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Article ; Online: Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells.

Staroverov, Vladimir / Galatenko, Alexei / Knyazev, Evgeny / Tonevitsky, Alexander

2024 Volume 12, Page(s) e16964

Abstract: Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of ... ...

Abstract	Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses. Adopting such models for results of
MeSH term(s)	Humans ; COVID-19 ; Caco-2 Cells ; SARS-CoV-2 ; Epithelium ; Models, Theoretical
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.16964
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Article ; Online: Endocytosis and Transcytosis of SARS-CoV-2 Across the Intestinal Epithelium and Other Tissue Barriers.

Knyazev, Evgeny / Nersisyan, Stepan / Tonevitsky, Alexander

Frontiers in immunology

2021 Volume 12, Page(s) 636966

Abstract: Since 2003, the world has been confronted with three new betacoronaviruses that cause human respiratory infections: SARS-CoV, which causes severe acute respiratory syndrome (SARS), MERS-CoV, which causes Middle East respiratory syndrome (MERS), and SARS- ... ...

Abstract	Since 2003, the world has been confronted with three new betacoronaviruses that cause human respiratory infections: SARS-CoV, which causes severe acute respiratory syndrome (SARS), MERS-CoV, which causes Middle East respiratory syndrome (MERS), and SARS-CoV-2, which causes Coronavirus Disease 2019 (COVID-19). The mechanisms of coronavirus transmission and dissemination in the human body determine the diagnostic and therapeutic strategies. An important problem is the possibility that viral particles overcome tissue barriers such as the intestine, respiratory tract, blood-brain barrier, and placenta. In this work, we will 1) consider the issue of endocytosis and the possibility of transcytosis and paracellular trafficking of coronaviruses across tissue barriers with an emphasis on the intestinal epithelium; 2) discuss the possibility of antibody-mediated transcytosis of opsonized viruses due to complexes of immunoglobulins with their receptors; 3) assess the possibility of the virus transfer into extracellular vesicles during intracellular transport; and 4) describe the clinical significance of these processes. Models of the intestinal epithelium and other barrier tissues for
MeSH term(s)	Antibodies, Viral/metabolism ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/transmission ; COVID-19/virology ; Clinical Trials as Topic ; Endocytosis/drug effects ; Humans ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/virology ; Models, Biological ; SARS-CoV-2/drug effects ; SARS-CoV-2/immunology ; SARS-CoV-2/metabolism ; Tight Junctions/metabolism ; Tight Junctions/virology ; Transcytosis/drug effects ; Virus Attachment
Chemical Substances	Antibodies, Viral ; Antiviral Agents
Language	English
Publishing date	2021-09-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.636966
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Article: HIF-Dependent

Knyazev, Evgeny / Maltseva, Diana / Raygorodskaya, Maria / Shkurnikov, Maxim

Frontiers in genetics

2021 Volume 12, Page(s) 791640

Abstract: Intestinal epithelial cells exist in physiological hypoxia, leading to hypoxia-inducible factor (HIF) activation and supporting barrier function and cell metabolism of the intestinal epithelium. In contrast, pathological hypoxia is a common feature of ... ...

Abstract	Intestinal epithelial cells exist in physiological hypoxia, leading to hypoxia-inducible factor (HIF) activation and supporting barrier function and cell metabolism of the intestinal epithelium. In contrast, pathological hypoxia is a common feature of some chronic disorders, including inflammatory bowel disease (IBD). This work was aimed at studying HIF-associated changes in the intestinal epithelium in IBD. In the first step, a list of genes responding to chemical activation of hypoxia was obtained in an
Language	English
Publishing date	2021-11-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.791640
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Article ; Online: Chemical Induction of Trophoblast Hypoxia by Cobalt Chloride Leads to Increased Expression of DDIT3.

Knyazev, E N / Paul, S Yu / Tonevitsky, A G

Doklady. Biochemistry and biophysics

2021 Volume 499, Issue 1, Page(s) 251–256

Abstract: Choriocarcinoma cells BeWo b30 are used to model human placental trophoblast hypoxia using cobalt (II) chloride and hydroxyquinoline derivative (HD) as chemical inducers of hypoxia-inducible factor (HIF). In this study, it was shown that both substances ... ...

