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Документ A rare case of Bordetella avium pneumonia complicated by Raoultella planticola(John Wiley & Sons Ltd, 2020) Lavrenko, A.; Digtiar, N.; Gerasymenko, N.; Kaidashev, I.; Лавренко, Анна Володимирівна; Дігтяр, Наталія Іванівна; Герасименко, Наталія Дмитрівна; Кайдашев, Ігор ПетровичBordetella avium pneumonia immunocompromised the patient with subsequent complication by a rare opportunistic Raoultella planticola infection, which became a nosocomial pathogen in the healthcare setting. Пневмонія Bordetella avium знизила імунітет пацієнта з подальшим ускладненням рідкісною умовно-патогенною інфекцією Raoultella planticola, яка стала нозокоміальним патогеном у медичних закладах.Документ 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 ПетровичThe 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.Документ Clinical and genetic predictors and prognostic model of rapidly progressive hepatic fibrosis in chronic hepatitis C(Агенство медицинской информации Ассоциации деловой прессы Грузии, Академия медицинских наук Грузии, Международная академия наук, индустрии, образования и искусств США, 2016) Dubynska, G.; Sizova, L.; Koval, T. I.; Kovalova, O.; Kaidashev, I.; Дубинская, Галина Михайловна; Сизова, Людмила Михайловна; Коваль, Татьяна Игоревна; Ковалева, Елена Михайловна; Кайдашев, Игорь Петрович; Кайдашев, Ігор Петрович; Дубинська, Галина Михайлівна; Сизова, Людмила Михайлівна; Коваль, Тетяна Ігорівна; Ковальова, Олена МихайлівнаIntroduction. The search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. Materials and Methods. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. Results. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender – ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) – ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity – ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) – ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) – ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin – ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase – ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity – 85.5%, specificity – 68.3%, total number of the appropriate assignments – 76.8%, positive and negative predictive value – 74,7% and 88,0%, respectively, the AUC ROC-curve – 0.840). Conclusions. Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual approaches to prescribing antiviral therapy for CHC; Введение. Поиск факторов риска быстрого прогрессирования фиброза печени (ФП) при хроническом гепатите С (ХГС) является актуальной научно-практической задачей. Целью данного исследования была идентификация клинико-генетических предикторов и создание прогностической модели быстро прогрессирующего ФП при ХГС. Материалы и методы. Проведено ретроспективное когортное исследование 125 больных ХГС. Для статистической обработки данных применялись логистическая регрессия и ROC-анализ. Результаты. В результате анализа 46 потенциальных предикторов быстро прогрессирующего ФП при ХГС идентифицированы значимые: мужской пол – ОR=3,44 [95% СΙ 1,60-7,39], р=0,001; повышенные уровни аланинаминотрасферазы (АЛТ) – ОR= ОR=4,93 [95% СΙ 1,54-15,76], р=0,007, в частности, умеренная активность цитолиза – ОR=2,36, [95% СΙ 1,08-5,16]р=0,031; аспартатаминотрансферазы (АСТ) – ОR=3,65 [95% СΙ 1,41-9,43], р=0,007; γ-глутамилтранспептидазы (ГГТП) – ОR=3,63 [95% СΙ 1,73-7,61], р=0,001; общего билирубина – ОR=3,53 [95% СΙ 1,47-8,47], р=0,005); щелочной фосфатазы – ОR=9,18 [95% 1,11-75,80], р=0,039; титр; употребление алкоголя >40 г/сутки – ОR=3,53 [95% СΙ 1,36-9,17], р=0,009; генотип Gln11Gln гена TLR7 – ОR=4,56 [95% СΙ 1,57-13,22], р=0,005; наличие хронического холецистита и/или панкреатита – ОR=5,30 [95% СΙ 1,84-15,25], р=0,002. Создана прогностическая модель из 6 предикторов (уровень ГГТП>верхней границы нормы (ВГН), мужской пол, генотип Gln11Gln гена TLR7, хронический холецистит и/или панкреатит, уровни общего билирубина и АСТ>ВГН), которая продемонстрировала статистическую значимость (р=0,000) и высокие операционные характеристики (чувствительность – 85,5%, специфичность – 68,3%, общее количество правильных отнесений – 76,8%, позитивное и негативное предиктивное значение – 72,6%, и 82,7% соответственно, AUC ROC-кривой – 0,840).Документ Clinіcal and genetic predictors and prognostic model of rapidly progressive hepatic fibrosis in chronic hepatitis C(Тбилисский национальный государственный университет, 2016) Dubynska, G.; Sizova, L.; Koval, T. I.; Kovalova, O.; Kaidashev, I.; Дубинская, Галина Михайловна; Сизова, Людмила Михайловна; Коваль, Татьяна Игоревна; Ковалева, Елена Михайловна; Кайдашев, Игорь Петрович; Кайдашев, Ігор Петрович; Дубинська, Галина Михайлівна; Сизова, Людмила Михайлівна; Коваль, Тетяна Ігорівна; Ковальова, Олена МихайлівнаThe search for risk factors for rapid progression of hepatic fibrosis (HF) in chronic hepatitis C (CHC) is a topical scientific and practical task. The purpose of the study is to identify clinical and genetic predictors and create the prognostic model of rapidly progressive HF in CHC. A retrospective cohort study of 125 patients with CHC has been carried out. The logistic regression and ROC-analysis have been applied for statistical data processing. The resulting analysis of 46 potential predictors of rapidly progressive HF in CHC identified the following significant ctiteria: male gender – ОR=3.44 [95% СΙ 1.60-7.39], р=0.001; increased levels of alanine aminotransferase (ALT) – ОR=4.93 [95% СΙ 1.54-15.76], р=0.007, particularly, moderate cytolytic activity – ОR=2.36 [95% СΙ 1.08-5.16], р=0.031; aspartate aminotransferase (АSТ) – ОR=3.65 [95% СΙ 1.41-9.43] р=0.007; γ-glutamiltranspeptidase (GGTP) – ОR=3.63 [95% СΙ 1.73-7.61], р=0.001; total bilirubin – ОR=3.53 [95% СΙ 1.47-8.47], р=0.005; alkaline phosphatase – ОR=9.18 [95% 1.11-75.80], р=0.039; alcohol intake>40 g/day (ОR=3.53 [95% СΙ 1.36-9.17], р=0.009), Gln11Gln genotype of the TLR7 gene (ОR=4.56 [95% СΙ 1.57-13.22], р=0.005), presence of chronic cholecystitis and/or pancreatitis (ОR=5.30 [95% СΙ 1.84-15.25], р=0.002). The prognostic model, comprising 6 predictors (level of GGTP>upper limit of normal (ULN), male gender, Gln11Gln genotype of the TLR7 gene chronic cholecystitis and/or pancreatitis, levels of total bilirubin and АSТ>ULN) have been created, demonstrating the statistical significance (p=0.000) and high operational characteristics (sensitivity – 85.5%, specificity – 68.3%, total number of the appropriate assignments – 76.8%, positive and negative predictive value – 72,6% and 82.7%,, respectively, the AUC ROC-curve – 0.840). Use of the created model will help to predict the rapid progression of HF in CHC and form the risk-group, requiring individual approaches to prescribing antiviral therapy for CHC; Поиск факторов риска быстрого прогрессирования фиброза печени (ФП) при хроническом гепатите С (ХГС) является актуальной научно-практической задачей. Целью данного исследования была идентификация клинико-генетических предикторов и создание прогностической модели быстро прогрессирующего ФП при ХГС. Проведено ретроспективное когортное исследование 125 больных ХГС. Для статистической обработки данных применялись логистическая регрессия и ROC-анализ. В результате анализа 46 потенциальных предикторов быстро прогрессирующего ФП при ХГС идентифицированы значимые: мужской пол – ОR=3,44 [95% СΙ 1,60-7,39], р=0,001; повышенные уровни аланин-аминотрасферазы (АЛТ) – ОR= ОR=4,93 [95% СΙ 1,54-15,76], р=0,007, в частности, умеренная активность цитолиза – ОR=2,36, [95% СΙ 1,08-5,16]р=0,031; аспартатаминотрансферазы (АСТ) – ОR=3,65 [95% СΙ 1,41-9,43], р=0,007; γ-глутамилтранспептидазы (ГГТП) – ОR=3,63 [95% СΙ 1,73-7,61], р=0,001; общего билирубина – ОR=3,53 [95% СΙ 1,47-8,47], р=0,005); щелочной фосфатазы – ОR=9,18 [95% 1,11-75,80], р=0,039; титр; употребление алкоголя >40 г/сутки – ОR=3,53 [95% СΙ 1,36-9,17], р=0,009; генотип Gln11Gln гена TLR7 – ОR=4,56 [95% СΙ 1,57-13,22], р=0,005; наличие хронического холецистита и/или панкреатита – ОR=5,30[95% СΙ 1,84-15,25], р=0,002. Создана прогностическая модель из 6 предикторов (уровень ГГТП>верхней границы нормы (ВГН), мужской пол, генотип Gln11Gln гена TLR7, хронический холецистит и/или панкреатит, уровни общего билирубина и АСТ>ВГН), которая продемонстрировала статистическую значимость (р=0,000) и высокие операционные характеристики (чувствительность – 85,5%, специфичность – 68,3%, общее количество правильных отнесений – 76,8%, позитивное и негативное предиктивное значение – 72,6%, и 82,7% соответственно, AUC ROC-кривой – 0,840). Предложенная модель позволит определить быстро прогрессирующий ФП при ХГС и сформировать группы риска для индивидуального подхода при применении противовирусной терапии ХГС.