one differentially expressed proteins were identified, in which vitamin D binding protein (VDBP) was higher in CSU patients than that in healthy subjects after verification. Our results indicated that sera of CSU patients induced the production of vascular endothelial growth factor (VEGF) in mast cells through PI3K/Akt/p38 MAPK/HIF-1α axis in an IgE-depended way, and 25(OH)D3 suppressed the expression of VEGF by inhibiting this signaling pathway axis in this process. Collectively, these results suggest VDBP to be a potential biomarker and propose a potential mechanism of benefit for vitamin D therapy in CSU.

Prevalence of allergen sensitization among 1,091 patients with urticaria.

The etiology of urticaria is heterogeneous and allergic responses may be involved in it. The aim of the present study was to investigate the prevalence and distribution of sensitivity to inhaled and food allergens among patients with urticaria in Henan province (China). The levels of specific immunoglobulin E (sIgE) were detected using the AllergyScreen test and a total of 524/1,091 cases (48.0%) tested positive for sIgE to at least one of the 19 allergens. The most common inhaled allergens the urticaria patients were sensitive to were D. pteronyssinus (34.5%), cockroach (12.5%) and tree pollen mix (11.1%), while the food allergens with the highest rate of allergic reactions were cashew nut (8.1%), shrimp (6.8%) and crab (6.4%). The positive rates for D. pteronyssinus, dog hair, cockroach, mold mix, tree pollen mix and shrimp in the chronic urticaria group were higher than those in the acute urticaria group (P<0.05). Furthermore, positive rates for the majority of allergens were higher in males than in females and were significantly different between age groups (P<0.05). The results of the present study provided information on the characteristics of allergen sensitization of patients with urticaria and may facilitate the prevention, diagnosis and management of urticaria in Henan province.

[A Systematic Review of the Value of Thrombelastography or Thromboelastometry for Prediction of Venous Thromboembolism].

OBJECTIVE: To systematically collect the thrombelastography (TEG)-or thromboelastometry (ROTEM)-related data, and predict to evaluate their values for the prediction of thromboembolic events. METHODS: Databases including PubMed, Central and Embase were searched for the related clinical trials, and the references were retrieved manually; these included references were assessed qualitatively by the QUADAS-2 tool; finally the enrolled researches were qualitatively analyzed. RESULTS: A total of 15 studies consisting of 293 VTE patients met the inclusion criteria. The overall quality and the accuracy of TEG or ROTEM in predicting VTE varied a lot. Two thirds of the studies displayed that the changes of TEG parameters or ROTEM were related to the occurrence of VTE. CONCLUSION: The present studies showed that the TEG or ROTEM for predicting the VTE display higher difference in accuracy, therefore, the combination of TEG or ROTEM with other laboratory tests may improve the accuracy of VTE diagnosis.