Understanding neurocognitive recovery in older adults after total hip arthroplasty-neurocognitive assessment, blood biomarkers and patient experiences: a mixed-methods study.

Objective: Delayed neurocognitive recovery, previously known as postoperative cognitive dysfunction, is a common complication affecting older adults after surgery. This study aims to address the knowledge gap in postoperative neurocognitive recovery by exploring the relationship between subjective experiences, performance-based measurements, and blood biomarkers.

Design: Mixed-methods study with a convergent parallel (QUAL+quan) design.

Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of Cancer.

The interest in galectin-3 as a drug target in the cancer and fibrosis space has grown during the past few years with several new classes of compounds being developed. The first orally available galectin-3 inhibitor, (h-galectin-3 K = 0.025 μM), is currently in phase 2 clinical trials.

Sulfonamide-derivatized galactosides selectively target an unexplored binding site in the galectin-9N-terminal domain.

Four directional and positional variants of sulfonamide-derivatized galactopyranosides were synthesized and evaluated against human galectin-1, -3, -4C (C-terminal), -7, -8N (N-terminal), -8C (C-terminal), -9N (N-terminal), and -9C (C-terminal), which revealed that one of the sulfonamide positions and directionalities (methyl 3-{4-[2-(phenylsulfonylamino)-phenyl]-triazolyl}-3-deoxy-α-d-galactopyranosides) bound with 6-15 fold higher affinity than the corresponding phenyltriazole (lacking the phenylsulfonamide moiety) for galectin-9N. Molecular dynamic simulations suggested that inhibitor adopted a conformation that is complementary to the galectin-9N binding site and where the sulfonamide moiety protrudes into an unexplored and non-conserved binding site perpendicular to and below the A-B subsite to interact with a His61 NH proton. This resulted in the discovery of galectin-9N inhibitors with unprecedented selectivity over other galectins, thus constituting valuable tools for studies of the biological functions of galectin-9.

Effect of GB1107, a novel galectin-3 inhibitor on pro-fibrotic signalling in the liver.

Background And Purpose: Galectin-3 (Gal-3) is a pro-fibrotic β-galactoside binding lectin highly expressed in fibrotic liver and implicated in hepatic fibrosis. GB1107 is a novel orally active Gal-3 small molecule inhibitor that has high affinity for Gal-3 >1000-fold selectively over other galectins. The aim of this study was to characterise GB1107 and galectin-3 in vitro and in vivo in the context of fibrosis signalling and liver disease.