A Study of the Physical and Mechanical Properties of Aerogels Obtained from Bacterial Cellulose.

Aerogels with a density of 4.2-22.8 kg/m3 were obtained from bacterial cellulose synthesized under static and dynamic cultivation conditions on a molasses medium. The strength properties and porous structure of the aerogels strongly depended on their density. With an aerogel density of 22.8 kg/m3, the modulus of elasticity at 80% compression of the sample was 0.1 MPa. The decrease in the density of aerogels led to an increase in the pore sizes ranging from 20 to 1000 µm and a decrease in the modulus of elasticity. These characteristics were more pronounced in aerogels obtained from bacterial cellulose under static cultivation conditions. The aerogels had a low coefficient of thermal conductivity (0.0257 W m-1 °C-1), which is comparable to the thermal conductivity of air, and moderate thermal stability because the degradation processes of the aerogels began at 237 °C. The aerogels obtained from bacterial cellulose had high sound absorption coefficients in the frequency range of 200-5000 Hz, which makes it possible to use the aerogels as heat- and sound-insulating materials.

The phenomenon of atherosclerosis reversal and regression: Lessons from animal models.

Studies in non-rodent and murine models showed that atherosclerosis can be reversed. Atherosclerosis progression induced by high-fat or cholesterol-rich diet can be reduced and reversed to plaque regression after switching to a normal diet or through administration of lipid-lowering agents. The similar process should exist in humans after implementation of lipid-lowering therapy and as a result of targeting of small rupture-prone plaques that are major contributors for acute atherosclerotic complications. Lowering of low density lipoprotein (LDL) cholesterol and the activation of reverse cholesterol transport lead to a decline in foam cell content, to the depletion of plaque lipid reservoirs, a decrease in lesional macrophage numbers through the activation of macrophage emigration and, probably, apoptosis, dampening plaque inflammation, and the induction of anti-inflammatory macrophages involved in clearance of the necrotic core and plaque healing. By contrast, plaque regression is characterized by opposite events, leading to the retention of atherogenic LDL and oxidized LDL particles in the plaque, an increased flux of monocytes, the immobilization of macrophages in the intimal vascular tissues, and the propagation of intraplaque inflammation. Transfer of various apolipoprotein (apo) genes to spontaneously hypercholesterolemic mice deficient for either apoE or LDL receptor and, especially, the implementation of the transplantation murine model allowed studying molecular mechanisms of atherosclerotic regression, associated with the depletion of atherogenic lipids in the plaque, egress of macrophages and phenotypic switch of macrophages from the proinflammatory M1 to the anti-inflammatory M2.

Production and сharacterization of the exopolysaccharide from strain Paenibacillus polymyxa 2020.

Paenibacillus spp. exopolysaccharides (EPSs) have become a growing interest recently as a source of biomaterials. In this study, we characterized Paenibacillus polymyxa 2020 strain, which produces a large quantity of EPS (up to 68 g/L),and was isolated from wasp honeycombs. Here we report its complete genome sequence and full methylome analysis detected by Pacific Biosciences SMRT sequencing. Moreover, bioinformatic analysis identified a putative levan synthetic operon. SacC and sacB genes have been cloned and their products identified as glycoside hydrolase and levansucrase respectively. The Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectra demonstrated that the EPS is a linear ß-(2→6)-linked fructan (levan). The structure and properties of levan polymer produced from sucrose and molasses were analyzed by FT-IR, NMR, scanning electron microscopy (SEM), high performance size exclusion chromatography (HPSEC), thermogravimetric analysis (TGA), cytotoxicity tests and showed low toxicity and high biocompatibility. Thus, P. polymyxa 2020 could be an exceptional cost-effective source for the industrial production of levan-type EPSs and to obtain functional biomaterials based on it for a broad range of applications, including bioengineering.

What is the potential of p53 isoforms as a predictive biomarker in the treatment of cancer?

INTRODUCTION: For decades, p53 was researched as a single protein with alterations described as mutants. The discovery of 12 human p53 isoforms expressed from 9 transcripts changed this perception, eloquently explaining the numerous roles p53 plays, including apoptosis, senescence, and regeneration. Area covered: Here, we summarise the p53 isoforms and their relevance to cancer to establish an understanding and theorise on potential applications of the isoforms in clinical practice. Expert commentary: Pertaining to the different expression of isoforms in different tumors, it is concluded that the clinical use of isoforms as prognostic and predictive biomarkers will be different depending on the cell type, the tissue origin of the tumors, the position of the TP53 mutation and the driver-oncogene.

