Репозиторий Университета

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Hydrophobic segments made of oligo(l,l- or d,l-lactides) or poly(l,l-lactide) are grafted onto chitosan backbone in order to use their amphiphilic behavior to prepare degradable microcarriers intended to be used for tissue engineering. Hydrophilic–lipophilic balance of these copolymers is adjusted playing on the respective length of their hydrophilic and hydrophobic moieties. Thanks to their self-emulsifying properties, these graft copolymers are processed into microspheres in the absence of hydrophilic emulsifier commonly added in the aqueous phase of the oil/water emulsion. The copolymers containing amorphous oligolactide segments of medium length are demonstrated to be the most effective ones for microparticle fabrication. The microparticles are characterized using SEM, EDX, and FTIR. The reactivity of amine group is demonstrated using fluorescein isothiocyanate staining. The resulting microspheres disclose a porous core and a shell enriched by the hydrophilic polysaccharide moieties. Stabilization of the oil/water interface during the microsphere fabrication, total yield, size distribution, and microparticle surface morphology are mainly affected by the macromolecular features of the copolymers.

© 2019 Wiley Periodicals, Inc. Background: Clinical measures and implant design innovation to improve primary osseointegration and reduce the bacterial contamination of the peri-implant area are intended to reduce the incidence of late inflammatory complications in dental implantation. Purpose: To study the effect of nanostructured coating and antiseptic sealant on the outcomes of dental implantation. Materials and methods: Ninety-six individuals were clinically supervised. In the first group (Screw Ti + sealant), a special antiseptic sealant matrix was used; the same sealant was used with nanocoated implants in the second group (Nanocoat + sealant), and the conventional treatment protocol was used in the control group (Screw Ti). Patients were evaluated longitudinally during treatment and rehabilitation phases with clinical examinations, radiography, periodontal pathogen detection, and patient experience surveys. Results: For patients who received a nanocoated implant and an antiseptic sealant (Nanocoat + sealant), relatively better hygienic indices were observed; there was less contamination with periodontal pathogens, bone density remained at the required level, and the overall results of treatment were better. Conclusions: Using a matrix for sealing the dental implant-abutment interface with a nanostructured surface provides reliable results regarding stable osseointegration and clinical and patient-reported outcomes of treatment success.

© 2019 Elsevier Ltd Oxysterols are derivatives of cholesterol and biologically active molecules that are involved in a number of functions, including cholesterol homeostasis, immune response, embryogenic development and pathophysiology of neurodegenerative diseases. Enzymes catalyzing their synthesis and metabolism are of particular interest as potential or evaluated drug targets. Here we report for the first time biochemical analysis of purified human oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. Binding analyses indicated a tight binding of the oxysterols and estrone. Ligand screening revealed that CYP39A1 binds with high affinity antifungal drugs and prostate cancer drug galeterone (TOK-001). Site-directed mutagenesis of conserved Asn residue in the active site revealed its crucial role for protein folding and heme incorporation. Developed protocol for expression and purification enables further investigation of this hepatic enzyme as off-target in development of specific drugs targeting cytochrome P450 enzymes.

© 2019 Background: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient's condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA. Methods: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years). Results: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy. Conclusion: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high.

© 2019, Pleiades Publishing, Ltd. Abstract: A promising method for preparation of new functional nanocomposite materials based on bacterial cellulose and Au nanoparticles was proposed for the first time. The Au nanoparticles were obtained by biocompatible and environmentally friendly metal vapor synthesis. The structure and composition of the surface of composite films were studied by XPS, SEM, and IR spectroscopy. Gold nanoparticles were found to efficiently chemisorb nanofibrils of bacterial cellulose, which gave nanoparticles of approximately 25 nm in size with a “metal core–hydrocarbon shell” structure.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly attributed to excessive product formation. Underrated so far is, however, that HO may exert effects additionally via modulation of the cellular heme levels. Heme, besides being an often-quoted generator of oxidative stress, plays also an important role as a signaling molecule. Heme controls the anti-oxidative defense, circadian rhythms, activity of ion channels, glucose utilization, erythropoiesis, and macrophage function. This broad spectrum of effects depends on its interaction with proteins ranging from transcription factors to enzymes. In degrading heme, HO has the potential to exert effects also via modulation of heme-mediated pathways. In this review, we will discuss the multitude of pathways regulated by heme to enlarge the view on HO and its role in cell physiology. We will further highlight the contribution of HO to pathophysiology, which results from a dysregulated balance between heme and the degradation products formed by HO.

