Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC ‘stemness’ affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations. This activity requires the plant homeodomain region of ING5 that interacts specifically with the H3K4me3 mark. ING5 also enhances PI3K/AKT and MEK/ERK activity to sustain self-renewal of BTICs over serial passage of stem cell-like spheres. ING5 exerts these effects by activating transcription of calcium channel and follicle stimulating hormone pathway genes. In silico analyses of The Cancer Genome Atlas data suggest that ING5 is a positive regulator of BTIC stemness, whose expression negatively correlates with patient prognosis, especially in the Proneural and Classical subtypes, and in tumors with low SOX2 expression. These data suggest that altering histone acetylation status and signaling pathways induced by ING5 may provide useful clinical strategies to target tumor resistance and recurrence in glioblastoma.

No abstract

Nearly 40% of novel chemical entities show evidence of low solubility in water and low bioavailability. Self-emulsifying formulations have showed the power to improve the bioavailability of hydrophobic drugs. Self-emulsifying formulations belong to lipid formulations, and their size range from 100 nm in case of self-emulsifying drug delivery systems and less than 50 nm in case of self-microemulsifying drug delivery systems. In general self-emulsifying formulations s represent isotropic mixtures of oils, surfactants and co-surfactants, which emulsify spontaneous in aqueous media under conditions of gentle stirring. Usually self-emulsifying formulations presented liquids, which fill the soft gelatinous capsules. However, the dosage form has drawbacks, especially in the production process. In this regard, the use of the methodology of solidification of liquid or semi-solid components of self-emulsifying formulations and their transformation into powders for the preparation of solid dosage forms is relevant. This paper summarizes the main features, a classification of lipid forms, auxiliary substances for the preparation of self-emulsifying formulations, techniques of solidification, the phases of the development of self-emulsifying formulations, evaluation of parameters of quality of liquid and solid self-emulsifying formulations, approaches to development of medicinal forms on the basis of the self-emulsifying formulations, as well as an overview of the drugs, presented on the market in the form of self-emulsifying formulations.

Optical methods for analysis of non-uniform liquid mediums have been considered, correlational and functional connections between the optical density and parameters characterizing industrial wastewaters’ type, content and pollution level have been investigated. Have been demonstrated main tendencies related to development of technology and equipment for optoelectronic control of industrial wastewaters’ pollution. Approximation of emission and absorption spectra for optical radiation’s emitter and receiver using the known Laplace function allows carry out calculations for a choice of optical couples’ coordinated parameters for two-frequency optical control, and as a result to increase reliability of identification for a type and degree of pollution for wastewaters and industrial effluents in comparison with use of one emission source. The method of pollution two-frequency laser sounding differs in improved control characteristics compared with the ones offered in patents, as well as in scientific and technical literature.

No Abstract