Effect of Staggered vs. Simultaneous Co-Administration of Bempedoic Acid on Pharmacokinetics of Pravastatin: Randomized, Cross-Over Clinical Trial in Healthy Volunteers.

: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it is an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake transporters regulating the intrahepatic availability of statins, it increases the systemic exposure of co-administered statins. This interaction could raise the risk of myopathy.

Sitting time at work and cardiovascular disease risk-a longitudinal analysis of the Study on Mental Health at Work (S-MGA).

Purpose: This study analyzed longitudinal data to examine whether occupational sitting time is associated with increases in body mass index (BMI) and five-year cardiovascular disease (CVD) risk.

Methods: We included 2,000 employed men and women (aged 31-60) from the German Study on Mental Health at Work (S-MGA) for a BMI analysis and 1,635 participants free of CVD at baseline (2011/2012) for a CVD analysis. Occupational sitting time was categorized into five groups (< 5, 5 to < 15, 15 to < 25, 25 to < 35, and ≥ 35 h per week).

Combining SNAC and C10 in oral tablet formulations for gastric peptide delivery: A preclinical and clinical study.

Current oral formulations of macromolecules including peptides typically rely on single permeation enhancer (PE) to promote absorption and thus bioavailability. In this work, we combined two PEs, namely sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) and sodium caprate (C10), in one tablet formulation to potentially gain a synergistic effect for enhanced gastric absorption of a GLP-1 analogue and a PCSK9 inhibitor. Permeability tests on a gastric organoids-based cell model showed that the combination of SNAC and C10 can significantly improve peptide permeability compared to either SNAC or C10 alone.

Anxiety modulators elicit different behavioral outcomes in adult zebrafish: Emphasis on homebase-related parameters and spatio-temporal exploration.

Anxiety is an emotion that represents a crucial anticipatory reaction of aversive stimuli, with clinical relevance in cases of disproportional and severe occurrences. Although distinct animal models have contributed to elucidate anxiety-related mechanisms, the influence of anxiogenic and anxiolytic modulations on both locomotion and exploration-related parameters in the open field test (OFT) is not fully elucidated. Here, we aimed to assess the influence of anxiogenic and anxiolytic manipulations on the exploratory dynamics of adult zebrafish (Danio rerio) focusing on homebase-related behaviors.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.