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Nanoporous glassy polymers are perspective materials for the fabrication of gas separation membranes, especially for the application of gaseous hydrocarbon separation. However, the drawback of such materials is the pronounced physical aging resulting in the dramatic drop of gas transport properties due to relaxation of high-free-volume fraction in time. Herein, a novel and readily available group of such glassy polymers is reported based on 5-alkylnorbornenes. These polymers are easily synthesized from dicyclopentadiene and α-olefins by Diels-Alder reaction and vinyl (addition) polymerization of the formed cycloadducts in the presence of ([(η3-C3H5)PdCl]2/PCy3/Na+[B(3,5-(CF3)2C6H3)4]− catalyst. The obtained polymers display low-fraction free volume, stable gas permeability over time, and possess a unique feature for the glassy polymers—solubility controlled permeation of hydrocarbons and enhanced C4H10/CH4 selectivity.

© 2019, Ecozone, OAIMDD. All rights reserved. Spirituality is the fourth aspect of health, along with the physical, mental and social ones. At the same time, religiosity is a private manifestation of spirituality. The purpose of the study is to find out the relationship between health care on the one hand, and spirituality, religious life, a subjective feeling of happiness and good health indicators, on the other. A review of literary sources shows that positive values, beliefs, and the power of faith contribute to health and happiness. Religious participation and spiritual practices have a positive effect on the survival of the sick, low disease incidence, prolonged remissions of chronic diseases, lower anxiety and depression level, healthy lifestyle and compliance. At the same time, better results in treating patients are achieved when doctors and patients have common spiritual and/or religious attitudes.

© 2019 The Authors This article is essentially a dataset necessary for analysing the taxation. The data analysis has allowed to determine the optimal taxation model, when the criteria of economic efficiency and equity are incompatible. The dataset has allowed the use of the method of successive concessions in tax optimization. The practical significance of the dataset lies in the ability to simultaneously improve the efficiency and equity in taxation. The dataset was obtained by using the method of expert estimates. A group of experts was asked to rank the taxes established by the Tax Code of the Russian Federation, in descending order of importance. Only strict rankings were allowed. The consistency of expert opinion was evaluated using the Kendall coefficient of concordance. The data set was supplemented with the expert ranking data of the basic principles of taxation, such as the principle of equity; the principle of certainty and accuracy of taxes; the principle of ease of tax collection for taxpayers; the principle of efficiency; the principle of commitment. The dataset can be used in the future to determine a rational amount of taxation depending on the established criteria.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Adiponectin is encoded by the ADIPOQ gene and participates in the pathogenesis of cardiovascular and metabolic diseases. The goal of the study was to assess associations of rs17300539, rs266729, rs182052, rs2241766, and rs17366743 single nucleotide polymorphisms (SNPs) of the ADIPOQ gene with concentrations of serum adiponectin and with coronary atherosclerosis and type 2 diabetes mellitus in 447 patients (316 men and 131 women) subjected to coronary angiography. SNPs of the ADIPOQ gene of the study participants were genotyped using real-time PCR. Multivariate linear regression adjusted for covariates revealed significant association between rs182052 SNP and serum adiponectin concentration (β= –0.11; 95% confidence interval (95%CI): – 0.19, –0.03; p = 0.016). Regression analysis revealed an increase in prevalence of unstable angina (OR (odds ratio) = 2.55; 95%CI 1.4–4.82; p = 0.018) and coronary artery disease (OR = 1.55; 95%CI 1.15– 2.09; p = 0.021) per copy of the rs182052 A allele. Prevalence of type 2 diabetes mellitus was higher in subjects with the rs182052 A allele (OR = 2.29; 95%CI 1.29-4.21; p = 0.024). Regression analysis of rs266729 showed that prevalence of unstable angina was increased (OR = 3.59; 95%CI 1.17–10.01; p = 0.045) in the subjects with the GG genotype and prevalence of coronary artery disease (CAD) was significantly increased (OR = 1.48; 95%CI 1.09–2.03; p = 0.045) per copy of the G allele. Haplotype analysis revealed that the subjects with the GCATT haplotype have lower adiponectin levels (β= – 0.15; p = 0.042) and higher prevalence of unstable angina (OR = 3.597; p = 0.007) compared with reference haplotype carriers. Thus, the results indicate that minor A allele of rs182052 of the ADIPOQ gene is significantly associated with a decrease in serum adiponectin levels, and two SNPs (rs182052 and rs266729) of the ADIPOQ gene are significantly associated with cardiovascular and metabolic diseases.

© 2019 Elsevier B.V. Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellular‑calcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm2, 100 mW/cm2, 500 mW/cm2, 1000 mW/cm2, 1500 mW/cm2, 2000 mW/cm2) irradiated with a “standard” (Gaussian fluence distribution) hand-piece or with a “flat-top” (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.

