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Kashtanova D.,Russian National Research Medical University | Tkacheva O.,Russian National Research Medical University | Popenko A.,Institute for Physical Chemical Medicine | Egshatyan L.,Federal State Budgetary Establishment Endocrinology Research Center | And 5 more authors.
Artery Research | Year: 2017

The aim of this research was to study the association between the gut microbiota composition and arterial wall properties. The study included 92 participants, men and women aged 25–76 years old without clinical manifestation of chronic diseases but with the possible presence of cardiovascular risk factors. Carbohydrate metabolism examination, duplex scanning of the carotid arteries with the measurement of the intima-media thickness (IMT), the carotid-femoral pulse wave velocity (PWV) measurement, and 16S rRNA (V3[sbnd]V4 regions) sequencing of the gut microbiota were performed in all participants. Higher Serratia abundance was associated with the increased IMT and CRP levels. Blautia representation was associated with IMT. Higher Bacteroides representation was associated with higher pulse wave velocity in non-diabetic subjects. Although this study had some limitations, we have demonstrated that the composition of the gut microbiota was associated both with atherosclerotic and arterial stiffness markers. © 2017 Association for Research into Arterial Structure and Physiology


Beniaminov A.D.,RAS Engelhardt Institute of Molecular Biology | Novikov R.A.,RAS Engelhardt Institute of Molecular Biology | Mamaeva O.K.,RAS Engelhardt Institute of Molecular Biology | Mitkevich V.A.,RAS Engelhardt Institute of Molecular Biology | And 4 more authors.
Nucleic Acids Research | Year: 2016

Structure-specific ligands are convenient tools for the recognition, targeting or probing of noncanonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(Ncarboxymethyl-4-pyridinium)porphyrin (ZnP1) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)3) at submicromolar concentrations without any detectible disturbance of the particular fold. Among different folds, potassium (3+1) hybrid G4-structure. reveal the highest affinity to ZnP1. The pattern of guanine oxidation is specific for each telomeric DNA conformation and may serve as an additional tool for probing the G4 topology. The potassium (3+1) and parallel G4 conformations are more susceptible to light-induced oxidation than the sodium G4 conformation or double helix of the telomeric DNA. The major products of the guanine modifications are spiroiminodihydantoin (Sp) and 8-oxoguanine (8-oxoG). ZnP1-induced oxidation of guanines results in the structural rearrangement of parallel and (3+1) G4 conformations yielding an antiparallel-like G4 conformation. The mechanism of the observed light-induced conformational changes is discussed. © 2016 The Author(s).


Kostyuk V.A.,Instituto Dermopatico dellImmacolata IDI IRCCS | Kostyuk V.A.,Belarusian State University | Potapovich A.I.,Instituto Dermopatico dellImmacolata IDI IRCCS | Potapovich A.I.,Belarusian State University | And 12 more authors.
Antioxidants and Redox Signaling | Year: 2010

Oxidative stress due to increased epidermal levels of H2O 2 with consequent inhibition of catalase activity is generally accepted as a leading cytotoxic mechanism of melanocyte loss in vitiligo. Keratinocyte-derived cytokines are considered key factors in the maintenance of melanocyte structure and functions. We hypothesized that abnormal redox control may lead to impaired cytokine production by keratinocytes, thus causing noncytotoxic defects in melanocyte proliferation and melanogenesis. We found significantly suppressed mRNA and protein expression of glutathione-S- transferase (GST) M1 isoform, and higher-than-normal levels of both 4-hydroxy-2-nonenal (HNE)-protein adducts and H2O2 in the cultures of keratinocytes derived from unaffected and affected skin of vitiligo patients, and in their co-cultures with allogeneic melanocytes. GST and catalase activities, as well as glutathione levels, were dramatically low in erythrocytes, whilst HNE-protein adducts were high in the plasma of vitiligo patients. The broad spectrum of major cytokines, chemokines, and growth factors was dysregulated in both blood plasma and cultured keratinocytes of vitiligo patients, when compared to normal subjects. Exogenous HNE added to normal keratinocytes induced a vitiligo-like cytokine pattern, and H2O 2 overproduction accompanied by adaptive upregulation of catalase and GSTM1 genes, and transient inhibition of Erk1/2 and Akt phosphorylation. Based on these results, we suggest a novel GST-HNE-H2O2-based mechanism of dysregulation of cytokine-mediated keratinocyte-melanocyte interaction in vitiligo. © 2010 Mary Ann Liebert, Inc.


