vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2026-1-164-180vtio-2069Research ArticleТрансплантомикаTransplantomicsЭпигенетика в клинической трансплантологии: диагностическая, предиктивная и терапевтическая значимость молекул микроРНК (систематический обзор)Epigenetics in clinical transplantology: diagnostic, predictive, and therapeutic significance of microRNA molecules (systematic review)https://orcid.org/0000-0001-9295-9136ШарапченкоС. О.SharapchenkoS. О.

Шарапченко Софья Олеговна

123182, Москва, ул. Щукинская, д. 1. Тел. (499) 193-87-62

Sofya Sharapchenko

1, Shchukinskaya str., Moscow, 123182

Phone: (499) 193-87-62

Nyashka1512@yandex.ruhttps://orcid.org/0000-0002-8742-5102ВеликийД. А.VelikiyD. A.

Москва

Moscow

dim_vel@mail.ruhttps://orcid.org/0000-0001-6964-6465ШевченкоО. П.ShevchenkoО. P.

Москва

Moscow

transplant2009@mail.ruФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава РоссииРоссияShumakov National Medical Research Center of Transplantology and Artificial OrgansRussian FederationФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России; ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Минздрава России (Сеченовский университет)РоссияShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityRussian Federation202631032026281164180Copyright © Шарапченко С.О., Великий Д.А., Шевченко О.П., 20262026Шарапченко С.О., Великий Д.А., Шевченко О.П.Sharapchenko S.О., Velikiy D.A., Shevchenko О.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/2069

Эпигенетика – наука, изучающая изменения в экспрессии генов, не связанные с модификациями первичной структуры ДНК. Эти изменения регулируются химическими модификациями ДНК, гистонов и некодирующих РНК, формируя «эпигеном», который определяет функциональную активность генома. Эпигенетические механизмы играют ключевую роль в дифференцировке клеток, развитии организма и адаптации к внешним условиям. В медицине они стали объектом пристального внимания из-за их связи с онкологическими, аутоиммунными и нейродегенеративными заболеваниями. Молекулы микроРНК, будучи элементами эпигенетических механизмов, играют важную роль в регуляции иммунного ответа, в том числе после трансплантации органов, что открывает новые горизонты для персонализированного подхода к ведению пациентов трансплантологического профиля. Совокупность прежде накопленных данных о роли микроРНК при трансплантации солидных органов свидетельствует о возможности расширения существующего арсенала диагностических критериев путем внедрения омиксных технологий в качестве вспомогательного диагностического инструмента для обеспечения эффективного функционирования трансплантированных органов. В настоящем обзоре представлены результаты систематического анализа современной литературы, посвященной клинической значимости молекул микроРНК в современной трансплантологии; показан диагностический и предиктивный потенциал отдельных микроРНК в отношении развития осложнений у реципиентов серд ца, легких, почки, печени; рассмотрены современные подходы к применению микроРНК в качестве мишеней для терапии.

Epigenetics is the study of changes in gene expression that occur without alterations in the primary DNA sequence. These changes are mediated by chemical modifications of DNA, histones, and non-coding RNAs, collectively forming the epigenome, that determines the functional activity of the genome. Epigenetic mechanisms play a fundamental role in cellular differentiation, organismal development, and adaptation to external conditions. In medicine, they have attracted considerable attention due to their involvement in the pathogenesis of oncological, autoimmune, and neurodegenerative diseases. MicroRNAs (miRNAs), as key components of epigenetic mechanisms, play a critical role in controlling immune responses, including those occurring after organ transplantation. This has opened new opportunities for a personalized approach to the management of transplant recipients. Accumulating evidence on the role of miRNAs in solid organ transplantation suggests that integration of omics technologies may expand the existing arsenal of diagnostic criteria, serving as an auxiliary diagnostic tool for monitoring graft function. This systematic review presents a comprehensive analysis of the current literature on the clinical significance of miRNAs in modern transplantology. It highlights the diagnostic and predictive potential of specific miRNAs in relation to the development of complications in recipients of heart, lung, kidney, and liver transplants, and examines current approaches to the use of miRNAs as therapeutic targets.

