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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">farmaec</journal-id><journal-title-group><journal-title xml:lang="en">FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology</journal-title><trans-title-group xml:lang="ru"><trans-title>ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2070-4909</issn><issn pub-type="epub">2070-4933</issn><publisher><publisher-name>IRBIS LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.17749/2070-4909/farmakoekonomika.2021.114</article-id><article-id custom-type="elpub" pub-id-type="custom">farmaec-625</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ПУБЛИКАЦИИ</subject></subj-group></article-categories><title-group><article-title>Peptides of Laennec® preparation that contribute to the elimination of endotheliopathy</article-title><trans-title-group xml:lang="ru"><trans-title>Пептиды в составе препарата Лаеннек®, способствующие устранению эндотелиопатии</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2659-7998</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Торшин</surname><given-names>И. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Torshin</surname><given-names>I. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Торшин Иван Юрьевич – к.ф-м.н., к.х.н., старший научный сотрудник</p><p>WoS ResearcherID: C-7683-2018</p><p>Scopus Author ID: 7003300274</p><p>РИНЦ SPIN-код: 1375-1114 </p><p>ул. Вавилова, д. 4, Москва 119333</p></bio><bio xml:lang="en"><p>Ivan Yu. Torshin – PhD (Phys. Math.), PhD (Chem.), Senior Researcher</p><p>Wos ResearcherID: C-7683-2018</p><p>Scopus Author ID: 7003300274</p><p>RSCI SPIN-code: 1375-1114</p><p>4 Vavilov Str., Moscow 119333</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7663-710X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Громова</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Gromova</surname><given-names>О. А.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Громова Ольга Алексеевна – д.м.н., профессор, научный руководитель</p><p>WoS ResearcherID: J-4946-2017</p><p>Scopus Author ID: 7003589812</p><p>РИНЦ SPIN-код: 6317-9833 </p><p>ул. Вавилова, д. 4, Москва 119333</p></bio><bio xml:lang="en"><p>Olga A. Gromova – Dr. Med. Sc., Professor, Research Supervisor</p><p>Wos ResearcherID: J-4946-2017</p><p>Scopus Author ID: 7003589812</p><p>RSCI SPIN-code: 6317-9833 </p><p>4 Vavilov Str., Moscow 119333</p></bio><email xlink:type="simple">unesco.gromova@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4532-4274</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Згода</surname><given-names>В. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Zgoda</surname><given-names>V. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Згода Виктор Гаврилович – д.б.н.</p><p>WoS ResearcherID: F-1791-2017</p><p>Scopus Author ID: 6602917155</p><p>РИНЦ SPIN-код: 7840-1330 </p><p>ул. Погодинская, д. 10, стр. 8, Москва 119121</p></bio><bio xml:lang="en"><p>Viktor G. Zgoda – Dr. Biol. Sc.</p><p>WoS ResearcherID: F-1791-2017</p><p>Scopus Author ID: 6602917155</p><p>RSCI SPIN-code: 7840-1330 </p><p>10 bld. 8. Pogodinskaya Str., Moscow 119121</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5070-5450</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чучалин</surname><given-names>А. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Chuchalin</surname><given-names>А. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Чучалин Александр Григорьевич – д.м.н., профессор, академик РАН, пульмонолог, заведующий кафедрой госпитальной терапии педиатрического факультета</p><p>РИНЦ SPIN-код: 7742-2054 </p><p>ул. 1-я Леонова, д. 16, Москва 129226</p></bio><bio xml:lang="en"><p>Aleksandr G. Chuchalin – Dr. Med. Sc., Professor, Academician of RAS, Pulmonologist, Head of Chair of Hospital Therapy, Faculty of Pediatrics</p><p>RSCI SPIN-code: 7742-2054 </p><p>16 Pervaya Leonov Str., Moscow 129226</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4120-1071</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Максимов</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Maksimov</surname><given-names>V. А.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Максимов Валерий Алексеевич – д.м.н., профессор кафедры диетологии и нутрициологии</p><p>Scopus Author ID: 55901011200 </p><p>ул. Баррикадная, д. 2, стр. 1, Москва 123995</p></bio><bio xml:lang="en"><p>Valeriy А. Maksimov – Dr. Med. Sc., Professor, Chair of Dietetics and Nutritionology</p><p>Scopus Author ID: 55901011200 </p><p>2 bld. 1 Barrikadnaya Str., Moscow 123995</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2810-566X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тихонова</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Tikhonova</surname><given-names>О. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Тихонова Ольга Валентиновна – к.б.н.</p><p>WoS ResearcherID: F-5115-2017</p><p>Scopus Author ID: 57189102916</p><p>РИНЦ SPINкод: 8320-9820 </p><p>ул. Погодинская, д. 10, стр. 8, Москва 119121</p></bio><bio xml:lang="en"><p>Olga V. Tikhonova – PhD (Biol.)</p><p>WoS ResearcherID: F-5115-2017</p><p>Scopus Author ID: 57189102916</p><p>RSCI SPIN-code </p><p>10 bld. 8. Pogodinskaya Str., Moscow 119121</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Федеральный исследовательский центр «Информатика и управление» Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Federal Research Center “Informatics and Management”, Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Федеральное государственное бюджетное научное учреждение «Научно-исследовательский институт биомедицинской химии им. В.Н. Ореховича», Центр коллективного пользования «Протеом человека»<country>Россия</country></aff><aff xml:lang="en">Orekhovich Research Institute of Biomedical Chemistry, Center for Collective Use “Human Proteome”<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Федеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Министерства здравоохранения Российской Федерации<country>Россия</country></aff><aff xml:lang="en">Pirogov Russian National Research Medical University<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru">Федеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации<country>Россия</country></aff><aff xml:lang="en">Russian Medical Academy of Continuing Professional Education<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>15</day><month>01</month><year>2022</year></pub-date><volume>14</volume><issue>4</issue><fpage>468</fpage><lpage>479</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Torshin I.Y., Gromova О.А., Zgoda V.G., Chuchalin А.G., Maksimov V.А., Tikhonova О.V., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Торшин И.Ю., Громова О.А., Згода В.Г., Чучалин А.Г., Максимов В.А., Тихонова О.В.</copyright-holder><copyright-holder xml:lang="en">Torshin I.Y., Gromova О.А., Zgoda V.G., Chuchalin А.G., Maksimov V.А., Tikhonova О.V.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmacoeconomics.ru/jour/article/view/625">https://www.pharmacoeconomics.ru/jour/article/view/625</self-uri><abstract><p>Objective: identification of peptides in the composition of Laennec®, which can inhibit the development of endotheliopathy (endothelial dysfunction).Material and methods. Hybrid mass spectrometry followed by data analysis based on topological recognition theory was performed. The analysis of the peptide composition of Laennec® included four stages: purification of the drug, chromatographic separation of peptides, determination of the multidimensional mass spectrum of the peptide fraction, and de novo sequencing of the isolated peptides.Results. The preparation contains peptides-inhibitors of specific target proteins (PRKCZ, PKB, PKD1, MAPK14, IKKB, PDPK1) involved in the activation of the pro-inflammatory transcription factor NF-κB. Inhibition of CDK5 and SHC1 kinases helps to reduce endothelial cell apoptosis. The peptides of the drug also block enzymes involved in the synthesis and maturation of the tumor necrosis factor alpha (MAPKAPK2/3, ADAM17).Conclusion. In the composition of Laennec®, peptides have been found that contribute to a complex pathogenetic action against endotheliopathy. Endothelial regeneration is especially important in the rehabilitation of patients who have recovered from COVID-19.</p></abstract><trans-abstract xml:lang="ru"><p>Цель: выявление пептидов в составе препарата Лаеннек®, которые могут тормозить развитие эндотелиопатии (эндотелиальной дисфункции).Материал и методы. Проведена гибридная масс-спектрометрия с последующим анализом данных на основе топологической теории распознавания. Анализ пептидного состава Лаеннека® включал четыре этапа: очистка препарата, хроматографическое разделение пептидов, определение многомерного масс-спектра пептидной фракции и de novo секвенирование выделенных пептидов.Результаты. В составе препарата идентифицированы пептиды-ингибиторы специфических таргетных белков (PRKCZ, PKB, PKD1, MAPK14, IKKB, PDPK1), вовлеченные в активацию провоспалительного транскрипционного фактора NF-κB. Ингибирование киназ CDK5 и SHC1 способствует снижению апоптоза эндотелиоцитов. Пептиды препарата также блокируют ферменты, участвующие в синтезе и вызревании фактора некроза опухолей альфа (MAPKAPK2/3, ADAM17).Заключение. В составе препарата Лаеннек® найдены пептиды, которые способствуют комплексному патогенетическому действию против эндотелиопатии. Регенерация эндотелия особенно актуальна в реабилитации пациентов, переболевших COVID-19.