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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">RUDN Journal of Medicine</journal-id><journal-title-group><journal-title xml:lang="en">RUDN Journal of Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник Российского университета дружбы народов. Серия: Медицина</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-0245</issn><issn publication-format="electronic">2313-0261</issn><publisher><publisher-name xml:lang="en">Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">50514</article-id><article-id pub-id-type="doi">10.22363/2313-0245-2025-30-2-177-199</article-id><article-id pub-id-type="edn">GJBIWF</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ФИЗИОЛОГИЯ. ЭКСПЕРИМЕНТАЛЬНАЯ ФИЗИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Deciphering the role of angiotensin converting enzyme2 in health and diseases</article-title><trans-title-group xml:lang="ru"><trans-title>Расшифровка роли ангиотензинпревращающего фермента 2 в норме и при заболеваниях</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2021-4906</contrib-id><name-alternatives><name xml:lang="en"><surname>Sivasakthivel</surname><given-names>Shivani</given-names></name><name xml:lang="ru"><surname>Сивасактивел</surname><given-names>Ш.</given-names></name></name-alternatives><email>jsshivaninarayanan@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5426-3506</contrib-id><name-alternatives><name xml:lang="en"><surname>Ramani</surname><given-names>Pratibha</given-names></name><name xml:lang="ru"><surname>Рамани</surname><given-names>П.</given-names></name></name-alternatives><email>jsshivaninarayanan@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences</institution></aff><aff><institution xml:lang="ru">Стоматологический колледж больницы Савита, Институт медицинских и технических наук Савита</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2026-06-07" publication-format="electronic"><day>07</day><month>06</month><year>2026</year></pub-date><volume>30</volume><issue>2</issue><issue-title xml:lang="en">PHISIOLOGY. EXPERIMENTAL PHYSIOLOGY</issue-title><issue-title xml:lang="ru">ФИЗИОЛОГИЯ. ЭКСПЕРИМЕНТАЛЬНАЯ ФИЗИОЛОГИЯ</issue-title><fpage>177</fpage><lpage>199</lpage><history><date date-type="received" iso-8601-date="2026-06-07"><day>07</day><month>06</month><year>2026</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Sivasakthivel S., Ramani P.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Сивасактивел Ш., Рамани П.</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">Sivasakthivel S., Ramani P.</copyright-holder><copyright-holder xml:lang="ru">Сивасактивел Ш., Рамани П.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.rudn.ru/medicine/article/view/50514">https://journals.rudn.ru/medicine/article/view/50514</self-uri><abstract xml:lang="en"><p>Relevance. Angiotensin converting enzyme 2 (ACE 2) is recognised as a significant regulator of cardiovascular and pulmonary homeostasis owing to its involvement in the renin-angiotensin system (RAAS). This extensive review addresses ACE 2’s conventional role in converting Angiotensin II (Ang II) to the Angiotensin-(1-7) to its broader implications in cardiovascular illness, pulmonary pathology, metabolic diseases, and cancers. Conclusion. Recent research has shed light on ACE2’s significance beyond its enzymatic capabilities, specifically as a cellular receptor of various pathogens. Furthermore, recent evidence shows that ACE2 is involved in inflammation, glucose metabolism, and gut microbiome modulation. The tissue distribution patterns, regulatory mechanisms, and therapeutic possibilities show its dual role as a protective factor in and a possible entryway for the viral infections. Understanding these multiple processes in health and disease state serves to be essential in establishing tailored treatments for the diseases. This review outlines the existing understanding of ACE 2 and emphasizes areas for further research, notably its potential as a therapeutic target. Furthermore, we have discussed the challenges and future directions in ACE2-based therapeutics.</p></abstract><trans-abstract xml:lang="ru"><p>Актуальность. Ангиотензинпревращающий фермент 2 (АПФ 2) признан важным регулятором сердечно-сосудистого и легочного гомеостаза благодаря его участию в РААС (ренин-ангиотензиновой системе). В этом обширном обзоре рассматривается как традиционная роль АПФ 2 в превращении ангиотензина II (Ang II) в ангиотензин-(1-7), так и его более широкое значение в сердечно-сосудистых заболеваниях, легочной патологии, метаболических заболеваниях и раке. Выводы. Недавние исследования пролили свет на значение АПФ 2, выходящее за рамки его ферментативных возможностей, в частности, как клеточного рецептора различных патогенов. Кроме того, недавние исследования показывают, что ACE2 участвует в воспалении, метаболизме глюкозы и модуляции микробиома кишечника. Распределение в тканях, механизмы регуляции и терапевтические возможности демонстрируют его двойную роль: защитного фактора и возможного пути проникновения вирусных инфекций. Понимание этих множественных процессов в состоянии здоровья и болезни имеет важное значение для разработки персонализированных методов лечения заболеваний. В данном обзоре изложено существующее понимание ACE2 и выделены области для дальнейших исследований, в частности, его потенциал в качестве терапевтической мишени. Кроме того, обобщены проблемы и будущие направления в терапии на основе ACE2.