Publications by authors named "Vladimir V Ivanov"

30 Publications

  • Page 1 of 1

Metabolic Homeostasis in Chronic Helminth Infection Is Sustained by Organ-Specific Metabolic Rewiring.

ACS Infect Dis 2021 04 25;7(4):906-916. Epub 2021 Mar 25.

Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 2333ZA, The Netherlands.

Opisthorchiasis, is a hepatobiliary disease caused by flukes of the trematode family . A chronic form of the disease implies a prolonged coexistence of a host and the parasite. The pathological changes inflicted by the worm to the host's hepatobiliary system are well documented. Yet, the response to the infection also triggers a deep remodeling of the host systemic metabolism reaching a new homeostasis and affecting the organs beyond the worm location. Understanding the metabolic alternation in chronic opisthorchiasis, could help us to pinpoint pathways that underlie infection opening possibilities for the development of more selective treatment strategies. Here, with this report we apply an integrative, multicompartment metabolomics analysis, using multiple biofluids, stool samples and tissue extracts to describe metabolic changes in infected animals at the chronic stage. We show that the shift in lipid metabolism in the serum, a depletion of the amino acids pool, an alteration of the ketogenic pathways in the jejunum and a suppressed metabolic activity of the spleen are the key features of the metabolic host adaptation at the chronic stage of infection. We describe this combination of the metabolic changes as a "metabolically mediated immunosuppressive status of organism" which develops during a chronic infection. This status in combination with other factors (e.g., parasite-derived immunomodulators) might increase risk of infection-related malignancy.
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http://dx.doi.org/10.1021/acsinfecdis.1c00026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154418PMC
April 2021

A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation.

Molecules 2020 Sep 30;25(19). Epub 2020 Sep 30.

Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against . 3-Ethyl--(3-fluorobenzyl)--(4-methoxyphenyl)-[1,2,4]triazolo[4,3-]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-]pyridin-3(2)-one showed in vitro good antimalarial activity with inhibitory concentration IC = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.
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http://dx.doi.org/10.3390/molecules25194485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582516PMC
September 2020

Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies.

Molecules 2020 Sep 16;25(18). Epub 2020 Sep 16.

Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.

Consecutive alkylation of 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by CHI has been investigated to establish regioselectivity of the reaction for reliable design and synthesis of combinatorial libraries. In the first stage, the product of S-methylation-methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate was obtained. The subsequent alkylation with CHI led to the formation of both - and -methylation products mixture-methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate and methyl 1-methyl-2-(methylthio)-4-oxo-1,4-dihydroquinoline-3-carboxylate with a predominance of -methylated product. The structure of synthesized compounds was confirmed by means of elemental analysis, H-NMR, C-NMR, LC/MS, and single-crystal X-ray diffraction. The quantum chemical calculations of geometry and electron structure of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate's anion were carried out. According to molecular docking simulations, the studied compounds can be considered as potent inhibitors of Hepatitis B Virus replication. Experimental in vitro biological studies confirmed that studied compounds demonstrated high inhibition of HBV replication in 10 µM concentration.
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http://dx.doi.org/10.3390/molecules25184238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570464PMC
September 2020

Plasma metabolomics of the time resolved response to Opisthorchis felineus infection in an animal model (golden hamster, Mesocricetus auratus).

PLoS Negl Trop Dis 2020 01 24;14(1):e0008015. Epub 2020 Jan 24.

Center for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands.

Background: Opisthorchiasis is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. Opisthorchiasis can lead to severe hepatobiliary morbidity and is classified as a carcinogenic agent. Here we investigate the time-resolved metabolic response to Opisthorchis felineus infection in an animal model.

Methodology: Thirty golden hamsters were divided in three groups: severe infection (50 metacercariae/hamster), mild infection (15 metacercariae/hamster) and uninfected (vehicle-PBS) groups. Each group consisted of equal number of male and female animals. Plasma samples were collected one day before the infection and then every two weeks up to week 22 after infection. The samples were subjected to 1H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical modelling.

Principal Findings: The time-resolved study of the metabolic response to Opisthorchis infection in plasma in the main lines agrees with our previous report on urine data. The response reaches its peak around the 4th week of infection and stabilizes after the 10th week. Yet, unlike the urinary data there is no strong effect of the gender in the data and the intensity of infection is presented in the first two principal components of the PCA model. The main trends of the metabolic response to the infection in blood plasma are the transient depletion of essential amino acids and an increase in lipoprotein and cholesterol concentrations.

Conclusions: The time resolved metabolic signature of Opisthorchis infection in the hamster's plasma shows a coherent shift in amino acids and lipid metabolism. Our work provides insight into the metabolic basis of the host response on the helminth infection.
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http://dx.doi.org/10.1371/journal.pntd.0008015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002010PMC
January 2020

Crystal structure, Hirshfeld analysis and a mol-ecular docking study of a new inhibitor of the Hepatitis B virus (HBV): ethyl 5-methyl-1,1-dioxo-2-{[5-(pentan-3-yl)-1,2,4-oxa-diazol-3-yl]meth-yl}-2-1,2,6-thia-diazine-4-carboxyl-ate.