Abstract	Choriocarcinoma cells BeWo b30 are used to model human placental trophoblast hypoxia using cobalt (II) chloride and hydroxyquinoline derivative (HD) as chemical inducers of hypoxia-inducible factor (HIF). In this study, it was shown that both substances activate the hypoxic pathway and the epithelial-mesenchymal transition and inhibit the pathways of cell proliferation. However, CoCl
MeSH term(s)	Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Hypoxia/drug effects ; Cell Line, Tumor ; Cobalt/pharmacology ; Female ; Gene Expression Regulation/drug effects ; Humans ; Pregnancy ; Transcription Factor CHOP/metabolism ; Trophoblasts/cytology ; Trophoblasts/drug effects
Chemical Substances	DDIT3 protein, human ; Transcription Factor CHOP (147336-12-7) ; Cobalt (3G0H8C9362) ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-) ; cobaltous chloride (EVS87XF13W)
Language	English
Publishing date	2021-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2062390-2
ISSN	1608-3091 ; 1607-6729
ISSN (online)	1608-3091
ISSN	1607-6729
DOI	10.1134/S1607672921040104
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Article ; Online: KDM5 Family Demethylase Inhibitor KDOAM-25 Reduces Entry of SARS-CoV-2 Pseudotyped Viral Particles into Cells.

Knyazev, E N / Kalinin, R S / Abrikosova, V A / Mokrushina, Yu A / Tonevitskaya, S A

Bulletin of experimental biology and medicine

2023 Volume 175, Issue 1, Page(s) 150–156

Abstract: We studied the effect of KDM5 family demethylase inhibitors (JIB-04, PBIT, and KDOAM-25) on the penetration of SARS-CoV-2 pseudotyped viruses into differentiated Caco-2 cells and HEK293T cells with ACE2 hyperexpression. The above drugs were not cytotoxic. ...

Abstract	We studied the effect of KDM5 family demethylase inhibitors (JIB-04, PBIT, and KDOAM-25) on the penetration of SARS-CoV-2 pseudotyped viruses into differentiated Caco-2 cells and HEK293T cells with ACE2 hyperexpression. The above drugs were not cytotoxic. Only KDOAM-25 significantly reduced virus entry into the cells. The expression of ACE2 mRNA in Caco-2 significantly increased, while TMPRSS2 expression did not significantly change under these conditions. In differentiated Caco-2 cells, KDOAM-25 did not affect the expression of BRCA1, CDH1, TP53, SNAI1, VIM, and UGCG genes, for which an association with knockdown or overexpression of KDM5 demethylases or with the action of demethylase inhibitors had previously been shown. In undifferentiated Caco-2 cells, the expression of BRCA1, SNAI1, VIM, and CDH1 was significantly increased under the action of KDOAM-25.
MeSH term(s)	Humans ; SARS-CoV-2 ; Viral Pseudotyping ; COVID-19 ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Angiotensin-Converting Enzyme 2/pharmacology ; Caco-2 Cells ; HEK293 Cells ; Virion
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; KDOAM-25
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	390407-6
ISSN	1573-8221 ; 0007-4888 ; 0365-9615
ISSN (online)	1573-8221
ISSN	0007-4888 ; 0365-9615
DOI	10.1007/s10517-023-05827-w
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Article ; Online: Factors Involved in miRNA Processing Change Its Expression Level during Imitation of Hypoxia in BeWo b30 Cells.

Nersisyan, S A / Shkurnikov, M Yu / Knyazev, E N

Doklady. Biochemistry and biophysics

2020 Volume 493, Issue 1, Page(s) 205–207

Abstract: One of the main complications of pregnancy and causes of maternal and perinatal mortality is preeclampsia. The pathophysiology of preeclampsia is associated with the development of placenta and fetal hypoxia and secretion of a number of effective ... ...

Abstract	One of the main complications of pregnancy and causes of maternal and perinatal mortality is preeclampsia. The pathophysiology of preeclampsia is associated with the development of placenta and fetal hypoxia and secretion of a number of effective molecules. The human choriocarcinoma cell line BeWo b30 is often used as a model of the placental barrier. It was shown that oxyquinoline derivatives can mimic hypoxia by suppressing HIF-prolyl hydroxylases and the accumulation of HIF-1α. This effect also leads to a change in the expression of microRNAs and their target genes. However, with hypoxia in cells, not only the level of individual miRNAs but also the ratio of miRNA isoforms (isomiRs) can change, presumably due to inaccuracies in the work of the Drosha and Dicer enzymes. In this work, we showed a change in the expression of the factors involved in the maturation of miRNAs when simulating hypoxia in BeWo b30 cells with an oxyquinoline derivative, which may be one of the causes for the change in the ratio of miRNA isoforms.
MeSH term(s)	Cell Hypoxia/physiology ; Cell Line, Tumor ; Choriocarcinoma/genetics ; Choriocarcinoma/pathology ; Female ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Pregnancy ; RNA Processing, Post-Transcriptional ; Uterine Neoplasms/genetics ; Uterine Neoplasms/pathology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2020-09-07
Publishing country	Russia (Federation)
Document type	Journal Article
ZDB-ID	2062390-2
ISSN	1608-3091 ; 1607-6729
ISSN (online)	1608-3091
ISSN	1607-6729
DOI	10.1134/S1607672920040110
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Article ; Online: Overcoming inefficient detection in sub-shot-noise absorption measurement and imaging.

