Macrophage migration inhibitory factor (MIF) is a multifunctional protein that exhibits an intrinsic thiol protein oxidoreductase activity and proinflammatory activities. In the present study to examine intracellular MIF redox function, exposure of MIF-deficient cardiac fibroblasts to oxidizing conditions resulted in a 2.3-fold increase (p < 0.001) in intracellular ROS that could be significantly reduced by adenoviral-mediated reexpression of recombinant MIF. In an animal model of myocardial injury by ischemia/reperfusion (I/R), MIF-deficient hearts exhibited higher levels of oxidative stress than did wild-type hearts, as measured by significantly higher oxidized glutathione levels (decreased GSH/GSSG ratio), increased protein oxidation, reduced aconitase activity, and increased mitochondrial injury (increased cytochrome c release). The increased myocardial oxidative stress after I/R was reflected by larger infarct size (INF) in MIF-deficient hearts versus wild-type (WT) hearts (21 ± 6% vs. 8 ± 3% INF/LV; p < 0.05). In vivo hemodynamic measurements showed that left ventricular (LV) contractile function of MIF-deficient hearts subjected to 15-min ischemia failed to recover during reperfusion compared with WT hearts (LV developed pressure and ± dP/dt; p = 0.02). These data represent the first in vivo evidence in support of a cardioprotective role of MIF in the postischemic heart by reducing oxidative stress.

MIF-induced neutrophil accumulation in the alveolar space results from interaction with CD74 expressed on the surface of alveolar macrophage cells. This interaction induces p44/p42 MAPK activation and chemokine release. The data suggest that MIF and its receptor, CD74, may be useful targets to reduce neutrophilic lung inflammation, and acute lung injury.

Cancer in adolescents and young adults is an important public health issue, because there are approximately 1 million new cases annually. The distribution of diseases in this age group varies geographically, contributing to differences in survival rates. Although an overall survival rate exceeding 80 % has been reported in optimal circumstances, emerging knowledge about distinctions in tumor biology and enhanced clinical accrual to clinical trials should lead to further gains. The challenges of cancer survivorship demand further attention with a particular focus on the quality of life of survivors and amelioration of the long‐term complications of treatment. Programs in cancer screening and prevention provide potential for considerable benefits in this age group. A renewed perspective on the adolescent and young adult cohort is required; and, in all of these opportunities for change, there are important roles to be played by advocacy groups internationally. Cancer 2011;117(10 suppl):2245–9. © 2011 American Cancer Society.

α‐Amino acids imidazolium salt smoothly reacted with diphenylcarbonate to afford the corresponding urethanes. The urethanes were activated by adding carboxylic acid to undergo selective cyclization, leading to successful development of a new phosgene‐free process for synthesizing α‐amino acid N‐carboxyanhydrides (NCAs).

A new convenient access to N‐carboxyanhydride (NCA) monomers has been achieved based on the utilization of bisarylcarbonates as a carbonyl source, which are activated by electron‐withdrawing substituents on their aryl groups such as fluorine atom and nitro group. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

We report a useful synthetic method of polypeptides using a series of urethane derivative of α‐amino acids (l‐leucine, l‐phenylalanine, l‐valine, l‐alanine, l‐isoleucine, l‐methionine), which are readily synthesized by N‐carbamoylation of tetrabutylammonium salts of α‐amino acids with diphenyl carbonate. Heating these urethane derivatives in N,N‐dimethylacetamide in the presence of n‐butylamine successfully gave the corresponding polypeptides with well‐defined structures through polycondensation with the elimination of phenol and CO2. The matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry investigation showed that the resulting polypeptides had an n‐BuNH2‐incorporated initiating end and an amino group at propagating end. These results strongly indicated that primary amines served as an initiator in this polycondensation system. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3726–3731

Macrophage migration inhibitory factor (MIF) functions as a proinflammatory cytokine when secreted from the cell, but it also exhibits antioxidant properties by virtue of its intrinsic oxidoreductase activity. Since increased production of ROS is implicated in the development of left ventricular hypertrophy, we hypothesized that the redox activity of MIF protects the myocardium when exposed to hemodynamic stress. In a mouse model of myocardial hypertrophy induced by transverse aortic coarctation (TAC) for 10 days, we showed that growth of the MIF-deficient heart was significantly greater by 32% compared with wild-type (WT) TAC hearts and that fibrosis was increased by fourfold (2.62 Ϯ 0.2% vs. 0.6 Ϯ 0.1%). Circulating MIF was increased in TAC animals, and expression of MIF receptor, CD74, was increased in the hypertrophic myocardium. Gene expression analysis showed a 10-fold increase (P Ͻ 0.01) in ROS-generating mitochondrial NADPH oxidase and 2-to 3-fold reductions (P Ͻ 0.01) in mitochondrial SOD2 and mitochondrial aconitase activities, indicating enhanced oxidative injury in the hypertrophied MIF-deficient ventricle. Hypertrophic signaling pathways showed that phosphorylation of cytosolic glycogen synthase kinase-3␣ was greater (P Ͻ 0.05) at baseline in MIF-deficient hearts than in WT hearts and remained elevated after 10-day TAC. In the hemodynamically stressed MIFdeficient heart, nuclear p21 CIP1 increased sevenfold (P Ͻ 0.01), and the cytosolic increase of phospho-p21 CIP1 was significantly greater than in WT TAC hearts. We conclude that MIF antagonizes myocardial hypertrophy and fibrosis in response to hemodynamic stress by maintaining a redox homeostatic phenotype and attenuating stressinduced activation of hypertrophic signaling pathways.

A new convenient synthesis of N‐carboxyanhydrides (NCAs) of α‐amino acids was achieved by selective cyclization of urethane derivatives of α‐amino acids. The urethanes were readily synthesized via N‐carbamoylation of α‐amino acids by bis(4‐nitrophenyl)carbonate quantitatively. These urethanes having 4‐nitrophenoxy moiety were tolerant to air and moisture to allow their facile purification and storage. When the obtained urethanes were heated in 2‐butanone at 60 °C, they underwent the selective cyclization via intramolecular nucleophilic attack of the carboxyl moiety to the urethane moiety with releasing 4‐nitrophenol, leading to the successful formation of the corresponding NCAs. Addition of carboxylic acids remarkably stabilized the formed NCAs during the reaction, allowing their isolation in high yields. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3839–3844, 2009