Vol 12, No 3 (2020)


Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

Gaponova A.V., Rodin S., Mazina A.A., Volchkov P.V.


About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cell–cell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelial–mesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

Acta Naturae. 2020;12(3):4-23
pages 4-23 views

Supramolecular organization as a factor of ribonuclease cytotoxicity

Dudkina E.V., Ulyanova V.V., Ilinskaya O.N.


One of the approaches used to eliminate tumor cells is directed destruction/modification of their RNA molecules. In this regard, ribonucleases (RNases) possess a therapeutic potential that remains largely unexplored. It is believed that the biological effects of secreted RNases, namely their antitumor and antiviral properties, derive from their catalytic activity. However, a number of recent studies have challenged the notion that the activity of RNases in the manifestation of selective cytotoxicity towards cancer cells is exclusively an enzymatic one. In this review, we have analyzed available data on the cytotoxic effects of secreted RNases, which are not associated with their catalytic activity, and we have provided evidence that the most important factor in the selective apoptosis-inducing action of RNases is the structural organization of these enzymes, which determines how they interact with cell components. The new idea on the preponderant role of non-catalytic interactions between RNases and cancer cells in the manifestation of selective cytotoxicity will contribute to the development of antitumor RNase-based drugs.

Acta Naturae. 2020;12(3):24-33
pages 24-33 views

Development of antimicrobial therapy methods to overcome the antibiotic resistance of Acinetobacter baumannii

Kisil O.V., Efimenko T.A., Gabrielyan N.I., Efremenkova O.V.


The spread of antibiotic resistance among pathogens represents a threat to human health around the world. In 2017, the World Health Organization published a list of 12 top-priority antibiotic-resistant pathogenic bacteria for which new effective antibiotics or new ways of treating the infections caused by them are needed. This review focuses on Acinetobacter baumannii, one of these top-priority pathogens. The pathogenic bacterium A. baumannii is one of the most frequently encountered infectious agents in the world; its clinically significant features include resistance to UV light, drying, disinfectants, and antibiotics. This review looks at the various attempts that have been made to tackle the problem of drug resistance relating to A. baumannii variants without the use of antibiotics. The potential of bacteriophages and antimicrobial peptides in the treatment of infections caused by A. baumannii in both planktonic and biofilm form is assessed. Such topics as research into the development of vaccines based on the outer membrane proteins of A. baumannii and the use of silver nanoparticles, as well as photodynamic and chelate therapy, are also covered.

Acta Naturae. 2020;12(3):34-45
pages 34-45 views

Infectious plant diseases: etiology, current status, problems and prospects in plant protection

Nazarov P.A., Baleev D.N., Ivanova M.I., Sokolova L.M., Karakozova M.V.


In recent years, there has been an increase in the number of diseases caused by bacterial, fungal, and viral infections. Infections affect plants at different stages of agricultural production. Depending on weather conditions and the phytosanitary condition of crops, the prevalence of diseases can reach 70–80% of the total plant population, and the yield can decrease in some cases down to 80–98%. Plants have innate cellular immunity, but specific phytopathogens have an ability to evade that immunity. This article examined phytopathogens of viral, fungal, and bacterial nature and explored the concepts of modern plant protection, methods of chemical, biological, and agrotechnical control, as well as modern methods used for identifying phytopathogens.

Acta Naturae. 2020;12(3):46-59
pages 46-59 views

Promising molecular targets for pharmacological therapy of neurodegenerative pathologies

Neganova M.E., Aleksandrova Y.R., Nebogatikov V.O., Klochkov S., Ustyugov A.A.


Drug development for the treatment of neurodegenerative diseases has to confront numerous problems occurring, in particular, because of attempts to address only one of the causes of the pathogenesis of neurological disorders. Recent advances in multitarget therapy research are gaining momentum by utilizing pharmacophores that simultaneously affect different pathological pathways in the neurodegeneration process. The application of such a therapeutic strategy not only involves the treatment of symptoms, but also mainly addresses prevention of the fundamental pathological processes of neurodegenerative diseases and the reduction of cognitive abilities. Neuroinflammation and oxidative stress, mitochondrial dysfunction, dysregulation of the expression of histone deacetylases, and aggregation of pathogenic forms of proteins are among the most common and significant pathological features of neurodegenerative diseases. In this review, we focus on the molecular mechanisms and highlight the main aspects, including reactive oxygen species, the cell endogenous antioxidant system, neuroinflammation triggers, metalloproteinases, α-synuclein, tau proteins, neuromelanin, histone deacetylases, presenilins, etc. The processes and molecular targets discussed in this review could serve as a starting point for screening leader compounds that could help prevent or slow down the development of neurodegenerative diseases.

