medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.05.40-53medgen-2290Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВлияние антипсихотической терапии на вариацию числа копий рибосомного повтора в составе циркулирующей ДНК плазмы крови больных шизофрениейThe effect of antipsychotic therapy to the ribosomal repeat copy number variation in the the composition of plasma circulating DNA in patients with schizophreniaЕршоваЕ. С.ErshovaE. S.

115478, г. Москва, ул. Москворечье д.1

1, Moskvorechye st., Moscow, 115522

es-ershova@rambler.ruЖестковаЕ. М.JestkovaE. M.

107076, г. Москва, ул. Потешная, д.3

3, Poteshnaya st., Moscow, 115447

МартыновА. В.MartynovA. V.

115478, г. Москва, ул. Москворечье д.1

1, Moskvorechye st., Moscow, 115522

ЗахароваН. В.ZakharovaN. V.

117152, г. Москва, Загородное шоссе, д. 2

2, Zagorodnoye shosse, Moscow, 115447

БраввеЛ. В.BravveL. V.

117152, г. Москва, Загородное шоссе, д. 2

2, Zagorodnoye shosse, Moscow, 115447

КостюкГ. П.KostyukG. P.

117152, г. Москва, Загородное шоссе, д. 2

2, Zagorodnoye shosse, Moscow, 115447

ВейкоН. Н.VeikoN. N.

115478, г. Москва, ул. Москворечье д.1

1, Moskvorechye st., Moscow, 115522

КостюкС. В.KostyukS. V.

115478, г. Москва, ул. Москворечье д.1

1, Moskvorechye st., Moscow, 115522

ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian FederationГБУЗ города Москвы «Психиатрическая клиническая больница № 4 им. П.Б. Ганнушкина Департамента здравоохранения города Москвы»РоссияPsychiatric Hospital No. 4 of Moscow City Health DepartmentRussian FederationГБУЗ города Москвы «Психиатрическая клиническая больница № 1 им. Н.А. Алексеева Департамента здравоохранения города Москвы»РоссияPsychiatric Hospital no. 1 Named after N.A. Alexeev of the Department of Health of MoscowRussian Federation2023270720232254053Copyright © Ершова Е.С., Жесткова Е.М., Мартынов А.В., Захарова Н.В., Бравве Л.В., Костюк Г.П., Вейко Н.Н., Костюк С.В., 20232023Ершова Е.С., Жесткова Е.М., Мартынов А.В., Захарова Н.В., Бравве Л.В., Костюк Г.П., Вейко Н.Н., Костюк С.В.Ershova E.S., Jestkova E.M., Martynov A.V., Zakharova N.V., Bravve L.V., Kostyuk G.P., Veiko N.N., Kostyuk S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2290

Циркулирующая внеклеточная ДНК (вкДНК) при патологии оказывает негативное действие на клетки организма, поддерживая системное воспаление. Фрагменты рибосомного повтора (рДНК), которые накапливаются в составе вкДНК, активируют транскрипционный фактор NF-kB, который регулирует транскрипцию генов провоспалительных цитокинов. В работе показано, что антипсихотическая терапия ассоциирована со значительным снижением концентрации биологически активных фрагментов рДНК в плазме крови больных. Поиск малотоксичных синтетических и природных соединений на основе молекулярных структур, входящих в состав антипсихотиков, может привести к появлению лекарств, изменяющих биологическую активность вкДНК.

Circulating extracellular DNA (cfDNA) in pathology has a negative effect on the cells of the body, supporting systemic inflammation. Ribosomal repeat fragments (rDNA), which accumulate in cfDNA, activate the transcription factor NF-kB, which regulates the transcription of pro-inflammatory cytokine genes. The work shows that antipsychotic therapy is associated with a significant decrease in the concentration of biologically active rDNA fragments in the blood plasma of patients. The search for low-toxic synthetic and natural compounds based on the molecular structures that make up antipsychotics may lead to the emergence of drugs that change the biological activity of cfDNA.

