Publications by authors named "Olga Ivanova"

120 Publications

CeO Nanoparticle-Containing Polymers for Biomedical Applications: A Review.

Polymers (Basel) 2021 Mar 17;13(6). Epub 2021 Mar 17.

Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, 119991 Moscow, Russia.

The development of advanced composite biomaterials combining the versatility and biodegradability of polymers and the unique characteristics of metal oxide nanoparticles unveils new horizons in emerging biomedical applications, including tissue regeneration, drug delivery and gene therapy, theranostics and medical imaging. Nanocrystalline cerium(IV) oxide, or nanoceria, stands out from a crowd of other metal oxides as being a truly unique material, showing great potential in biomedicine due to its low systemic toxicity and numerous beneficial effects on living systems. The combination of nanoceria with new generations of biomedical polymers, such as PolyHEMA (poly(2-hydroxyethyl methacrylate)-based hydrogels, electrospun nanofibrous polycaprolactone or natural-based chitosan or cellulose, helps to expand the prospective area of applications by facilitating their bioavailability and averting potential negative effects. This review describes recent advances in biomedical polymeric material practices, highlights up-to-the-minute cerium oxide nanoparticle applications, as well as polymer-nanoceria composites, and aims to address the question: how can nanoceria enhance the biomedical potential of modern polymeric materials?
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http://dx.doi.org/10.3390/polym13060924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002506PMC
March 2021

Integrated intra- and intercellular signaling knowledge for multicellular omics analysis.

Mol Syst Biol 2021 03;17(3):e9923

Faculty of Medicine and Heidelberg University Hospital, Institute of Computational Biomedicine, Heidelberg University, Heidelberg, Germany.

Molecular knowledge of biological processes is a cornerstone in omics data analysis. Applied to single-cell data, such analyses provide mechanistic insights into individual cells and their interactions. However, knowledge of intercellular communication is scarce, scattered across resources, and not linked to intracellular processes. To address this gap, we combined over 100 resources covering interactions and roles of proteins in inter- and intracellular signaling, as well as transcriptional and post-transcriptional regulation. We added protein complex information and annotations on function, localization, and role in diseases for each protein. The resource is available for human, and via homology translation for mouse and rat. The data are accessible via OmniPath's web service (https://omnipathdb.org/), a Cytoscape plug-in, and packages in R/Bioconductor and Python, providing access options for computational and experimental scientists. We created workflows with tutorials to facilitate the analysis of cell-cell interactions and affected downstream intracellular signaling processes. OmniPath provides a single access point to knowledge spanning intra- and intercellular processes for data analysis, as we demonstrate in applications studying SARS-CoV-2 infection and ulcerative colitis.
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http://dx.doi.org/10.15252/msb.20209923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983032PMC
March 2021

Thyroid doses in Ukraine due to I intake after the Chornobyl accident. Report I: revision of direct thyroid measurements.

Radiat Environ Biophys 2021 Mar 4. Epub 2021 Mar 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 9609 Medical Center Drive, Room 7E548 MSC 9778, Bethesda, MD, 20892-9778, USA.

The increased risk of thyroid cancer among individuals exposed during childhood and adolescence to Iodine-131 (I) is the main statistically significant long-term effect of the Chornobyl accident. Several radiation epidemiological studies have been carried out or are currently in progress in Ukraine, to assess the risk of radiation-related health effects in exposed populations. About 150,000 measurements of I thyroid activity, so-called 'direct thyroid measurements', performed in May-June 1986 in the Ukrainian population served as the main sources of data used to estimate thyroid doses to the individuals of these studies. However, limitations in the direct thyroid measurements have been recently recognized including improper measurement geometry and unknown true values of calibration coefficients for unchecked thyroid detectors. In the present study, a comparative analysis of I thyroid activity measured by calibrated and unchecked devices in residents of the same neighboring settlements was conducted to evaluate the correct measurement geometry and calibration coefficients for measuring devices. As a result, revised values of I thyroid activity were obtained. On average, in Vinnytsia, Kyiv, Lviv and Chernihiv Oblasts and in the city of Kyiv, the revised values of the I thyroid activities were found to be 10-25% higher than previously reported, while in Zhytomyr Oblast, the values of the revised activities were found to be lower by about 50%. New sources of shared and unshared errors associated with estimates of I thyroid activity were identified. The revised estimates of thyroid activity are recommended to be used to develop an updated Thyroid Dosimetry system (TD20) for the entire population of Ukraine as well as to revise the thyroid doses for the individuals included in post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort and the Chornobyl Tissue Bank.
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http://dx.doi.org/10.1007/s00411-021-00896-9DOI Listing
March 2021

Markers of muscle damage and strength performance in professional football (soccer) players during the competitive period.

Ann Transl Med 2021 Jan;9(2):113

Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Background: The present study investigated the impact of competitive soccer on the short-term changes in isometric strength of the adductor muscle group during the competitive season.

Methods: In this cohort study we evaluated the association between a serum marker of muscle damage [creatine phosphokinase (CPK)] and isometric strength of the adductor muscles of the hip in 30 professional football players (age: 26.7±2.9 years) during two seasons of the national top-level championship. Serum CPK level was determined the day before the match, 12-20, 36-48, 60-72 h after the match. The maximum voluntary isometric contraction force of the adductor muscles complex was determined immediately after having taken blood samples.

