Irkutsk Scientific Center SB RAS (otdel mediko-biologicheskih issledovaniy i tehnologiy, zaveduyuschiy)
Irkutsk, Irkutsk region, Russian Federation
The results of basic and translational research of the Department of Biomedical Research and Technology of Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences in 2012–2016 The paper presents the results of interdisciplinary research carried out in 2012–2016. The review includes the study of molecular mechanisms of pathogenesis of reparative regeneration, experimental substantiation of methods of diagnosis and prognosis of systemic disturbances of regeneration process, carrying out clinical trials of medicinal products and the formation of observational studies in the field of personalized medicine, the preparation of practical recommendations on the testing of previously developed surgical methods of prevention or correction of postoperative recovery disorders. New data are obtained on the role of the MAP-kinase cascade in the process of regeneration of muscle tissue. It has been established, that with a significant increase of VEGF concentration at the site of the repair of ischemic myocardium, progenitor cells with the CD34+CD45+ phenotype appear, which opens up prospects for the development of biotechnology to restore the damaged myocardium with its own pool of progenitor cells. The new data on the role of growth factors in the post-infarction remodeling are found. It has been revealed, that in local increase of selenium concentration low intensity of mineralization of forming callus in the area of the damage is observed and the formation of bone regeneration slows down. Prospects for the use of nanocomposites of elemental selenium for modulation of reparative response are marked. The dynamics of the level of free circulating mitochondrial DNA (mtDNA) of blood in the early stages of experimental dyslipidemia has been studied. Atherogenic blood factors do not have a significant effect on the release of the mtDNA from dyslipidemia target cells. On the model of acute small-focal myocardial ischemia, we revealed the increase in the mtDNA levels. Prospects of broadcast of diagnostic mtDNA monitoring technology in myocardial ischemia have been marked. The mtDNA monitoring was first tested as a molecular risk pattern in acute coronary syndrome. In survived patients, the concentration of freely circulating mtDNA in blood plasma was 164 times lower. The probability of death of the patient with a high level of mtDNA (over 4000 copies/mL) was 50 % (logit analysis). Methodological level of translational research in the ISC SB RAS has increased due to effective participation in international multi-center clinical trials of drugs, mainly direct anticoagulants: fondaparinux, edoksabana, betriksabana. “Feedback broadcast” of the results of clinical trials of p38-kinase inhibitor, was carried out in the process of changing the model (initially – neuropathic pain) for coronary atherosclerosis. Technologies of pharmacogenetic testing and personalized treatment of diseases in the employees of the Irkutsk Scientific Center were applied. Step T2. Previously developed at the Irkutsk State Medical University and the Irkutsk Scientific Center of Surgery and Traumatologies approaches to surgical prevention and medicinal correction of postoperative hyposplenism were translated into practical health care. Thus, these results obtained in different areas of translational medicine will determine scientific topics of the department in future research cycle.
translational medicine, reparative regeneration, the MAP kinase cascade, VEGF, myocardial remodeling, free circulating mitochondrial DNA, acute coronary syndrome, clinical trials, observational studies, reverse translation, T2-translation, personalized therapy, interventional epidemiolog y, post operative h yposplenism
Направление междисциплинарных исследований в форме трансляционной медицины, выбранных в качестве ведущих для работы ОМБИТ ИНЦ СО РАН, предусматривает широкий круг вопросов – от оценки перспективности клинического применения прекурсоров лекарственных средств с заданными свойствами, синтезированными в Иркутском институте химии им. А.Е. Фаворского (направление разработки лекарственных средств), фундаметальной разработки молекулярных механизмов патогенеза нарушений репаративной регенерации (блок 1 исследований, выполненный г.н.с. докторами мед. наук М.Г. Шурыгиным и И.А. Шурыгиной), экспериментального обоснования способов диагностики/прогнозирования системных нарушений процессов регенерации (блок 2 исследований, выполненный г.н.с. докт. биолог. наук С.А. Л епеховой и с.н.с. канд. мед. наук Н.П. Судаковым) до проведения клинических испытаний лекарственных средств и формирования наблюдательных исследований с применением технологии персонализированной медицины, подготовки практических рекомендаций по апробации разработанных ранее методов хирургической профилактики или коррекции послеоперационных нарушений регенерации (блок 3 исследований, выполненный г.н.с. докт. мед. наук, профессором Г.И. Л ифшиц и с.н.с. канд. мед. наук
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67. Büller H.R., Décousus H., Grosso M.A., Mercuri M. et al. Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism // N. Engl. J. Med. - 2013. - Vol. 369 (15). - P. 1406-1415. doi:https://doi.org/10.1056/NEJMoa1306638.