The Influence of Oxidative Stress and Natural Antioxidants on Morphometric Parameters of Red Blood Cells, the Hemoglobin Oxygen Binding Capacity, and the Activity of Antioxidant Enzymes.

Using a wide range of different physical and chemical methods, it was found that the oxidative stress caused by addition of hydrogen peroxide to the incubation medium has a significant effect on the conformation of haematoporphyrin, influencing the oxygen-binding properties of haemoglobin in red blood cells. Morphofunctional characteristics of red blood cells change; in particular, we have observed the transformation of erythrocytes, their transition into echinocytes. In erythrocytes, in response to increased lipid peroxidation (LPO) antioxidant enzymes become active. The use of natural antioxidants (ß-carotene and resveratrol) works towards reducting the level of oxidative processes. Resveratrol has the greatest antioxidant effect.

The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2.

The mononuclear phagocytes control the body homeostasis through the involvement in resolving tissue injury and further wound healing. Indeed, local tissue microenvironmental changes can significantly influence the functional behavior of monocytes and macrophages. Such microenvironmental changes for example occur in an atherosclerotic plaque during all progression stages. In response to exogenous stimuli, macrophages show a great phenotypic plasticity and heterogeneity. Exposure of monocytes to inflammatory or anti-inflammatory conditions also induces predominant differentiation to proinflammatory (M1) or anti-inflammatory (M2) macrophage subsets and phenotype switch between macrophage subsets. The phenotype transition is accompanied with great changes in the macrophage transcriptome and regulatory networks. Interferon-regulatory factors (IRFs) play a key role in hematopoietic development of monocytes, their differentiation to macrophages, and regulating macrophage maturation, phenotypic polarization, phenotypic switch, and function. Of 9 IRFs, at least 3 (IRF-1, IRF-5, and IRF-8) are involved in the commitment of proinflammatory M1 whereas IRF-3 and IRF-4 control M2 polarization. The role of IRF-2 is context-dependent. The IRF impact on macrophage phenotype plasticity and heterogeneity is complex and involves activating and repressive function in triggering transcription of target genes.

Physical and Chemical Processes and the Morphofunctional Characteristics of Human Erythrocytes in Hyperglycaemia.

Background: This study examines the effect of graduated hyperglycaemia on the state and oxygen-binding ability of hemoglobin, the correlation of phospholipid fractions and their metabolites in the membrane, the activity of proteolytic enzymes and the morphofunctional state of erythrocytes. Methods: Conformational changes in the molecule of hemoglobin were determined by Raman spectroscopy. The structure of the erythrocytes was analyzed using laser interference microscopy (LIM). To determine the activity of NADN-methemoglobinreductase, we used the P.G. Board method. The degree of glycosylation of the erythrocyte membranes was determined using a method previously described by Felkoren et al. Lipid extraction was performed using the Bligh and Dyer method. Detection of the phospholipids was performed using V. E. Vaskovsky method. Results: Conditions of hyperglycaemia are characterized by a low affinity of hemoglobin to oxygen, which is manifested as a parallel decrease in the content of hemoglobin oxyform and the growth of deoxyform, methemoglobin and membrane-bound hemoglobin. The degree of glycosylation of membrane proteins and hemoglobin is high. For example, in the case of hyperglycaemia, erythrocytic membranes reduce the content of all phospholipid fractions with a simultaneous increase in lysoforms, free fatty acids and the diacylglycerol (DAG). Step wise hyperglycaemia in incubation medium and human erythrocytes results in an increased content of peptide components and general trypsin-like activity in the cytosol, with a simultaneous decreased activity of µ-calpain and caspase 3. Conclusions: Metabolic disorders and damage of cell membranes during hyperglycaemia cause an increase in the population of echinocytes and spherocytes. The resulting disorders are accompanied with a high probability of intravascular haemolysis.

Study of Erythrocyte Indices, Erythrocyte Morphometric Indicators, and Oxygen-Binding Properties of Hemoglobin Hematoporphyrin Patients with Cardiovascular Diseases.

The current study investigates the functional state of erythrocytes and indices of the oxygen-binding capacity of hemoglobin in blood samples from healthy donors and from patients with coronary artery disease and myocardial infarction before and after treatment. It has been established that, in cardiovascular diseases, erythrocyte morphology and hemoglobin oxygen-transporting disorders are observed. Standard therapy does not result in the restoration of the structure and properties of erythrocytes. The authors believe that it is necessary for future therapeutic treatment to include preparations other than cardiovascular agents to enhance the capacity of hemoglobin to transport oxygen to the tissues.

Role of Membrane Lipids in the Regulation of Erythrocytic Oxygen-Transport Function in Cardiovascular Diseases.