© 2019 Photodynamic therapy (PDT) is a non-invasive FDA and EMA-approved anticancer treatment modality. Initially developed for elimination of malignant cells, PDT affects all cells in the tumor bed including stromal cells. Stroma represents not only an important component of tumor microenvironment, but has a significant impact on tumor susceptibility to PDT and other anticancer therapies. However, the effects of PDT on stromal cells are poorly investigated. During PDT the tumor stroma can receive low-dose irradiation as a result of chosen regimen or limited depth of light penetration. Here, we characterized response of human mesenchymal stromal cells (MSCs) to low-dose PDT. In an in vitro model we demonstrated that low-dose PDT resulted in activation of Erk1/2 and inhibition of GSK-3 signaling in MSCs. PDT-mediated induction of intracellular reactive oxygen species (ROS) resulted in reorganization of MSC cytoskeleton and decreased cell motility. More importantly, low-dose PDT dramatically upregulated secretion of various proangiogenic factors (VEGF-A, IL-8, PAI-1, MMP-9, etc.) by MSCs and improved MSC ability to promote angiogenesis suggesting an increase in the pro-tumorigenic potential of MSCs. In contrast, co-cultivation of PDT-treated MSCs with lymphocytes resulted in significant decrease of MSC viability and potential increase in MSC immunogenicity, which may lead to increased anti-tumor immunity. Low-dose PDT in MSCs significantly inhibited secretion of CCL2 (MCP-1) potentially limiting infiltration of pro-tumorigenic macrophages. Altogether, our findings demonstrate that low-dose PDT significantly modifies functional properties of MSCs improving their pro-tumorigenic potential while simultaneously increasing potential immune stimulation suggesting possible mechanisms of stromal cell contribution to PDT efficacy.

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Polydimethylsiloxane (PDMS) is a long-standing material of significant interest in microfluidics due to its unique features. As such, rapid prototyping of PDMS-based microchannels is of great interest. The most prevalent and conventional method for fabrication of PDMS-based microchips relies on softlithography, the main drawback of which is the preparation of a master mold, which is costly and time-consuming. To prevent the attachment of PDMS to the master mold, silanization is necessary, which can be detrimental for cellular studies. Additionally, using coating the mold with a cell-compatible surfactant adds extra preprocessing time. Recent advances in 3D printing have shown great promise in expediting microfabrication. Nevertheless, current 3D printing techniques are sub-optimal for PDMS softlithography. The feasibility of producing master molds suitable for rapid softlithography is demonstrated using a newly developed 3D-printing resin. Moreover, the utility of this technique is showcased for a number of widely used applications, such as concentration gradient generation, particle separation, cell culture (to show biocompatibility of the process), and fluid mixing. This can open new opportunities for biologists and scientists with minimum knowledge of microfabrication to build functional microfluidic devices for their basic and applied research.

© 2019 Elsevier Inc. Over the last years, the experimental compound olesoxime, a mitochondria-targeting cholesterol derivative, has emerged as a promising drug candidate for neurodegenerative diseases. Numerous preclinical studies have successfully proved olesoxime's neuroprotective properties in cell and animal models of clinical conditions such as amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, peripheral neuropathy and spinal muscular atrophy. The beneficial effects were attributed to olesoxime's potential impact on oxidative stress, mitochondrial permeability transition or cholesterol homoeostasis. Although no significant benefits have been demonstrated in patients of amyotrophic lateral sclerosis, and only the first 12 months of a phase II/III clinical trial showed an improvement in motor symptoms of spinal muscular atrophy, this orphan drug may still offer undiscovered potential in the treatment of neurological diseases. In our earlier preclinical studies, we demonstrated that administration of olesoxime in mouse and rat models of Huntington disease improved psychiatric and molecular phenotypes. Aside from stabilising mitochondrial function, the drug reduced the overactivation of calpains, a class of calcium-dependent proteases entangled in neurodegenerative conditions. This observation may be credited to olesoxime's action on calcium dyshomeostasis, a further hallmark in neurodegeneration, and linked to its targets TSPO and VDAC, two proteins of the outer mitochondrial membrane associated with mitochondrial calcium handling. Further research into the mode of action of olesoxime under pathological conditions, including its effect on neuronal calcium homeostasis, may strengthen the untapped potential of olesoxime or other similar compounds as a therapeutic for neurodegenerative diseases.

© 2019 Elsevier GmbH We report a case of severe babesiosis caused by the bovine pathogen Babesia divergens with the development of multisystem failure in a splenic host. Immunosuppression other than splenectomy can also predispose people to B. divergens. There was heavy multiple invasion of up to 14 parasites inside the erythrocyte, which had not been previously observed even in asplenic hosts. The piroplasm 18S rRNA sequence from our patient was identical B. divergens EU lineage with identity 99.5–100%.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM.

