Degrading the key component of the inflammasome: development of an NLRP3 PROTAC.

This study explores PROTACs for NLRP3, the key player in innate immunity. We utilised a thiophene analogue of the NLRP3 inhibitor MCC950 and employed CuAAC chemistry for the assembly of PROTACs bearing various linkers and recruiting three different E3 ligases. Compounds were evaluated in bidirectional thermal stability studies with NLRP3 and E3 ligases.

Lipopolysaccharide-Neutralizing Peptide Modulates P2X7 Receptor-Mediated Interleukin-1β Release.

Lipopolysaccharide (LPS)-neutralizing peptides are emerging as new potential therapeutic modalities to treat sepsis and skin infections. Purinergic ligand-gated ion channels (P2X receptors) play a critical role in various biological processes, including inflammation. Recent drug development efforts have significantly focused on the modulation of P2X receptors.

Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.

Cystic fibrosis (CF) is caused by mutations in the (). While gene therapy holds promise as a cure, the cell-type-specific heterogeneity of expression in the lung presents significant challenges. Current CF ferret models closely replicate the human disease phenotype but have limitations in studying functional complementation through cell-type-specific CFTR restoration.

An extended PFAS profiling of a Swedish subpopulation and mixture risk assessments using multiple approaches.

Per- and polyfluoroalkyl substances (PFAS) have been detected worldwide, from the deep seas to polar regions. A previous review showed that PFAS are risk drivers of the chemical mixture present in human blood. This study focused on establishing the PFAS exposure of a Swedish subpopulation and investigated whether the exposure poses a risk of adverse health effects.

CFTR represses a PDX1 axis to govern pancreatic ductal cell fate.

Inflammation, acinar atrophy, and ductal hyperplasia drive pancreatic remodeling in newborn cystic fibrosis (CF) ferrets lacking a functional cystic fibrosis conductance regulator (CFTR) channel. These changes are associated with a transient phase of glucose intolerance that involves islet destruction and subsequent regeneration near hyperplastic ducts. The phenotypic changes in CF ductal epithelium and their impact on islet function are unknown.