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Документ Expression of periferal core molecular clock genes in oral mucosa depends on the chronotype in patients with maxillofacial cellulitis(Journal of Oral Biology and Craniofacial Research, 2023-09) Lokes, Kateryna; Lychman, Vitaliy; Izmailova, Olga; Shlykova, Oksana; Avetikov, David; Kaidashev, Igor; Локес, Катерина Петрівна; Личман, Віталій Олександрович; Ізмайлова, Ольга Віталіївна; Шликова, Оксана Анатоліївна; Аветіков, Давид Соломонович; Кайдашев, Ігор ПетровичIntroduction: Accurate determination of the patient’s chronotype is one of the problems of personalized medicine. Recent studies have shown that determining of the expression of timing genes is a valuable method that can help gain molecular insight into a patient’s intrinsic circadian timing. Odontogenic cellulitis is very common pathology. Since acute inflammatory diseases are an urgent pathology, the time of surgical intervention can correspond depend on the time of the patient’s hospitalization. Materials and methods: The level of mRNA expression of peripheral circadian clock genes clock and bmal1, per1, cry1 in buccal epithelial cells in patients with odontogenic purulent inflammatory diseases of maxillofacial area in the morning and evening was investigated.Документ Influence of age, gender characteristics, chronotype on the expression of core clock genes Per1, Clock, Bmal1 and Cry1 in buccal epithelium(Acta Biochimica Polonica, 2022) Vasko, Maryna; Marchenko, Iryna; Shundryk, Maryna; Shlykova, Oksana; Tkachenko, Iryna; Kaidashev, Igor; Васько, Марина Юріївна; Марченко, Ірина Ярославівна; Шундрик, Марина Аркадіївна; Шликова, Оксана Анатоліївна; Ткаченко, Ірина Михайлівна; Кайдашев, Ігор ПетровичThe purpose of the study is to determine the expression of the core clock genes in buccal epithelial cells of healthy people with different chronotypes. Materials and methods. Fourteen healthy volunteers with a healthy periodontium and oral mucosa (7 women and 7 men) were selected for participation in the trial. The buccal epithelium sampling was performed at 07:00 am and 07:00 pm in one day by cytological brush. The surveyed patients were examined chronotypically using the Horn-Ostberg test. The determination of the mRNA expression of the Per1, Clock, Bmal1, Cry1 genes was performed by quantitative real-time PCR. Statistical analysis was performed using two-way analysis of variance followed by Bonferroni post hoc tests. Results. Per1 expression was higher in the morning, regardless of chronotype, age, and gender. The expression of the Clock demonstrated the prevalence of the evening in both chronotypes, in both men and women. Bmal1 was better expressed in the evening, regardless of age, gender, and chronotype. The expression of Cry1 did not show statistically significant differences between the indicators. Conclusions. The evening expression of Clock was higher in people with the evening chronotype than in people with the morning chronotype. The chronotype did not show any effect on the expression of Per1, Bmal1, and Cry1. Age and sex did not show any effect on the expression of the core clock genes.Документ Interleukin-26 is associated with the level of systemic inflammation and lung functions in obese and non-obese moderate-to-severe asthmatic patients(2022) Avramenko, Yanina; Izmailova, Olha; Shlykova, Oksana; Kaidashev, Igor; Авраменко, Яніна Миколаївна; Ізмайлова, Ольга Віталіївна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор ПетровичIntroduction: Obese asthma is a complex syndrome, which includes different phenotypes of disease. At present, these phenotypes only have started to acquire a suffcient understanding. It was suggested that IL-26 is a potential biomarker of disease severity in asthma without signs of Th2-mediated infammation. In this study, we investigated the serum and exhaled levels of IL-26 and its associations with the level of systemic infammation, lung functions, and body weight in obese and non-obese moderate-to-severe asthmatic patientsMaterial