Документ Effects of l-arginine and l-ornithine supplementations on the treatment of chronic periodontitis: A preliminary randomized short-term clinical trial(Elsevier Ltd., 2021-11-09) Shynkevych, V.; Kolomiiets, S.; Kaidashev, I.; Шинкевич, Вікторія Ігорівна; Коломієць, Світлана Веніамінівна; Кайдашев, Ігор ПетровичAbstract The growing interest in the possibilities of modulating macrophages in inflammatory diseases with therapeutic purpose has prompted the development of new approaches for the treatment of periodontitis. This randomized add-on open preliminary clinical study evaluated the short-term effects of L-arginine or L-ornithine as an adjuvant to scaling and root planing (SRP) in patients with chronic periodontitis. Materials and methods Seventy-five periodontitis patients were recruited and monitored clinically and immunologically at baseline (before SRP) and 30 ± 5 days after SRP. All patients were assigned by stratified randomization to SRP (SRP only, n = 25), Arg (SRP + L-arginine, n = 25) or Control (SRP + L-ornithine, n = 25) Group. The medicines were used according to available instructions for 10 and 15 days, respectively. During the study, all patients were on a stable diet, without changing their rations and regiments. As immunological monitoring immunohistochemical study of CD68+ and CD163 + single positive gingival macrophages for 5 patients per group in the same time-point was conducted. The data were statistically analyzed. Results Reduction of periodontal pocket depth (PPD) and bleeding on probing (BoP) was observed in all groups, with significant between-group differences for BoP in the Arg Group (p < 0.0001) at 30 days. The SRP and Arg groups demonstrated nonsignificantly increased density of CD68+ and CD163 + cells. The Orn Group showed an increase in the density of CD68+ and CD163 + macrophages at intragroup (p = 0.0066 and p < 0.0001) and between-group levels (p = 0.001 and p < 0.0001), and these changes corresponded to clinical PPD and BoP reduction. In the Arg and Orn groups at 30 days, CD163 + macrophages significantly predominated over CD68+ (p = 0.013, p < 0.0001). Conclusion The use of L-arginine and L-ornithine as an adjunct to SRP promotes additional limited immunological benefit in the treatment of periodontitis. Metabolic stimulation with L-ornithine, but not L-arginine, is preferable for CD163+ Mφs subpopulation in periodontitis-affected gingiva.Документ Etiology and efficacy of anti-microbial treatment for community-acquired pneumonia in adults requiring hospital admission in Ukraine(2022) Kaidashev, I.; Lavrenko, A.; Baranovskaya, T.; Blazbko, V.; Digtiar, N.; Dziublyk, O.; Gerasymenko, N.; Iasdyna, L.; Kryvetskyi, V.; Kuryk, L.; Rodionova, V.; Stets, R.; Vysbnyvetskyy, I.; Fesbcbenko, Yu.; Кайдашев, Ігор Петрович; Лавренко, Анна Володимирівна; Дігтяр, Наталія Іванівна; Герасименко, Наталія ДмитрівнаBackground and aim: Empiric therapy of community-acquired pneumonia (CAP) remains the standard care and guidelines are mostly based on published data from the United States or Europe. In this study, we determined the bacterial etiology of CAP and evaluated the clinical outcomes under antimicrobial treatment of CAP in Ukraine. Methods: A total of 98 adult subjects with CAP and PORT risk II-IV were recruited for the study. The sputum diagnostic samples were obtained from all patients for causative pathogen identification. Subjects were randomly assigned in a 1:1 ratio to receive delafloxacin 300 mg (n=51) or moxifloxacin 400 mg (n=47) with blinding placebo. The switch to oral treatment was after a minimum of 6 IV doses according to clinical criteria. The total duration of antibacterial treatment was 5-10 days. In vitro susceptibility of pathogens to delafloxacin and other comparator antibiotics was determined. Results: The most frequently isolated pathogens in adults with CAP were S. pneumoniae - 19.5%, M. pneumoniae - 15.3%, H. influenzae - 13.2%, S. aureus - 10.5%, K. pneumoniae - 10.1%, and H. parainfluenzae - 6.4%. All isolates of S. pneumoniae, S. aureus, M. pneumoniae had sufficient susceptibility to appropriate antibiotics. 