Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, reprogramming the recipient cells upon their bioactive compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo, cell-targeting specificity are of immense biological interest considering extremely high potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic nanocarriers. In present review, we outline and discuss recent progress in the elucidation of the regulatory mechanisms of exosome biogenesis, the molecular composition of exosomes, and technologies used in exosome research. Furthermore, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their cell-lineage and state-specific contents, and possibilities as therapeutic vehicles for drug and gene delivery. Exosome research is now in its infancy, in-depth understanding of subcellular components and mechanisms involved in exosome formation and specific cell-targeting will bring light on their physiological activities.

PRIMARY GOAL OF THERAPY FOR patients with chronic disease is to improve their health status, including symptoms, functional status, and quality of life. In patients with coronary disease, cardiovascular interventions are known to improve health status, 1-4 but the extent to which such benefits result from changes in cardiac vs noncardiac factors is unclear. Most studies have found only limited associations between cardiac function and health status measures, 5-9 suggesting that other factors may be as important as cardiac function in determining the health status of patients with heart disease. Depressive symptoms are known to be associated with worse health status among patients with coronary artery disease, 10-12 but their relative contributions compared with physiologic measures of disease severity are unknown. 13 To examine the relative influence of depressive symptoms and cardiac function on health status, we measured depressive symptoms, cardiac function (including left ventricular ejection fraction, exercise capacity, and ischemia), and a range of health status outcomes among 1024 patients with coronary ar

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The Toll-interleukin 1 receptor (TIR) superfamily, defined by the presence of an intracellular TIR domain, initiates innate immunity through activation of the transcription factor NF-kappa B, leading to the production of proinflammatory cytokines. ST2 is a member of the TIR family that does not activate NF-kappa B and has been suggested as an important effector molecule of T helper type 2 (T(H)2) responses. We show here that the membrane-bound form of ST2 negatively regulated type I interleukin 1 receptor (IL-1RI) and Toll-like receptor 4 (TLR4) but not TLR3 signaling by sequestrating the adaptors MyD88 and Mal. In contrast to wild-type mice, ST2-deficient mice failed to develop endotoxin tolerance. Thus, these results provide a molecular explanation for the function of ST2 in T(H)2 responses, as inhibition of TLRs promotes a T(H)2 response, and also identify ST2 as a key regulator of endotoxin tolerance.

Heparin is unique as one of the oldest drugs currently still in widespread clinical use as an anticoagulant, a natural product, one of the first biopolymeric drugs, and one of the few carbohydrate drugs. Recently, certain batches of heparin have been associated with anaphylactoid-type reactions, some leading to hypotension and death. These reactions were traced to contamination with a semi-synthetic oversulfated chondroitin sulfate (OSCS). This Highlight reviews the heparin contamination crisis, its resolution, and the lessons learned. Pharmaceutical scientists now must consider dozens of natural and synthetic heparinoids as potential heparin contaminants. Effective assays, which can detect both known and unknown contaminants, are required to monitor the quality of heparin. Safer and better-regulated processes are needed for heparin production.