</p></trans-abstract><kwd-group xml:lang="en"><kwd>ACE2</kwd><kwd>angiotensin converting enzyme 2</kwd><kwd>health</kwd><kwd>ailments</kwd><kwd>physiology</kwd><kwd>CVS</kwd><kwd>pulmonary</kwd><kwd>renal</kwd><kwd>cancer</kwd><kwd>immuno</kwd><kwd>skin</kwd><kwd>gut</kwd><kwd>neuro</kwd><kwd>ocular</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>ACE2</kwd><kwd>ангиотензин превращающий фермент 2</kwd><kwd>здоровье</kwd><kwd>заболевания</kwd><kwd>физиология</kwd><kwd>сердечно-сосудистая система</kwd><kwd>легочная система</kwd><kwd>почечная система</kwd><kwd>рак</kwd><kwd>иммунология</kwd><kwd>кожа</kwd><kwd>кишечник</kwd><kwd>нейрофизиология</kwd></kwd-group><funding-group/></article-meta><fn-group/></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Mizuiri S, Ohashi Y. ACE and ACE2 in kidney disease. World J Nephrol. 2015;4(1):74–82. doi:10.5527/wjn.v4.i1.74</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel Angiotensin-­Converting Enzyme–Related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circulation Research. 2000;87(5): E1–9. doi:10.1161/01.res.87.5.e1</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Ferreira AJ, Shenoy V, Yamazato Y. Evidence for angiotensin-­converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med. 2009;179(11):1048–1054. doi:10.1164/rccm.200811-1678OC</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Wiese O, Zemlin AE, Pillay TS. Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2). J Clin Pathol. 2021;74(5):285–290. doi:10.1136/jclinpath-2020-206954</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Devaux CA, Camoin-­Jau L. An update on angiotensin-­converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection. Frontiers in Microbiology. 2022;13:1042200. doi:10.3389/fmicb.2022.1042200</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Varagic J, Ahmad S, Nagata S, Ferrario CM. ACE2: Angiotensin II/Angiotensin-(1–7) balance in cardiac and renal injury. Current Hypertension Reports. 2014;16(3):420. doi:10.1007/s11906–014–0420–5</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Magazine R, Chogtu B, Bhat A. Role of Angiotensin Converting Enzyme‑2 and its modulation in disease: exploring new frontiers. Medicine and Pharmacy Reports. 2023;96(2):146–153. doi:10.15386/mpr-2345</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Kazemi-­Bajestani SMR, Patel VB, Wang W, Oudit GY. Targeting the ACE2 and Apelin pathways are novel therapies for heart failure: Opportunities and challenges. Cardiology Research and Practice. 2012;2012:1–11. doi:10.1155/2012/823193</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Sevá Pessôa B, van der Lubbe N, Verdonk K, Roks AJ, Hoorn EJ, Danser AH. Key developments in renin-­angiotensin-aldosterone system inhibition. Nat Rev Nephrol. 2013;9(1):26–36. doi:10.1038/nrneph.2012.249</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/Angiotensin 1–7 Axis of the Renin-­Angiotensin System in Heart Failure. Circ Res. 2016;118(8):1313–1326. doi:10.1161/CIRCRESAHA.116.307708</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Santos RA, Ferreira AJ. Angiotensin-(1–7) and the renin-­angiotensin system. Curr Opin Nephrol Hypertens. 2007;16(2):122–128. doi:10.1097/MNH.0b013e328031f362</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ, Raizada MK, Grant MB, Oudit GY. Angiotensin-­Converting enzyme 2: SARS-COV‑2 receptor and regulator of the Renin-­Angiotensin system. Circulation Research.2020;126(10):1456–1474. doi:10.1161/circresaha.120.317015</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Kuriakose J, Montezano AC, Touyz RM. ACE2/Ang-(1–7)/Mas1 axis and the vascular system: vasoprotection to COVID‑19‑associated vascular disease. Clinical Science. 2021;135(2):387–407. doi:10.1042/cs20200480</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Norambuena-­Soto I, Lopez-­Crisosto C, Martinez-­Bilbao J, Hernandez-­Fuentes C, Parra V, Lavandero S, Chiong M. Angiotensin-(1–9) in hypertension. Biochemical Pharmacology. 2022;203:115183. doi:10.1016/j.bcp.2022.115183</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-­Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM. Angiotensin-­converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112–116. doi:10.1038/nature03712</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Morganstein T, Haidar Z, Trivlidis J, Azuelos I, Huang MJ, Eidelman DH, Baglole CJ. Involvement of the ACE2/ANG-(1–7)/MASR axis in pulmonary fibrosis: Implications for COVID‑19. International Journal of Molecular Sciences. 2021;22(23):12955. doi:10.3390/ijms222312955</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Beyerstedt S, Casaro EB, Rangel ÉB. COVID‑19: angiotensin-­converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV‑2 infection. European Journal of Clinical Microbiology &amp; Infectious Diseases. 2021;40(5):905–919. doi:10.1007/s10096–020–04138–6</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-­Long Structural Studies of SARS Coronavirus. Journal of Virology. 2020;94(7). doi:10.1128/jvi.00127-20</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-­converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–454. doi:10.1038/nature02145</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020;395(10224):565–574. doi:10.1016/s0140-6736 (20) 30251–8</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Sun G, Xue L, He Q, Zhao Y, Xu W, Wang Z. Structural insights into SARS-CoV‑2 infection and therapeutics development. Stem Cell Research. 2021;52:102219. doi:10.1016/j.scr.2021.102219</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Suh SH, Kwon S MA, Kim SW, Bae EH. Angiotensin-­converting enzyme 2 and kidney diseases in the era of coronavirus disease 2019. The Korean Journal of Internal Medicine. 2020;36(2):247–262. doi:10.3904/kjim.2020.355</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Williams VR, Scholey JW. Angiotensin-­converting enzyme 2 and renal disease. Current Opinion in Nephrology &amp; Hypertension. 2017;27(1):35–41. doi:10.1097/mnh.0000000000000378</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Sun X, Wang M, Xu C, Wang S, Li L, Zou S, Yu J, Wei Y. Positive effect of a Pea–Clam Two-­Peptide composite on hypertension and organ protection in spontaneously hypertensive rats. Nutrients. 2022;14(19):4069. doi:10.3390/nu14194069</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Sanad AM, Qadri F, Popova E, Rodrigues AF, Heinbokel T, Quach S, Schulz A, Bachmann S, Kreutz R, Alenina N, Bader M. Transgenic angiotensin-­converting enzyme 2 overexpression in the rat vasculature protects kidneys from ageing-­induced injury. Kidney International. 2023;104(2):293–304. doi:10.1016/j.kint.2023.04.007</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Maksimowski N, Williams VR, Scholey JW. Kidney ACE2 expression: Implications for chronic kidney disease. PLoS ONE. 2020;15(10): e0241534. doi:10.1371/journal.pone.0241534</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Bosso M, Thanaraj TA, Abu-­Farha M, Alanbaei M, Abubaker J, Al-­Mulla F. The two faces of ACE2: the role of ACE2 receptor and its polymorphisms in hypertension and COVID‑19. Molecular Therapy — Methods &amp; Clinical Development. 2020;18:321–327. doi:10.1016/j.omtm.2020.06.017</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Komatsu T, Suzuki Y, Imai J, Sugano S, Hida M, Tanigami A, Muroi S, Yamada Y, Hanaoka K. Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-­converting enzyme-­related carboxypeptidase (MACE2). DNA Sequence. 2002;13(4):217–220. doi:10.1080/1042517021000021608</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>McClements L, Kautzky-­Willer A, Kararigas G, Ahmed SB, Stallone JN. The role of sex differences in cardiovascular, metabolic, and immune functions in health and disease: a review for “Sex Differences in Health Awareness Day.” Biology of Sex Differences. 2025;16(1):33. doi:10.1186/s13293-025-00714-7</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Zheng J, Hao H. Targeting renal damage: The ACE2/Ang-(1–7)/mas axis in chronic kidney disease. Cellular Signalling. 2024;124:111413. doi:10.1016/j.cellsig.2024.111413</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Young MJ, Clyne CD, Chapman KE. Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV‑2. Journal of Endocrinology. 2020;247(2): R45-R62. doi:10.1530/joe-20-0260</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Caroccia B, Vanderriele PE, Seccia TM, Piazza M, Lenzini L, Prisco S, Torresan F, Domenig O, Iacobone M, Poglitsch M, Rossi GP. Aldosterone and cortisol synthesis regulation by angiotensin-(1–7) and angiotensin-­converting enzyme 2 in the human adrenal cortex. Journal of Hypertension. 2021;39(8):1577–1585. doi:10.1097/hjh.0000000000002816</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Acevedo-Rodriguez A, Kauffman AS, Cherrington BD, Borges CS, Roepke TA, Laconi M. Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling. Journal of Neuroendocrinology. 2018;30(10): e12590. doi:10.1111/jne.12590</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Chen F, Chen Y, Ke Q, Wang Y, Gong Z, Chen X, Cai Y, Li S, Sun Y, Peng X, Ji Y, Zhang T, Wu W, Cui L, Wang Y. ApoE4 associated with severe COVID‑19 outcomes via downregulation of ACE2 and imbalanced RAS pathway. Journal of Translational Medicine. 