Vol 11, No 4 (2019)


The Contribution of Major Histocompatibility Complex Class II Genes to an Association with Autoimmune Diseases

Zakharova M.Y., Belyanina T.A., Sokolov A.V., Kiselev I.S., Mamedov A.E.


Genetic studies of patients with autoimmune diseases have shown that one of the most important roles in the developing of these diseases is played by a cluster of genes of the major histocompatibility complex (MHC), as compared with other genome areas. Information on the specific contribution of MHC alleles, mostly MHC class II ones, to the genetic predisposition to autoimmune diseases is crucial for understanding their pathogenesis. This review dwells on the most relevant aspects of this problem: namely, the correlation between carriage of certain MHC II alleles and an increased (positively associated allele) or reduced (negatively associated allele) probability of developing the most common autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, autoimmune thyroiditis, etc. The most universal haplotypes, DR3-DQ2 and DR4-DQ8, are positively associated with many of these diseases, while the universal allele HLA-DRB1*0701 is protective.

Acta Naturae. 2019;11(4):4-12
pages 4-12 views

The Role of Interleukin-37 in the Pathogenesis of Allergic Diseases

Shilovskiy I.P., Dyneva M.E., Kurbacheva O.M., Kudlay D.A., Khaitov M.R.


Cytokines of the interleukin-1 (IL-1) family play an important role in the realization of the protective functions of innate immunity and are the key mediators involved in the pathogenesis of a wide range of diseases, including various manifestations of allergy. The IL-1 family includes more than 11 members. However, the functions of many of them remain to be elucidated. Recently, new members of the IL-1 family have been discovered. In 2000, several independent research groups reported the discovery of a new interleukin of this family, which was named IL-37, or IL-1F7 (according to the new nomenclature). IL-37 was assigned to the IL-1 family based on its structural similarity with other members of this family. The study of its biological properties showed that its activity changes in inflammatory diseases, such as rheumatoid arthritis, psoriasis, as well as allergic diseases (allergic rhinitis, bronchial asthma, and atopic dermatitis). However, unlike most members of the IL-1 family, IL-37 acts as a negative regulator of inflammation. Activation of IL-37 suppresses inflammation, resulting in the suppression of inflammatory cytokines and chemokines, which in turn prevents infiltration of pro-inflammatory cells, mainly eosinophils and neutrophils. The exact molecular and cellular mechanisms of the anti-inflammatory effect of IL-37 in the development of allergic diseases (AD) have not been fully studied. This review summarizes and analyzes the accumulated experimental data on the role of IL-37 in the pathogenesis of AD, such as allergic rhinitis, bronchial asthma, and atopic dermatitis.

Acta Naturae. 2019;11(4):54-64
pages 54-64 views

DARPins: Promising Scaffolds for Theranostics

Shilova O.N., Deyev S.M.


Monoclonal antibodies are the classical basis for targeted therapy, but the development of alternative binding proteins has made it possible to use non-immunoglobulin proteins as targeting modules. The advantages of DARPins, scaffold proteins based on ankyrin repeats, over antibodies are as follows: small size, stability over a wide range of temperatures and pH values, low aggregation tendency, and ease of production in heterologous expression systems. The differences in the structure of the paratope of DARPin and antibodies broaden the spectrum of target molecules, while the ease of creating hybrid fusion proteins allows one to obtain bispecific and multivalent constructs. In this article, we summarize recent data on the development of therapeutic and imaging compounds based on DARPins.

Acta Naturae. 2019;11(4):42-53
pages 42-53 views

The Role of Tumor-Derived Vesicles in the Regulation of Antitumor Immunity

Ukrainskaya V.M., Rubtsov Y.P., Knorre V.D., Maschan M.A., Gabibov A.G., Stepanov A.V.


In this article, we present a comprehensive, updated, and elucidative review of the current knowledge on the function played by tumor-derived vesicles (TDVs) in the crosstalk between tumor and immune cells. Characterization of the structure, biogenesis, and the major functions of TDVs is reported. The review focuses on particular ways of suppression or activation of CD4+/CD8+ Т cells by tumor-derived vesicles. Tumor-derived vesicles play an important role in the suppression of antitumor immunity. During the last 15 years, vesicle research has elucidated and improved our knowledge about the role of the vesicles in intercellular communication. Nevertheless, there are still blinds spots concerning vesicle heterogeneity and isolation methods, their uptake by target cells, and the role of mRNA in T-cell transformation or suppression. Along with the substantial progress in understanding of the role of tumor-derived vesicles in intercellular communication, novel antitumor therapy strategies based on vesicle inhibition in a tumor microenvironment are likely to appear very soon.

Acta Naturae. 2019;11(4):33-41
pages 33-41 views

Non-neutralizing Antibodies Directed at Conservative Influenza Antigens

Sedova E.S., Scherbinin D.N., Lysenko A.A., Alekseeva S.V., Artemova E.A., Shmarov M.M.


