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Article ; Online: Finely tuned Prussian blue-based nanoparticles and their application in disease treatment.

Gao, Yong / Yu, Guocan / Xing, Kuoran / Gorin, Dmitry / Kotelevtsev, Yuri / Tong, Weijun / Mao, Zhengwei

2020 Volume 8, Issue 32, Page(s) 7121–7134

Abstract: The Prussian blue (PB) based nanostructure is a mixed-valence coordination network with excellent biosafety, remarkable photothermal effect and multiple enzyme-mimicking behaviours. Compared with other nanomaterials, PB-based nanoparticles (NPs) exhibit ... ...

Abstract	The Prussian blue (PB) based nanostructure is a mixed-valence coordination network with excellent biosafety, remarkable photothermal effect and multiple enzyme-mimicking behaviours. Compared with other nanomaterials, PB-based nanoparticles (NPs) exhibit several unparalleled advantages in biomedical applications. This review begins with the chemical composition and physicochemical properties of PB-based NPs. The tuning strategies of PB-based NPs and their biomedical properties are systemically demonstrated. Afterwards, the biomedical applications of PB-based NPs are comprehensively recounted, mainly focusing on treatment of tumors, bacterial infection and inflammatory diseases. Finally, the challenges and future prospects of PB-based NPs and their application in disease treatment are discussed.
MeSH term(s)	Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Biocompatible Materials/chemistry ; Biocompatible Materials/pharmacology ; Ferrocyanides/chemistry ; Ferrocyanides/pharmacology ; Humans ; Magnetic Resonance Imaging ; Metal Nanoparticles/chemistry ; Multimodal Imaging ; Nanocomposites/chemistry ; Optical Imaging ; Phototherapy ; Polylysine/chemistry ; Polyvinyls/chemistry ; Porosity ; Pyrrolidines/chemistry ; Theranostic Nanomedicine
Chemical Substances	Anti-Bacterial Agents ; Anti-Inflammatory Agents ; Antineoplastic Agents ; Biocompatible Materials ; Ferrocyanides ; Polyvinyls ; Pyrrolidines ; poly(N-vinylpyrrolidine) ; Polylysine (25104-18-1) ; ferric ferrocyanide (TLE294X33A)
Language	English
Publishing date	2020-07-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d0tb01248c
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Article ; Online: 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.

Tsitrina, Alexandra A / Halimani, Noreen / Andreichenko, Irina N / Sabirov, Marat / Nesterchuk, Mikhail / Dashenkova, Nataliya O / Romanov, Roman / Bulgakova, Elena V / Mikaelyan, Arsen / Kotelevtsev, Yuri

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: 4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin ... ...

Abstract	4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin resistance. It also inhibits tumor progression and metastasis. The broad spectrum of effects suggests multiple and yet unknown targets of 4MU. Aiming at 4MU target deconvolution, we have analyzed publicly available data bases, including: 1. Small molecule library Bio Assay screening (PubChemBioAssay); 2. GO pathway databases screening; 3. Protein Atlas Database. We also performed comparative liver transcriptome analysis of mice on normal diet and mice fed with 4MU for two weeks. Potential targets of 4MU public data base analysis fall into two big groups, enzymes and transcription factors (TFs), including 13 members of the nuclear receptor superfamily regulating lipid and carbohydrate metabolism. Transcriptome analysis revealed changes in the expression of genes involved in bile acid metabolism, gluconeogenesis, and immune response. It was found that 4MU feeding decreased the accumulation of the glycogen granules in the liver. Thus, 4MU has multiple targets and can regulate cell metabolism by modulating signaling via nuclear receptors.
MeSH term(s)	Mice ; Animals ; Hymecromone/pharmacology ; Transcriptome ; Liver/metabolism ; Inflammation/metabolism ; Signal Transduction ; Lipid Metabolism
Chemical Substances	Hymecromone (3T5NG4Q468)
Language	English
Publishing date	2023-01-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032129
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Article ; Online: Steroid signaling: ligand-binding promiscuity, molecular symmetry, and the need for gating.

Lathe, Richard / Kotelevtsev, Yuri

Steroids

2014 Volume 82, Page(s) 14–22

Abstract: Steroid/sterol-binding receptors and enzymes are remarkably promiscuous in the range of ligands they can bind to and, in the case of enzymes, modify - raising the question of how specific receptor activation is achieved in vivo. Estrogen receptors (ER) ... ...