2023;21(1):103. doi:10.1186/s12967-023-03945-7</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Rath S, Perikala V, Jena AB, Dandapat J. Factors regulating dynamics of angiotensin-­converting enzyme‑2 (ACE2), the gateway of SARS-CoV‑2: Epigenetic modifications and therapeutic interventions by epidrugs. Biomedicine &amp; Pharmacotherapy. 2021;143:112095. doi:10.1016/j.biopha.2021.112095</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Oliveira AC, Karas MM, Alves M, He J, De Kloet AD, Krause EG, Richards EM, Bryant AJ, Raizada MK. ACE2 overexpression in corticotropin-­releasing-hormone cells offers protection against pulmonary hypertension. Frontiers in Neuroscience. 2023;17:1223733. doi:10.3389/fnins.2023.1223733</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Sriramula S, Xia H, Xu P, Lazartigues E. Brain-targeted angiotensin-­converting enzyme 2 overexpression attenuates neurogenic hypertension by inhibiting cyclooxygenase-­mediated inflammation. Hypertension. 2015;65(3):577–586. doi:10.1161/HYPERTENSIONAHA.114.04691</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Li J, Kong X, Liu T, Xian M, Wei J. The role of ACE2 in neurological disorders: From underlying mechanisms to the neurological impact of COVID‑19. International Journal of Molecular Sciences. 2024;25(18):9960. doi:10.3390/ijms25189960</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Memon B, Abdelalim EM. ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV‑2 and diabetes. Acta Physiol (Oxf). 2021;233(4): e13733. doi:10.1111/apha.13733</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Wang L, Liang J, Leung PS. The ACE2/ANG-(1–7)/MAS axis regulates the development of pancreatic endocrine cells in mouse embryos. PLoS ONE. 2015;10(6): e0128216. doi:10.1371/journal.pone.0128216</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Shoemaker R, Yiannikouris F, Thatcher S, Cassis L. ACE2 deficiency reduces β-cell mass and impairs β-cell proliferation in obese C57BL/6 mice. Am J Physiol Endocrinol Metab. 2015;309(7): E621-E631. doi:10.1152/ajpendo.00054.2015</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Shukla AK, Awasthi K, Usman K, Banerjee M. Role of renin-­angiotensin system/angiotensin converting enzyme‑2 mechanism and enhanced COVID‑19 susceptibility in type 2 diabetes mellitus. World J Diabetes. 2024;15(4):606–622. doi:10.4239/wjd.v15.i4.606</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Mukherjee A, Wanjari U, Gopalakrishnan A, Kannampuzha S, Murali R, Namachivayam A, Ganesan R, Renu K, Dey A, Vellingiri B, Prabakaran D. Insights into the Scenario of SARS-CoV‑2 Infection in Male Reproductive Toxicity. Vaccines. 2023;11(3):510. doi:10.3390/vaccines11030510</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Achua JK, Chu KY, Ibrahim E, Khodamoradi K, Delma KS, Iakymenko OA, Kryvenko ON, Arora H, Ramasamy R. Histopathology and ultrastructural findings of fatal COVID‑19 infections on testis. The World Journal of Men S Health. 2020;39(1):65. doi:10.5534/wjmh.200170</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Jing Y, Run-­Qian L, Hao-­Ran W, Hao-­Ran C, Ya-­Bin L, Yang G, Fei C. Potential influence of COVID‑19/ACE2 on the female reproductive system. Molecular Human Reproduction. 2020;26(6):367–373. doi:10.1093/molehr/gaaa030</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Zafari Zangeneh F. Interaction of SARS-CoV‑2 With RAS/ACE2 in the Female Reproductive System. J Family Reprod Health. 2022;16(1):1–8. doi:10.18502/jfrh.v16i1.8588</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Rotondi M, Coperchini F, Ricci G, Denegri M, Croce L, Ngnitejeu ST, Villani L, Magri F, Latrofa F, Chiovato L. Detection of SARS-COV‑2 receptor ACE‑2 mRNA in thyroid cells: a clue for COVID‑19‑related subacute thyroiditis. Journal of Endocrinological Investigation. 2020;44(5):1085–1090. doi:10.1007/s40618-020-01436-w</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Narayan SS, Lorenz K, Ukkat J, Hoang-­Vu C, Trojanowicz B.</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Angiotensin converting enzymes ACE and ACE2 in thyroid cancer progression. Neoplasma. 2020;67(2):402–409. doi:10.4149/neo_2019_190506N405</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med. 2010;2(7):247–257. doi:10.1002/emmm.201000080</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Binesh A, Devaraj SN, Devaraj H. Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis. J Biochem Mol Toxicol. 2020;34(2): e22422. doi:10.1002/jbt.22422</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Cortez-­Retamozo V, Etzrodt M, Newton A, Ryan R, Pucci F, Sio SW, Kuswanto W, Rauch PJ, Chudnovskiy A, Iwamoto Y, Kohler R, Marinelli B, Gorbatov R, Wojtkiewicz G, Panizzi P, Mino-­Kenudson M, Forghani R, Figueiredo JL, Chen JW, Xavier R, Swirski FK, Nahrendorf M, Weissleder R, Pittet MJ. Angiotensin II drives the production of Tumor-­Promoting macrophages. Immunity. 