and methods: The study included 10 healthy subjects, 10 obese subjects without lung pathologies, 10 non-obese asthmatics (NOA) (BMI 18.5–24.9 kg/m2 ), and 40 obese asthmatics (OA) (BMI 25.0–49.9 kg/m2 ). During the visit, patients’ examination and spirometry with the bronchodilator reversibility test were conducted, the exhaled breath condensate (EBC) was obtained, and the blood samples were collected. The level of IL-26, interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), TNF-α, interleukin-10 (IL-10), total and specifc immunoglobulin E (IgE), and high sensitive C reactiveprotein (hs-CRP) were measured using the ELISA kits. Statistical comparison between 2 groups was analyzed using the Mann–Whitney rank-sum test. Chi-square with Yates’ correction was used to compare frequencies. Spearman’s rank test was used for correlating nonparametric variables. The Receiver Operating Characteristic (ROC) curve and the area under ROC curve (AUC) were used for evaluating the diagnostic power of IL-26 as a possible biomarker. Results: NOA had a reversible airway obstruction with reduced FEV1, FEV1/FVC, FVC 25/75, and positive post-bronchodilator test (PBT), signifcantly increased serum levels of IL-10, IL-4, and slightly increased IL-26. NOA had signifcantly increased exhaled IL-26 in comparison with healthy subjects. The obese subjects had a normal ventilatory pattern without airway obstruction, and differences in serum IL-26, IL-10, and IL-4 concentrations in comparison with healthy subjects. Obese subjects had a signifcant escalation of hs-CRP and no differences in the levels of exhaled IL-26, IL-10, and hs-CRP as compared with healthy subjects. OA had reduced FEV1, FEV1/FVC, and FEV25–75 in comparison with non-obese asthmatics. OA had elevated IL-26, IL-10, IL-4, and hs-CRP concentrations as compared with healthy subjects. These patients had a partial similarity with both non-obese asthmatics (elevated IL-26, IL-10, and IL-4) and obese subjects (elevated, IL-1β, IL-6, TNF-α, hs-CRP). OA had a reduced concentration of exhaled IL-26 in comparison with NOA and elevated exhaled IL-10 in comparison with obese subjects. Furthermore, OA had an increased concentration of IL-1β and TNF-α in comparison with healthy individuals and NOA. Exhaled IL-26 concentration distin-guished non-obese asthmatics from healthy subjects, asthmatic patients from non-asthmatics (healthy and obese subjects), all asthmatic patients from non-asthmatics (healthy and obese subjects).Conclusions: Exhaled IL-26 elevated in obese and non-obese moderate-to-severe asthmatic patients. Exhaled IL-26 might be a perspective biomarker in non-obese and obese asthmatics. The obese asthmatic phenotype comprised the combined systemic and local airway infammation.Документ Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes(2024-05-31) Kabaliei, Alina; Palchyk, Vitalina; Izmailova, Olga; Shynkevych, Viktoriya; Shlykova, Oksana; Kaidashev, Igor; Кабалєй, Аліна Вікторівна; Пальчик, Віталіна Вікторівна; Ізмайлова, Ольга Віталіївна; Шинкевич, Вікторія Ігорівна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор ПетровичIntroduction. PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Methods. Healthy adult male BALB/c mice were randomly divided into three equal groups ( in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 μl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. Result. The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in β-cell numbers between groups. Conclusion. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.Документ Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population(Acta Biomed, 2023-02-13) Izmailova, Olga; Shlykova, Oksana; Kabaliei, Alina; Vatsenko, Anastasia; Ivashchenko, Dmytro; Dudchenko, Maksym; Volianskyi, Andrii; Zelinskyy, Gennadiy; Koval, Tetiana; Dittmer, Ulf; Kaidashev, Igor; Ізмайлова, Ольга Віталіївна; Дудченко, Максим Олександрович; Іващенко, Дмитро Миколайович; Кабалєй, Аліна Вікторівна; Волянський, Андрій Юрійович; Дітмер, Ульф; Зелінський, Геннадій; Шликова, Оксана Анатоліївна; Ваценко, Анастасія Ігорівна; Коваль, Тетяна Ігорівна; Кайдашев, Ігор ПетровичGene polymorphism, coding the host proteases, which are involved in the virus entry into the cells can influence the susceptibility to and mortality from coronavirus disease 19 (COVID-19). Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that ex-erts such influence. The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population. Methods: The study population consisted of the Ukrainian population with COVID-19: patients without oxygen therapy (n=62), with non-invasive (n=92) and invasive (n=35) oxygen therapy, as well as control subjects (n=92). Al-lelic polymorphisms of ace2 rs4240157, tmprss2 rs12329760, and tmprss11a rs353163 were determined by real-time PCR, and cd147 rs8259 polymorphism was detected by PCR with subsequent restrictase analysis. We compared investigated polymorphisms distribution with other populations by meta-analysis. Results: Our study is the first to obtain data about the distribution of investigated gene polymorphisms in the Ukrainian population: tmprss2 rs12329760 – CC 60.9%, CT 35.9%, TT 3.2%; tmprss11a rs353163 – CC 46.7%, CT 40.2%, TT 13.1%; ace2 rs4240157 – CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%; cd147 rs8259 – TT 60.9%, AT 32.6%, AA 6.5%. This distribution was similar to the Northern, Western and Southern European populations. There was a statistically significant difference in the frequency of tmprss2 polymorphic geno-types CC 57.1%, CT 28.6%, and TT 14.3% (P<0.05) in COVID-19 patients with invasive oxygen therapy in comparison with non-invasive oxygen therapy. This tmprss2 mutation occurs in the scavenger receptor cysteine-rich (SRCR) domain and might be important for protein-protein interaction in a calcium-depend-ent manner. Conclusions: Our study indicated the presence of an association between the tmprss2 rs12329760 polymorphism and the severity of COVID-19 in the Ukrainian population.Документ PPARG agonist pioglitazone influences diurnal kidney medulla mRNA expression of core clock, inflammation- , and metabolism- related genes disrupted by reverse feeding in mice(Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society, 2022-11) Izmailova, Olga; Kabaliei, Alina; Shynkevych, Viktoriya; Shlykova, Oksana; Kaidashev, Igor; Ізмайлова, Ольга Віталіївна; Кабалєй, Аліна Вікторівна; Шинкевич, Вікторія Ігорівна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор ПетровичThis study examined the influence of PPARG activation by pioglitazone (PG) on the mRNA of core clock, inflammation‐ and metabolism‐related genes in the mouse kidney medulla as well as urinary sodium/potassium excretion rhythms disrupted by reverse feeding. Mice were assigned to daytime feeding and nighttime feeding groups. PG 20 mg/kg was administered at 7 am or 7 pm. On day 8 of the feeding intervention, mice were killed at noon and midnight. Kidney medulla expression of Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, Per2, Nfe2l2, Pparg, and Scnn1g was determined by qRT PCR. We measured urinary K+, Na+, urine volume, food, and H2O intake. The reverse feeding uncoupled the peripheral clock gene rhythm in mouse kidney tissues. It was accompanied by a decreased expression of Nfe2l2 and Pparg as well as an increased expression of Rela and Scnn1g. These changes in gene expressions concurred with an increase in urinary Na+, K+, water excretion, microcirculation disorders, and cell loss, especially in distal tubules. PG induced the restoration of diurnal core clock gene expression as well as Nfe2l2, Pparg, Scnn1g mRNA, and decreased Rela expressions, stimulating Na+ reabsorption and inhibiting K+ excretion. PG intake at 7 pm was more effective than at 7 am.