трансплантация солидных органовмикроРНКдиагностикапрогнозбиомаркерыдисфункцияотторжениефиброзsolid organ transplantationmiRNAsdiagnosisprognosisbiomarkersdysfunctionrejectionfibrosisReferencesCippà PE. New ideas for old problems: how scientific advances can change the future of organ transplantation. Transpl Int. 2019; 32 (6): 561–562. doi: 10.1111/tri.13419.Cippà PE. New ideas for old problems: how scientific advances can change the future of organ transplantation. Transpl Int. 2019; 32 (6): 561–562. doi: 10.1111/tri.13419.Guetta O, Osyntsov A, Rahamimov R, Tobar A, Israeli M, Masarwa Y et al. The Role of Early Sequential Biopsies in Delayed Renal Graft Function of Transplanted Kidney Is Reduced in Modern Immunosuppression Era. Nephron. 2023; 147 (3–4): 127–133. doi: 10.1159/000525912.Guetta O, Osyntsov A, Rahamimov R, Tobar A, Israeli M, Masarwa Y et al. The Role of Early Sequential Biopsies in Delayed Renal Graft Function of Transplanted Kidney Is Reduced in Modern Immunosuppression Era. Nephron. 2023; 147 (3–4): 127–133. doi: 10.1159/000525912.Elisseeff J, Badylak SF, Boeke JD. Immune and Genome Engineering as the Future of Transplantable Tissue. N Engl J Med. 2021; 385 (26): 2451–2462. doi: 10.1056/NEJMra1913421.Elisseeff J, Badylak SF, Boeke JD. Immune and Genome Engineering as the Future of Transplantable Tissue. N Engl J Med. 2021; 385 (26): 2451–2462. doi: 10.1056/NEJMra1913421.Vasco M, Benincasa G, Fiorito C, Faenza M, De Rosa P, Maiello C et al. Clinical epigenetics and acute/chronic rejection in solid organ transplantation: An update. Transplant Rev (Orlando). 2021; 35 (2): 100609. doi: 10.1016/j.trre.2021.100609.Vasco M, Benincasa G, Fiorito C, Faenza M, De Rosa P, Maiello C et al. Clinical epigenetics and acute/chronic rejection in solid organ transplantation: An update. Transplant Rev (Orlando). 2021; 35 (2): 100609. doi: 10.1016/j.trre.2021.100609.Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001; 107 (7): 823–826. doi: 10.1016/s00928674(01)00616-x.Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001; 107 (7): 823–826. doi: 10.1016/s00928674(01)00616-x.Koch PF, Ludwig K, Krenzien F, Hillebrandt KH, Schöning W, Pratschke J et al. miRNA as potential biomarkers after liver transplantation: A systematic review. Transplant Rev (Orlando). 2024; 38 (2): 100831. doi: 10.1016/j.trre.2024.100831.Koch PF, Ludwig K, Krenzien F, Hillebrandt KH, Schöning W, Pratschke J et al. miRNA as potential biomarkers after liver transplantation: A systematic review. Transplant Rev (Orlando). 2024; 38 (2): 100831. doi: 10.1016/j.trre.2024.100831.Douvris A, Viñas JL, Akbari S, Tailor K, Lalu MM, Burger D, Burns KD. Systematic review of microRNAs in human acute kidney injury. Ren Fail. 2024; 46 (2): 2419960. doi: 10.1080/0886022X.2024.2419960.Douvris A, Viñas JL, Akbari S, Tailor K, Lalu MM, Burger D, Burns KD. Systematic review of microRNAs in human acute kidney injury. Ren Fail. 2024; 46 (2): 2419960. doi: 10.1080/0886022X.2024.2419960.Paladini SV, Pinto GH, Bueno RH, Calloni R, Recamonde-Mendoza M. Identification of Candidate Biomarkers for Transplant Rejection from Transcriptome Data: A Systematic Review. Mol Diagn Ther. 2019; 23 (4): 439– 458. doi: 10.1007/s40291-019-00397-y.Paladini SV, Pinto GH, Bueno RH, Calloni R, Recamonde-Mendoza M. Identification of Candidate Biomarkers for Transplant Rejection from Transcriptome Data: A Systematic Review. Mol Diagn Ther. 2019; 23 (4): 439– 458. doi: 10.1007/s40291-019-00397-y.Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012; 41 (1): 10. doi: 10.1093/ije/dyr184.Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012; 41 (1): 10. doi: 10.1093/ije/dyr184.Смирнов ВВ, Леонов ГЕ. Эпигенетика: теоретические аспекты и практическое значение. Лечащий врач. 2016; 12: 26–30.Smirnov VV, Leonov GE. Epigenetics: theoretical aspects and practical value. Lechashchij vrach. 2016; 12: 26–30.Паткин Е.Л., Софронов Г.А. Экологозависимые болезни человека. Эпигенетические механизмы возникновения и наследования. Медицинский академический журнал. 2015; 15 (3): 7–23. doi: 10.17816/MAJ115019.Patkin E.L., Sofronov G.A. Environment-dependent human diseases: the epigenetic mechanisms of their development and inheritance. Medical academic journal. 2015; 15 (3): 7–23. [In Russ, English abstract] doi: 10.17816/MAJ115019.Щуко АГ, Веселов АА, Юрьева ТН, Волкова НВ, Шабанов ГА, Рыбченко АА, Почтаренко ТВ. Эпигенетика и способы ее реализации. Сибирский научный медицинский журнал. 2017; 37 (4): 26–35.Shchuko AG, Veselov AA, Yurieva TN, Volkova NV, Shabanov GA, Rybchenko AA, Pochtarenko TV. Epigenetics and methods of its realization. The siberian scientific medical journal. 2017; 37 (4): 26–35.Wakimoto BT. Beyond the nucleosome: epigenetic aspects of position-effect variegation in Drosophila. Cell. 1998; 93 (3): 321–324. doi: 10.1016/s0092-8674(00)81159-9.Wakimoto BT. Beyond the nucleosome: epigenetic aspects of position-effect variegation in Drosophila. Cell. 1998; 93 (3): 321–324. doi: 10.1016/s0092-8674(00)81159-9.Gluckman PD, Hanson MA, Pinal C. The developmental origins of adult disease. Matern Child Nutr. 2005; 1 (3): 130–141. doi: 10.1111/j.1740-8709.2005.00020.x.Gluckman PD, Hanson MA, Pinal C. The developmental origins of adult disease. Matern Child Nutr. 2005; 1 (3): 130–141. doi: 10.1111/j.1740-8709.2005.00020.x.Tobi EW, Slieker RC, Luijk R, Dekkers KF, Stein AD, Xu KM et al. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood. Sci Adv. 2018; 4 (1): eaao4364. doi: 10.1126/sciadv.aao4364.Tobi EW, Slieker RC, Luijk R, Dekkers KF, Stein AD, Xu KM et al. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood. Sci Adv. 2018; 4 (1): eaao4364. doi: 10.1126/sciadv.aao4364.Mirzabekov AD et al. DNA methylation and gene regulation. Proceedings of the USSR Academy of Sciences. 1978; 241 (3): 732–735.Mirzabekov AD et al. DNA methylation and gene regulation. Proceedings of the USSR Academy of Sciences. 1978; 241 (3): 732–735.Ashapkin VV, Kutueva LI, Vanyushin BF. Aging as an Epigenetic Phenomenon. Curr Genomics. 2017; 18 (5): 385–407. doi: 10.2174/1389202918666170412112130.Ashapkin VV, Kutueva LI, Vanyushin BF. Aging as an Epigenetic Phenomenon. Curr Genomics. 2017; 18 (5): 385–407. doi: 10.2174/1389202918666170412112130.Khlebovich VV. Stress-induced epigenetic changes in plants. Russian Journal of Genetics. 1998; 34 (8): 912– 918.Khlebovich VV. Stress-induced epigenetic changes in plants. Russian Journal of Genetics. 1998; 34 (8): 912– 918.Salina EA et al. Epigenetic engineering of salt-tolerant wheat. Plant Biotechnology Journal. 2020; 18 (2): 210– 225.Salina EA et al. Epigenetic engineering of salt-tolerant wheat. Plant Biotechnology Journal. 2020; 18 (2): 210– 225.Вохмянина НВ. Эпигенетика и мультифакторные болезни. Российский журнал персонализированной медицины. 2023; 3 (6): 42–49. https://doi.org/10.18705/27823806-2023-3-6-42-49.Vokhmyanina NV. Еpigenetics and multifactorial diseases. Russian Journal For Personalized Medicine. 2023; 3 (6): 42–49. [In Russ, English abstract]. https://doi.org/10.18705/27823806-2023-3-6-42-49.Das A. Epigenetics, the Environment, and Children’s Health Across Lifespans. Berlin: Springer. 2016: 353– 359.Das A. Epigenetics, the Environment, and Children’s Health Across Lifespans. Berlin: Springer. 2016: 353– 359.Ашапкин ВВ, Линькова НС, Хавинсон ВХ, Ванюшин БФ. Эпигенетические механизмы пептидергической регуляции экспрессии генов при старении клеток человека. Биохимия. 2015; 80 (3): 374–388.Ashapkin VV, Linkova NS, Khavinson VK, Vanyushin BF. Еpigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells. Biochemistry (Moscow). 2015; 80 (3): 310–322.Skulachev VP. Programmed aging: Mitochondria, oxygen radicals, and epigenetics. Biochemistry. 2005; 70 (3): 247–258.Skulachev VP. Programmed aging: Mitochondria, oxygen radicals, and epigenetics. Biochemistry. 2005; 70 (3): 247–258.Horvath S. DNA methylation age of human tissues and cell types. Genome Biology. 2013; 14 (10): R115.Horvath S. DNA methylation age of human tissues and cell types. Genome Biology. 2013; 14 (10): R115.Dugger DT, Calabrese DR, Gao Y, Deiter F, Tsao T, Maheshwari J et al. Lung Allograft Epithelium DNA Methylation Age Is Associated With Graft Chronologic Age and Primary Graft Dysfunction. Front Immunol. 2021; 12: 704172. doi: 10.3389/fimmu.2021.704172.Dugger DT, Calabrese DR, Gao Y, Deiter F, Tsao T, Maheshwari J et al. Lung Allograft Epithelium DNA Methylation Age Is Associated With Graft Chronologic Age and Primary Graft Dysfunction. Front Immunol. 2021; 12: 704172. doi: 10.3389/fimmu.2021.704172.Flippin MS, Canter CE, Balzer DT. Increased morbidity and high variability of cyclosporine levels in pediatric heart transplant recipients. J Heart Lung Transpl. 2000; 19 (4): 343–349. doi: 10.1016/s1053-2498(00)00061-9.Flippin MS, Canter CE, Balzer DT. Increased morbidity and high variability of cyclosporine levels in pediatric heart transplant recipients. J Heart Lung Transpl. 2000; 19 (4): 343–349. doi: 10.1016/s1053-2498(00)00061-9.Boer K, Hesselink DA, Baan CC. Variations in DNA methylation and allograft rejection. Curr Opin Organ Transplant. 2021; 26 (1): 30–36. doi: 10.1097/MOT.0000000000000833.Boer K, Hesselink DA, Baan CC. Variations in DNA methylation and allograft rejection. Curr Opin Organ Transplant. 2021; 26 (1): 30–36. doi: 10.1097/MOT.0000000000000833.Suárez-Álvarez B, Baragaño Raneros A, Ortega F, López-Larrea C. Epigenetic modulation of the immune function: a potential target for tolerance. Epigenetics. 2013; 8 (7): 694–702. doi: 10.4161/epi.25201.Suárez-Álvarez B, Baragaño Raneros A, Ortega F, López-Larrea C. Epigenetic modulation of the immune function: a potential target for tolerance. Epigenetics. 2013; 8 (7): 694–702. doi: 10.4161/epi.25201.Xiang X, Zhu J, Dong G, Dong Z. Epigenetic Regulation in Kidney Transplantation. Front Immunol. 2022; 13: 861498. doi: 10.3389/fimmu.2022.861498.Xiang X, Zhu J, Dong G, Dong Z. Epigenetic Regulation in Kidney Transplantation. Front Immunol. 2022; 13: 861498. doi: 10.3389/fimmu.2022.861498.McCaughan JA, McKnight AJ, Courtney AE, Maxwell AP. Epigenetics: time to translate into transplantation. Transplantation. 2012; 94 (1): 1–7. doi: 10.1097/TP.0b013e31824db9bd.McCaughan JA, McKnight AJ, Courtney AE, Maxwell AP. Epigenetics: time to translate into transplantation. Transplantation. 2012; 94 (1): 1–7. doi: 10.1097/TP.0b013e31824db9bd.Soler-Botija C, Gálvez-Montón C, BayésGenís A. Epigenetic Biomarkers in Cardiovascular Diseases. Front Genet. 