Acta Crystallogr E Crystallogr Commun 2020 Jan 1;76(Pt 1):12-17. Epub 2020 Jan 1.

University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria.

The title compound, CHNOS, was prepared alkyl-ation of 3-(chloro-meth-yl)-5-(pentan-3-yl)-1,2,4-oxa-diazole in anhydrous dioxane in the presence of tri-ethyl-amine. The thia-diazine ring has an envelope conformation with the S atom displaced by 0.4883 (6) Å from the mean plane through the other five atoms. The planar 1,2,4-oxa-diazole ring is inclined to the mean plane of the thia-diazine ring by 77.45 (11)°. In the crystal, mol-ecules are linked by C-H⋯N hydrogen bonds, forming chains propagating along the axis direction. Hirshfeld surface analysis and two-dimensional fingerprint plots have been used to analyse the inter-molecular contacts present in the crystal. Mol-ecular docking studies were use to evaluate the title compound as a potential system that inter-acts effectively with the capsid of the Hepatitis B virus (HBV), supported by an experimental HBV replication model.
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http://dx.doi.org/10.1107/S2056989019015986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944089PMC
January 2020

Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate.

Heliyon 2019 Nov 14;5(11):e02738. Epub 2019 Nov 14.

Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090, Vienna, Austria.

A method of 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate synthesis has been developed and the electronic and spatial structure of a new biologically active molecule has been studied both theoretically and experimentally. The title compound was crystallized from acetonitrile and the single crystal X-ray analysis has revealed that it exists in a monoclinic P2/c space group, with one molecule in the asymmetric part of the unit cell. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking study evaluates the investigated compound as a new potential inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance demonstrates nanomolar inhibitory activity against HBV.
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http://dx.doi.org/10.1016/j.heliyon.2019.e02738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895763PMC
November 2019

Hemozoin From the Liver Fluke, , Modulates Dendritic Cell Responses in Bronchial Asthma Patients.

Front Vet Sci 2019 16;6:332. Epub 2019 Oct 16.

Department of Microbiology, Immunology and Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, United States.

There is a general, inverse relationship between helminth infection and allergic diseases including bronchial asthma (BA). Proteins and other mediators released from parasitic worms exert cogent downmodulation of atopic and other allergic reactivity. We investigated the immune activities of an immortalized murine dendritic cell (mDC) line (JAWSII) and of primary human dendritic cells (hDCs) collected from study participants with and without BA after hemozoin (Hz) treatment. , expression of lymphocyte-activating factors-T helper 1 (Th1) induction and anti-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), IL-10, and IL-12β-increased significantly in mDCs pulsed with Hz. In parallel, primary dendritic cells (hDC) from cases clinically diagnosed with BA along with healthy controls were exposed to Hz in combination with lipopolysaccharide (LPS). Whereas no significant change in the cellular maturation markers, CD83, CD86, and CD40, was apparent in BA vs. healthy hDC, pulsing hDC from BA with Hz with LPS induced significant increases in expression of IL-10 and IL-12β, although not of TNF-α or tumor growth factor-beta (TGF-β). Liver fluke hemozoin Hz stimulated production of Th1 inducer and anti-inflammatory cytokines IL-10 and IL-12β from BA-hDC pulsed with Hz, an outcome that enhances our understanding of the mechanisms whereby opisthorchiasis contributes to protection against the atopic disease in liver fluke infection-endemic regions.
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http://dx.doi.org/10.3389/fvets.2019.00332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843058PMC
October 2019

pH-triggered delivery of magnetic nanoparticles depends on tumor volume.

Nanomedicine 2020 01 23;23:102086. Epub 2019 Aug 23.

Siberian State Medical University, Tomsk, Russia.

Nowadays there is growing recognition of the fact that biological systems have a greater impact on nanoparticle target delivery in tumors than nanoparticle design. Here we investigate the targeted delivery of FeO magnetic nanoparticles conjugated with pH-low-insertion peptide (MNP-pHLIP) on orthotopically induced MDA-MB-231 human breast carcinoma xenografts of varying volumes as a model of cancer progression. Using in vivo magnetic resonance imaging and subsequent determination of iron content in tumor samples by inductively coupled plasma atomic emission spectroscopy we found that MNP-pHLIP accumulation depends on tumor volume. Transmission electron microscopy, histological analysis and immunohistochemical staining of tumor samples suggest that blood vessel distribution is the key factor in determining the success of the accumulation of nanoparticles in tumors.
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http://dx.doi.org/10.1016/j.nano.2019.102086DOI Listing
January 2020

Modification of titanium surface via Ag-, Sr- and Si-containing micro-arc calcium phosphate coating.

Bioact Mater 2019 Dec 2;4:224-235. Epub 2019 Aug 2.

Siberian State Medical University, Moscovskii Tract 2, Tomsk, 634050, Russia.

