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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">actabiomedica</journal-id><journal-title-group><journal-title xml:lang="ru">Acta Biomedica Scientifica</journal-title><trans-title-group xml:lang="en"><trans-title>Acta Biomedica Scientifica</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2541-9420</issn><issn pub-type="epub">2587-9596</issn><publisher><publisher-name>Scientific Centre for Family Health and Human Reproduction Problems</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29413/ABS.2024-9.5.7</article-id><article-id custom-type="elpub" pub-id-type="custom">actabiomedica-5035</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>БИОЛОГИЯ И МЕДИЦИНСКАЯ БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOLOGY AND MEDICAL BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Показатели оксидативного стресса и тканевой гипоксии при различных фазах активности эндокринной офтальмопатии</article-title><trans-title-group xml:lang="en"><trans-title>Indicators of oxidative stress and tissue hypoxia in various phases of Graves’ orbitopathy activity</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6223-8888</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Таскина</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Taskina</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Таскина Елизавета Сергеевна – кандидат медицинских наук, доцент кафедры офтальмологии</p><p>672000, г. Чита, ул. Горького, 39а</p></bio><bio xml:lang="en"><p>Elizaveta S. Taskina – Cand. Sc. (Med.), Associate Professor at the Department of Ophthalmology</p><p>Gorkogo str. 39A, Chita 672000</p></bio><email xlink:type="simple">taskins@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/0000-0002-8899-5465</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Харинцева</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kharintseva</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Харинцева Светлана Владимировна – доктор медицинских наук, профессор, заведующая кафедрой офтальмологии</p><p>672000, г. Чита, ул. Горького, 39а</p></bio><bio xml:lang="en"><p>Svetlana V. Kharintseva – Dr. Sc. (Med.), Professor, Head of the Department of Ophthalmology</p><p>Gorkogo str. 39A, Chita 672000</p></bio><email xlink:type="simple">s.v.19.28@mail.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/0000-0002-0487-6275</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Караваева</surname><given-names>Т. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Karavaeva</surname><given-names>T. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Караваева Татьяна Михайловна – кандидат медицинских наук, доцент, старший научный сотрудник лаборатории клинической и экспериментальной биохимии и иммунологии Научно-исследовательского института молекулярной медицины</p><p>672000, г. Чита, ул. Горького, 39а</p></bio><bio xml:lang="en"><p>Tatyana M. Karavaeva – Cand. Sc. (Med.), Docent, Senior Research Officer at the Laboratory of Clinical and Experimental Biochemistry and Immunology, Research Institute of Molecular Medicine</p><p>Gorkogo str. 39A, Chita 672000</p></bio><email xlink:type="simple">KaTany1@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Читинская государственная медицинская академия» Минздрава России</institution></aff><aff xml:lang="en"><institution>Chita State Medical Academy</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>22</day><month>11</month><year>2024</year></pub-date><volume>9</volume><issue>5</issue><fpage>66</fpage><lpage>74</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Таскина Е.С., Харинцева С.В., Караваева Т.М., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Таскина Е.С., Харинцева С.В., Караваева Т.М.</copyright-holder><copyright-holder xml:lang="en">Taskina E.S., Kharintseva S.V., Karavaeva T.M.