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  1. Article: [Transcription Factor NRF2 in Endothelial Functions].

    Kondratenko, N D / Zinovkina, L A / Zinovkin, R A

    Molekuliarnaia biologiia

    2023  Volume 57, Issue 6, Page(s) 1058–1076

    Abstract: The transcription factor NRF2 is a major regulator of cell antioxidant defense. NRF2 is activated by various stimuli, such as oxidants and electrophiles, to induce transcription of a number of genes whose products are involved in xenobiotic metabolism ... ...

    Abstract The transcription factor NRF2 is a major regulator of cell antioxidant defense. NRF2 is activated by various stimuli, such as oxidants and electrophiles, to induce transcription of a number of genes whose products are involved in xenobiotic metabolism and contribute to the reduction of oxidative stress. NRF2 is one of the key transcription factors that ensure the endothelial cell function. The endothelium is a cell layer that lines the lumens of blood vessels and performs various homeostatic functions, controlling migration of leukocytes, regulating thrombosis and vascular tone, and playing a role in angiogenesis. Endothelial dysfunction is often accompanied by inflammation and oxidative stress, which may lead to cell aging and cell death by apoptosis, necrosis, or ferroptosis. Endothelial dysfunction contributes to the development of diabetes and common cardiovascular disorders, such as hypertension and atherosclerosis. Many pathophysiological processes in the endothelium, including senile changes, are associated with decreased NRF2 activity, leading to inflammatory activation and decreasing activity of the cell antioxidant defense systems. Activation of the NRF2 signaling pathway generally contributes to the resolution of inflammation and oxidative stress. The review focuses on the role that NRF2 plays in basic functions of the endothelium in normal and pathological conditions. Advantages and disadvantages of NRF2 activation as a way to prevent and treat cardiovascular diseases are discussed additionally.
    MeSH term(s) Humans ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Antioxidants/metabolism ; Endothelium/metabolism ; Gene Expression Regulation ; Oxidative Stress ; Cardiovascular Diseases/genetics ; Inflammation/genetics ; Inflammation/metabolism
    Chemical Substances NF-E2-Related Factor 2 ; Antioxidants
    Language Russian
    Publishing date 2023-12-08
    Publishing country Russia (Federation)
    Document type English Abstract ; Journal Article
    ZDB-ID 213542-5
    ISSN 0026-8984
    ISSN 0026-8984
    DOI 10.31857/S0026898423060101, EDN: QXHFSB
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  2. Article ; Online: Transcription Factor Nrf2 as a Potential Therapeutic Target for Prevention of Cytokine Storm in COVID-19 Patients.

    Zinovkin, R A / Grebenchikov, O A

    Biochemistry. Biokhimiia

    2020  Volume 85, Issue 7, Page(s) 833–837

    Abstract: Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the ... ...

    Abstract Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.
    MeSH term(s) Animals ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Betacoronavirus ; COVID-19 ; Catechin/analogs & derivatives ; Catechin/pharmacology ; Catechin/therapeutic use ; Coronavirus Infections/drug therapy ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; Cytokines/antagonists & inhibitors ; Cytokines/metabolism ; Dimethyl Fumarate/pharmacology ; Dimethyl Fumarate/therapeutic use ; Female ; Humans ; Immunosuppressive Agents/pharmacology ; Immunosuppressive Agents/therapeutic use ; Inflammation/metabolism ; Isothiocyanates/pharmacology ; Isothiocyanates/therapeutic use ; Male ; Mice ; Molecular Targeted Therapy/methods ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/drug effects ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/virology ; Respiratory Distress Syndrome/drug therapy ; Respiratory Distress Syndrome/metabolism ; Respiratory Distress Syndrome/virology ; Resveratrol/pharmacology ; Resveratrol/therapeutic use ; SARS-CoV-2 ; Signal Transduction/drug effects ; Sulfoxides ; Thiosulfates/pharmacology ; Thiosulfates/therapeutic use ; COVID-19 Drug Treatment
    Chemical Substances Antioxidants ; Cytokines ; Immunosuppressive Agents ; Isothiocyanates ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Sulfoxides ; Thiosulfates ; Catechin (8R1V1STN48) ; epigallocatechin gallate (BQM438CTEL) ; Dimethyl Fumarate (FO2303MNI2) ; sulforaphane (GA49J4310U) ; sodium thiosulfate (HX1032V43M) ; Resveratrol (Q369O8926L)
    Keywords covid19
    Language English
    Publishing date 2020-10-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297920070111
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  3. Article: Transcription Factor Nrf2 as a Potential Therapeutic Target for Prevention of Cytokine Storm in COVID-19 Patients

    Zinovkin, R A / Grebenchikov, O A

    Biochemistry (Mosc)

    Abstract: Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the ... ...