The current research is devoted to the study of the modification of the titanium implants by the micro-arc oxidation with bioactive calcium phosphate coatings containing Ag or Sr and Si elements. The coatings' microstructure, phase composition, morphology, physicochemical and biological properties were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). Ag-containing and Sr-Si-incorporated coatings were formed in alkaline and acid electrolytes, respectively. The formation of the coatings occurred at different ranges of the applied voltages, which led to the significant difference in the coatings properties. The trace elements Ag, Sr and Si participated intensively in the plasma-chemical reactions of the micro-arc coatings formation. Ag-containing coatings demonstrated strong antibacterial effect against AТСС 6538-P. MTT test with 3T3-L1 fibroblasts showed no cytotoxicity appearance on Sr-Si-incorporated coatings.
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http://dx.doi.org/10.1016/j.bioactmat.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684518PMC
December 2019

Impact of cold adaptation on cardiac tolerance to ischemia/reperfusion and glucocorticoid, thyroid hormone levels.

Gen Physiol Biophys 2019 May;38(3):245-251

Department of Pathology, University of Kentucky College of Medicine, Lexington, United States.

We have established that the continuous cold exposure (CCE, 4°C, 4 weeks) causes cold adaptation, increases systolic blood pressure, exerts infarct-limiting effect during coronary artery occlusion (45 min) and reperfusion (2 h). The CCE increases adrenal weight, heart weight and triiodothyronine (T3) level but does not change thymus, spleen weight, serum cortisol, corticosterone and thyroxin (T4) levels. The long-term (4°C, 8 h/day, 4 weeks) intermittent cold exposure (LICE) induces adaptation to the cold and increases T4 level. The brief (4°C, 1.5 h/day, 4 weeks) intermittent cold exposure (BICE) also evokes adaptation to the cold but had no effect on the blood pressure, the cardiac tolerance to ischemia/reperfusion, and does not change thymus, spleen weight, serum cortisol, corticosterone, T3 and T4 levels.
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http://dx.doi.org/10.4149/gpb_2019002DOI Listing
May 2019

Imbalance in the glutathione system in Opisthorchis felineus infected liver promotes hepatic fibrosis.

Acta Trop 2019 Apr 23;192:41-48. Epub 2019 Jan 23.

Siberian State Medical University, 2, Moskovsky trakt, Tomsk, 634050, Russia.

Although data on oxidative stress during liver fluke infection have been previously presented, a comprehensive study of the glutathione system that plays a crucial role in scavenging of reactive oxygen species (ROS) and detoxification of primary and secondary oxidation products has not been addressed yet. In the present study, the hepatic glutathione system was investigated in a hamster model of experimental opisthorchiasis infection. It was shown that chronic oxidative stress in an Opisthorchis felineus infected liver, evidenced by abundant hydroperoxide accumulation, leads to strong imbalance in the hepatic glutathione system, namely the depletion of reduced form of glutathione (GSH), lowering of the GSH/GSSG ratio, and a decrease in the glutathione peroxidase and glyoxalase 1 activity. O. felineus infection provokes hepatocellular damage that results in the progression of liver fibrosis, accompanied by an increase in collagen deposition in the hepatic tissue. Modulation of hepatic GSH levels in the O. felineus infected liver through N-acetylcysteine (NAC) or l-buthionine-S, R-sulfoxinine (BSO) treatments lead to changes in expression and activity of glutathione S-transferase and glyoxalase I as well as markedly decreases or increases collagen content in the O. felineus infected liver and the severity of liver fibrosis, respectively. Thus, the glutathione system can be considered as a target for liver protection from O. felineus-induced injury.
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http://dx.doi.org/10.1016/j.actatropica.2019.01.017DOI Listing
April 2019

Is oxidative stress of adipocytes a cause or a consequence of the metabolic syndrome?

J Clin Transl Endocrinol 2019 Mar 9;15:1-5. Epub 2018 Nov 9.

Department of Pathology, University of Kentucky College of Medicine, Lexington, KY, USA.

Metabolic syndrome is accompanied by oxidative stress in animals and humans. The main source of ROS in experimental metabolic syndrome is NADPH oxidase and possibly adipocyte mitochondria. It is now documented that oxidative stress induces insulin resistance of adipocytes and increases secretion of leptin, MCP-1, IL-6, and TNF-α by adipocytes. It was established that oxidative stress induces a decrease in adiponectin production by adipocytes. It has also been shown that obesity itself can induce oxidative stress. Oxidative stress can cause an alteration of intracellular signaling in adipocytes that apparently leads to the formation of insulin resistance of adipocytes. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α also play an important role in the pathogenesis of oxidative stress of adipocytes. Oxidative stress is not only a consequence of metabolic syndrome, but also a reason and a foundational link in the pathogenesis of the metabolic syndrome.
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http://dx.doi.org/10.1016/j.jcte.2018.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240632PMC
March 2019

Size-Dependent Ability of Liposomes to Accumulate in the Ischemic Myocardium and Protect the Heart.

