PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow.

Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils to suppress host immunity during polymicrobial sepsis, virus and parasite infections. However, the role of PD-L1 on neutrophil-mediated antifungal immunity remains wholly unknown. Here, we show that the expression of PD-L1 on murine and human neutrophils was upregulated upon the engagement of C-type lectin receptor Dectin-1 with its ligand β-glucans, exposed on fungal pathogen Candida albicans yeast.

Effects of 27 CYP3A4 protein variants on saxagliptin metabolism in vitro.

Saxagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor widely used in patients with type 2 diabetes. It can increase the amount of insulin after meals and lower blood sugar. CYP450 3A4 (CYP3A4) can metabolize about 30%-40% of therapeutic drugs.

Identification and Enzymatic Activity Evaluation of a Novel Allelic Variant Discovered in a Patient.

Warfarin is a widely prescribed anticoagulant but the doses required to attain the optimum therapeutic effect exhibit dramatic inter-individual variability. Pharmacogenomics-guided warfarin dosing has been recommended to improve safety and effectiveness. We analyzed the cytochrome P450 2C9 () and vitamin K epoxide reductase complex subunit 1 () genes among 120 patients taking warfarin.

Functional characterization of 27 CYP3A4 variants on macitentan metabolism in vitro.

Objective: Macitentan is a new choice for pulmonary hypertension treatment which is converted to active metabolite ACT132577 by human cytochrome P450 3A4. Human cytochrome P450 3A4 often occurred gene mutations. Gene polymorphism might cause a variety of changes of protein expression and thus give rise to metabolic difference.

Characterization of Genetic Variation in CYP3A4 on the Metabolism of Cabozantinib in Vitro.

Cabozantinib is a multityrosine kinase inhibitor and has a wide range of applications in the clinic, whose metabolism is predominately dependent on CYP3A4. This study was performed to characterize the enzymatic properties of 29 CYP3A4 alleles toward cabozantinib and the functional changes of five selected alleles (the wild-type, CYP3A4.2.

Enzymatic Activities of Allelic Variants on Quinine 3-Hydroxylation .

Cytochrome P450 3A4 (CYP3A4) enzyme activity is known to show considerable ethnic heterogeneity and inter-individual differences, affecting the outcome of drug treatment. genetic polymorphisms are believed to be one of the important causes, leading to inter-individual variability in drug metabolism. Quinine is an antipyretic drug with antimalarial properties that is metabolized primarily by CYP3A4.

Determination and pharmacokinetic study of Enasidenib in rat plasma by UPLC-MS/MS.

Enasidenib, an oral product for treating Acute Myeloid Leukemia, has been approved by FDA in Aug, 2017. In this study, we set up an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for measuring Enasidenib and imatinib (internal standard, IS), simultaneously. Enasidenib and imatinib were separated on an ACQUITY UPLC BEH C Column (2.