Results: There was evidence of a statistically significant positive association between age, body mass index (BMI), percentage of body fat, and muscle strength, and between weight and muscle strength. There was evidence of a statistically significant negative association between the level of CPK and the maximum isometric strength of the adductors of soccer players. Changes in CPK levels were associated with the muscle strength recovery trend (P<0.001). The strength/CPK ratio at different time points had a U-shaped curve.

Conclusions: Exercise induced muscle damage significantly affects the strength of the adductor muscle group of professional soccer players during the competitive period. The lower the CPK level, the greater the athletes' strength at a given time point. Also, the greater the decrease in CPK level, the greater the rate of strength restoration.
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http://dx.doi.org/10.21037/atm-20-2923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867942PMC
January 2021

Protic Ionic Liquid as Reagent, Catalyst, and Solvent: 1-Methylimidazolium Thiocyanate.

Angew Chem Int Ed Engl 2021 Mar 26;60(14):7927-7934. Epub 2021 Feb 26.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, 117997, Moscow, Russian Federation.

We propose a new concept of the triple role of protic ionic liquids with nucleophilic anions: a) a regenerable solvent, b) a Brønsted acid inducing diverse transformations via general acid catalysis, and c) a source of a nucleophile. The efficiency of this strategy was demonstrated using thiocyanate-based protic ionic liquids for the ring-opening of donor-acceptor cyclopropanes. A wide variety of activated cyclopropanes were found to react with 1-methylimidazolium thiocyanate under mild metal-free conditions via unusual nitrogen attack of the ambident thiocyanate ion on the electrophilic center of the three-membered ring affording pyrrolidine-2-thiones bearing donor and acceptor substituents at the C(5) and C(3) atoms, respectively, in a single time-efficient step. The ability of 1-methylimidazolium thiocyanate to serve as a triplex reagent was exemplarily illustrated by (4+2)-annulation with 1-acyl-2-(2-hydroxyphenyl)cyclopropane, epoxide ring-opening and other organic transformations.
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http://dx.doi.org/10.1002/anie.202016593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048580PMC
March 2021

Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes.

Cells 2020 12 4;9(12). Epub 2020 Dec 4.

Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, Russia.

Studies on the mechanisms of activation of cytotoxic lymphocyte subpopulations are an important research direction in modern immunology. This study provides a detailed analysis of the effect of Tag7 (PGRP-S, PGLYRP1) on the development of lymphocyte subpopulations cytotoxic against MHC-negative tumor cells in a pool of peripheral blood mononuclear cells (PBMCs). The results show that Tag7 can bind to the TREM-1 receptor on the surfaces of monocytes, thereby triggering the expression of mRNA TNFα and IFNγ. The appearance of these cytokines in conditioned medium leads to IL-2 cytokine secretion by CD3CD4 lymphocytes. In turn, IL-2 facilitates unspecific activation of three cytotoxic cell subpopulations in the PBMC pool: NK (CD16CD56), CD3CD4 and CD3CD8. These subpopulations appear after a certain period of incubation with Tag7 and show toxicity against tumor cells.
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http://dx.doi.org/10.3390/cells9122602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761954PMC
December 2020

Synthesis of (Het)aryl 2-(2-hydroxyaryl)cyclopropyl Ketones.

Molecules 2020 Dec 5;25(23). Epub 2020 Dec 5.

N. D. Zelinsky Institute of Organic Chemistry, Leninsky pr. 47, Moscow 119991, Russia.

A simple general method for the synthesis of 1-acyl-2-(-hydroxyaryl)cyclopropanes, which belong to the donor-acceptor cyclopropane family, has been developed. This method, based on the Corey-Chaykovsky cyclopropanation of 2-hydroxychalcones, allows for the preparation of a large diversity of hydroxy-substituted cyclopropanes, which can serve as promising building blocks for the synthesis of various bioactive compounds.
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http://dx.doi.org/10.3390/molecules25235748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729819PMC
December 2020

Antimicrobial resistance of commensal from food-producing animals in Russia.

Vet World 2020 Oct 2;13(10):2053-2061. Epub 2020 Oct 2.

Department of Biotechnology, Russian State Center for Animal Feed and Drug Standardization and Quality, Zvenigorodskoe Highway, Russia.

Background And Aim: Commensal is an important indicator of antimicrobial resistance (AMR) in animals and food of animal origin. Therefore, it was recommended by the World Health Organization and OIE for inclusion in resistance surveillance programs. At the same time, the data on isolates from animals in Russia are scarce. The aim of this work was to determine the current prevalence of resistance and genetic markers of non-pathogenic commensal collected from major food-producing animals (poultry, pigs, and cows) in different regions of Russia and to compare these data with data from other countries to prioritize antimicrobials for limiting their use according to the National Action Plan.

Materials And Methods: Samples (n=306) were collected from biomaterial of chicken, turkey, cows, and pigs raised on 11 farms in the European part of Russia, Siberia, and North Caucasus. Isolates (n=306) of were tested for resistance to 11 antimicrobials from ten classes using the broth microdilution method. MICs were interpreted against EUCAST microbiological and clinical breakpoints. For data analysis and statistical processing, the AMRcloud online platform was used. The data are presented in comparison with other countries.