J Cardiovasc Pharmacol 2018 09;72(3):143-152

Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Liposomes have the potential to be used for drug delivery. Meanwhile, liposome size may affect their accumulation in the target tissue. We investigated the myocardial accumulation of 2 populations of liposomes (∼70 and 110 nm diameter) during ischemia and their effect on ischemia/reperfusion injury. Isolated rat hearts were subjected to 30 minutes of low-flow ischemia with the liposomes, followed by 30 minutes of liposome-free reperfusion. The liposomes were loaded with the fluorescent dye Nile Red to assess their accumulation in the myocardium. The cardiac functional recovery during reperfusion was evaluated using force-velocity characteristics and coronary flow (CF). Reperfusion injury was evaluated by lactate dehydrogenase release. In addition, CF and contractility were assessed in hearts perfused normally with 70 nm liposomes. There was a 6- and 4-fold greater accumulation of the small liposomes in the myocardium and mitochondria, respectively, compared with the large liposomes. Importantly, even without any incorporated drugs, both populations of liposomes improved functional recovery and reduced lactate dehydrogenase release. However, the smaller liposomes showed significantly higher protective and vasodilatory effects during reperfusion than the larger particles. These liposomes also increased CF and contractility during normal perfusion. We suggest that the protective properties of the liposomes could be related to their membrane-stabilizing effect.
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http://dx.doi.org/10.1097/FJC.0000000000000606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125753PMC
September 2018

PMIDA-Modified FeO Magnetic Nanoparticles: Synthesis and Application for Liver MRI.

Langmuir 2018 03 6;34(11):3449-3458. Epub 2018 Mar 6.

Siberian State Medical University , 2 Moskovsky Trakt , 634050 Tomsk , Russia.

The surface modification of FeO-based magnetic nanoparticles (MNPs) with N-(phosphonomethyl)iminodiacetic acid (PMIDA) was studied, and the possibility of their use as magnetic resonance imaging contrast agents was shown. The effect of the added PMIDA amount, the reaction temperature and time on the degree of immobilization of this reagent on MNPs, and the hydrodynamic characteristics of their aqueous colloidal solutions have been systematically investigated for the first time. It has been shown that the optimum condition for the modification of MNPs is the reaction at 40 °C with an equimolar amount of PMIDA for 3.5 h. The modified MNPs were characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric, and CHN elemental analyses. The dependence of the hydrodynamic characteristics of the MNP colloidal solutions on the concentration and pH of the medium was studied by the dynamic light scattering method. On the basis of the obtained data, we can assume that the PMIDA molecules are fixed on the surface of the MNPs as a monomolecular layer. The modified MNPs had good colloidal stability and high magnetic properties. The calculated relaxivities r and r were 341 and 102 mmol s, respectively. The possibility of using colloidal solutions of PMIDA-modified MNPs as a T contrast agent for liver studies in vivo (at a dose of 0.6 mg kg) was demonstrated for the first time.
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http://dx.doi.org/10.1021/acs.langmuir.7b04023DOI Listing
March 2018

Exploratory metabolomics study of the experimental opisthorchiasis in a laboratory animal model (golden hamster, Mesocricetus auratus).

PLoS Negl Trop Dis 2017 Oct 31;11(10):e0006044. Epub 2017 Oct 31.

Center for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands.

Background: Opisthorchiasis is a parasitic infection caused by the liver flukes of the Opisthorchiidae family. Both experimental and epidemiological data strongly support a role of these parasites in the etiology of the hepatobiliary pathologies and an increased risk of intrahepatic cholangiocarcinoma. Understanding a functional link between the infection and hepatobiliary pathologies requires a detailed description a host-parasite interaction on different levels of biological regulation including the metabolic response on the infection. The last one, however, remains practically undocumented. Here we are describing a host response on Opisthorchiidae infection using a metabolomics approach and present the first exploratory metabolomics study of an experimental model of O. felineus infection.

Methodology And Principal Findings: We conducted a Nuclear Magnetic Resonance (NMR) based longitudinal metabolomics study involving a cohort of 30 animals with two degrees of infection and a control group. An exploratory analysis shows that the most noticeable trend (30% of total variance) in the data was related to the gender differences. Therefore further analysis was done of each gender group separately applying a multivariate extension of the ANOVA-ASCA (ANOVA simultaneous component analysis). We show that in the males the infection specific time trends are present in the main component (43.5% variance), while in the females it is presented only in the second component and covers 24% of the variance. We have selected and annotated 24 metabolites associated with the observed effects and provided a physiological interpretation of the findings.

Conclusions: The first exploratory metabolomics study an experimental model of O. felineus infection is presented. Our data show that at early stage of infection a response of an organism unfolds in a gender specific manner. Also main physiological mechanisms affected appear rather nonspecific (a status of the metabolic stress) the data provides a set of the hypothesis for a search of the more specific metabolic markers of the Opisthorchiidae infection.
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http://dx.doi.org/10.1371/journal.pntd.0006044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681294PMC
October 2017

Green synthesis of silver nanoparticles using transgenic Nicotiana tabacum callus culture expressing silicatein gene from marine sponge Latrunculia oparinae.

