Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia‐reperfusion (I/R) injury. Here, nanoparticle‐encapsulated SOD (NP‐SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome‐c assay. In an in vitro I/R model, free and NP‐SOD reduce active ROS, preserve mitochondrial integrity, and improve cell viability compared to controls. In a rat in vivo I/R injury model, NP‐encapsulation of fluorescent‐tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP‐SOD administration in vivo improves left ventricular contractility at 3‐h post‐reperfusion by echocardiography and 4‐weeks by echocardiography and invasive pressure–volume catheter analysis. These findings suggest that NP‐SOD mitigates ROS damage in cardiac I/R injury in vitro and maximizes retention in vivo. NP‐SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP‐SOD as a therapy to mitigate myocardial I/R injury.

No abstract

Renal olfactory receptor 1393 (Olfr1393) is an understudied sensory receptor that contributes to glucose handling in the proximal tubule. Our previous studies have indicated that this receptor may serve as a regulator of the sodium glucose co‐transporters (SGLTs) and contributes to the development of glucose intolerance and hyperfiltration in the setting of diet‐induced obesity. We hypothesized that Olfr1393 may have a similar function in Type 1 Diabetes. Using Olfr1393 wildtype (WT) and knockout (KO) mice along with streptozotocin (STZ) to induce pancreatic β‐cell depletion, we tracked the development and progression of diabetes over 12 weeks. Here we report that diabetic male Olfr1393 KO mice have a significant improvement in hyperglycemia and glucose tolerance, despite remaining susceptible to STZ. We also confirm that Olfr1393 localizes to the renal proximal tubule, and have uncovered additional expression within the glomerulus. Collectively, these data indicate that loss of renal Olfr1393 affords protection from STZ‐induced type 1 diabetes and may be a general regulator of glucose handling in both health and disease.

Purpose of reviewSignificant limitations in organ availability and postoperative graft dysfunction plague lung transplantation and there is continual need for innovation. Ex-vivo lung perfusion (EVLP) has emerged over the last decade as an alternative and/or complementary allograft storage and assessment tool, however logistical hurdles have limited its widespread dissemination. As such, the overall current and potential value of EVLP on modern-day lung transplantation should be considered as innovation moves forward.Recent findingsSince inception, EVLP has made important safety strides in conclusively showing noninferiority to cold storage in several trials. Recent advances have highlighted potential mechanisms by which EVLP in its current form may reduce the pathogenic origins of primary graft dysfunction. Exciting work on organ reconditioning with EVLP via reduction in intermediaries of acute inflammation and oxidative stress have been performed in animal models. In addition, cross-circulation during EVLP has emerged as a method to achieve more prolonged ex situ storage. The impending translation of these to clinical use will markedly improve the overall value of EVLP.SummaryThis review will highlight the current status of EVLP as it pertains to overall value in lung transplantation, focusing on historical and recent preclinical work and how innovation therein will improve lung transplantation as a field.

No abstract