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Allele С (rs5186) of at1r is associated with the severity of COVID-19 in the Ukrainian population
(2022) Izmailova, O.; Shlykova, O.; Vatsenko, A.; Ivashchenko, D.; Dudchenko, M.; Koval, T.; Kaidashev, I.; Ізмайлова, Ольга Віталіївна; Шликова, Оксана Анатоліївна; Ваценко, Анжела Володимирівна; Іващенко, Дмитро Миколайович; Дудченко, Максим Олександрович; Коваль, Тетяна Ігорівна; Кайдашев, Ігор Петрович
The severity of SARS-CoV-2 induced coronavirus disease 19 (COVID-19) depends on the presence of risk factors and the hosts’ gene variability. There are preliminary results that gene polymorphisms of the renin- angiotensin system can infuence the susceptibility to and mortality from COVID-19. Angiotensin II type 1 receptor (AT1R) might be a gene candidate that exerts such infuence. The aim of this study was to elaborate on the association between A1166C at1r polymorphic variants and the susceptibility to and severity of COVID-19 in the Ukrainian population. Methods: The study population consisted of the Ukrainian population (Poltava region) with COVID-19, divided into three clinical groups in accordance with oxygen requirement: patients without oxygen therapy (n = 110), with non-invasive (n = 136) and invasive (n = 36) oxygen therapy. The A1166C polymorphism of the at1r was determined by polymerase chain reaction with subsequent restrictase analysis. In an attempt to better explain the role of the A1166C at1r polymorphism we compared its association with COVID-19, essential hypertension (n = 79), renoparenchimal hypertension (n = 30) and dyscirculatory en- cephalopathy (n = 112). The data for this comparison were obtained by meta-analysis. Results: We observed signifcant differences in the frequency of AA, AC and CC genotypes in the groups of COVID- 19 patients with non-invasive and invasive oxygen therapy in comparison with control subjects as well as in the frequency of combined AC + CC genotype between the groups of COVID-19 patients with any types of oxygen therapy and patients without oxygen therapy. The frequency of the 1166C allele was higher in COVID-19 patients with invasive oxygen therapy (OR = 2.06; CI (1.20–3.53); p = 0.013). We obtained important results indicating that there were no differences between the frequency of at1r polymorphisms in patients with cardiovascular disease and severe COVID-19 with invasive oxygen therapy as well as those who died due to COVID-19. Conclusion: Our study indicated the presence of an association between the A1166C at1r polymorphisms and the severity of COVID-19 in the Ukrainian population. It seems that in carriers of 1166C at1r, the severity of COVID- 19 and oxygen dependency is higher as compared to the A allele carriers, possibly, due to cardiovascular disorders.
Analysis of specific groups of microorganisms isolated from atherosclerotic coronary arteries of patients depending on Asp299Giy polymorphism of TLR4 gene.
(Вищий державний навчальний заклад України "Українська медична стоматологічна академія", 2013) Skochko, О.; Vesnina, L.; Bobrova, N.; Shlykova, O.; Mamontova, T.; Izmailova, O.; Kaidashev, I. P.; Кайдашев, Ігор Петрович; Скочко, Ольга Вікторівна; Весніна, Людмила Едуардівна; Боброва, Нелля Олександрівна; Шликова, Оксана Анатоліївна; Мамонтова, Тетяна Василівна; Ізмайлова, Ольга Віталіївна
The aim of this work was to establish the presence of specific groups of microorganisms, including paradontopathogenic in atherosclerotic plaque and surrounding tissues and the dependence of microbial contamination of polymorphism 896A / G gene TLR4 (rs4986790), and to identify the possible relationship of atherosclerosis and Asp299Giy gene polymorphism TLR4 in patients with coronary heart disease (CHD). Materials and methods: The 31 autopsies of coronary arteries from patients whodied from coronary arteries disease and 5 from healthy individuals. Results and discussions: The presence of periodontal pathogenic microorganisms in atherosclerotic plaques was observed in 83,9%. In 51,6% two or more species of microorganisms were found. Only in 11,1%> samples with atherosclerotic plaques the microorganisms were found in undamaged tissues. The patients who died from coronary arteries disease had 299Giy allele of TLR4 gene more frequent than healthy individuals (p=0,04) OR 2,92 (1,15-7,41). The presence of TLR4 gene polymorphic allele G in the individual genotype determines the increased contamination of atherosclerotic plaque tissues by the representatives of the following genera: Lactobacillus sp, Enterobacterium sp, Sneathia sp. /Leptotrihia sp. /Fusobacterium sp, Mobiiuncus sp. /Corynebacterium sp., Peptostreptococcus sp. The emergence of new correlation pairs with participation of Lachnobacterium sp. /Corynebacterium sp. among the carriers of G allele has been revealed via the intragroup correiation analysis. Conclusion: The obtained results confirm the possible involvement of the represented groups of microorganisms in the pathogenesis of atherosclerosis and the role of the TLR4 gene polymorphic variant G in the increased microbial contamination of the coronary arteries tissues. The presence of299Giy allele of TLR4 gene increases the risk of this disease.
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, K.; Lychman, V.; Izmailova, O.; Shlykova, O.; Avetikov, D.; Kaidashev, I.; Локес, Катерина Петрівна; Личман, Віталій Олександрович; Ізмайлова, Ольга Віталіївна; Шликова, Оксана Анатоліївна; Аветіков, Давид Соломонович; Кайдашев, Ігор Петрович
Introduction: 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.
Features of NF-κB -mediated signal transduction and development of systemic inflammation in patients with diseases of internal organs are determined by microbial factor and individual reactivity of the body (review of own research findings)
(Вищий державний навчальний заклад України "Українська медична стоматологічна академія", 2015) Vesnina, L.; Izmailova, O.; Shlykova, O.; Kaidashev, I. P.; Кайдашев, Ігор Петрович; Весніна, Людмила Едуардівна; Ізмайлова, Ольга Віталіївна; Шликова, Оксана Анатоліївна
The paper identifies the etiological significance of periodontopathogenic microflora in the initiation of low-intensity systemic inflammation, which together with insulin resistance and lipid metabolism determines the development of atherosclerosis and coronary heart disease. On the basis of obtained data, the paper substantiates the concept of permanent activation of transcription factor NF-κB as the molecular foundation of systemic inflammation and other components that form the metabolic syndrome. The role of polymorphic variants of TLR 2,4,3,6 genes in shaping the individual reactivity of patients has been determined. The participation of genetic variation of receptor and structural proteins in determining the individual sensitivity, clinical course and complications of infectious diseases – hepatitis C, influenza, and EBV-viral infection has been justified. The up-to-date role of fundamental processes of innate and acquired immunity in the pathogenesis of atopic dermatitis, allergic rhinitis and bronchial asthma has been demonstrated. The efficiency of developed methods of therapy with additional inclusion of metformin and pioglitazone has been demonstrated, the application of pharmacogenetic approach to treatment has been substantiated. The obtained results will contribute to the formation of a systematic approach to the development and use of new technologies for prevention and effective pharmacogenetic treatment of diseases which are based on chronic inflammation.
Host gene variability and SARS-CoV-2 infection: A review article
(2021) Kaidashev, I.; Shlykova, O.; Izmailova, O.; Torubarа, O.; Yushchenko, Ya.; Tyshkovska, T.; Kyslyi, V.; Belyaeva, A.; Maryniak, D.; Кайдашев, Ігор Петрович; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна; Торубара, Олександра Олексіївна; Ющенко, Яна Олександрівна; Кислий, Владислав Федорович; Мариняк, Дар'я Костянтинівна; Бєляєва, Антоніна Олександрівна
SARS-CoV-2 is a global threat that inﬂuenced healthcare systems around the world. This virus caused an infection in humans with different clinical signs and syndromes, severity, and mortality. The key components of the COVID-19 molecular pathogenesis are coronavirus entry and replication, antigen presentation, humoral and cellular immunity, cytokine storm, coronavirus immune evasion. The analysis of recent literature displayed possible molecular targets in the key components of the COVID-19 pathogenesis. Some of these targets might have gene polymorphisms that inﬂuenced the COVID-19 course. Un- fortunately, several ﬁndings are still putative or extrapolated from SARS and MERS experimental investigations orclinical trials. We systematised original data about gene polymorphisms of possible molecular targets and associations with the COVID-19 course. Most data were obtained for angiotensin-converting enzymes 1 and 2, TMPRSS2 gene polymorphisms. Only a few results were found for gene polymorphisms of adhesion molecules, interferon system components, cytokines, and transcriptional factors, oxidative stress and metabolic molecules, as well as haemocoagulation. Understanding the host gene variability and its associations with COVID-19 can provide insights into the disease pathogenesis, individual susceptibility to SARS-CoV-2 infection, severity, complications, and mortality prognosis for the disease. Besides, these data might help in the identiﬁcation of appropriate targets for intervention.
