Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma.

Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor () to the proliferative isoform.

Predictors of hypercontractile heart phenotype in patients with chronic coronary syndromes or heart failure.

Hypercontractile phenotype (HP) of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS) or heart failure (HF), but its clinical recognition remains difficult. To assess the clinical variables associated with the HP. In a prospective, observational, multicenter study, we recruited 5122 patients (age 65 ± 11 years, 2974 males, 58%) with CCS and/or HF with preserved ejection fraction (EF).

Reduction of RAD23A extends lifespan and mitigates pathology in TDP-43 mice.

Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis.