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The most important task of cell transplantology is to activate the proliferative potential of mesenchymal stem cells (MSCs) before receiving bone marrow cells from a donor. This is necessary to increase a sufficient number of MSCs in early passages, when the probability of chromosomal mutations is still low. The proliferative activity of cells can be activated using photobiomodulation (PBM) by exposure to lowintensity laser radiation in the visible and near-infrared ranges. Recently, it was shown in vitro that the combination of PBM and moderate laserinduced heating can lead to a significant increase in the efficiency of MSC colony formation. The main objectives of the study are to find the optimal parameters for such a combined effect and answer the question about the possibility of a synergistic effect of thermal heating and laser radiation. MSCs isolated from rat bone marrow were used for the experiments. MSCs were exposed to short-term laser radiation of moderate power with a wavelength of 980 nm and an energy density of 68-340 J/cm2, accompanied by moderate heating of the cell suspension. Vials with grown colonies were photographed, then their number, size and number of cells in individual colonies were determined using special digital image processing methods. It was found that under optimal parameters, exposure to laser radiation of moderate power leads to an increase in the number of colonies by 4.1±0.5 times, and the total number of cells by 3.3±0.4 times compared to the control. It has been shown that this increase in cell number occurs as a result of the synergistic effect of photobiomodulation and moderate heating. Activation of colony formation after laser stimulation of MSCs occurs due to the migration of cells from the initially formed colonies with the subsequent formation of additional colonies by separated cells.

The paper presents the results of bench tests of diaphragm membrane-piston pumps made of composite materials based on two- component polyurethane. The tests were carried out with the help of a rupture machine, equipped with special equipment, which allows to imitate the complex stress-strain state in the diaphragm, which is characteristic of the operation of pumps in real conditions. According to the results of the tests, the diaphragm with the content of basalt is 1 and 2 ob. % showed the same ultimate strength.

The article is devoted to the development of methods that provide an effective transition to digitalization of industry. The proposed approach is aimed at developing a basic abstraction to describe the activities performed by employees at the enterprise. The proposed description is formed for the purpose of further analysis and selection of digitalization tools in accordance with the identified functional needs. The structure of the basic abstraction of describing the organization of an action in the form of a mechanism is proposed, the composition of the components of the mechanism in the form of elements, functions, tools, goals and results of the action is described. A graphical form of displaying the spatial representation of the mechanism of action has been developed. Approaches to the objectification of the organization of an action reflecting the process of preparing an action, including the representation of the components of an action in the form of nested mechanisms, are considered. The direction of further research in this area is to develop a methodology for describing activities as an interconnected set of actions of individual users, as well as a procedure for assessing compliance between the activities of an enterprise and existing or developing systems for digitalizing its work. Another area of research may be the formation of functional requirements for the design of an information system for a specific enterprise, taking into account all the details and logic of the performance of production activities. The development of the proposed approach can become the basis for increasing the efficiency of the realization of digital technologies into the industry activities of enterprises and reducing the costs of implementing this process.

Background and aimsWe previously reported that Oxy210, an oxysterol-based drug candidate, exhibits antifibrotic and anti-inflammatory properties. We also showed that, in mice, it ameliorates hepatic hallmarks of non-alcoholic steatohepatitis (NASH), including inflammation and fibrosis, and reduces adipose tissue inflammation. Here, we aim to investigate the effects of Oxy210 on atherosclerosis, an inflammatory disease of the large arteries that is linked to NASH in epidemiologic studies, shares many of the same risk factors, and is the major cause of mortality in people with NASH.MethodsOxy210 was studied in vivo in APOE*3-Leiden.CETP mice, a humanized mouse model for both NASH and atherosclerosis, in which symptoms are induced by consumption of a high fat, high cholesterol "Western" diet (WD). Oxy210 was also studied in vitro using two cell types that are important in atherogenesis: human aortic endothelial cells (HAECs) and macrophages treated with atherogenic and inflammatory agents.ResultsOxy210 reduced atherosclerotic lesion formation by more than 50% in hyperlipidemic mice fed the WD for 16 weeks. This was accompanied by reduced plasma cholesterol levels and reduced macrophages in lesions. In HAECs and macrophages, Oxy210 reduced the expression of key inflammatory markers associated with atherosclerosis, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule-1 (VCAM-1), and E-Selectin. In addition, cholesterol efflux was significantly enhanced in macrophages treated with Oxy210.ConclusionsThese findings suggest that Oxy210 could be a drug candidate for targeting both NASH and atherosclerosis, as well as chronic inflammation associated with the manifestations of metabolic syndrome.

