Back pain (BP), associated with the degenerative disc disease (DDD), poses a heavy social and economic burden due to early disability and indications to surgery, emerging in young adults. Pathophysiological basis of premature intervertebral disc (IVD) degeneration is being actively studied. The study was aimed to define the profiles of inflammatory cytokines in DDD, as well as their relationship to the structural spine diseases. The molecular genetic analysis of the mRNA gene abundance in patients with BP and herniated IVD after discectomy and healthy individuals was performed by the quantitative polymerase chain reaction method. High expression of TNFα, IL17 was revealed in the IVD tissues of the affected patients (p < 0.01); the levels of TNFα and IL1β correlated with the DDD severity (r = 0.301 and 0.37; p < 0.05). Elevated expression of IL1β, IL6 was found in peripheral white blood cells (p < 0.01); the levels of IL6 negatively correlated with Modic type 1 and 2 changes (r = –0.31; p < 0.05), and the levels of IL17 positively correlated with the IVD herniation in combination with erosions of the adjacent vertebral body endplates and Modic changes (r = 0.401; p < 0.05). The expression of VEGF-А in the IVD tissues and white blood cells negatively correlated with the DDD grades (r = –0.85; p < 0.001), indicating reduced vascularization in the terminal phase of the disease. The findings on DDD demonstrate the contribution of the local low-immune inflammation, coupled with the intense disc vascularization at the earlier stages, and associated with the reactive inflammation in vertebral bodies. The results are prerequisites for developing the anti-inflammatory and reparative therapy based on the DDD grade and the presence of Modic changes in young adults with BP.

Bol' v spine (BS), associirovannaya s degenerativnoj bolezn'yu diska (DBD), — tyazheloe social'noe i ekonomicheskoe bremya vsledstvie rannej invalidizacii i vozniknoveniya pokazanij k operativnomu vmeshatel'stvu uzhe v molodom vozraste. Patofiziologicheskie osnovy prezhdevremennoj degeneracii mezhpozvonkovogo diska (MPD) nahodyatsya na stadii aktivnogo izucheniya. Cel'yu issledovaniya bylo opredelit' profil' vospalitel'nyh citokinov pri DBD i ih svyaz' so strukturnymi narusheniyami v pozvonochnike. U pacientov molodogo vozrasta s BS i gryzhej MPD, podvergshihsya diskektomii, i u zdorovyh lic provodili molekulyarno-geneticheskij analiz predstavlennosti genov mRNK metodom kolichestvennoj polimeraznoj cepnoj reakcii. U bol'nyh v tkani MPD vyyavlen vysokij uroven' ekspressii TNFα, IL17 (p < 0,01); urovni TNFα i IL1β korrelirovali s tyazhest'yu DBD (r = 0,301 i 0,37; p < 0,05). V lejkocitah perifericheskoj krovi obnaruzhena povyshennaya ekspressiya IL1β, IL6 (p < 0,01); uroven' IL6 otricatel'no korreliroval s I i II stadiyami Modic-izmenenij (r = –0,31; p < 0,05), IL17 pryamo korreliroval s gryzhej MPD v sochetanii s eroziej zamykatel'nyh plastin i Modic (r = 0,401; p < 0,05). Ekspressiya VEGF-A v tkani MPD i v lejkocitah krovi otricatel'no korrelirovala so stadiej DBD (r = –0,85; p < 0,001), ukazyvaya na snizhenie aktivnosti vaskulyarizacii v terminal'noj stadii. Dannye, vyyavlennye pri DBD, govoryat o vklade lokal'nogo nizkoimmunnogo vospaleniya, sopryazhennogo s aktivnoj vaskulyarizaciej diska na bolee rannih stadiyah i associirovannogo s reaktivnym vospaleniem tel pozvonkov. Poluchennye rezul'taty sluzhat predposylkoj k razrabotke protivovospalitel'noj i reparativnoj terapii v zavisimosti ot stadii DBD i nalichiya Modic-izmenenij u lic molodogo vozrasta s BS.