At the moment, developing new broad-spectrum influenza vaccines which would help avoid annual changes in a vaccine’s strain set is urgency. In addition, developing new vaccines based on highly conserved influenza virus proteins could allow us to better prepare for potential pandemics and significantly reduce the damage they cause. Evaluation of the humoral response to vaccine administration is a key aspect of the characterization of the effectiveness of influenza vaccines. In the development of new broad-spectrum influenza vaccines, it is important to study the mechanisms of action of various antibodies, including non-neutralizing ones, as well as to be in the possession of methods for quantifying these antibodies after immunization with new vaccines against influenza. In this review, we focused on the mechanisms of anti-influenza action of non-neutralizing antibodies, such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and antibody-mediated complement-dependent cytotoxicity (CDC). The influenza virus antigens that trigger these reactions are hemagglutinin (HA) and neuraminidase (NA), as well as highly conserved antigens, such as M2 (ion channel), M1 (matrix protein), and NP (nucleoprotein). In addition, the mechanisms of action and methods for detecting antibodies to neuraminidase (NA) and to the stem domain of hemagglutinin (HA) of the influenza virus are considered.

Acta Naturae. 2019;11(4):22-32
pages 22-32 views

Double-Stranded RNAs in Plant Protection Against Pathogenic Organisms and Viruses in Agriculture

Morozov S.Y., Solovyev A.G., Kalinina N.O., Taliansky M.E.


Recent studies have shown that plants are able to express the artificial genes responsible for the synthesis of double-stranded RNAs (dsRNAs) and hairpin double-stranded RNAs (hpRNAs), as well as uptake and process exogenous dsRNAs and hpRNAs to suppress the gene expression of plant pathogenic viruses, fungi, or insects. Both endogenous and exogenous dsRNAs are processed into small interfering RNAs (siRNAs) that can spread locally and systemically through the plant, enter pathogenic microorganisms, and induce RNA interference-mediated pathogen resistance in plants. There are numerous examples of the development of new biotechnological approaches to plant protection using transgenic plants and exogenous dsRNAs. This review summarizes new data on the use of transgenes and exogenous dsRNAs for the suppression of fungal and insect virulence genes, as well as viruses to increase the resistance of plants to these pathogens. We also analyzed the current ideas about the mechanisms of dsRNA processing and transport in plants.

Acta Naturae. 2019;11(4):13-21
pages 13-21 views

The Role of Heritable Tumors in Evolution of Development: a New Theory of Carcino-evo-devo

Kozlov A.P.


The hypothesis of evolution by tumor neofunctionalization (the “main hypothesis”) describes the possible role of hereditary tumors in evolution. The present article examines the relationship of the main hypothesis to other biological theories. As shown in this paper, the main hypothesis does not contradict to the existing biological theories, but fills the lacunas between them and explains some unexplained (or not completely understood) questions. Common features of embryonic development and tumorigenesis are described by several recognized theories. Similarities between normal development and tumorigenesis suggest that tumors could participate in the evolution of ontogenesis and in the origin of new cell types, tissues and organs. A wide spectrum of non-trivial explanations and non-trivial predictions in different fields of biology, suggested by the main hypothesis, is an indication of its fundamental nature and the potential to become a new biological theory, a theory of the role of tumors in evolution of development, or carcino-evo-devo.

Acta Naturae. 2019;11(4):65-72
pages 65-72 views

Research Articles

Surface Charge Mapping on Virions and Virus-Like Particles of Helical Plant Viruses

Arkhipenko M.V., Nikitin N.A., Baranov O.A., Evtushenko E.A., Atabekov J.G., Karpova O.V.


Currently, the assembly of helical plant viruses is poorly understood. The viral assembly and infection may be affected by the charge distribution on the virion surface. However, only the total virion charge (isoelectric point) has been determined for most plant viruses. Here, we report on the first application of positively charged magnetic nanoparticles for mapping the surface charge distribution of helical plant viruses. The charge was demonstrated to be unevenly distributed on the surface of viruses belonging to different taxonomic groups, with the negative charge being predominantly located at one end of the virions. This charge distribution is mainly controlled by viral RNA.

Acta Naturae. 2019;11(4):73-78
pages 73-78 views

“Shielding” of Cytokine Induction by the Periodontal Microbiome in Patients with Periodontitis Associated with Type 2 Diabetes Mellitus

Balmasova I.P., Lomakin Y.A., Babaev E.A., Tsarev V.N., Gabibov A.G., Smirnov I.V., Knorre V.D., Ovchinnikova L.A., Gnuchev N.V., Khurs E.N., Deev M.S., Kostin N.N., Arutyunov S.D.