2013;38(2):296–308. doi:10.1016/j.immuni.2012.10.015</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Zhou S, Lu H, Chen R, Tian Y, Jiang Y, Zhang S, Ni D, Su Z, Shao X. Angiotensin II enhances the acetylation and release of HMGB1 in RAW264.7 macrophage. Cell Biology International. 2018;42(9):1160–1169. doi:10.1002/cbin.10984</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. European Journal of Pharmacology. 2020;877:173090. doi:10.1016/j.ejphar.2020.173090</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Song X, Hu W, Yu H, Zhao L, Zhao Y, Zhao Y, Zhao X, Xue H, Zhao Y, Zhao Y. Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytometry Part A. 2020;103(2):136–145. doi:10.1002/cyto.a.24285</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, Nemati M. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID‑19: Lessons from SARS and MERS, and potential therapeutic interventions. Life Sci. 2020;257:118102. doi:10.1016/j.lfs.2020.118102</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Vardhana SA, Wolchok JD. The many faces of the anti-­COVID immune response. The Journal of Experimental Medicine. 2020;217(6). doi:10.1084/jem.20200678</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Welch JL, Xiang J, Chang Q, Houtman JCD, Stapleton JT. T-Cell Expression of Angiotensin-­Converting Enzyme 2 and Binding of Severe Acute Respiratory Coronavirus 2. J Infect Dis. 2022;225(5):810–819. doi:10.1093/infdis/jiab595</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of immune response in patients with coronavirus 2019 (COVID‑19) in Wuhan, China. Clinical Infectious Diseases. 2020;71(15):762–768. doi:10.1093/cid/ciaa248</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Bhari VK, Kumar D, Kumar S, Mishra R. SARS-CoV‑2 cell receptor gene ACE2 -mediated immunomodulation in breast cancer subtypes. Biochemistry and Biophysics Reports. 2020;24:100844. doi:10.1016/j.bbrep.2020.100844</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Beyerstedt S, Casaro EB, Rangel ÉB. COVID‑19: angiotensin-­converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV‑2 infection. European Journal of Clinical Microbiology &amp; Infectious Diseases. 2021;40(5):905–919. doi:10.1007/s10096–020–04138–6</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Song Y, Myers R, Mehl F, Murphy L, Brooks B, Wilson JM, Kadl A, Woodfolk J, Zeichner SL. ACE‑2‑like enzymatic activity is associated with immunoglobulin in COVID‑19 patients. mBio. 2024;15(4): e0054124. doi:10.1128/mbio.00541-24</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID‑19. Science. 2022;375(6585):1122–1127. doi:10.1126/science.abm8108</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I. COVID‑19 cytokine storm: The anger of inflammation. Cytokine. 2020;133:155151. doi:10.1016/j.cyto.2020.155151</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, Mast AE, Justice A, Aronow B, Jacobson D. A mechanistic model and therapeutic interventions for COVID‑19 involving a RAS-mediated bradykinin storm. eLife. 2020;9. doi:10.7554/elife.59177</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Alabsi S, Dhole A, Hozayen S, Chapman SA. Angiotensin-­Converting enzyme 2 Expression and severity of SARS-COV‑2 infection. Microorganisms. 2023;11(3):612. doi:10.3390/microorganisms11030612</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>McMillan P, Dexhiemer T, Neubig RR, Uhal BD. COVID‑19—A theory of autoimmunity against ACE‑2 explained. Frontiers in Immunology. 2021;12:582166. doi:10.3389/fimmu.2021.582166</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Mohammed M, Berdasco C, Lazartigues E. Brain angiotensin converting enzyme‑2 in central cardiovascular regulation. Clinical Science. 2020;134(19):2535–2547. doi:10.1042/cs20200483</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Cui H, Su S, Cao Y, Ma C, Qiu W. The altered anatomical distribution of ACE2 in the brain with Alzheimer’s disease pathology. Frontiers in Cell and Developmental Biology. 2021;9:684874. doi:10.3389/fcell.2021.684874</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-­converting enzyme. Journal of Biological Chemistry. 2000;275(43):33238–33243. doi:10.1074/jbc.m002615200</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Pop D, Dădârlat-­Pop A, Tomoaia R, Zdrenghea D, Caloian B. Updates on the Renin–Angiotensin–Aldosterone system and the cardiovascular continuum. Biomedicines. 2024;12(7):1582. doi:10.3390/biomedicines12071582</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Li J, Kong X, Liu T, Xian M, Wei J. The role of ACE2 in neurological disorders: From underlying mechanisms to the neurological impact of COVID‑19. International Journal of Molecular Sciences. 