Artif Cells Nanomed Biotechnol 2018 Dec 12;46(8):1646-1658. Epub 2017 Oct 12.

a Federal Scientific Centre of the East Asia Terrestrial Biodiversity, Department of Biotechnology, Far East Branch of Russian Academy of Sciences , Vladivostok , Russia.

In the present investigation, transgenic tobacco callus cultures and plants overexpressing the silicatein gene LoSilA1 from marine sponge Latrunculia oparinae were obtained and their bioreduction behaviour for the synthesis of silver nanoparticles (AgNPs) was studied. Synthesized nanoparticles were characterized using UV-visible spectroscopy, Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic flame electron microscopy (AFM) and nanoparticle tracking analysis (NTA). Our measurements showed that the reduction of silver nitrate produced spherical AgNPs with diameters in the range of 12-80 nm. The results of XRD analysis proved the crystal nature of the obtained AgNPs. FTIR analysis indicated that particles are reduced and stabilized in solution by the capping agent, which is likely to be proteins present in the callus extract. Interestingly, the reduction potential of LoSiLA1-transgenic callus line was increased three-fold compared with the empty vector-transformed calli. The synthesized AgNPs were found to exhibit strong antibacterial activity against Escherichia coli and Agrobacterium rhizogenes. The present study reports the first evidence for using genetic engineering for activation of the reduction potential of plant cells for synthesis of biocidal AgNPs.
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http://dx.doi.org/10.1080/21691401.2017.1388248DOI Listing
December 2018

Magnetic resonance imaging and spectroscopy for differential assessment of liver abnormalities induced by Opisthorchis felineus in an animal model.

PLoS Negl Trop Dis 2017 Jul 14;11(7):e0005778. Epub 2017 Jul 14.

Central Research Laboratory, Siberian State Medical University, Tomsk, Russia.

Background: European liver fluke Opisthorchis felineus, causing opisthorchiasis disease, is widespread in Russia, Ukraine, Kazakhstan and sporadically detected in the EU countries. O. felineus infection leads to hepatobiliary pathological changes, cholangitis, fibrosis and, in severe cases, malignant transformation of bile ducts. Due to absence of specific symptoms, the infection is frequently neglected for a long period. The association of opisthorchiasis with almost incurable bile duct cancer and rising international migration of people that increases the risk of the parasitic etiology of liver fibrosis in non-endemic regions determine high demand for development of approaches to opisthorchiasis detection.

Methodology/principal Findings: In vivo magnetic resonance imaging and spectroscopy (MRI and MRS) were applied for differential assessment of hepatic abnormalities induced by O. felineus in an experimental animal model. Correlations of the MR-findings with the histological data as well as the data of the biochemical analysis of liver tissue were found. MRI provides valuable information about the severity of liver impairments induced by opisthorchiasis. An MR image of O. felineus infected liver has a characteristic pattern that differs from that of closely related liver fluke infections. 1H and 31P MRS in combination with biochemical analysis data showed that O. felineus infection disturbed hepatic metabolism of the host, which was accompanied by cholesterol accumulation in the liver.

Conclusions: A non-invasive approach based on the magnetic resonance technique is very advantageous and may be successfully used not only for diagnosing and evaluating liver damage induced by O. felineus, but also for investigating metabolic changes arising in the infected organ. Since damages induced by the liver fluke take place in different liver lobes, MRI has the potential to overcome liver biopsy sampling variability that limits predictive validity of biopsy analysis for staging liver fluke-induced fibrosis.
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http://dx.doi.org/10.1371/journal.pntd.0005778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529022PMC
July 2017

Greater role for Atlantic inflows on sea-ice loss in the Eurasian Basin of the Arctic Ocean.

Science 2017 04 6;356(6335):285-291. Epub 2017 Apr 6.

Arctic and Antarctic Research Institute, 38 Bering Street, Saint Petersburg 199397, Russia.

Arctic sea-ice loss is a leading indicator of climate change and can be attributed, in large part, to atmospheric forcing. Here, we show that recent ice reductions, weakening of the halocline, and shoaling of the intermediate-depth Atlantic Water layer in the eastern Eurasian Basin have increased winter ventilation in the ocean interior, making this region structurally similar to that of the western Eurasian Basin. The associated enhanced release of oceanic heat has reduced winter sea-ice formation at a rate now comparable to losses from atmospheric thermodynamic forcing, thus explaining the recent reduction in sea-ice cover in the eastern Eurasian Basin. This encroaching "atlantification" of the Eurasian Basin represents an essential step toward a new Arctic climate state, with a substantially greater role for Atlantic inflows.
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http://dx.doi.org/10.1126/science.aai8204DOI Listing
April 2017

3-Aminopropylsilane-modified iron oxide nanoparticles for contrast-enhanced magnetic resonance imaging of liver lesions induced by .

Int J Nanomedicine 2016;11:4451-4463. Epub 2016 Sep 6.

Siberian State Medical University.