Results: In Russia, higher levels of microbiological and clinical resistance of to critically important antimicrobials, including colistin, cefotaxime, and ciprofloxacin, were found compared to other countries, especially in poultry: About 30% of isolates from chicken were resistant to colistin, 8% to cefotaxime, and 88% to ciprofloxacin according to EUCAST ECOFFs. Only 10% of isolates from cows were resistant to cefotaxime. About 47% of isolates of from chicken had a moderate relative resistance for ampicillin and 56% for tetracycline. For most antimicrobials, isolates from cows demonstrated a lower resistance than isolates from poultry and pigs. All tested isolates from chicken, turkey, and pigs showed a simultaneous microbiological resistance to at least three classes of antimicrobials. No pan-resistant isolates were found.

Conclusion: High levels of AMR of commensal from poultry, especially for critically important drugs, are a matter of concern and should be taken into account when choosing antimicrobials to be restricted for use in animal husbandry according to the National Action Plan.
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http://dx.doi.org/10.14202/vetworld.2020.2053-2061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704320PMC
October 2020

Identification of novel variants in the gene in Russian patients with familial hypercholesterolemia using targeted sequencing.

Biomed Rep 2021 Jan 17;14(1):15. Epub 2020 Nov 17.

Genetic Laboratory of City Hospital No. 40, Saint-Petersburg, 197706, Russian Federation.

Familial hypercholesterolemia (FH) is caused by mutations in various genes, including the , and genes; however, the spectrum of these mutations in Russian individuals has not been fully investigated. In the present study, mutation screening was performed on the gene and other FH-associated genes in patients with definite or possible FH, using next-generation sequencing. In total, 59 unrelated patients were recruited and sorted into two separate groups depending on their age: Adult (n=31; median age, 49; age range, 23-70) and children/adolescent (n=28; median age, 11; age range, 2-21). FH-associated variants were identified in 18 adults and 25 children, demonstrating mutation detection rates of 58 and 89% for the adult and children/adolescent groups, respectively. In the adult group, 13 patients had FH-associated mutations in the gene, including two novel variants [NM_000527.4: c.433_434dupG p.(Val145Glyfs*35) and c.1186G>C p.(Gly396Arg)], 3 patients had mutations and two had mutations. In the children/adolescent group, 21 patients had FH-causing mutations in the gene, including five novel variants [NM_000527.4: c.325T>G p.(Cys109Gly), c.401G>C p.(Cys134Ser), c.616A>C p.(Ser206Arg), c.1684_1691delTGGCCCAA p.(Pro563Hisfs*14) and c.940+1_c.940+4delGTGA], and 2 patients had mutations, as well as and mutations, being found in different patients. The present study reported seven novel variants considered to be pathogenic or likely pathogenic. Among them, four missense variants were located in the coding regions, which corresponded to functional protein domains, and two frameshifts were identified that produced truncated proteins. These variants were observed only once in different patients, whereas a splicing variant in intron 6 (c.940+1_c.940+4delGTGA) was detected in four unrelated individuals. Previously reported variants in the and genes were observed in 33 patients. The p.(Gly592Glu) variant was detected in 6 patients, representing 10% of the FH cases reported in the present study, thus it may be a major variant present in the Russian population. In conclusion, the present study identified seven novel variants of the gene and broadens the spectrum of mutations in FH-related genes in the Russian Federation.
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http://dx.doi.org/10.3892/br.2020.1391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694592PMC
January 2021

New Insights into Therapy-Induced Progression of Cancer.

Int J Mol Sci 2020 Oct 23;21(21). Epub 2020 Oct 23.

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.

The malignant tumor is a complex heterogeneous set of cells functioning in a no less heterogeneous microenvironment. Like any dynamic system, cancerous tumors evolve and undergo changes in response to external influences, including therapy. Initially, most tumors are susceptible to treatment. However, remaining cancer cells may rapidly reestablish the tumor after a temporary remission. These new populations of malignant cells usually have increased resistance not only to the first-line agent, but also to the second- and third-line drugs, leading to a significant decrease in patient survival. Multiple studies describe the mechanism of acquired therapy resistance. In past decades, it became clear that, in addition to the simple selection of pre-existing resistant clones, therapy induces a highly complicated and tightly regulated molecular response that allows tumors to adapt to current and even subsequent therapeutic interventions. This review summarizes mechanisms of acquired resistance, such as secondary genetic alterations, impaired function of drug transporters, and autophagy. Moreover, we describe less obvious molecular aspects of therapy resistance in cancers, including epithelial-to-mesenchymal transition, cell cycle alterations, and the role of intercellular communication. Understanding these molecular mechanisms will be beneficial in finding novel therapeutic approaches for cancer therapy.
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http://dx.doi.org/10.3390/ijms21217872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660620PMC
October 2020

Case of Poliomyelitis Caused by Significantly Diverged Derivative of the Poliovirus Type 3 Vaccine Sabin Strain Circulating in the Orphanage.

Viruses 2020 09 1;12(9). Epub 2020 Sep 1.

