Репозиторий Университета

Background: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. Methods: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. Results: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. Conclusions: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.

Recently, mesenchymal stem/stromal cells (MSCs) and their widespread biomedical applications have attracted great consideration from the scientific community around the world. However, reports have shown that the main populations of the transplanted MSCs are trapped in the liver, spleen, and lung upon administration, highlighting the importance of the development of cell-free therapies. Concerning rising evidence suggesting that the beneficial effects of MSC therapy are closely linked to MSC-released components, predominantly MSC-derived exosomes, the development of an MSC-based cell-free approach is of paramount importance. The exosomes are nano-sized (30–100 nm) lipid bilayer membrane vesicles, which are typically released by MSCs and are found in different body fluids. They include various bioactive molecules, such as messenger RNA (mRNA), microRNAs, proteins, and bioactive lipids, thus showing pronounced therapeutic competence for tissues recovery through the maintenance of their endogenous stem cells, the enhancement of regenerative phenotypic traits, inhibition of apoptosis concomitant with immune modulation, and stimulation of the angiogenesis. Conversely, the specific roles of MSC exosomes in the treatment of various tumors remain challenging. The development and clinical application of novel MSC-based cell-free strategies can be supported by better understanding their mechanisms, classifying the subpopulation of exosomes, enhancing the conditions of cell culture and isolation, and increasing the production of exosomes along with engineering exosomes to deliver drugs and therapeutic molecules to the target sites. In the current review, we deliver a brief overview of MSC-derived exosome biogenesis, composition, and isolation methods and discuss recent investigation regarding the therapeutic potential of MSC exosomes in regenerative medicine accompanied by their double-edged sword role in cancer.

Background: Malaria is a disease annually causing over 400,000 deaths. Deep understanding of molecular and genetic processes underlying its life cycle and pathogenicity is required to efficiently resist it. RNA interference is a mechanism of the gene expression regulation typical for a wide variety of species. Even though the existence of this phenomenon in Plasmodium falciparum has long been rejected, several recent works pose hypotheses and provide direct and indirect evidence of the existence of mechanisms similar to RNA interference in this organism. In particular, the possibility of regulation of P. falciparum gene expression through human microRNAs is of great importance both for fundamental biology and for medicine. In the present work we address the problem of possibility of the existence in the P. falciparum genome of the nucleotide sequences such that mRNAs transcribed from genes containing these sequences could form duplexes with human microRNAs. Using bioinformatics methods we have analysed genomes of 15 P. falciparum isolates for sequences homological to these microRNAs. Results: The analysis has demonstrated the existence of a vast number of genes that could potentially be regulated by the human microRNAs in the plasmodial genome. Conclusions: Despite the fact that the numbers of homological intervals vary significantly between isolates, the hsa-miR-451a and hsa-miR-223-3p microRNAs are expected to make the most notable contribution to the pathogenesis of P. falciparum malaria. The majority of homological intervals occur in genes encoding cell adhesion proteins.

Background: The aim of this paper was to systematically review the root canal configuration (RCC) and morphology literature of the mandibular second premolar (Mn2P). Methods: Systematic research of five electronic databases was performed to identify published literature concerning the root canal configuration (RCC) of the Mn2P up through July 2020. Studies were selected according to predefined search terms and keywords inclusion criteria: “root canal configuration”, “root canal system”, “root canal morphology”, “mandibular second premolar”, “mandibular premolars”, “morphology” and “anatomy”. Further possible studies were identified by cross-referencing and screening the bibliographies of the selected articles. Results: From 1622 retrieved studies, 44 studies investigating the internal morphology of 17,839 Mn2Ps were included. Most examined Mn2Ps were single-rooted (89.5–100%); two-rooted (0.1–8%) and three-rooted (0.1–3.5%) Mn2Ps at lower frequency. Most frequent RCCs reported were 1–1–1/1 (55.3–99.6%) followed by 1–1–2/2 (0.5–57%) and 2–2–2/2 (0.6–18%). The meta-analysis of seven studies demonstrated that a significantly higher number of RCC type 1–2–1/1 (OR [95%CI] = 2.05 [1.27, 3.33]) and 2–2–2/2 (OR [95%CI] = 2.32 [0.65, 8.63]) were observed in male than in female patients. Conclusions: Different RCC research methods have been reported. Whereas clearing and radiographs were commonly used in the past, CBCT has been prevalent in recent years. A globally high frequency of a 1–1–1/1 RCC in the Mn2P has been reported. Nevertheless, the probability that different, more complicated RCCs can appear in Mn2Ps should not be underestimated and, thus, should be taken into consideration when making decisions during an endodontic treatment.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