68. Samama C.M., Lecoules N., Kierzek G., Claessens Y.E. et al. Groupe FONDACAST Étude comparant le fondaparinux à une héparine de bas poids moléculaire dans la prévention de la maladie thromboembolique veineuse en cas d’immobilisation rigide ou semi-rigide après traumatisme isolé non chirurgical du membre inférieur au-dessous du genou // Ann. Fr. Med. Urgence. - 2014. - Vol. 4. - P. 153-166. doihttps://doi.org/10.1007/s13341-014-0405-z.
69. Vybivanceva A.V., Aparcin K.A. Ocenka venoznogo tromboembolizma i gemorragicheskih oslozhneniy v otdalennom periode posle ortopedicheskih vmeshatel'stv // Nauka v sovremennom informacionnom obschestve: Mater. mezhdunar. nauch.-prakt. konf. (North Charleston, USA, 28-29 avgusta 2014 g.). - S. 45-48.
70. Aparcin K.A., Gorohova A.V., Demkova O.V. Klinicheskie issledovaniya v INCHT: itogi i perspektivy // Byulleten' VSNC SO RAMN. - 2016. - № 4 (110). - S. 129-134.
71. Mihaylenko V.L., Kizhnyaev V.N., Verhoturova S.I., Aparcin K.A. i dr. Sintez i svoystva novogo semeystva fosfor-azotsoderzhaschih ionenov // Doklady akademii nauk. - 2015. - T. 465, № 4. - S. 446-450.
72. M i k h a i l e n k o V. L . , K i z h n y a e v V. N . , Verkhoturova S.I., Apartsin K.A. i dr. Synthesis and Properties of a New Family of Phosphorus and Nitrogen Containing Ionenes // Doklady Akademii Nauk, 2015. - Vol. 465, N 4. - P. 446-450. doi:https://doi.org/10.1134/S0012500815120034.
73. Verkhoturova S.I., Gusarova N.K., Trofimov B.A., Mikhailenko V.L. et al. Synthesis and properties of a new family of phosphorus and nitrogen containing ionenes // Doklady Chemistry. - 2015. - Vol. 465, N 2. - P. 286-290. doi:https://doi.org/10.1134/S0012500815120034.
74. Kireeva V.V., Aparcin K.A. Farmakogeneticheskoe testirovanie kak metod issledovaniya translyacionnoy mediciny // Farmakogeneticheskoe testirovanie i personalizirovannaya terapiya: Mater. mezhdunar. nauch.-prakt. konf. «Nauka v sovremennom informacionnom obschestve» (Moskva, 3-4 aprelya 2013 g.). - M., 2013. - T. 2. - S. 80-82.
75. Lifshic G.I., Aparcin K.A., Zelenskaya E.M., Vybivanceva A.V. Personalizirovannaya terapiya klopidogrelem pri stentirovanii po povodu ostrogo koronarnogo sindroma s uchetom geneticheskih polimorfizmov // Farmakogeneticheskoe testirovanie i personalizirovannaya terapiya V mezhdunarodnyy kongress «Kardiologiya na perekrestke nauk»: Tez. dokl. - Tyumen', 2014. - S. 128.
76. Kireeva V.V., Lifshic G.I., Aparcin K.A. Translyacionnye issledovaniya faktorov tolerantnosti k povrezhdeniyu sosudistoy stenki i ee regeneratornogo potenciala // Mater. mezhdunar. nauch.-prakt. konf. «Nauka v sovremennom informacionnom obschestve» (North Charleston, USA, 28-29 avgusta 2014 g.). - S. 42-44.