© 2019, Federación de Sociedades Españolas de Oncología (FESEO). Purpose: To evaluate the added value of diffusion-weighted imaging (DWI) to T2-weighted imaging (T2WI) for improved identification of pelvic lymph nodes (LN) by radiation oncologists. Methods/patients: This retrospective study included 20 patients with histopathologically proven node-negative prostate cancer. All patients underwent 3T-MRI of the prostate; matched axial T2WI and DWI sequences were assessed by an experienced uro-radiologist as the reference standard. Consultant and specialist registrar radiation oncologists were asked to identify all LN first on T2WI alone (read 1) and then on T2WI and DWI combined (read 2); LN were measured in size and divided into true positives (TP), false positives (FP) and false negatives (FN). Sensitivity, positive predictive value (PPV) and false negative rate (FNR) were then calculated and compared using Pearson’s Chi square test. Results: A total of 177 LN comprised the reference standard. 16 TP, 16 FP and 161 FN LN (sensitivity 9.0%, PPV 50.0%, FNR 91.0%) and 124, 15 and 53 LN (70.1%, 89.2%, 30%) were identified by reader 1 on reads 1 and 2, respectively; χ2 (2, N = 385) = 137.8, p < 0.0001. 27, 21 and 150 LN (15.3%, 56.3%, 84.8%) and 120, 13 and 57 LN (67.8%, 90.2%, 32.2%) were identified by reader 2 on the two reads; χ2 (2, N = 388) = 102.4, p < 0.0001. Conclusions: Adding DWI to T2WI significantly improved identification of pelvic LN by radiation oncologists and can therefore be regarded as a useful LN contouring technique for RT planning in pelvic malignancies.

© 2019 International Union of Crystallography. During a comprehensive study of a series of 2-(N-arylimino)coumarin-3-carboxamides with the aryl group substituted in the ortho-position by either a halogen atom, a methyl group or a methoxy group, the existence of three groups of isotypic crystal structures has been revealed. The similarity of crystal structures belonging to the same groups was confirmed by the analysis based on the comparison of pairwise interactions energies obtained from quantum chemical calculations. Group I includes unsubstituted, methyl-substituted and polymorphic modification 1 of fluoro-substituted 2-(N-arylimino)coumarin-3-carboxamide. Structures of polymorphic modification 2 of fluoro-substituted derivative, chloro-substituted and polymorphic modification 1 of bromo-substituted 2-(N-arylimino)coumarin-3-carboxamide may represent group II. Group III contains structures of polymorphic modification 2 of bromo-substituted derivative, iodine-and methoxy-substituted 2-(N-arylimino)coumarin-3-carboxamides. Structures of the same type group have extremely close parameters of the unit cell as well as those of molecular and crystal structures. But they are not identical. Polymorphic modifications of fluoro-and bromo-substituted 2-(N-arylimino)coumarin-3-carboxamides belong to different crystal types mainly due to different arrangement of basic structural motifs separated out using quantum chemical calculations.

© Copyright © 2019 Klochkov, Pukhov, Afanasieva, Neganova, Ananiev, Avila-Rodriguez, Tarasov and Aliev. Natural sesquiterpene lactones which contain an exocyclic methylene group in the β-position of the lactone ring react readily with N-nucleophiles. When studying the reaction of the natural epoxyalantolactone with the primary amines we demonstrate the formation of a new heterocyclic system—the hydrogenated benzo[g]furo[4,3,2-cd]indol-3(1H)-one. Spectral data on the characteristics of the synthesized compounds are presented. The data on the reaction mechanisms and its applicability for the preparation are discussed.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. WWP2 is an E3 ubiquitin ligase that differentially regulates the contextual tumour suppressor/progressor TGFβ signalling pathway by alternate isoform expression. WWP2 isoforms select signal transducer Smad2/3 or inhibitor Smad7 substrates for degradation through different compositions of protein-protein interactionWWdomains. The WW4 domain-containing WWP2-C induces Smad7 turnover in vivo and positively regulates the metastatic epithelial-mesenchymal transition programme. This activity and the overexpression of these isoforms in human cancers make them candidates for therapeutic intervention. Here, we use NMR spectroscopy to solve the solution structure of the WWP2 WW4 domain and observe the binding characteristics of Smad7 substrate peptide. We also reveal that WW4 has an enhanced affinity for a Smad7 peptide phosphorylated at serine 206 adjacent to the PPxY motif. Using the same approach, we show that the WW3 domain also binds Smad7 and has significantly enhanced Smad7 binding affinity when expressed in tandem with the WW4 domain. Furthermore, and relevant to these biophysical findings, we present evidence for a novel WWP2 isoform (WWP2C-DHECT) comprising WW3-WW4 tandem domains and a truncated HECT domain that can inhibit TGFβ signalling pathway activity, providing a further layer of complexity and feedback to the WWP2 regulatory apparatus. Collectively, our data reveal a structural platform for Smad substrate selection by WWP2 isoform WW domains that may be significant in the context of WWP2 isoform switching linked to tumorigenesis.