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, M.; Marchenko, I.; Shundryk, M.; Shlykova, O.; Tkachenko, I.; Kaidashev, I.; Васько, Марина Юріївна; Марченко, Ірина Ярославівна; Шундрик, Марина Аркадіївна; Шликова, Оксана Анатоліївна; Ткаченко, Ірина Михайлівна; Кайдашев, Ігор Петрович
The 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.
Influence of metformin on lipid мetabolism and chronic inflammation in the liver тissues of mice on a diet rich in fructose
(Вищий державний навчальний заклад України "Українська медична стоматологічна академія", 2014) Shlykova, O.; Mikityuk, M.; Bobrova, N.; Izmailova, O.; Mamontova, T.; Baranova, A.; Vesnina, L.; Kaidashev, I. P.; Кайдашев, Ігор Петрович; Шликова, Оксана Анатоліївна; Микитюк, Марина Володимирівна; Боброва, Нелля Олександрівна; Ізмайлова, Ольга Віталіївна; Мамонтова, Тетяна Василівна; Баранова, Алла Федорівна; Весніна, Людмила Едуардівна
The effect of metformin on lipid metabolism and the expression of pro-inflammatory factors in the liver tissue of mice that were on a diet rich in fructose (DRF) (60 g fructose / 100 g of food) has been studied. The concentrations of total cholesterol (TC), triglycerides (TG), ceruloplasmin (CP), glucose in serum and mRNA expression of inhibitor of NF-kB (IkBα), mRNA of tumor necrosis factor α (TNFα) have been determined in homogenates of liver tissues in 3-monthsaged mice of BALBc line weighing 25-30 g. It has been demonstrated that increasing the content of fructose in the diet leads to increased concentrations of glucose, TC and TG in the blood of mice. Manifestations of systemic inflammatory response become stronger, as evidenced by the increase in CP in the blood serum and the expression level of mRNA of TNFα in liver tissues of animals that were on a DRF. Metformin in the dose of 50 mg / kg per day reduced the production of triglycerides in the blood serum of mice that were on a DRF; it contributed to the normalization of hepatic gluconeogenesis. Administering metformin caused anti-inflammatory effect by lowering serum CP and expression of mRNA of TNFα in liver tissues of these animals. Thus, the data suggest the protective effect of metformin on lipid metabolism and the expression of pro-inflammatory factors associated with NF-kB-signaling pathway in the liver tissues of mice which were on a DRF.
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, Ya.; Izmailova, O. ; Shlykova, O.; Kaidashev, I.; Авраменко, Яніна Миколаївна; Ізмайлова, Ольга Віталіївна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор Петрович
Introduction: 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 patients Material 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.
Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes
(2024-05-31) Kabaliei, A.; Palchyk, V.; Izmailova, O.; Shynkevych, V.; Shlykova, O.; Kaidashev, I.; Кабалєй, Аліна Вікторівна; Пальчик, Віталіна Вікторівна; Ізмайлова, Ольга Віталіївна; Шинкевич, Вікторія Ігорівна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор Петрович
Introduction. 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.
Pathogenic mechanisms of generalized periodontitis from the position of polymorphism of nuclear transcription factor NF- KBI
(Тернопільський державний медичний університет імені І. Я. Горбачевського, 2017-05) Hasiuk, N.; Vesnina, L.; Shlykova, O.; Izmailova, O.; Гасюк, Наталія Володимирівна; Весніна, Людмила Едуардівна; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна
Background. Periodontal diseases are a topical issue of contemporary dentistry because they are accompanied by severe morphological and functional disorders of maxillodental system; and are characterized by polyetiology and a number of metabolic disorders. The purpose of this study was to substantiate the pathogenic mechanisms of generalized periodontitis in relation to polymorphism of nuclear transcription factor NF- κB1. Objective. The aim of the study was to determine the genetic factors in the development of generalized periodontitis and the relationship of this parameter with immunohistochemical affiliation for cellular infiltrate of the lamina propria of gum at this nosology in young people. Hence, 2 groups were formed: І – control and II – observational. Methods. Polymorphic gene section NF-κB1 was determined using the cells of buccal epithelium of the examined people by means of polymerase chain reaction. Collection of material was performed with sterile disposable dental brush, followed by the introduction of a reagent in ependorph with DNA Express reagent (LyTeh NPF, Russia). Genome deoxyribonucleic acid was isolated by DNA Express set (LyTeh, Moscow). Results. The lack of correlation in this case indicates that no matter how parameters change, relatively major genotype (Del/Del) in this case is unchanged and the determining factor causes the development of generalized periodontitis, clinical picture of which is rapidly progressing. Conclusions. Results of correlation analysis proved that genotype (Del/Del), as polymorphic variant of gene transcription factor NF-κB1, was significantly associated with the emergence of rapidly progressive periodontitis in young people.
