Vol 13, No 2 (2021)


MicroRNAs in the Myelodysplastic Syndrome

Veryaskina Y.A., Titov S.E., Kovynev I.B., Fedorova S.S., Pospelova T.I., Zhimulev I.F.


The myelodysplastic syndrome (MDS) holds a special place among blood cancers, as it represents a whole spectrum of hematological disorders with impaired differentiation of hematopoietic precursors, bone marrow dysplasia, genetic instability and is noted for an increased risk of acute myeloid leukemia. Both genetic and epigenetic factors, including microRNAs (miRNAs), are involved in MDS development. MicroRNAs are short non-coding RNAs that are important regulators of normal hematopoiesis, and abnormal changes in their expression levels can contribute to hematological tumor development. To assess the prognosis of the disease, an international assessment system taking into account a karyotype, the number of blast cells, and the degree of deficiency of different blood cell types is used. However, the overall survival and effectiveness of the therapy offered are not always consistent with predictions. The search for new biomarkers, followed by their integration into the existing prognostic system, will allow for personalized treatment to be performed with more precision. Additionally, this paper explains how miRNA expression levels correlate with the prognosis of overall survival and response to the therapy offered.

Acta Naturae. 2021;13(2):4-15
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Photoluminescent Nanomaterials for Medical Biotechnology

Guryev E.L., Shanwar S., Zvyagin A.V., Deyev S.M., Balalaeva I.V.


Creation of various photoluminescent nanomaterials has significantly expanded the arsenal of approaches used in modern biomedicine. Their unique photophysical properties can significantly improve the sensitivity and specificity of diagnostic methods, increase therapy effectiveness, and make a theranostic approach to treatment possible through the application of nanoparticle conjugates with functional macromolecules. The most widely used nanomaterials to date are semiconductor quantum dots; gold nanoclusters; carbon dots; nanodiamonds; semiconductor porous silicon; and up-conversion nanoparticles. This paper considers the promising groups of photoluminescent nanomaterials that can be used in medical biotechnology: in particular, for devising agents for optical diagnostic methods, sensorics, and various types of therapy.

Acta Naturae. 2021;13(2):16-31
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Quality Control Mechanisms in Bacterial Translation

Zarechenskaia A.S., Sergiev P.V., Osterman I.A.


Ribosome stalling during translation significantly reduces cell viability, because cells have to spend resources on the synthesis of new ribosomes. Therefore, all bacteria have developed various mechanisms of ribosome rescue. Usually, the release of ribosomes is preceded by hydrolysis of the tRNA–peptide bond, but, in some cases, the ribosome can continue translation thanks to the activity of certain factors. This review describes the mechanisms of ribosome rescue thanks to trans-translation and the activity of the ArfA, ArfB, BrfA, ArfT, HflX, and RqcP/H factors, as well as continuation of translation via the action of EF-P, EF-4, and EttA. Despite the ability of some systems to duplicate each other, most of them have their unique functional role, related to the quality control of bacterial translation in certain abnormalities caused by mutations, stress cultivation conditions, or antibiotics.

Acta Naturae. 2021;13(2):32-44
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DNA Methylation As an Epigenetic Mechanism in the Development of Multiple Sclerosis

Kiselev I.S., Kulakova O.G., Boyko A.N., Favorova O.O.


The epigenetic mechanisms of gene expression regulation are a group of the key cellular and molecular pathways that lead to inherited alterations in genes’ activity without changing their coding sequence. DNA methylation at the C5 position of cytosine in CpG dinucleotides is amongst the central epigenetic mechanisms. Currently, the number of studies that are devoted to the identification of methylation patterns specific to multiple sclerosis (MS), a severe chronic autoimmune disease of the central nervous system, is on a rapid rise. However, the issue of the contribution of DNA methylation to the development of the different clinical phenotypes of this highly heterogeneous disease has only begun to attract the attention of researchers. This review summarizes the data on the molecular mechanisms underlying DNA methylation and the MS risk factors that can affect the DNA methylation profile and, thereby, modulate the expression of the genes involved in the disease’s pathogenesis. The focus of our attention is centered on the analysis of the published data on the differential methylation of DNA from various biological samples of MS patients obtained using both the candidate gene approach and high-throughput methods.

Acta Naturae. 2021;13(2):45-57
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Poly(ADP-Ribosyl) Code Functions

Maluchenko N.V., Koshkina D.O., Feofanov A.V., Studitsky V.M., Kirpichnikov M.P.