Tatarinova O.,Institute for Physical Chemical Medicine | Tsvetkov V.,RAS Topchiev Institute of Petrochemical Synthesis | Basmanov D.,Institute for Physical Chemical Medicine | Barinov N.,Institute for Physical Chemical Medicine | And 7 more authors.
PLoS ONE | Year: 2014

Noncanonically structured DNA aptamers to thrombin were examined. Two different approaches were used to improve stability, binding affinity and biological activity of a known thrombin-binding aptamer. These approaches are chemical modification and the addition of a duplex module to the aptamer core structure. Several chemically modified aptamers and the duplex-bearing ones were all studied under the same conditions by a set of widely known and some relatively new methods. A number of the thrombin-binding aptamer analogs have demonstrated improved characteristics. Most importantly, the study allowed us to compare directly the two approaches to aptamer optimization and to analyze their relative advantages and disadvantages as well as their potential in drug design and fundamental studies. © 2014 Tatarinova et al.


Shevchenko O.V.,Smolensk State Medical Academy | Mudrak D.Y.,Moscow Medical Academy | Skleenova E.Y.,Smolensk State Medical Academy | Kozyreva V.K.,Smolensk State Medical Academy | And 5 more authors.
Clinical Microbiology and Infection | Year: 2012

An Escherichia coli isolate co-producing VIM-4 metallo-β-lactamase and CTX-M-15 extended spectrum β-lactamase was recovered from the urine of a patient with head trauma in Moscow, Russia. The bla VIM-4 and bla CTX-M-15 genes were carried, respectively, by transmissible plasmids of IncW and IncI1 groups. The nucleotide sequence of the VIM-4-encoding integron was nearly identical to that of In416, which represent a large group of structurally related integrons previously found in Enterobacteriaceae all around the Mediterranean basin. This is the first report of a metallo-β-lactamase-producing E. coli in Russia. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.


Varizhuk A.,RAS Engelhardt Institute of Molecular Biology | Chizhov A.,RAS N. D. Zelinsky Institute of Organic Chemistry | Smirnov I.,Institute for Physical Chemical Medicine | Kaluzhny D.,RAS Engelhardt Institute of Molecular Biology | Florentiev V.,RAS Engelhardt Institute of Molecular Biology
European Journal of Organic Chemistry | Year: 2012

A new class of backbone-modified oligonucleotide analogs has emerged since the discovery of the Cu I-catalyzed [3+2] azide/alkyne cycloaddition reaction. These are oligonucleotide analogs with 1,4-disubstituted 1,2,3-triazoles as the internucleotide linkages. Of all such analogs known, only the triazole-linked deoxythymidine decamer [(dT) 10] has been reported to show enhanced binding affinity to complementary DNA. Importantly, it is a fully modified (dT) 10 analog. To date, sequentially heterogeneous oligonucleotides bearing the same backbone modification have not been described. With the goal of investigating sequence and regularity dependence of the effect of this modification on duplex stability, we have designed partially modified mixed-base oligonucleotides, which can be prepared by using a modified dinucleoside block. In this paper we report the synthesis of a dithymidine phosphoramidite analog with a triazole linker, its use in oligonucleotide synthesis and hybridization data of the resulting oligonucleotide analogs. The effect of single and multiple modifications on stability of mixed-base duplexes is assessed and compared with published data for the oligo(T)/oligo(A) duplex. We also compared the effect of the linker concerned with that of a shorter triazole linker. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Zaitseva M.,Institute for Physical Chemical Medicine | Kaluzhny D.,RAS Engelhardt Institute of Molecular Biology | Shchyolkina A.,RAS Engelhardt Institute of Molecular Biology | Borisova O.,RAS Engelhardt Institute of Molecular Biology | And 2 more authors.
Biophysical Chemistry | Year: 2010

The thrombin-binding aptamer d(GGTTGGTGTGGTTGG) (TBA) is an efficient tool for the inhibition of thrombin function. We have studied conformations and thermodynamic stability of a number of modified TBA oligonucleotides containing thiophosphoryl substitution at different internucleotide sites. Using circular dichroism such modifications were found not to disrupt the antiparallel intramolecular quadruplex specific for TBA. Nevertheless, the presence of a single thiophosphoryl bond between two G-quartet planes led to a significant decrease in the quadruplex thermostability. On the contrary, modifications in each of the loop regions either stabilized an aptamer structure or did not reduce its stability. According to the thrombin time test, the aptamer with thio-modifications in both TT loops (LL11) exhibits the same antithrombin efficiency as the original TBA. This aptamer shows better stability against DNA nuclease compared to that of TBA. We conclude that such thio-modification patterns are very promising for the design of anticoagulation agents. © 2009 Elsevier B.V. All rights reserved.


Varizhuk A.M.,RAS Engelhardt Institute of Molecular Biology | Tsvetkov V.B.,RAS Topchiev Institute of Petrochemical Synthesis | Tatarinova O.N.,Institute for Physical Chemical Medicine | Kaluzhny D.N.,RAS Engelhardt Institute of Molecular Biology | And 8 more authors.
European Journal of Medicinal Chemistry | Year: 2013

A series of DNA aptamers bearing triazole internucleotide linkages that bind to thrombin was synthesized. The novel aptamers are structurally analogous to the well-known thrombin-inhibiting G-quadruplexes TBA15 and TBA31. The secondary structure stability, binding af finity for thrombin and anticoagulant effects of the triazole-modifi ed aptamers were measured. A modification in the central loop of the aptamer quadruplex resulted in increased nuclease resistance and an inhibition efficiency similar to that of TBA15. The likely aptamer-thrombin binding mode was determined by molecular dynamics simulations. Due to their relatively high activity and the increased resistance to nuclease digestion imparted by the triazole internucleotide linkages, the novel aptamers are a promising alternative to known DNA-based anticoagulant agents. © 2013 Elsevier Masson SAS. All rights reserved.


PubMed | Institute for Physical Chemical Medicine
Type: Journal Article | Journal: Physical chemistry chemical physics : PCCP | Year: 2014

Recently it has been shown that Chlorin e6 (Ce6) when complexed with Pluronics (hydrophilic ethylene and propylene oxide block copolymers) and poly(N-vinylpyrrolidone) (PVP) exhibits considerably higher phototoxicity towards tumor cells than free Ce6. The present work aimed to model Ce6 interactions with hydrophilic Pluronic F127 and PVP and find out the nature of intermolecular forces stabilizing these complexes. Modeling included 3 steps: (i) application of molecular dynamics to study polymer folding using AMBER 8 program, (ii) evaluation of partial charges in the Ce6 molecule using different quantum mechanical, semi-empirical and topological approaches and (iii) docking analysis of Ce6 interactions with polymer coils using AUTODOCK 4.2. It was found that the folding in regular polymers does not occur stochastically, but involves the formation of primary helical structures, which further combined to form hairpin-like secondary structures. The latter in turn associated to form coils with minimal solvent accessible hydrophobic area. The Ce6 ring lies flat on the surface of the polymer coil at the interface between hydrophobic and hydrophilic regions. Calculations showed higher affinity of Ce6 for PVP in comparison to Pluronic and revealed marginal contribution of Coulomb forces to the stabilization of both complexes, which are mainly stabilized by van der Waals and hydrogen interactions.

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