2024;25(18):9960. doi:10.3390/ijms25189960</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: properties and future directions. Journal of Neurochemistry. 2008;107(6):1482–1494. doi:10.1111/j.1471-4159.2008.05723.x</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Labandeira-­Garcia JL, Rodríguez-­Perez AI, Garrido-­Gil P, Rodriguez-­Pallares J, Lanciego JL, Guerra MJ. Brain Renin-­Angiotensin system and microglial polarization: Implications for aging and neurodegeneration. Frontiers in Aging Neuroscience. 2017;9:129. doi:10.3389/fnagi.2017.00129</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Chen Q, Gao Y, Yang F, Deng H, Wang Y, Yuan L. Angiotensin-­converting enzyme 2 improves hepatic insulin resistance by regulating GABAergic signaling in the liver. Journal of Biological Chemistry. 2022;298(12):102603. doi:10.1016/j.jbc.2022.102603</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Becker ES, Rinck M, Türke V, Kause P, Goodwin R, Neumer S, Margraf J. Epidemiology of specific phobia subtypes: Findings from the Dresden Mental Health Study. European Psychiatry. 2006;22(2):69–74. doi:10.1016/j.eurpsy.2006.09.006</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL, Lazartigues E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-­angiotensin system. American Journal of Physiology-­Regulatory, Integrative and Comparative Physiology. 2006;292(1): R373-R381. doi:10.1152/ajpregu.00292.2006</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Kim JE, Dager SR, Lyoo IK. The role of the amygdala in the pathophysiology of panic disorder: evidence from neuroimaging studies. Biology of Mood &amp; Anxiety Disorders. 2012;2(1):20. doi:10.1186/2045–5380–2–20</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Kehoe PG, Passmore PA. The Renin-­Angiotensin system and antihypertensive drugs in Alzheimer’s disease: Current standing of the angiotensin hypothesis? Journal of Alzheimer S Disease. 2012;30(s2): S251-S268. doi:10.3233/jad-2012-111376</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Barzegar M, Stokes KY, Chernyshev O, Kelley RE, Alexander JS. The role of the ACE2/MASR axis in Ischemic Stroke: New insights for therapy. Biomedicines. 2021;9(11):1667. doi:10.3390/biomedicines9111667</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Penninger JM, Grant MB, Sung JJY. The role of angiotensin converting enzyme 2 in modulating gut microbiota, intestinal inflammation, and coronavirus infection. Gastroenterology. 2020;160(1):39–46. doi:10.1053/j.gastro.2020.07.067</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Qin W h., Liu C l., Jiang Y h., Hu B, Wang H y., Fu J. Gut ACE2 expression, tryptophan deficiency, and inflammatory responses the potential connection that should not be ignored during SARS-COV‑2 infection. Cellular and Molecular Gastroenterology and Hepatology. 2021;12(4):1514–1516.e4. doi:10.1016/j.jcmgh.2021.06.014</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Li J, Yan Y, Fu Y, Chen Z, Yang Y, Li Y, Pan J, Li F, Zha C, Miao K, Ben L, Saleemi MK, Zhu Y, Ye H, Yang L, Wang W. ACE2 mediates tryptophan alleviation on diarrhea by repairing intestine barrier involved mTOR pathway. Cellular &amp; Molecular Biology Letters. 2024;29(1):90. doi:10.1186/s11658-024-00603-8</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>Perrotta F, Matera MG, Cazzola M, Bianco A. Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter? Respiratory Medicine. 2020;168:105996. doi:10.1016/j.rmed.2020.105996</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Nowak JK, Lindstrøm JC, Kalla R, Ricanek P, Halfvarson J, Satsangi J. Age, inflammation, and disease location are critical determinants of intestinal expression of SARS-COV‑2 receptor ACE2 and TMPRSS2 in inflammatory bowel disease. Gastroenterology. 2020;159(3):1151–1154.e2. doi:10.1053/j.gastro.2020.05.030</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Burgueño JF, Reich A, Hazime H, Quintero MA, Fernandez I, Fritsch J, Santander AM, Brito N, Damas OM, Deshpande A, Kerman DH, Zhang L, Gao Z, Ban Y, Wang L, Pignac-­Kobinger J, Abreu MT. Expression of SARS-COV‑2 entry molecules ACE2 and TMPRSS2 in the gut of patients with IBD. Inflammatory Bowel Diseases. 2020;26(6):797–808. doi:10.1093/ibd/izaa085</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>Neurath MF. COVID‑19: biologic and immunosuppressive therapy in gastroenterology and hepatology. Nature Reviews Gastroenterology &amp; Hepatology. 2021;18(10):705–715. doi:10.1038/s41575-021-00480-y</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>Song L, Ji W, Cao X. Integrated analysis of gut microbiome and its metabolites in ACE2‑knockout and ACE2‑overexpressed mice. Frontiers in Cellular and Infection Microbiology. 