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. Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am J Physiol Endocrinol Metab 285: E363-E371, 2003. First published April 29, 2003 10.1152/ajpendo.00487.2002The mechanisms by which excessive glucocorticoids cause muscular atrophy remain unclear. We previously demonstrated that dexamethasone increases the expression of myostatin, a negative regulator of skeletal muscle mass, in vitro. In the present study, we tested the hypothesis that dexamethasone-induced muscle loss is associated with increased myostatin expression in vivo. Daily administration (60, 600, 1,200 g/kg body wt) of dexamethasone for 5 days resulted in rapid, dose-dependent loss of body weight (Ϫ4.0, Ϫ13.4, Ϫ17.2%, respectively, P Ͻ 0.05 for each comparison), and muscle atrophy (6.3, 15.0, 16.6% below controls, respectively). These changes were associated with dose-dependent, marked induction of intramuscular myostatin mRNA (66.3, 450, 527.6% increase above controls, P Ͻ 0.05 for each comparison) and protein expression (0.0, 260.5, 318.4% increase above controls, P Ͻ 0.05). We found that the effect of dexamethasone on body weight and muscle loss and upregulation of intramuscular myostatin expression was time dependent. When dexamethasone treatment (600 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) was extended from 5 to 10 days, the rate of body weight loss was markedly reduced to ϳ2% within this extended period. The concentrations of intramuscular myosin heavy chain type II in dexamethasonetreated rats were significantly lower (Ϫ43% after 5-day treatment, Ϫ14% after 10-day treatment) than their respective corresponding controls. The intramuscular myostatin concentration in rats treated with dexamethasone for 10 days returned to basal level. Concurrent treatment with RU-486 blocked dexamethasone-induced myostatin expression and significantly attenuated body loss and muscle atrophy. We propose that dexamethasone-induced muscle loss is mediated, at least in part, by the upregulation of myostatin expression through a glucocorticoid receptor-mediated pathway.regulation;

Many organisms construct structural ceramic (biomineral) composites from seemingly mundane materials; cell-mediated processes control both the nucleation and growth of mineral and the development of composite microarchitecture. Living systems fabricate biocomposites by: (i) confining biomineralization within specific subunit compartments; (ii) producing a specific mineral with defined crystal size and orientation; and (iii) packaging many incremental units together in a moving front process to form fully densified, macroscopic structures. By adapting biological principles, materials scientists are attempting to produce novel materials. To date, neither the elegance of the biomineral assembly mechanisms nor the intricate composite microarchitectures have been duplicated by nonbiological processing. However, substantial progress has been made in the understanding of how biomineralization occurs, and the first steps are now being taken to exploit the basic principles involved.

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Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of the anticancer drug 5-fluorouracil have been devised. The target is always to provide the proper dose of the antitumor agent only at the desired locus of action, thus reducing the unwanted side effects. In this review, the main strategies and the more significant results in the development of 5-fluorouracil carriers for cancer treatment are discussed.

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This study reports the design of a novel theragnostic nanomedicine which combines (i) the ability to target a prodrug of gemcitabine to an experimental solid tumor under the influence of a magnetic field with (ii) the imaging of the targeted tumoral nodule. This concept is based on the inclusion of magnetite nanocrystals into nanoparticles (NPs) constructed by self-assembling molecules of the squalenoyl gemcitabine (SQgem) bioconjugate. The nanocomposites are characterized by an unusually high drug loading, a significant magnetic susceptibility, and a low burst release. When injected to the L1210 subcutaneous mice tumor model, these magnetite/SQgem NPs were magnetically guided, and they displayed considerably greater anticancer activity than the other anticancer treatments (magnetite/SQgem NPs nonmagnetically guided, SQgem NPs, or gemcitabine free in solution). The histology and immunohistochemistry investigation of the tumor biopsies clearly evidenced the therapeutic superiority of the magnetically guided nanocomposites, while Prussian blue staining confirmed their accumulation at the tumor periphery. The superior therapeutic activity and enhanced tumor accumulation has been successfully visualized using T(2)-weighted imaging in magnetic resonance imaging (MRI). This concept was further enlarged by (i) the design of squalene-based NPs containing the T(1) Gd(3+) contrast agent instead of magnetite and (ii) the application to other anticancer squalenoyls, such as, cisplatin, doxorubicin, and paclitaxel. Thus, by combining different anticancer medicines as well as contrast imaging agents in NPs, we open the door toward generic conceptual framework for cancer treatment and diagnosis. This new theragnostic nanotechnology platform is expected to have important applications in cancer therapy.