Acta Naturae. 2020;12(3):60-80
pages 60-80 views

Molecular principles of insect chemoreception

Sokolinskaya E.L., Kolesov D.V., Lukyanov K.A., Bogdanov A.M.


Chemoreception, an ability to perceive specific chemical stimuli, is one of the most evolutionarily ancient forms of interaction between living organisms and their environment. Chemoreception systems are found in organisms belonging to all biological kingdoms. In higher multicellular animals, chemoreception (along with photo- and mechanoreception) underlies the functioning of five traditional senses. Insects have developed a peculiar and one of the most sophisticated chemoreception systems, which exploits at least three receptor superfamilies providing perception of smell and taste, as well as chemical communication in these animals. The enormous diversity of physiologically relevant compounds in the environment has given rise to a wide-ranging repertoire of chemoreceptors of various specificities. Thus, in insects, they are represented by several structurally and functionally distinct protein classes and are encoded by hundreds of genes. In the current review, we briefly characterize the insect chemoreception system by describing the main groups of receptors that constitute it and putting emphasis on the peculiar architecture and mechanisms of functioning possessed by these molecules.

Acta Naturae. 2020;12(3):81-91
pages 81-91 views

Cytokine profile as a marker of cell damage and immune dysfunction after spinal cord injury

Telegin G.B., Chernov A.S., Konovalov N.A., Belogurov A.A., Balmasova I.P., Gabibov A.G.


This study reviews the findings of recent experiments designed to investigate the cytokine profile after a spinal cord injury. The role played by key cytokines in eliciting the cellular response to trauma was assessed. The results of the specific immunopathogenetic interaction between the nervous and immune systems in the immediate and chronic post-traumatic periods are summarized. It was demonstrated that it is reasonable to use the step-by-step approach to the assessment of the cytokine profile after a spinal cord injury and take into account the combination of the pathogenetic and protective components in implementing the regulatory effects of individual cytokines and their integration into the regenerative processes in the injured spinal cord. This allows one to rationally organize treatment and develop novel drugs.

Acta Naturae. 2020;12(3):92-101
pages 92-101 views

Near-infrared activated cyanine dyes as agents for photothermal therapy and diagnosis of tumors

Shramova E.I., Kotlyar A.B., Lebedenko E.N., Deyev S.M., Proshkina G.M.


Today, it has become apparent that innovative treatment methods, including those involving simultaneous diagnosis and therapy, are particularly in demand in modern cancer medicine. The development of nanomedicine offers new ways of increasing the therapeutic index and minimizing side effects. The development of photoactivatable dyes that are effectively absorbed in the first transparency window of biological tissues (700–900 nm) and are capable of fluorescence and heat generation has led to the emergence of phototheranostics, an approach that combines the bioimaging of deep tumors and metastases and their photothermal treatment. The creation of near-infrared (NIR) light-activated agents for sensitive fluorescence bioimaging and phototherapy is a priority in phototheranostics, because the excitation of drugs and/or diagnostic substances in the near-infrared region exhibits advantages such as deep penetration into tissues and a weak baseline level of autofluorescence. In this review, we focus on NIR-excited dyes and discuss prospects for their application in photothermal therapy and the diagnosis of cancer. Particular attention is focused on the consideration of new multifunctional nanoplatforms for phototheranostics which allow one to achieve a synergistic effect in combinatorial photothermal, photodynamic, and/or chemotherapy, with simultaneous fluorescence, acoustic, and/or magnetic resonance imaging.