Knyazev, Eugene / Khalili, Farid Ya / Chekhova, Maria V

Optics express

2019 Volume 27, Issue 6, Page(s) 7868–7885

Abstract: Photon-number squeezing and correlations enable measurement of absorption with an accuracy exceeding that of the shot-noise limit. However, sub-shot noise imaging and sensing based on these methods require high detection efficiency, which can be a ... ...

Abstract	Photon-number squeezing and correlations enable measurement of absorption with an accuracy exceeding that of the shot-noise limit. However, sub-shot noise imaging and sensing based on these methods require high detection efficiency, which can be a serious obstacle if measurements are carried out in "difficult" spectral ranges. We show that this problem can be overcome through the phase-sensitive amplification before detection. Here we propose an experimental scheme of sub-shot-noise imaging with tolerance to detection losses.
Language	English
Publishing date	2019-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1491859-6
ISSN	1094-4087 ; 1094-4087
ISSN (online)	1094-4087
ISSN	1094-4087
DOI	10.1364/OE.27.007868
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Article ; Online: Integrative analysis of miRNA and mRNA sequencing data reveals potential regulatory mechanisms of ACE2 and TMPRSS2.

Nersisyan, Stepan / Shkurnikov, Maxim / Turchinovich, Andrey / Knyazev, Evgeny / Tonevitsky, Alexander

PloS one

2020 Volume 15, Issue 7, Page(s) e0235987

Abstract: Development of novel approaches for regulating the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) is becoming increasingly important within the context of the ongoing COVID-19 pandemic since these ... ...

Abstract	Development of novel approaches for regulating the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) is becoming increasingly important within the context of the ongoing COVID-19 pandemic since these enzymes play a crucial role in cell infection. In this work we searched for putative ACE2 and TMPRSS2 expression regulation networks mediated by various miRNA isoforms (isomiR) across different human organs using publicly available paired miRNA/mRNA-sequencing data from The Cancer Genome Atlas (TCGA) project. As a result, we identified several miRNA families targeting ACE2 and TMPRSS2 genes in multiple tissues. In particular, we found that lysine-specific demethylase 5B (JARID1B), encoded by the KDM5B gene, can indirectly affect ACE2 / TMPRSS2 expression by repressing transcription of hsa-let-7e / hsa-mir-125a and hsa-mir-141 / hsa-miR-200 miRNA families which are targeting these genes.
MeSH term(s)	3' Untranslated Regions ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/enzymology ; Coronavirus Infections/virology ; Databases, Genetic ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Nuclear Proteins/genetics ; Pandemics ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/enzymology ; Pneumonia, Viral/virology ; RNA Isoforms/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Seq ; Repressor Proteins/genetics ; SARS-CoV-2 ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Single-Cell Analysis
Chemical Substances	3' Untranslated Regions ; MicroRNAs ; Nuclear Proteins ; RNA Isoforms ; RNA, Messenger ; Repressor Proteins ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; KDM5B protein, human (EC 1.14.11.-) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0235987
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Article ; Online: MicroRNA miR-27a as a possible regulator of anti-inflammatory macrophage phenotype in preeclamptic placenta.

Vishnyakova, Polina / Gantsova, Elena / Kiseleva, Viktoriia / Lazarev, Dmitry / Knyazev, Evgeny / Poltavets, Anastasiya / Iskusnykh, Marina / Muminova, Kamilla / Potapova, Alena / Khodzhaeva, Zulfiya / Elchaninov, Andrey / Fatkhudinov, Timur / Sukhikh, Gennady

Placenta

2023 Volume 145, Page(s) 151–161

Abstract: Introduction: The role of the TGFβ signaling pathway, an important cascade responsible for the anti-inflammatory polarization of macrophages, in the development of both early- and late-onset preeclampsia (eoPE and loPE), remains poorly understood. In ... ...

