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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="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mrj</journal-id><journal-title-group><journal-title xml:lang="ru">Современная ревматология</journal-title><trans-title-group xml:lang="en"><trans-title>Modern Rheumatology Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1996-7012</issn><issn pub-type="epub">2310-158X</issn><publisher><publisher-name>IMA-PRESS, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14412/1996-7012-2021-5-26-32</article-id><article-id custom-type="elpub" pub-id-type="custom">mrj-1193</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="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL INVESTIGATIONS</subject></subj-group></article-categories><title-group><article-title>Роль метаболического статуса лимфоцитов в патогенезе ревматоидного артрита</article-title><trans-title-group xml:lang="en"><trans-title>The role of the metabolic status of lymphocytes in the pathogenesis of rheumatoid arthritis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6233-5944</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Скупневский</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Skupnevsky</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сергей Валерьевич Скупневский</p><p>362025, Владикавказ, Пушкинская ул., 47</p></bio><bio xml:lang="en"><p>47, Pushkin Street, Vladikavkaz 362025</p></bio><email xlink:type="simple">dreammas@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0850-2537</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пухаева</surname><given-names>Е. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Pukhaeva</surname><given-names>E. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>362025, Владикавказ, Пушкинская ул., 47</p></bio><bio xml:lang="en"><p>47, Pushkin Street, Vladikavkaz 362025</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/0000-0001-5850-5173</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бадтиев</surname><given-names>А. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Badtiev</surname><given-names>A. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>362025, Владикавказ, Пушкинская ул., 47</p></bio><bio xml:lang="en"><p>47, Pushkin Street, Vladikavkaz 362025</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/0000-0001-9424-0467</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Руруа</surname><given-names>Ф. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Rurua</surname><given-names>F. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>362025, Владикавказ, Пушкинская ул., 47</p></bio><bio xml:lang="en"><p>47, Pushkin Street, Vladikavkaz 362025</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/0000-0001-9105-0350</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Батагова</surname><given-names>Ф. Э.</given-names></name><name name-style="western" xml:lang="en"><surname>Batagova</surname><given-names>F. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>362025, Владикавказ, Пушкинская ул., 47</p></bio><bio xml:lang="en"><p>47, Pushkin Street, Vladikavkaz 362025</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/0000-0002-9154-4729</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фарниев</surname><given-names>Ж. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Farnieva</surname><given-names>Zh. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>362025, Владикавказ, Пушкинская ул., 47</p></bio><bio xml:lang="en"><p>47, Pushkin Street, Vladikavkaz 362025</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУН «Институт биомедицинских исследований Владикавказского научного центра&#13;
Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute for Biomedical Research, Vladikavkaz Scientific Center</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>19</day><month>10</month><year>2021</year></pub-date><volume>15</volume><issue>5</issue><fpage>26</fpage><lpage>32</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Скупневский С.В., Пухаева Е.Г., Бадтиев А.К., Руруа Ф.К., Батагова Ф.Э., Фарниев Ж.Г., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Скупневский С.В., Пухаева Е.Г., Бадтиев А.К., Руруа Ф.К., Батагова Ф.Э., Фарниев Ж.Г.</copyright-holder><copyright-holder xml:lang="en">Skupnevsky S.V., Pukhaeva E.G., Badtiev A.K., Rurua F.K., Batagova F.E., Farnieva Z.G.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" 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://mrj.ima-press.net/mrj/article/view/1193">https://mrj.ima-press.net/mrj/article/view/1193</self-uri><abstract><p>Цель исследования – изучение метаболических изменений лимфоцитов в динамике на модели адъювант-индуцированного ревматоидного артрита (РА) у теплокровных животных.Материал и методы. Модель РА вызывали введением полного адъюванта Фрейнда (АФ) крысам-самцам линии Wistar. Корректировку метаболизма лимфоцитов осуществляли смесью лимонной и янтарной кислот, которую вводили на протяжении 4 нед. (в дозах 17 и 88 мг/кг массы тела) с первого дня формирования модели. Животным контрольной группы подкожно вводили изотонический раствор натрия хлорида. Определяли в динамике общее количество лейкоцитов, размеры лимфоцитов и активность в них лактатдегидрогеназы (ЛДГ) и сукцинатдегидрогеназы (СДГ). Изменения опорно-двигательного аппарата оценивали рентгенографически и актометрически в модели «открытое поле».Результаты и обсуждение. В первые 2 нед эксперимента в модельной группе животных отмечены повышение уровня лейкоцитов на 65% по сравнению с контролем (р=0,002), а также рост активности СДГ лимфоцитов на 51% и снижение общей («горизонтальной») подвижности животных на 30%. В последующем уровень лейкоцитов снижался на 25%, активность ЛДГ и СДГ – на 38%, радиус лимфоцитов – на 14% (p&lt;0,01). Действие карбоновых кислот носило дозозависимый характер: при максимальной дозе статистически значимых различий в общем количестве лейкоцитов, активности ЛДГ и СДГ в лимфоцитах, а также их размерах между группой адъювант-индуцированного РА и контрольной группой не выявлено.Заключение. У животных с адъювант-индуцированным РА коррекция метаболического статуса лимфоцитов смесью лимонной и янтарной кислот, являющихся ключевыми субстратами цикла Кребса, приводила к уменьшению структурных повреждений опорно-двигательного аппарата и, как следствие, к сохранению нормального объема движений.</p></abstract><trans-abstract xml:lang="en"><p>Objective: to study in dynamics metabolic changes in lymphocytes on the model of adjuvant-induced rheumatoid arthritis (RA) in warm-blooded animals.Material and methods. The RA model was elicited by administering Freund's complete adjuvant (AF) to male Wistar rats. Lymphocyte metabolism was corrected with a mixture of citric and succinic acids, which was injected for 4 weeks (at doses of 17 and 88 mg/kg body weight) from the first day of model formation. Animals of the control group were injected subcutaneously with isotonic sodium chloride solution. The total number of leukocytes, the size of lymphocytes and the activity of lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these cells were determined. Changes in the musculoskeletal system were assessed radiographically and actometrically in the «open field» model.Results and discussion. In the first 2 weeks of the experiment in the model group, an increase in the level of leukocytes by 65% compared to the control (p=0.002) was noted, an increase in the activity of lymphocytes SDH by 51% and a decrease in the total («horizontal») mobility of animals by 30% were also revealed. Subsequently, the level of leukocytes decreased by 25%, the activity of LDH and SDH – by 38%, the radius of lymphocytes – by 14% (p&lt;0.01). The action of carboxylic acids was dose-dependent: at the maximum dose, no statistically significant differences in the total number of leukocytes, LDH and SDH activity in lymphocytes, as well as their sizes were found between the group with adjuvant- induced RA and the control group.Conclusion. In animals with adjuvant-induced RA, correction of the metabolic status of lymphocytes with a mixture of citric and succinic acids, which are key substrates of the Krebs cycle, led to a decrease in structural damage of musculoskeletal system and, as a consequence, to the maintenance of normal range of motion.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>воспалительный процесс</kwd><kwd>двигательная активность</kwd><kwd>лактатдегидрогеназа</kwd><kwd>лимонная кислота</kwd><kwd>метаболизм лимфоцитов</kwd><kwd>ревматоидный артрит</kwd><kwd>субхондральный склероз</kwd><kwd>сукцинатдегидрогеназа</kwd><kwd>энерготропный эффект</kwd><kwd>янтарная кислота</kwd></kwd-group><kwd-group xml:lang="en"><kwd>inflammatory process</kwd><kwd>physical activity</kwd><kwd>lactate dehydrogenase</kwd><kwd>citric acid</kwd><kwd>lymphocyte metabolism</kwd><kwd>rheumatoid arthritis</kwd><kwd>subchondral sclerosis</kwd><kwd>succinate dehydrogenase</kwd><kwd>energotropic effect</kwd><kwd>succinic acid</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4 Suppl 3(Suppl 3):S265-72. doi: 10.1186/ar578. Epub 2002 May 9.