2024;14:1404678. doi:10.3389/fcimb.2024.1404678</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Duan Y, Prasad R, Feng D, Beli E, Calzi SL, Longhini ALF, Lamendella R, Floyd JL, Dupont M, Noothi SK, Sreejit G, Athmanathan B, Wright J, Jensen AR, Oudit GY, Markel TA, Nagareddy PR, Obukhov AG, Grant MB. Bone Marrow-­Derived cells restore functional integrity of the gut epithelial and vascular barriers in a model of diabetes and ACE2 deficiency. Circulation Research. 2019;125(11):969–988. doi:10.1161/circresaha.119.315743</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Afsar B, Afsar RE, Ertuglu LA, Kuwabara M, Ortiz A, Covic A, Kanbay M. Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics. Clinical &amp; Translational Oncology. 2020;23(4):682–696. doi:10.1007/s12094–020–02488–3</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>Zhang Z, Li L, Li M, Wang X. The SARS-CoV‑2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression. Computational and Structural Biotechnology Journal. 2020;18:2438–2444. doi:10.1016/j.csbj.2020.08.024</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>Feng H, Wei X, Pang L, Wu Y, Hu B, Ruan Y, Liu Z, Liu J, Wang T. Prognostic and immunological value of Angiotensin-­Converting enzyme 2 in Pan-­Cancer. Frontiers in Molecular Biosciences. 2020;7:189. doi:10.3389/fmolb.2020.00189</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>Zhang Q, Lu S, Li T, Yu L, Zhang Y, Zeng H, Qian X, Bi J, Lin Y. ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway. Journal of Experimental &amp; Clinical Cancer Research. 2019;38(1):173. doi:10.1186/s13046–019–1156–5</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>Wan. The angiotensin-­converting enzyme 2 in tumor growth and tumor-­associated angiogenesis in non-small cell lung cancer. Oncology Reports. 2010;23(4):941–948. doi:10.3892/or_00000718</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>Zhou L, Zhang R, Yao W, Wang J, Qian A, Qiao M, Zhang Y, Yuan Y. Decreased Expression of Angiotensin-­Converting Enzyme 2 in Pancreatic Ductal Adenocarcinoma Is Associated with Tumor Progression. The Tohoku Journal of Experimental Medicine. 2009;217(2):123–131. doi:10.1620/tjem.217.123</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>Zong H, Yin B, Zhou H, Cai D, Ma B, Xiang Y. Loss of angiotensin-­converting enzyme 2 promotes growth of gallbladder cancer. Tumor Biology. 2015;36(7):5171–5177. doi:10.1007/s13277-015-3171-2</mixed-citation></ref><ref id="B97"><label>97.</label><mixed-citation>Xu J, Fan J, Wu F, Huang Q, Guo M, Lv Z, Han J, Duan L, Hu G, Chen L, Liao T, Ma W, Tao X, Jin Y. The ACE2/Angiotensin-(1–7)/MAS receptor axis: Pleiotropic roles in cancer. Frontiers in Physiology. 2017;8:276. doi:10.3389/fphys.2017.00276</mixed-citation></ref><ref id="B98"><label>98.</label><mixed-citation>Huang WJ, He WY, Li JD, He RQ, Huang ZG, Zhou XG, Li JJ, Zeng DT, Chen JT, Wu WZ, Dang YW, Chen G. Clinical significance and molecular mechanism of angiotensin-­converting enzyme 2 in hepatocellular carcinoma tissues. Bioengineered. 2021;12(1):4054–4069. doi:10.1080/21655979.2021.1952791</mixed-citation></ref><ref id="B99"><label>99.</label><mixed-citation>Song T, Choi CH, Kim MK, Kim ML, Yun BS, Seong SJ. The effect of angiotensin system inhibitors (angiotensin-­converting enzyme inhibitors or angiotensin receptor blockers) on cancer recurrence and survival: a meta-analysis. European Journal of Cancer Prevention. 2016;26(1):78–85. doi:10.1097/cej.0000000000000269</mixed-citation></ref><ref id="B100"><label>100.</label><mixed-citation>Yu C, Tang W, Wang Y, Shen Q, Wang B, Cai C, Meng X, Zou F. Downregulation of ACE2/Ang-(1–7)/Mas axis promotes breast cancer metastasis by enhancing store-­operated calcium entry. Cancer Letters. 2016;376(2):268–277. doi:10.1016/j.canlet.2016.04.006</mixed-citation></ref><ref id="B101"><label>101.</label><mixed-citation>Errarte P, Beitia M, Perez I, Manterola L, Lawrie CH, Solano-­Iturri JD, Calvete-­Candenas J, Unda M, López JI, Larrinaga G. Expression and activity of angiotensin-­regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients. PLoS ONE. 2017;12(8): e0181711. doi:10.1371/journal.pone.0181711</mixed-citation></ref><ref id="B102"><label>102.</label><mixed-citation>Bernardi S, Zennaro C, Palmisano S, Velkoska E, Sabato N, Toffoli B, Giacomel G, Buri L, Zanconati F, Bellini G, Burrell LM, De Manzini N, Fabris B. Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma. Journal of the Renin-­Angiotensin-­Aldosterone System. 2011;13(1):202–209. doi:10.1177/1470320311426023</mixed-citation></ref><ref id="B103"><label>103.</label><mixed-citation>Sivasakthivel S, Ramani P, Krishnan RP. Systematic Review and Meta-­Analysis on Angiotensin Converting Enzyme 2 in Head and neck region. Cureus. 2023;15(1): e33673. doi:10.7759/cureus.33673</mixed-citation></ref><ref id="B104"><label>104.</label><mixed-citation>Wan H. Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro. Oncology Reports. 2011;26(5):1157–1164. doi:10.3892/or.2011.1394</mixed-citation></ref><ref id="B105"><label>105.