The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins

Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors

The Role of Microparticles of β-TCP and Wollastonite in the Creation of Biocoatings on Mg0.8Ca Alloy

The introduction of particles into the composition of coatings can significantly expand the range of properties and possibilities of the modified materials. In this work, the coatings containing microparticles of β-tricalcium phosphate (β-TCP) and wollastonite separately and in combination with each other were created on the surface of an Mg0.8Ca alloy. The morphology and microstructure of the coatings were examined by scanning and transmission electron microscopy. Their phase composition was determined with the help of X-ray diffraction analysis. The coating-to-substrate adhesion evaluation was carried out via the scratch-test method. Potentiodynamic polarization curves of the coatings were obtained during their immersion in 0.9% NaCl solution and their electrochemical properties were determined. Cytotoxic properties of the coatings were investigated by means of the MTT assay and flow cytometry in the course of the biological studies. In addition, NIH/3T3 cell morphology was analyzed using scanning electron microscopy. The structure, morphology, physical and mechanical, corrosive, and biological properties of the coatings depended on the type of particles they contained. Whereas the coating with β-TCP microparticles had higher adhesive properties, the coatings with wollastonite microparticles, as well as the combined coating, were less soluble and more biocompatible. In addition, the wollastonite-containing coating had the highest corrosion resistance

Effect of the Porosity, Roughness, Wettability, and Charge of Micro-Arc Coatings on the Efficiency of Doxorubicin Delivery and Suppression of Cancer Cells

Porous calcium phosphate coatings were formed by the micro-arc oxidation method on the surface of titanium for the loading and controlled release of the anticancer drug doxorubicin. The coatings’ morphology and microstructure were examined by scanning electron microscopy. The phase composition was determined with the help of X-ray diffraction analysis. Studies of the hydrophilic properties of the coatings and their zeta potential were carried out. Data on the kinetics of doxorubicin adsorption-desorption were obtained. In addition, the effect of calcium phosphate coatings impregnated with doxorubicin on the viability of the Neuro-2a cell line was revealed. The coating formed at low voltages of 200–250 V contained a greater number of branched communicating pores, and therefore they were able to adsorb a greater amount of doxorubicin. The surface charge also contributes to the process of the adsorption-desorption of doxorubicin, but this effect is not fully understood and further studies are required to identify it

Characterization of the Micro-Arc Coatings Containing β-Tricalcium Phosphate Particles on Mg-0.8Ca Alloy

The characterization of the microstructure, morphology, topography, composition, and physical and chemical properties of the coatings containing β-tricalcium phosphate (β-TCP) particles deposited by the micro-arc oxidation (MAO) method on biodegradable Mg-0.8Ca alloy has been performed. The electrolyte for the MAO process included the following components: Na2HPO4·12H2O, NaOH, NaF, and β-Ca3(PO4)2 (β-TCP). The coating morphology, microstructure, and compositions have been studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). With increasing of the MAO voltage from 350 to 500 V, the coating thickness and surface average roughness of the coatings increased linearly from 6 to 150 µm and from 2 to 8 µm, respectively. The coating deposited at 350 V had more homogeneous porous morphology with numerous pores similar by sizes (2–3 µm) than the coatings formed at 450–500 V. The β-TCP isometric particles were included in the coating surface. The XRD recognized the amorphous-crystalline structure in the coatings with incorporation of the following phases: β-TCP, α-TCP, MgO (periclase) and hydroxyapatite (HA). The corrosion experiments showed that the biodegradation rate of the Mg-0.8Ca alloy coated by calcium phosphates is almost 10 times less than that of uncoated alloy