Репозиторий Университета

© 2019 Elsevier Ltd Immunosuppressive chemoresistance is a major barrier in lung cancer treatment. Tumor immunosuppressive environments mediated by myeloid-derived suppressor cells (MDSCs) play a key role in chemotherapy induced MDSC development and differentiation but their mechanistic role has not been elucidated. Here, we define a role for carboplatin based chemotherapy in potentiating an MDSC-dependent pathway that triggers the chemoresistance mechanism. Findings reveal MDSC differentiation and activation of IL-13/IL-33-mediated pathway through VCAM/RANTES following carboplatin treatment. Furthemore, secretion of T regulatory IL-10-producing CD4+Foxp3+ cells was increased followed by expression of co-inhibitory receptor TIGIT on T cells, leading to a dysfunctional T cell phenotype. These cells were characterized by an immunosuppressive phenotype with impaired activation, proliferation and cytokine production. Lung cancer tissues expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. This TIGIT expression on tumor-infiltrating T cells was found to be associated with tumor progression and was linked to functional exhaustion of T cells. In addition, the presence of plasmacytoid dendritic cells (pDCs) exposed to tumor-derived factors further enhanced tumor progression through IL-10 production and up-regulation of the inducible co-stimulatory ligand (ICOS-L). Deciphering these deranged immune mechanisms and how they are impacted by chemotherapy induction is essential for incorporation of novel immune-based strategies in order to restore immunity and inhibit the immunosuppressive phenotype of metastatic lung cancer.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2018, © 2018 Informa UK Limited, trading as Taylor  &  Francis Group. Background: Mesenchymal dysplasias or inherited connective tissue diseases are the group of diseases with deficiency of various components of connective tissue. Connective tissue disorders can affect different organs: skeleton, sight organ, skin, lungs, heart. But the most dangerous is vascular wall insufficiency leading to high risk of hemorrhage, especially during pregnancy and delivery due to hemodynamic and hormonal effects on the walls of the modified vessels. Aim: To evaluate the risk of complications during the pregnancy and delivery in patients with mesenchymal dysplasias. Study design: Fifty-six pregnancies in patients with mesenchymal dysplasias, including subclinical forms of diseases: 23 with Marfan syndrome (I group), 22 with Ehlers–Danlos syndrome (II group), and 11 with Osler–Weber–Rendu syndrome (hereditary hemorrhagic telangiectasia) (III group) of the age from 18 to 36. The study included retrospective analysis (for the period from 1993 to 2005) and prospective study. Results of study showed high risk of life-threatening complications during pregnancy and delivery, especially the risk of hemorrhage and cardiovascular complications. In all the patients, we observed the progression of bleeding or development of bleeding in new localizations (epistaxis in 27 patients, easy brushing in 22, skin and mucosa telangiectasia in 20, gastrointestinal bleedings in 4, hemoptysis in 4, hematomas for minor traumas in 14, conjunctivas hemorrhages in 5). Conclusion: The pathogenesis of bleeding in such patients has mixed pattern: besides vascular wall pathology coagulation deficiency plays some role. The preferred delivery method for such patients is caesarean section. Deep vaginal ruptures and serious hemorrhage accompany vaginal delivery.

© 2019 Elsevier Ltd Immunosuppressive chemoresistance is a major barrier in lung cancer treatment. Tumor immunosuppressive environments mediated by myeloid-derived suppressor cells (MDSCs) play a key role in chemotherapy induced MDSC development and differentiation but their mechanistic role has not been elucidated. Here, we define a role for carboplatin based chemotherapy in potentiating an MDSC-dependent pathway that triggers the chemoresistance mechanism. Findings reveal MDSC differentiation and activation of IL-13/IL-33-mediated pathway through VCAM/RANTES following carboplatin treatment. Furthemore, secretion of T regulatory IL-10-producing CD4+Foxp3+ cells was increased followed by expression of co-inhibitory receptor TIGIT on T cells, leading to a dysfunctional T cell phenotype. These cells were characterized by an immunosuppressive phenotype with impaired activation, proliferation and cytokine production. Lung cancer tissues expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. This TIGIT expression on tumor-infiltrating T cells was found to be associated with tumor progression and was linked to functional exhaustion of T cells. In addition, the presence of plasmacytoid dendritic cells (pDCs) exposed to tumor-derived factors further enhanced tumor progression through IL-10 production and up-regulation of the inducible co-stimulatory ligand (ICOS-L). Deciphering these deranged immune mechanisms and how they are impacted by chemotherapy induction is essential for incorporation of novel immune-based strategies in order to restore immunity and inhibit the immunosuppressive phenotype of metastatic lung cancer.

