Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction.

Background: Phosphorylation of diacylglycerol by diacylglycerol-kinases represents a major inhibitory event constraining T cell activation upon antigen engagement. Efficient TCR signalling requires the inhibition of the alpha isoform of diacylglycerol kinase, DGKα, by an unidentified signalling pathway triggered by the protein adaptor SAP. We previously demonstrated that, in SAP absence, excessive DGKα activity makes the T cells resistant to restimulation-induced cell death (RICD), an apoptotic program counteracting excessive T cell clonal expansion.

Circulating Peptidome Is Strongly Altered in COVID-19 Patients.

Whilst the impact of coronavirus disease 2019 (COVID-19) on the host proteome, metabolome, and lipidome has been largely investigated in different bio-fluids, to date, the circulating peptidome remains unexplored. Thus, the present study aimed to apply an untargeted peptidomic approach to provide insight into alterations of circulating peptides in the development and severity of SARS-CoV-2 infection. The circulating peptidome from COVID-19 severe and mildly symptomatic patients and negative controls was characterized using LC-MS/MS analysis for identification and quantification purposes.

Exosomes in chronic respiratory diseases.

Exosomes are nano-sized vesicles released by almost all cell types, with a central role as mediators of intercellular communication. In addition to physiological conditions, these extracellular vesicles seem to play a pivotal role in inflammatory processes. This assumption offers the opportunity to study exosomes as promising biomarkers and therapeutic tools for chronic respiratory disorders.

Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors.

Store-operated calcium entry (SOCE) is important in the maintenance of calcium homeostasis and alterations in this mechanism are responsible for several pathological conditions, including acute pancreatitis. Since the discovery of SOCE, many inhibitors have been identified and extensively used as chemical probes to better elucidate the role played by this cellular mechanism. Nevertheless, only a few have demonstrated drug-like properties so far.

Metabolic Fate of the Isocyanide Moiety: Are Isocyanides Pharmacophore Groups Neglected by Medicinal Chemists?

Despite the isolation of hundreds of bioactive isocyanides from terrestrial fungi and bacteria as well as marine organisms, the isocyanide functionality has so far received little attention from a medicinal chemistry standpoint. The widespread tenet that isocyanides are chemically and metabolically unstable has restricted bioactivity studies to their antifouling properties and technical applications. In order to confirm or refute this idea, the hepatic metabolism of six model isocyanides was investigated.