FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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Renal transplantation remains the best treatment option for patients with end-stage renal failure. However, the shortage of renal grafts remains a big challenge. Renal graft ischemic injuries that occur before and after graft retrieval have a devastating effect on graft survival, especially on grafts from marginal donors. ⋯ The release of the apoptogenic factors cytochrome c, apoptosis-inducing factor (AIF), and proinflammatory high-mobility group protein B1 (HMGB-1) was effectively suppressed. This study thus demonstrated for the first time that Xe confers renoprotection on renal grafts ex vivo and is likely to stabilize cellular structure during ischemic insult. The current study has significant clinical implications, in which the use of Xe ex vivo could enhance the marginal donor pool of renal grafts by preventing graft loss due to ischemia.
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We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of acute lung injury (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all models requiring availability of both C5a receptors (C5aR and C5L2) for full development of ALI. Ligation of C5aR and C5L2 with C5a triggered the appearance of histones (H3 and H4) in bronchoalveolar lavage fluid (BALF). ⋯ The direct lung damaging effects of extracellular histones were demonstrated by airway administration of histones into mice and rats (Sprague-Dawley), which resulted in ALI that was C5a receptor-independent, and associated with intense inflammation, PMN accumulation, damage/destruction of alveolar epithelial cells, together with release into lung of cytokines/chemokines. High-resolution magnetic resonance imaging demonstrated lung damage, edema and consolidation in histone-injured lungs. These studies confirm the destructive C5a-dependent effects in lung linked to appearance of extracellular histones.
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Pigment epithelium-derived factor (PEDF), the protein product of the SERPINF1 gene, has been linked to distinct diseases involving adipose or bone tissue, the metabolic syndrome, and osteogenesis imperfecta (OI) type VI. Since mesenchymal stem cell (MSC) differentiation into adipocytes vs. osteoblasts can be regulated by specific factors, PEDF-directed dependency of murine and human MSCs was assessed. PEDF inhibited adipogenesis and promoted osteoblast differentiation of murine MSCs, osteoblast precursors, and human MSCs. ⋯ In PEDF knockout (KO) mice, total body adiposity was increased by >50% compared with controls, illustrating its systemic role as a negative regulator of adipogenesis. Bones from KO mice demonstrated a reduction in mineral content recapitulating the OI type VI phenotype. These results demonstrate that the human diseases associated with PEDF reflect its ability to modulate MSC differentiation.
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Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. ⋯ Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.
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Historical Article
Increased co-first authorships in biomedical and clinical publications: a call for recognition.
There has been a dramatic increase in the number and percentage of publications in biomedical and clinical journals in which two or more coauthors claim first authorship, with a change in some journals from no joint first authorship in 1990 to co-first authorship of >30% of all research publications in 2012. As biomedical and clinical research become increasingly complex and team-driven, and given the importance attributed to first authorship by grant reviewers and promotion and tenure committees, the time is ripe for journals, bibliographic databases, and authors to highlight equal first author contributions of published original research.