    Abstract Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #772260
    Database COVID19

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  4. Article: TRANSCRIPTION FACTOR Nrf2 AS A THERAPEUTIC TARGET FOR THE PREVENTION OF CYTOKINE STORM IN COVID-19

    Zinovkin, R. A. / Grebenchikov, O. A.

    Biokhimiya

    Abstract: Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the ... ...

    Abstract Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients Nrf2 является ключевым фактором транскрипции, ответственным за антиоксидантную защиту во многих тканях и клетках, включая альвеолярный эпителий, эндотелий и макрофаги Кроме того, Nrf2 функционирует как транскрипционный репрессор, подавляющий экспрессию цитокинов воспаления в макрофагах Пациенты с COVID-19 в критическом состоянии зачастую имеют чрезвычайно высокие параметры окислительного стресса и системного воспаления, которое служит одной из основных причин летальности В данной статье представлено обоснование использования индукторов транскрипционного фактора Nrf2 для предотвращения развития избыточного воспалительного ответа при COVID-19
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #859407
    Database COVID19

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  5. Article: Effect of Antioxidants on the Production of MCP-1 Chemokine by EA.hy926 Cells in Response to IL-6.

    Chelombitko, M A / Galkin, I I / Pletjushkina, O Yu / Zinovkin, R A / Popova, E N

    Moscow University biological sciences bulletin

    2022  Volume 77, Issue 3, Page(s) 184–191

    Abstract: An elevated level of circulatory interleukin 6 (IL-6) is a biomarker for cytokine storm of various etiologies, including COVID-19, and contributes to poor prognosis. Vascular endothelial cells are one of the main targets of pathological action of IL-6. ... ...

    Abstract An elevated level of circulatory interleukin 6 (IL-6) is a biomarker for cytokine storm of various etiologies, including COVID-19, and contributes to poor prognosis. Vascular endothelial cells are one of the main targets of pathological action of IL-6. IL-6 activates the trans-signaling pathway via the formation of the IL-6/sIL-6Ra/gp130 receptor complex and subsequent activation of the JAK/STAT3 signaling pathway and PI3K/AKT and MEK/ERK kinases in some cases. Previously, it was shown by the authors' group and other researchers that reactive oxygen species (ROS), including mitochondrial ROS (mito-ROS), contribute to the induction of IL-6 expression in the endothelium, mainly due to increased activation of the transcription factor NF-kB. We have also shown that the mitochondria-targeted antioxidant SkQ1 (Plastoquinolyl-10(6'-decyltriphenyl)phosphonium) prevented tumor necrosis factor (TNF)-induced cytokine storm and death in mice. In the aortas of these animals, SkQ1 also prevented the increase in the expression of NF-kB-dependent genes, including the cytokine IL-6 and the chemokine MCP-1. In the current work, the hypothesis of mito-ROS involvement in the IL-6-signaling-mediated proinflammatory gene expression in endothelial cells is tested. SkQ1 suppressed the expression and secretion of the MCP-1 chemokine, induced by IL-6 in combination with sIL-6-Ra, but not the expression of ICAM-1 adhesion molecules in EA.hy926 human endothelial cells. Using specific inhibitors, the authors have shown that, in EA.hy926 cells, IL-6-induced expression of MCP-1 and ICAM-1 depends on the signaling protein and transcription activator STAT3 and, in some cases, on JNK, PI3K, and MEK1/2 kinases and is independent of p38 kinase. In this model, IL-6 induced rapid STAT3 activation, while ERK1/2 activation was less pronounced, and there was no IL-6 effect on Akt and JNK activation. SkQ1 partially suppressed STAT3 and ERK1/2 activation. Thus, we have shown that SkQ1 suppresses not only NF-kB-dependent expression of IL-6 and other proinflammatory genes but also IL-6-induced activation of JAK/STAT3 and STAT3-dependent expression of MCP-1, which probably contributes to the overall therapeutic effect of SkQ1.
    Language English
    Publishing date 2022-11-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2325902-4
    ISSN 1934-791X ; 0096-3925
    ISSN (online) 1934-791X
    ISSN 0096-3925
    DOI 10.3103/S0096392522030026
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  6. Article ; Online: T19

    D. Zinovkin

    EJC Supplements, Vol 13, Iss 1, p

    2015  Volume 73

    Abstract: Endometrioid endometrial adenocarcimoma is the most frequent gynecologic malignancy in the western world. It is well known that inflammation plays a key role in the initiation and development of cancer as well as promotes both specific and innate immune ... ...