Документ PPARG stimulation restored lung mRNA expression of core clock, inflammation- and metabolism-related genes disrupted by reversed feeding in male mice(John Wiley & Sons Inc., 2023-09-13) Shlykova, Oksana; Izmailova, Olga; Kabaliei, Alina; Palchyk, Vitalina; Shynkevych, Viktoriya; Kaidashev, Igor; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна; Кабалєй, Аліна Вікторівна; Пальчик, Віталіна Вікторівна; Шинкевич, Вікторія Ігорівна; Кайдашев, Ігор ПетровичThe circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating rhythm. Peroxisome proliferator-activated receptor gamma (PPARG) is a key molecule involved in circadian rhythm regulation, lung functions, and metabolic processes. We described the effect of the PPARG agonist pioglitazone (PZ) on the diurnal mRNA expression profile of core circadian clock genes (Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, and Per2) and metabolism- and inflammation-related genes (Nfe2l2, Pparg, Rela, and Cxcl5) in the male murine lung disrupted by reversed feeding (RF). In mice, RF disrupted the diurnal expression pattern of core clock genes. It decreased Nfe2l2 and Pparg and increased Rela and Cxcl5 expression in lung tissue. There were elevated levels of IL-6, TNF-alpha, total cells, macrophages, and lymphocyte counts in bronchoalveolar lavage (BAL) with a significant increase in vascular congestion and cellular infiltrates in male mouse lung tissue. Administration of PZ regained the diurnal clock gene expression, increased Nfe2l2 and Pparg expression, and reduced Rela, Cxcl5 expression and IL-6, TNF-alpha, and cellularity in BAL. PZ administration at 7 p.m. was more efficient than at 7 a.m.Документ Prevalence of polymorphic alleles 2258G / A gene TLR2 and its relationship with some immunological parameters among patients with allergic rhinitis(Національна академія медичних наук України, ДУ «Національний інститут фтизіатрії і пульмонології ім. Ф. Г. Яновського НАМН України», Асоціація спеціалістів з проблем бронхіальної астми та алергії України, 2013) Sakevych, Victoria D.; Shlykova, Oksana; Bobrova, Nelia A.; Kaydashev, Igor P.; Сакевич, Вікторія Дмитрівна; Шликова, Оксана Анатоліївна; Боброва, Нелля Олександрівна; Кайдашев, Ігор ПетровичIn the studied polymorphisms Asp299Gly TLR4 gene of patients with AR frequency of «wild-type» TLR2 GG genotype was 93.3 %, the frequency of heterozygous genotype GA–6,6 %, mutant genotype AA was not detected. As a result of the studies found significant differences between the groups of patients with AR with the presence of mutant alleles 2258G / A TLR2 gene and homozygous carriers of «wild» alleles in terms of CD4 + (U (n = 42; n = 3) = 12,00; p = 0,020). Group of patients with mutant AR alel- lyu 2258G / A gene for TLR2 differ significantly higher value of lympho- cytes (U (n = 42; n = 3) = 11,50; p = 0,019) from a group of patients with AR homozygous carriers of “wild” alleles. This study makes it possible to speculate polymorphism 2258G/A gene TLR2 is important in determining the course of the disease, confirming the pathogenetic link between innate and adaptive immunity in ARДокумент Prevention of preeclampsia in pregnant women with obesity(Journal of Education, Health and Sport, 2021-03) Zelinka-Khobzey, Marta; Tarasenko, Kostiantyn; Mamontova, Tetiana; Shlykova, Oksana; Зелінка-Хобзей, Марта Миколаївна; Тарасенко, Костянтин Володимирович; Мамонтова, Тетяна Василівна; Шликова, Оксана АнатоліївнаReducing the occurrence of preeclampsia is one of the key tasks in modern obstetrics, especially in pregnant women with concomitant obesity, who are at high risk for preeclampsia, the leading pathogenetic segment of which is endothelial dysfunction. The purpose of this work is to evaluate the effectiveness of the integrated therapeutic and preventive complex (TPC) in order to prevent preeclampsia in pregnant women. These parameters were evaluated using such markers as the concentration of vascular endothelial growth factor (VEGF) in blood serum and the content of circulating endothelial microparticles (CEM) CD32+CD40+ in peripheral blood in pregnant women with obesity of varying severity over the course of treatment we proposed. 