Quercetin and tin protoporphyrin attenuate hepatic ischemia reperfusion injury: role of HO-1

Naunyn-Schmiedeberg's Arch Pharmacol (2017) 390:871–881 DOI 10.1007/s00210-017-1389-

Lessons from Natural Cold-Induced Dormancy to Organ Preservation in Medicine and Biotechnology: From the “Backwoods to the Bedside”

Hypothermia is a powerful modulator of all life processes, and this has been harnessed over the past 50 years in clinical sciences where tissues or organs for transplantation need to be stored outside the body for periods of time. However for human organs (as an obligate homoeothermic), cooling alone cannot provide sufficient time for the clinical logistics of transplantation, and a series of interventions to further control metabolism have been developed empirically. In retrospect, it can be seen that these approaches mimic to some degree the ways in which cold tolerance in the natural world has developed in evolutionary terms. This chapter reviews the history and the current state of the art of applied hypothermic preservation, and compares and contrasts what is known about natural cold tolerance, highlighting areas for further research and development to meet the challenges for organ and tissue preservation in the next few years. © 2010 Springer-Verlag Berlin Heidelberg

Translational implications of endothelial cell dysfunction in association with chronic allograft rejection

International audienceAdvances in therapeutics have dramatically improved short-term graft survival, while the incidence of chronic rejection has not changed in the past 20 years. New insights into mechanism are sorely needed at this time and it is hoped that the development of predictive biomarkers will pave the way for the emergence of preventative therapeutics. In this review, we discuss a paradigm suggesting that sequential changes within graft endothelial cells (EC) lead to an intragraft microenvironment that favors the development of chronic rejection. Key changes include EC injury, activation and uncontrolled leukocyte-induced angiogenesis. We propose that all of these changes may lead to abnormal blood flow patterns, local tissue hypoxia and an associated overexpression of HIF-1α-inducible genes including Vascular Endothelial Growth Factor. We also discuss how regulators of mTOR-mediated signaling within EC are of critical importance in microvascular stability and the inhibition of chronic rejection. Finally, we discuss recent findings indicating that miRNAs regulate EC stability, and their potential as novel noninvasive biomarkers of allograft rejection. Altogether, this review provides insights into molecular events, genes and signals that promote chronic rejection and their potential as biomarkers for the future development of interruption therapeutics