77. Kireeva V.V., Koh N.V., Lifshic G.I., Aparcin K.A. Disfunkciya endoteliya kak kraeugol'nyy kamen' serdechno-sosudistyh sobytiy: molekulyarno- i farmakogeneticheskie aspekty // Rossiyskiy kardiologicheskiy zhurnal. - 2014. - № 10 (114). - S. 64-68.
78. Lifshic G.I., Aparcin K.A., Zelenskaya E.M., Vybivanceva A.V. i dr. Personalizirovannaya antiagregantnaya terapiya pacientov s ostrym koronarnym sindromom, zhiteley sibirskogo regiona Rossii // Postgenomnye metody analiza v biologii, laboratornoy i klinicheskoy medicine: Sb. tr. IV mezhdunar. nauch.-prakt. konf. (Kazan', 29 oktyabrya - 1 noyabrya 2014 g.). - Kazan', 2014. - S. 252.
79. Vybivantseva A.V., Demkova O.V., Koryakina L.B., Andreeva E.O. Impact of preanalytical delay on results of light transmittance aggregometry in STEMI patients // ISTH Congress (Toronto, June 20-25, 2015). - 2015. - Suppl. 2. - P. 283.
80. Lifshic G.I., Koh N.V., Aparcin K.A. Sozdanie portativnogo pribora dlya mul'tiparametricheskogo kontrolya antitromboticheskoy terapii s uchetom geneticheskih polimorfizmov // Personalizirovannaya medicina i global'noe zdorov'e: mater. mezhdunar. konf. (Astana, Kazahstan, 13-14 maya 2015 g.). - 2015. - S. 59-60.
81. Lifshic G.I., Aparcin K.A. Prospektivnoe mnogocentrovoe nablyudatel'noe issledovanie PROTOKOL: Personalizirovannaya terapiya klopidogrelom pri stentirovanii po povodu ostrogo koronarnogo sindroma s uchetom geneticheskih polimorfizmov // Kachestvennaya klinicheskaya praktika. - 2015. - № 1. - S. 78-86.
82. Zelenskaya E.M., Slepuhina A.A., Koh N.V., Aparcin K.A. i dr. Geneticheskie, patofiziologicheskie i klinicheskie aspekty antikoagulyantnoy terapii // Farmakogenetika i farmakogenomika. - 2015. - № 1. - S. 12-19.
83. Lifshic G.I., Koh N.V., Kireeva V.V., Aparcin K.A. Translyacionnye issledovaniya effektivnosti lecheniya u pacientov s serdechno-sosudistoy patologiey // Serdechno-sosudistye bolezni i komorbidnost': Sb. mater. IX Baykal'skoy mezhregion. konf. (Irkutsk, 27-28 maya 2015 g.) / Pod red. F.I. Belyalova. - Irkutsk, 2015. - S. 37-38.
84. Zelenskaya E.M., Subbotovskaya A.I., Ganyukov V.I., Kochergin N.A. Issledovanie «PROTOKOL»: predvaritel'nye rezul'taty v ramkah proekta // Rossiyskiy kardiologicheskiy zhurnal. - 2015. - № 10. - S. 75-80.
85. Zelenskaya E.M., Koh N.V., Kireeva V.V., Aparcin K.A. i dr. Associaciya gena CYP11B2 s riskom razvitiya gipertonicheskoy bolezni i aterotromboticheskih oslozhneniy // Kardiovaskulyarnaya terapiya i profilaktika. - 2016. - № 15 (3). - S. 63-68 Rezhim dostupa: http://dx.doi.org/10.15829/1728-8800-2016-3-63-68.
86. Kireeva V.V., Lepehova S.A., Usol'cev Yu.K., Aparcin K.A. Translyacionnye metody diagnostiki mitohondrial'noy disfunkcii u pacientov s hronicheskoy ishemiey miokarda i/ili golovnogo mozga Farmakogeneticheskoe testirovanie i personalizirovannaya terapiya: Mater. mezhdunar. nauch.-prakt. konf. «Fundamental'naya nauka i tehnologii - perspektivnye razrabotki» (North Charleston, USA, 18-19 aprelya 2016 g.). - 2016. - S. 14-18.
