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  1. Article: ELOVL5

    Nikulin, Sergey / Razumovskaya, Alexandra / Poloznikov, Andrey / Zakharova, Galina / Alekseev, Boris / Tonevitsky, Alexander

    Frontiers in molecular biosciences

    2023  Volume 10, Page(s) 1075704

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2023-01-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2023.1075704
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Post-Processing Algorithm for miRNA Microarray Data.

    Nersisyan, Stepan / Shkurnikov, Maxim / Poloznikov, Andrey / Turchinovich, Andrey / Burwinkel, Barbara / Anisimov, Nikita / Tonevitsky, Alexander

    International journal of molecular sciences

    2020  Volume 21, Issue 4

    Abstract: One of the main disadvantages of using DNA microarrays for miRNA expression profiling is the inability of adequate comparison of expression values across different miRNAs. This leads to a large amount of miRNAs with high scores which are actually not ... ...

    Abstract One of the main disadvantages of using DNA microarrays for miRNA expression profiling is the inability of adequate comparison of expression values across different miRNAs. This leads to a large amount of miRNAs with high scores which are actually not expressed in examined samples, i.e., false positives. We propose a post-processing algorithm which performs scoring of miRNAs in the results of microarray analysis based on expression values, time of discovery of miRNA, and correlation level between the expressions of miRNA and corresponding pre-miRNA in considered samples. The algorithm was successfully validated by the comparison of the results of its application to miRNA microarray breast tumor samples with publicly available miRNA-seq breast tumor data. Additionally, we obtained possible reasons why miRNA can appear as a false positive in microarray study using paired miRNA sequencing and array data. The use of DNA microarrays for estimating miRNA expression profile is limited by several factors. One of them consists of problems with comparing expression values of different miRNAs. In this work, we show that situation can be significantly improved if some additional information is taken into consideration in a comparison.
    MeSH term(s) Algorithms ; Breast Neoplasms/metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/genetics ; Oligonucleotide Array Sequence Analysis/methods ; Sensitivity and Specificity ; Sequence Analysis, RNA
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2020-02-12
    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/ijms21041228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Probable Mechanisms of Doxorubicin Antitumor Activity Enhancement by Ginsenoside Rh2.

    Popov, Alexander / Klimovich, Anna / Styshova, Olga / Tsybulsky, Alexander / Hushpulian, Dmitry / Osipyants, Andrey / Khristichenko, Anna / Kazakov, Sergey / Ahuja, Manuj / Kaidery, Navneet / Thomas, Bobby / Tishkov, Vladimir / Brown, Abraham / Gazaryan, Irina / Poloznikov, Andrey

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 3

    Abstract: Ginsenoside Rh2 increases the efficacy of doxorubicin (DOX) treatment in murine models of solid and ascites Ehrlich's adenocarcinoma. In a solid tumor model (treatment commencing 7 days after inoculation), DOX + Rh2 co-treatment was significantly more ... ...

    Abstract Ginsenoside Rh2 increases the efficacy of doxorubicin (DOX) treatment in murine models of solid and ascites Ehrlich's adenocarcinoma. In a solid tumor model (treatment commencing 7 days after inoculation), DOX + Rh2 co-treatment was significantly more efficacious than DOX alone. If treatment was started 24 h after inoculation, the inhibition of tumor growth of a solid tumor for the DOX + Rh2 co-treatment group was complete. Furthermore, survival in the ascites model was dramatically higher for the DOX + Rh2 co-treatment group than for DOX alone. Mechanisms underlying the combined DOX and Rh2 effects were studied in primary Ehrlich's adenocarcinoma-derived cells and healthy mice's splenocytes. Despite the previously established Rh2 pro-oxidant activity, DOX + Rh2 co-treatment revealed no increase in ROS compared to DOX treatment alone. However, DOX + Rh2 treatment was more effective in suppressing Ehrlich adenocarcinoma cell adhesion than either treatment alone. We hypothesize that the benefits of DOX + Rh2 combination treatment are due to the suppression of tumor cell attachment/invasion that might be effective in preventing metastatic spread of tumor cells. Ginsenoside Rh2 was found to be a modest activator in a Neh2-luc reporter assay, suggesting that Rh2 can activate the Nrf2-driven antioxidant program. Rh2-induced direct activation of Nrf2 might provide additional benefits by minimizing DOX toxicity towards non-cancerous cells.
    MeSH term(s) Adenocarcinoma ; Animals ; Doxorubicin/pharmacology ; Drugs, Chinese Herbal/pharmacology ; Ginsenosides/pharmacology ; Mice
    Chemical Substances Drugs, Chinese Herbal ; Ginsenosides ; ginsenoside Rh2 (78214-33-2) ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2022-01-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27030628
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Impedance Spectroscopy as a Tool for Monitoring Performance in 3D Models of Epithelial Tissues.

    Gerasimenko, Tatiana / Nikulin, Sergey / Zakharova, Galina / Poloznikov, Andrey / Petrov, Vladimir / Baranova, Ancha / Tonevitsky, Alexander

    Frontiers in bioengineering and biotechnology

    2020  Volume 7, Page(s) 474

    Abstract: In contrast to traditional 2D cell cultures, both 3D models and organ-on-a-chip devices allow the study of the physiological responses of human cells. These models reconstruct human tissues in conditions closely resembling the body. Translation of these ... ...

    Abstract In contrast to traditional 2D cell cultures, both 3D models and organ-on-a-chip devices allow the study of the physiological responses of human cells. These models reconstruct human tissues in conditions closely resembling the body. Translation of these techniques into practice is hindered by associated labor costs, a need which may be remedied by automation. Impedance spectroscopy (IS) is a promising, automation-compatible label-free technology allowing to carry out a wide range of measurements both in real-time and as endpoints. IS has been applied to both the barrier cultures and the 3D constructs. Here we provide an overview of the impedance-based analysis in different setups and discuss its utility for organ-on-a-chip devices. Most attractive features of impedance-based assays are their compatibility with high-throughput format and supports for the measurements in real time with high temporal resolution, which allow tracing of the kinetics. As of now, IS-based techniques are not free of limitations, including imperfect understanding of the parameters that have their effects on the impedance, especially in 3D cell models, and relatively high cost of the consumables. Moreover, as the theory of IS stems from electromagnetic theory and is quite complex, work on popularization and explanation of the method for experimental biologists is required. It is expected that overcoming these limitations will lead to eventual establishing IS based systems as a standard for automated management of cell-based experiments in both academic and industry environments.
    Language English
    Publishing date 2020-01-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2719493-0
    ISSN 2296-4185
    ISSN 2296-4185
    DOI 10.3389/fbioe.2019.00474
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Structure-Activity Relationships and Transcriptomic Analysis of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors.

    Poloznikov, Andrey A / Nikulin, Sergey V / Hushpulian, Dmitry M / Khristichenko, Anna Yu / Osipyants, Andrey I / Asachenko, Andrey F / Shurupova, Olga V / Savin, Svyatoslav S / Lee, Sue H / Gaisina, Irina N / Thatcher, Gregory R J / Narciso, Anthony / Chang, Eric P / Kazakov, Sergey V / Krucher, Nancy / Tishkov, Vladimir I / Thomas, Bobby / Gazaryan, Irina G

    Antioxidants (Basel, Switzerland)

    2022  Volume 11, Issue 2

    Abstract: To evaluate the differences in action of commercially available 2-oxoglutarate mimetics and "branched-tail" oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD), the inhibitors' ... ...

    Abstract To evaluate the differences in action of commercially available 2-oxoglutarate mimetics and "branched-tail" oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD), the inhibitors' IC
    Language English
    Publishing date 2022-01-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11020220
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: 9-ING-41, a Small Molecule Inhibitor of GSK-3β, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells.

    Poloznikov, Andrey / Nikulin, Sergey / Bolotina, Larisa / Kachmazov, Andrei / Raigorodskaya, Maria / Kudryavtseva, Anna / Bakhtogarimov, Ildar / Rodin, Sergey / Gaisina, Irina / Topchiy, Maxim / Asachenko, Andrey / Novosad, Victor / Tonevitsky, Alexander / Alekseev, Boris

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 777114

    Abstract: Colorectal cancer (CRC) is one of the most common and lethal types of cancer. Although researchers have made significant efforts to study the mechanisms underlying CRC drug resistance, our knowledge of this disease is still limited, and novel therapies ... ...

    Abstract Colorectal cancer (CRC) is one of the most common and lethal types of cancer. Although researchers have made significant efforts to study the mechanisms underlying CRC drug resistance, our knowledge of this disease is still limited, and novel therapies are in high demand. It is urgent to find new targeted therapy considering limited chemotherapy options.
    Language English
    Publishing date 2021-12-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.777114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Challenges and Limitations of Targeting the Keap1-Nrf2 Pathway for Neurotherapeutics: Bach1 De-Repression to the Rescue.

    Hushpulian, Dmitry M / Ammal Kaidery, Navneet / Ahuja, Manuj / Poloznikov, Andrey A / Sharma, Sudarshana M / Gazaryan, Irina G / Thomas, Bobby

    Frontiers in aging neuroscience

    2021  Volume 13, Page(s) 673205

    Abstract: The Keap1-Nrf2 signaling axis is a validated and promising target for cellular defense and survival pathways. This minireview discusses the potential off-target effects and their impact on future drug development originating from Keap1-targeting small ... ...

