-Biphenyl Pyrrolinones and Dibenzofurans as RNA-Binding Protein LIN28 Inhibitors Disrupting the LIN28- Interaction.

The RNA-binding protein LIN28 is a regulator of miRNA biogenesis. Inhibitors of LIN28 are highly sought after given the central role that LIN28 plays in tumorigenesis and development of cancer stem cells as well as LIN28's association with poor clinical prognosis. Although LIN28 inhibitors of different scaffolds have been reported, the potential of most LIN28 inhibiting small molecules was not fully explored since very limited structure-activity relationship (SAR) studies have been performed.

Prevalence of Sarcopenia in Older Patients in Rehabilitation Wards.

The multidisciplinary assessment of hospitalized patients via validated scales and tools has become crucial in the early identification of sarcopenia. The objective of this study was to determine the prevalence of sarcopenia and its related factors in patients aged ≥65 years admitted to the neurological rehabilitation departments of cognitive motor disorders and functional motor rehabilitation at the IRCCS Hospital San Raffaele in Milan. Using the algorithm reported by the European Working Group on Sarcopenia in Older People (EWGSOP2), the prevalence of sarcopenia in patients was investigated from 2019-2020.

Clinical outcomes of left atrial appendage occlusion in patients with previous intracranial or gastrointestinal bleeding: Insights from the LOGIC (Left atrial appendage Occlusion in patients with Gastrointestinal or IntraCranial bleeding) International Multicenter Registry.

Aims: To compare outcomes of patients who underwent left atrial appendage occlusion (LAAO) for nonvalvular atrial fibrillation (NVAF) and contraindication to anticoagulants due to history of either gastrointestinal (GI) or intracranial (IC) bleeding.

Methods: Patients with NVAF that underwent LAAO for GI or IC bleeding from seven centers were included in this observational study. Baseline characteristics, procedural features, and follow-up data were collected, and compared between the two groups.

Matching Ablation Endpoints to Long-Term Outcome: The Prospective Multicenter Italian Ventricular Tachycardia Ablation Registry.

Background: Multicenter ventricular tachycardia (VT) ablation studies have shown poorer outcomes compared with single-center experiences. This difference could be related to heterogeneous mapping and ablation strategies.

Objectives: This study evaluated a homogenous simplified catheter ablation strategy for different substrates and compared the results with those of a single referral center.

Designing Selective Drug-like Molecular Glues for the Glucocorticoid Receptor/14-3-3 Protein-Protein Interaction.

The ubiquitously expressed glucocorticoid receptor (GR) is a nuclear receptor that controls a broad range of biological processes and is activated by steroidal glucocorticoids such as hydrocortisone or dexamethasone. Glucocorticoids are used to treat a wide variety of conditions, from inflammation to cancer but suffer from a range of side effects that motivate the search for safer GR modulators. GR is also regulated outside the steroid-binding site through protein-protein interactions (PPIs) with 14-3-3 adapter proteins.

Check the Need-Prevalence and Outcome after Transvenous Cardiac Implantable Electric Device Extraction without Reimplantation.

Background: after transvenous lead extraction (TLE) of cardiac implantable electric devices (CIEDs), some patients may not benefit from device reimplantation. This study sought to analyse predictors and long-term outcome of patients after TLE with vs. without reimplantation in a high-volume centre.

Phosphorylated full-length Tau interacts with 14-3-3 proteins via two short phosphorylated sequences, each occupying a binding groove of 14-3-3 dimer.

Protein-protein interactions (PPIs) remain poorly explored targets for the treatment of Alzheimer's disease. The interaction of 14-3-3 proteins with Tau was shown to be linked to Tau pathology. This PPI is therefore seen as a potential target for Alzheimer's disease.

Design of Drug-Like Protein-Protein Interaction Stabilizers Guided By Chelation-Controlled Bioactive Conformation Stabilization.

Protein-protein interactions (PPIs) of 14-3-3 proteins are a model system for studying PPI stabilization. The complex natural product Fusicoccin A stabilizes many 14-3-3 PPIs but is not amenable for use in SAR studies, motivating the search for more drug-like chemical matter. However, drug-like 14-3-3 PPI stabilizers enabling such studies have remained elusive.