Within the scope of consumer-oriented production, individuality and cost-effectiveness are two essential aspects, which can barely be met by traditional manufacturing technologies. Conventional metal forming techniques are suitable for large batch sizes. If variants or individualized components have to be formed, the unit costs rise due to the inevitable tooling costs. For such applications, additive manufacturing (AM) processes, which do not require tooling, are more suitable. Due to the low production rates and limited build space of AM machines, the manufacturing costs are highly dependent on part size and batch size. Hence, a combination of both manufacturing technologies i.e. conventional metal forming and additive manufacturing seems expedient for a number of applications. The current study develops a process chain combining forming and additive manufacturing. First, a semi-finished product is formed with forming tools of reduced complexity and then finished by additive manufacturing. This research investigates the addition of features using AlSi12 created by Wire Arc Additive Manufacturing (WAAM) on formed EN-AW 6082 preforms. By forming, the strength of the material was increased, while this effect was partly reduced by the heat input of the WAAM process.

The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren’t available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

Chronic HIV infection may exacerbate atherosclerotic vascular disease, which at advanced stages presents as necrotic plaques rich in crystalline cholesterol. Such lesions can catastrophically rupture precipitating myocardial infarct and stroke, now important causes of mortality in those living with HIV. However, in this population little is known about plaque structure relative to crystalline content and its chemical composition. Here, we first interrogated plaque crystal structure and composition in atherosclerotic SIV-infected macaques using non-linear optical microscopy. By stimulated Raman scattering and second harmonic generation approaches both amorphous and crystalline plaque lipid was detected and the crystal spectral profile indicated a cholesterol ester (CE) dominated composition. Versus controls, SIV+ samples had a greater number of cholesterol crystals (CCs), with the difference, in part, accounted for by crystals of a smaller length. Given the ester finding, we profiled HIV+ plaques and also observed a CE crystalline spectral signature. We further profiled plaques from Ldlr-/- mice fed a high fat diet, and likewise, found CE-dominate crystals. Finally, macrophage exposure to CCs or AcLDL induced auto-fluorescent puncta that co-stained with the LC3B autophagy sensor. In aggregate, we show that atheromatous plaques from mice, macaques and humans, display necrotic cores dominated by esterified CCs, and that plaque macrophages may induce autophagic vesicle formation upon encountering CCs. These findings help inform our knowledge of plaque core lipid evolution and how the process may incite systemic inflammation.

ObjectiveAIBP (apolipoprotein A-I binding protein) is an effective and selective regulator of lipid rafts modulating many metabolic pathways originating from the rafts, including inflammation. The mechanism of action was suggested to involve stimulation by AIBP of cholesterol efflux, depleting rafts of cholesterol, which is essential for lipid raft integrity. Here we describe a different mechanism contributing to the regulation of lipid rafts by AIBP. Approach and Results: We demonstrate that modulation of rafts by AIBP may not exclusively depend on the rate of cholesterol efflux or presence of the key regulator of the efflux, ABCA1 (ATP-binding cassette transporter A-I). AIBP interacted with phosphatidylinositol 3-phosphate, which was associated with increased abundance and activation of Cdc42 and rearrangement of the actin cytoskeleton. Cytoskeleton rearrangement was accompanied with reduction of the abundance of lipid rafts, without significant changes in the lipid composition of the rafts. The interaction of AIBP with phosphatidylinositol 3-phosphate was blocked by AIBP substrate, NADPH (nicotinamide adenine dinucleotide phosphate), and both NADPH and silencing of Cdc42 interfered with the ability of AIBP to regulate lipid rafts and cholesterol efflux.ConclusionsOur findings indicate that an underlying mechanism of regulation of lipid rafts by AIBP involves PIP-dependent rearrangement of the cytoskeleton.

Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli, affecting a diverse range of physiologic and pathologic processes. This Thematic Review Series focuses on Biology of Lipid Rafts rather than on their composition or structure. The aim is to provide an overview of ideas on how lipid rafts are involved in regulation of different pathways and how they interact with other layers of metabolic regulation. Articles in the series will review the involvement of lipid rafts in regulation of hematopoiesis, production of extracellular vesicles, host interaction with infection, and the development and progression of cancer, neuroinflammation, and neurodegeneration, as well as the current outlook on therapeutic targeting of lipid rafts.

Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.jlr;61/5/687/F1F1f1.