</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://www.actabiomedica.ru/jour/article/view/5035">https://www.actabiomedica.ru/jour/article/view/5035</self-uri><abstract><p>Эндокринная офтальмопатия (ЭОП) является экстратиреоидным осложнением дисфункции щитовидной железы, характеризующимся хроническим аутоиммунным воспалением мягких ретробульбарных тканей. Данные по изучению роли окислительного и гипоксического стресса при ЭОП неоднородны, что обуславливает необходимость дальнейшего их исследования.Цель исследования. Оценить показатели оксидативного стресса и тканевой гипоксии при различных фазах активности эндокринной офтальмопатии.Материалы и методы. Проведено клинико-инструментальное и лабораторное обследование пациентов с ЭОП (n = 32), с аутоиммунной патологией щитовидной железы (n = 18) и здоровых лиц (n = 15). Исследование включало офтальмологическое обследование и забор крови на определение концентрации антител к рецептору тиреотропного гормона, интерлейкина 17A (ИЛ-17A), гипоксия-индуцибельного фактора 1α (HIF-1α, hypoxia-inducible factor 1α), ТБК-активных продуктов и расчёт общей антиоксидантной активности (ОАО).Результаты исследования. Выявлено повышение концентрации ТБК-активных продуктов в клинической группе по сравнению с контролем (р &lt; 0,001). Показатель ОАО снижен при всех фазах активности ЭОП в сравнении с контрольной группой (р &lt; 0,001). Уровень HIF-1α не имел различий в группах исследования (Н = 3,29; р = 0,51). Выявлены прямые умеренные связи между концентрацией ИЛ-17A и уровнем ТБК-активных продуктов (р = 0,001), а также обратные умеренные связи – со значением ОАО (р = 0,007). Активность ЭОП по Сlinical Аctivity Score имела слабые обратные связи с ОАО (р &lt; 0,001). Статистически значимые зависимости между показателями окислительного стресса и тканевой гипоксии не обнаружены.Заключение. При ЭОП независимо от фазы активности наблюдается нарушение баланса между параметрами системы «перекисное окисление липидов – антиоксидантная защита», которое проявляется увеличением ТБК-активных продуктов при одновременном уменьшении ОАО. Показатели тканевой гипоксии не имели различий в группах исследования. Выявленные связи между показателями активности аутоиммунного воспаления в орбите и оксидативным стрессом подчёркивают патогенетическую обусловленность назначения антиоксидантных препаратов в терапии ЭОП.</p></abstract><trans-abstract xml:lang="en"><p>Graves’ orbitopathy (GO) is an extrathyroid complication of thyroid dysfunction characterized by chronic autoimmune inflammation of soft retrobulbar tissues. The data on the role of oxidative and hypoxic stress in GO are heterogeneous, which necessitates further research.The aim of the study. To evaluate the indicators of oxidative stress and tissue hypoxia at various phases of Graves’ orbitopathy activity.Material and methods. Examination of patients with GO (n = 32), with autoimmune thyroid pathology (n = 18) and healthy individuals (n = 15) was performed. The study included ophthalmological examination and blood sampling to determine the concentration of antibodies to the thyroid-stimulating hormone receptor, interleukin 17A (IL-17A), hypoxia inducible factor 1a (HIF-1a), TBK-active products and calculation of total antioxidant activity.Results. An increase in the concentration of TBK-active products in the clinical group was revealed compared with the control (p &lt; 0.001). The total antioxidant activity was reduced at all phases of GO activity than in the control (p &lt; 0.001). The level of HIF-1α did not differ in the study groups (H = 3.29; p = 0.51). Direct moderate correlations were found between the concentration of IL-17A and the level of TBA-active substances (p = 0.001), as well as inverse moderate correlations with the value of total antioxidant activity (p = 0.007). The activity of GO had weak correlations with total antioxidant activity (p &lt; 0.001). Significant correlations between indicators of oxidative stress and tissue hypoxia were not found.Conclusion. In GO, regardless of the activity phase, there is an imbalance between the parameters of the “lipid peroxidation – antioxidant protection” system, which is manifested by an increase in TBA-active substances while reducing the total antioxidant activity. The indicators of tissue hypoxia did not differ in the study groups. The revealed correlations between the autoimmune inflammation activity in the orbit and oxidative stress emphasize the pathogenetic conditionality of the antioxidant drugs appointment in the therapy of GO.