Federal State Budgetary Scientific Institution "Chumakov Federal Scientific Centre for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences" (FSBSI "Chumakov FSC R&D IBP RAS"), 108819 Moscow, Russia.

Significantly divergent polioviruses (VDPV) derived from the oral poliovirus vaccine (OPV) from Sabin strains, like wild polioviruses, are capable of prolonged transmission and neuropathology. This is mainly shown for VDPV type 2. Here we describe a molecular-epidemiological investigation of a case of VDPV type 3 circulation leading to paralytic poliomyelitis in a child in an orphanage, where OPV has not been used. Samples of feces and blood serum from the patient and 52 contacts from the same orphanage were collected twice and investigated. The complete genome sequencing was performed for five polioviruses isolated from the patient and three contact children. The level of divergence of the genomes of the isolates corresponded to approximately 9-10 months of evolution. The presence of 61 common substitutions in all isolates indicated a common intermediate progenitor. The possibility of VDPV3 transmission from the excretor to susceptible recipients (unvaccinated against polio or vaccinated with inactivated poliovirus vaccine, IPV) with subsequent circulation in a closed children's group was demonstrated. The study of the blood sera of orphanage residents at least twice vaccinated with IPV revealed the absence of neutralizing antibodies against at least two poliovirus serotypes in almost 20% of children. Therefore, a complete rejection of OPV vaccination can lead to a critical decrease in collective immunity level. The development of new poliovirus vaccines that create mucosal immunity for the adequate replacement of OPV from Sabin strains is necessary.
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http://dx.doi.org/10.3390/v12090970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552002PMC
September 2020

Aseptic meningitis outbreak associated with echovirus 4 in Northern Europe in 2013-2014.

J Clin Virol 2020 08 7;129:104535. Epub 2020 Jul 7.

University of Helsinki and Helsinki University Hospital, Virology and Immunology, Helsinki, Finland. Electronic address:

Picornaviruses (family Picornaviridae) are small, nonenveloped, positive-sense, single-stranded RNA viruses. The members of this family are currently classified into 47 genera and 110 species. Of picornaviruses, entero- and parechoviruses are associated with aseptic meningitis. They are transmitted via fecal-oral and respiratory routes, and occasionally, these viruses may cause a brief viremia and gain access to central nervous system (CNS). During the diagnostic screening of entero- and parechovirus types in Finland in year 2013-14, we detected a cluster of echovirus 4 (E4) infections in young adults and adolescents. As E4 is infrequently detected in Finland, we contacted several Northern and Central European laboratories that conduct routine surveillance for enteroviruses and, for those who have had E4 cases, we send a query for E4 sequences and data. Here we report CNS infections caused by E4 in Finland, Sweden, Norway, Denmark, Iceland and Germany in 2013 and 2014, and show that the E4 detected in these countries form a single lineage. In contrast, E4 strains circulating in these countries preceding the year 2013, and those circulating elsewhere in Europe during 2013-2014, formed several independent clusters.
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http://dx.doi.org/10.1016/j.jcv.2020.104535DOI Listing
August 2020

Mitochondria-targeted 1,4-naphthoquinone (SkQN) is a powerful prooxidant and cytotoxic agent.

Biochim Biophys Acta Bioenerg 2020 08 17;1861(8):148210. Epub 2020 Apr 17.

A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russian Federation. Electronic address:

An increase in the production of reactive oxygen species (ROS) in mitochondria due to targeted delivery of redox active compounds may be useful in studies of modulation of cell functions by mitochondrial ROS. Recently, the mitochondria-targeted derivative of menadione (MitoK) was synthesized. However, MitoK did not induce mitochondrial ROS production and lipid peroxidation while exerting significant cytotoxic action. Here we synthesized 1,4-naphthoquinone conjugated with alkyltriphenylphosphonium (SkQN) as a prototype of mitochondria-targeted prooxidant, and its redox properties, interactions with isolated mitochondria, yeast cells and various human cell lines were investigated. According to electrochemical measurements, SkQN was more active redox agent and, due to the absence of methyl group in the naphthoquinone ring, more reactive as electrophile than MitoK. SkQN (but not MitoK) stimulated hydrogen peroxide production in isolated mitochondria. At low concentrations, SkQN stimulated state 4 respiration in mitochondria, decreased membrane potential, and blocked ATP synthesis, being more efficient uncoupler of oxidative phosphorylation than MitoK. In yeast cells, SkQN decreased cell viability and induced oxidative stress and mitochondrial fragmentation. SkQN killed various tumor cells much more efficiently than MitoK. Since many tumors are characterized by increased oxidative stress, the use of new mitochondria-targeted prooxidants may be a promising strategy for anticancer therapy.
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http://dx.doi.org/10.1016/j.bbabio.2020.148210DOI Listing
August 2020

A 12-mer Peptide of Tag7 (PGLYRP1) Forms a Cytotoxic Complex with Hsp70 and Inhibits TNF-Alpha Induced Cell Death.

Cells 2020 02 20;9(2). Epub 2020 Feb 20.

Laboratory of Molecular immunogenetics of cancer, Institute of gene biology RAS, Vavilova 34/5, 111394 Moscow, Russia.

