Proteomic analysis of cervicovaginal fluid of patients with HPV-associated cervical lesions treated with activated glycyrrhizic acid


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Abstract

Objective: To investigate the proteome of cervicovaginal fluid (CVF) in patients with HPV-associated cervical lesions treated with activated glycyrrhizic acid (AGA). Materials and methods: The study included 80 HPV-positive females aged 18 to 49 with cytologically confirmed NILM and chronic cervicitis (group I, n=40) and LSIL (group II, n=40). All patients received a drug with the active AGA substance (Epigen Intim spray 0.1%) for 18 months according to the protocol. The proteomic composition of CVF was analyzed by HPLC-MS/MS at four time points (before therapy, after 6, 12, and 18 months). Results: In a proteomic study, we compared two groups of CVF samples from 10 patients after AGA administration. Group 1 samples (n=5) showed positive changes (HPV elimination) and group 2 (n=5) had no changes (HPV persistence). Comparison of the proteomic composition of CVF samples in the dynamics revealed a change in 48 proteins. Levels of 27 proteins increased in the positive-change group, while the level of 21 proteins decreased compared to the no-change group. Annotation of proteins showing increase in their levels revealed their involvement in immune system processes (MPO, AZU1, LYZ, RNASE7, PPL, TXN, CD59, UBA52, CRISP3, ELANE), in particular, in the innate immune response (MPO, AZU1, LYZ, RNASE7, TXN, CD59, UBA52, CRISP3, ELANE) as well as in neutrophil degranulation (MPO, AZU1, LYZ, CD59, CRISP3, ELANE), and antimicrobial activity (AZU1, ELANE). Conclusion: The study findings suggest that long-term topical application of AGA affects CVF protein levels in small cervical lesions, in partcular reducesproinflammatory proteins during HPV elimination.

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About the authors

Vladimir E. Frankevich

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
Ph.D., Head of the Department of System Biology in Reproduction

Niso M. Nazarova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: grab2@yandex.ru
Dr. Med. Sci., Leading Researcher

Emira R. Dovlethanova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_dovletkhanova@oparina4.ru
PhD, Senior Researcher

Kirill I. Gusakov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: kigusakov@gmail.com
PhD, Researcher

Aleksey S. Kononikhin

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Skolkovo Institute of Science and Technology

Email: konoleha@yandex.ru
Ph.D., Researcher at the Laboratory of Proteomics of Human Reproduction

Anna E. Bugrova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; N.M. Emanuel Institute of Biochemical Physics of RAS

Email: a_bugrova@oparina4.ru
Ph.D., Senior Researcher, at the Laboratory of Proteomics of Human Reproduction

Alexander G. Brzhozovskiy

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Skolkovo Institute of Science and Technology

Email: agb.imbp@gmail.com
Researcher at the Laboratory of Proteomics of Human Reproduction

Vera N. Prilepskaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_prilepskaya@oparina4.ru
Dr. Med. Sci., Professor, Honored Scientist of the Russian Federation, Head of the Scientific Polyclinic Department

Vitaliy V. Chagovets

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: vvchagovets@gmail.com
PhD, Senior Researcher at the Laboratory of Proteomics and Metabolomics of Human Reproduction

Natalia L. Starodubtseva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_starodubtseva@oparina4.ru
Ph.D., Head of the Laboratory of Proteomics of Human Reproduction

Gennady T. Sukhikh

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
Dr. Med. Sci., Professor, Academician of the RAS

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