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>дисфункция эндотелия</kwd><kwd>протеомика</kwd><kwd>коронавирусная инфекция</kwd><kwd>полипептидная терапия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>endothelial dysfunction</kwd><kwd>proteomics</kwd><kwd>coronavirus infection</kwd><kwd>polypeptide therapy</kwd></kwd-group><funding-group xml:lang="ru"><funding-statement>Статья подготовлена при поддержке компании «Рхана».</funding-statement></funding-group><funding-group xml:lang="en"><funding-statement>This work was financially supported by the Rhana company.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Пузик С.Г. Эндотелиальная дисфункция в патогенезеартериальной гипертензии и прогрессировании атеросклероза. Семейная медицина. 2018; 2: 69–74.</mixed-citation><mixed-citation xml:lang="en">Puzik S.G. Endothelial dysfunction in the pathogenesis of arterial hypertension and the progression of atherosclerosis. Semeynaya meditsina / Family Medicine. 2018; 2: 69–74 (in Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Чучалин А.Г. Роль оксида азота в современной клинической практике: научный доклад на V Всероссийском конгрессе «Легочная гипертензия» (13 декабря 2017 г.). Пульмонология. 2018; 28 (4): 503–11. https://doi.org/10.18093/0869-0189-2018-28-4-503-511.</mixed-citation><mixed-citation xml:lang="en">Chuchalin A.G. A role of nitric oxide for the modern clinical practice: a scientific report at the 5th Pan-Russian Congress on pulmonary hypertension, December 13, 2017. Pulmonologiya. 2018; 28 (4): 503–11 (in Russ.). https://doi.org/10.18093/0869-0189-2018-28-4-503-511.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Панина И.Ю., Петрищев Н.Н., Смирнов А.В. и др. Артериальная гипертензия и эндотелиальная дисфункция при хронической болезни почек. Артериальная гипертензия. 2006; 12 (4): 352–7. https://doi.org/10.18705/1607-419X-2006-12-4-352-357.</mixed-citation><mixed-citation xml:lang="en">Panina I.Y., Petrichshtev N.N., Smirnov A.V., et al. Arterial hypertension and endothelial dysfunction in chronic kidney diseases. Arterial’naya gipertenziya / Arterial Hypertension. 2006; 12 (4): 352–7 (in Russ.). https://doi.org/10.18705/1607-419X-2006-12-4-352-357.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Шолкова М.В., Доценко Э.А. Эндотелиальная дисфункция при хронических обструктивных заболеваниях легких. Неотложная кардиология и кардиооваскулярные риски. 2019; 3 (1): 539–45.</mixed-citation><mixed-citation xml:lang="en">Sholkava M.V., Dotsenko E.A. Endothelial dysfunction in chronic obstructive pulmonary diseases. Emergency Cardiology and Cardiovascular Risks. 2019; 3 (1): 539–45 (in Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Liu C., Jiang Z.C., Shao C.X., Zhang H.G., et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study]. Zhonghua Gan Zang Bing Za Zhi. 2020; 28 (2): 148–52 (на кит. яз.). https://doi.org/10.3760/cma.j.issn.1007-3418.2020.02.003.</mixed-citation><mixed-citation xml:lang="en">Liu C., Jiang Z.C., Shao C.X., Zhang H.G., et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study. Zhonghua Gan Zang Bing Za Zhi. 2020; 28 (2): 148–52 (in Chinese). https://doi.org/10.3760/cma.j.issn.1007-3418.2020.02.003.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18 (4): 844–7. https://doi.org/10.1111/jth.14768.</mixed-citation><mixed-citation xml:lang="en">Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18 (4): 844–7. https://doi.org/10.1111/jth.14768.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Jin X., Lian J.S., Hu J.H., et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020; 69 (6): 1002–9. https://doi.org/10.1136/gutjnl-2020-320926.</mixed-citation><mixed-citation xml:lang="en">Jin X., Lian J.S., Hu J.H., et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020; 69 (6): 1002–9. https://doi.org/10.1136/gutjnl-2020-320926.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Iba T., Connors J.M., Levy J.H. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020; 69 (12): 1181–9. https://doi.org/10.1007/s00011-020-01401-6.</mixed-citation><mixed-citation xml:lang="en">Iba T., Connors J.M., Levy J.H. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020; 69 (12): 1181–9. https://doi.org/10.1007/s00011-020-01401-6.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang J., McCullough P.A., Tecson K.M. Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19. Rev Cardiovasc Med. 2020; 21 (3): 339–44. https://doi.org/10.31083/j.rcm.2020.03.131.</mixed-citation><mixed-citation xml:lang="en">Zhang J., McCullough P.A., Tecson K.M. Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19. Rev Cardiovasc Med. 2020; 21 (3): 339–44. https://doi.org/10.31083/j.rcm.2020.03.131.