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  1. Article ; Online: Best practices for artificial intelligence in life sciences research.

    Makarov, Vladimir A / Stouch, Terry / Allgood, Brandon / Willis, Chris D / Lynch, Nick

    Drug discovery today

    2021  Volume 26, Issue 5, Page(s) 1107–1110

    Abstract: We describe 11 best practices for the successful use of artificial intelligence and machine learning in pharmaceutical and biotechnology research at the data, technology and organizational management levels. ...

    Abstract We describe 11 best practices for the successful use of artificial intelligence and machine learning in pharmaceutical and biotechnology research at the data, technology and organizational management levels.
    MeSH term(s) Artificial Intelligence ; Biotechnology/methods ; Humans ; Machine Learning ; Research Design ; Technology, Pharmaceutical/methods
    Language English
    Publishing date 2021-01-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2021.01.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4725: Show issues Location:
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  2. Article: Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design.

    Frolova, Anastasia S / Petushkova, Anastasiia I / Makarov, Vladimir A / Soond, Surinder M / Zamyatnin, Andrey A

    Biology

    2020  Volume 9, Issue 12

    Abstract: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and ... ...

    Abstract Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types.
    Language English
    Publishing date 2020-12-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology9120480
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Cathepsin S Cleaves BAX as a Novel and Therapeutically Important Regulatory Mechanism for Apoptosis.

    Soond, Surinder M / Savvateeva, Lyudmila V / Makarov, Vladimir A / Gorokhovets, Neonila V / Townsend, Paul A / Zamyatnin, Andrey A

    Pharmaceutics

    2021  Volume 13, Issue 3

    Abstract: Certain lysosomal cathepsin proteins have come into focus as being good candidates for therapeutic targeting, based on them being over-expressed in a variety of cancers and based on their regulation of the apoptotic pathway. Here, we report novel ... ...

    Abstract Certain lysosomal cathepsin proteins have come into focus as being good candidates for therapeutic targeting, based on them being over-expressed in a variety of cancers and based on their regulation of the apoptotic pathway. Here, we report novel findings that highlight the ability of cathepsin S expression to be up-regulated under Paclitaxel-stimulatory conditions in kidney cell lines and it being able to cleave the apoptotic p21 BAX protein in intact cells and in vitro. Consistent with this, we demonstrate that this effect can be abrogated in vitro and in mammalian cells under conditions that utilize dominant-inhibitory cathepsin S expression, cathepsin S expression-knockdown and through the activity of a novel peptide inhibitor, CS-PEP1. Moreover, we report a unique role for cathepsin S in that it can cleave a polyubiquitinated-BAX protein intermediate and is a step that may contribute to down-regulating post-translationally-modified levels of BAX protein. Finally, CS-PEP1 may possess promising activity as a potential anti-cancer therapeutic against chemotherapeutic-resistant Renal Clear Cell Carcinoma kidney cancer cells and for combined uses with therapeutics such as Paclitaxel.
    Language English
    Publishing date 2021-03-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics13030339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design

    Frolova, Anastasia S / Petushkova, Anastasiia I / Makarov, Vladimir A / Soond, Surinder M / Zamyatnin, Andrey A

    Biology. 2020 Dec. 19, v. 9, no. 12

    2020  

    Abstract: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and ... ...

    Abstract Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types.
    Keywords apoptosis ; area ; cell growth ; degradation ; drug design ; extracellular matrix proteins ; genes ; homeostasis ; immune response ; metalloproteinases ; metastasis ; neoplasm cells ; neoplasm progression ; nuclear matrix ; research ; therapeutics ; tissues
    Language English
    Dates of publication 2020-1219
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-light
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology9120480
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Toroidal sensor arrays for real-time photoacoustic imaging.

    Bychkov, Anton S / Cherepetskaya, Elena B / Karabutov, Alexander A / Makarov, Vladimir A

    Journal of biomedical optics

    2017  Volume 22, Issue 7, Page(s) 76003

    Abstract: This article addresses theoretical and numerical investigation of image formation in photoacoustic (PA) imaging with complex-shaped concave sensor arrays. The spatial resolution and the size of sensitivity region of PA and laser ultrasonic (LU) imaging ... ...

    Abstract This article addresses theoretical and numerical investigation of image formation in photoacoustic (PA) imaging with complex-shaped concave sensor arrays. The spatial resolution and the size of sensitivity region of PA and laser ultrasonic (LU) imaging systems are assessed using sensitivity maps and spatial resolution maps in the image plane. This paper also discusses the relationship between the size of high-sensitivity regions and the spatial resolution of real-time imaging systems utilizing toroidal arrays. It is shown that the use of arrays with toroidal geometry significantly improves the diagnostic capabilities of PA and LU imaging to investigate biological objects, rocks, and composite materials.
    MeSH term(s) Computer Systems ; Phantoms, Imaging ; Photoacoustic Techniques/instrumentation ; Ultrasonography
    Language English
    Publishing date 2017-07-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1309154-2
    ISSN 1560-2281 ; 1083-3668
    ISSN (online) 1560-2281
    ISSN 1083-3668
    DOI 10.1117/1.JBO.22.7.076003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4699: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Comparison of EMT-Related and Multi-Drug Resistant Gene Expression, Extracellular Matrix Production, and Drug Sensitivity in NSCLC Spheroids Generated by Scaffold-Free and Scaffold-Based Methods.

    Qi, Xiaoli / Prokhorova, Alexandra V / Mezentsev, Alexander V / Shen, Ningfei / Trofimenko, Alexander V / Filkov, Gleb I / Sulimanov, Rushan A / Makarov, Vladimir A / Durymanov, Mikhail O

    International journal of molecular sciences

    2022  Volume 23, Issue 21

    Abstract: Multicellular 3D tumor models are becoming a powerful tool for testing of novel drug products and personalized anticancer therapy. Tumor spheroids, a commonly used 3D multicellular tumor model, more closely reproduce the tumor microenvironment than ... ...

    Abstract Multicellular 3D tumor models are becoming a powerful tool for testing of novel drug products and personalized anticancer therapy. Tumor spheroids, a commonly used 3D multicellular tumor model, more closely reproduce the tumor microenvironment than conventional 2D cell cultures. It should be noted that spheroids can be produced using different techniques, which can be subdivided into scaffold-free (SF) and scaffold-based (SB) methods. However, it remains unclear, to what extent spheroid properties depend on the method of their generation. In this study, we aimed to carry out a head-to-head comparison of drug sensitivity and molecular expression profile in SF and SB spheroids along with a monolayer (2D) cell culture. Here, we produced non-small cell lung cancer (NSCLC) spheroids based on human lung adenocarcinoma cell line A549. Drug sensitivity analysis of the tested cell cultures to five different chemotherapeutics resulted in IC50 (A549-SB) > IC50 (A549-SF) > IC50 (A549-2D) trend. It was found that SF and SB A549 spheroids displayed elevated expression levels of epithelial-to-mesenchymal transition (EMT) markers and proteins associated with drug resistance compared with the monolayer A549 cell culture. Enhanced drug resistance of A549-SB spheroids can be a result of larger diameters and elevated deposition of extracellular matrix (ECM) that impairs drug penetration into spheroids. Thus, the choice of the spheroid production method can influence the properties of the generated 3D cell culture and their drug resistance. This fact should be considered for correct interpretation of drug testing results.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Spheroids, Cellular/pathology ; Cell Line, Tumor ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Extracellular Matrix/pathology ; Drug Resistance ; Gene Expression ; Tumor Microenvironment
    Language English
    Publishing date 2022-11-01
    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/ijms232113306
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  7. Article: Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.

    Soond, Surinder M / Savvateeva, Lyudmila V / Makarov, Vladimir A / Gorokhovets, Neonila V / Townsend, Paul A / Zamyatnin, Andrey A

    Cancers

    2020  Volume 12, Issue 11

    Abstract: While viewed as the "guardian of the genome", the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved ... ...

    Abstract While viewed as the "guardian of the genome", the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. As an important step in determining the fate of cells in response to cytotoxicity or during stress response, lysosomal-mediated cell death has also become strongly interwoven with the key components that give the lysosome functionality in the form of the cathepsin proteases. While a number of articles have been published highlighting the independent input of p53 or cathepsins to cellular homeostasis and disease progression, one key area that warrants further focus is the regulatory relationship that p53 and its isoforms share with such proteases in regulating lysosomal-mediated cell death. Herein, we review recent developments that have shaped this relationship and highlight key areas that need further exploration to aid novel therapeutic design and intervention strategies.
    Language English
    Publishing date 2020-11-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12113476
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: "Terhune-like" transformation of the terahertz polarization ellipse "mutually induced" by three-wave joint propagation in liquid.