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>эндокринная офтальмопатия</kwd><kwd>перекисное окисление липидов</kwd><kwd>антиоксидантная активность</kwd><kwd>гипоксия-индуцибельный фактор 1α</kwd><kwd>антитела к рецептору тиреотропного гормона</kwd><kwd>интерлейкин 17А</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Graves’ orbitopathy</kwd><kwd>lipid peroxidation</kwd><kwd>antioxidant activity</kwd><kwd>hypoxia inducible factor 1a</kwd><kwd>antibodies to the thyroid-stimulating hormone receptor</kwd><kwd>interleukin 17A</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">Zheng J, Duan H, You S, Liang B, Chen Y, Huang H. Research progress on the pathogenesis of Graves’ ophthalmopathy: Based on immunity, noncoding RNA and exosomes. Front Immunol. 2022; 13: 952954. doi: 10.3389/fimmu.2022.952954</mixed-citation><mixed-citation xml:lang="en">Zheng J, Duan H, You S, Liang B, Chen Y, Huang H. Research progress on the pathogenesis of Graves’ ophthalmopathy: Based on immunity, noncoding RNA and exosomes. Front Immunol. 2022; 13: 952954. doi: 10.3389/fimmu.2022.952954</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020; 16(2): 104-116. doi: 10.1038/s41574-019-0305-4</mixed-citation><mixed-citation xml:lang="en">Taylor PN, Zhang L, Lee RWJ, Muller I, Ezra DG, Dayan CM, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020; 16(2): 104-116. doi: 10.1038/s41574-019-0305-4</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Hoang TD, Stocker DJ, Chou EL, Burch HB. 2022 update on clinical management of Graves disease and thyroid eye disease. Endocrinol Metab Clin North Am. 2022; 51(2): 287-304. doi: 10.1016/j.ecl.2021.12.004</mixed-citation><mixed-citation xml:lang="en">Hoang TD, Stocker DJ, Chou EL, Burch HB. 2022 update on clinical management of Graves disease and thyroid eye disease. Endocrinol Metab Clin North Am. 2022; 51(2): 287-304. doi: 10.1016/j.ecl.2021.12.004</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Таскина Е.С., Харинцева С.В. Морфофункциональная характеристика и иммунологическая регуляция функции орбитальных фибробластов при эндокринной офтальмопатии. Клиническая и экспериментальная тиреоидология. 2018; 14(4): 183-191.</mixed-citation><mixed-citation xml:lang="en">Taskina ES, Kharintseva SV. Morphofunctional characteristics and immunological regulation of the orbital fibroblasts function in endocrine ophthalmopathy. Clinical and Experimental Thyroidology. 2018; 14(4): 183-191. (In Russ.). doi: 10.14341/ket10147</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Longo CM, Higgins PJ. Molecular biomarkers of Graves’ ophthalmopathy. Exp Mol Pathol. 2019; 106: 1-6. doi: 10.1016/j.yexmp.2018.11.004</mixed-citation><mixed-citation xml:lang="en">Longo CM, Higgins PJ. Molecular biomarkers of Graves’ ophthalmopathy. Exp Mol Pathol. 2019; 106: 1-6. doi: 10.1016/j.yexmp.2018.11.004</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Харинцева С.В., Таскина Е.С. Значение интерлейкинов 17, 23 и антител к рецептору тиреотропного гормона в патогенезе эндокринной офтальмопатии. Клиническая и экспериментальная тиреоидология. 2018; 14(2): 72-80.</mixed-citation><mixed-citation xml:lang="en">Charinzeva SV, Taskina ES. The role of interleukins 17, 23 and antibodies to the thyroid-stimulating hormone receptor in the pathogenesis of endocrine ophthalmopathy. Clinical and Experimental Thyroidology. 2018; 14(2): 72-80. (In Russ.). doi: 10.14341/ket9703</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Hou TY, Wu SB, Kau HC, Tsai CC. The role of oxidative stress and therapeutic potential of antioxidants in Graves’ ophthalmopathy. Biomedicines. 