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Kang S., Tanaka T., Inoue H., et al. IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome. Proc Natl Acad Sci USA. 2020; 117 (36): 22351–6. https://doi.org/10.1073/pnas.2010229117.</mixed-citation><mixed-citation xml:lang="en">Kang S., Tanaka T., Inoue H., et al. IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome. Proc Natl Acad Sci USA. 2020; 117 (36): 22351–6. https://doi.org/10.1073/pnas.2010229117.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">McConnell M.J., Kawaguchi N., Kondo R., et al. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. J Hepatol. 2021: 75 (3): 647–58. https://doi.org/10.1016/j.jhep.2021.04.050.</mixed-citation><mixed-citation xml:lang="en">McConnell M.J., Kawaguchi N., Kondo R., et al. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. J Hepatol. 2021: 75 (3): 647–58. https://doi.org/10.1016/j.jhep.2021.04.050.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Philippe A., Chocron R., Gendron N., et al. Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality. Angiogenesis. 2021: 24 (3): 505–17. https://doi.org/10.1007/s10456-020-09762-6.</mixed-citation><mixed-citation xml:lang="en">Philippe A., Chocron R., Gendron N., et al. Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality. Angiogenesis. 2021: 24 (3): 505–17. https://doi.org/10.1007/s10456-020-09762-6.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Syed F., Li W., Relich R.F., et al. Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19. medRxiv. 2021 Jan 20: 2021.01.19.21250115. https://doi.org/10.1101/2021.01.19.21250115.</mixed-citation><mixed-citation xml:lang="en">Syed F., Li W., Relich R.F., et al. Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19. medRxiv. 2021 Jan 20: 2021.01.19.21250115. https://doi.org/10.1101/2021.01.19.21250115.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Chioh F.W., Fong S.W., Young B.E., et al. Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. Elife. 2021; 10: e64909. https://doi.org/10.7554/eLife.64909.</mixed-citation><mixed-citation xml:lang="en">Chioh F.W., Fong S.W., Young B.E., et al. Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. Elife. 2021; 10: e64909. https://doi.org/10.7554/eLife.64909.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Pine A.B., Meizlish M.L., Goshua G., et al. Circulating markers of angiogenesis and endotheliopathy in COVID-19. Pulm Circ. 2020; 10 (4): 2045894020966547. https://doi.org/10.1177/2045894020966547.</mixed-citation><mixed-citation xml:lang="en">Pine A.B., Meizlish M.L., Goshua G., et al. Circulating markers of angiogenesis and endotheliopathy in COVID-19. Pulm Circ. 2020; 10 (4): 2045894020966547. https://doi.org/10.1177/2045894020966547.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Nicosia R.F., Ligresti G., Caporarello N., et al. COVID-19 vasculopathy: mounting evidence for an indirect mechanism of endothelial injury. Am J Pathol. 2021; 191 (8): 1374–84. https://doi.org/10.1016/j.ajpath.2021.05.007.</mixed-citation><mixed-citation xml:lang="en">Nicosia R.F., Ligresti G., Caporarello N., et al. COVID-19 vasculopathy: mounting evidence for an indirect mechanism of endothelial injury. Am J Pathol. 2021; 191 (8): 1374–84. https://doi.org/10.1016/j.ajpath.2021.05.007.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Федин А.И., Старых Е.П., Парфёнов А.С. и др. Фармакологическая коррекция эндотелиальной дисфункции при атеросклеротической хронической ишемии головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2013; 113 (10): 45–8.</mixed-citation><mixed-citation xml:lang="en">Fedin A.I., Starykh E.P., Parfenov A.S., et al. Pharmacotherapy of endothelial dysfunction in patients with atherosclerotic brain ischemia. S.S. Korsakov’s Journal of Neurology and Psychiatry. 2013; 113 (10): 45–8 (in Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Филиппов Е.В. Возможности коррекции эндотелиальной дисфункции у пациентов с артериальной гипертензией и ишемической болезнью сердца. Медицинский cовет. 2019; 5: 64– 7. https://doi.org/10.21518/2079-701X-2019-5-64-67.</mixed-citation><mixed-citation xml:lang="en">Filippov E.V. Possibilities for correcting endothelial dysfunction in patients with arterial hypertension and coronary heart disease. Meditsinskiy sovet / Medical Council. 2019; 5: 64–7 (in Russ.). https://doi.org/10.21518/2079-701X-2019-5-64-67.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Торшин И.Ю., Громова О.А. Микронутриенты против коронавирусов. М.: ГЭОТАР-Медиа; 2020: 112 с.