Investigation of interactions between a pro-inflammatory cytokine tumor necrosis factor (TNFα) and its receptor is required for the development of new treatments for autoimmune diseases associated with the adverse effects of TNFα. Earlier, we demonstrated that the innate immunity protein Tag7 (PGRP-S, PGLYRP1) can interact with the TNFα receptor, TNFR1, and block the transduction of apoptotic signals through this receptor. A complex formed between the Tag7 protein and the major heat shock protein Hsp70 can activate TNFR1 receptor and induce tumor cell death via either apoptotic or necroptotic pathway. In this study, we show that a 12-mer peptide, designated 17.1, which was derived from the Tag7 protein, can be regarded as a novel TNFα inhibitor, also is able to form a cytotoxic complex with the heat shock protein Hsp70. This finding demonstrates a new role for Hsp70 protein in the immune response. Also, this new inhibitory 17.1 peptide demonstrates an anti-inflammatory activity in the complete Freund's adjuvant (CFA)-induced autoimmune arthritis model in laboratory mice. It appears that the 17.1 peptide could potentially be used as an anti-inflammatory agent.
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http://dx.doi.org/10.3390/cells9020488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072780PMC
February 2020

Mega-plasmid found worldwide confers multiple antimicrobial resistance in Salmonella Infantis of broiler origin in Russia.

Int J Food Microbiol 2020 Apr 26;319:108497. Epub 2019 Dec 26.

The Russian State Center for Animal Feed and Drug Standardization and Quality (FGBU "VGNKI"), Zvenigorodskoe shosse 5, Moscow 132022, Russia.

Plasmids which are the mobile part of the bacterial genome can acquire and carry over genes conferring antimicrobial resistance, thus contributing to rapid adaptation of bacterial community to human-defined environment. In 2014, Israeli scientists have reported a large conjugative mega-plasmid pESI (plasmid for emerging S. Infantis) that provides multiple drug resistance (MDR) of Salmonella Infantis isolated from broilers. Later, very similar pESI-like plasmids have been found in Salmonella isolated from poultry in the United States, Italy, Switzerland, Hungary, and Japan. Here we report detection of pESI-like plasmids in Salmonella Infantis isolated from chicken food products in Russia. Whole genome sequencing of three MDR isolates revealed pESI-like plasmids in all three cases. These plasmids have such typical pESI features as a locus for siderophore yersiniabactin, a cluster of IncI1 conjugative genes, a cluster of type IV pilus genes, and three toxin-antitoxin modules. The pESI-like plasmids carry from two to five resistance genes in each isolate. In total, we observed six antimicrobial resistance genes associated with pESI-like plasmids (aadA1, bla, dfrA14, sul1, tetA/tetR, tetM). Besides plasmid genes of antimicrobial resistance, all three MDR isolates of S. Infantis harbor a mutation in chromosomal gene gyrA (p.S83Y or p.D87Y) that is associated with resistance to fluoroquinolones. In addition, we performed a comparative bioinformatics meta-analysis of 25 pESI-like plasmids hosted by S. Infantis from the USA, Europe, Latin America, Israel, and Japan. This analysis identified a 173 kB sequence that is common for all pESI-like plasmids and carries virulence operons and toxin-antitoxin modules.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2019.108497DOI Listing
April 2020

PVP-stabilized tungsten oxide nanoparticles: pH sensitive anti-cancer platform with high cytotoxicity.

Mater Sci Eng C Mater Biol Appl 2020 Mar 26;108:110494. Epub 2019 Nov 26.

Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia; National Research Tomsk State University, Tomsk 634050, Russia. Electronic address:

Photochromic tungsten oxide (WO) nanoparticles stabilized by polyvinylpyrrolidone (PVP) were synthesized to evaluate their potential for biomedical applications. PVP-stabilized tungsten oxide nanoparticles demonstrated a highly selective cytotoxic effect on normal and cancer cells in vitro. WO nanoparticles were found to induce substantial cell death in osteosarcoma cells (MNNG/HOS cell line) with a half-maximal inhibitory concentration (IC50) of 5 mg/mL, while producing no, or only minor, toxicity in healthy human mesenchymal stem cells (hMSc). WO nanoparticles induced intracellular oxidative stress, which led to apoptosis type cell death. The selective anti-cancer effects of WO nanoparticles are due to the pH sensitivity of tungsten oxide and its capability of reactive oxygen species (ROS) generation, which is expressed in the modulation of genes involved in reactive oxygen species metabolism, mitochondrial dysfunction, and apoptosis.
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http://dx.doi.org/10.1016/j.msec.2019.110494DOI Listing
March 2020

Photochromic and Photocatalytic Properties of Ultra-Small PVP-Stabilized WO Nanoparticles.

Molecules 2019 Dec 30;25(1). Epub 2019 Dec 30.

Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, 31 Leninsky av., 119991 Moscow, Russia.

