Репозиторий Университета

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.

© 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.

© Copyright © 2019 Veremeyko, Yung, Dukhinova, Strekalova and Ponomarev. Twenty years ago, the scientific community exhibited relatively little interest in the study of microglial cells. However, recent technical and conceptual advances in this field have greatly increased interest in the basic biology of these cells within various neurodegenerative diseases, including multiple sclerosis, Alzheimer’s disease, and traumatic brain/spinal cord injuries. The main functions of these cells in the normal central nervous system (CNS) remain poorly understood, despite considerable elucidation of their roles in pathological conditions. Microglia populate the brain before birth and remain in close lifelong contact with CNS-resident cells under the influence of the local microenvironment. Within the CNS parenchyma, microglia actively interact with two main cell types, astrocytes and neurons, which produce many factors that affect microglia phenotypes in the normal CNS and during neuroinflammation. These factors include interleukin (IL)-34, macrophage colony-stimulating factor, transforming growth factor-β, and IL-4, which promote microglial expansion, survival, and differentiation to an anti-inflammatory phenotype in the normal CNS. Under inflammatory conditions, however, astrocytes produce several pro-inflammatory factors that contribute to microglial activation. The interactions of microglia with neurons in the normal and diseased CNS are especially intriguing. Microglia are known to interact actively with neurons by facilitating axonal pruning during development, while neurons provide specific factors that alter microglial phenotypes and functions. This review focuses mainly on the roles of soluble neuronal factors that affect microglial phenotypes and functions and the possible involvement of these factors in the pathology of neurodegenerative diseases.

© 2018 Veremeyko, Yung, Dukhinova, Kuznetsova, Pomytkin, Lyundup, Strekalova, Barteneva and Ponomarev. Although it has been demonstrated that cAMP pathway affect both adaptive and innate cell functions, the role of this pathway in the regulation of T-cell-mediated central nervous system (CNS) autoimmune inflammation, such as in experimental autoimmune encephalomyelitis (EAE), remains unclear. It is also unclear how cAMP pathway affects the function of CD4 T cells in vivo at the site of inflammation. We found that adenylyl cyclase activator Forskolin besides inhibition of functions autoimmune CD4 T cells also upregulated microRNA (miR)-124 in the CNS during EAE, which is associated with M2 phenotype of microglia/macrophages. Our study further established that in addition to direct influence of cAMP pathway on CD4 T cells, stimulation of this pathway promoted macrophage polarization toward M2 leading to indirect inhibition of function of T cells in the CNS. We demonstrated that Forskolin together with IL-4 or with Forskolin together with IL-4 and IFNγ effectively stimulated M2 phenotype of macrophages indicating high potency of this pathway in reprogramming of macrophage polarization in Th2-and even in Th1/Th2-mixed inflammatory conditions such as EAE. Mechanistically, Forskolin and/or IL-4 activated ERK pathway in macrophages resulting in the upregulation of M2-associated molecules miR-124, arginase (Arg)1, and Mannose receptor C-type 1 (Mrc1), which was reversed by ERK inhibitors. Administration of Forskolin after the onset of EAE substantially upregulated M2 markers Arg1, Mrc1, Fizz1, and Ym1 and inhibited M1 markers nitric oxide synthetase 2 and CD86 in the CNS during EAE resulting in decrease in macrophage/microglia activation, lymphocyte and CD4 T cell infiltration, and the recovery from the disease. Forskolin inhibited proliferation and IFNγ production by CD4 T cells in the CNS but had rather weak direct effect on proliferation of autoimmune T cells in the periphery and in vitro, suggesting prevalence of indirect effect of Forskolin on differentiation and functions of autoimmune CD4 T cells in vivo. Thus, our data indicate that Forskolin has potency to skew balance toward M2 affecting ERK pathway in macrophages and indirectly inhibit pathogenic CD4 T cells in the CNS leading to the suppression of autoimmune inflammation. These data may have also implications for future therapeutic approaches to inhibit autoimmune Th1 cells at the site of tissue inflammation.