The first weeks of life are extremely important for the development of the immunity-virome interaction that affects human health in adulthood. In this study we analyzed Torque teno virus (TTV) dynamics during the first weeks of life in the full-term/premature infants in relation with the maternal TTV load and the type of feeding. 152 infants aged 1-14 weeks (63 full-term and 89 premature) and 33 mother-child pairs were analyzed for the whole blood TTV load by qPCR with test sensitivity of 1000 viral copies/ml. 50 infants were retested (at 2-11 time points) for TTV dynamics data. All one-week babies (n = 71) from TTV-positive mothers were TTV-negative, consistently with the previous findings of the lack of transplacental transmission of the virus. TTV was not detectable in newborns under two weeks of age. Most infants are TTV-positive by 14 weeks of age. Whole blood TTV load does not show significant correlation with full-term/prematurity, maternal TTV load, or feeding type. Keywords: Torque teno virus; transfusion-transmitted virus; commensal virus; TTV; viral load dynamics; TORCH infections; full-term and premature babies; breastfeeding; virome.

Uterine leiomyomas are a worrying reproductive health issue that has serious social implications. The aim of this study was to conduct a search for marker single nucleotide polymorphisms (SNPs) associated with uterine leiomyoma. To test the hypothesis about the contribution of genetic predisposition to the pathogenesis of myomas, the initial group of 100 patients with a verified diagnosis of uterine leiomyoma was divided into 2 subgroups: subgroup Ia (women with a family history of the disease) and subgroup 1b (women with no family history of the disease). The control group consisted of 30 postmenopausal patients who did not have a medical history of uterine fibroids and denied uterine fibroids in their close female relatives. DNA sequences were read using Sanger sequencing. Statistically significant differences (p < 0.05) were discovered between the analyzed groups in terms of genotype frequencies for rs12637801 and rs12457644. Also, previously unknown protective SNPs were identified whose rare alleles could predict the reduced risk of uterine leiomyomas.

One of the key challenges facing today’s oncology is the discovery of early predictors of malignant neoplasms in patients’ biological samples. Liquid biopsy is a noninvasive diagnostic technique based on the detection and isolation of tumor cells, tumor-derived nucleic acid and exosomes circulating in the blood plasma of cancer patients. There is a plethora of research studies of circulating tumor DNA in patients with MN. The active proliferation of tumor cells occurs in the backdrop of altered gene expression. The presence of tissue-specific transcripts in the circulating RNA fraction suggests that levels of circulating RNA reflect the development of the primary tumor. We think that cell-free RNA circulating in the blood plasma is a promising molecular biomarker for early cancer detection.

Torque teno virus (TTV) is a commensal human virus observed as a circular single-negative-strand DNA molecule in various tissues and biological samples, notably in blood serum and lymphocytes. TTV has no apparent clinical significance, although it might be very useful as a prospective tool for gene delivery or as an epidemiological marker. Human populations are ubiquitously infected with TTV; the prevalence may reach 100%. The majority of babies become spontaneously infected with TTV, so that by the end of the first year of life, the prevalence reaches 'adult' values. TTV positivity in healthy early infancy and the presence of TTV in umbilical cord blood samples have been reported. The mechanism of infection and the dynamics of TTV prevalence in infants with age remain understudied. Meanwhile, the potential diagnostic and prognostic value of TTV as a marker deserves special attention and study, along with the possibility, causes and consequences of placental transmission of TTV under normal or pathological conditions.

Одна из ключевых задач современной онкодиагностики — поиск ранних предикторов злокачественных новообразований (ЗНО) при анализе наиболее доступных видов биоматериала. Жидкостная биопсия представляет собой одну из неинвазивных методик и включает в себя обнаружение и выделение циркулирующих опухолевых клеток, циркулирующих опухолевых нуклеиновых кислот и экзосом из плазмы крови у пациентов со злокачественными заболеваниями. Множество работ посвящено исследованию внеклеточной фракции ДНК при ЗНО. Вместе с тем активную пролиферацию трансформированных клеток при развитии опухолей сопровождают значительные изменения экспрессии определенных генов. Обнаружение тканеспецифичных транскриптов в составе внеклеточной РНК плазмы крови (внРНК) позволяет предположить, что представленность циркулирующих в плазме РНК связана с развитием патологического процесса непосредственно в первичном очаге. На наш взгляд, внРНК плазмы крови представляют практическую ценность в качестве молекулярно-генетических маркеров ранней диагностики в онкологии.