Tungsten oxide-based bulk and nanocrystalline materials are widely used as photocatalytic and photo- and electrochromic materials, as well as materials for biomedical applications. In our work, we focused our attention on the effect of sodium cations on the structure and photochromic properties of the WO@PVP aqueous sols. To establish the effect, the sols were synthesized by either simple pH adjusting of sodium or ammonium tungstates' solutions, or using an ion exchange technique to remove the cations from the materials to the greatest possible extent. We showed that the presence of sodium cations in WO@PVP favors the formation of reduced tungsten species (W) upon UV irradiation of the materials, strongly affecting their photochromic and photocatalytic properties. The pronounced photoreductive properties of WO@PVP sols in photocatalytic reactions were demonstrated. Due to photoreductive properties, photochromic sols of tungsten oxide can act as effective photoprotectors in photooxidation processes. We believe that our work provides a considerable contribution to the elucidation of photochromic and redox phenomena in WO-based materials.
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http://dx.doi.org/10.3390/molecules25010154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982781PMC
December 2019

HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist.

Oxid Med Cell Longev 2019 2;2019:6016278. Epub 2019 Dec 2.

NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.

HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of "non-AIDS-defining" malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. In tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression of and . These properties, particularly, the expression of , correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A and . No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression.
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http://dx.doi.org/10.1155/2019/6016278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915010PMC
June 2020

A framework for exhaustive modelling of genetic interaction patterns using Petri nets.

Bioinformatics 2020 04;36(7):2142-2149

Department of Computer Science, Centre for Integrative Bioinformatics (IBIVU), Vrije Universiteit Amsterdam, 1081 HV Amsterdam, Netherlands.

Motivation: Genetic interaction (GI) patterns are characterized by the phenotypes of interacting single and double mutated gene pairs. Uncovering the regulatory mechanisms of GIs would provide a better understanding of their role in biological processes, diseases and drug response. Computational analyses can provide insights into the underpinning mechanisms of GIs.

Results: In this study, we present a framework for exhaustive modelling of GI patterns using Petri nets (PN). Four-node models were defined and generated on three levels with restrictions, to enable an exhaustive approach. Simulations suggest ∼5 million models of GIs. Generalizing these we propose putative mechanisms for the GI patterns, inversion and suppression. We demonstrate that exhaustive PN modelling enables reasoning about mechanisms of GIs when only the phenotypes of gene pairs are known. The framework can be applied to other GI or genetic regulatory datasets.

Availability And Implementation: The framework is available at http://www.ibi.vu.nl/programs/ExhMod.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btz917DOI Listing
April 2020

Ring Opening of Donor-Acceptor Cyclopropanes with Cyanide Ion and Its Surrogates.

J Org Chem 2020 01 19;85(2):1146-1157. Epub 2019 Dec 19.

Department of Chemistry , M. V. Lomonosov Moscow State University , Leninskie gory 1-3 , Moscow 119991 , Russian Federation.

A straightforward method for ring opening of donor-acceptor cyclopropanes with trimethylsilyl cyanide as a surrogate of cyanide ion in the presence of B(CF) or trifluoromethanesulfonic acid as a catalyst has been developed. The methodology provides a short route to γ-cyanoesters that can be useful synthetic intermediates for the synthesis of diverse bioactive molecules such as glutaric and δ-aminovaleric acid derivatives, 3-arylpiperidines, or other substituted phenethylamines. Oppositely, the attempts to synthesize these γ-cyanoesters by direct reaction of cyclopropanes with sodium cyanide under typical S2 conditions led to the formation of 2-arylsuccinonitriles.
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http://dx.doi.org/10.1021/acs.joc.9b03098DOI Listing
January 2020

Electrochemical Properties of Carbon Aerogel Electrodes: Dependence on Synthesis Temperature.

Molecules 2019 Oct 25;24(21). Epub 2019 Oct 25.

Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severnij pr., Chernogolovka 142432, Russia.

A series of carbon aerogels (C-AGs) were prepared by the pyrolysis of resorcinol-formaldehyde aerogels at 700-1100 °C as potential supercapacitor electrodes, and their texture and electrochemical properties were determined. The specific surface area of all C-AGs was in the range of 700-760 m/g, their electron conductivity increased linearly from 0.4 to 4.46 S/cm with an increase of the pyrolysis temperature. The specific capacitance of electrode material based on C-AGs reached 100 F/g in sulfuric acid and could be realized at a 2 A/g charge-discharge current, which makes it possible to use carbon aerogels as electrode materials.
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http://dx.doi.org/10.3390/molecules24213847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864835PMC
October 2019

Hepatitis C Virus RNA-Dependent RNA Polymerase Is Regulated by Cysteine S-Glutathionylation.

Oxid Med Cell Longev 2019 3;2019:3196140. Epub 2019 Sep 3.

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Hepatitis C virus (HCV) triggers massive production of reactive oxygen species (ROS) and affects expression of genes encoding ROS-scavenging enzymes. Multiple lines of evidence show that levels of ROS production contribute to the development of various virus-associated pathologies. However, investigation of HCV redox biology so far remained in the paradigm of oxidative stress, whereas no attention was given to the identification of redox switches among viral proteins. Here, we report that one of such redox switches is the NS5B protein that exhibits RNA-dependent RNA polymerase (RdRp) activity. Treatment of the recombinant protein with reducing agents significantly increases its enzymatic activity. Moreover, we show that the NS5B protein is subjected to S-glutathionylation that affects cysteine residues 89, 140, 170, 223, 274, 521, and either 279 or 295. Substitution of these cysteines except C89 and C223 with serine residues led to the reduction of the RdRp activity of the recombinant protein in a primer-dependent assay. The recombinant protein with a C279S mutation was almost inactive in vitro and could not be activated with reducing agents. In contrast, cysteine substitutions in the NS5B region in the context of a subgenomic replicon displayed opposite effects: most of the mutations enhanced HCV replication. This difference may be explained by the deleterious effect of oxidation of NS5B cysteine residues in liver cells and by the protective role of S-glutathionylation. Based on these data, redox-sensitive posttranslational modifications of HCV NS5B and other proteins merit a more detailed investigation and analysis of their role(s) in the virus life cycle and associated pathogenesis.
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http://dx.doi.org/10.1155/2019/3196140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800943PMC
March 2020

Surfactant-Switched Positive/Negative Electrorheological Effect in Tungsten Oxide Suspensions.