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, O.; Shlykova, O.; Kabaliei, A.; Vatsenko, A.; Ivashchenko, D.; Dudchenko, M.; Volianskyi, A.; Zelinskyy, G.; Koval, T.; Dittmer, U.; Kaidashev, I.; 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 Петрович
Gene 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.
PPAR-γ agonist pioglitazone restored mouse liver m RNA expression of clock genes and inflammation-related genes disrupted by reversed feeding
(Hindawi, 2022) Fedchenko, T.; Izmailova, O.; Shynkevych, V.; Shlykova, O.; Kaidashev, I.; Федченко, Тетяна Юріївна; Ізмайлова, Ольга Віталіївна; Шинкевич, Вікторія Ігорівна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор Петрович
The master clock, which is located in the suprachiasmatic nucleus (SCN), harmonizes clock genes present in the liver to synchronize life rhythms and bioactivity with the surrounding environment. The reversed feeding disrupts the expression of clock genes in the liver. Recently, a novel role of PPAR-γ as a regulator in correlating circadian rhythm and metabolism was demonstrated. This study examined the influence of PPAR-γ agonist pioglitazone (PG) on the mRNA expression profile of principle clock genes and inflammation-related genes in the mouse liver disrupted by reverse feeding. Methods. Mice were randomly assigned to daytime-feeding and nighttime-feeding groups. Mice in daytime-feeding groups received food from 7 AM to 7 PM, and mice in nighttime-feeding groups received food from 7 PM to 7 AM. PG was administered in the dose of 20 mg/kg per os as aqueous suspension 40 μl at 7 AM or 7 PM. Each group consisted of 12 animals. On day 8 of the feeding intervention, mice were sacrificed by cervical dislocation at noon (05 hours after light onset (HALO)) and midnight (HALO 17). Liver expressions of Bmal1, Clock, Rev-erb alpha, Cry1, Cry2, Per1, Per2, Cxcl5, Nrf2, and Ppar-γ were determined by quantitative reverse transcription PCR. Liver expression of PPAR-γ, pNF-κB, and IL-6 was determined by Western blotting. Glucose, ceruloplasmin, total cholesterol, triglyceride concentrations, and ALT and AST activities were measured in sera by photometric methods. The null hypothesis tested was that PG and the time of its administration have no influence on the clock gene expression impaired by reverse feeding. Results. Administration of PG at 7 AM to nighttime-feeding mice did not reveal any influence on the expression of the clock or inflammation-related genes either at midnight or at noon. In the daytime-feeding group, PG intake at 7 PM led to an increase in Per2 and Rev-erb alpha mRNA at noon, an increase in Ppar-γ mRNA at midnight, and a decrease in Nfκb (p65) mRNA at noon. In general, PG administration at 7 PM slightly normalized the impaired expression of clock genes and increased anti-inflammatory potency impaired by reversed feeding. This pattern was supported by biochemical substrate levels—glucose, total cholesterol, ALT, and AST activities. The decrease in NF-κB led to the inhibition of serum ceruloplasmin levels as well as IL-6 in liver tissue. According to our data, PG intake at 7 PM exerts strong normalization of clock gene expression with a further increase in Nrf2 and, especially, Ppar-γ and PPAR-γ expression with inhibition of Nfκb and pNF-κB expression in daytime-feeding mice. These expression changes resulted in decreased hyperglycemia, hypercholesterolemia, ALT, and AST activities. Thus, PG had a potent chronopharmacological effect when administered at 7 PM to daytime-feeding mice. Conclusions. Our study indicates that reversed feeding induced the disruption of mouse liver circadian expression pattern of clock genes accompanied by increasing Nfκb and pNF-κB and IL-6 expression and decreasing Nrf2 and PPAR-γ. Administration of PG restored the clock gene expression profile and decreased Nfκb, pNF-κB, and IL-6, as well as increased Nrf2, Ppar-γ, and PPAR-γ expression. PG intake at 7 PM was more effective than at 7 AM in reversed feeding mice.
