No abstract

Intraportal islet transplantation suffers from low efficiency caused by substantial islet mass loss after transplantation. How this process is regulated is still unclear. Here, we show that NF-j B activation was detectable in islet grafts shortly after transplantation of porcine islets to diabetic NMRI nu/nu mice, and systemic NF-j B inhibition in transplanted animals significantly prolonged islet graft survival. Proinflammatory cytokines alone did not cause evident cell death in pancreatic islet within 24 h, while the combination of cytokines with hypoxia resulted in a strong induction of cell death that could be blocked dose-dependently by a selective IKK-b inhibitor. Under hypoxia, NF-j B activity impaired expression of antiapoptotic gene BCL-xL, c-FLIP and survivin. NF-j B activation in isolated islets was reduced by hypoxia in a time-dependent manner, accordingly, NF-j B activation in transplanted islets diminished by time. Our data indicate that, while NF-j B has an antiapoptotic role under normoxia, low oxygen conditions decrease its activity and transform it to a proapoptotic transcription factor in pancreatic islets. We conclude that NF-j B inhibition represents a potential strategy to improve islet transplantation efficiency.Key words: Islet transplantation, transplantation efficiency, engraftment, NF-kappaB, hypoxia, innate immunity Abbreviations: IKK-b , inhibitor of kappaB kinase beta; NF-j B, nuclear factor kappa B; T1D, type 1 diabetes; IEQ, islet equivalent; PI, Propidium Iodide; RPL13A, ribosomal protein L13a; Ct, threshold cycle; HIF-1a , hypoxia inducible factor 1, alpha subunit.

SummaryIslet transplantation is an extremely effective therapy for patients with type I diabetes, providing tight control of blood glucose and persistent insulin release. Islet grafts struggle with various stress responses and immunity attacks, which contribute to loss of islet grafts in the long term. In this review we focus upon the innate immunity and heat shock responses, which are closely relevant to the outcome of islet grafts. Potential strategies provided by more comprehensive interventions to control innate immunity and by selective induction of heat shock proteins may ameliorate the outcome of islet transplantation.

The task of mapping and explaining the spectrum of baryons and the structure of these states in terms of quarks and gluons is a longstanding challenge in hadron physics, which is likely to persist for another decade or more. We review the progress made in this topic using a functional method based on Dyson-Schwinger equations. This framework provides a non-perturbative, Poincarécovariant continuum formulation of Quantum Chromodynamics which is able to extract novel insight on baryon properties since the physics at the hadron level is directly related with the underlying quark-gluon substructure, via convolution of Green functions.