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Yu., Gromova O.A. Micronutrients against coronaviruses. Мoscow: GEOTAR-Media; 2020: 112 pp. (in Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Максимов В.А., Торшин И.Ю., Чучалин А.Г. и др. Опыт применения препарата Лаеннек у пациентов с высоким риском развития «цитокинового шторма» на фоне COVID-19 и гиперферритинемии. Пульмонология. 2020; 30 (5): 587–98. https://doi.org/10.18093/0869-0189-2020-30-5-587-598.</mixed-citation><mixed-citation xml:lang="en">Maksimov V.A., Torshin I.Yu., Chuchalin A.G., et al. An experience of using Laennec in patients at high risk of a cytokine storm with COVID-19 and hyperferritinemia. Pulmonologiya. 2020; 30 (5): 587–98 (in Russ.). https://doi.org/10.18093/0869-0189-2020-30-5-587-598.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Громова О.А., Торшин И.Ю., Максимов В.А. и др. Пептиды в составе препарата Лаеннек, способствующие устранению гиперферритинемии и перегрузки железом. ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология. 2020; 13 (4): 413–25. https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.070.</mixed-citation><mixed-citation xml:lang="en">Gromova O.A., Torshin I.Yu., Maksimov V.A., et al. Peptides contained in the composition of Laennec that contribute to the treatment of hyperferritinemia and iron overload disorders.FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (4): 413–25 (in Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.070.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Торшин И.Ю., Громова О.А., Диброва Е.А. и др. Пептиды в составе препарата Лаеннек, потенцирующие его антивирусные эффекты в лечении атопического дерматита герпетической инфекции. Российский аллергологический журнал. 2018; 15 (1): 82–90. https://doi.org/10.36691/rja191.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Y., Gromova O.A., Dibrova E.A., et al. Peptides in the composition of Laennec that show antiviral effects in the therapy of atopic dermatitis and herpes infection. Russian Journal of Allergy. 2018; 15 (1): 82–90 (in Russ.). https://doi.org/10.36691/rja191.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Torshin I.Y., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 1: Factorization approach. Pattern Recognit Image Anal. 2017; 27 (1): 16–28. https://doi.org/10.1134/S1054661817010151.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Y., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 1: Factorization approach. Pattern Recognit Image Anal. 2017; 27 (1): 16–28. https://doi.org/10.1134/S1054661817010151.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Torshin I.Yu., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: Metric approach within the framework of the theory of classification of feature values. Pattern Recognit Image Anal. 2017; 27 (2): 184–99. https://doi.org/10.1134/S1054661817020110.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Yu., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: Metric approach within the framework of the theory of classification of feature values. Pattern Recognit Image Anal. 2017; 27 (2): 184–99. https://doi.org/10.1134/S1054661817020110.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Torshin I.Y. Optimal dictionaries of the final information on the basis of the solvability criterion and their applications in bioinformatics. Pattern Recognit Image Anal. 2013; 23 (2): 319–27. https://doi.org/10.1134/S1054661813020156.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Y. Optimal dictionaries of the final information on the basis of the solvability criterion and their applications in bioinformatics. Pattern Recognit Image Anal. 2013; 23 (2): 319–27. https://doi.org/10.1134/S1054661813020156.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Torshin I.Yu., Rudakov K.V. On the procedures of generation of numerical features over partitions of sets of objects in the problem of predicting numerical target variables. Pattern Recognit Image Anal. 2019; 29 (4): 654–67. https://doi.org/10.1134/S1054661819040175.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Yu., Rudakov K.V. On the procedures of generation of numerical features over partitions of sets of objects in the problem of predicting numerical target variables. Pattern Recognit Image Anal. 2019; 29 (4): 654–67. https://doi.org/10.1134/S1054661819040175.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Torshin I.Y., Rudakov K.V. On the application of the combinatorial theory of solvability to the analysis of chemographs. Part 1: Fundamentals of modern chemical bonding theory and the concept of the chemograph. Pattern Recognit Image Anal. 2014; 24 (1): 11−23. https://doi.org/10.1134/S1054661814010209.