Poly(ADP-ribosyl)ation plays a key role in cellular metabolism. Covalent poly(ADP-ribosyl)ation affects the activity of the proteins engaged in DNA repair, chromatin structure regulation, gene expression, RNA processing, ribosome biogenesis, and protein translation. Non-covalent PAR-dependent interactions are involved in the various types of cellular response to stress and viral infection, such as inflammation, hormonal signaling, and the immune response. The review discusses how structurally different poly(ADP-ribose) (PAR) molecules composed of identical monomers can differentially participate in various cellular processes acting as the so-called “PAR code.” The article describes the ability of PAR polymers to form functional biomolecular clusters through a phase-separation in response to various signals. This phase-separation contributes to rapid spatial segregation of biochemical processes and effective recruitment of the necessary components. The cellular PAR level is tightly controlled by a network of regulatory proteins: PAR code writers, readers, and erasers. Impaired PAR metabolism is associated with the development of pathological processes causing oncological, cardiovascular, and neurodegenerative diseases. Pharmacological correction of the PAR level may represent a new approach to the treatment of various diseases.

Acta Naturae. 2021;13(2):58-69
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Parkinson’s Disease Associated with GBA Gene Mutations: Molecular Aspects and Potential Treatment Approaches

Senkevich K.A., Kopytova A.E., Usenko T.S., Emelyanov A.K., Pchelina S.N.


Parkinson’s disease (PD) is a multifactorial neurodegenerative disease. To date, genome-wide association studies have identified more than 70 loci associated with the risk of PD. Variants in the GBA gene encoding glucocerebrosidase are quite often found in PD patients in all populations across the world, which justifies intensive investigation of this gene. A number of biochemical features have been identified in patients with GBA-associated Parkinson’s disease (GBA-PD). In particular, these include decreased activity of glucocerebrosidase and accumulation of the glucosylceramide substrate. These features were the basis for putting forward a hypothesis about treatment of GBA-PD using new strategies aimed at restoring glucocerebrosidase activity and reducing the substrate concentration. This paper discusses the molecular and genetic mechanisms of GBA-PD pathogenesis and potential approaches to the treatment of this form of the disease.

Acta Naturae. 2021;13(2):70-78
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Pathogenesis, Diagnosis, and Treatment of Hemostatic Disorders in COVID-19 Patients

Khalirakhmanov A.F., Idrisova K.F., Gajfullina R.F., Zinchenko S.V., Litvinov R.I., Sharafeev A.Z., Kiyasov A.P., Rizvanov A.A.


The novel coronavirus infection named COVID-19 was first detected in Wuhan, China, in December 2019, and it has been responsible for significant morbidity and mortality in scores of countries. At the time this article was being written, the number of infected and deceased patients continued to grow worldwide. Most patients with severe forms of the disease suffer from pneumonia and pulmonary insufficiency; in many cases, the disease is generalized and causes multiple organ failures and a dysfunction of physiological systems. One of the most serious and prognostically ominous complications from COVID-19 is coagulopathy, in particular, decompensated hypercoagulability with the risk of developing disseminated intravascular coagulation. In most cases, local and diffuse macro- and microthromboses are present, a condition which causes multiple-organ failure and thromboembolic complications. The causes and pathogenic mechanisms of coagulopathy in COVID-19 remain largely unclear, but they are associated with systemic inflammation, including the so-called cytokine storm. Despite the relatively short period of the ongoing pandemic, laboratory signs of serious hemostatic disorders have been identified and measures for specific prevention and correction of thrombosis have been developed. This review discusses the causes of COVID-19 coagulopathies and the associated complications, as well as possible approaches to their early diagnosis, prevention, and treatment.

Acta Naturae. 2021;13(2):79-84
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Molecular Mechanisms of Muscle Tone Impairment under Conditions of Real and Simulated Space Flight

Shenkman B.S., Tsaturyan A.K., Vihlyantsev I.M., Kozlovskaya I.B., Grigoriev A.I.


Kozlovskaya et al. [1] and Grigoriev et al. [2] showed that enormous loss of muscle stiffness (atonia) develops in humans under true (space flight) and simulated microgravity conditions as early as after the first days of exposure. This phenomenon is attributed to the inactivation of slow motor units and called reflectory atonia. However, a lot of evidence indicating that even isolated muscle or a single fiber possesses substantial stiffness was published at the end of the 20th century. This intrinsic stiffness is determined by the active component, i.e. the ability to form actin-myosin cross-bridges during muscle stretch and contraction, as well as by cytoskeletal and extracellular matrix proteins, capable of resisting muscle stretch. The main facts on intrinsic muscle stiffness under conditions of gravitational unloading are considered in this review. The data obtained in studies of humans under dry immersion and rodent hindlimb suspension is analyzed. The results and hypotheses regarding reduced probability of cross-bridge formation in an atrophying muscle due to increased interfilament spacing are described. The evidence of cytoskeletal protein (titin, nebulin, etc.) degradation during gravitational unloading is also discussed. The possible mechanisms underlying structural changes in skeletal muscle collagen and its role in reducing intrinsic muscle stiffness are presented. The molecular mechanisms of changes in intrinsic stiffness during space flight and simulated microgravity are reviewed.