2021; 9(12): 1871. doi: 10.3390/biomedicines9121871</mixed-citation><mixed-citation xml:lang="en">Hou TY, Wu SB, Kau HC, Tsai CC. The role of oxidative stress and therapeutic potential of antioxidants in Graves’ ophthalmopathy. Biomedicines. 2021; 9(12): 1871. doi: 10.3390/biomedicines9121871</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Görtz GE, Philipp S, Bruderek K, Jesenek C, Horstmann M, Henning Y, et al. Macrophage-orbital fibroblast interaction and hypoxia promote inflammation and adipogenesis in Graves’ orbitopathy. Endocrinology. 2022; 164(2): bqac203. doi: 10.1210/endocr/bqac203</mixed-citation><mixed-citation xml:lang="en">Görtz GE, Philipp S, Bruderek K, Jesenek C, Horstmann M, Henning Y, et al. Macrophage-orbital fibroblast interaction and hypoxia promote inflammation and adipogenesis in Graves’ orbitopathy. Endocrinology. 2022; 164(2): bqac203. doi: 10.1210/endocr/bqac203</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Werner SC. Modification of the classification of the eye changes of Graves’ disease. Am J Ophthalmol. 1977; 83(5): 725-727. doi: 10.1016/0002-9394(77)90140-4</mixed-citation><mixed-citation xml:lang="en">Werner SC. Modification of the classification of the eye changes of Graves’ disease. Am J Ophthalmol. 1977; 83(5): 725-727. doi: 10.1016/0002-9394(77)90140-4</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velazquez-Villoria A, Galofre JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015; 2015: 249125. doi: 10.1155/2015/249125</mixed-citation><mixed-citation xml:lang="en">Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velazquez-Villoria A, Galofre JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015; 2015: 249125. doi: 10.1155/2015/249125</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Mourits MP, Koornneef L, Wiersinga WM. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: A novel approach. Br J Ophthalmol. 1989; 73(8): 639-644. doi: 10.1136/bjo.73.8.639</mixed-citation><mixed-citation xml:lang="en">Mourits MP, Koornneef L, Wiersinga WM. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: A novel approach. Br J Ophthalmol. 1989; 73(8): 639-644. doi: 10.1136/bjo.73.8.639</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Алексеев В.В., Карпищенко А.И. Медицинские лабораторные технологии: руководство по клинической и лабораторной диагностике; 3-е изд., перераб. И доп. М.: ГЕОТАР-Медиа; 2013; 2.</mixed-citation><mixed-citation xml:lang="en">Alekseev VV, Karpishchenko AI. Medical laboratory technologies: Guideline to clinical and laboratory diagnostics. 3rd edition, revised and enlarged. Moscow: GEOTAR-Media; 2013; 2. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Промыслов М.Ш., Демчук М.Л. Модификация метода определения суммарной антиоксидантной активности сыворотки крови. Вопросы медицинской химии. 1990; 36(4): 90-92.</mixed-citation><mixed-citation xml:lang="en">Promyshlov MSh, Demchuk ML. A modified method of determination of the total serum antioxidant activity. Voprosy meditsinskoi khimii. 1990; 36(4): 90-92. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Мудров В.А. Алгоритмы статистического анализа количественных признаков биомедицинских исследованиях с помощью пакета программ SPSS. Забайкальский медицинский вестник. 2020; 1: 140-150.</mixed-citation><mixed-citation xml:lang="en">Mudrov VA. Statistical analysis algorithms of quantitative features in biomedical research using the SPSS software package. Transbaikalian Medical Bulletin. 2020; 1: 140-150. (In Russ.) doi: 10.52485/19986173_2020_1_140</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Lanzolla G, Marcocci C, Marinò M. Antioxidant therapy in Graves’ orbitopathy. Front Endocrinol (Lausanne). 2020; 11: 608733. doi: 10.3389/fendo.2020.608733</mixed-citation><mixed-citation xml:lang="en">Lanzolla G, Marcocci C, Marinò M. Antioxidant therapy in Graves’ orbitopathy. Front Endocrinol (Lausanne). 