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Y., Rudakov K.V. On the application of the combinatorial theory of solvability to the analysis of chemographs. Part 1: Fundamentals of modern chemical bonding theory and the concept of the chemograph. Pattern Recognit Image Anal. 2014; 24 (1): 11–23. https://doi.org/10.1134/S1054661814010209.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Торшин И.Ю., Громова О.А. Мировой опыт использования гидролизатов плаценты человека в терапии. Экспериментальная и клиническая гастроэнтерология. 2019; 170 (10): 79–89. https://doi.org/10.31146/1682-8658-ecg-170-10-79-89.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Yu., Gromova O.A. Worldwide experience of the therapeutic use of the human placental hydrolytes. Experimental and Clinical Gastroenterology. 2019; 170 (10): 79–89 (in Russ.). https://doi.org/10.31146/1682-8658-ecg-170-10-79-89.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Торшин И.Ю., Громова О.А. Экспертный анализ данных в молекулярной фармакологии. М.: МЦНМО; 2012: 748 с. 30. Xu S., Yan Y., Yan Z., et al. Septic serum mediates inflammatory injury in human umbilical vein endothelial cells via reactive oxygen species, mitogen activated protein kinases and nuclear factor-κB. Int J Mol Med. 2021; 47 (1): 267–75. https://doi.org/10.3892/ijmm.2020.4785.</mixed-citation><mixed-citation xml:lang="en">Torshin I.Yu., Gromova O.A. Expert data analysis in molecular pharmacology. Мoscow: MTsNMO; 2012: 748 pp. (in Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Vrints C.J., Krychtiuk K.A., Van Craenenbroeck E.M., et al. Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications. Acta Cardiol. 2021; 76 (2): 109–24. https://doi.org/10.1080/00015385.2020.1846921.</mixed-citation><mixed-citation xml:lang="en">Xu S., Yan Y., Yan Z., et al. Septic serum mediates inflammatory injury in human umbilical vein endothelial cells via reactive oxygen species, mitogen activated protein kinases and nuclear factor-κB. Int J Mol Med. 2021; 47 (1): 267–75. https://doi.org/10.3892/ijmm.2020.4785.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Pan Y., Wang Y., Xu J., et al. TG and VLDL cholesterol activate NLRP1 inflammasome by Nuclear Factor-κB in endothelial cells. Int J Cardiol. 2017; 234: 103. https://doi.org/10.1016/j.ijcard.2016.12.156.</mixed-citation><mixed-citation xml:lang="en">Vrints C.J., Krychtiuk K.A., Van Craenenbroeck E.M., et al. Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications. Acta Cardiol. 2021; 76 (2): 109–24. https://doi.org/10.1080/00015385.2020.1846921.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Baer J.T., Du Laney T.V., Wyrick P.B., et al. Nuclear factor-kappaB activation in endothelium by Chlamydia pneumoniae without active infection. J Infect Dis. 2003; 188 (8): 1094–7. https://doi.org/10.1086/378564.</mixed-citation><mixed-citation xml:lang="en">Pan Y., Wang Y., Xu J., et al. TG and VLDL cholesterol activate NLRP1 inflammasome by Nuclear Factor-κB in endothelial cells. Int J Cardiol. 2017; 234: 103. https://doi.org/10.1016/j.ijcard.2016.12.156.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Song D., Ye X., Xu H., Liu S.F. Activation of endothelial intrinsic NF- {kappa}B pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice. Blood. 2009; 114 (12): 2521–9. https://doi.org/10.1182/blood-2009-02-205914.</mixed-citation><mixed-citation xml:lang="en">Baer J.T., Du Laney T.V., Wyrick P.B., et al. Nuclear factor-kappaB activation in endothelium by Chlamydia pneumoniae without active infection. J Infect Dis. 2003; 188 (8): 1094–7. https://doi.org/10.1086/378564.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Morita M., Yano S., Yamaguchi T., Sugimoto T. Advanced glycation end products-induced reactive oxygen species generation is partly through NF-kappa B activation in human aortic endothelial cells. J Diabetes Complications. 2013; 27 (1): 11–5. https://doi.org/10.1016/j.jdiacomp.2012.07.006.</mixed-citation><mixed-citation xml:lang="en">Song D., Ye X., Xu H., Liu S.F. Activation of endothelial intrinsic NF- {kappa}B pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice. Blood. 2009; 114 (12): 2521–9. https://doi.org/10.1182/blood-2009-02-205914.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Pan W., Yu H., Huang S., Zhu P. Resveratrol protects against TNF-α-induced injury in human umbilical endothelial cells through promoting sirtuin-1-induced repression of NF-KB and p38 MAPK. PLoS One. 2016; 11 (1): e0147034. https://doi.org/10.1371/journal.pone.0147034.</mixed-citation><mixed-citation xml:lang="en">Morita M., Yano S., Yamaguchi T., Sugimoto T. Advanced glycation end products-induced reactive oxygen species generation is partly through NF-kappa B activation in human aortic endothelial cells. J Diabetes Complications. 