Reproducibility and research integrity are essential tenets of every scientific study and discovery. They serve as proof that an established and documented work can be verified, repeated, and reproduced. New knowledge in the biomedical science is built on the shoulders of established and proven principles. Thus, scientists must be able to trust and build on the knowledge of their colleagues. Scientific innovation and research discoveries especially in the field of medicine has contributed to improving the lives of patients and increasing life expectancies. However, the growing concerns of failure to comply with good scientific principles has resulted in issues with research integrity and reproducibility. Poor reproducibility and integrity, therefore, may lead to ineffective interventions and applications. Here we comment on research reproducibility in basic medical and life sciences with regards to issues arising and outline the role of stakeholders such as research institutions and their employees in addressing this crisis.

The causative role of inflammation in hypertension-related cardiovascular diseases is evident and calls for development of specific immunomodulatory therapies. We tested the therapeutic efficacy and mechanisms of action of developmental endothelial locus-1 (DEL-1), an endogenous antiinflammatory factor, in angiotensin II– (ANGII–) and deoxycorticosterone acetate–salt–induced (DOCA-salt–induced) cardiovascular organ damage and hypertension. By using mice with endothelial overexpression of DEL-1 (EC-Del1 mice) and performing preventive and interventional studies by injecting recombinant DEL-1 in mice, we showed that DEL-1 improved endothelial function and abrogated aortic adventitial fibrosis, medial thickening, and loss of elastin. DEL-1 also protected the mice from cardiac concentric hypertrophy and interstitial and perivascular coronary fibrosis and improved left ventricular function and myocardial coronary perfusion. DEL-1 prevented aortic stiffness and abolished the progression of hypertension. Mechanistically, DEL-1 acted by inhibiting α_vβ₃ integrin–dependent activation of pro-MMP2 in mice and in human isolated aorta. Moreover, DEL-1 stabilized α_vβ₃ integrin–dependent CD25⁺FoxP3⁺ Treg numbers and IL-10 levels, which were associated with decreased recruitment of inflammatory cells and reduced production of proinflammatory cytokines in cardiovascular organs. The demonstrated effects and immune-modulating mechanisms of DEL-1 in abrogation of cardiovascular remodeling and progression of hypertension identify DEL-1 as a potential therapeutic factor.

ALDH2 deficiency and LTC4 synthesis enhance NET formation during myocardial I/RI. Myocardial ischaemia results in down-regulation of mitochondrial ALDH2 in the heart. Aldehyde dehydrogenase-2 (ALDH2) deficiency promotes endoplasmic reticulum (ER) stress-mediated reactive oxygen species (ROS) production via microsomal glutathione S-transferase 2 (MGST2)-based biosynthesis of leukotriene C4 (LTC4). ROS mediate myocardial reperfusion injury by inducing the opening of the mitochondrial permeability transition pore (MPTP), acting as a neutrophil chemoattractant, and mediating dysfunction of the sarcoplasmic reticulum. Factors such as ROS, protein-arginine deiminase type-4 (PAD4), interleukin-1β, and tumour necrosis factor-α induce the formation of neutrophil extracellular traps (NETs) by activated neutrophils. The lack of proper clearance by macrophages as well as defects in DNase enzymes contributes to the release of the NET-derived debris. The NET contents are exposed to the immune system and are identified as autoantigens, driving autoantibody production, increased inflammation, tissue damage, and pathological fibrosis. Inhibition of the LTC4 receptor abolishes ER stress-induced ROS production and NET formation, contributing to cardioprotective effects during myocardial ischaemia/reperfusion injury (I/RI). Repurposing the antiasthmatic drug pranlukast, an FDA-approved LTC4 receptor antagonist, may serve as potential therapeutic strategy for myocardial I/RI. MMP, matrix metalloproteinase; NOX2, NAPDH oxidase 2

In Figure 7H, the Vehicle+Fc flow cytometry panel was incorrect. In Figure 9M, the ANGII+DEL-1-FC panel was incorrect. In Figure 10M, the ANGII+DEL-1-RGE-Fc was incorrect. The correct images, provided from the original source data, are shown below.