Antiphospholipid Antibody Testing in a Maximum Care Hospital: Method-Dependent Differences.

Antiphospholipid antibody (aPL) testing is critical for the classification of antiphospholipid syndrome. The 2023 ACR/EULAR classification criteria recommend the use of enzyme-linked immunosorbent assays (ELISAs) and specific thresholds for aPL positivity. Since non-ELISA methods are increasingly used, we compared and evaluated ELISA and non-ELISA aPL assays in a real-world maximum care hospital setting.

IGF1 promotes human myotube differentiation toward a mature metabolic and contractile phenotype.

Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle models in vitro are incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a growth factor secreted by myofibers in vivo, we aimed to overcome these limitations.

Skeletal Muscle Gene Expression Signatures of Obese High and Low Responders to Endurance Exercise Training.

Context: Exercise training is known to improve glucose tolerance and reverse insulin resistance in people with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention.

Objective: This study focused on gene expression and DNA methylation signatures in skeletal muscle of low (LRE) and high responders (RES) to 8 weeks of supervised endurance training.

Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes.

Metformin-induced glycolysis and lactate production can lead to acidosis as a life-threatening side effect, but slight increases in blood lactate levels in a physiological range were also reported in metformin-treated patients. However, how metformin increases systemic lactate concentrations is only partly understood. Because human skeletal muscle has a high capacity to produce lactate, the aim was to elucidate the dose-dependent regulation of metformin-induced lactate production and the potential contribution of skeletal muscle to blood lactate levels under metformin treatment.

The Acute Cytokine Response to 30-Minute Exercise Bouts Before and After 8-Week Endurance Training in Individuals With Obesity.

Context: One acute bout of exercise leads to a rapid increase in the systemic cytokine concentration. Regular exercise might alter the cytokine response, in particular in beforehand untrained and obese individuals.

Objective: Using a proximity extension assay, we studied the effects of acute exercise as well as endurance training on a panel of 92 cytokines related to inflammation.

LRH-1/NR5A2 interacts with the glucocorticoid receptor to regulate glucocorticoid resistance.

Nuclear receptors are transcription factors with important functions in a variety of physiological and pathological processes. Targeting glucocorticoid receptor (GR) activity using glucocorticoids is a cornerstone in the treatment of patients with T cell acute lymphoblastic leukemia (T-ALL), and resistance to GC-induced cell death is associated with poor outcome and a high risk for relapse. Next to ligand-binding, heterodimerization with other transcription factors presents an important mechanism for the regulation of GR activity.

Specific Attenuation of Purinergic Signaling during Bortezomib-Induced Peripheral Neuropathy In Vitro.

Human peripheral neuropathies are poorly understood, and the availability of experimental models limits further research. The PeriTox test uses immature dorsal root ganglia (DRG)-like neurons, derived from induced pluripotent stem cells (iPSC), to assess cell death and neurite damage. Here, we explored the suitability of matured peripheral neuron cultures for the detection of sub-cytotoxic endpoints, such as altered responses of pain-related P2X receptors.