9.0% of H. influenzae strains were susceptible to azithromycin. 94.8 % of patients had a successful clinical response to delafloxacin at the end of treatment and 93.9 % - at test-of-cure. Conclusions: In Ukraine, the major bacterial agents that induced CAP in adults were S. pneumoniae, M. pneumoniae, H. influenzae, S. aureus, K. pneumoniae, H. parainfluenzae, E. cloacae, L. pneumophila. Delafloxacin is a promising effective antibiotic for monotherapy for CAP in adults and could be used in cases of antimicrobial-resistant strains.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, 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 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 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 ОлександрівнаSARS-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.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, 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 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, Ya.; Izmailova, O. ; Shlykova, O.; Kaidashev, I.; 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 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.Документ 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 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 Modern aspects of the study of biomarkers in patients with diabetic kidney disease and type 2 diabetes(European Journal of Case Reports in Internal Medicine, 2023) Borzykh, O.; Mormol, I.; Lavrenko, A.; Avramenko, Ya.; Kaidashev, I. ; Борзих, Оксана Анатоліївна; Мормоль, Ірина Анатоліївна; Лавренко, Анна Володимирівна; Авраменко, Яніна Миколаївна; Кайдашев, Ігор ПетровичThe study was designed to evaluate the potential significance of the urine biomarkers for the early diagnosis and development of the personalized management plan for the patients with type 2 diabetes and associated kidney disease regardless of other complications.The study was designed to determine the significance of the modern serum and urine biomarkers for the diagnosis and development of the personalized management plan for the patients with type 2 diabetes and associated kidney disease. The initial data results confirm the importance of setting the new approaches to the early diagnosis and reasonable personalized treatment for patients with type 2 diabetes and cardio-vascular and renal complications, as this can work as an effective tool for the prevention of further complications and so the improvement of prognosis and the quality of life for such patients.Документ Patterns in Google Trends terms reporting rhinitis and alternaria season in Ukraine(Полтавський державний медичний університет, 2020) Kaidashev, I.; Morokhovets, H.; Rodinkova, V.; Bilous, O.; DuBuske, L. M.; Bousquet, J; Кайдашев, Ігор Петрович; Мороховець, Галина ЮріївнаThis article presents a literary review on the issue of using the innovative Web-based surveillance tools provided by Google Trends (GT) in order to determine the precise onset of the mold spore season. Mold allergy is a considerable trigger for the development of widespread respiratory disorders – allergic rhinitis and asthma, chronic obstructive pul-monary diseases, etc.The study aimed to examine the seasonality of GT queries in Ukraine with Alternaria pollen counts. Spores of the genus Alternaria belong to one of the most prevailing constituents of the air in all regions of the world. They form infectious inoculum of numerous plant species as well as severe inhaled allergies. A precise definition of the mold spore season onset is crucial to confirm the mold allergy diagnosis and to develop personalized treatment for patients with allergic rhinitis and asthma. The most comprehensive approach is the development of a pan-European sen-tinel network, which combines all these strategies. GT may be a useful tool in the differentiation of the mold spore sea-sons, especially when they overlap as in the case ofAmbrosia. Four terms “running nose”, “tears”, “dyspnea”, and “cough” (in Cyrillic equivalents) are required in Ukraine to account for Alternaria spore exposure. The combination of GT tools with spore counts may be used in large-scale epidemiological studies. The development of a pan-European sentinel network for allergic diseases has raised the problem