Purpose: Liver fluke causes severe liver damage in an infected human. However, the infection often remains neglected due to the lack of pathognomonic signs. Nanoparticle-enhanced magnetic resonance imaging (MRI) offers a promising technique for detecting liver lesions induced by parasites.

Materials And Methods: Surface modification of iron oxide nanoparticles produced by coprecipitation from a solution of Fe and Fe salts using 3-aminopropylsilane (APS) was carried out. The APS-modified nanoparticles were characterized by transmission electron microscopy, fourier transform infrared spectroscopy, and thermogravimetric analysis. Magnetic resonance properties of MNPs were investigated in vitro and in vivo.

Results: The amount of APS grafted on the surface of nanoparticles (0.60±0.06 mmol g) was calculated based on elemental analysis and infrared spectroscopy data. According to transmission electron microscopy data, there were no essential changes in the structure of nanoparticles during the modification. The APS-modified nanoparticles exhibit high magnetic properties; the calculated relaxivity was 271 mmol s. To obtain suspension with optimal hydrodynamic characteristics, amino groups on the surface of nanoparticles were converted into an ionic form with HCl. Cellular uptake of modified nanoparticles by rat hepatoma cells and human monocytes in vitro was 74.1±4.5 and 10.0±3.7 pg [Fe] per cell, respectively. Low cytotoxicity of the nanoparticles was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin V/7-aminoactinomycin D flow cytometry assays. For the first time, magnetic nanoparticles were applied for contrast-enhanced MRI of liver lesions induced by .

Conclusion: The synthesized APS-modified iron oxide nanoparticles showed high efficiency as an MRI contrast agent for the evaluation of opisthorchiasis-related liver damage.
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http://dx.doi.org/10.2147/IJN.S111880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019273PMC
September 2016

Carbonyl stress phenomena during chronic infection with Opisthorchis felineus.

Parasitol Int 2017 Aug 8;66(4):453-457. Epub 2016 Jan 8.

Central Research Laboratory, Siberian State Medical University, 2 Moskovsky trakt, Tomsk 634050, Tomsk, Russian Federation; Lomonosov Moscow State University, 1 Leninskie Gory, Moscow 119991, Russian Federation.

Infection with the fish borne liver fluke Opisthorchis felineus is common in the Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Better understanding of the molecular pathogenesis of the biliary tract and liver during chronic opisthorchiasis can be expected to improve protection against and management of complications of this disease. We hypothesize that infection with O. felineus associates with formation of methylglyoxal and carbonyl stress in the liver and hence here we investigated the glyoxalase system and the receptor for advanced glycated end products (RAGE) in the liver of hamsters infected with this liver fluke. Expression of mRNA encoding glyoxalase 1 decreased at 8weeks of the infection and catalytic activity as well decreased at 8 and 12weeks after infection, and the expression of the glyoxalase 2 decreased until 36week post-infection, which associated with the decreasing activity of the enzyme at 8 and 12weeks post-infection. Glutathione levels in infected livers had decreased at week 8, whereas up-regulation of RAGE at mRNA levels was seen for the extended duration of the experimental infection of the hamsters. This outcome supported the notion of hepatic dicarbonyl stress during chronic opisthorchiasis. The inhibition of the glyoxalase system and accumulation of methylglyoxal at the early stages of the infection may underpin development of insulin resistance during opisthorchiasis.
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http://dx.doi.org/10.1016/j.parint.2016.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938777PMC
August 2017

Hemozoin "knobs" in Opisthorchis felineus infected liver.

Parasit Vectors 2015 Sep 17;8:459. Epub 2015 Sep 17.

Siberian State Medical University, 2, Moskovsky trakt, 634050, Tomsk, Russia.

Background: Hemozoin is the pigment produced by some blood-feeding parasites. It demonstrates high diagnostic and therapeutic potential. In this work the formation of co-called hemozoin "knobs" - the bile duct ectasia filled up by hemozoin pigment - in Opisthorhis felineus infected hamster liver has been observed.

Methods: The O. felineus infected liver was examined by histological analysis and magnetic resonance imaging (MRI). The pigment hemozoin was identified by Fourier transform infrared spectroscopy and high resolution electrospray ionization mass spectrometry analysis. Hemozoin crystals were characterised by high resolution transmission electron microscopy.

Results: Hemozoin crystals produced by O. felineus have average length 403 nm and the length-to-width ratio equals 2.0. The regurgitation of hemozoin from parasitic fluke during infection leads to formation of bile duct ectasia. The active release of hemozoin from O. felineus during in vitro incubation has also been evidenced. It has been shown that the hemozoin knobs can be detected by magnetic resonance imaging.

Conclusions: In the paper for the first time the characterisation of hemozoin pigment extracted from liver fluke O. felineus has been conducted. The role of hemozoin in the modification of immune response by opisthorchiasis is assumed.
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http://dx.doi.org/10.1186/s13071-015-1061-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574221PMC
September 2015

Discontinuities-free complete-active-space state-specific multi-reference coupled cluster theory for describing bond stretching and dissociation.

J Chem Phys 2015 Jul;143(2):024109

Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA.