    Abstract Endometrioid endometrial adenocarcimoma is the most frequent gynecologic malignancy in the western world. It is well known that inflammation plays a key role in the initiation and development of cancer as well as promotes both specific and innate immune response. There is no information on the status of the local anti-tumor cellular immunity in endometrioid adenocarcinoma of the corpus uteri microenvironment in the Russian and English language medical scientific literature. Various studies have shown that high intratumor microvessel density in endometrial cancer is associated with advanced stage, increased risk of recurrent disease and with poor prognosis. Vascular endothelial growth factor (VEGF) is a glycoprotein with potent mitogenic activity. It has been demonstrated to be a key component in the promotion of angiogenesis. Materials and methods: There were singlet 24 cases of endometrioid adenocarcinoma with retrospectively known good (survival) and poor (death) outcomes. All cases were immunohistochemically stained for CD3, CD20, CD57, CD68, S100, CD34 and VEGF, expression of was evaluated by IHC-profiler. The number and the area of vessels was count in “hot spot” zones and calculated per 1 mm. For compare of the characteristics of signs was used comparison of two independent samples – U-Mann–Whitney test. The level of statistical significance was accepted by p < 0.05 Results: T-lymphocytes cells were situated predominantly in desmoplastic stroma of the tumor. CD3 expression was significant higher in the group of good outcome (p = 0.00042), B-lymphocytes cells were predominantly in epithelial component of tumor. CD20 was expressed in endometriod adenocarcinoma with good and poor outcome without statistically significant difference (p = 0.976). NK-lymphocytes were predominantly in peritumoral stroma. CD57 expression was statistically significant higher in the group of good outcome (p = 0.000307). Tumor infiltrating macrophages can were frequent in tumor stroma than in tumor islets. CD68 expression cells ...
    Keywords Medicine ; R ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 616
    Language English
    Publishing date 2015-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: FN14 mRNA Expression Correlates with an Increased Number of Veins during Angiogenesis in the Process of Liver Fibrosis.

    Lebedeva, Elena I / Babenka, Andrei S / Hastemir, Pelin / Shchastniy, Anatoliy T / Zinovkin, Dmitry A / Pranjol, Md Zahidul Islam

    International journal of molecular and cellular medicine

    2023  Volume 11, Issue 4, Page(s) 274–284

    Abstract: ... of Fn14 correlated with the number of veins in liver fibrosis (r=0.44, p=0.008). Our data shows ...

    Abstract In this study, we hypothesize that angiogenesis of special hepatic vessels such as sinusoid capillaries or veins is closely associated with increasing production of connective tissue in fibrogenesis. Thirty-six male Wistar rats were induced with hepatitis and cirrhosis of the liver using thioacetamide. The number of sinusoidal capillaries, veins, arteries and the area of connective tissue were counted and determined. Immunohistochemical study was performed on paraffin sections using monoclonal mouse anti-CD31. mRNA expression was determined using qPCR. We found a statistically significant reduction in the number of sinusoidal capillaries (p<0.0001) and an increase in the number of interlobular veins (p<0.0001) in the fibrosis and cirrhosis groups compared to the control group. There are no differences in the number of interlobular arteries (p=0.282) in the three groups. In our analysis, we found that the expression (mRNA) of Fn14 correlated with the number of veins in liver fibrosis (r=0.44, p=0.008). Our data shows that modulation of veins angiogenesis during fibrosis in chronic liver diseases may play an important role in increasing pathological changes of the liver.
    Language English
    Publishing date 2023-09-01
    Publishing country Iran
    Document type Journal Article
    ZDB-ID 2697015-6
    ISSN 2251-9645 ; 2251-9637
    ISSN (online) 2251-9645
    ISSN 2251-9637
    DOI 10.22088/IJMCM.BUMS.11.4.274
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  8. Article ; Online: DNA Methylation, Mitochondria, and Programmed Aging.

    Zinovkina, L A / Zinovkin, R A

    Biochemistry. Biokhimiia

    2015  Volume 80, Issue 12, Page(s) 1571–1577

    Abstract: DNA methylation is a key epigenetic process involved in the regulation of nuclear gene expression. Progress in the study of genomic DNA methylation led to the precise identification of methylation sites reflecting biological age of cells and tissues. ... ...

    Abstract DNA methylation is a key epigenetic process involved in the regulation of nuclear gene expression. Progress in the study of genomic DNA methylation led to the precise identification of methylation sites reflecting biological age of cells and tissues. However, the functional significance of mitochondrial DNA (mtDNA) methylation remains unknown. Growing evidence suggests that mtDNA methylation is linked to aging and oxidative stress. This mini-review summarizes information about the methylation of nuclear and mtDNA in mammals, indicating the connection of these processes to programmed aging.
    MeSH term(s) Aging/genetics ; Aging/metabolism ; Animals ; DNA Methylation ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Epigenesis, Genetic ; Epigenomics ; Humans ; Mitochondria/genetics ; Mitochondria/metabolism ; Oxidative Stress/genetics
    Chemical Substances DNA, Mitochondrial
    Language English
    Publishing date 2015-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297915120044
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  9. Article ; Online: УРОВЕНЬ СОДЕРЖАНИЯ ТРОМБОЦИТОВ В КРОВИ У ПАЦИЕНТОВ С СИНДРОМОМ ДИАБЕТИЧЕСКОЙ СТОПЫ КАК КРИТЕРИЙ ТЯЖЕСТИ ПОРАЖЕНИЯ

