Public Release:  JCI early table of contents for Oct. 1, 2013

Journal of Clinical Investigation

Hemin and sickle cell disease-associated acute chest syndrome development

Acute chest syndrome (ACS) is a complication of sickle cell disease that is characterized by sudden pain and difficulty breathing. Sickle cell disease can also cause red blood cells to suddenly breakdown and release their contents, which may trigger the onset of ACS. In this issue of the Journal of Clinical Investigation, Solomon Fiifi Ofori-Acquah and colleagues at Emory University asked if hemin, a product released by red blood cells during lysis, triggers ACS in a mouse model of sickle cell disease. They found that hemin injection caused labored breathing, acute lung injury and rapid death in sickle mice, but not in control mice. They determined that hemin acts through the immune receptor TLR4, since blocking or deleting this receptor prevented symptoms of hemin injection in sickle mice. Hemopexin, a protein that sequesters hemin was an effective treatment against hemin-induced lung injury both before and after symptom onset. These data suggest that therapies aimed at targeting hemin and/or blocking TLR4 signaling may be valuable approaches for treatment or prevention of acute chest syndrome.

TITLE: Extracellular hemin crisis triggers acute chest syndrome in sickle mice

AUTHOR CONTACT: Solomon Ofori-Acquah
Emory Univeristy School of Medicine, Atlanta, GA, USA
Phone: 4047272293; Fax: ; E-mail: soforia@emory.edu

View this article at: http://www.jci.org/articles/view/64578?key=3765dd65ee3f475d9df3


A link between type 2 diabetes and mitochondrial function

Type 2 diabetes is a chronic condition that is characterized by resistance to or insufficient production of insulin, a hormone that controls sugar movement into cells. In certain tissues, insulin resistance has been associated with dysfunction of mitochondria, which supply most of the cell's chemical energy. In this issue of the Journal of Clinical Investigation, C. Ronald Kahn and colleagues at Harvard Medical School evaluated mitochondrial involvement in insulin resistance. They found that heat shock protein 60 (HSP60), which is involved in mitochondrial protein import and macromolecule assembly, was required for appropriate mitochondrial function and insulin responses. Additionally, they demonstrated that leptin, a hormone that regulates metabolism and appetite, was important for HSP60 regulation. This study provides new insight into type 2 diabetes development and implicates leptin regulation of HSP60 as a potential therapeutic target.

TITLE: Leptin regulation of Hsp60 impacts hypothalamic insulin signaling

AUTHOR CONTACT: Andre Kleinridders
Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Phone: 617-309-4404; E-mail: andre.kleinridders@joslin.harvard.edu

View this article at: http://www.jci.org/articles/view/67615?key=89f85116db026aa40f0b


ALSO IN THIS ISSUE

TITLE: Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies

AUTHOR CONTACT: Hal Hoffman
Univ of California at San Diego, La Jolla, CA, USA
Phone: 858-534-2108; Fax: 858-534-2110; E-mail: hahoffman@ucsd.edu

View this article at: http://www.jci.org/articles/view/71543?key=286191294728b5973d05

TITLE: MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment

AUTHOR CONTACT: Stefan Kaufmann
Max Planck Institute for Infection Biology, Berlin, , DEU
E-mail: kaufmann@mpiib-berlin.mpg.de

View this article at: http://www.jci.org/articles/view/67604?key=4f0a74957298bbf8c2e7

TITLE: NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia

AUTHOR CONTACT: Denis Guttridge
The Ohio State University, Columbus, OH, USA
Phone: 614-688-3137; E-mail: denis.guttridge@osumc.edu

View this article at: http://www.jci.org/articles/view/68523?key=7647658bed787efac81b

TITLE: FGF19 action in the brain induces insulin-independent glucose lowering

AUTHOR CONTACT: Gregory Morton
University of Washington, Seattle, WA, USA
Phone: 206-897-5292; Fax: 206-897-5293; E-mail: gjmorton@u.washington.edu

View this article at: http://www.jci.org/articles/view/70710?key=eed7655287e23f9d5af8

TITLE: Ras pathway inhibition prevents neovascularization by repressing endothelial cell sprouting

AUTHOR CONTACT: Martin Friedlander
Scripps Research Institute, La Jolla, CA, USA
Phone: 858-784-9138; Fax: 858-784-9135; E-mail: friedlan@scripps.edu

View this article at: http://www.jci.org/articles/view/70230?key=e4e1d7ff332232cb3770

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