© 2019 Elsevier B.V. Fabry disease (FD [MIM:301500]) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficient activity of its product, lysosomal enzyme α-galactosidase A (α-Gal A), leads to excessive accumulation of glycosphingolipids in cells of multiple organs. The establishing of the diagnosis is challenge in female patients because of milder clinical manifestation and normal α-Gal A activity. The globotriaosylsphingosine (lysoGb3) is described as a more sensitive diagnostic biomarker for females with pathogenic mutation in the GLA gene. Thus, the aim of this study is to improve the biochemical diagnostic efficiency for FD in females. Here we report the α-Gal A/lysoGb3 ratio as the novel biochemical criteria for diagnosis of female patients with FD, using dried blood spots (DBS) as test samples. It showed 100% sensitivity in distinguishing our group of 35 female patients from control (n = 140). Whereas measurement of α-Gal A and lysoGb3 alone showed 8.6% and 74.4% respectively. A new approach of using the ratio of α-Gal A activity to lysoGb3 concentration in DBS may provide a more accurate screening tool for identification of FD females.

© 2019 Wiley Periodicals, Inc. Control over biomaterials surface characteristics through surface modification or deposition of coatings is one of the key aspects of tissue engineering. This work was aimed to evaluate an effectiveness of various methods of chitosan-coating formations onto polylactide films using a number of techniques, such as vacuum deposition by electron-beam sputtering, chemical entrapment method, and electrospray procedure. Differently coated films were studied in terms of surface morphology (scanning electron and atomic-force microscopy), chemical structure (FTIR and X-ray photoelectron spectroscopy), and hydrophilic/hydrophobic balance (goniometry). The effect of coating technique on homogeneity of chitosan distribution over the substrate surface was evaluated using genipin and fluorescein isothiocyanate labeling as well as FTIR-microscopy. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48287.

© 2020 by the authors; licensee Growing Science, Canada. The article reviews methods of transportation for various types of imported medicinal plant materials of ginseng roots from China to the Russian Federation, with due consideration for risks. Logistic supply chains for ginseng roots have been developed and proposed based on the systemic method of research and the information analytical method. The optimal method for transportation of pharmaceutical substances of plant origin is chosen on the basis of the priority criteria for the cargo owner, as well as with due consideration for the peculiarities of the type of medicinal plant materials of ginseng roots.

© Springer Nature Switzerland AG 2020. The author considers an important problem of using the Huff model for obtaining quantitative estimates of trade turnover of the shopping center. The aim of the article is to identify the actual limitations of the specified model, which when conducting a practical assessment of potential trade turnover of large objects of commercial real estate in a significant way affect the quantitative results of the calculation and the quality of the conclusions. In accordance with the goal, the author solved the following tasks: –economic and mathematical structure of the Huff model is considered; –the calibration parameters of the model are revealed, the accuracy of which determines the accuracy of calculations and the correctness of conclusions; –an algorithm for estimating the potential trade turnover of the trading center based on a combination of the Huff model and econometric methods is constructed. The hypothesis of the research: For correct application of the Huff model in practice it is necessary to use econometric methods of estimation of calibration parameters. The article shows that the evaluation of calibration parameters of the model significantly affects the accuracy of the evaluation. As a result, the necessity of using empirical data and constructing econometric model based on them is proved by obtaining accurate quantitative estimates. The author presents the algorithm of correct estimation of potential trade turnover of the shopping center using econometric estimation of parameters of the Huff model, empirical and expert data and a calculation example. Conclusions on the use in practice of the Huff model with its methodological and actual limitations are formulated.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. We describe here the Oncobox method for scoring efficiencies of anticancer target drugs (ATDs) using high throughput gene expression data. The method rationale, design, and validation are given along with the examples of its practical applications in biomedicine. The method is based on the analysis of intracellular molecular pathways activation and measuring expressions of molecular target genes for every ATD under consideration. Using Oncobox method requires collection of normal (control) expression profiles and annotated databases of molecular pathways and drug target genes. Both microarray and RNA sequencing profiles are acceptable, although the latter type of data prevails in the most recent applications of this technique.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. Intracellular molecular pathways (IMPs) control all major events in the living cell. IMPs are considered hotspots in biomedical sciences and thousands of IMPs have been discovered for humans and model organisms. Knowledge of IMPs activation is essential for understanding biological functions and differences between the biological objects at the molecular level. Here we describe the Oncobox system for accurate quantitative scoring activities of up to several thousand molecular pathways based on high throughput molecular data. Although initially designed for gene expression and mainly RNA sequencing data, Oncobox is now also applicable for quantitative proteomics, microRNA and transcription factor binding sites mapping data. The Oncobox system includes modules of gene expression data harmonization, aggregation and comparison and a recursive algorithm for automatic annotation of molecular pathways. The universal rationale of Oncobox enables scoring of signaling, metabolic, cytoskeleton, immunity, DNA repair, and other pathways in a multitude of biological objects. The Oncobox system can be helpful to all those working in the fields of genetics, biochemistry, interactomics, and big data analytics in molecular biomedicine.