Миома матки является одной из важнейших социально значимых проблем женского репродуктивного здоровья. Целью исследования было найти маркерные однонуклеотидные полиморфизмы (SNP), ассоциированные с развитием миомы матки. Для проверки гипотезы о том, что наследственность играет важную роль в патогенезе миом, группу из 100 пациенток с подтвержденным диагнозом миомы матки разделили на две подгруппы: подгруппу Iа с отягощенным семейным анамнезом, подгруппу Iб с неотягощенным семейным анамнезом по миоме матки. Группа сравнения была сформирована из 30 пациенток (женщины в постменопаузе, не имевшие в анамнезе миому матки, отрицавшие наличие миом у ближайших родственниц). Первичную нуклеотидную последовательность определяли с помощью секвенирования по методу Сэнгера. Были выявлены статистически значимые (p < 0,05) различия между исследованными группами по частотам генотипов по rs12637801 и rs12457644. Впервые обнаружены «протективные» SNP, редкие аллели которых могут служить маркерами пониженного риска развития лейомиом матки.

Цель: оценить уровень экспрессии генов (TNF, IL6, IL8, IL18, VEGF121, VEGF165 и VEGF189), ассоциированных с опухолеобразованием, в плазме крови больных РМЖ и контрольной группе женщин. Материал и методы. Для определения уровня представленности мРНК исследуемых генов в плазме крови использовали методы обратной транскрипции и количественной полимеразной цепной реакции (наборы реагентов производства ДНКТехнология , Россия). Реакцию амплификации проводили в детектирующем амплификаторе DTprime 4 ( ДНКТехнология , Россия). Результаты. В плазме крови больных РМЖ и женщин контрольной группы относительные количества мРНК генов TNF, IL8, IL18 и VEGF189 были достоверно повышены у больных РМЖ в сравнении со здоровым контролем (p0,01). При сравнении группы контроля с группой больных РМЖ на различных стадиях высокий уровень экспрессии мРНК генов IL8 и IL18 наблюдается преимущественно в группе больных РМЖ с 0 стадией заболевания. Относительное количество мРНК гена IL8 в плазме больных РМЖ всех стадий (0, I и II) существенно превышало относительное количество мРНК этого цитокина в плазме крови женщин здоровой группы (p0,01), при этом различия между группой контроля и группой больных РМЖ III стадии были выявлены при p0,05. Достоверные различия в уровне экспрессии мРНК IL18 были выявлены между группой контроля и группами больных РМЖ 0, I и II стадиями (p0,01), при этом различия в уровне экспрессии мРНК гена IL18 между группой контроля и группой больных РМЖ III стадии заболевания оказались не значимыми (p0,05). Достоверные различия в уровне экспрессии мРНК TNF обнаружены между группой контроля и группой больных РМЖ I стадии заболевания (p0,01) и между группой контроля и группами больных РМЖ с II и III стадиями заболевания (p0,05). Статистически значимые различия в уровне мРНК гена VEGF189 наблюдаются в группах больных РМЖ на 0 и I стадиях по сравнению с группой контроля, где уровень мРНК VEGF189 значительно повышен в этих группах (p0,01). Также достоверные различия наблюдаются между группой контроля и группами больных РМЖ II и III стадий заболевания (p0,05). Заключение. Полученные результаты об уровне представленности мРНК исследованных генов свидетельствуют о том, что мРНК цитокинов (TNF, IL8, IL18) в плазме крови имеют статистически значимый повышенный уровень экспрессии при РМЖ по сравнению с группой контроля. Для доказательства того, что мРНК этих генов возможно использовать в качестве маркеров ранней диагностики рака молочной железы, следует увеличить выборку группы больных РМЖ с 0 стадией заболевания. Для получения статистически достоверных выводов о повышении экспрессии мРНК гена VEGF189 в плазме крови больных РМЖ также необходимы дополнительные исследования с увеличением выборки группы больных РМЖ с 0 стадией заболевания. Purpose: to evaluate the level of gene expression (TNF, IL6, IL8, IL18, VEGF121, VEGF165 and VEGF189) associated with tumor formation in the blood plasma of breast cancer patients and the control group of women. Material and methods. To determine the level of mRNA representation of the studied genes in blood plasma, the methods of reverse transcription and quantitative polymerase chain reaction were used (reagent kits manufactured by DNATechnology, Russia). The amplification reaction was carried out in a DTprime 4 detection amplifier (DNATechnology, Russia). Results. In the blood plasma of breast cancer patients and women in the control group, the relative amounts of mRNA of the TNF, IL8, IL18, and VEGF189 genes were significantly increased in patients with breast cancer compared with the healthy control (p 0.01). When comparing the control group with a group of breast cancer patients at various stages, a high level of IL8 and IL18 mRNA expression is observed mainly in the group of breast cancer patients with stage 0 disease. The relative amount of mRNA of IL8 gene in the plasma of patients with breast cancer of all stages (0, I and II) significantly exceeded the relative amount of mRNA of this cytokine in the blood plasma of women in the healthy group (p 0.01), while the differences between the control group and the group of patients with breast cancer III stages were identified at p 0.05. Significant differences in the level of IL18 mRNA expression were detected between the control group and breast cancer groups of stages 0, I and II (p 0.01), while differences in the level of IL18 mRNA expression between the control group and stage III breast cancer patients the diseases were not significant (p 0.05). Significant differences in the level of TNF mRNA expression were found between the control group and the group of patients with breast cancer stage I disease (p 0.01) and between the control group and the groups of patients with breast cancer with stage II and III disease (p 0.05). Statistically significant differences in the mRNA level of the VEGF189 gene are observed in groups of breast cancer at stages 0 and I compared with the control group, where the level of VEGF189 mRNA is significantly increased in these groups (p 0.01). Significant differences are also observed between the control group and the groups of patients with breast cancer of the II and III stages of the disease (p 0.05). Conclusion The obtained results on the level of mRNA representation of the studied genes indicate that mRNA of cytokines (TNF, IL8, IL18) in blood plasma have a statistically significant increased level of expression in breast cancer compared with the control group. To prove that the mRNA of these genes can be used as markers for early diagnosis of breast cancer, the sample of the group of breast cancer patients with stage 0 disease should be increased. To obtain statistically valid conclusions about the increased expression of the VEGF189 mRNA gene in the blood plasma of breast cancer patients, additional studies with an increase in the sample of the group of breast cancer patients with stage 0 disease are also required.