Background: Risky sexual behaviour (RSB) is regarded as a major health problem during adolescence. Russia has one of the highest rates of teenage pregnancy, abortion and newly diagnosed HIV infections in the world, but research on RSB in Russian youth has been limited. To address this deficit, this study examined the role of several factors, including internalizing and externalizing symptoms, in RSB among Russian adolescents. Methods: Self-reported data were collected from 2573 Russian adolescents aged 13–17 years old (59.4 % girls; Mean age = 14.89) regarding RSB (unprotected sex, early pregnancy, multiple sexual partners and substance use during sexual encounters). Information was also obtained on externalizing (conduct problems and delinquent behaviour) and internalizing (depression, anxiety and posttraumatic stress) symptoms, as well as interpersonal risk and protective factors (affiliation with delinquent peers, parental involvement and teacher support). Hierarchical multiple binary logistic regression analysis was used to examine the associations between these variables and RSB. Results: Boys reported engaging in more RSB than girls. Externalizing symptoms and affiliation with delinquent peers were most strongly associated with RSB, whereas symptoms of anxiety were negatively associated with RSB. There was an interaction effect for sex and affiliation with delinquent peers on RSB with boys reporting RSB when having more delinquent peers. Neither parental involvement nor teacher support were protective against RSB. Conclusions: Early detection of and interventions for RSB and associated externalizing symptoms may be important for adolescent physical and mental wellbeing. Affiliation with delinquent peers should, especially among boys, be regarded as a risk marker for RSB.

Background: Risky sexual behaviour (RSB) is regarded as a major health problem during adolescence. Russia has one of the highest rates of teenage pregnancy, abortion and newly diagnosed HIV infections in the world, but research on RSB in Russian youth has been limited. To address this deficit, this study examined the role of several factors, including internalizing and externalizing symptoms, in RSB among Russian adolescents. Methods: Self-reported data were collected from 2573 Russian adolescents aged 13–17 years old (59.4 % girls; Mean age = 14.89) regarding RSB (unprotected sex, early pregnancy, multiple sexual partners and substance use during sexual encounters). Information was also obtained on externalizing (conduct problems and delinquent behaviour) and internalizing (depression, anxiety and posttraumatic stress) symptoms, as well as interpersonal risk and protective factors (affiliation with delinquent peers, parental involvement and teacher support). Hierarchical multiple binary logistic regression analysis was used to examine the associations between these variables and RSB. Results: Boys reported engaging in more RSB than girls. Externalizing symptoms and affiliation with delinquent peers were most strongly associated with RSB, whereas symptoms of anxiety were negatively associated with RSB. There was an interaction effect for sex and affiliation with delinquent peers on RSB with boys reporting RSB when having more delinquent peers. Neither parental involvement nor teacher support were protective against RSB. Conclusions: Early detection of and interventions for RSB and associated externalizing symptoms may be important for adolescent physical and mental wellbeing. Affiliation with delinquent peers should, especially among boys, be regarded as a risk marker for RSB.

© 2020 Elsevier B.V. Magnetic hyperthermia (MH) is a perspective tool to treat the tumor while the magnetic material is delivered. The key problems in MH development is to ensure an effective local heating within cancer cell without overheating other cells. In order to do that one has to reach substantial local accumulation of magnetic nanoparticles (MNPs) and/or magnetically sensitive objects with advanced heat properties. Absorbing heat energy for destroying tumor cells can be generated only if there is sufficient amount of locally placed MNPs. In this work, we propose polyelectrolyte microcapsules modified with iron oxide nanoparticles as an approach to tie magnetic materials in high concentration locally. These microcapsules (about 3 microns in diameter) can be readily internalized by various cells. The human fibroblasts uptake of the microcapsules and cytotoxic effect upon the influence of alternating magnetic field (AMF) while magnetic capsules are inside the cells is under study in this work. The cytotoxicity of the magnetic microcapsules was compared with the cytotoxicity of the MNPs while free in the solution to evaluate the effect of bounding MNPs. A cytotoxic effect on cells was found in the case of preliminary incubation of fibroblasts with capsules while the AMF is applied. In the case of MNPs in an equivalent dose per mass of magnetic material, there was no cytotoxic effect noticed after the treatment with the field. It is noteworthy that during the treatment of cells with the AMF, the increase in temperature of the incubation medium was not registered. The morphological changes on fibroblasts were consistent with the data of the viability assessment. Thus, the synthesized capsules are shown as a means for local enhancement of magnetic hyperthermia in the treatment of tumor diseases.