</mixed-citation><mixed-citation xml:lang="en">Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4 Suppl 3(Suppl 3):S265-72. doi: 10.1186/ar578. Epub 2002 May 9.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">http://www.revmo-nadegda.ru/sites/default/files/file_files/revmatoidnyy_artrit_versiya_2015.pdf</mixed-citation><mixed-citation xml:lang="en">http://www.revmo-nadegda.ru/sites/default/files/file_files/revmatoidnyy_artrit_versiya_2015.pdf</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Jagpal A, Navarro-Millan I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC Rheumatol. 2018 Apr 11;2:10. doi: 10.1186/s41927-018-0014-y.eCollection 2018.</mixed-citation><mixed-citation xml:lang="en">Jagpal A, Navarro-Millan I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC Rheumatol. 2018 Apr 11;2:10. doi: 10.1186/s41927-018-0014-y.eCollection 2018.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Hsieh PH, Wu O, Geue C, et al. Economic burden of rheumatoid arthritis: a systematic review of literature in biologic era. Ann Rheum Dis. 2020 Jun;79(6):771-7. doi: 10.1136/annrheumdis-2019-216243. Epub 2020 Apr 3.</mixed-citation><mixed-citation xml:lang="en">Hsieh PH, Wu O, Geue C, et al. Economic burden of rheumatoid arthritis: a systematic review of literature in biologic era. Ann Rheum Dis. 2020 Jun;79(6):771-7. doi: 10.1136/annrheumdis-2019-216243. Epub 2020 Apr 3.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Mikhaylenko DS, Nemtsova MV, Bure IV, et al. Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response. Int J Mol Sci. 2020 Jul 11;21(14):4911. doi: 10.3390/ijms21144911.</mixed-citation><mixed-citation xml:lang="en">Mikhaylenko DS, Nemtsova MV, Bure IV, et al. Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response. Int J Mol Sci. 2020 Jul 11;21(14):4911. doi: 10.3390/ijms21144911.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford). 2013 Jan;52(1):53-61. doi: 10.1093/rheumatology/kes305. Epub 2012 Nov 28.</mixed-citation><mixed-citation xml:lang="en">Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford). 2013 Jan;52(1):53-61. doi: 10.1093/rheumatology/kes305. Epub 2012 Nov 28.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Никулина СЮ, Чернова АА, Большакова ТЮ и др. Гены предрасположенности к ревматоидному артриту. Сибирское медицинское обозрение. 2014;(3):11-8.</mixed-citation><mixed-citation xml:lang="en">Nikulina SYu, Chernova AA, Bol'shakova TYu, et al. Genes for predisposition to rheumatoid arthritis. Sibirskoe meditsinskoe obozrenie. 2014;(3):11-8. (in Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, Насонова ВА, редакторы. Ревматология: национальное руководство. Москва: ГЭОТАР-Медиа; 2010. 720 с.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, Nasonova VA, editors. Revmatologiya: natsional'noe rukovodstvo [Rheumatology. National guidelines]. Moscow: GEOTAR-Media; 2010. 720 p..</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Hussain T, Tan B, Yin Y, et al. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev. 2016; 2016:7432797. doi: 10.1155/2016/7432797.Epub 2016 Sep 22.</mixed-citation><mixed-citation xml:lang="en">Hussain T, Tan B, Yin Y, et al. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev. 2016; 2016:7432797. doi: 10.1155/2016/7432797.Epub 2016 Sep 22.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Moro-Garcia MA, Mayo JC, Sainz RM, et al. Influence of Inflammation in the Process of T Lymphocyte Differentiation: Proliferative, Metabolic, and Oxidative Changes. Front Immunol. 2018 Mar 1;9:339.doi: 10.3389/fimmu.2018.00339. eCollection 2018.</mixed-citation><mixed-citation xml:lang="en">Moro-Garcia MA, Mayo JC, Sainz RM, et al. Influence of Inflammation in the Process of T Lymphocyte Differentiation: Proliferative, Metabolic, and Oxidative Changes. Front Immunol. 2018 Mar 1;9:339.doi: 10.3389/fimmu.2018.00339. eCollection 2018.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Владимиров ЮА, Арчаков АИ. Перекисное окисление липидов в биологических мембранах. Москва: Наука; 1972. 252 с.</mixed-citation><mixed-citation xml:lang="en">Vladimirov YuA, Archakov AI. Perekisnoe okislenie lipidov v biologicheskikh membranakh [Lipid peroxidation in biological membranes]. Moscow: Nauka; 1972. 252 p.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Almeida L, Lochner M, Berod L, Sparwasser T. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016 Oct;28(5):514-24. doi: 10.1016/j.smim.2016.10.009.Epub 2016 Nov 4.</mixed-citation><mixed-citation xml:lang="en">Almeida L, Lochner M, Berod L, Sparwasser T. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016 Oct;28(5):514-24. doi: 10.1016/j.smim.2016.10.009.Epub 2016 Nov 4.