Acta Naturae. 2020;12(3):102-113
pages 102-113 views

Research Articles

Preclinical studies of immunogenity, protectivity, and safety of the combined vector vaccine for prevention of the middle east respiratory syndrome

Dolzhikova I.V., Grousova D.M., Zubkova O.V., Tukhvatulin A.I., Kovyrshina A.V., Lubenets N.L., Ozharovskaia T.A., Popova O., Esmagambetov I.B., Shcheblyakov D.V., Evgrafova I.M., Nedorubov A.A., Gordeichuk I.V., Gulyaev S.A., Botikov A.G., Panina L.V., Mishin D.V., Loginova S.Y., Borisevich S.V., Deryabin P.G., Naroditsky B.S., Logunov D.Y., Gintsburg A.L.


The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.


Acta Naturae. 2020;12(3):114-123
pages 114-123 views

GLAD-PCR assay of R(5mC)GY sites in the regulatory region of tumor-suppressor genes associated with gastric cancer

Malyshev B.S., Netesova N.A., Smetannikova N.A., Abdurashitov M.A., Akishev A.G., Dubinin E.V., Azanov A.Z., Vihlyanov I.V., Nikitin M.K., Karpov A.B., Degtyarev S.K.


At early stages of carcinogenesis, the regulatory regions of some tumor suppressor genes become aberrantly methylated at RCGY sites, which are substrates of DNA methyltransferase Dnmt3. Identification of aberrantly methylated sites in tumor DNA is considered to be the first step in the development of epigenetic PCR test systems for early diagnosis of cancer. Recently, we have developed a GLAD-PCR assay, a method for detecting the R(5mC)GY site in the genome position of interest even at significant excess of DNA molecules with a non-methylated RCGY site in this location. The aim of the present work is to use the GLAD-PCR assay to detect the aberrantly methylated R(5mC)GY sites in the regulatory regions of tumor suppressor genes (brinp1, bves, cacna2d3, cdh11, cpeb1, epha7, fgf2, galr1, gata4, hopx, hs3st2, irx1, lrrc3b, pcdh10, rprm, runx3, sfrp2, sox17, tcf21, tfpi2, wnt5a, zfp82, and znf331) in DNA samples obtained from gastric cancer (GC) tissues. The study of the DNA samples derived from 29 tumor and 25 normal gastric tissue samples demonstrated a high diagnostic potential of the selected RCGY sites in the regulatory regions of the irx1, cacna2d3, and epha7 genes; the total indices of sensitivity and specificity for GC detection being 96.6% and 100%, respectively.

Acta Naturae. 2020;12(3):124-133
pages 124-133 views

Synthesis and antiviral properties of 1-substituted 3-[ω-(4-oxoquinazolin-4(3h)-yl)alkyl]uracil derivatives

Paramonova M.P., Khandazhinskaya A.L., Ozerov A.A., Kochetkov S.N., Snoeck R., Andrei G., Novikov M.S.


А series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.

Acta Naturae. 2020;12(3):134-139
pages 134-139 views

Identification of a novel substrate-derived spermine oxidase inhibitor

Dunston T.T., Khomutov M.A., Gabelli S.B., Stewart T.M., Foley J.R., Kochetkov S.N., Khomutov A.R., Casero Jr. R.A.


Homeostasis of the biogenic polyamines spermine (Spm) and spermidine (Spd), present in μM-mM concentrations in all eukaryotic cells, is precisely regulated by coordinated activities of the enzymes of polyamine synthesis, degradation, and transport, in order to sustain normal cell growth and viability. Spermine oxidase (SMOX) is the key and most recently discovered enzyme of polyamine metabolism that plays an essential role in regulating polyamine homeostasis by catalyzing the back-conversion of Spm to Spd. The development of many types of epithelial cancer is associated with inflammation, and disease-related inflammatory stimuli induce SMOX. MDL72527 is widely used in vitro and in vivo as an irreversible inhibitor of SMOX, but it is also potent towards N1-acetylpolyamine oxidase. Although SMOX has high substrate specificity, Spm analogues have not been systematically studied as enzyme inhibitors. Here we demonstrate that 1,12-diamino-2,11-bis(methylidene)-4,9-diazadodecane (2,11-Met2-Spm) has, under standard assay conditions, an IC50 value of 169 μM towards SMOX and is an interesting instrument and lead compound for studying polyamine catabolism.

Acta Naturae. 2020;12(3):140-144
pages 140-144 views

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