2019; 10: 950. doi: 10.3389/fgene.2019.00950.Soler-Botija C, Gálvez-Montón C, BayésGenís A. Epigenetic Biomarkers in Cardiovascular Diseases. Front Genet. 2019; 10: 950. doi: 10.3389/fgene.2019.00950.Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016; 37 (33): 2602–2611. doi: 10.1093/eurheartj/ehv713.Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016; 37 (33): 2602–2611. doi: 10.1093/eurheartj/ehv713.Van Aelst LN, Summer G, Li S, Gupta SK, Heggermont W, De Vusser K et al. RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection. Am J Transplant. 2016; 16 (1): 99–110. doi: 10.1111/ajt.13421.Van Aelst LN, Summer G, Li S, Gupta SK, Heggermont W, De Vusser K et al. RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection. Am J Transplant. 2016; 16 (1): 99–110. doi: 10.1111/ajt.13421.Vitalone MJ, Sigdel TK, Salomonis N, Sarwal RD, Hsieh SC, Sarwal MM. Transcriptional Perturbations in Graft Rejection. Transplantation. 2015; 99 (9): 1882– 1893. doi: 10.1097/TP.0000000000000809.Vitalone MJ, Sigdel TK, Salomonis N, Sarwal RD, Hsieh SC, Sarwal MM. Transcriptional Perturbations in Graft Rejection. Transplantation. 2015; 99 (9): 1882– 1893. doi: 10.1097/TP.0000000000000809.Duong Van Huyen JP, Tible M, Gay A, Guillemain R, Aubert O, Varnous S et al. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014; 35 (45): 3194–3202. doi: 10.1093/eurheartj/ehu346.Duong Van Huyen JP, Tible M, Gay A, Guillemain R, Aubert O, Varnous S et al. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014; 35 (45): 3194–3202. doi: 10.1093/eurheartj/ehu346.Singh N, Heggermont W, Fieuws S, Vanhaecke J, Van Cleemput J, De Geest B. Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy. J Heart Lung Transplant. 2015; 34 (11): 1376–1384. doi: 10.1016/j.healun.2015.06.008.Singh N, Heggermont W, Fieuws S, Vanhaecke J, Van Cleemput J, De Geest B. Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy. J Heart Lung Transplant. 2015; 34 (11): 1376–1384. doi: 10.1016/j.healun.2015.06.008.Sukma Dewi I, Hollander Z, Lam KK, McManus JW, Tebbutt SJ, Ng RT et al. Association of Serum MiR-1423p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation. PLoS One. 2017; 12 (1): e0170842. doi: 10.1371/journal.pone.0170842.Sukma Dewi I, Hollander Z, Lam KK, McManus JW, Tebbutt SJ, Ng RT et al. Association of Serum MiR-1423p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation. PLoS One. 2017; 12 (1): e0170842. doi: 10.1371/journal.pone.0170842.Neumann A, Napp LC, Kleeberger JA, Benecke N, Pfanne A, Haverich A et al. MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy. Transplantation. 2017; 101 (1): e26–e33. doi: 10.1097/TP.0000000000001477.Neumann A, Napp LC, Kleeberger JA, Benecke N, Pfanne A, Haverich A et al. MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy. Transplantation. 2017; 101 (1): e26–e33. doi: 10.1097/TP.0000000000001477.Великий ДА, Гичкун ОЕ, Шарапченко СО, Можейко НП, Курабекова РМ, Шевченко ОП. Диагностическое значение микроРНК-101 и микроРНК-27 при остром отторжении трансплантированного сердца. Вестник трансплантологии и искусственных органов. 2020; 22 (4): 20–26. doi: 10.15825/1995-1191-2020-4-20-26.Velikiy DA, Gichkun OE, Sharapchenko SO, Mozheiko NP, Kurabekova RM, Shevchenko OP. Diagnostic value of miRNA-101 and miRNA-27 in acute heart transplant rejection. Russian Journal of Transplantology and Artificial Organs. 2020; 22 (4): 20–26. [In Russ, English abstract]. doi: 10.15825/1995-1191-2020-4-20-26.Шевченко ОП, Великий ДА, Шарапченко СО, Гичкун ОЕ, Марченко АВ, Улыбышева АА и др. МикроРНК-27 и -339 при фиброзе миокарда трансплантированного серд ца: анализ диагностической значимости. Вестник трансплантологии и искусственных органов. 2021; 23 (3): 73–81. doi: 10.15825/1995-1191-20213-73-81.Shevchenko OP, Velikiy DA, Sharapchenko SO, Gichkun OE, Marchenko AV, Ulybysheva AA et al. Diagnostic value of microRNA-27 and -339 in heart transplant recipients with myocardial fibrosis. Russian Journal of Transplantology and Artificial Organs. 2021; 23 (3): 73–81. [In Russ, English abstract]. doi: 10.15825/1995-1191-20213-73-81.Pérez-Carrillo L, Sánchez-Lázaro I, Triviño JC, Feijóo-Bandín S, Lago F, González-Juanatey JR et al. Diagnostic value of serum miR-144-3p for the detection of acute cellular rejection in heart transplant patients. J Heart Lung Transplant. 2022; 41 (2): 137–147. doi: 10.1016/j.healun.2021.10.004.Pérez-Carrillo L, Sánchez-Lázaro I, Triviño JC, Feijóo-Bandín S, Lago F, González-Juanatey JR et al. Diagnostic value of serum miR-144-3p for the detection of acute cellular rejection in heart transplant patients. J Heart Lung Transplant. 2022; 41 (2): 137–147. doi: 10.1016/j.healun.2021.10.004.Shevchenko O, Tsirulnikova O, Sharapchenko S, Gichkun O, Velikiy D, Gabrielyan N et al. Upregulated circulating miR-424 and its’ diagnostic value for gram-negative bacteremia after thoracic transplantation. Noncoding RNA Res. 2022; 7 (4): 217–225. doi: 10.1016/j.ncrna.2022.08.001.Shevchenko O, Tsirulnikova O, Sharapchenko S, Gichkun O, Velikiy D, Gabrielyan N et al. Upregulated circulating miR-424 and its’ diagnostic value for gram-negative bacteremia after thoracic transplantation. Noncoding RNA Res. 2022; 7 (4): 217–225. doi: 10.1016/j.ncrna.2022.08.001.Способ дооперационного прогнозирования острого клеточного отторжения трансплантированного сердц а. Шевченко О.