The composition and condition of membrane lipids, the morphology of erythrocytes, and hemoglobin distribution were explored with the help of laser interference microscopy (LIM) and Raman spectroscopy. It is shown that patients with cardiovascular diseases (CVD) have significant changes in the composition of their phospholipids and the fatty acids of membrane lipids. Furthermore, the microviscosity of the membranes and morphology of the erythrocytes are altered causing disordered oxygen transport by hemoglobin. Basic therapy carried out with the use of antiaggregants, statins, antianginals, beta-blockers, and calcium antagonists does not help to recover the morphofunctional properties of erythrocytes. Based on the results the authors assume that, for the relief of the ischemic crisis and further therapeutic treatment, it is necessary to include, in addition to cardiovascular disease medicines, medication that increases the ability of erythrocytes' hemoglobin to transport oxygen to the tissues. We assume that the use of LIM and Raman spectroscopy is advisable for early diagnosis of changes in the structure and functional state of erythrocytes when cardiovascular diseases develop.

Development of Antiatherosclerotic Drugs on the basis of Natural Products Using Cell Model Approach.

Atherosclerosis including its subclinical form is one of the key medical and social problems. At present, there is no therapy available for widespread use against subclinical atherosclerosis. The use of synthetic drugs for the prevention of arteriosclerosis in its early stages is not sufficient because of the limited indications for severe side effects and high cost of treatment. Obviously, effective antiatherosclerotic drugs based on natural products would be a preferred alternative. Simple cell-based models for testing different natural products have been developed and the ability of natural products to prevent intracellular lipid accumulation in primary cell culture was evaluated. This approach utilizing cell models allowed to test effects of such direct antiatherosclerotic therapy, analyzing the effects mimicking those which can occur "at the level" of arterial wall via the inhibition of intracellular lipid deposition. The data from the carried out clinical trials support a point of view that the identification of antiatherosclerotic activity of natural products might offer a great opportunity for the prevention and treatment of atherosclerotic disease, reducing cardiovascular morbidity and mortality.

Vascular endothelium: functioning in norm, changes in atherosclerosis and current dietary approaches to improve endothelial function.

The endothelium represents not only a simple cellular monolayer that lines the vascular tree in humans and other vertebrates. Depending on the location, the endothelium shows significant morphological and functional heterogeneity through differentiated expression of pro- and anticoagulant factors, presence and frequency of intercellular contacts, variable contractility, cell shape, and volume. Altogether, these properties are crucial for adjustment of the endothelial function and further maintenance of the adequate homeostasis in response in local microenvironmental changes. Endothelial cells (ECs) play a critical role in coordinated regulation of blood flow. This is achieved due to the capacity of ECs to create the active anti-thrombotic surface that supports blood fluidity and transfer of blood cells and biomolecules. However, in certain vascular regions that can occur in inflamed sites or in sites with high hydrodynamic shear stress, ECs could lost their anti-thrombotic properties and switch their normal quiescent phenotype towards the prothrombotic, proadhesion, and proinflammatory state. In such an athero-prone site, the proper endothelial function is impaired that increases risk for formation of the atherosclerotic plaque. The endothelial dysfunction not only precedes atherosclerosis but greatly contributes to atherogenesis in all disease stages. Healthy lifestyle and regular intake of correct antioxidant-rich diet such as fresh fruits, vegetables, olive oil, red wine, and tea have beneficial effects on endothelial function and could therefore reduce the cardiovascular risk.

Mitochondrial aging and age-related dysfunction of mitochondria.

Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

Quantitative assessment of heteroplasmy of mitochondrial genome: perspectives in diagnostics and methodological pitfalls.

The role of alterations of mitochondrial DNA (mtDNA) in the development of human pathologies is not understood well. Most of mitochondrial mutations are characterized by the phenomenon of heteroplasmy which is defined as the presence of a mixture of more than one type of an organellar genome within a cell or tissue. The level of heteroplasmy varies in wide range, and the expression of disease is dependent on the percent of alleles bearing mutations, thus allowing consumption that an upper threshold level may exist beyond which the mitochondrial function collapses. Recent findings have demonstrated that some mtDNA heteroplasmic mutations are associated with widely spread chronic diseases, including atherosclerosis and cancer. Actually, each etiological mtDNA mutation has its own heteroplasmy threshold that needs to be measured. Therefore, quantitative evaluation of a mutant allele of mitochondrial genome is an obvious methodological challenge, since it may be a keystone for diagnostics of individual genetic predisposition to the disease. This review provides a comprehensive comparison of methods applicable to the measurement of heteroplasmy level of mitochondrial mutations associated with the development of pathology, in particular, in atherosclerosis and its clinical manifestations.