© 2019 Elsevier Ltd Attenuation and velocity (Speed-of-Sound) in a trabecular bone were calculated and evaluated from ultrasound pulse-echoes detection and their processing, applying a single US transducer that operates in transmit/receive mode. The processing of US pulse-echoes utilized development of algorithms for the attenuation and the Speed-of-Sound in trabecular bone. These ultra-sound pulse-echoes were obtained from the front and rear surfaces of a trabecular bone sample. The motivation for this work was to develop an efficient intraosseous monitoring device that provides the Speed-of-Sound and attenuation intraoperatively and in real-time and therefore can be implemented during a surgery. Ultrasonic measurements were performed in the frequency range of 3.5–6.5 [MHz]. In these experiments, the fresh trabecular bone samples were from sheep femora and humerus. The measuring results were correlated (R2 ≥ 0.95) with those obtained previously, mainly during transmission mode studies. According to the obtained results, the presented method presumably will be utilized as a clinical tool in bone surgical procedures and therefore will be able to provide better outcomes, while monitoring intraoperatively and in real-rime intraosseous trabecular bone attenuation and its velocity: In the next stage of this study, the method will be carried out on human tissues and also intraoperatively, during human clinical trials. It is planned to perform it on long bones/tibia, vertebra, in neurosurgery – for drilling the skull and also in dental implantation surgery.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. DNA mutations govern cancer development. Cancer mutation profiles vary dramatically among the individuals. In some cases, they may serve as the predictors of disease progression and response to therapies. However, the biomarker potential of cancer mutations can be dramatically (several orders of magnitude) enhanced by applying molecular pathway-based approach. We developed Oncobox system for calculation of pathway instability (PI) values for the molecular pathways that are aggregated mutation frequencies of the pathway members normalized on gene lengths and on number of genes in the pathway. PI scores can be effective biomarkers in different types of comparisons, for example, as the cancer type biomarkers and as the predictors of tumor response to target therapies. The latter option is implemented using mutation drug score (MDS) values, which algorithmically rank the drugs capacity of interfering with the mutated molecular pathways. Here, describe the mathematical basis and algorithms for PI and MDS values calculation, validation and implementation. The example analysis is provided encompassing 5956 human tumor mutation profiles of 15 cancer types from The Cancer Genome Atlas (TCGA) project, that totally make 2,316,670 mutations in 19,872 genes and 1748 molecular pathways, thus enabling ranking of 128 clinically approved target drugs. Our results evidence that the Oncobox PI and MDS approaches are highly useful for basic and applied aspects of molecular oncology and pharmacology research.