П., Великий Д.А., Шарапченко С.О., Гичкун О.Е., Можейко Н.П., Колоскова Н.Н., Шевченко А.О., Готье С.В. Патент на изобретение RU 2798948 C1, 29.06.2023. Method for preoperative prediction of acute cellular rejection of a transplanted heart. Shevchenko O.P., Velikij D.A., Sharapchenko S.O., Gichkun O.E., Mozhejko N.P., Koloskova N.N., Shevchenko A.O., Gote S.V. Patent for invention RU 2798948 C1, 29.06.2023.Method for preoperative prediction of acute cellular rejection of a transplanted heart. Shevchenko O.P., Velikij D.A., Sharapchenko S.O., Gichkun O.E., Mozhejko N.P., Koloskova N.N., Shevchenko A.O., Gote S.V. Patent for invention RU 2798948 C1, 29.06.2023.Bansal S, Itabashi Y, Guerrero-Alba A, Fleming T, Smith MA, Bremner RM, Mohanakumar T. Regulation of cardiac allograft immune responses by microRNA-155. Transpl Immunol. 2024; 87: 102113. doi: 10.1016/j.trim.2024.102113.Bansal S, Itabashi Y, Guerrero-Alba A, Fleming T, Smith MA, Bremner RM, Mohanakumar T. Regulation of cardiac allograft immune responses by microRNA-155. Transpl Immunol. 2024; 87: 102113. doi: 10.1016/j.trim.2024.102113.Gharib SA, Edelman JD, Ge L, Chen P. Acute cellular rejection elicits distinct microRNA signatures in airway epithelium of lung transplant patients. Transplant Direct. 2015; 1 (10): e44. doi: 10.1097/TXD.0000000000000551.Gharib SA, Edelman JD, Ge L, Chen P. Acute cellular rejection elicits distinct microRNA signatures in airway epithelium of lung transplant patients. Transplant Direct. 2015; 1 (10): e44. doi: 10.1097/TXD.0000000000000551.Zhu L, Xu H, Lv W, He Z, Ye P, Wang Y, Hu J. miR-199b5p Regulates Immune-Mediated Allograft Rejection after Lung Transplantation Through the GSK3β and NFκB Pathways. Inflammation. 2018; 41 (4): 1524–1535. doi: 10.1007/s10753-018-0799-2.Zhu L, Xu H, Lv W, He Z, Ye P, Wang Y, Hu J. miR-199b5p Regulates Immune-Mediated Allograft Rejection after Lung Transplantation Through the GSK3β and NFκB Pathways. Inflammation. 2018; 41 (4): 1524–1535. doi: 10.1007/s10753-018-0799-2.Dong M, Wang X, Guan Y, Li T. MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis. Cell Stress Chaperones. 2019; 24 (5): 883–889. doi: 10.1007/s12192-019-01026-7.Dong M, Wang X, Guan Y, Li T. MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis. Cell Stress Chaperones. 2019; 24 (5): 883–889. doi: 10.1007/s12192-019-01026-7.Palleschi A, Gaudioso G, Edefonti V, Musso V, Terrasi A, Ambrogi F et al. Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome After Lung Transplantation. Transplant Direct. 2020; 6 (5): e547. doi: 10.1097/TXD.0000000000000994.Palleschi A, Gaudioso G, Edefonti V, Musso V, Terrasi A, Ambrogi F et al. Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome After Lung Transplantation. Transplant Direct. 2020; 6 (5): e547. doi: 10.1097/TXD.0000000000000994.Shevchenko O, Tsirulnikova O, Sharapchenko S, Pashkov I, Bekov M, Shigaev E et al. MiR-339 and galectin-3: diagnostic value in patients with airway obstruction after lung transplantation. Transpl Int. 2021; 34 (9): 1733–1739. doi: 10.1111/tri.13986.Shevchenko O, Tsirulnikova O, Sharapchenko S, Pashkov I, Bekov M, Shigaev E et al. MiR-339 and galectin-3: diagnostic value in patients with airway obstruction after lung transplantation. Transpl Int. 2021; 34 (9): 1733–1739. doi: 10.1111/tri.13986.Dong M, Wang X, Li T, Jing Y, Liu Y, Zhao H. МiR-27a3p alleviates lung transplantation-induced bronchiolitis obliterans syndrome (BOS) via suppressing Smad-mediated myofibroblast differentiation and TLR4-induced dendritic cells maturation. Transpl Immunol. 2023; 78: 101806. doi: 10.1016/j.trim.2023.101806.Dong M, Wang X, Li T, Jing Y, Liu Y, Zhao H. МiR-27a3p alleviates lung transplantation-induced bronchiolitis obliterans syndrome (BOS) via suppressing Smad-mediated myofibroblast differentiation and TLR4-induced dendritic cells maturation. Transpl Immunol. 2023; 78: 101806. doi: 10.1016/j.trim.2023.101806.Yang J, Yin X, Zhang T. miR-124-3p derived from plasma exosomes enhances M2 macrophage polarization to treat acute lung injury. J Immunol. 2025; 214 (9): 2281–2297. doi: 10.1093/jimmun/vkaf097.Yang J, Yin X, Zhang T. miR-124-3p derived from plasma exosomes enhances M2 macrophage polarization to treat acute lung injury. J Immunol. 2025; 214 (9): 2281–2297. doi: 10.1093/jimmun/vkaf097.Danger R, Paul C, Giral M, Lavault A, Foucher Y, Degauque N et al. Expression of miR-142-5p in peripheral blood mononuclear cells from renal transplant patients with chronic antibody-mediated rejection. PLoS One. 2013; 8 (4): e60702. doi: 10.1371/journal.pone.0060702.Danger R, Paul C, Giral M, Lavault A, Foucher Y, Degauque N et al. Expression of miR-142-5p in peripheral blood mononuclear cells from renal transplant patients with chronic antibody-mediated rejection. PLoS One. 2013; 8 (4): e60702. doi: 10.1371/journal.pone.0060702.Sui W, Yang M, Li F, Chen H, Chen J, Ou M et al. Serum microRNAs as new diagnostic biomarkers for pre- and post-kidney transplantation. Transplant Proc. 2014; 46 (10): 3358–3362. doi: 10.1016/j.transproceed.2014.08.050.Sui W, Yang M, Li F, Chen H, Chen J, Ou M et al. Serum microRNAs as new diagnostic biomarkers for pre- and post-kidney transplantation. Transplant Proc. 2014; 46 (10): 3358–3362. doi: 10.1016/j.transproceed.2014.08.050.Zununi Vahed S, Poursadegh Zonouzi A, Mahmoodpoor F, Samadi N, Ardalan M, Omidi Y. Circulating miR-150, miR-192, miR-200b, and miR-423-3p as Noninvasive Biomarkers of Chronic Allograft Dysfunction. Arch Med Res. 2017; 48 (1): 96–104. doi: 10.1016/j.arcmed.2017.03.004.Zununi Vahed S, Poursadegh Zonouzi A, Mahmoodpoor F, Samadi N, Ardalan M, Omidi Y. Circulating miR-150, miR-192, miR-200b, and miR-423-3p as Noninvasive Biomarkers of Chronic Allograft Dysfunction. Arch Med Res. 2017; 48 (1): 96–104. doi: 10.1016/j.arcmed.2017.03.004.Cabral A, da Silva Cândido D, Monteiro SM, Lemos F, Saitovitch D, Noronha IL et al. Differential microRNA Profile in Operational Tolerance: A Potential Role in Favoring Cell Survival. Front Immunol. 