of translating the Google search terms into different European lan-guages. GT analysis is a tool to improve and tailor our communication with patients and the general public along with building our sentinel network languages. Our data can be used as a successful tool for allergy patients to prevent or minimize exposure during the mold spore season. У статті представлено літературний огляд проблеми використання інноваційних інструментів веб-спостереження, зокрема Google Trends (GT), з метою визначення точного початку сезону спор цвілі. Алергія на цвіль є значним пусковим механізмом розвитку поширених респіраторних розладів –алергічного риніту та астми, хронічного обструктивного захворювання легень тощо. Метою дослідження було вивчення сезонності запитів GT в Україні з кількістю спор Alternaria. Спори роду Alternaria – найпоширеніша складова повітря у всіх регіонах світу, що утворюють інфекційний посівний матеріал численних видів рослин, а також спричиняють важку інгаляційну алергію. Точне визначення настання сезону спор цвілі є вирішальним для підтвердження діагнозу алергії на цвіль та розробки персоналізованого лікування для пацієнтів з алергічним ринітом та астмою. Найбільш комплексним підходом є розвиток загальноєвропейської мережі моніторингу, яка поєднує всі ці стратегії. GT може бути корисним інструментом для диференціації сезонів спор Alternaria, особливо коли вони співпадають з сезоном цвітіння амброзії. Чотири терміни "нежить", "сльози", "задишка" та "кашель" (кирилицею) слід використовувати в Україні для пояснення впливу спор Alternaria. Поєднання запитів GT з кількістю спор може бути використано в масштабних епідеміологічних дослідженнях. Розвиток загальноєвропейської сигнальної мережі моніторингу алергічних захворювань зумовлює проблему перекладу пошукових термінів різними європейськими мовами. Отримані результати можна використовувати як ефективний інструмент запобігання або мінімізації впливу алергену на пацієнтів під час сезону Alternaria.Документ Personalized approach to the management of patients with type 2 diabetes and comorbidities(European Journal of Case Reports in Internal Medicine, 2023) Borzykh, O.; Mormol, I.; Kaidashev, I. ; Борзих, Оксана Анатоліївна; Мормоль, Ірина Анатоліївна; Кайдашев, Ігор ПетровичThe results of this work make an important contribution to the development of new approaches for the diagnosis and control of complications of type 2 diabetes on the local and regional levels.The information about diabetes mellitus type 2, that is a severe chronic disease, characterized by the high risk of lethal complications, primary renal damage and cardio-vascular events. To prevent severe complications, it’s important to focus on the early diagnostics and appropriate management of these conditions.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, 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 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 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 ПетровичThe 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.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, O.; Kabaliei, A.; Shynkevych, V.; Shlykova, O.; Kaidashev, I.; 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, 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 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 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 ПетровичThe 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-6Документ Prophylaxis of decidual CD68+/CD163+ macrophage disbalance in extracorporeal fertilized women(Полтавський державний медичний університет, 2023-10) Likhachov, V.; Shimanska, Ya.; Akimov, O.; Vashchenko, V.; Taranovska, O.; Zhabchenko, I.; Kaidashev, I.; Ліхачов, Володимир Костянтинович; Шиманська, Яніна Вікторівна ; Акімов, Олег Євгенович; Ващенко, Вікторія Леонідівна; Тарановська, Олена Олексіївна; Жабченко, Ірина Анатоліївна; Кайдашев, Ігор ПетровичThe demographic crisis that prevailed in Ukraine in recent years, the state of war as a result of the aggression of the Russian Federation, reproductive losses among women of childbearing age are one of the most urgent problems in modern obstetrics and gynecology. One of the most effective methods of correcting impaired reproductive function is in vitro fertilization.