Purpose: to evaluate the level of gene expression (TNF, IL6, IL8, IL18, VEGF121, VEGF165 and VEGF189) associated with tumor formation in the blood plasma of breast cancer patients and the control group of women. Material and methods. To determine the level of messenger ribonucleic acid (mRNA) representation of the studied genes in blood plasma, the methods of reverse transcription and quantitative polymerase chain reaction were used (reagent kits manufactured by DNA-Technology, Russia). The amplification reaction was carried out in a DTprime 4 detection amplifier (DNA-Technology, Russia). Results. In the blood plasma of breast cancer patients and women in the control group, the relative amounts of mRNA of the TNF, IL8, IL18, and VEGF189 genes were significantly increased in patients with breast cancer compared with the healthy control (p 0.01). When comparing the control group with a group of breast cancer patients at various stages, a high level of IL8 and IL18 mRNA expression is observed mainly in the group of breast cancer patients with stage 0 disease. The relative amount of mRNA of IL8 gene in the plasma of patients with breast cancer of all stages (0, I and II) significantly exceeded the relative amount of mRNA of this cytokine in the blood plasma of women in the healthy group (p 0.01), while the differences between the control group and the group of patients with breast cancer III stages were identified at p 0.05. Significant differences in the level of IL18 mRNA expression were detected between the control group and breast cancer groups of stages 0, I and II (p 0.01), while differences in the level of IL18 mRNA expression between the control group and stage III breast cancer patients the diseases were not significant (p 0.05). Significant differences in the level of TNF mRNA expression were found between the control group and the group of patients with breast cancer stage I disease (p 0.01) and between the control group and the groups of patients with breast cancer with stage II and III disease (p 0.05). Statistically significant differences in the mRNA level of the VEGF189 gene are observed in groups of breast cancer at stages 0 and I compared with the control group, where the level of VEGF189 mRNA is significantly increased in these groups (p 0.01). Significant differences are also observed between the control group and the groups of patients with breast cancer of the II and III stages of the disease (p 0.05). Conclusion The obtained results on the level of mRNA representation of the studied genes indicate that mRNA of cytokines (TNF, IL8, IL18) in blood plasma have a statistically significant increased level of expression in breast cancer compared with the control group. To prove that the mRNA of these genes can be used as markers for early diagnosis of breast cancer, the sample of the group of breast cancer patients with stage 0 disease should be increased. To obtain statistically valid conclusions about the increased expression of the VEGF189 mRNA gene in the blood plasma of breast cancer patients, additional studies with an increase in the sample of the group of breast cancer patients with stage 0 disease are also required.