2019; 10: 740. doi: 10.3389/fimmu.2019.00740.Cabral A, da Silva Cândido D, Monteiro SM, Lemos F, Saitovitch D, Noronha IL et al. Differential microRNA Profile in Operational Tolerance: A Potential Role in Favoring Cell Survival. Front Immunol. 2019; 10: 740. doi: 10.3389/fimmu.2019.00740.De Necochea Campion R, Pesqueira M, Vallejos P, McCullough C, Bloesch A, LaRosa SP. A lectin affinity plasmapheresis device removes extracellular vesicles and microRNAs from renal perfusates following controlled oxygenated rewarming of discarded donor kidneys. Transpl Immunol. 2025; 90: 102215. doi: 10.1016/j.trim.2025.102215.De Necochea Campion R, Pesqueira M, Vallejos P, McCullough C, Bloesch A, LaRosa SP. A lectin affinity plasmapheresis device removes extracellular vesicles and microRNAs from renal perfusates following controlled oxygenated rewarming of discarded donor kidneys. Transpl Immunol. 2025; 90: 102215. doi: 10.1016/j.trim.2025.102215.Wei L, Gong X, Martinez OM, Krams SM. Differential expression and functions of microRNAs in liver transplantation and potential use as non-invasive biomarkers. Transpl Immunol. 2013; 29 (1–4): 123–129. doi: 10.1016/j.trim.2013.08.005.Wei L, Gong X, Martinez OM, Krams SM. Differential expression and functions of microRNAs in liver transplantation and potential use as non-invasive biomarkers. Transpl Immunol. 2013; 29 (1–4): 123–129. doi: 10.1016/j.trim.2013.08.005.Ruiz P, Millán O, Ríos J, Díaz A, Sastre L, Colmenero J et al. MicroRNAs 155-5p, 122-5p, and 181a-5p Identify Patients With Graft Dysfunction Due to T Cell-Mediated Rejection After Liver Transplantation. Liver Transpl. 2020; 26 (10): 1275–1286. doi: 10.1002/lt.25842.Ruiz P, Millán O, Ríos J, Díaz A, Sastre L, Colmenero J et al. MicroRNAs 155-5p, 122-5p, and 181a-5p Identify Patients With Graft Dysfunction Due to T Cell-Mediated Rejection After Liver Transplantation. Liver Transpl. 2020; 26 (10): 1275–1286. doi: 10.1002/lt.25842.Julian J, Millán O, Titos E, Ruiz P, Fundora Y, Díaz A et al. Donor-derived cell-free DNA and miRNA monitoring for the early prediction and diagnosis of liver allograft rejection and patient outcomes. Front Immunol. 2025; 16: 1604200. doi: 10.3389/fimmu.2025.1604200.Julian J, Millán O, Titos E, Ruiz P, Fundora Y, Díaz A et al. Donor-derived cell-free DNA and miRNA monitoring for the early prediction and diagnosis of liver allograft rejection and patient outcomes. Front Immunol. 2025; 16: 1604200. doi: 10.3389/fimmu.2025.1604200.Anam M, Watkins C, Rucker G, Marlow K, Khalil M, Dogan M et al. Comparative Landscape of Small RNAs in Tissue and Liquid Biopsies for Liver Transplant Outcomes. bioRxiv [Preprint]. 2025 Sep 18:2025.09.16.676609. doi: 10.1101/2025.09.16.676609.Anam M, Watkins C, Rucker G, Marlow K, Khalil M, Dogan M et al. Comparative Landscape of Small RNAs in Tissue and Liquid Biopsies for Liver Transplant Outcomes. bioRxiv [Preprint]. 2025 Sep 18:2025.09.16.676609. doi: 10.1101/2025.09.16.676609.Zhou M, Hara H, Dai Y, Mou L, Cooper DK, Wu C, Cai Z. Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation. Int J Mol Sci. 2016; 17 (8): 1232. doi: 10.3390/ijms17081232.Zhou M, Hara H, Dai Y, Mou L, Cooper DK, Wu C, Cai Z. Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation. Int J Mol Sci. 2016; 17 (8): 1232. doi: 10.3390/ijms17081232.Harris A, Krams SM, Martinez OM. MicroRNAs as immune regulators: implications for transplantation. Am J Transplant. 2010; 10 (4): 713–719. doi: 10.1111/j.16006143.2010.03032.x.Harris A, Krams SM, Martinez OM. MicroRNAs as immune regulators: implications for transplantation. Am J Transplant. 2010; 10 (4): 713–719. doi: 10.1111/j.16006143.2010.03032.x.Mas VR, Dumur CI, Scian MJ, Gehrau RC, Maluf DG. MicroRNAs as biomarkers in solid organ transplantation. Am J Transplant. 2013; 13 (1): 11–19. doi: 10.1111/j.1600-6143.2012.04313.x.Mas VR, Dumur CI, Scian MJ, Gehrau RC, Maluf DG. MicroRNAs as biomarkers in solid organ transplantation. Am J Transplant. 2013; 13 (1): 11–19. doi: 10.1111/j.1600-6143.2012.04313.x.Amrouche L, Rabant M, Anglicheau D. MicroRNAs as biomarkers of graft outcome. Transplant Rev (Orlando). 2014; 28 (3): 111–118. doi: 10.1016/j.trre.2014.03.003.Amrouche L, Rabant M, Anglicheau D. MicroRNAs as biomarkers of graft outcome. Transplant Rev (Orlando). 2014; 28 (3): 111–118. doi: 10.1016/j.trre.2014.03.003.Hamdorf M, Kawakita S, Everly M. The Potential of MicroRNAs as Novel Biomarkers for Transplant Rejection. J Immunol Res. 2017; 2017: 4072364. doi: 10.1155/2017/4072364.Hamdorf M, Kawakita S, Everly M. The Potential of MicroRNAs as Novel Biomarkers for Transplant Rejection. J Immunol Res. 2017; 2017: 4072364. doi: 10.1155/2017/4072364.