Spondias species have been used in traditional medicine for different human ailments. In this study, the effect of different solvents (ethyl acetate, methanol, and water) and extraction methods (infusion, maceration, and Soxhlet extraction) on the enzyme inhibitory activity against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, α-glucosidase, and antioxidant properties of S. mombin and S. dulcis leaves and stem bark were evaluated. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) yield in the identification and/or annotation of 98 compounds showing that the main secondary metabolites of the plant are gallic and ellagic acids and their derivatives, ellagitannins, hydroxybenzoic, hydroxycinnamic, acylquinic acids and flavonols, flavanones, and flavanonols. The leaves infusion of both Spondias species showed highest inhibition against acetylcholinesterase (AChE) (10.10 and 10.45 mg galantamine equivalent (GALAE)/g, for S. dulcis and S. mombin, respectively). The ethyl acetate extracts of the stem bark of S. mombin and S. dulcis actively inhibited α-glucosidase. Methanolic extracts of the leaves and stem bark exhibited highest tyrosinase inhibitory action. Antioxidant activity and higher levels of phenolics were observed for the methanolic extracts of Spondias. The results suggested that the Spondias species could be considered as natural phyto-therapeutic agents in medicinal and cosmeceutical applications.
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of RAG-mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic RAG variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons. T helper 2 (TH2) cell skewing and a prominent inflammatory signature characterize Omenn syndrome, whereas more hypomorphic forms of RAG deficiency are associated with a type 1 immune profile both in blood and tissues. We used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis to define the cell lineage-specific contribution to the immunopathology of the distinct RAG phenotypes. These insights may help improve the diagnosis and clinical management of the various forms of the disease.