    Abstract The Keap1-Nrf2 signaling axis is a validated and promising target for cellular defense and survival pathways. This minireview discusses the potential off-target effects and their impact on future drug development originating from Keap1-targeting small molecules that function as displacement activators of the redox-sensitive transcription factor Nrf2. We argue that small-molecule displacement activators, similarly to electrophiles, will release both Nrf2 and other Keap1 client proteins from the ubiquitin ligase complex. This non-specificity is likely unavoidable and may result in off-target effects during Nrf2 activation by targeting Keap1. The small molecule displacement activators may also target Kelch domains in proteins other than Keap1, causing additional off-target effects unless designed to ensure specificity for the Kelch domain only in Keap1. A potentially promising and alternative therapeutic approach to overcome this non-specificity emerging from targeting Keap1 is to inhibit the Nrf2 repressor Bach1 for constitutive activation of the Nrf2 pathway and bypass the Keap1-Nrf2 complex.
    Language English
    Publishing date 2021-04-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2021.673205
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Structure–Activity Relationships and Transcriptomic Analysis of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors

    Poloznikov, Andrey A. / Nikulin, Sergey V. / Hushpulian, Dmitry M. / Khristichenko, Anna Yu / Osipyants, Andrey I. / Asachenko, Andrey F. / Shurupova, Olga V. / Savin, Svyatoslav S. / Lee, Sue H. / Gaisina, Irina N. / Thatcher, Gregory R. J. / Narciso, Anthony / Chang, Eric P. / Kazakov, Sergey V. / Krucher, Nancy / Tishkov, Vladimir I. / Thomas, Bobby / Gazaryan, Irina G.

    Antioxidants. 2022 Jan. 24, v. 11, no. 2

    2022  

    Abstract: To evaluate the differences in action of commercially available 2-oxoglutarate mimetics and “branched-tail” oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD), the inhibitors’ IC₅₀ values in the activation of HIF1 ODD- ... ...

    Abstract To evaluate the differences in action of commercially available 2-oxoglutarate mimetics and “branched-tail” oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD), the inhibitors’ IC₅₀ values in the activation of HIF1 ODD-luciferase reporter were selected for comparative transcriptomics. Structure–activity relationship and computer modeling for the oxyquinoline series of inhibitors led to the identification of novel inhibitors, which were an order of magnitude more active in the reporter assay than roxadustat and vadadustat. Unexpectedly, 2-methyl-substitution in the oxyquinoline core of the best HIF PHD inhibitor was found to be active in the reporter assay and almost equally effective in the pretreatment paradigm of the oxygen-glucose deprivation in vitro model. Comparative transcriptomic analysis of the signaling pathways induced by HIF PHD inhibitors showed high potency of the two novel oxyquinoline inhibitors (#4896-3249 and #5704-0720) at 2 μM concentrations matching the effect of 30 μM roxadustat and 500 μM dimethyl oxalyl glycine in inducing HIF1 and HIF2-linked pathways. The two oxyquinoline inhibitors exerted the same activation of HIF-triggered glycolytic pathways but opposite effects on signaling pathways linked to alternative substrates of HIF PHD 1 and 3, such as p53, NF-κB, and ATF4. This finding can be interpreted as the specificity of the 2-methyl-substitute variant for HIF PHD2.
    Keywords computers ; glycolysis ; models ; procollagen-proline dioxygenase ; structure-activity relationships ; transcriptomics
    Language English
    Dates of publication 2022-0124
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11020220
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Effect of the Expression of

    Nikulin, Sergey / Zakharova, Galina / Poloznikov, Andrey / Raigorodskaya, Maria / Wicklein, Daniel / Schumacher, Udo / Nersisyan, Stepan / Bergquist, Jonas / Bakalkin, Georgy / Astakhova, Lidiia / Tonevitsky, Alexander

    Frontiers in genetics

    2021  Volume 12, Page(s) 662843

    Abstract: Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression ... ...

    Abstract Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression of
    Language English
    Publishing date 2021-06-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.662843
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: LAMA4

    Shkurnikov, Maxim / Nikulin, Sergey / Nersisyan, Stepan / Poloznikov, Andrey / Zaidi, Shan / Baranova, Ancha / Schumacher, Udo / Wicklein, Daniel / Tonevitsky, Alexander

    Frontiers in molecular biosciences

    2019  Volume 6, Page(s) 122

    Abstract: Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork ... ...

    Abstract Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on
    Language English
    Publishing date 2019-11-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2019.00122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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