Acta Naturae. 2021;13(2):85-97
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The Role of the MCTS1 and DENR Proteins in Regulating the Mechanisms Associated with Malignant Cell Transformation

Shyrokova E.Y., Prassolov V.S., Spirin P.V.


The mutations associated with malignant cell transformation are believed to disrupt the expression of a significant number of normal, non-mutant genes. The proteins encoded by these genes are involved in the regulation of many signaling pathways that are responsible for differentiation and proliferation, as well as sensitivity to apoptotic signals, growth factors, and cytokines. Abnormalities in the balance of signaling pathways can lead to the transformation of a normal cell, which results in tumor formation. Detection of the target genes and the proteins they encode and that are involved in the malignant transformation is one of the major evolutions in anti-cancer biomedicine. Currently, there is an accumulation of data that shed light on the role of the MCTS1 and DENR proteins in oncogenesis.

Acta Naturae. 2021;13(2):98-105
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At the Crossroads: Mechanisms of Apoptosis and Autophagy in Cell Life and Death

Shliapina V.L., Yurtaeva S.V., Rubtsova M.P., Dontsova O.A.


Apoptosis and autophagy are conserved processes that regulate cell survival and death under stress conditions. real rolex submariner vs fake Apoptosis aims to remove cells from the body with minimal damage to surrounding tissues. Autophagy promotes removal of damaged organelles, protein aggregates, and cellular pathogens, stimulating cell survival. The signaling pathways involved in the regulation of apoptosis and autophagy largely overlap, leading to both competition and unidirectional interaction, which is of particular interest in investigating them as potential targets for cancer, paul newman rolex replica for saleautoimmune, and neurodegenerative disease therapies. This review analyzes the main pathways of molecular interactions between autophagy and apoptosis, which is necessary for understanding the mechanism maintaining rolex iced out fake the balance between cell death and survival under unfavorable conditions.

Acta Naturae. 2021;13(2):106-115
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Research Articles

Efficacy of (R)-6-Adamantane-Derivatives of 1,3-Oxazinan-2-One and Piperidine-2,4-Dione in The Treatment of Mice Infected by the A/California/04/2009 influenza Virus

Glubokova E.A., Leneva I.A., Kartashova N.P., Falynskova I.N., Tikhov R.M., Kuznetsov N.Y.


The World Health Organization (WHO) recommends antivirals as an additional line of defense against influenza. One of such drugs is rimantadine. However, most of the circulating strains of influenza A viruses are resistant to this drug. Thus, a search for analogs effective against rimantadine-resistant viruses is of the utmost importance. Here, we examined the efficiency of two adamantane azaheterocyclic rimantadine derivatives on a mouse model of pneumonia caused by the rimantadine-resistant influenza A virus /California/04/2009 (H1N1). BALB/c mice inoculated with the virus were treated with two doses (15 mg and 20 mg/kg a day) of tested analogs via oral administration for 5 days starting 4 hours before the infection. The efficacy was assessed by survival rate, mean day to death, weight loss, and viral titer in the lungs. Oral treatment with both compounds in both doses protected 60–100% of the animals, significantly increased the survival rate, and abolished weight loss. The treatments also inhibited virus titer in the lungs in comparison to the control group. This treatment was more effective compared to rimantadine at the same scheme and dosage. Moreover, the study of the sensitivity of the virus isolated from the lungs of the treated mice and grown in MDCK cells showed that no resistance had emerged during the 5 days of treatment with both compounds.

Acta Naturae. 2021;13(2):116-125
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Short communications

Forces for Folding

Crane-Robinson C.


Understanding the nature of the forces driving the folding of proteins, nucleic acids and the formation of their complexes absolutely requires thermodynamic data, in addition to structural information. In practical terms, this means the use of super-sensitive scanning and titration calorimeters for experimental determination of the heats (enthalpies) characterising these processes. Peter Privalov was both an experimental thermodynamicist and a calorimeter designer/manufacturer who followed and propagated this credo. The sum total of his many publications, every one of which addresses a fundamental question, is his lasting epitaph.

Acta Naturae. 2021;13(2):126-128
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