</label><mixed-citation>Cheng Q, Zhou L, Zhou J, Wan H, Li Q, Feng Y. ACE2 overexpression inhibits acquired platinum resistance-­induced tumor angiogenesis in NSCLC. Oncology Reports. 2016;36(3):1403–1410. doi:10.3892/or.2016.4967</mixed-citation></ref><ref id="B106"><label>106.</label><mixed-citation>Holappa M, Valjakka J, Vaajanen A. Angiotensin(1–7) and ACE2, “The hot spots” of Renin-­Angiotensin system, detected in the human aqueous humor. The Open Ophthalmology Journal. 2015;9(1):28–32. doi:10.2174/1874364101509010028</mixed-citation></ref><ref id="B107"><label>107.</label><mixed-citation>Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID‑19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. 2020;8(4):420–422. doi:10.1016/s2213-2600(20)30076-x</mixed-citation></ref><ref id="B108"><label>108.</label><mixed-citation>Ma D, Chen CB, Jhanji V, Xu C, Yuan XL, Liang JJ, Huang Y, Cen LP, Ng TK. Expression of SARS-CoV‑2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea. Eye. 2020;34(7):1212–1219. doi:10.1038/s41433–020–0939–4</mixed-citation></ref><ref id="B109"><label>109.</label><mixed-citation>Zhou L, Xu Z, Guerra J, Rosenberg AZ, Fenaroli P, Eberhart CG, Duh EJ. Expression of the SARS-COV‑2 receptor ACE2 in human retina and Diabetes — Implications for Retinopathy. Investigative Ophthalmology &amp; Visual Science. 2021;62(7):6. doi:10.1167/iovs.62.7.6</mixed-citation></ref><ref id="B110"><label>110.</label><mixed-citation>Colin M, Delaitre C, Foulquier S, Dupuis F. The AT1/AT2 Receptor Equilibrium Is a Cornerstone of the Regulation of the Renin Angiotensin System beyond the Cardiovascular System. Molecules. 2023;28(14):5481. doi:10.3390/molecules28145481</mixed-citation></ref><ref id="B111"><label>111.</label><mixed-citation>Foureaux G, Nogueira JC, Nogueira BS, Fulgêncio GO, Menezes GB, Fernandes SOA, Cardoso VN, Fernandes RS, Oliveira GP, Franca JR, Faraco A a. G, Raizada MK, Ferreira AJ. Antiglaucomatous effects of the activation of intrinsic Angiotensin-­Converting enzyme 2. Investigative Ophthalmology &amp; Visual Science. 2013;54(6):4296. doi:10.1167/iovs.12-11427</mixed-citation></ref><ref id="B112"><label>112.</label><mixed-citation>Verma A, Shan Z, Lei B, Yuan L, Liu X, Nakagawa T, Grant MB, Lewin AS, Hauswirth WW, Raizada MK, Li Q. ACE2 and ANG-(1–7) confer protection against development of diabetic retinopathy. Molecular Therapy. 2011;20(1):28–36. doi:10.1038/mt.2011.155</mixed-citation></ref><ref id="B113"><label>113.</label><mixed-citation>Fu X, Lin R, Qiu Y, Yu P, Lei B. Overexpression of Angiotensin-­Converting enzyme 2 ameliorates amyloid Β-Induced inflammatory response in human primary retinal pigment epithelium. Investigative Ophthalmology &amp; Visual Science. 2017;58(7):3018. doi:10.1167/iovs.17-21546</mixed-citation></ref><ref id="B114"><label>114.</label><mixed-citation>Kaplan N, Gonzalez E, Peng H, Batlle D, Lavker RM. Emerging importance of ACE2 in external stratified epithelial tissues. Molecular and Cellular Endocrinology. 2021;529:111260. doi:10.1016/j.mce.2021.111260</mixed-citation></ref><ref id="B115"><label>115.</label><mixed-citation>Hamming I, Timens W, Bulthuis M, Lely A, Navis G, Van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology. 2004;203(2):631–637. doi:10.1002/path.1570</mixed-citation></ref><ref id="B116"><label>116.</label><mixed-citation>Li RJ, Wu CY, Ke HL, Wang XP, Zhang YW. Qing Fei Hua Xian Decoction ameliorates bleomycin-­induced pulmonary fibrosis by suppressing oxidative stress through balancing ACE-AngII-AT1R/ACE2-Ang-(1–7)-Mas axis. Iran J Basic Med Sci. 2023;26(1):107–113. doi:10.22038/IJBMS.2022.67042.14700</mixed-citation></ref><ref id="B117"><label>117.</label><mixed-citation>Liu X, Liu X, Li M, Zhang Y, Chen W, Zhang M, Zhang M, Zhang C, Zhang M, Zhang M. Mechanical stretch induces smooth muscle cell dysfunction by regulating ACE2 via P38/ATF3 and post-transcriptional regulation by MIR‑421. Frontiers in Physiology. 2021;11:540591. doi:10.3389/fphys.2020.540591</mixed-citation></ref><ref id="B118"><label>118.</label><mixed-citation>Csekes E, Račková L. Skin aging, cellular senescence and natural polyphenols. International Journal of Molecular Sciences. 2021;22(23):12641. doi:10.3390/ijms222312641</mixed-citation></ref><ref id="B119"><label>119.</label><mixed-citation>Xue X, Mi Z, Wang Z, Pang Z, Liu H, Zhang F. High expression of ACE2 on keratinocytes reveals skin as a potential target for SARS-COV‑2. Journal of Investigative Dermatology. 2020;141(1):206–209.e1. doi:10.1016/j.jid.2020.05.087</mixed-citation></ref><ref id="B120"><label>120.</label><mixed-citation>Pho DM. ACE2 Receptor in the skin and Cutaneous Manifestations of SARS-Cov‑2: A Review of the Literature. Bioscientia Medicina Journal of Biomedicine and Translational Research. 2020;5(1):204–211. doi:10.32539/bsm.v5i1.209</mixed-citation></ref></ref-list></back></article>