© 2020 Microcapsules are ideal cargo platform for variety of applications such as drug delivery, sensing and imaging due to the combination of a simplicity fabrication and flexibility in the design. We developed remotely collapsing polymer capsules to response to external microwave treatment. The multilayer structure of the capsules was designed to create a polyfunctional system intercalating with nanodiamonds (NDs) and upconversion nanoparticles (UCNPs) into the polyelectrolyte shell. NDs empower local overheating to the microcapsules, while UCNPs provide opportunity to luminescent thermal sensing. UCNPs consist of inorganic crystalline host matrix - hexagonal β-phase NaYF4, doped with pairs of trivalent lanthanide ions, which play role of sensitizer (Yb3+) and activator (Er3+). The microwave triggering followed by the capsule heating results in the controlled destruction of the polyelectrolyte shell with subsequent cargo release. UCNPs luminescence was utilized to determine the local temperature of the capsule shell at nanoscale under GHz ultrasonic treatment. Our novel approach provides on demand microcapsule system destruction, which can be used in the development of nanotheranostic platform for the unification of diagnosis and treatment of various diseases.

© 2021, Advanced Scientific Research. All rights reserved. The state of human health is an important factor in the optimal for the existence in biological and social terms. It is now recognized that the best way to keep health – to lead healthy lives and avoid the negative influences of the environment. This is extremely important in the workplace and at home. The basis of life must be feasible rational muscular activity. Dosed physical loads provide balanced revitalizing effect on the body. They regulate the metabolism and have a pronounced training effect on motor and autonomic functions. Adequate and regular physical activity steadfastly increases the efficiency of the myocardium, improves blood flow to the brain and heart, improves the efficiency of peripheral circulation and venous return to the heart increases the body's tolerance to stress and the level of absorption of oxygen and nutrients to the tissues. In this regard, rational physical activity are considered the basis of healthy lifestyles, active aging, and high adaptation to the external environment.

© 2021, Advanced Scientific Research. All rights reserved. The state of human health is an important factor in the optimal for the existence in biological and social terms. It is now recognized that the best way to keep health – to lead healthy lives and avoid the negative influences of the environment. This is extremely important in the workplace and at home. The basis of life must be feasible rational muscular activity. Dosed physical loads provide balanced revitalizing effect on the body. They regulate the metabolism and have a pronounced training effect on motor and autonomic functions. Adequate and regular physical activity steadfastly increases the efficiency of the myocardium, improves blood flow to the brain and heart, improves the efficiency of peripheral circulation and venous return to the heart increases the body's tolerance to stress and the level of absorption of oxygen and nutrients to the tissues. In this regard, rational physical activity are considered the basis of healthy lifestyles, active aging, and high adaptation to the external environment.

© 2020 Elsevier B.V. Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and decline in the quality of life. It develops due to loss of dopaminergic neurons in the substantia nigra pars compacta, and among its pathogenic factors oxidative stress plays a critical role in disease progression. Pesticides are a broad class of chemicals widely used in agriculture and households for the protection of crops from insects and fungi. Several of them have been incriminated as risk factors for PD, but the underlying mechanisms have yet to be fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in regulating mRNA translation and protein synthesis. miRNA levels have been shown to be affected in several diseases as well. Since the studies on the association between pesticides and PD have yet to reach definitive conclusions, here we review recent evidence on deregulated microRNAs upon pesticide exposure, and attempt to find an overlap between miRNAs deregulated in PD and pesticides, as a missing link between the two, and enhance future research in this direction.

© 2020 Elsevier Ltd Background: Understanding the pattern of non-linguistic abilities in aphasia has been a controversial question. We hypothesized that only some aphasia patients, particularly patients with fluent forms of aphasia and global aphasia, would present deficits in non-linguistic abilities. Methods & procedures: We studied 200 vascular aphasia patients (119 men and 81 women; mean age = 57.37 years, SD = 15.56) at the Cognitive Communicative Speech Language Pathology Unit at the Clinical Hospital University of Chile (Santiago, Chile). The mean time post onset was 6.57 months (SD = 12.94). The Spanish versions of Western Aphasia Battery Revised (SWAB-R) and the Spanish version of the Boston Diagnostic Aphasia Examination (SBDAE) were administered. We used the SWAB-R Part 1 to determine the aphasia severity (Aphasia Quotient: AQ). SWAB-R Part 2 was used to study nonverbal abilities; a Non-Linguistic Quotient (NLQ) was calculated. The SBDAE was used in determining the type of aphasia. Outcomes & results: Deficits were particularly evident in Global, Mixed non-fluent, and Transcortical Motor aphasia, followed by Wernicke and Transcortical Sensory aphasia. Deficits were mildest in Amnesic, Conduction, and Broca aphasia. Correlation between linguistic and non-linguistic deficits were found to be statistically significant. Conclusion: Our results support previous studies: non-linguistic abilities can be affected in aphasia, but there is an important variability. Some aphasia patients can present non-linguistic deficits. Verbal and nonverbal deficits are significantly correlated, suggesting some communality in their brain organization.