шизофрениявнеклеточная ДНК (вкДНК)рибосомный повторCirculating free DNA (cfDNA)ribosomal repeatSchizophreniaГосударственное задание Министерства науки и высшего образования для ФГБНУ МГНЦ.The work was supported by the state task of the Ministry of Science and Higher Education for Research Centre for Medical Genetics.ReferencesWan J.C.M., Massie C., Garcia-Corbacho J., Mouliere F., Brenton J.D., Caldas C., Pacey S., Baird R., Rosenfeld N. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238. doi: 10.1038/nrc.2017.7.Wan J.C.M., Massie C., Garcia-Corbacho J., Mouliere F., Brenton J.D., Caldas C., Pacey S., Baird R., Rosenfeld N. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238. doi: 10.1038/nrc.2017.7.Heitzer E., Haque I.S., Roberts C.E.S., Speicher M.R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71-88. doi: 10.1038/s41576-018-0071-5.Heitzer E., Haque I.S., Roberts C.E.S., Speicher M.R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71-88. doi: 10.1038/s41576-018-0071-5.Kustanovich A., Schwartz R., Peretz T., Grinshpun A. Life and death of circulating cell-free DNA. Cancer Biol Ther. 2019;20(8):1057-1067. doi: 10.1080/15384047.2019.1598759.Kustanovich A., Schwartz R., Peretz T., Grinshpun A. Life and death of circulating cell-free DNA. Cancer Biol Ther. 2019;20(8):1057-1067. doi: 10.1080/15384047.2019.1598759.Duvvuri B., Lood C. Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases. Front Immunol. 2019;10:502. doi: 10.3389/fimmu.2019.00502.Duvvuri B., Lood C. Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases. Front Immunol. 2019;10:502. doi: 10.3389/fimmu.2019.00502.Han D.S.C., Lo Y.M.D. The Nexus of cfDNA and Nuclease Biology. Trends Genet. 2021;37(8):758-770. doi: 10.1016/j.tig.2021.04.005.Han D.S.C., Lo Y.M.D. The Nexus of cfDNA and Nuclease Biology. Trends Genet. 2021;37(8):758-770. doi: 10.1016/j.tig.2021.04.005.Knight SR, Thorne A, Lo Faro ML. Donor-specific Cell-free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review. Transplantation. 2019;103(2):273-283. doi: 10.1097/TP.0000000000002482.Knight SR, Thorne A, Lo Faro ML. Donor-specific Cell-free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review. Transplantation. 2019;103(2):273-283. doi: 10.1097/TP.0000000000002482.Meddeb R., Dache Z.A.A., Thezenas S., Otandault A., Tanos R., Pastor B., Sanchez C., Azzi J., Tousch G., Azan S., Mollevi C., Adenis A., El Messaoudi S., Blache P., Thierry A.R. Quantifying circulating cell-free DNA in humans. Sci Rep. 2019;9(1):5220. doi: 10.1038/s41598-019-41593-4.Meddeb R., Dache Z.A.A., Thezenas S., Otandault A., Tanos R., Pastor B., Sanchez C., Azzi J., Tousch G., Azan S., Mollevi C., Adenis A., El Messaoudi S., Blache P., Thierry A.R. Quantifying circulating cell-free DNA in humans. Sci Rep. 2019;9(1):5220. doi: 10.1038/s41598-019-41593-4.Marsman G., Zeerleder S., Luken B.M. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation. Cell Death Dis. 2016;7(12):e2518. doi: 10.1038/cddis.2016.410.Marsman G., Zeerleder S., Luken B.M. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation. Cell Death Dis. 2016;7(12):e2518. doi: 10.1038/cddis.2016.410.Nie L., Cai S.Y., Shao J.Z, Chen J. Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals. Front Immunol. 2018;9:1523. doi: 10.3389/fimmu.2018.01523.Nie L., Cai S.Y., Shao J.Z, Chen J. Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals. Front Immunol. 2018;9:1523. doi: 10.3389/fimmu.2018.01523.Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W., Brohi K., Itagaki K., Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104-7. doi: 10.1038/nature08780.Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W., Brohi K., Itagaki K., Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104-7. doi: 10.1038/nature08780.Dwivedi D.J., Toltl L.J., Swystun L.L., Pogue J., Liaw K.L., Weitz J.I., Cook D.J., Fox-Robichaud A.E., Liaw P.C.; Canadian Critical Care Translational Biology Group. Prognostic utility and characterization of cell-free DNA in patients with severe sepsis. Crit Care. 2012;16(4):R151. doi: 10.1186/cc11466.Dwivedi D.J., Toltl L.J., Swystun L.L., Pogue J., Liaw K.L., Weitz J.I., Cook D.J., Fox-Robichaud A.E., Liaw P.C.; Canadian Critical Care Translational Biology Group. Prognostic utility and characterization of cell-free DNA in patients with severe sepsis. Crit Care. 2012;16(4):R151. doi: 10.1186/cc11466.Weber C., Jenke A., Chobanova V., Yazdanyar M., Chekhoeva A., Eghbalzadeh K., Lichtenberg A, Wahlers T, Akhyari P, Paunel-Görgülü A. Targeting of cell-free DNA by DNase I diminishes endothelial dysfunction and inflammation in a rat model of cardiopulmonary bypass. Sci Rep. 2019;9(1):19249. doi: 10.1038/s41598-019-55863-8.Weber C., Jenke A., Chobanova V., Yazdanyar M., Chekhoeva A., Eghbalzadeh K., Lichtenberg A, Wahlers T, Akhyari P, Paunel-Görgülü A. Targeting of cell-free DNA by DNase I diminishes endothelial dysfunction and inflammation in a rat model of cardiopulmonary bypass. Sci Rep. 2019;9(1):19249. doi: 10.1038/s41598-019-55863-8.Soni C., Reizis B. DNA as a self-antigen: nature and regulation. Curr Opin Immunol. 2018;55:31-37. doi: 10.1016/j.coi.2018.09.009.Soni C., Reizis B. DNA as a self-antigen: nature and regulation. Curr Opin Immunol. 2018;55:31-37. doi: 10.1016/j.coi.2018.09.009.Chan R.W., Jiang P., Peng X., Tam L.S., Liao G.J., Li E.K., Wong P.C., Sun H., Chan K.C., Chiu R.W., Lo Y.M. Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing. Proc Natl Acad Sci U S A. 2014;111(49):E5302-11. doi: 10.1073/pnas.1421126111.Chan R.W., Jiang P., Peng X., Tam L.S., Liao G.J., Li E.K., Wong P.C., Sun H., Chan K.C., Chiu R.W., Lo Y.M. Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing. Proc Natl Acad Sci U S A. 2014;111(49):E5302-11. doi: 10.1073/pnas.1421126111.Tamkovich S.N., Cherepanova A.V., Kolesnikova E.V., Rykova E.Y., Pyshnyi D.V., Vlassov V.V., Laktionov P.P. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci. 2006;1075:191-6. doi: 10.1196/annals.1368.026.Tamkovich S.N., Cherepanova A.V., Kolesnikova E.V., Rykova E.Y., Pyshnyi D.V., Vlassov V.V., Laktionov P.P. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci. 2006;1075:191-6. doi: 10.1196/annals.1368.026.Kawai Y., Yoshida M., Arakawa K., Kumamoto T., Morikawa N., Masamura K., Tada H., Ito S., Hoshizaki H., Oshima S., Taniguchi K., Terasawa H., Miyamori I., Kishi K., Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation. 