FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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Organ injury in sepsis is initially characterized by dysfunction without cell death and structural damage, and thus with the ability to recover organ function. Adaptive metabolic responses to sepsis can prevent bioenergetic failure and death. These studies were aimed at investigating the influence of sepsis on mitochondrial homeostasis, focusing on removal of dysfunctional mitochondria and restitution of a healthy mitochondrial population. ⋯ CLP-induced markers of mitochondrial biogenesis and mitochondrial number and density recovered over time. Furthermore, these data suggest that mitochondrial biogenesis was dependent on an autophagy and mitochondrial DNA/Toll-like receptor 9 (TLR9) signaling pathway. These results suggest that hepatocyte survival and maintenance of function in sepsis is dependent on a mitochondrial homeostasis pathway marked by mitophagy and biogenesis.
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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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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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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.
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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.