Molecules 2019 Sep 14;24(18). Epub 2019 Sep 14.

Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Moscow 119991, Russia.

The electrorheological (ER) effect was experimentally observed in dielectric suspensions containing tungsten oxide (WO) modified with surfactant molecules (sodium dodecyl sulfate (SDS) and dodecylamine (DDA)) in electric fields up to several kilovolts per millimeter. The dielectric properties of WO suspensions in silicone oil were analyzed, depending on the frequency of the electric field, in the range from 25 to 10 Hz. Unmodified WO suspensions, as well as suspensions modified with sodium dodecyl sulfate, were shown to exhibit a positive electrorheological effect, whereas suspensions modified with dodecylamine demonstrated a negative electrorheological effect. The quantitative characteristics of the negative electrorheological effect in the strain-compression and shear regimes were obtained for the first time. Visualization experiments were performed to see the chain structures formed by WO particles modified with sodium dodecyl sulfate, as well as for dynamic electroconvection in electrorheological fluids containing WO modified with dodecylamine. The negative electrorheological effect was shown to be associated with the processes of phase separation in the electric field, which led to a multiplicative effect and a strong electroconvection of the suspension at field strengths above 1 kV/mm.
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http://dx.doi.org/10.3390/molecules24183348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767292PMC
September 2019

The first inorganic mitogens: Cerium oxide and cerium fluoride nanoparticles stimulate planarian regeneration via neoblastic activation.

Mater Sci Eng C Mater Biol Appl 2019 Nov 27;104:109924. Epub 2019 Jun 27.

Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia; Lomonosov Moscow State University, Moscow, Russia. Electronic address:

We report the first experimental evidence for the mitogenic action of cerium(IV) oxide and cerium(III) fluoride nanoparticles (CONs and CFNs) on the regeneration of a whole organism - freshwater flatworms Schmidtea mediterranea (planarian). Both types of cerium-containing nanoparticles are shown to be a highly potent mitogen for planaria. Both CONs and CFNs, in micro- and nanomolar concentrations, markedly accelerate planarian blastema growth, due to the enhancement of cellular proliferation, causing an increase in the mitotic index and in the quantity of blastema cells in regenerating planaria. CONs provided maximum activity at concentrations which were two orders of magnitude lower than those for CeF. The valence state of cerium in cerium-containing nanoparticles plays a significant role in the planarian regeneration mechanism: CeO nanoparticles containing predominantly Ce species presumably scavenge wound induced reactive oxygen species and moderately activate gene expression processes, while the regenerative action of CeF nanoparticles containing only Ce species is manifested in the pronounced expression of the genes involved in cell division, differentiation and migration. This is the first report on the effect of cerium-containing nanoparticles on tissue regeneration in vivo, further revealing the mechanisms of their biological action, which enhances the possibility of their use in cellular technologies.
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http://dx.doi.org/10.1016/j.msec.2019.109924DOI Listing
November 2019

Investigating 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole as scaffold of butyrylcholinesterase-selective inhibitors with additional neuroprotective activities for Alzheimer's disease.

Eur J Med Chem 2019 Sep 28;177:414-424. Epub 2019 May 28.

Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy.

Due to the role of butyrylcholinesterase (BChE) in acetylcholine hydrolysis in the late stages of the Alzheimer's disease (AD), inhibitors of butyrylcholinesterase (BChE) have been recently envisaged, besides acetylcholinesterase (AChE) inhibitors, as candidates for treating mild-to-moderate AD. Herein, synthesis and AChE/BChE inhibition activity of some twenty derivatives of 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole (HHAI) is reported. Most of the newly synthesized HHAI derivatives achieved the inhibition of both ChE isoforms with ICs in the micromolar range, with a structure-dependent selectivity toward BChE. Apparently, molecular volume and lipophilicity do increase selectivity toward BChE, and indeed the N-(4-phenylbutyl) HHAI derivative 15d, which behaves as a mixed-type inhibitor, resulted the most potent (IC 0.17 μM) and selective (>100-fold) inhibitor toward either horse serum and human BChE. Moreover, 15d inhibited in vitro self-induced aggregation of neurotoxic amyloid-β (Aβ) peptide and displayed neuroprotective effects in neuroblastoma SH-SY5Y cell line, significantly recovering (P < 0.001) cell viability when impaired by Aβ and hydrogen peroxide insults. Overall, this study highlighted HHAI as useful and versatile scaffold for developing new small molecules targeting some enzymes and biochemical pathways involved in the pathogenesis of AD.
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http://dx.doi.org/10.1016/j.ejmech.2019.05.062DOI Listing
September 2019

Behavioural risk factors of arterial hypertension in the Evenk population of the Russian Arctic.