2004;109(20):2398-400. doi: 10.1161/01.CIR.0000129232.61483.43.Kawai Y., Yoshida M., Arakawa K., Kumamoto T., Morikawa N., Masamura K., Tada H., Ito S., Hoshizaki H., Oshima S., Taniguchi K., Terasawa H., Miyamori I., Kishi K., Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation. 2004;109(20):2398-400. doi: 10.1161/01.CIR.0000129232.61483.43.Yasuda T., Iida R., Kawai Y., Nakajima T., Kominato Y., Fujihara J., Takeshita H. Serum deoxyribonuclease I can be used as a useful marker for diagnosis of death due to ischemic heart disease. Leg Med (Tokyo). 2009;11 Suppl 1:S213-5. doi: 10.1016/j.legalmed.2009.01.092.Yasuda T., Iida R., Kawai Y., Nakajima T., Kominato Y., Fujihara J., Takeshita H. Serum deoxyribonuclease I can be used as a useful marker for diagnosis of death due to ischemic heart disease. Leg Med (Tokyo). 2009;11 Suppl 1:S213-5. doi: 10.1016/j.legalmed.2009.01.092.Ershova E., Sergeeva V., Klimenko M., Avetisova K., Klimenko P., Kostyuk E., Veiko N., Veiko R., Izevskaya V., Kutsev S., Kostyuk S. Circulating cell-free DNA concentration and DNase I activity of peripheral blood plasma change in case of pregnancy with intrauterine growth restriction compared to normal pregnancy. Biomed Rep. 2017;7(4):319-324. doi: 10.3892/br.2017.968.Ershova E., Sergeeva V., Klimenko M., Avetisova K., Klimenko P., Kostyuk E., Veiko N., Veiko R., Izevskaya V., Kutsev S., Kostyuk S. Circulating cell-free DNA concentration and DNase I activity of peripheral blood plasma change in case of pregnancy with intrauterine growth restriction compared to normal pregnancy. Biomed Rep. 2017;7(4):319-324. doi: 10.3892/br.2017.968.Velders M., Treff G., Machus K., Bosnyák E., Steinacker J., Schumann U. Exercise is a potent stimulus for enhancing circulating DNase activity. Clin Biochem. 2014;47(6):471-4. doi: 10.1016/j.clinbiochem.2013.12.017.Velders M., Treff G., Machus K., Bosnyák E., Steinacker J., Schumann U. Exercise is a potent stimulus for enhancing circulating DNase activity. Clin Biochem. 2014;47(6):471-4. doi: 10.1016/j.clinbiochem.2013.12.017.Вейко Н.Н., Шубаева Н.О., Иванова С.М., Сперанский А.И., Ляпунова Н.А., Спитковский Д.М. ДНК сыворотки крови больных ревматоидным артритом значительно обогащена фрагментами рибосомных повторов, содержащих иммуностимулирующие CpG–мотивы. Бюллетень экспериментальной биологии и медицины.2006; 9: 282-285.Veiko N.N., Shubaeva N.O., Ivanova S.M., Speransky A.I., Lyapunova N.A., Spitkovsky D.M. DNK syvorotki krovi bol’nykh revmatoidnym artritom znachitel’no obogashchena fragmentami ribosomnykh povtorov, soderzhashchikh immunostimuliruyushchiye CpG–motivy [Serum DNA of patients with rheumatoid arthritis is significantly enriched in fragments of ribosomal repeats containing immunostimulatory CpG motifs]. Byulleten’ eksperimental’noy biologii i meditsiny [Bulletin of Experimental Biology and Medicine]. 2006; 9:282-285. (In Russ.)Korzeneva I.B., Kostuyk S.V., Ershova E.S., Skorodumova E.N., Zhuravleva VF, Pankratova GV, Volkova IV, Stepanova EV, Porokhovnik LN, Veiko NN. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation. Mutat Res. 2016;791-792:49-60. doi: 10.1016/j.mrfmmm.2016.09.001.Korzeneva I.B., Kostuyk S.V., Ershova E.S., Skorodumova E.N., Zhuravleva VF, Pankratova GV, Volkova IV, Stepanova EV, Porokhovnik LN, Veiko NN. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation. Mutat Res. 2016;791-792:49-60. doi: 10.1016/j.mrfmmm.2016.09.001.Вейко Н.Н., Булычева Н.В., Рогинко О.А., Вейко Р.В., Ершова Е.С., Коздоба О.А., Кузьмин В.А., Виноградов A.M., Юдин А.А., Сперанский А.И. Фрагменты транскрибируемой области рибосомного повтора в составе внеклеточной ДНК — маркер гибели клеток организма. Биомедицинская химия. 2008; 54(1):78-93.Veiko N.N., Bulycheva N.A., Roginko O.A., Veiko R.V., Ershova E.S., Kozdoba O.A., Kuzmin V.A., Vinogradov A.M., Yudin A.A., Speranskyi A.I. Fragmenty transkribiruyemoy oblasti ribosomnogo povtora v sostave vnekletochnoy DNK — marker gibeli kletok organizma [Ribosomal repeat in the cell free DNA as a marker for cell death]. Biomeditsinskaya Khimiya [Biomedical Chemistry]. 2008; 54(1):78-93. (In Russ.)Aswani A., Manson J., Itagaki K., Chiazza F., Collino M., Wupeng W.L., Chan T.K., Wong W.S.F., Hauser C.J., Thiemermann C., Bro-hi K. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage. Front Immunol. 2018;9:891. doi: 10.3389/fimmu.2018.00891.Aswani A., Manson J., Itagaki K., Chiazza F., Collino M., Wupeng W.L., Chan T.K., Wong W.S.F., Hauser C.J., Thiemermann C., Bro-hi K. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage. Front Immunol. 2018;9:891. doi: 10.3389/fimmu.2018.00891.Ershova E.S., Jestkova E.M., Martynov A.V., Shmarina G.V., Umriukhin P.E., Bravve L.V., Zakharova N.V., Kostyuk G.P., Saveliev D.V., Orlova M.D., Bogush M., Kutsev S.I., Veiko N.N., Kostyuk S.V. Accumulation of Circulating Cell-Free CpG-Enriched Ribosomal DNA Fragments on the Background of High Endonuclease Activity of Blood Plasma in Schizophrenic Patients. Int J Genomics. 2019;2019:8390585. doi: 10.1155/2019/8390585.Ershova E.S., Jestkova E.M., Martynov A.V., Shmarina G.V., Umriukhin P.E., Bravve L.V., Zakharova N.V., Kostyuk G.P., Saveliev D.V., Orlova M.D., Bogush M., Kutsev S.I., Veiko N.N., Kostyuk S.V. Accumulation of Circulating Cell-Free CpG-Enriched Ribosomal DNA Fragments on the Background of High Endonuclease Activity of Blood Plasma in Schizophrenic Patients. Int J Genomics. 2019;2019:8390585. doi: 10.1155/2019/8390585.Ershova E.S., Jestkova E.M., Chestkov I.V., Porokhovnik L.N., Izevskaya V.L., Kutsev S.I., Veiko N.N., Shmarina G., Dolgikh O., Kostyuk S.V. Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients. J Psychiatr Res. 2017;87:15-22. doi: 10.1016/j.jpsychires.2016.12.006.Ershova E.S., Jestkova E.M., Chestkov I.V., Porokhovnik L.N., Izevskaya V.L., Kutsev S.I., Veiko N.N., Shmarina G., Dolgikh O., Kostyuk S.V. Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients. J Psychiatr Res. 2017;87:15-22. doi: 10.1016/j.jpsychires.2016.12.006.Jung M., Kristiansen G., Dietrich D. DNA Methylation Analysis of Free-Circulating DNA in Body Fluids. Methods Mol Biol. 2018;1708:621-641. doi: 10.1007/978-1-4939-7481-8_32.Jung M., Kristiansen G., Dietrich D. DNA Methylation Analysis of Free-Circulating DNA in Body Fluids. Methods Mol Biol. 2018;1708:621-641. doi: 10.1007/978-1-4939-7481-8_32.Jiang J., Chen X., Sun L., Qing Y., Yang X., Hu X., Yang C., Xu T., Wang J., Wang .P, He L., Dong C., Wan C. Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy. Transl Psychiatry. 2018;8(1):104. doi: 10.1038/s41398-018-0153-3.Jiang J., Chen X., Sun L., Qing Y., Yang X., Hu X., Yang C., Xu T., Wang J., Wang .P, He L., Dong C., Wan C. Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy. Transl Psychiatry. 2018;8(1):104. doi: 10.1038/s41398-018-0153-3.Qi J., Chen L.Y., Shen X.J., Ju .SQ. Analytical Value of Cell-Free DNA Based on Alu in Psychiatric Disorders. Front Psychiatry. 2020;10:992. doi: 10.3389/fpsyt.2019.00992.Qi J., Chen L.Y., Shen X.J., Ju .SQ. Analytical Value of Cell-Free DNA Based on Alu in Psychiatric Disorders. Front Psychiatry. 2020;10:992. doi: 10.3389/fpsyt.2019.00992.Ouyang H., Huang M., Xu Y., Yao Q., Wu X., Zhou D. Reduced Cell-Free Mitochondrial DNA Levels Were Induced by Antipsychotics Treatment in First-Episode Patients With Schizophrenia. Front Psychiatry. 2021;12:652314. doi: 10.3389/fpsyt.2021.652314.Ouyang H., Huang M., Xu Y., Yao Q., Wu X., Zhou D. Reduced Cell-Free Mitochondrial DNA Levels Were Induced by Antipsychotics Treatment in First-Episode Patients With Schizophrenia. Front Psychiatry. 2021;12:652314. doi: 10.3389/fpsyt.2021.652314.Ershova E.S., Shmarina G.V., Porokhovnik L.N., Zakharova N.V., Kostyuk G.P., Umriukhin P.E., Kutsev S.I., Sergeeva V.A., Veiko N.N., Kostyuk S.V. In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls. Genes (Basel). 2022;13(3):551. doi: 10.3390/genes13030551.Ershova E.S., Shmarina G.V., Porokhovnik L.N., Zakharova N.V., Kostyuk G.P., Umriukhin P.E., Kutsev S.I., Sergeeva V.A., Veiko N.N., Kostyuk S.V. In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls. Genes (Basel). 2022;13(3):551. doi: 10.3390/genes13030551.Chestkov I.V., Jestkova E.M., Ershova E.S., Golimbet V.E., Lezheiko T.V., Kolesina N.Y., Porokhovnik L.N., Lyapunova N.A., Izhevskaya V.L., Kutsev .SI., Veiko N.N., Kostyuk S.V. Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients. Schizophr Res. 2018;197:305-314. doi: 10.1016/j.schres.2018.01.001.Chestkov I.V., Jestkova E.M., Ershova E.S., Golimbet V.E., Lezheiko T.V., Kolesina N.Y., Porokhovnik L.N., Lyapunova N.A., Izhevskaya V.L., Kutsev .SI., Veiko N.N., Kostyuk S.V. Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients. Schizophr Res. 2018;197:305-314. doi: 10.1016/j.schres.2018.01.001.Жесткова Е.М., Ершова Е.С., Мартынов А.В., Захарова Н.В., Костюк Г.П., Вейко Н.Н., Костюк С.В. Концентрация циркулирующей внеклеточной ДНК в плазме периферической крови больных с острыми психозами эндогенной и экзогенной этиологии. Психиатрия. 2021; 19(3): 6-14.Jestkova E.M., Ershova E.S., Martynov A.V., Zakharova N.V., Kostyuk G.P., Veiko N.N., Kostyuk S.V. Kontsentratsiya tsirkuliruyushchey vnekletochnoy DNK v plazme perifericheskoy krovi bol’nykh s ostrymi psikhozami endogennoy i ekzogennoy etiologii [Concentration of Circulating Cell-Free DNA in the Peripheral Blood Plasma of Patients with Acute Endogenous and Exogenous Etiology Psychoses]. Psikhiatriya [Psikhiatriya]. 