Abstract	Steroid/sterol-binding receptors and enzymes are remarkably promiscuous in the range of ligands they can bind to and, in the case of enzymes, modify - raising the question of how specific receptor activation is achieved in vivo. Estrogen receptors (ER) are modulated by 27-hydroxycholesterol and 5α-androstane-3β,17β-diol (Adiol), in addition to estradiol (E2), and respond to diverse small molecules such as bisphenol A. Steroid-modifying enzymes are also highly promiscuous in ligand binding and metabolism. The specificity problem is compounded by the fact that the steroid core (hydrogenated cyclopentophenanthrene ring system) has several planes of symmetry. Ligand binding can be in symmetrical East-West (rotation) and North-South (inversion) orientations. Hydroxysteroid dehydrogenases (HSDs) can modify symmetrical 7 and 11, also 3 and 17/20, positions, exemplified here by yeast 3α,20β-HSD and mammalian 11β-HSD and 17β-HSD enzymes. Faced with promiscuity and symmetry, other strategies are clearly necessary to promote signaling selectivity in vivo. Gating regulates hormone access via enzymes that preferentially inactivate (or activate) a subclass of ligands, thereby governing which ligands gain receptor access - exemplified by 11β-HSD gating cortisol access to the mineralocorticoid receptor, and P450 CYP7B1 gating Adiol access to ER. Counter-intuitively, the specificity of steroid/sterol action is achieved not by intrinsic binding selectivity but by the combination of local metabolism and binding affinity.
MeSH term(s)	Binding Sites ; Ligands ; Peptides/chemistry ; Peptides/metabolism ; Proteins/chemistry ; Proteins/metabolism ; Signal Transduction ; Steroids/chemistry ; Steroids/metabolism
Chemical Substances	Ligands ; Peptides ; Proteins ; Steroids
Language	English
Publishing date	2014-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80312-1
ISSN	1878-5867 ; 0039-128X
ISSN (online)	1878-5867
ISSN	0039-128X
DOI	10.1016/j.steroids.2014.01.002
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Article ; Online: Endothelin signalling mediates experience-dependent myelination in the CNS.

Swire, Matthew / Kotelevtsev, Yuri / Webb, David J / Lyons, David A / Ffrench-Constant, Charles

eLife

2019 Volume 8

Abstract: Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B ...

Abstract	Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myelin sheaths formed by individual oligodendrocytes in mouse and zebrafish. We show that this phenotype is also observed in the prefrontal cortex of mice following social isolation, and is associated with reduced expression of vascular endothelin. Additionally, we show that increasing endothelin signalling rescues this myelination defect caused by social isolation. Together, these results indicate that the vasculature responds to changes in neuronal activity associated with experience by regulating endothelin levels, which in turn affect the myelinating capacity of oligodendrocytes. This pathway may be employed to couple the metabolic support function of myelin to activity-dependent demand and also represents a novel mechanism for adaptive myelination.
MeSH term(s)	Animals ; Endothelins/metabolism ; Mice ; Myelin Sheath/metabolism ; Oligodendroglia/metabolism ; Prefrontal Cortex/physiology ; Protein Kinase C-epsilon/metabolism ; Receptor, Endothelin B/metabolism ; Signal Transduction ; Zebrafish
Chemical Substances	EDNRB protein, mouse ; Endothelins ; Receptor, Endothelin B ; Protein Kinase C-epsilon (EC 2.7.11.13)
Language	English
Publishing date	2019-10-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.49493
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Article ; Online: Steroid promiscuity: Diversity of enzyme action. Preface.

Lathe, Richard / Kotelevtsev, Yuri / Mason, J Ian

The Journal of steroid biochemistry and molecular biology

2015 Volume 151, Page(s) 1–2

Abstract: This Special Issue on the topic of Steroid and Sterol Signaling: Promiscuity and Diversity, dwells on the growing realization that the 'one ligand, one binding site' and 'one enzyme, one reaction' concepts are out of date. Focusing on cytochromes P450 ( ... ...