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Sanchez-Lopez E, Cheng A, Guma M. Can Metabolic Pathways Be Therapeutic Targets in Rheumatoid Arthritis? J Clin Med. 2019 May 27;8(5):753. doi: 10.3390/jcm8050753.</mixed-citation><mixed-citation xml:lang="en">Sanchez-Lopez E, Cheng A, Guma M. Can Metabolic Pathways Be Therapeutic Targets in Rheumatoid Arthritis? J Clin Med. 2019 May 27;8(5):753. doi: 10.3390/jcm8050753.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Padda IS, Goyal A. Leflunomide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. 2021 May 24.</mixed-citation><mixed-citation xml:lang="en">Padda IS, Goyal A. Leflunomide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. 2021 May 24.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Asquith DL, Miller AM, McInnes IB, et al. Animal models of rheumatoid arthritis. Eur J Immunol. 2009 Aug;39(8):2040-4. doi: 10.1002/eji.200939578.</mixed-citation><mixed-citation xml:lang="en">Asquith DL, Miller AM, McInnes IB, et al. Animal models of rheumatoid arthritis. Eur J Immunol. 2009 Aug;39(8):2040-4. doi: 10.1002/eji.200939578.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Hong JI, Park IY, Kim HA. Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models. Int J Mol Sci. 2020 Jan 14;21(2):533. doi: 10.3390/ijms21020533.</mixed-citation><mixed-citation xml:lang="en">Hong JI, Park IY, Kim HA. Understanding the Molecular Mechanisms Underlying the Pathogenesis of Arthritis Pain Using Animal Models. Int J Mol Sci. 2020 Jan 14;21(2):533. doi: 10.3390/ijms21020533.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Таранов ОС, Якубицкий СН, Непомнящих ТС и др. Индуцированный адъювантом артрит у морских свинок. Acta naturae. 2016;8(4):119-26.</mixed-citation><mixed-citation xml:lang="en">Taranov OS, Yakubitskii SN, Nepomnyashchikh TS, et al. Adjuvantinduced arthritis in guinea pigs. Acta naturae. 2016;8(4):119-26. (in Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">https://www.ncbi.nlm.nih.gov/books/NBK54050/</mixed-citation><mixed-citation xml:lang="en">https://www.ncbi.nlm.nih.gov/books/NBK54050/</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">http://vnipchi.rospotrebnadzor.ru/s/203/files/ND/safety/95493_486.pdf</mixed-citation><mixed-citation xml:lang="en">http://vnipchi.rospotrebnadzor.ru/s/203/files/ND/safety/95493_486.pdf</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Бадтиев АК, Скупневский СВ, Пухаева ЕГ и др. Корригирующий эффект смеси лимонной и янтарной кислот в модели индуцированного аутоиммунного ревматоидного артрита у крыс. Современные проблемы науки и образования. 2020; (6):176.</mixed-citation><mixed-citation xml:lang="en">Badtiev AK, Skupnevskii SV, Pukhaeva EG, et al. The corrective effect of a mixture of citric and succinic acids in a model of induced autoimmune rheumatoid arthritis in rats. Sovremennye problemy nauki i obrazovaniya. 2020;(6):176. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">http://www.freepatent.ru/images/patents/100/2364868/patent-2364868.pdf</mixed-citation><mixed-citation xml:lang="en">http://www.freepatent.ru/images/patents/100/2364868/patent-2364868.pdf</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Шейбак ВМ, Павлюковец АЮ. Биохимическая гетерогенность Т-лимфоцитов. Вестник Витебского государственного медицинского университета. 2018;17(6):7-17.</mixed-citation><mixed-citation xml:lang="en">Sheibak VM, Pavlyukovets AYu. Biochemical heterogeneity of T-lymphocytes. Vestnik Vitebskogo gosudarstvennogo meditsinskogo universiteta. 2018;17(6):7-17. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Lin AP, Anderson SL, Minard KI, et al. Effects of excess succinate and retrograde control of metabolite accumulation in yeast tricarboxylic cycle mutants. J Biol Chem. 2011 Sep 30;286(39):33737-46. doi: 10.1074/jbc.M111.266890. Epub 2011 Aug 12.</mixed-citation><mixed-citation xml:lang="en">Lin AP, Anderson SL, Minard KI, et al. Effects of excess succinate and retrograde control of metabolite accumulation in yeast tricarboxylic cycle mutants. J Biol Chem. 2011 Sep 30;286(39):33737-46. doi: 10.1074/jbc.M111.266890. Epub 2011 Aug 12.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Цыганский РА. Физиология и патология животной клетки. Санкт-Петербург, Москва, Краснодар: Лань; 2009. 172 c.</mixed-citation><mixed-citation xml:lang="en">Tsyganskii RA. Fiziologiya i patologiya zhivotnoi kletki [Physiology and pathology of the animal cell]. Saint-Petersburg, Moscow, Krasnodar: Lan'; 2009. 172 p.</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>