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, O.; Kabaliei, A.; Shynkevych, V.; Shlykova, O.; Kaidashev, I.; Ізмайлова, Ольга Віталіївна; Кабалєй, Аліна Вікторівна; Шинкевич, Вікторія Ігорівна; Шликова, Оксана Анатоліївна; Кайдашев, Ігор Петрович
This 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.
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, O.; Izmailova, O.; Kabaliei, A.; Palchyk, V.; Shynkevych, V.; Kaidashev, I.; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна; Кабалєй, Аліна Вікторівна; Пальчик, Віталіна Вікторівна; Шинкевич, Вікторія Ігорівна; Кайдашев, Ігор Петрович
The 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.
Predictors of myocardial ischemia and central hemodynamic disorders in patients with coronary heart disease
(2018) Kazakov, Yu.; Gorach, N.; Vakulenko, K.; Shlykova, O.; Izmaylova, O.; Казаков, Юрій Михайлович; Горач, Н.; Вакуленко, Костянтин Євгенійович; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна
Coronary heart disease (CHD) ranks first among mortality causes in the world over the years Present scientific studies prove the leading role of chronic systemic inflammation (CSI) in the onset and progression of atherosclerosis (ASVD), which has been the morphological basis of CHD . Taking into account the above-mentioned, it is relevant to study the interaction of components of the pathogenetic process in the ASVD and CHD, the factors of formation and progression of the specified pathology in order to determine the diagnostic markers for the development and destabilization of these diseases and developing rational therapeutic approaches. The purpose of our research was to study the relationship between the indicators of systemic inflammation, the lipid spectrum of blood and the structural and functional condition of the heart in patients with stable CHD, and the search for predictors of its progression
Predictors of myocardial ischemia and central hemodynamic disorders in patients with coronary heart disease
(2018) Kazakov, Yu.; Gorach, N.; Vakulenko, K.; Shlykova, O.; Izmaylova, O.; Казаков, Юрій Михайлович; Вакуленко, Костянтин Євгенійович; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна
Materials and methods. One-time, open-label, single group clinical trial involved 115 patients with CHD: stable angina pectoris, FC II, НF 0-І (62 men and 53 women aged 54±6.2). Patients were given laboratory and instrumental studies. The levels of total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides (TG) by sedimentation, fibrinogen (Fg) concentration in blood by gravimetric analysis, the level of cytokines (CK) in the blood (interleukin 1β (IL-1β), tumor necrosis factor (TNFα), interleukin 10 (IL-10)) by the immune enzyme method, the content of circulating endothelial microparticles (EMP) of CD32+CD40+ in blood by cytofluorometry, mRNA gene expression of kappa B-alpha inhibitor (IkBα) of the nuclear kappa B transcription factor (NF-kB) in mononuclear cells of the peripheral blood by real-time polymerase chain reaction (Real-time PCR) were being determined [4, 5, 6]. Echocardiography and the 24 hour Holter ECG monitoring were performed by the standard method. A correlation and regression analysis was conducted.
Prevalence of herpesviruses among combatants during the Russian-Ukrainian war
(34 Annual Meeting th of the Society for Virology, 2025-03) Koval, T.; Bodnar, V.; Zdor, O.; Loban, G.; Faustova, M.; Herasymenko, L.; Shlykova, O.; Izmailova, O.; Kabaliei, A.; Zelinskyy, G.; Schrammel, U.; Elsner, C.; Trilling, M.; Dittmer, U.; Kaidashev, I.; Коваль, Тетяна Ігорівна; Боднар, Вадим Анатолійович; Здор, Олег Іванович; Лобань, Галина Андріївна; Фаустова, Марія Олексіївна; Герасименко, Лариса Олександрівна; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна; Кабалєй, Аліна Вікторівна; Кайдашев, Ігор Петрович
The war in the Ukraine is an unprecedented stressor that has negative consequences for the health of the Ukrainian population. A significant number of Ukrainian soldiers suffers from clinical symptoms of anxiety, depression, and sleep disorders. It has been shown that changes in the immune regulation under the influence of stress are quite significant and can lead to health consequences, including the reactivation of latent infections, including herpesviruses. However, there is no reliable information on the possible consequences of a war on the spread and reactivation of herpesviruses such as HSV-1/2; VZV, CMV, EBV, and HHV-6