Abstract	This Special Issue on the topic of Steroid and Sterol Signaling: Promiscuity and Diversity, dwells on the growing realization that the 'one ligand, one binding site' and 'one enzyme, one reaction' concepts are out of date. Focusing on cytochromes P450 (CYP), hydroxysteroid dehydrogenases (HSDs), and related enzymes, the Special Issue highlights that a single enzyme can bind to diverse substrates, and in different conformations, and can catalyze multiple different conversions (and in different directions), thereby, generating an unexpectedly wide spectrum of ligands that can have subtly different biological actions. This article is part of a Special Issue entitled 'Steroid/Sterol Signaling' .
MeSH term(s)	Cytochrome P-450 Enzyme System/metabolism ; Hydroxysteroid Dehydrogenases/metabolism ; Ligands ; Steroids/metabolism ; Sterol O-Acyltransferase/metabolism
Chemical Substances	Ligands ; Steroids ; Cytochrome P-450 Enzyme System (9035-51-2) ; Hydroxysteroid Dehydrogenases (EC 1.1.-) ; Sterol O-Acyltransferase (EC 2.3.1.26)
Language	English
Publishing date	2015-07
Publishing country	England
Document type	Introductory Journal Article
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2015.01.008
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Article ; Online: Hypotensive effect of bi-potassium salt of 1-hexadecyl-2-methylcarbamoylphosphatidic acid in rats with renovascular hypertension

N. Y. Khromova / S. I. Malekin / S. A. Gavrilova / S. V. Kotelevtsev / Yu. V. Kotelevtsev

Бюллетень сибирской медицины, Vol 17, Iss 4, Pp 163-

2018 Volume 170

Abstract: The study describes the synthesis and hypotensive effects of stable platelet activation factor (PAF) precursor 1-hexadecyl-2-m ethylcarbamoyl-phosphatidic acid (HMCP) оn outbred Wistar rats with 1-kidney 1-clip (1K1C) renovascular hypertension. ... ...

Abstract	The study describes the synthesis and hypotensive effects of stable platelet activation factor (PAF) precursor 1-hexadecyl-2-m ethylcarbamoyl-phosphatidic acid (HMCP) оn outbred Wistar rats with 1-kidney 1-clip (1K1C) renovascular hypertension. Intravenous injection of 0.1, 0.5, 1 and 5 mg/kg HMCP resulted in a sharp decline of up to 50% of MAP with subsequent restoration to initial level. In some hypertensive 1K1C rats HMCP has a prolonged effect with blood pressure stabilized at 75% of initial level after 30 min post injection. HMCP was toxic at higher doses with a LD50 around 3 mg/kg.
Keywords	артериальное давление ; антигипертензивный препарат ; фактор активации тромбоцитов ; Medicine ; R
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Siberian State Medical University (Tomsk)
Document type	Article ; Online
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Article ; Online: Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature.

Lathe, Richard / Sapronova, Alexandra / Kotelevtsev, Yuri

BMC geriatrics

2014 Volume 14, Page(s) 36

Abstract: Background: Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology?: Discussion: ... ...

Abstract	Background: Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Discussion: Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Mechanism: Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of 'immunosterol' 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. Summary: We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology.
MeSH term(s)	Aging/metabolism ; Aging/pathology ; Alzheimer Disease/blood ; Alzheimer Disease/etiology ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/blood ; Animals ; Atherosclerosis/blood ; Atherosclerosis/etiology ; Atherosclerosis/pathology ; Brain/blood supply ; Brain/metabolism ; Brain/pathology ; Humans ; Hydroxycholesterols/blood ; Inflammation/blood ; Inflammation/complications ; Inflammation/pathology ; Inflammation Mediators/blood
Chemical Substances	Amyloid beta-Peptides ; Hydroxycholesterols ; Inflammation Mediators ; 25-hydroxycholesterol (767JTD2N31)
Language	English
Publishing date	2014-03-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/1471-2318-14-36
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Article ; Online: Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors.

Tsitrina, Alexandra A / Krasylov, Igor V / Maltsev, Dmitry I / Andreichenko, Irina N / Moskvina, Viktoria S / Ivankov, Dmitry N / Bulgakova, Elena V / Nesterchuk, Mikhail / Shashkovskaya, Vera / Dashenkova, Nataliya O / Khilya, Vladimir P / Mikaelyan, Arsen / Kotelevtsev, Yuri

Glycobiology

2021 Volume 31, Issue 8, Page(s) 959–974

Abstract: Elevated plasma levels of hyaluronic acid (HA) is a disease marker in liver pathology and other inflammatory disorders. Inhibition of HA synthesis with coumarin 4-methylumbelliferone (4MU) has a beneficial effect in animal models of fibrosis, ... ...