2021;19(3):6-14. (In Russ.) https://doi.org/10.30629/2618-6667-2021-19-3-6-14Костюк С.В. Роль внеклеточной ДНК в функциональной активности генома человека. Диссертация …. доктора биологических наук. Москва, 2014.- 450 с.Kostyuk S.V. Rol’ vnekletochnoy DNK v funktsional’noy aktivnosti genoma cheloveka. Dissertatsiya …. doktora biologicheskikh nauk [The role of extracellular DNA in the functional activity of the human genome. Thesis…. Doctor of Biological Sciences]. Moscow, 2014.- 450 p. (In Russ.)Kumar R., Sonkar V.K., Swamy J., Ahmed A., Sharathkumar A.A., Pierce G.L., Dayal S. DNase 1 Protects From Increased Thrombin Generation and Venous Thrombosis During Aging: Cross-Sectional Study in Mice and Humans. J Am Heart Assoc. 2022;11(2):e021188. doi: 10.1161/JAHA.121.021188.Kumar R., Sonkar V.K., Swamy J., Ahmed A., Sharathkumar A.A., Pierce G.L., Dayal S. DNase 1 Protects From Increased Thrombin Generation and Venous Thrombosis During Aging: Cross-Sectional Study in Mice and Humans. J Am Heart Assoc. 2022;11(2):e021188. doi: 10.1161/JAHA.121.021188.Dawulieti J., Sun M., Zhao Y., Shao D., Yan H., Lao Y.H., Hu H., Cui L., Lv X., Liu F., Chi C.W., Zhang Y., Li M., Zhang M., Tian H., Chen X., Leong K.W., Chen L. Treatment of severe sepsis with nanoparticulate cell-free DNA scavengers. Sci Adv. 2020;6(22):eaay7148. doi: 10.1126/sciadv.aay7148.Dawulieti J., Sun M., Zhao Y., Shao D., Yan H., Lao Y.H., Hu H., Cui L., Lv X., Liu F., Chi C.W., Zhang Y., Li M., Zhang M., Tian H., Chen X., Leong K.W., Chen L. Treatment of severe sepsis with nanoparticulate cell-free DNA scavengers. Sci Adv. 2020;6(22):eaay7148. doi: 10.1126/sciadv.aay7148.Liang H., Peng B., Dong C., Liu L., Mao J., Wei S., Wang X., Xu H., Shen J., Mao H.Q., Gao X., Leong K.W., Chen Y. Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation. Nat Commun. 2018;9(1):4291. doi: 10.1038/s41467-018-06603-5.Liang H., Peng B., Dong C., Liu L., Mao J., Wei S., Wang X., Xu H., Shen J., Mao H.Q., Gao X., Leong K.W., Chen Y. Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation. Nat Commun. 2018;9(1):4291. doi: 10.1038/s41467-018-06603-5.Liu F., Sheng S., Shao D., Xiao Y., Zhong Y., Zhou J., Quek C.H., Wang Y., Hu Z., Liu H., Li Y., Tian H., Leong K.W., Chen X. A Cationic Metal-Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management. Nano Lett. 2021;21(6):2461-2469. doi: 10.1021/acs.nanolett.0c04759.Liu F., Sheng S., Shao D., Xiao Y., Zhong Y., Zhou J., Quek C.H., Wang Y., Hu Z., Liu H., Li Y., Tian H., Leong K.W., Chen X. A Cationic Metal-Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management. Nano Lett. 2021;21(6):2461-2469. doi: 10.1021/acs.nanolett.0c04759.Chen Y., Wang Y., Jiang X., Cai J., Chen Y., Huang H., Yang Y., Zheng L., Zhao J., Gao M. Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy. Bioact Mater. 2022;18:409-420. doi: 10.1016/j.bioactmat.2022.03.028.Chen Y., Wang Y., Jiang X., Cai J., Chen Y., Huang H., Yang Y., Zheng L., Zhao J., Gao M. Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy. Bioact Mater. 2022;18:409-420. doi: 10.1016/j.bioactmat.2022.03.028.

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