The earlier proposed multi-reference state-specific coupled-cluster theory with the complete active space reference [CASCC; Lyakh et al., J. Chem. Phys. 122, 024108 (2005)] suffered from a problem of energy discontinuities when the formal reference state was changing in the calculation of the potential energy curve (PEC). A simple remedy to the discontinuity problem is found and is presented in this work. It involves using natural complete active space self-consistent field active orbitals in the complete active space coupled-cluster calculations. The approach gives smooth PECs for different types of dissociation problems, as illustrated in the calculations of the dissociation of the single bond in the hydrogen fluorine molecule and of the symmetric double-bond dissociation in the water molecule.
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http://dx.doi.org/10.1063/1.4926392DOI Listing
July 2015

Ascorbic acid glucoside reduces neurotoxicity and glutathione depletion in mouse brain induced by nitrotriazole radiosensitazer.

J Cancer Res Ther 2013 Jul-Sep;9(3):364-9

Cancer Research Institute of Siberian Branch of the Russian Acad. Med. Sci, Tomsk, Russia.

Aim: To investigate the potential of the anti-oxidant ascorbic acid glucoside (AA-2G) to modulate neurotoxicity induced by high doses of nitrotriazole radiosensitizer.

Materials And Methods: Male and female C56Bl/6xCBA hybrid mice aged 8-14 weeks (weight 18-24 g) were used. Nitrotriazole drug radiosensitizer sanazole at a high dose of 2, 1 g/kg was per os administered to induce neurotoxicity at mice. Ascorbic acid glucoside was given 30 min before the sanazole administration. Serum ascorbic acid, brain glutathione level, as well as behavioral performance using open field apparatus were measured.

Results: Administration of high (non-therapeutic) doses of the nitrotriazole drug sanazole results in neurotoxicity in mice as evidenced from behavioral performance, emotional activity and depletion of the cellular antioxidant, glutathione, in the brain. The serum levels of ascorbic acid was also found reduced in high dose sanazole treated animals. Per os administration of ascorbic acid glucoside significantly reduced the neurotoxicity. This effect was associated with the prevention of glutathione depletion in mouse brain and restoring the ascorbic acid level in serum.

Conclusion: Administration of ascorbic acid glucoside, but not ascorbic acid, before sanazole administration protected from sanazole-induced neurotoxicity by preventing the decrease in the brain reduced glutathione level and providing high level of ascorbic acid in plasma.
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http://dx.doi.org/10.4103/0973-1482.119303DOI Listing
August 2014

Multireference state-specific coupled-cluster methods. State-of-the-art and perspectives.

Phys Chem Chem Phys 2009 Apr 13;11(14):2355-70. Epub 2009 Feb 13.

Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.

This work reviews the state-specific multireference coupled-cluster (CC) approaches which have been developed as approximate methods for performing high-level quantum mechanical calculations on quasidegenerate ground and excited states of atomic and molecular systems. The term "quasidegenerate" refers to a state that cannot be described even in the first approximation by a single-determinant wavefunction (a Slater determinant), but requires two or more determinants for this purpose. The main challenge with applying the coupled-cluster theory to such states is in describing the electron correlation effects in the wavefunctions representing these states in a manner that is size-extensive, yet accurate and simple enough so the method can be routinely applied to small and medium-size molecular systems. We are describing how this can be accomplished within a theory that focuses on only one state of the system in a single CC calculation (the state-specific theory).
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http://dx.doi.org/10.1039/b818590pDOI Listing
April 2009

A generalization of the state-specific complete-active-space coupled-cluster method for calculating electronic excited states.

J Chem Phys 2008 Feb;128(7):074101

Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.

The complete-active-space coupled-cluster approach with single and double excitations (CASCCSD) based on the ansatz of Oliphant and Adamowicz [J. Chem. Phys. 94, 1229 (1991); 96, 3739 (1992)] is used to derive an approach termed XCASCCSD for calculating potential energy surfaces of ground and excited electronic states with different multiplicities and symmetries. The XCASCCSD approach explicitly includes a procedure for spin and spatial orbital-momentum symmetry adaptation of the wave function that has allowed us to consider states with degenerate formal references. The XCASCCSD method is applied to calculate potential energy surfaces of the ground and some lowest singlet and triplet excited states of the FH and C(2) molecules. Some states of C(2) are known to have a very strong "multireference" character making their description difficult with single-reference methods. The problem of the change of the formal reference determinant along the potential energy surface is discussed. Also, vertical excitation energies of formaldehyde calculated with the XCASCCSD approach are presented.
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http://dx.doi.org/10.1063/1.2828548DOI Listing
February 2008

Excited states in the multireference state-specific coupled-cluster theory with the complete active space reference.

J Chem Phys 2006 May;124(18):184302

Department of Chemistry, V.N. Karazin Kharkov National University, Kharkov, Ukraine.

The recently proposed multireference state-specific coupled-cluster theory with the complete active space reference has been used to study electronically excited states with different spatial and spin symmetries. The algorithm for the method has been obtained using the computerized approach for automatic generation of coupled-cluster diagrams with an arbitrary level of the electronic excitation from a formal reference determinant. The formal reference is also used to generate the genuine reference state in the form of a linear combination of determinants contracted to a configuration with the spin and spatial symmetries of the target state. The natural-orbital expansions of the one-electron configuration inferaction density matrix allowed us to obtain the most compact orbital space for the expansion of the reference function. We applied our approach in the calculations of singlet and triplet states of different spatial symmetries of the water molecule. The comparisons of the results with values obtained using other many-particle methods and with the full configuration interaction results demonstrate good ability of the approach to deal with electronic excited states.
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http://dx.doi.org/10.1063/1.2190221DOI Listing
May 2006

Automated generation of coupled-cluster diagrams: implementation in the multireference state-specific coupled-cluster approach with the complete-active-space reference.

J Chem Phys 2005 Jan;122(2):024108

Department of Chemistry, Kharkov National University, Kharkov, Ukraine.

An algorithm for generation of the spin-orbital diagrammatic representation, the corresponding algebraical formulas, and the computer code of the coupled-cluster (CC) method with an arbitrary level of the electronic excitations has been developed. The method was implemented in the general case as well as for specific application in the state-specific multireference coupled-cluster theory (SSMRCC) based on the concept of a "formal reference state." The algorithm was tested in SSMRCC calculations describing dissociation of a single bond and in calculations describing simultaneous dissociation of two single bonds--the problem requiring up to six-particle excitations in the CC operator.
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http://dx.doi.org/10.1063/1.1824897DOI Listing
January 2005

Catalytic efficiency of a new tridentate ferrocenyl phosphine auxiliary: Sonogashira cross-coupling reactions of alkynes with aryl bromides and chlorides at low catalyst loadings of 10(-1) to 10(-4) mol %.

Org Lett 2004 Sep;6(20):3473-6

Laboratoire de Synthèse et d'Electrosynthèse Organométalliques UMR-CNRS 5188, Université de Bourgogne, 9 Avenue Alain Savary, 21078 Dijon, France.

[structure: see text] The catalytic activity in Sonogashira cross-coupling reactions of alkynes with a variety of aryl halides (including chlorides) using a multidentate ferrocenyl phosphine is presented. The novel mixed ferrocenyl aryl/alkyl triphosphine is thermally stable and insensitive to air or moisture, and its robustness allows aryl alkynylation at 10(-1) to 10(-4) mol % catalyst loadings with TONs up to 250,000. Copper-free coupling using phenylacetylene is also accessible in good yield.
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http://dx.doi.org/10.1021/ol048870zDOI Listing
September 2004

"Through-space" nuclear spin-spin J(PP) coupling in tetraphosphine ferrocenyl derivatives: a (31)P NMR and X-ray structure correlation study for coordination complexes.

J Am Chem Soc 2004 Sep;126(35):11077-87

Contribution from the Laboratoire de Synthèse et d'Electrosynthèse Organométalliques, UMR-CNRS 5188, Université de Bourgogne, Facultés des Sciences Mirande, 9 Avenue Alain Savary, BP 47870 F-21078 Dijon Cedex, France.

Herein, we report on (31)P(31)P solution-phase "through-space" nuclear spin-spin coupling constants (J(PP)) from a novel family of organometallic tetraphosphine nickel and palladium complexes. These J(PP) constants were accurately determined through NMR iterative simulation based on the second-order spectra obtained for the compounds. The corresponding solid-state X-ray structures of the complexes were determined, and the "through-space" P.P distances are reported. Due to the blocked conformation of the species in solution, a qualitative and semiquantitative experimental correlation is obtained, which links the geometric parameters and the intensity of the corresponding P.P coupling constant. The lone-pair overlap theory developed for (19)F(19)F and (15)N(19)F "through-space" couplings in organic compounds [J. Am. Chem. Soc. 1973, 95, 7747-7752; 2000, 122, 4108-4116] appears to be a reliable foundation on which to account for our results. Based on the reported observations, the lone-pair overlap model is extended to "through-space" (31)P(31)P coupling, and the model is broadened to encompass metal orbital contributions for coordination complexes. Some of the predictions and consequences of the proposed theory are discussed.
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http://dx.doi.org/10.1021/ja048907aDOI Listing
September 2004

Amplified spontaneous emission in a Ti:sapphire regenerative amplifier.

Appl Opt 2003 Dec;42(36):7231-4

Department of Physics/220, College of Art and Science, University of Nevada, Reno, Nevada 89557-0058 , USA.

Amplified spontaneous emission power and contrast ratio in a linear miltipass Ti:sapphire regenerative amplifier with a wavelength centered at 1054 nm are calculated and measured. It is shown that the passive losses of a seed pulse and the losses in coupling to the regenerative amplifier cavity mode degrade the intensity contrast ratio to 10(-6)-10(-7). The advantage of an optical parametric chirped pulse amplifier with respect to the contrast ratio is discussed.
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http://dx.doi.org/10.1364/ao.42.007231DOI Listing
December 2003
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