    Balakin, Alexei V / Garnov, Sergey V / Makarov, Vladimir A / Kuzechkin, Nikolay A / Obraztsov, Petr A / Solyankin, Peter M / Shkurinov, Alexander P / Zhu, Yiming

    Optics letters

    2018  Volume 43, Issue 18, Page(s) 4406–4409

    Abstract: In this Letter, we show experimentally for the first time, to the best of our knowledge, the possibility to observe the effect of polarization mutual action of three elliptically polarized waves, with one of them at terahertz frequency, when they ... ...

    Abstract In this Letter, we show experimentally for the first time, to the best of our knowledge, the possibility to observe the effect of polarization mutual action of three elliptically polarized waves, with one of them at terahertz frequency, when they propagate in the isotropic nonlinear medium. When three light pulses are propagated at frequencies
    Language English
    Publishing date 2018-09-11
    Publishing country United States
    Document type Journal Article
    ISSN 1539-4794
    ISSN (online) 1539-4794
    DOI 10.1364/OL.43.004406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Cysteine Cathepsins Inhibition Affects Their Expression and Human Renal Cancer Cell Phenotype.

    Rudzińska, Magdalena / Parodi, Alessandro / Maslova, Valentina D / Efremov, Yuri M / Gorokhovets, Neonila V / Makarov, Vladimir A / Popkov, Vasily A / Golovin, Andrey V / Zernii, Evgeni Y / Zamyatnin, Andrey A

    Cancers

    2020  Volume 12, Issue 5

    Abstract: Renal cancer would greatly benefit from new therapeutic strategies since, in advanced stages, it is refractory to classical chemotherapeutic approaches. In this context, lysosomal protease cysteine cathepsins may represent new pharmacological targets. In ...

    Abstract Renal cancer would greatly benefit from new therapeutic strategies since, in advanced stages, it is refractory to classical chemotherapeutic approaches. In this context, lysosomal protease cysteine cathepsins may represent new pharmacological targets. In renal cancer, they are characterized by a higher expression, and they were shown to play a role in its aggressiveness and spreading. Traditional studies in the field were focused on understanding the therapeutic potentialities of cysteine cathepsin inhibition, while the direct impact of such therapeutics on the expression of these enzymes was often overlooked. In this work, we engineered two fluoromethyl ketone-based peptides with inhibitory activity against cathepsins to evaluate their potential anticancer activity and impact on the lysosomal compartment in human renal cancer. Molecular modeling and biochemical assays confirmed the inhibitory properties of the peptides against cysteine cathepsin B and L. Different cell biology experiments demonstrated that the peptides could affect renal cancer cell migration and organization in colonies and spheroids, while increasing their adhesion to biological substrates. Finally, these peptide inhibitors modulated the expression of LAMP1, enhanced the expression of E-cadherin, and altered cathepsin expression. In conclusion, the inhibition of cysteine cathepsins by the peptides was beneficial in terms of cancer aggressiveness; however, they could affect the overall expression of these proteases.
    Language English
    Publishing date 2020-05-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12051310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Filamentation of arbitrary polarized femtosecond laser pulses in case of high-order Kerr effect.

    Panov, Nikolay A / Makarov, Vladimir A / Fedorov, Vladimir Y / Kosareva, Olga G

    Optics letters

    2013  Volume 38, Issue 4, Page(s) 537–539

    Abstract: We developed a model of femtosecond filamentation which includes high-order Kerr effect and an arbitrary polarization of a laser pulse. We show that a circularly polarized pulse has maximum filament intensity. Also, we show that, independently of the ... ...

    Abstract We developed a model of femtosecond filamentation which includes high-order Kerr effect and an arbitrary polarization of a laser pulse. We show that a circularly polarized pulse has maximum filament intensity. Also, we show that, independently of the initial pulse polarization, the value of a maximum filament intensity tends to the maximum intensity of either linearly or circularly polarized pulse.
    Language English
    Publishing date 2013-02-15
    Publishing country United States
    Document type Journal Article
    ISSN 1539-4794
    ISSN (online) 1539-4794
    DOI 10.1364/OL.38.000537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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