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, V. D.; Shlykova, O.; Bobrova, N. A.; Kaydashev, I. P.; Сакевич, Вікторія Дмитрівна; Шликова, Оксана Анатоліївна; Боброва, Нелля Олександрівна; Кайдашев, Ігор Петрович
In 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 AR
Resveratrol reduces the level of chronic systemic inflammation in stable coronary artery disease
(London : Open Access Text Pvt. Ltd, 2016-11) Chekalina, N.; Shlykova, O.; Mykytiuk, M.; Izmailova, O.; Vesnina, L.; Kazakov, Yu.; Kaidashev, I. P.; Кайдашев, Ігор Петрович; Чекаліна, Наталія Ігорівна; Шликова, Оксана Анатоліївна; Микитюк, Марина Володимирівна; Ізмайлова, Ольга Віталіївна; Весніна, Людмила Едуардівна; Казаков, Юрій Михайлович
This study aimed to investigate the effects of plant polyphenol of resveratrol on chronic systemic inflammation indicators of stable coronary artery disease. 85 patients with coronary heart disease were recruited and prescribed a standard therapy (β-blockers, statins, aspirin). 30 patients received resveratrol at a dose of 100 mg daily and the other serves as the control group. Cytokines and the expression of mRNA gene of inhibitor of kappa B α (IkBα) of nuclear factor of transcription kappa B (NF-kB) were determined. The results show that patients with coronary artery disease exhibited increased levels of interleukin-1β (IL-1β), tumor necrosis factor (TNFα), and IL-10 in the blood. Resveratrol treatment led to a reliable reduction IL-1β and TNFα, the content of IL-10 tended to reduce. In addition, we failed to notice any significant difference in the inhibitor of kappa B α (IkBα) of nuclear factor of transcription kappa B between groups. In conclusion, in patients with coronary artery disease, resveratrol shows anti-inflammatory properties via reducing the content of proinflammatory cytokines in the blood, such as IL-1β and TNFα.
SIRT1 contributes to polarization of peripheral blood monocytes by increasing STAT6 expression in young people with overweight and low-risk obesity
(Georgian Med News, 2021-04) Kolinko, L.; Shlykova, O.; Izmailova, O.; Vesnina, L.; Kaidashev, I.; Колинько, Людмила Михайловна; Шлыкова, Оксана Анатольевна; Измайлова, Ольга Витальевна; Веснина, Людмила Эдуардовна; Кайдашев, Игорь Петрович; Колінько, Людмила Михайлівна; Шликова, Оксана Анатоліївна; Ізмайлова, Ольга Віталіївна; Весніна, Людмила Едуардівна; Кайдашев, Ігор Петрович
Obesity contributes to the formation of low-intensity systemic inflammation with major participation of monocytes/macrophages. Nicotinamide adenine dinucleotide (NAD+ )-dependent deacetylase class III SIRT1 regulates the polarization of macrophages, controlling the inhibition of the M1 subpopulation and stimulating the activation of M2 macrophages. The aim of our study was to determine the regulatory role of SIRT1 in M1/M2 polarization of peripheral blood monocytes in young people with overweight and Class I obesity. 30 subjects of both gender, aged 18-25 years have been examined. Groups were formed by the BMI: the subjects with normal body weight (n=10, BMI 18.50–24.99 kg/m2 ), the subjects with overweight (n=10, BMI 25.00–29.99 kg/m2 ), the subjects with Class I obesity (n=10, BMI 30.00–34.99 kg/m2 ). Peripheral blood mononuclear suspension was isolated from venous blood. E. coli lipopolysaccharide (LPS) at a dose of 100 ηg/mL and γ-interferon (γIFN) at a dose of 100 ηg/mL were used to induce polarization of macrophages by the M1 phenotype. Unstimulated monocytes/macrophages were used as controls. The level of the stat1, stat6 and sirt1 gene expression was determined by Polymerase Chain Reaction Real-time PCR. The findings showed an increase in the level of the sirt1 gene expression with weight gain. The highest rates of sirt1 expression were found in IL-4-stimulated cells of the subjects with Class I obesity. It has been concluded that SIRT1 promotes M2 polarization of peripheral blood monocytes toward the antiinflammatory phenotype in young people with overweight and Class I obesity, mediated by increased stat6 gene expression. The direction of polarization toward the anti-inflammatory phenotype is indicated by a decrease in the stat/stat6 ratio and the formation of correlation between the sirt1 and stat6 expression in LPS and γIFN-stimulated cells and IL-4-stimulated cells.

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