110 pregnant women were included in the study: women with physiological body weight (n=26); women with class I obesity (n=42), and women with class II-III obesity. The groups of pregnant women with concomitant obesity were divided into two equal subgroups; one of the subgroups received the TPC (acetylsalicylic acid, calcium supplements, L-arginine, diosmin). The findings obtained demonstrate a significant improvement of endothelial status over the course of the therapy that is manifested with an increase in the serum VEGF concentration and a decrease in the content of CD32+CD40+ CEM in the peripheral blood. Our clinical assessment of pregnancy course, childbirth and the postpartum period in women with obesity and physiological body weight has shown a decrease in the occurrence of complications due to taking the integrated TPC. We have registered a decrease in the incidence of preeclampsia, placental dysfunction, occurrence of miscarriage, operative delivery and postpartum complications.Документ Нейротрофічний фактор мозку як маркер відновлення моторних та когнітивних функцій у гострому періоді кардіоемболічного та атеротромботичного ішемічного інсульту(2022) Гавловська, Ярослава Юріївна; Литвиненко, Наталія Володимирівна; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна; Гавловський, Олександр Леонідович; Шкодіна, Анастасія Дмитрівна; Havlovska, Yaroslava; Lytvynenko, Nataliia; Shlykova, Oksana; Izmailova, Olga; Havlovskyi, Oleksandr; Shkodina, AnastasiiaЦеребральний ішемічний інсульт - одне з найбільш поширених захворювань, що спричиняють психоемоційні, когнітивні та рухові розлади. Сучасні дослідження спрямовані на пошук біологічних маркерів ураження головного мозку при діагностиці інсультів, зокрема, фізичних, візуалізаційних, електрофізіологічних, гістологічних, генетичних та нейрональних, визначення яких може прискорити диференційну діагностику. Мета дослідження – оцінити рівень нейротрофічного фактору мозку в крові, стан моторних і когнітивних функцій в гострому періоді ішемічного інсульту на 1 та 14 добу, а також можливість використання рівня нейротрофічного фактору мозку крові в якості маркера відновлення рухової та інтелектуально-мнестичної сфери при атеротромботичному та кардіоемболічному підтипах ішемічного інсульту. У дослідження було включено 34 особи з діагнозом гострий ішемічний інсульт. Залежно від результатів клінічного обстеження пацієнтів було розподілено на 2 групи: група 1 – пацієнти, в яких ішемічний інсульт виник внаслідок атеросклеротичного ураження судин каротидної системи з розвитком оклюзії за механізмом атеротромбозу (17 осіб), група 2 – пацієнти, у яких ішемічний інсульт виник внаслідок ураження судин каротидної системи з розвитком оклюзії за кардіоемболічним механізмом (17 осіб). Для порівняння клініко-лабораторних показників додатково було виділено контрольну групу (пацієнти неврологічного відділення, які не мали ураження центральної нервової системи - 11 осіб). Обстеження пацієнтів проведено на 1 та 14 добу захворювання. Моторні функції оцінювали за ступенем повсякденної активності життя, що визначали за індексом Бартел, стан когнітивних функцій - за шкалою Mini- Mental State Examination. Індекс Бартел на 1 добу гострого періоду ішемічного інсульту перебував в межах легкої залежності для кардіоемболічного підтипу та помірної - для атеротромботичного. Протягом 14 днів у досліджуваних пацієнтів обох груп відбувалосязростання індексу до рівня повної незалежності у групі 1 та легкого ступеню залежності у групі 2. У обстежених пацієнтів із ішемічним інсультом було визначено середні значення за шкалою Mini-Mental State Examination на рівні помірного когнітивного дефіциту на 1 добу при обох підтипах ішемічного інсульту. Відновлення когнітивних функцій протягом 14 днів після ішемічного інсульту відбувалося тільки у другій групі до легких когнітивних розладів. Концентрація нейротрофічного фактору мозку на 1 добу ішемічного інсульту різко знижувалася порівняно з контрольною групою. Отримані результати дозволяють розглядати визначення мозкового нейротрофічного фактору об’єктивним біомаркером як тяжкості перебігу кардіоемболічного та атеротромботичного ішемічного інсульту, так іпрогнозу відновлення моторних і когнітивних функцій