© 2020 Global-Science Press In this paper we introduce a new mathematical model for the active contraction of cardiac muscle, featuring different thermo-electric and nonlinear conductivity properties. The passive hyperelastic response of the tissue is described by an orthotropic exponential model, whereas the ionic activity dictates active contraction incorporated through the concept of orthotropic active strain. We use a fully incompressible formulation, and the generated strain modifies directly the conductivity mechanisms in the medium through the pull-back transformation. We also investigate the influence of thermo-electric effects in the onset of multiphysics emergent spatiotemporal dynamics, using nonlinear diffusion. It turns out that these ingredients have a key role in reproducing pathological chaotic dynamics such as ventricular fibrillation during inflammatory events, for instance. The specific structure of the governing equations suggests to cast the problem in mixed-primal form and we write it in terms of Kirchhoff stress, displacements, solid pressure, dimensionless electric potential, activation generation, and ionic variables. We also advance a new mixed-primal finite element method for its numerical approximation, and we use it to explore the properties of the model and to assess the importance of coupling terms, by means of a few computational experiments in 3D.

© 2019 Elsevier Ltd Background: Single studies suggest that nursing students perceive caring as more an instrumental than expressive behaviour and indicate some differences between caring perceptions in junior and senior nursing students. However, there are limited studies investigating caring perceptions in nursing students across multiple cultures. Objective: To determine perceptions of caring in Slovene, Croatian, Chinese and Russian nursing students and explore whether there are statistically significant differences in perceptions of caring between countries and between first and third-year nursing students. Design: A cross-sectional descriptive study design was used. Settings and participants: The study included 604 nursing students enrolled in first and third year in seven different nursing faculties in four countries: Slovenia; China; Croatia; and the Russian Federation. Methods: The 25-item Caring Dimension Inventory (CDI-25) was used to measure caring perceptions. We also included demographic questions regarding age, gender, country, year of study and type of study. Demographic data were analysed using descriptive analysis while a two-way analysis of variance (ANOVA) adjusted for unequal sample sizes was performed together with a post hoc analysis of the results. Results: The results of two-way ANOVA showed that both main effects (country and year of study) were statistically significant, as well as their interaction at the 0.05 significance level. The main effect for country was F(3, 596) = 3.591, p < 0.0136 indicating a significant difference in CDI-25 between Slovenia (M = 108.9, SD = 9.2), Russian Federation (M = 107.1, SD = 8.2), China (M = 102.8, SD = 9.7) and Croatia (M = 110.0, SD = 8.6). Conclusions: Perceptions of caring in nursing students differ across countries, probably due to different educational systems, curricula, cultural differences and societal values. Implementing caring theories in nursing curricula could help students to cultivate caring during their education.

© 2019 Elsevier B.V. Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30–70 kDa with a presumably safer low molecular mass PVA 9–10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.

© 2019 The Authors Sylvian fissure arachnoid cysts are known intracranial lesion in pediatric population. We describe a case of symptomatic cyst of Sylvian fissure that was managed with a standard endoscopic cystocisternostomy and re-endoscopy. We also describe the techniques of fenestration of medial wall cyst and partial removal of arachnoid membrane over third cranial nerve in anterior part (region near Dolenc medial triangle) and posterior part (region near Fukushima superior (paramedial) triangle) prevent closure of fenestration and recurrence of hypertension. A 6 years old girl presented with progressively increasing headache, left side hemiparesis, drag resistant of symptomatic epilepsy. MRI and CT scan showed right Sylvian fissure arachnoid cyst. The first endoscopic fenestration of cyst was done on standard basis. After operation patient improve clinically and radiologically. Two years later the patient came back with recurrent symptoms. The operation was performed by prof. Sufianov A. Endoscopic reoperation showed closure of fenestration in arachnoid membrane. Endoscopic re-fenestration with partial excision of arachnoid on over third cranial nerve in anterior and posterior part was excised. The patient again recovered radiologically and clinically till last follow up. In Sylvian fissure arachnoid cysts, endoscopic treatment with wide fenestration of medial wall of cyst preferably with partial removal of arachnoid may be very useful and preventing recurrent symptoms.

