Stromal and Tumor Glioma-Derived Cells with Similar Characteristics have Differences in α-Smooth Muscle Actin Expression and Localization

Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal components. The study of the interactions between the perivascular niche and its surrounding cells is of great value in unraveling mechanisms of drug resistance in malignant gliomas. In this study, we isolated the stromal diploid cell population from oligodendroglioma and a mixed population of tumor aneuploid and stromal diploid cells from astrocytoma specimens. The stromal cells expressed neural stem/progenitor and mesenchymal markers showing the same discordant phenotype that is typical for glioma cells. Moreover, some of the stromal cells expressed CD133. For the first time, we demonstrated that this type of stromal cells had the typical myofibroblastic phenotype as the α-SMA+ cells formed α-SMA fibers and exhibited the specific function to deposit extracellular matrix (ECM) proteins at least in vitro. Immunofluorescent analysis showed diffuse or focal α-SMA staining in the cytoplasm of the astrocytoma-derived, A172, T98G, and U251MG glioma cells. We could suggest that α-SMA may be one of the main molecules, bearing protective functions. Possible mechanisms and consequences of α-SMA disruptions in gliomas are discussed

Cell-Based Drug Delivery and Use of Nano-and Microcarriers for Cell Functionalization

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Cell functionalization with recently developed various nano- and microcarriers for therapeutics has significantly expanded the application of cell therapy and targeted drug delivery for the effective treatment of a number of diseases. The aim of this progress report is to review the most recent advances in cell-based drug vehicles designed as biological transporter platforms for the targeted delivery of different drugs. For the design of cell-based drug vehicles, different pathways of cell functionalization, such as covalent and noncovalent surface modifications, internalization of carriers are considered in greater detail together with approaches for cell visualization in vivo. In addition, several animal models for the study of cell-assisted drug delivery are discussed. Finally, possible future developments and applications of cell-assisted drug vehicles toward targeted transport of drugs to a designated location with no or minimal immune response and toxicity are addressed in light of new pathways in the field of nanomedicine

Cell-Based Drug Delivery and Use of Nano-and Microcarriers for Cell Functionalization

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Cell functionalization with recently developed various nano- and microcarriers for therapeutics has significantly expanded the application of cell therapy and targeted drug delivery for the effective treatment of a number of diseases. The aim of this progress report is to review the most recent advances in cell-based drug vehicles designed as biological transporter platforms for the targeted delivery of different drugs. For the design of cell-based drug vehicles, different pathways of cell functionalization, such as covalent and noncovalent surface modifications, internalization of carriers are considered in greater detail together with approaches for cell visualization in vivo. In addition, several animal models for the study of cell-assisted drug delivery are discussed. Finally, possible future developments and applications of cell-assisted drug vehicles toward targeted transport of drugs to a designated location with no or minimal immune response and toxicity are addressed in light of new pathways in the field of nanomedicine

Modulation of slow inactivation in class A Ca2+ channels by β-subunits

β-subunit modulation of slow inactivation of class A calcium (Ca2+) channels was studied with two-microlectrode voltage clamp after expression of the α1A- (BI-2) together with β1a-, β2a-, β3- or β4-subunits in Xenopus oocytes.On- and off-rates of slow inactivation were estimated from the kinetics of recovery from slow inactivation. Ca2+ channels with an α1A/β-subunit composition inducing the slower rate of fast inactivation displayed the faster rate of slow inactivation. The corresponding order of slow inactivation time constants (τonset) was: α1A/β2a, 33 ± 3 s; α1A/β4, 42 ± 4 s; α1A/β1a, 59 ± 4 s; α1A/β3, 67 ± 5 s (n ≥ 7).Recovery of class A Ca2+ channels from slow inactivation was voltage dependent and accelerated at hyperpolarized voltages. At a given holding potential recovery kinetics were not significantly modulated by different β-subunits.Two mutations in segment IIIS6 (IF1612/1613AA) slowed fast inactivation and accelerated the onset of slow inactivation in the resulting mutant (α1A/IF-AA/β3) in a similar manner as coexpression of the β2a-subunit. Recovery from slow inactivation was slightly slowed in the double mutant.Our data suggest that class A Ca2+ channels enter the ‘slow inactivated’ state more willingly from the open than from the ‘fast inactivated’ state. The rate of slow inactivation is, therefore, indirectly modulated by different β-subunits.Fast and slow inactivation in class A Ca2+ channels appears to represent structurally independent conformational changes. Fast inactivation is not a prerequisite for slow inactivation

Portable optical dust measuring instrument VOG-2

Наведено конструкцію, принцип дії, основні технічні характеристики переносного оптичного пиловимірювача ВОГ-2. Представлено функціональну схему приладу. Детально описана робота пиловимірювача. Описані особливості експлуатації приладу. Технічні рішення приладу захищені патентом України.The design is presented, action principles are described, the basic characteristics of portable optical dust measuring instrument VOG-2 are given. The functional diagram of device is presented. Work of dust measuring instrument is written up. The features of exploitation of device are described. The technical decisions of device are protected by the patent of Ukraine.Приведена конструкция, принцип действия, основные технические характеристики переносного оптического пылемера ВОГ-2. Представлена функциональная схема прибора. Подробно описана работа пылемера. Описаны особенности эксплуатации прибора. Технические решения прибора защищены патентом Украины

Molecular determinants of inactivation in voltage-gated Ca2+ channels

Evolution has created a large family of different classes of voltage-gated Ca2+ channels and a variety of additional splice variants with different inactivation properties. Inactivation controls the amount of Ca2+ entry during an action potential and is, therefore, believed to play an important role in tissue-specific Ca2+ signalling. Furthermore, mutations in a neuronal Ca2+ channel (Cav2.1) that are associated with the aetiology of neurological disorders such as familial hemiplegic migraine and ataxia cause significant changes in the process of channel inactivation. Ca2+ channels of a given subtype may inactivate by three different conformational changes: a fast and a slow voltage-dependent inactivation process and in some channel types by an additional Ca2+-dependent inactivation mechanism. Inactivation kinetics of Ca2+ channels are determined by the intrinsic properties of their pore-forming α1-subunits and by interactions with other channel subunits. This review focuses on structural determinants of Ca2+ channel inactivation in different parts of Ca2+ channel α1-subunits, including pore-forming transmembrane segments and loops, intracellular domain linkers and the carboxyl terminus. Inactivation is also affected by the interaction of the α1-subunits with auxiliary β-subunits and intracellular regulator proteins. The evidence shows that pore-forming S6 segments and conformational changes in extra- (pore loop) and intracellular linkers connected to pore-forming segments may play a principal role in the modulation of Ca2+ channel inactivation. Structural concepts of Ca2+ channel inactivation are discussed

Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles

Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs