Репозиторий Университета

© 2021, The Author(s). Background: HIV infection is a major health problem in Russia. We aimed to assess HIV prevalence in different population groups and to compare the characteristics of 4th generation immunoassays from Abbott, Bio-Rad, Vector-Best, Diagnostic Systems, and Medical Biological Unit. Methods: The study included 4452 individuals from the general population (GP), 391 subjects at high risk of HIV infection (HR) and 699 with potentially interfering conditions. HIV positivity was confirmed by immunoblot and by HIV RNA, seroconversion and virus diversity panels were also used. HIV avidity was employed to assess recent infections. Results: The prevalence in GP was 0.40%, higher in males (0.62%) and in people aged < 40 years (0.58%). Patients attending dermo-venereal centers and drug users had a high prevalence (34.1 and 58.8%). Recent infections were diagnosed in 20% of GP and in 4.2% of HR. Assay sensitivity was 100% except for one false negative (99,54%, MBU). Specificity was 99.58–99.89% overall, but as low as 93.26% on HR (Vector-Best). Small differences on early seroconversion were recorded. Only the Abbott assay detected all samples on the viral diversity panel. Conclusion: HIV infection rate in the high-risk groups suggests that awareness and screening campaigns should be enhanced. Fourth generation assays are adequate but performance differences must be considered.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Persistent organic pollutants (POPs) are heterogeneous carbon-based compounds that can seriously affect human health. The aim of this study was to measure serum concentrations of POPs in women residing in the Euro-Arctic Region of Russia. A total of 204 women from seven rural settlements of the Nenets Autonomous Okrug (NAO) took part in the study. We measured serum concentrations of 11 polychlorinated biphenyls (PCBs) and 17 organochlorine pesticides (OCPs) across the study sites and among Nenets and non-Nenets residents. Measurement of POPs was performed using an Agilent 7890A gas chromatograph equipped with an Agilent 7000 series MS/MS triple quadrupole system. The concentrations of all POPs were low and similar to findings from other Arctic countries. However, significant geographic differences between the settlements were observed with exceptionally high concentrations of PCBs in Varnek located on Vaygach Island. Both ΣDDT (p = 0.011) and ΣPCB (p = 0.038) concentrations were significantly lower in Nenets. Our main findings suggest that the serum concentrations of the legacy POPs in women in the Euro-Arctic Region of Russia are low and similar to those in other Arctic countries. Significant variations between settlements, and between Nenets and non-Nenets residents, were found. Arctic biomonitoring research in Russia should include studies on the associations between nutrition and concentrations of POPs.

© 2021, The Author(s). A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

© 2021, The Author(s). A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

Posttranscriptional gene regulation includes mRNA transport, localization, translation, and regulation of mRNA stability. CPEB (cytoplasmic polyadenylation element binding) family proteins bind to specific sites within the 3′-untranslated region and mediate poly- and deadenylation of transcripts, activating or repressing protein synthesis. As part of ribonucleoprotein complexes, the CPEB proteins participate in mRNA transport and localization to different sub-cellular compartments. The CPEB proteins are evolutionarily conserved and have similar functions in vertebrates and invertebrates. In the nervous system, the CPEB proteins are involved in cell division, neural development, learning, and memory. Here we consider the functional features of these proteins in the nervous system of phylogenetically distant organisms: Drosophila, a well-studied model, and mammals. Disruption of the CPEB proteins functioning is associated with various pathologies, such as autism spectrum disorder and brain cancer. At the same time, CPEB gene regulation can provide for a recovery of the brain function in patients with fragile X syndrome and Huntington's disease, making the CPEB genes promising targets for gene therapy.

The family of Tribbles proteins play many critical nonenzymatic roles and regulate a wide range of key signaling pathways. Tribbles homolog 2 (Trib2) is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. Trib2 can interact with E3 ubiquitin ligases and control protein stability of downstream effectors. This protein is induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic. Thus, Trib2 can be a predictive and valuable biomarker for the diagnosis and treatment of cancer. Recent studies have illustrated that Trib2 plays a major role in cell fate determination of stem cells. Stem cells have the capacity to self-renew and differentiate into specific cell types. Stem cells are important sources for cell-based regenerative medicine and drug screening. Trib2 has been found to increase the self-renewal ability of embryonic stem cells, the reprogramming efficiency of somatic cells, and chondrogenesis. In this review, we will focus on the recent advances of Trib2 function in tumorigenesis and stem cell fate decisions. [MediaObject not available: see fulltext.]

Objective: The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods: Female F1 hybrid mice (C Bl/  x DBA/2) and male and female linear mice C BL/  were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results: The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion: The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269. 57 6 57 6

Objective: The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods: Female F1 hybrid mice (C Bl/  x DBA/2) and male and female linear mice C BL/  were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results: The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion: The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269. 57 6 57 6

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.

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.

Introduction: The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders. Objective: Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases. Materials and methods: A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases. Results: Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.

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.

Introduction: The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders. Objective: Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases. Materials and methods: A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases. Results: Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.

© 2021 Elsevier Ltd This review examines investigations into the functionalization of polysaccharides by substituents containing multiple (C[dbnd]C) bonds and thiol (SH) groups that are prone to (co)polymerization in the presence of thermal, redox and photoinitiators or Michael addition reactions. A comparative analysis of the approaches to grafting the mentioned substituents onto the polysaccharide macromolecules was conducted. The use of the modified polysaccharides for the design of the 3D structures, including for the development of the pore bearing matrixes of cells or scaffolds utilized in regenerative medicine was examined. These modified polymers were also examined toward the design of excipient matrixes in pharmacological compositions, including with controllable release of active pharmaceuticals, as wel as of antibacterial and antifungal agents and others. In addition, a few examples of the use of modified derivatives in other areas are given.

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2020 Elsevier Inc. Background: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. Methods: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. Results and conclusions: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.

© 2021 Elsevier B.V. The Astrakhan region of Russia is endemic for the number of arboviruses. In this paper, we describe the results of the detection of the list of neglected arboviruses in the Astrakhan region for the 2018 season. For the purpose of the study in-house PCR assays for detection of 18 arboviruses have been developed and validated using arboviruses obtained from Russian State Collection of Viruses. Pools of ticks (n = 463) and mosquitoes (n = 312) as well as 420 samples of human patients sera have been collected and analyzed. Using developed multiplex real-time PCR assays we were able to detect RNA of eight arboviruses (Crimean-Congo hemorrhagic fever virus, Dhori (Batken strain) virus, Batai virus, Tahyna virus, Uukuniemi virus, Inkoo virus, Sindbis virus and West Nile fever virus). All discovered viruses are capable of infecting humans causing fever and in some cases severe forms with hemorrhagic or neurologic symptoms. From PCR-positive samples, we were able to recover one isolate each of Dhori (Batken strain) virus and Crimean-Congo hemorrhagic fever virus which were further characterized by next-generation sequencing. The genomic sequences of identified Dhori (Batken strain) virus strain represent the most complete genome of Batken virus strain among previously reported.

© 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 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.