2020; 11: 608733. doi: 10.3389/fendo.2020.608733</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Wang F, Li C, Li S, Cui L, Zhao J, Liao L. Selenium and thyroid diseases. Front Endocrinol (Lausanne). 2023; 14: 1133000. doi: 10.3389/fendo.2023.1133000</mixed-citation><mixed-citation xml:lang="en">Wang F, Li C, Li S, Cui L, Zhao J, Liao L. Selenium and thyroid diseases. Front Endocrinol (Lausanne). 2023; 14: 1133000. doi: 10.3389/fendo.2023.1133000</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Liu CT, Yen JJ, Brown DA, Song YC, Chu MY, Hung YH, et al. Targeting Nrf2 with 3H-1,2-dithiole-3-thione to moderate OXPHOS-driven oxidative stress attenuates IL-17A-induced psoriasis. Biomed Pharmacother. 2023; 159: 114294. doi: 10.1016/j.biopha.2023.114294</mixed-citation><mixed-citation xml:lang="en">Liu CT, Yen JJ, Brown DA, Song YC, Chu MY, Hung YH, et al. Targeting Nrf2 with 3H-1,2-dithiole-3-thione to moderate OXPHOS-driven oxidative stress attenuates IL-17A-induced psoriasis. Biomed Pharmacother. 2023; 159: 114294. doi: 10.1016/j.biopha.2023.114294</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Gross CJ, Mishra R, Schneider KS, Medard G, Wettmarshausen J, Dittlein DC, et al. K(+) efflux-independent NLRP3 inflammasome activation by small molecules targeting mitochondria. Immunity. 2016; 45(4): 761-773. doi: 10.1016/j.immuni.2016.08.010</mixed-citation><mixed-citation xml:lang="en">Gross CJ, Mishra R, Schneider KS, Medard G, Wettmarshausen J, Dittlein DC, et al. K(+) efflux-independent NLRP3 inflammasome activation by small molecules targeting mitochondria. Immunity. 2016; 45(4): 761-773. doi: 10.1016/j.immuni.2016.08.010</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Mogilenko DA, Haas JT, L’Homme L, Fleury S, Quemener S, Levavasseur M, et al. Metabolic and innate immune cues merge into a specific inflammatory response via the UPR. Cell. 2019; 177(5): 1201-1216 e19. doi: 10.1016/j.cell.2019.03.018</mixed-citation><mixed-citation xml:lang="en">Mogilenko DA, Haas JT, L’Homme L, Fleury S, Quemener S, Levavasseur M, et al. Metabolic and innate immune cues merge into a specific inflammatory response via the UPR. Cell. 2019; 177(5): 1201-1216 e19. doi: 10.1016/j.cell.2019.03.018</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Ece H, Mehmet E, Cigir BA, Yavuz D, Muammer K, Cumhur G, et al. Serum 8-OHdG and HIF-1α levels: Do they affect the development of malignancy in patients with hypoactive thyroid nodules? Contemp Oncol (Pozn). 2013; 17(1): 51-57. doi: 10.5114/wo.2013.33774</mixed-citation><mixed-citation xml:lang="en">Ece H, Mehmet E, Cigir BA, Yavuz D, Muammer K, Cumhur G, et al. Serum 8-OHdG and HIF-1α levels: Do they affect the development of malignancy in patients with hypoactive thyroid nodules? Contemp Oncol (Pozn). 2013; 17(1): 51-57. doi: 10.5114/wo.2013.33774</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Görtz GE, Horstmann M, Aniol B, Reyes BD, Fandrey J, Eckstein A, et al. Hypoxia-dependent HIF-1 activation impacts on tissue remodeling in Graves’ ophthalmopathy-implications for smoking. J Clin Endocrinol Metab. 2016; 101: 4834-4842. doi: 10.1210/jc.2016-1279</mixed-citation><mixed-citation xml:lang="en">Görtz GE, Horstmann M, Aniol B, Reyes BD, Fandrey J, Eckstein A, et al. Hypoxia-dependent HIF-1 activation impacts on tissue remodeling in Graves’ ophthalmopathy-implications for smoking. J Clin Endocrinol Metab. 2016; 101: 4834-4842. doi: 10.1210/jc.2016-1279</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Malkov MI, Lee CT, Taylor CT. Regulation of the hypoxiainducible factor (HIF) by pro-inflammatory cytokines. Cells. 2021; 10: 2340. doi: 10.3390/cells10092340</mixed-citation><mixed-citation xml:lang="en">Malkov MI, Lee CT, Taylor CT. Regulation of the hypoxiainducible factor (HIF) by pro-inflammatory cytokines. Cells. 2021; 10: 2340. doi: 10.3390/cells10092340</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>