Abstract	Elevated plasma levels of hyaluronic acid (HA) is a disease marker in liver pathology and other inflammatory disorders. Inhibition of HA synthesis with coumarin 4-methylumbelliferone (4MU) has a beneficial effect in animal models of fibrosis, inflammation, cancer and metabolic syndrome. 4MU is an active compound of approved choleretic drug hymecromone with low bioavailability and a broad spectrum of action. New, more specific and efficient inhibitors of hyaluronan synthases (HAS) are required. We have tested several newly synthesized coumarin compounds and commercial chitin synthesis inhibitors to inhibit HA production in cell culture assay. Coumarin derivative compound VII (10'-methyl-6'-phenyl-3'H-spiro[piperidine-4,2'-pyrano[3,2-g]chromene]-4',8'-dione) demonstrated inhibition of HA secretion by NIH3T3 cells with the half-maximal inhibitory concentration (IC50) = 1.69 ± 0.75 μΜ superior to 4MU (IC50 = 8.68 ± 1.6 μΜ). Inhibitors of chitin synthesis, etoxazole, buprofezin, triflumuron, reduced HA deposition with IC50 of 4.21 ± 3.82 μΜ, 1.24 ± 0.87 μΜ and 1.48 ± 1.44 μΜ, respectively. Etoxazole reduced HA production and prevented collagen fibre formation in the CCl4 liver fibrosis model in mice similar to 4MU. Bioinformatics analysis revealed homology between chitin synthases and HAS enzymes, particularly in the pore-forming domain, containing the proposed site for etoxazole binding.
MeSH term(s)	Animals ; Chitin ; Hyaluronan Synthases/metabolism ; Hyaluronic Acid/metabolism ; Hymecromone/pharmacology ; Mice ; NIH 3T3 Cells
Chemical Substances	Chitin (1398-61-4) ; Hymecromone (3T5NG4Q468) ; Hyaluronic Acid (9004-61-9) ; Hyaluronan Synthases (EC 2.4.1.212)
Language	English
Publishing date	2021-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1067689-2
ISSN	1460-2423 ; 0959-6658
ISSN (online)	1460-2423
ISSN	0959-6658
DOI	10.1093/glycob/cwab038
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Zs.A 3150: Show issues

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Article ; Online: lncRNA in the liver: Prospects for fundamental research and therapy by RNA interference.

Smekalova, Elena M / Kotelevtsev, Yuri V / Leboeuf, Dominique / Shcherbinina, Evgeniya Y / Fefilova, Anna S / Zatsepin, Timofei S / Koteliansky, Victor

Biochimie

2016 Volume 131, Page(s) 159–172

Abstract: Long non-coding RNAs constitute the most abundant part of the transcribed mammalian genome. lncRNAs affect all essential processes in the living cell including transcription, splicing, translation, replication, shaping of chromatin and post translational ...

Abstract	Long non-coding RNAs constitute the most abundant part of the transcribed mammalian genome. lncRNAs affect all essential processes in the living cell including transcription, splicing, translation, replication, shaping of chromatin and post translational modification of proteins. Alterations in lncRNA expression have been linked to a number of diseases; thus, modulation of lncRNA expression holds a huge potential for gene-based therapy. In this review we summarize published data about lncRNAs in the context of hepatic carcinogenesis and liver fibrosis, and the corresponding potential targets for gene therapy. Recent advancements in targeted delivery to the liver made RNA interference an invaluable tool to decipher hepatic lncRNA function and to develop lncRNA-oriented therapies for liver-involved diseases in the future. Different approaches for RNA delivery that can be used for functional studies in the lab and for clinical lncRNA based applications are critically discussed in this review.
MeSH term(s)	Animals ; Biomedical Research/methods ; Gene Expression Regulation ; Genetic Therapy/methods ; Humans ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/therapy ; RNA Interference ; RNA, Long Noncoding/genetics
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2016-12
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2016.06.007
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Article: Application of gene expression profiling to cardiovascular disease.

Henriksen, P A / Kotelevtsev, Y

Cardiovascular research

2002 Volume 54, Issue 1, Page(s) 16–24

Abstract: The number of cardiovascular publications featuring gene expression profiling technologies is growing rapidly. This article introduces four profiling techniques; serial analysis of gene expression, differential display, subtractive hybridisation and DNA ... ...

Abstract	The number of cardiovascular publications featuring gene expression profiling technologies is growing rapidly. This article introduces four profiling techniques; serial analysis of gene expression, differential display, subtractive hybridisation and DNA microarrays. Illustrations of their application towards cardiovascular research are given and their potential for gene discovery and improving our understanding of gene function is discussed.
MeSH term(s)	Animals ; Cardiovascular Diseases/embryology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/genetics ; Cells, Cultured ; Gene Expression Profiling ; Humans ; Image Processing, Computer-Assisted ; Models, Animal ; Myocardium/metabolism ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction
Language	English
Publishing date	2002-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1016/s0008-6363(01)00516-8
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