Anti-FAS monoclonal antibody, clone LOB 3/11

Background: Artemisia annua is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for Artemisia annua-induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for Artemisia annua-related AR. Methods: This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 Artemisia annua-sensitized eligible patients were randomized in a ratio of 2:1 to receive Artemisia annua-SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced. Results: Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 +/- 0.47 vs 1.88 +/- 0.42, P < 0.0001 in full analysis set [FAS]; 1.49 +/- 0.52 vs 1.95 +/- 0.46, P < 0.0001 in per protocol set [PPS]); representing a 22.3% and 23.6% reduction, respectively, relative to placebo. In specifically Artemisia annua monosensitized patients, mean daily CSMRS reductions were demonstrated as 24.1% and 27.0% in the FAS and PPS populations, respectively, when comparing the active treatment to placebo treatment. Similarly, SLIT decreased dTNSS in peak pollen period by 19.0% in FAS and 22.3% in PPS, respectively, relative to placebo. In coincidence, dRMS in peak pollen period was reduced by 22.0% in FAS and 26.0% in PPS. 65.8% patients in SLIT group experienced treatment-related AEs, none of which was serious. Conclusion: This study indicates that SLIT with Artemisia annua drops is an effective and safe treatment option in Chinese patients with Artemisia Annua-induced AR.

Polyp bail-out is a stress response exhibited by some pocilloporid corals, with mechanisms and consequences distinct from those of bleaching. Although induction of polyp bail-out has been demonstrated in the laboratory, molecular mechanisms underlying this response have rarely been discussed. We conducted genetic analyses ofPocillopora acutaduring initiation of hyperosmosis-induced polyp bail-out, using both transcriptomic and qPCR techniques. Beyond upregulation of apoptosis and proteolysis, corals showed significant activation of tumor necrosis factor and fibroblast growth factor (FGF) signaling pathways during induction of polyp bail-out. In our qPCR analysis, a common upregulation profile, peaking at 43.0 parts per thousand salinity, was found in the FAS and CASP8 genes, whereas a different profile, showing significant upregulation up to 45.0 parts per thousand, was displayed by matrix metalloproteinases and genes in the FGF signaling pathway. These results suggest parallel involvement of an extrinsic apoptotic signaling pathway and FGF-mediated extracellular matrix degradation in polyp bail-out. Furthermore, in the XIAP, JNK, and NFKB1 genes, we detected a third expression profile showing linear upregulation that becomes maximal at the endpoint salinity level of the experiment (46.0 parts per thousand), indicating activation of anti-apoptotic and cell survival signals during polyp bail-out. Our results provide new insights into signaling pathways responsible for polyp bail-out and suggest the feasibility of inducing bail-out by specifically triggering these pathways without exerting lethal stresses on the corals, which in turn will facilitate acquisition of viable polyps for possible use in coral reef restoration.