© 2019, The Author(s). Background: Sudden cardiac death (SCD) refers to unanticipated death as a consequence of cardiac failure which takes place over a brief time period (typically within an hour of the commencement of symptoms) in an individual, who may or may not be known to be subject to cardiac disease, but in whom no fatal condition has been diagnosed. The objective of this investigation was to identify the potential cause of SCD in the young population in Moscow. Result: Analysis revealed that the mean age of the deceased amongst men was 24.6 years, and amongst women was 29.1 years. Seventy-six percent of sudden deaths were found to result from some previously undiagnosed pathology of the cardiovascular system, and cardiomyopathy is the most common cause of death in young people. Coronary heart disease is the most common cause of death in people above 40 years old. Conclusion: Investigation to diagnose the causes of SCD constitutes a relevant, comprehensive, and multidisciplinary undertaking, which ought to be founded upon the application of novel and current diagnostic methodologies. An integrated strategy to the quest for the underlying reason for sudden death ought to be founded upon the outcomes of biochemical, anatomical, genetic, pathophysiological, and other investigations. The search and development of objective risk factors will permit timely therapeutic intervention for patients with cardiovascular pathology to minimise and prevent the risk of sudden cardiac death.

© 2019 Elsevier Ltd The effect of different initiators (tert-butyl chloride (t-BuCl) and 2-chloro-2-phenylpropane (CumCl) on the cationic polymerization of isobutylene co-initiated by acidic chloroferrate imidazole-based ionic liquid emimCl-FeCl3 (emimCl: 1-ethyl-3-methylimidazolium chloride, molar fraction of FeCl3 (χ(FeCl3)) ≥ 0.6) in the presence of diisopropyl ether at 0 °C and [IB] = 5.2 M has been investigated. Generally, the use of all above-mentioned initiators results in increase of the monomer conversion from 30% to 60% as well as in decrease of molecular weight from 2500 g mol−1 to 1100 g mol−1 and polydispersity from 2.6 to 1.7, respectively, but does not influence the content of exo-olefin end group. It was demonstrated that CumCl does not initiated directly the polymerization at 0 °C or −20 °C, rather, it decomposed with the formation of the proton, a true initiator of the polymerization. It was also found that addition of small amounts (1% by volume) of benzene or its derivatives into the polymerization system leads to further increase of the monomer conversion (>90%). The rate of isobutylene polymerization depends on basicity of aromatic compounds added and increases in the following order: benzene < toluene ≈ mesitylene.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: An anterior glottic web consists of the formation of a bridge of scar tissue covered by epithelium between the anterior free edges of the true vocal cords and represents one of the most common complications of laryngeal endoscopic surgery for tumors involving the anterior commissure. Endoscopic surgery is the therapy of choice, but simple section of the web is burdened by a high recurrence rate. Topical application of mitomycin C, intracordal stents, and the use of mucosal microflaps have been proposed to improve outcomes. We report our experience with the use of single and double mucosal microflaps (sliding technique) during the management of iatrogenic anterior glottic web (IAGW). Methods: From November 2010 to December 2018, 30 patients (29 males, 1 female, mean age 65 years, range 47–87 years) were observed for IAGW, and 11 of these patients (36.7%) required surgical treatment. The Voice Handicap Index (VHI) and the GRBAS were used for the perceptive evaluation of pre- and post-operative voice quality. Results: A reduction of the web length was observed in all cases, and we did not observe any residual web at the mid-third of the glottis. The mean post-operative VHI score decreased from 45 to 24, and the mean post-operative GRBAS values were reduced from 2.8, 2.4, 2.3, 2.1, and 1.1 to 1.9, 1.4, 1.3, 1.1, and 0, respectively. Conclusions: The microflap technique represents an effective and reproducible one-step procedure that, in expert hands, allows to obtain good anatomical and functional results in a high percentage of cases.

© 2019 Elsevier B.V. This study aimed at evaluating the remineralization effect promoted by different bioactive fillers on simulated early caries lesions in enamel (ECLE). Forty sound bovine incisors were used to prepare buccal enamel specimens (6 × 6 × 2 mm). The specimens were divided into two areas (3 × 3 mm²): control (CTR) and experimental (EXP). All the enamel specimens were then submitted to a specific protocol for a period of 48 h to induce simulated caries lesions. Subsequently, the specimens were treated for 7 days (2 min, twice a day) with a slurry pastes containing different bioactive particles (P/L ratio: 1 g/mL). All the specimens were analyzed by laser speckle before and after treatments. The results showed after the first analysis that the ECLE had very low average intensity (back-scattered light). Conversely, after application of the bioactive pastes, higher average intensity was always detected; this was comparable to CTR sound specimens. In conclusion, innovative pastes/gels developed for enamel remineralization should contain bioactive particles that when applied daily on early caries lesions may “boost” the remineralization process to reestablish a sound enamel.