© Ima-Press Publishing House. All rights reserved. Stroke is one of the leading causes of death and disability in the population, has a complex multifactorial nature and develops through the interaction of environmental factors and genetic predisposition, the pattern and mechanisms of which have been insufficiently studied. Ischemic stroke (IS) is most commonly encountered. Objective: to investigate the differential expression of microRNAs (miRNAs) in the plasma of patients in the acute and subacute stages of stroke. Patients and methods. The investigation enrolled 10 patients (5 men and 5 women; mean age, 64.5 years) with IS and 10 gender- and age-matched volunteers (a control group). A real-time polymerase chain reaction (PCR) was used to analyze the expression of 45 miRNAs isolated from the plasma samples of the patients on days 1 and 8 after onset of IS and isolated once from those of the controls. Results. A list of 45 miRNAs, that might be potential biomarkers and/or prognostic factors of stroke, was compiled. The investigation showed a decrease in let-7i-3p and miR-23a-3p miRNA expression in patients on the first day after onset of IS compared to the control group. The expression of miR-23a-3p increased in the patients at 8 days after IS. The patients with IS and the controls both showed gender differences in the expression of let-7i-5p and miR-92b-3p. Conclusion. The in-silico analysis revealed specific miRNA clusters associated with the peculiarities of clinical manifestations of IS. This may suggest that the patients with the favorable and unfavorable course of stroke may have its different molecular basis. In addition, it is necessary to take into account gender differences in the expression of individual miRNAs in assessing their significance in the pathogenesis and prognosis of IS.

© 2018 Ruslania. All rights reserved. This review summarizes the published literature devoted to the analysis of diagnostic role of microRNAs in cardiovascular disease. MicroRNAs are a class of small non-coding RNAs that regulate gene expression and affect various cellular functions. Modern methods for the detection ofmicroRNA are described. The data of variations in their concentration in ischemic heart disease, heart failure and other diseases are analyzed. At present, the accumulation of clinical data on the role of these biomarkers will allow to determine the diagnostic and prognostic significance of microRNAs (microRNA sets) in cardiovascular diseases.

© 2018 Morozov et al. Trans-acting small interfering RNAs (ta-siRNAs) are transcribed from protein noncoding genomic TAS loci and belong to a plant-specific class of endogenous small RNAs. These siRNAs have been found to regulate gene expression in most taxa including seed plants, gymnosperms, ferns and mosses. In this study, bioinformatic and experimental PCR-based approaches were used as tools to analyze TAS3 and TAS6 loci in transcriptomes and genomic DNAs from representatives of evolutionary distant non-vascular plant taxa such as Bryophyta, Marchantiophyta and Anthocerotophyta. We revealed previously undiscovered TAS3 loci in plant classes Sphagnopsida and Anthocerotopsida, as well as TAS6 loci in Bryophyta classes Tetraphidiopsida, Polytrichopsida, Andreaeopsida and Takakiopsida. These data further unveil the evolutionary pathway of the miR390-dependent TAS3 loci in land plants. We also identified charophyte alga sequences coding for SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for generation of ta-siRNAs in plants, and hypothesized that the appearance of TAS3-related sequences could take place at a very early step in evolutionary transition from charophyte algae to an earliest common ancestor of land plants.

Today, stroke is the third most common pathology after cardiovascular disease and cancer, as well as the leading cause of disability in the world. Although some progress has been made in the field of primary and secondary stroke prevention over the past few decades, a deeper knowledge of the pathophysiology of the disease is needed to significantly improve diagnosis and therapy. MicroRNA (miRNA) is an important, recently identified class of posttranscriptional regulators of gene expression. MiRNA can be used as a tool for therapeutic interventions. This review considers a role of miRNAs in the regulation of experimental stroke and in the development of carotid artery stroke. A potential role of miRNAs as promising biomarkers of stroke is discussed.