Periodontal diseases, especially those with polymicrobial etiology, are often associated with type 2 diabetes mellitus, proceeding more severely and affecting the course of diabetes mellitus. Recently, this feature has been associated with the ability of periodontopathogen microflora to cause not only a local infectious process in the oral cavity, but also to interact with the human immune system and induce various systemic effects. We investigated changes in the salivary cytokine profile of patients with chronic periodontitis, associated and not associated with type 2 diabetes mellitus. We observed a statistically significant decrease of MCP-1/CCL2, GM-CSF, IL-5, IL-6, and IFN-γ in the saliva of patients with chronic periodontitis associated with type 2 diabetes mellitus in comparison with patients with chronic periodontitis only. All of these cytokines are associated with macrophage activation. These data are an important contribution to the elucidation of the mechanism of periodontopathogens involvement in the manifestation of the systemic effects of type 2 diabetes.

Acta Naturae. 2019;11(4):79-87
pages 79-87 views

Calcitonin Gene-Related Peptide and Substance P As Predictors of Venous Pelvic Pain

Gavrilov S.G., Vasilieva G.Y., Vasiliev I.M., Efremova O.I.


The purpose of this work was to study the contents of calcitonin gene-related peptide (CGRP) and substance P (SP) in the blood plasma of patients with pelvic varicose veins. Thirty women with pelvic varicosities and a reflux blood flow were investigated using duplex ultrasonography. Group 1 included 18 patients with clinical signs of the pelvic congestion syndrome (PCS), including venous pelvic pain (VPP). Group 2 consisted of 12 patients with pelvic varicosities with no clinical signs of PCS. Group 1. The score of VPP intensity ranged from 4 to 8; the mean score being 4.84 ± 0.43. The CGRP level in the studied group ranged from 0.39 to 1.01 ng/mL; the SP level ranged from 0.005 to 1.33 ng/mL. Group 2. The CGRP values were 0.15-0.32 ng/mL, and the SP range was 0.003-0.3 ng/mL. In this group, the levels of the studied peptides were 3-5 times lower than those for the patients with VPP. Group 3. The mean CGRP values were 0.06 ± 0.003 ng/mL, and the mean SP values were 0.03 ± 0.001 ng/mL. These values were considered as the reference parameters; a statistical analysis was performed for them. The correlation analysis revealed a strong relationship between the CGRP and VPP levels (r = 0.82) and a medium correlation between the SP level and pelvic pain in Group 1. The CGRP and SP levels in blood plasma highly correlate with the presence of pelvic venous pain.

Acta Naturae. 2019;11(4):88-92
pages 88-92 views

Genetic Variability of the AcrAB-TolC Multidrug Efflux Pump Underlies SkQ1 Resistance in Gram-Negative Bacteria

Nazarov P.A., Kotova E.A., Skulachev V.P., Antonenko Y.N.


SkQ1, a novel antibiotic targeting bacterial bioenergetics, is highly effective against both gram-positive and gram-negative bacteria. However, some gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, are highly resistant to it. In different gram-negative bacteria, this resistance is associated with the identity of their AcrB transporter protein sequence with the sequence of the AcrB protein from E. coli. SkQ1 is expelled from E. coli cells by the AcrAB-TolC multidrug efflux pump. In this study, we demonstrate that SkQ1 resistance in E. coli, in contrast to chloramphenicol resistance, does not depend on the presence of the multidrug efflux pump accessory protein AcrZ.

Acta Naturae. 2019;11(4):93-98
pages 93-98 views

Short communications

Tear Fluid Catecholamines As Biomarkers of the Parkinson’s Disease: A Clinical and Experimental Study

Kim A.R., Nodel M.R., Pavlenko T.A., Chesnokova N.B., Yakhno N.N., Ugrumov M.V.


An important approach to an early diagnosis of Parkinson’s disease (PD) is screening for peripheral biomarkers in patients at the early clinical stage. In this study, we evaluated catecholamine concentration changes in the tear fluid of untreated PD patients as biomarkers. Norepinephrine and dopamine concentrations in the tear fluid of patients were found to increase compared to those in age controls, which was especially pronounced on the side where motor symptoms appeared. On the contrary, the epinephrine concentration in the tear fluid of patients was reduced bilaterally. Since there was no reason to consider the markers found in the clinical stage of PD as markers of the preclinical stage, we additionally studied the tear fluid composition in mouse neurotoxic models of PD preclinical and clinical stages. The norepinephrine concentration in the tear fluid of mice from the clinical stage model was found to be higher than that in controls; in the preclinical stage model, the norepinephrine concentration had a tendency to increase. Therefore, both PD patients and mice from PD preclinical and clinical stage models manifest unidirectional changes in their tear fluid compositions, which may be considered as promising biomarkers for the development of early diagnosis.

Acta Naturae. 2019;11(4):99-103
pages 99-103 views

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