87. Lifshic G.I., Slepuhina A.A., Subbotovskaya A.I. Aparcin K.A. i dr. Izmerenie parametrov gemostaza: pribornaya baza i perspektivy razvitiya // Medicinskaya tehnika. - 2016. - № 4. - S. 48-52.
88. Slepuhina A.A., Subbotovskaya A.I., Aparcin K.A. Sovremennye podhody k izmereniyu parametrov gemostaza v klinicheskoy praktike. Novye aspekty etiopatogeneza, diagnostiki i lecheniya arterial'nyh i venoznyh trombozov. - Novosibirsk: Novosibirskiy nacional'nyy issledovatel'skiy gosudarstvennyy universitet, 2016. - S. 20-36.
89. Lifshic G.I., Aparcin K.A., Tronin A.V. Razrabotka portativnogo ustroystva dlya monitorirovaniya parametrov svertyvayuschey sistemy krovi // Tromboz, gemostaz i reologiya. - 2016. - № 3, T. 67, Pril. 1. - S. 254-255.
90. Grigor'ev S.E., Zarickaya L.V., Lepehova S.A., Aparcin K.A. Metabolicheskaya korrekciya tafcinovoy nedostatochnosti pri giposplenizme // Mater. mezhdunar. nauch.-prakt. konf. «Nauka v sovremennom informacionnom obschestve» (Moskva, 3-4 aprelya 2013 g.). - T. 1. - S. 23-26.
91. Grigor'ev S.E., Lepehova S.A., Aparcin K.A. Translyacionnye issledovaniya tafcin-soderzhaschih preparatov dlya korrekcii postsplenektomicheskogo giposplenizma // Sb. tez. nauch. konf. «Fundamental'nye nauki - medicine», posv. 10-letiyu Medicinskogo fakul'teta NGU (Novosibirsk, 16-20 oktyabrya 2013 g.). - 2013. - S. 124-125.
92. Grigor'ev S.E., Lepehova S.A., Aparcin K.A. Korrekciya posledstviy splenektomii tafcinosoderzhaschimi preparatami. - 2014. - 149 c.
93. Aparcin K.A. Hirurgiya sochetannyh povrezhdeniy // Sibirskiy medicinskiy zhurnal (g. Irkutsk). - 2014. - T. 126, № 3. - S. 129-133.
94. Aparcin K.A., Belyaeva O.A., Boyko T.N., Galeev Yu.M. i dr. Neoperativnoe lechenie povrezhdeniy selezenki u detey / Pod red. V.V. Podkameneva, K.A. Aparcina, E.G. Grigor'eva. - Novosibirsk: Nauka; Irkutsk: NC RVH, 2014. - 256 c.
95. Podkamenev V.V., Aparcin K.A., Grigor'ev E.G. (red.) Neoperativnoe lechenie povrezhdeniy selezenki v detskom vozraste. - Saarbrucken: Lambert Academic Publishing, 2015. - 228 s.
96. Sposob endoskopicheskoy retrogradnoy holangiopankreatografii u pacienta s vypolnennoy ranee holecistostomiey: Pat. 2488356 Ros. Federaciya / Aparcin K.A., Hramcov E.V., Panasyuk A.I., Kiseleva M.Yu. - № 2014109996/14; zareg. 14.03.2014; opubl. 27.05.2015, Byul. № 15.
97. Aparcin K.A., Grigor'ev E.G. Hirurgicheskie bolezni selezenki: Abdominal'naya hirurgiya. Nacional'noe rukovodstvo: kratkoe izdanie / Pod red. I.I. Zatevahina, A.I. Kirienko, V.A. Kubyshkina. - M.: GEOTAR Media, 2016. - S. 704-716.
98. Grigor'ev S.E., Aparcin K.A. Primenenie principov dokazatel'noy mediciny k izucheniyu hirurgicheskih zabolevaniy selezenki // Annaly hirurgicheskoy gepatologii. - 2016. - T. 21, № 1. - 119-124.
99. Lekcii po gospital'noy hirurgii, v 3-h tt. / Pod red. E.G. Grigor'eva. - Irkutsk: INCHT, 2016. - T. 1. - 308 s.