Int J Circumpolar Health 2019 12;78(1):1611329

a M.K. Ammosov North-Eastern Federal University , Yakutsk , Russia.

The urgency of the problem under study is determined by the high prevalence of arterial hypertension among the indigenous minorities of the North in modern socio-economic conditions. The following article is aimed to evaluate the prevalence of behavioural arterial hypertension risk factors according to the results of single-step epidemiological research of Evenk people in the Republic of Sakha (Yakutia), Russian Federation. The leading approach to the study of this problem was the questioning of the population using the international questionnaire for behavioural risk factors (CYNDI). As a result of research, widespread smoking was found among native population (52.0% of men and 23.7% of women). The frequency of alcohol consumption among the male Evenki is comparable to that in the Yakut population, and among the female, the number is much lower. Evenks including young men belong to the physically inactive population. The frequency of arterial hypertension (AH) cases along with the factors listed above are significantly influenced by: marital status, employment, education, and housing conditions. Article materials may be useful for a differentiated approach in the development of prevention and rehabilitation programs for the indigenous peoples of the North.
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http://dx.doi.org/10.1080/22423982.2019.1611329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534235PMC
December 2019

Multirecombinant Enterovirus A71 Subgenogroup C1 Isolates Associated with Neurologic Disease, France, 2016-2017.

Emerg Infect Dis 2019 06;25(6):1204-1208

In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children.
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http://dx.doi.org/10.3201/eid2506.181460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537711PMC
June 2019

The ability of transcription factors to differentially regulate gene expression is a crucial component of the mechanism underlying inversion, a frequently observed genetic interaction pattern.

PLoS Comput Biol 2019 05 13;15(5):e1007061. Epub 2019 May 13.

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.

Genetic interactions, a phenomenon whereby combinations of mutations lead to unexpected effects, reflect how cellular processes are wired and play an important role in complex genetic diseases. Understanding the molecular basis of genetic interactions is crucial for deciphering pathway organization as well as understanding the relationship between genetic variation and disease. Several hypothetical molecular mechanisms have been linked to different genetic interaction types. However, differences in genetic interaction patterns and their underlying mechanisms have not yet been compared systematically between different functional gene classes. Here, differences in the occurrence and types of genetic interactions are compared for two classes, gene-specific transcription factors (GSTFs) and signaling genes (kinases and phosphatases). Genome-wide gene expression data for 63 single and double deletion mutants in baker's yeast reveals that the two most common genetic interaction patterns are buffering and inversion. Buffering is typically associated with redundancy and is well understood. In inversion, genes show opposite behavior in the double mutant compared to the corresponding single mutants. The underlying mechanism is poorly understood. Although both classes show buffering and inversion patterns, the prevalence of inversion is much stronger in GSTFs. To decipher potential mechanisms, a Petri Net modeling approach was employed, where genes are represented as nodes and relationships between genes as edges. This allowed over 9 million possible three and four node models to be exhaustively enumerated. The models show that a quantitative difference in interaction strength is a strict requirement for obtaining inversion. In addition, this difference is frequently accompanied with a second gene that shows buffering. Taken together, these results provide a mechanistic explanation for inversion. Furthermore, the ability of transcription factors to differentially regulate expression of their targets provides a likely explanation why inversion is more prevalent for GSTFs compared to kinases and phosphatases.
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http://dx.doi.org/10.1371/journal.pcbi.1007061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532943PMC
May 2019

Environmental Surveillance for Poliovirus and Other Enteroviruses: Long-Term Experience in Moscow, Russian Federation, 2004⁻2017.

Viruses 2019 05 8;11(5). Epub 2019 May 8.

Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

Polio and enterovirus surveillance may include a number of approaches, including incidence-based observation, a sentinel physician system, environmental monitoring and acute flaccid paralysis (AFP) surveillance. The relative value of these methods is widely debated. Here we summarized the results of 14 years of environmental surveillance at four sewage treatment plants of various capacities in Moscow, Russia. A total of 5450 samples were screened, yielding 1089 (20.0%) positive samples. There were 1168 viruses isolated including types 1-3 polioviruses (43%) and 29 different types of non-polio enteroviruses (51%). Despite using the same methodology, a significant variation in detection rates was observed between the treatment plants and within the same facility over time. The number of poliovirus isolates obtained from sewage was roughly 60 times higher than from AFP surveillance over the same time frame. All except one poliovirus isolate were Sabin-like polioviruses. The one isolate was vaccine-derived poliovirus type 2 with 17.6% difference from the corresponding Sabin strain, suggesting long-term circulation outside the scope of the surveillance. For some non-polio enterovirus types (e.g., Echovirus 6) there was a good correlation between detection in sewage and incidence of clinical cases in a given year, while other types (e.g., Echovirus 30) could cause large outbreaks and be almost absent in sewage samples. Therefore, sewage monitoring can be an important part of enterovirus surveillance, but cannot substitute other approaches.
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http://dx.doi.org/10.3390/v11050424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563241PMC
May 2019