2013; 27 (1): 11–5. https://doi.org/10.1016/j.jdiacomp.2012.07.006.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Dong H.J., Shang C.Z., Peng D.W., et al. Curcumin attenuates ischemia-like injury induced IL-1β elevation in brain microvascular endothelial cells via inhibiting MAPK pathways and nuclear factor-κB activation. Neurol Sci. 2014; 35 (9): 1387–92. https://doi.org/10.1007/s10072-014-1718-4.</mixed-citation><mixed-citation xml:lang="en">Pan W., Yu H., Huang S., Zhu P. Resveratrol protects against TNF-α-induced injury in human umbilical endothelial cells through promoting sirtuin-1-induced repression of NF-KB and p38 MAPK. PLoS One. 2016; 11 (1): e0147034. https://doi.org/10.1371/journal.pone.0147034.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Hu W., Zhang Q., Yang X., et al. Puerarin inhibits adhesion molecule expression in tnf-alpha-stimulated human endothelial cells via modulation of the nuclear factor kappaB pathway. Pharmacology. 2010; 85 (1): 27–35. https://doi.org/10.1159/000264938.</mixed-citation><mixed-citation xml:lang="en">Dong H.J., Shang C.Z., Peng D.W., et al. Curcumin attenuates ischemia-like injury induced IL-1β elevation in brain microvascular endothelial cells via inhibiting MAPK pathways and nuclear factor-κB activation. Neurol Sci. 2014; 35 (9): 1387–92. https://doi.org/10.1007/s10072-014-1718-4.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Ohkita M., Takaoka M., Shiota Y., et al. A nuclear factor-kappaB inhibitor BAY 11-7082 suppresses endothelin-1 production in cultured vascular endothelial cells. Jpn J Pharmacol. 2002; 89 (1): 81–4. https://doi.org/10.1254/jjp.89.81.</mixed-citation><mixed-citation xml:lang="en">Hu W., Zhang Q., Yang X., et al. Puerarin inhibits adhesion molecule expression in tnf-alpha-stimulated human endothelial cells via modulation of the nuclear factor kappaB pathway. Pharmacology. 2010; 85 (1): 27–35. https://doi.org/10.1159/000264938.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Guo G., Cheng X., Fu R. Losartan inhibits nuclear factor-κB activation induced by small, dense LDL cholesterol particles in human umbilical vein endothelial cells. Curr Ther Res Clin Exp. 2013; 76: 17–20. https://doi.org/10.1016/j.curtheres.2013.11.006.</mixed-citation><mixed-citation xml:lang="en">Ohkita M., Takaoka M., Shiota Y., et al. A nuclear factor-kappaB inhibitor BAY 11-7082 suppresses endothelin-1 production in cultured vascular endothelial cells. Jpn J Pharmacol. 2002; 89 (1): 81–4. https://doi.org/10.1254/jjp.89.81.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou S.J., Bai L., Lv L., et al. Liraglutide ameliorates renal injury in streptozotocin-induced diabetic rats by activating endothelial nitric oxide synthase activity via the downregulation of the nuclear factor-κB pathway. Mol Med Rep. 2014; 10 (5): 2587–94. https://doi.org/10.3892/mmr.2014.2555.</mixed-citation><mixed-citation xml:lang="en">Guo G., Cheng X., Fu R. Losartan inhibits nuclear factor-κB activation induced by small, dense LDL cholesterol particles in human umbilical vein endothelial cells. Curr Ther Res Clin Exp. 2013; 76: 17–20. https://doi.org/10.1016/j.curtheres.2013.11.006.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Lei L., Huaiyong C., Qi W., et al. The role of nuclear factor-κB in endothelial cell inflammatory injury by intermittent hypoxia in rat with emphysema. Zhonghua Jie He He Hu Xi Za Zhi. 2015; 38 (3): 196–201 (на кит. яз.).</mixed-citation><mixed-citation xml:lang="en">Zhou S.J., Bai L., Lv L., et al. Liraglutide ameliorates renal injury in streptozotocin-induced diabetic rats by activating endothelial nitric oxide synthase activity via the downregulation of the nuclear factor-κB pathway. Mol Med Rep. 2014; 10 (5): 2587–94. https://doi.org/10.3892/mmr.2014.2555.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Bian Y., Song C., Cheng K., et al. An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014; 96: 253–62. https://doi.org/10.1016/j.jprot.2013.11.014.</mixed-citation><mixed-citation xml:lang="en">Lei L., Huaiyong C., Qi W., et al. The role of nuclear factor-κB in endothelial cell inflammatory injury by intermittent hypoxia in rat with emphysema. Zhonghua Jie He He Hu Xi Za Zhi. 2015; 38 (3): 196–201 (in Chinese).</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Song P., Xie Z., Wu Y., et al. Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J Biol Chem. 2008; 283 (18): 12446–55. https://doi.org/10.1074/jbc.M708208200.</mixed-citation><mixed-citation xml:lang="en">Bian Y., Song C., Cheng K., et al. An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014; 96: 253–62. https://doi.org/10.1016/j.jprot.2013.11.014.