Abstract	Introduction: The role of the TGFβ signaling pathway, an important cascade responsible for the anti-inflammatory polarization of macrophages, in the development of both early- and late-onset preeclampsia (eoPE and loPE), remains poorly understood. In this study, we examined the components of the TGFβ signaling cascade and macrophage markers within placental tissue in normal pregnancy and in PE. Methods: Patients with eoPE, loPE, and normal pregnancy were enrolled in the study (n = 10 in each group). Following techniques were used for the investigation: immunohistochemistry analysis, western blotting, qRT-PCR, isolation of monocytes by magnetic sorting, transfection, microRNA sequencing, and bioinformatic analysis. Results: We observed a significant decrease in the anti-inflammatory macrophage marker CD206 in the loPE group, alongside with a significant down-regulation of CD206 protein production in both eoPE and loPE groups. The level of CD68-positive cells and relative levels of CD163 and MARCO production were comparable across the groups. However, we identified a significant decrease in the TGFβ receptor 2 production and its gene expression in the PE group. Further analysis revealed a link between TGFBR2 and MRC1 (CD206) genes through a single miRNA, hsa-miR-27a-3p. Transfecting CD14-derived macrophages with the hsa-miR-27a-3p mimic significantly changed TGFBR2 production, indicating the potential role of this miRNA in regulating the TGFβ signaling pathway. We also revealed the up-regulation of hsa-miR-27a-5p and hsa-miR-27a-3p in the trophoblast BeWo b30 cell line under the severe hypoxia condition and the fact that TGFBR2 3' UTR could serve as a potential target for these miRNAs. Discussion: Our findings uncover a novel potential therapeutic target for managing patients with PE, significantly contributing to a deeper comprehension of the underlying mechanisms involved in the development of this pathology.
MeSH term(s)	Female ; Humans ; Pregnancy ; Anti-Inflammatory Agents ; Eosine Yellowish-(YS)/analogs & derivatives ; Macrophages/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Phenotype ; Phosphatidylethanolamines ; Placenta/metabolism ; Receptor, Transforming Growth Factor-beta Type II/genetics ; Receptor, Transforming Growth Factor-beta Type II/metabolism ; Transforming Growth Factor beta/genetics
Chemical Substances	Anti-Inflammatory Agents ; Eosine Yellowish-(YS) (TDQ283MPCW) ; eosinylphosphatidylethanolamine ; MicroRNAs ; Phosphatidylethanolamines ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; Transforming Growth Factor beta ; MIRN27 microRNA, human
Language	English
Publishing date	2023-12-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	603951-0
ISSN	1532-3102 ; 0143-4004
ISSN (online)	1532-3102
ISSN	0143-4004
DOI	10.1016/j.placenta.2023.12.003
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Article ; Online: Relationship between the Expression Level of PSMD11 and Other Proteasome Proteins with the Activity of Ricin and Viscumin.

Maltseva, D V / Raigorodskaya, M P / Tikhonova, O V / Knyazev, E N / Tonevitsky, E A

Doklady. Biochemistry and biophysics

2020 Volume 493, Issue 1, Page(s) 198–200

Abstract: The role of proteasome proteins and proteins of the ERAD system in the cytotoxicity of type II ribosome-inactivating proteins ricin and viscumin was investigated. For this, the cell line of colorectal adenocarcinoma HT29, as well as the HT29-sh002 line ... ...

Abstract	The role of proteasome proteins and proteins of the ERAD system in the cytotoxicity of type II ribosome-inactivating proteins ricin and viscumin was investigated. For this, the cell line of colorectal adenocarcinoma HT29, as well as the HT29-sh002 line obtained on its basis, were used. On the basis on the proteome analysis of these lines and the estimation of the proportion of inactivated ribosomes, it was shown that the contribution of the proteasome to the degradation of the catalytic subunits of toxins is different. The role of the Cdc37 co-chaperone in maintaining the stability of A subunit of viscumin in the cytoplasm is shown.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chaperonins/genetics ; Chaperonins/metabolism ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Cytoplasm/metabolism ; Humans ; Proteasome Endopeptidase Complex/biosynthesis ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Ribosome Inactivating Proteins, Type 2/pharmacology ; Ribosomes/metabolism ; Ricin/pharmacology ; Toxins, Biological/pharmacology ; Tumor Cells, Cultured
Chemical Substances	CDC37 protein, human ; Cell Cycle Proteins ; Ribosome Inactivating Proteins, Type 2 ; Toxins, Biological ; mistletoe lectin I ; Ricin (9009-86-3) ; PSMD11 protein, human (EC 3.4.25.1) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Chaperonins (EC 3.6.1.-)
Language	English
Publishing date	2020-09-07
Publishing country	Russia (Federation)
Document type	Journal Article
ZDB-ID	2062390-2
ISSN	1608-3091 ; 1607-6729
ISSN (online)	1608-3091
ISSN	1607-6729
DOI	10.1134/S1607672920040080
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