MicroRNA-377 Regulates Mesenchymal Stem Cell-Induced Angiogenesis in Ischemic Hearts by Targeting VEGF

MicroRNAs have been appreciated in various cellular functions, including the regulation of angiogenesis. Mesenchymal-stem-cells (MSCs) transplanted to the MI heart improve cardiac function through paracrine-mediated angiogenesis. However, whether microRNAs regulate MSC induced angiogenesis remains to be clarified. Using microRNA microarray analysis, we identified a microRNA expression profile in hypoxia-treated MSCs and observed that among all dysregulated microRNAs, microRNA-377 was decreased the most significantly. We also validated that vascular endothelial growth factor (VEGF) is a target of microRNA-377 using dual-luciferase reporter assay and Western-blotting. Knockdown of endogenous microRNA-377 promoted tube formation in human umbilical vein endothelial cells. We then engineered rat MSCs with lentiviral vectors to either overexpress microRNA-377 (MSC^miR-377) or knockdown microRNA-377 (MSC^Anti-377) to investigate whether microRNA-377 regulated MSC-induced myocardial angiogenesis, using MSCs infected with lentiviral empty vector to serve as controls (MSC^Null). Four weeks after implantation of the microRNA-engineered MSCs into the infarcted rat hearts, the vessel density was significantly increased in MSC^Anti-377-hearts, and this was accompanied by reduced fibrosis and improved myocardial function as compared to controls. Adverse effects were observed in MSC^miR-377-treated hearts, including reduced vessel density, impaired myocardial function, and increased fibrosis in comparison with MSC^Null-group. These findings indicate that hypoxia-responsive microRNA-377 directly targets VEGF in MSCs, and knockdown of endogenous microRNA-377 promotes MSC-induced angiogenesis in the infarcted myocardium. Thus, microRNA-377 may serve as a novel therapeutic target for stem cell-based treatment of ischemic heart disease.     

Release of calcium from intracellular stores in rat basophilic leukemia cells monitored with the fluorescent probe chlortetracycline.

Release of calcium from intracellular stores of rat basophilic leukemia cells was monitored using the fluorescent probe chlortetracycline. The ability of chlortetracycline to indicate release from intracellular calcium stores was initially validated. The decrease of chlortetracycline fluorescence upon antigen-stimulation was not the result of secretion of granule-associated dye or of changes in the properties of the membranes. The chlortetracycline fluorescence signal was not influenced by Ca2+ influx across the plasma membrane. Results obtained from these chlortetracycline fluorescence measurements corresponded well with 45Ca efflux data, an indirect measurement of release of calcium from stores. Chlortetracycline was used to examine the rate of antigen-induced release of calcium from stores, the depletion of intracellular calcium stores by EGTA, and the relationship between the antigen-stimulated release of stored calcium and exocytosis. Chlortetracycline was shown to be a useful qualitative indicator for the release of intracellular calcium with a relatively rapid response time.     

Management of congenital bilateral cleft nose

A rare case of nasal clefting was presented to illustrate and emphasize the following points: The workup of nasal clefting should be complete to rule out associated deformities. Marked improvement may be noted with normal growth during the first few years of life. The surgical procedure employed a primary V-Y flap harvested from the central excess of nasal skin based on a very thin vascular area at the nasal columella. At this primary procedure, the flap was telescoped on itself to provide fullness in the nasal tip area. It was also split, and two transposition flaps were inset into the gap left behind by rotating the ala into normal position. The donor area of the V-Y flap provided easy access to the intercanthal area so that the excess skin on the bridge of the nose could be reduced. Two subsequent minor procedures were required for adjusting irregularities in the tip.     

Effects of photon flux density on carbon partitioning and rhizosphere carbon flow of Lolium perenne

The distribution and partitioning of dry matter and photoassimilateof Lolium perenne was investigated under two light regimes providingphotosynthetically active radiation of 350 µmol m^–2s^–1 (low light treatment) or 1000 µmol m^–2s^–1 (high light treatment). Plants were grown at specificgrowth conditions in either soil or sand microcosm units tofollow the subsequent release of carbon into the rhizosphereand its consequent incorporation into the microbial biomass(soil system) or recovery as exudates (sand system). The distributionof recent assimilate between the plant and root released carbonpools was determined using ¹⁴CO₂ pulse-chase methodology atboth light treatments and for both sand- and soil-grown seedlings.A significant (P     

Diffusible Fraction of Serum Cholesterol and Atherogenesis

CHOLESTEROL is found in the blood as a structural component of lipoproteins concerned with the transport of other lipids¹. The high resolution nuclear magnetic resonance spectra of high density serum lipoproteins are similar to that observed when lipids are dissolved in organic solvents, or dispersed in water by bile salts or detergents, or in sonicated form. The lipid component in lipoproteins is therefore probably in an extremely fluid condition². If human serum is mixed with paraffin oil, some of the cholesterol diffuses into the oil without affecting the ultraviolet absorption spectrum of serum proteins. This procedure avoids any protein denaturing action used for cholesterol extraction^3–5. It therefore seems that serum cholesterol has two fractions, one strongly bound by lipoprotein structures and the other loosely bound and diffusible in an oil phase. In this article I designate the loosely bound fraction “diffusible”.     

Treatment of Paget's Disease of Bone with Mithramycin

We report data from three patients with severe Paget''s disease of bone who were treated with mithramycin.Mithramycin infusion resulted in a fall in plasma calcium, phosphate, alkaline phosphatase, and urinary hydroxyproline excretion. There was an improvement in calcium and phosphorus balance in two of the three subjects studied. A pronounced or complete relief of bone pain occurred in all three.We suggest that mithramycin exerts its beneficial effect in Paget''s disease of bone by stimulating parathyroid hormone release. The parathyroid hormone released has a predominantly anabolic action on bone since its catabolic action is blocked by mithramycin, which inhibits bone resorption.     

Effect of cysteamine on suckling-induced prolactin secretion in the rat

We have examined the effects of the thiol agent cysteamine on physiological prolactin secretion in the female rat. Administration of cysteamine completely abolishes suckling-induced prolactin secretion in a dose-dependent manner. Cysteamine treatment does not alter nursing behavior of the mothers. Further, we have found that the prolactin-depleting ability of cysteamine is not altered by a prior suckling stimulus. These results indicate that cysteamine administration inhibits physiologically-induced prolactin secretion with similar potency and efficacy as previously reported for cysteamine effects on basal and pharmacologically-induced prolactin secretion. Furthermore, the effect of cysteamine is not compromised by a previous suckling stimulus, suggesting that "depletion-transformation" of pituitary prolactin stores does not protect against the effect of cysteamine.