Towards a robust test to detect gene doping for anabolic enhancement in human athletes.

Success in gene therapy in treating human disease makes this technology attractive to enhance athletic performance, creating the need for gene doping detection. In 2021, World Anti-Doping Agency (WADA) approved the first gene doping test. Here, we describe a new method to detect doping with four additional genes, follistatin, growth hormone 1, growth hormone-releasing hormone and insulin-like growth factor 1, that may improve performance by increasing muscle size and strength.

Multi-omics of a pre-clinical model of diabetic cardiomyopathy reveals increased fatty acid supply impacts mitochondrial metabolic selectivity.

The incidence of type 2 diabetes (T2D) is increasing globally, with long-term implications for human health and longevity. Heart disease is the leading cause of death in T2D patients, who display an elevated risk of an acute cardiovascular event and worse outcomes following such an insult. The underlying mechanisms that predispose the diabetic heart to this poor prognosis remain to be defined.

Optimizing the discovery and assessment of therapeutic targets in heart failure with preserved ejection fraction.

There is an urgent need for models that faithfully replicate heart failure with preserved ejection fraction (HFpEF), now recognized as the most common form of heart failure in the world. In vitro approaches have several shortcomings, most notably the immature nature of stem cell-derived human cardiomyocytes [induced pluripotent stem cells (iPSC)] and the relatively short lifespan of primary cardiomyocytes. Three-dimensional 'organoids' incorporating mature iPSCs with other cell types such as endothelial cells and fibroblasts are a significant advance, but lack the complexity of true myocardium.

A Global Profile of Reversible and Irreversible Cysteine Redox Post-Translational Modifications During Myocardial Ischemia/Reperfusion Injury and Antioxidant Intervention.

Cysteine (Cys) is a major target for redox post-translational modifications (PTMs) that occur in response to changes in the cellular redox environment. We describe multiplexed, peptide-based enrichment and quantitative mass spectrometry (MS) applied to globally profile reversible redox Cys PTM in rat hearts during ischemia/reperfusion (I/R) in the presence or absence of an aminothiol antioxidant, -2-mercaptopropionylglycine (MPG). Parallel fractionation also allowed identification of irreversibly oxidized Cys peptides (Cys-SOH/SOH).