Великий ДА, Гичкун ОЕ, Шевченко ОП. МикроРНК у реципиентов сердечного трансплантата. Вестник трансплантологии и искусственных органов. 2017; 19 (2): 126–132. doi: 10.15825/1995-1191-20172-126-132.Velikiy DA, Gichkun OE, Shevchenko OP. МicroRNAs in heart transplant reсipients. Russian Journal of Transplantology and Artificial Organs. 2017; 19 (2): 126–132. doi: 10.15825/1995-1191-20172-126-132.Великий ДА, Шарапченко СО, Шевченко АО, Шевченко ОП. Молекулярная диагностика отторжения трансплантата у реципиентов серд ца: векторы развития и перспективы клинического применения. Вестник трансплантологии и искусственных органов. 2025; 27 (2): 171–178. doi: 10.15825/1995-1191-2025-2-171-178.Velikiy DA, Sharapchenko SO, Shevchenko AO, Shevchenko OP. Molecular diagnostics of cardiac allograft rejection: development pathways and future clinical prospects. Russian Journal of Transplantology and Artificial Organs. 2025; 27 (2): 171–178. doi: 10.15825/1995-1191-2025-2-171-178.Шевченко ОП, Шарапченко СО, Цирульникова ОМ, Пашков ИВ, Гичкун ОЕ, Великий ДА и др. Экспрессия микроРНК у реципиентов легких: корреляции с клиническими и лабораторными данными. Вестник трансплантологии и искусственных органов. 2020; 22 (2): 86–96. doi: 10.15825/1995-1191-2020-2-86-96.Shevchenko OP, Sharapchenko SO, Tsirulnikova OM, Pashkov IV, Gichkun OE, Velikiy DA et al. MicroRNA expression levels in lung recipients: correlations with clinical and laboratory data. Russian Journal of Transplantology and Artificial Organs. 2020; 22 (2): 86–96. doi: 10.15825/1995-1191-2020-2-86-96.Abdelaal AM, Sohal IS, Iyer S, Sudarshan K, Kothandaraman H, Lanman NA et al. A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy. Oncogene. 2023; 42: 2985– 2999. doi: 10.1038/s41388-023-02801-8.Abdelaal AM, Sohal IS, Iyer S, Sudarshan K, Kothandaraman H, Lanman NA et al. A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy. Oncogene. 2023; 42: 2985– 2999. doi: 10.1038/s41388-023-02801-8.Ryu Y, Kim EH, Jang H, Kim Y, Park B, Choi J et al. Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer. Small. 2025; 21 (36): e04468. doi: 10.1002/smll.202504468.Ryu Y, Kim EH, Jang H, Kim Y, Park B, Choi J et al. Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer. Small. 2025; 21 (36): e04468. doi: 10.1002/smll.202504468.Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011; 19 (6): 1116– 1122. doi: 10.1038/mt.2011.48.Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011; 19 (6): 1116– 1122. doi: 10.1038/mt.2011.48.Zhao JL, Huang F, He F, Gao CC, Liang SQ, Ma PF et al. Forced Activation of Notch in Macrophages Represses Tumor Growth by Upregulating miR-125a and Disabling Tumor-Associated Macrophages. Cancer Res. 2016; 76 (6): 1403–1415. doi: 10.1158/0008-5472.CAN-15-2019.Zhao JL, Huang F, He F, Gao CC, Liang SQ, Ma PF et al. Forced Activation of Notch in Macrophages Represses Tumor Growth by Upregulating miR-125a and Disabling Tumor-Associated Macrophages. Cancer Res. 2016; 76 (6): 1403–1415. doi: 10.1158/0008-5472.CAN-15-2019.Ramchandani D, Lee SK, Yomtoubian S, Han MS, Tung CH, Mittal V. Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis. Mol Cancer Ther. 2019; 18 (3): 579–591. doi: 10.1158/1535-7163. MCT-18-0702.Ramchandani D, Lee SK, Yomtoubian S, Han MS, Tung CH, Mittal V. Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis. Mol Cancer Ther. 2019; 18 (3): 579–591. doi: 10.1158/1535-7163. MCT-18-0702.Chioccioli M, Roy S, Newell R, Pestano L, Dickinson B, Rigby K et al. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. EBioMedicine. 2022; 85: 104304. doi: 10.1016/j.ebiom.2022.104304.Chioccioli M, Roy S, Newell R, Pestano L, Dickinson B, Rigby K et al. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. EBioMedicine. 2022; 85: 104304. doi: 10.1016/j.ebiom.2022.104304.Montgomery RL, Yu G, Latimer PA, Stack C, Robinson K, Dalby CM et al. MicroRNA mimicry blocks pulmonary fibrosis. EMBO Mol Med. 2014; 6 (10): 1347–1356. doi: 10.15252/emmm.201303604.Montgomery RL, Yu G, Latimer PA, Stack C, Robinson K, Dalby CM et al. MicroRNA mimicry blocks pulmonary fibrosis. EMBO Mol Med. 2014; 6 (10): 1347–1356. doi: 10.15252/emmm.201303604.Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011; 124 (14): 1537– 1547. doi: 10.1161/CIRCULATIONAHA.111.030932.Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011; 124 (14): 1537– 1547. doi: 10.1161/CIRCULATIONAHA.111.030932.Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456: 980–984. https://doi.org/10.1038/nature07511.Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456: 980–984. https://doi.org/10.1038/nature07511.Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368 (18): 1685–1694. doi: 10.1056/NEJMoa1209026.Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368 (18): 1685–1694. doi: 10.1056/NEJMoa1209026.Drury RE, O’Connor D, Pollard AJ. The Clinical Application of MicroRNAs in Infectious Disease. Front Immunol. 2017; 8: 1182. doi: 10.3389/fimmu.2017.01182.Drury RE, O’Connor D, Pollard AJ. The Clinical Application of MicroRNAs in Infectious Disease. Front Immunol. 2017; 8: 1182. doi: 10.3389/fimmu.2017.01182.Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V. How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC. 2019; 30 (2): 114–127. PMID: 31263388.Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V. How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC. 2019; 30 (2): 114–127. PMID: 31263388.Seto AG, Beatty X, Lynch JM, Hermreck M, Tetzlaff M, Duvic M, Jackson AL. Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma. Br J Haematol. 2018; 183 (3): 428–444. doi: 10.1111/bjh.15547.Seto AG, Beatty X, Lynch JM, Hermreck M, Tetzlaff M, Duvic M, Jackson AL. Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma. Br J Haematol. 2018; 183 (3): 428–444. doi: 10.1111/bjh.15547.Padda IS, Mahtani AU, Patel P, Parmar M. Small Interfering RNA (siRNA) Therapy. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. 2024 Mar 20. PMID: 35593797.Padda IS, Mahtani AU, Patel P, Parmar M. Small Interfering RNA (siRNA) Therapy. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. 2024 Mar 20. PMID: 35593797.Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J et al. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol. 2017; 17 (1): 181. doi: 10.1186/s12883017-0948-5.Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J et al. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol. 2017; 17 (1): 181. doi: 10.1186/s12883017-0948-5.Воевода МИ, Гуревич ВС, Ежов МВ, Сергиенко ИВ. Инклисиран – новая эра в гиполипидемической терапии. Кардиология. 2022; 62 (6): 57–62. doi: 10.18087/cardio.2022.6.n2115.Voevoda MI, Gurevich VS, Ezhov MV, Sergienko IV. Inclisiran – a new era in lipid-lowering therapy. Kardiologiia. 2022; 62 (6): 57–62. doi: 10.18087/cardio.2022.6.n2115.Способ ингибирования метастазирования опухолей путем подавления дедифференцировки опухолевых клеток. Невская К.В., Першина А.Г., Кжышковска Ю.Г., Хмелевская Е.С., Ефимова Л.В., Ибрагимова М.К., Долгашева Д.С., Цыденова И.А., Уфандеев А.А., Буйко Е.Е., Перина Е.А., Гаптулбарова К.А., Кравцова Е.А., Кривощеков С.В., Иванов В.В., Гурьев А.М., Федорова О.С., Удут Е.В., Литвяков Н.В. Патент на изобретение RU 2840966 C1, 30.05.2025. Заявка № 2023133361 от 15.12.2023.Nevskaia K.V., Pershina A.G., Kzhyshkovska Iu.G., Khmelevskaia E.S., Efimova L.V., Ibragimova M.K., Dolgasheva D.S., Tsydenova I.A., Ufandeev A.A., Buiko E.E., Perina E.A., Gaptulbarova K.A., Kravtsova E.A., Krivoshchekov S.V., Ivanov V.V., Gurev A.M., Fedorova O.S., Udut E.V., Litviakov N.V. Method for inhibiting tumour metastasis by suppressing dedifferentiation of tumour cells. Patent for invention RU 2840966 C1, 30.05.2025. Application No. 2023133361 dated December 15, 2023.Silverman EK, Schmidt HHHW, Anastasiadou E, Altucci L, Angelini M, Badimon L et al. Molecular networks in Network Medicine: development and applications. Wiley Interdiscip Rev Syst Biol Med. 2020 Nov; 12 (6): e1489. doi: 10.1002/wsbm.1489.Silverman EK, Schmidt HHHW, Anastasiadou E, Altucci L, Angelini M, Badimon L et al. Molecular networks in Network Medicine: development and applications. Wiley Interdiscip Rev Syst Biol Med. 2020 Nov; 12 (6): e1489. doi: 10.1002/wsbm.1489.Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S et al. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010; 29: 914–956. doi: 10.1016/j.healun.2010.05.034.Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S et al. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010; 29: 914–956. doi: 10.1016/j.healun.2010.05.034.Benincasa G, Viglietti M, Coscioni E, Napoli C. «Transplantomics» for predicting allograft rejection: real-life applications and new strategies from Network Medicine. Hum Immunol. 2023; 84 (2): 89–97. doi: 10.1016/j.humimm.2022.11.00460.Benincasa G, Viglietti M, Coscioni E, Napoli C. «Transplantomics» for predicting allograft rejection: real-life applications and new strategies from Network Medicine. Hum Immunol. 2023; 84 (2): 89–97. doi: 10.1016/j.humimm.2022.11.00460.Alam A, Van Zyl J, Paul Milligan G, Michelle McKean S, Patel R, Anne Hall S. Evolving the surveillance and workup of heart transplant rejection: A real-world analysis of the molecular microscope diagnostic system. Am J Transplant. 2022; 22: 2443–2450. doi: 10.1111/ajt.17087.Alam A, Van Zyl J, Paul Milligan G, Michelle McKean S, Patel R, Anne Hall S. Evolving the surveillance and workup of heart transplant rejection: A real-world analysis of the molecular microscope diagnostic system. Am J Transplant. 2022; 22: 2443–2450. doi: 10.1111/ajt.17087.Benincasa G, Mansueto G, Napoli C. Fluid-based assays and precision medicine of cardiovascular diseases: the ‘hope’ for Pandora’s box? J Clin Pathol. 2019; 72: 785– 799. 10.1136/jclinpath-2019-206178.Benincasa G, Mansueto G, Napoli C. Fluid-based assays and precision medicine of cardiovascular diseases: the ‘hope’ for Pandora’s box? J Clin Pathol. 2019; 72: 785– 799. 10.1136/jclinpath-2019-206178.Picascia A, Grimaldi V, Pignalosa O, De Pascale MR, Schiano C, Napoli C. Epigenetic control of autoimmune diseases: from bench to bedside. Clin Immunol. 2015; 157: 1–15. 10.1016/j.clim.2014.12.013.Picascia A, Grimaldi V, Pignalosa O, De Pascale MR, Schiano C, Napoli C. Epigenetic control of autoimmune diseases: from bench to bedside. Clin Immunol. 2015; 157: 1–15. 10.1016/j.clim.2014.12.013.

The authors declare that there are no conflicts of interest present.