    E. L. Stavchikov / I. V. Zinovkin / A. V. Marochkov

    Žurnal Grodnenskogo Gosudarstvennogo Medicinskogo Universiteta, Vol 20, Iss 1, Pp 50-

    2022  Volume 54

    Abstract: Введение. Сахарный диабет – глобальная угроза общественному здоровью. Синдром диабетической стопы служит маркером повышенной смертности пациентов с диабетом. Важно понимать факторы, которые бы свидетельствовали о появлении осложнений сахарного диабета. ... ...

    Abstract Введение. Сахарный диабет – глобальная угроза общественному здоровью. Синдром диабетической стопы служит маркером повышенной смертности пациентов с диабетом. Важно понимать факторы, которые бы свидетельствовали о появлении осложнений сахарного диабета. Цель. Исследовать факторы, влияющие на возникновение осложнений у пациентов с сахарным диабетом, выявление независимых предикторов осложнений. Материал и методы. Проведено проспективное нерандомизированное обсервационное исследование с 01.06.2021 по 01.09.2021 гг. В исследовании приняли участие 47 пациентов. Пациенты были разделены на группу 1 – в анамнезе имеется сахарный диабет 2-го типа, и группу 2 – пациенты с сахарным диабетом 2-го типа, осложненным синдромом диабетической стопы. Результаты. На этапе исследования уровень тромбоцитов в крови у всех пациентов был равен 222,0 (177,5; 318,5)×109/л. Уровень тромбоцитов в группе 1 – 186 (154,5; 251,5)×109/л, а в группе 2 – 326,0 (239,25; 357,25)×109/л, статистические различия значимы (р<0,001). Пациенты с синдромом диабетической стопы нами были распределены по классификации Wagner, где в каждой из степени классификации определялись показатели содержания тромбоцитов. Уровень тромбоцитов был равен у пациентов 1-й степени – 267,0 (222,0; 322,5)×109/л, 2-й степени – 358,0 (234,75; 280,25)×109/л, 3-й степени – 340 (309,5; 360,5)×109/л, 4-й степени – 328 (305,75; 330,0)×109/л, 5-й степени – 404 (293,5; 407,75)×109/л. Полученные нами данные продемонстрировали, что содержание тромбоцитов в крови у пациентов с сахарным диабетом, осложненным синдромом диабетической стопы, больше, чем у пациентов с сахарным диабетом без осложнений. Содержание тромбоцитов у пациентов с синдромом диабетической стопы постепенно повышалось с увеличением степени по шкале Wagner. Содержание в крови тромбоцитов может быть полезно для оценки степени тяжести синдрома диабетической стопы. Выводы. Уровень содержания тромбоцитов в крови у пациентов с сахарным диабетом 2-го типа может рассматриваться как лабораторный критерий и независимый фактор риска ...
    Keywords синдром диабетической стопы ; тромбоциты ; критерии ; Medicine ; R
    Language Belarusian
    Publishing date 2022-03-01T00:00:00Z
    Publisher Grodno State Medical University
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: COVID-19 and Oxidative Stress.

    Chernyak, B V / Popova, E N / Prikhodko, A S / Grebenchikov, O A / Zinovkina, L A / Zinovkin, R A

    Biochemistry. Biokhimiia

    2021  Volume 85, Issue 12, Page(s) 1543–1553

    Abstract: Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the ... ...

    Abstract Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the body's systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death of the infected cells, activation of innate immune response, and secretion of inflammatory cytokines. All these processes are associated with the development of oxidative stress, which makes an important contribution to pathogenesis of the viral infections. This review analyzes information on the oxidative stress associated with the infections caused by SARS-CoV-2 and other respiratory viruses. The review also focuses on involvement of the vascular endothelium in the COVID-19 pathogenesis.
    MeSH term(s) Angiotensin II/metabolism ; Antioxidants/therapeutic use ; COVID-19/drug therapy ; COVID-19/pathology ; COVID-19/virology ; Cytokines/metabolism ; Endothelium/cytology ; Endothelium/metabolism ; Humans ; Immunity, Innate ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; SARS-CoV-2/isolation & purification
    Chemical Substances Antioxidants ; Cytokines ; Reactive Oxygen Species ; Angiotensin II (11128-99-7)
    Language English
    Publishing date 2021-04-22
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297920120068
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