Ischemia reperfusion injury is a complex process consisting of a seemingly chaotic but actually organized and compartmentalized shutdown of cell function, of which oxidative stress is a key component. Studying oxidative stress, which results in an imbalance between reactive oxygen species (ROS) production and antioxidant defense activity, is a multi-faceted issue, particularly considering the double function of ROS, assuming roles as physiological intracellular signals and as mediators of cellular component damage. Herein, we propose a comprehensive overview of the tools available to explore oxidative stress, particularly in the study of ischemia reperfusion. Applying chemistry as well as biology, we present the different models currently developed to study oxidative stress, spanning the vitro and the silico, discussing the advantages and the drawbacks of each set-up, including the issues relating to the use of in vitro hypoxia as a surrogate for ischemia. Having identified the limitations of historical models, we shall study new paradigms, including the use of stem cell-derived organoids, as a bridge between the in vitro and the in vivo comprising 3D intercellular interactions in vivo and versatile pathway investigations in vitro. We shall conclude this review by distancing ourselves from “wet” biology and reviewing the in silico, computer-based, mathematical modeling, and numerical simulation options: (a) molecular modeling with quantum chemistry and molecular dynamic algorithms, which facilitates the study of molecule-to-molecule interactions, and the integration of a compound in a dynamic environment (the plasma membrane...); (b) integrative systemic models, which can include many facets of complex mechanisms such as oxidative stress or ischemia reperfusion and help to formulate integrated predictions and to enhance understanding of dynamic interaction between pathways.

The growing use of marginal organs for transplantation pushes current preservation methods towards their limits, and the need for improvement is pressing. We previously demonstrated the benefits of M101, a natural extracellular oxygen carrier compatible with hypothermia, for the preservation of healthy renal grafts in a porcine model of auto‐transplantation. Herein, we use a variant of this pre‐clinical model to evaluate M101 potential benefits both in static storage (CS) and in machine perfusion (MP) preservation in the transplantation outcomes for marginal kidneys. In the CS arm, despite the absence of obvious benefits within the first two weeks of follow‐up, M101 dose‐dependently improved long‐term function, normalizing creatininemia after 1 and 3 months. In the MP arm, M101 improved short and long‐term functional outcomes as well as tissue integrity. Importantly, we provide evidence for the additivity of machine perfusion and M101 functional effects, showing that the addition of the compound further improves organ preservation, by reducing short‐term function loss, with no loss of function or tissue integrity recorded throughout the follow‐up. Extending previous observations with healthy kidneys, the present results point at the M101 oxygen carrier as a viable strategy to improve current organ preservation methods in marginal organ transplantation.

A post hoc analysis of the Diabeloop WP7 multicentre, randomized controlled trial was performed to investigate the efficacy of the Diabeloop Generation‐1 (DBLG1) closed‐loop system in controlling the hypoglycaemia induced by physical activity (PA) in real‐life conditions. Glycaemic outcomes were compared between days with and without PA in 56 patients with type 1 diabetes (T1D) using DBLG1 for 12 weeks. After the patient announces a PA, DBLG1 reduces insulin delivery and, if necessary, calculates the amount of preventive carbohydrates (CHO). Daily time spent in the interstitial glucose range less than 70 mg/dL was not significantly different between days with and without PA (2.0% ± 1.5% vs. 2.2% ± 1.1%), regardless of the intensity or duration of the PA. Preventive CHO intake recommended by the system was significantly higher in days with PA (41.1 ± 35.5 vs. 21.8 ± 28.5 g/day; P < .0001), and insulin delivery was significantly lower (31.5 ± 10.5 vs. 34.0 ± 10.5 U/day; P < .0001). The time spent in hyperglycaemia and the glycaemic variation coefficient increased significantly on days with PA. In real‐life conditions, the use of DBLG1 avoids PA‐induced hypoglycaemia. Insulin adjustments and preventive CHO recommendation may explain this therapeutic benefit.