Porcine Complement 3(C3) ELISA Kit

Filoviruses, including Ebolavirus (EBOV), Marburgvirus (MARV) and Cuevavirus, cause hemorrhagic fevers in humans with up to 90% mortality rates. In the 2014-2016 West Africa Ebola epidemic, there are 15,261 laboratory confirmed cases and 11,325 total deaths. The lack of effective vaccines and medicines for the prevention and treatment of filovirus infection in humans stresses the urgency to develop antiviral therapeutics against filovirus-associated diseases. Our previous study identified a histamine receptor antagonist compound CP19 as an entry inhibitor against both EBOV and MARV. The preliminary structure-activity relationship (SAR) studies of CP19 showed that its piperidine, coumarin and linker were related with its antiviral activities. In this study, we performed detailed SAR studies on these groups with synthesized CP19 derivatives. We discovered that 1) the piperidine group could be optimized with heterocycles, 2) the substitution groups of C3 and C4 of coumarin should be relatively large hydrophobic groups and 3) the linker part should be least substituted. Based on the SAR analysis, we synthesized compound 32 as a potent entry inhibitor of EBOV and MARV (IC50 = 0.5 mu M for EBOV and 1.5 mu M for MARV). The mutation studies of Ebola glycoprotein and molecular docking studies showed that the coumarin and its substituted groups of compound 32 bind to the pocket of Ebola glycoprotein in a similar way to the published entry inhibitor compound 118a. However, the carboxamide group of compound 32 does not have strong interaction with N61 as compound 118a does. The coumarin skeleton structure and the binding model of compound 32 elucidated by this study could be utilized to guide further design and optimization of entry inhibitors targeting the filovirus glycoproteins. (C) 2020 Elsevier Masson SAS. All rights reserved.

Programmed death ligand (PD-L) 2 and PD-L1 are the second and first ligands, respectively, for programmed cell death-1 protein (PD-1), which is one of the key factors responsible for inhibitory T cell signaling, mediating mechanisms of tolerance and providing immune homeostasis. Studies have shown that PD-1 and its ligand PD-L1 are abnormally expressed in autoimmune diseases, such as rheumatoid arthritis and autoimmune hepatitis, but its other ligand, PD-L2, has rarely been studied. This study analyzed the changes in membrane-bound PD-L2 expression in peripheral blood mononuclear cells and soluble PD-L2 (sPD-L2) levels in the serum of patients with systemic lupus erythematosus (SLE) to explore the relationship between PD-L2 expression with disease activity and related test parameters. Our results showed that membrane-bound PD-L2 expression on monocytes was significantly higher and the sPD-L2 levels were significantly lower in SLE patients than in healthy subjects. Patients with active SLE accompanied by lupus nephritis, joint pain, and clinical manifestations of oral ulcers had relatively low secretion of sPD-L2. In addition, this secretion level was significantly and positively correlated with complement components 3 and 4 (C3/C4). These results suggest that PD-L2 may be a promising biomarker associated with the pathogenesis of SLE.