© 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) Apart from being a conduit for photoassimilate transport in plants, the phloem serves as a pathway for transport of proteins and RNAs from sites of their synthesis to distant plant parts. As demonstrated for mRNAs and small RNAs such as miRNA and siRNA, their phloem transport is largely involved in responses to environmental cues including stresses and pathogen attacks. RNA molecules are believed to be transported in the phloem in the form of complexes with RNA-binding proteins; however, proteins forming such complexes are generally poorly studied. Here, we demonstrate that the Cucurbita maxima phloem serpin-1 (CmPS1), which has been previously described as a functional protease inhibitor capable of long-distance transport via the phloem, is able to bind RNA in vitro. Among different RNAs tested, CmPS1 exhibits a preference for imperfect RNA duplexes and the highest affinity to tRNA. A characteristic complex formed by CmPS1 with tRNA is not observed upon CmPS1 binding to tRNA-like structures of plant viruses. Mutational analysis demonstrates that the CmPS1 N-terminal region is not involved in RNA binding. Since antithrombin-III, the human protease inhibitor of serpin family most closely sequence-related to CmPS1, is found to be unable to bind RNA, one can suggest that, in its evolution, CmPS1 has gained the RNA binding capability as an additional function likely relevant to its specific activities in the plant phloem.

© 2019 The Author(s) The phloem sieve elements (SEs), enucleate cells, contain RNAs, which are imported from surrounding tissues and cells, mostly companion cells tightly associated with SEs, and transported via the phloem over the whole plant body. The RNA phloem transport is essential for plant individual development and responses to environmental cues. Recently, we identified primary miRNA (pri-miRNA) sequences in de novo assembled transcriptome of Cucurbita maxima phloem sap and reported 11 most abundant pri-miRNAs [1]. Here, we provide the output of this analysis in complete detail. For the full set of pri-miRNAs identified in the C. maxima phloem sap transcriptome, data on relative abundance are provided along with annotated sequence data.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. This chapter reports a library preparation protocol for efficient high-throughput sequencing of double-stranded RNA viruses. The protocol consists of four main steps, viz., enzyme treatment, precipitation using lithium chloride, full-length amplification of cDNAs, and tailing adapters for high-throughput sequencing. This protocol will be useful for all double-stranded RNA viruses and for all of the high-throughput sequencing platforms.

© 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 B.V. A detailed step-by-step procedure for revealing counterfeit and substandard tablets is presented. Non-invasive NIR measurements are used for data collection. The entire complex multi-layer object as the “packaging -coating-core” system requires special treatment at all stages of model development and validation. The influence of each layer is studied. A procedure that covers data collection, construction of the model, as well as special internal and external validation is advocated here. A special set of objects called ‘nearest of kin’ (NoK) collection, which consists of generic medications nearest to the target objects, assists in reliable assessment of the model specificity. The whole procedure summarizes the results obtained for over a thousand different dosage forms of tablets. Two real-world examples of genuine and counterfeit medicines are considered. The first example presents uncoated tablets with high concentration of active ingredient and fairly simple set excipients. Its NoK collection consists of six different manufacturers. The second example presents coated tablets with low concentration of active ingredient and rather complex set of excipients. Its NoK collection is presented by seven different manufacturers.

Statistical phylogenetic methods are a powerful tool for inferring the evolutionary history of viruses through time and space. The selection of mathematical models and analysis parameters has a major impact on the outcome, and has been relatively well-described in the literature. The preparation of a sequence dataset is less formalized, but its impact can be even more profound. This article used simulated datasets of enterovirus sequences to evaluate the effect of sample bias on picornavirus phylogenetic studies. Possible approaches to the reduction of large datasets and their potential for introducing additional artefacts were demonstrated. The most consistent results were obtained using "smart sampling", which reduced sequence subsets from large studies more than those from smaller ones in order to preserve the rare sequences in a dataset. The effect of sequences with technical or annotation errors in the Bayesian framework was also analyzed. Sequences with about 0.5% sequencing errors or incorrect isolation dates altered by just 5 years could be detected by various approaches, but the efficiency of identification depended upon sequence position in a phylogenetic tree. Even a single erroneous sequence could profoundly destabilize the whole analysis by increasing the variance of the inferred evolutionary parameters.