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Hurov J.B., Watkins J.L., Piwnica-Worms H. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr Biol. 2004; 14 (8): 736–41. https://doi.org/10.1016/j.cub.2004.04.007.</mixed-citation><mixed-citation xml:lang="en">Song P., Xie Z., Wu Y., et al. Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells. J Biol Chem. 2008; 283 (18): 12446–55. https://doi.org/10.1074/jbc.M708208200.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Preuss K.D., Pfreundschuh M., Fadle N., et al. Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A. Blood. 2011; 118 (12): 3340–6. https://doi.org/10.1182/blood-2011-04-351668.</mixed-citation><mixed-citation xml:lang="en">Hurov J.B., Watkins J.L., Piwnica-Worms H. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity. Curr Biol. 2004; 14 (8): 736–41. https://doi.org/10.1016/j.cub.2004.04.007.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Tsuchiya Y., Asano T., Nakayama K., et al. Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UVinduced NF-kappaB activation. Mol Cell. 2010; 39 (4): 570–82. https://doi.org/10.1016/j.molcel.2010.07.030.</mixed-citation><mixed-citation xml:lang="en">Preuss K.D., Pfreundschuh M., Fadle N., et al. Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A. Blood. 2011; 118 (12): 3340–6. https://doi.org/10.1182/blood-2011-04-351668.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Serra R.W., Fang M., Park S.M., et al. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife. 2014; 3: e02313. https://doi.org/10.7554/eLife.02313.</mixed-citation><mixed-citation xml:lang="en">Tsuchiya Y., Asano T., Nakayama K., et al. Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UVinduced NF-kappaB activation. Mol Cell. 2010; 39 (4): 570–82. https://doi.org/10.1016/j.molcel.2010.07.030.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Xu P., Derynck R. Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. Mol Cell. 2010; 37 (4): 551–66. https://doi.org/10.1016/j.molcel.2010.01.034.</mixed-citation><mixed-citation xml:lang="en">Serra R.W., Fang M., Park S.M., et al. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife. 2014; 3: e02313. https://doi.org/10.7554/eLife.02313.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Reinhardt H.C., Hasskamp P., Schmedding I., et al. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization. Mol Cell. 2010; 40 (1): 34–49. https://doi.org/10.1016/j.molcel.2010.09.018.</mixed-citation><mixed-citation xml:lang="en">Xu P., Derynck R. Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. Mol Cell. 2010; 37 (4): 551–66. https://doi.org/10.1016/j.molcel.2010.01.034.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Werz O., Szellas D., Steinhilber D., Rådmark O. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPKactivated protein kinase 2 (MK2). J Biol Chem. 2002; 277 (17): 14793– 800. https://doi.org/10.1074/jbc.M111945200.</mixed-citation><mixed-citation xml:lang="en">Reinhardt H.C., Hasskamp P., Schmedding I., et al. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization. Mol Cell. 2010; 40 (1): 34–49. https://doi.org/10.1016/j.molcel.2010.09.018.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Gimm T., Wiese M., Teschemacher B., et al. Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. FASEB J. 2010; 24 (11): 4443–58. https://doi.org/10.1096/fj.10-159806.</mixed-citation><mixed-citation xml:lang="en">Werz O., Szellas D., Steinhilber D., Rådmark O. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPKactivated protein kinase 2 (MK2). J Biol Chem. 2002; 277 (17): 14793– 800. https://doi.org/10.1074/jbc.M111945200.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Tanimoto K., Makino Y., Pereira T., Poellinger L. Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von HippelLindau tumor suppressor protein. EMBO J. 2000; 19 (16): 4298–309. https://doi.org/10.1093/emboj/19.16.4298.</mixed-citation><mixed-citation xml:lang="en">Gimm T., Wiese M., Teschemacher B., et al. Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. FASEB J. 2010; 24 (11): 4443–58. https://doi.org/10.1096/fj.10-159806.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Tanimoto K., Makino Y., Pereira T., Poellinger L. Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von HippelLindau tumor suppressor protein. EMBO J. 2000; 19 (16): 4298–309. https://doi.org/10.1093/emboj/19.16.4298.</mixed-citation><mixed-citation xml:lang="en">Tanimoto K., Makino Y., Pereira T., Poellinger L. Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von HippelLindau tumor suppressor protein. EMBO J. 2000; 19 (16): 4298–309. https://doi.org/10.1093/emboj/19.16.4298.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
