Актуальность Ишемическая болезнь сердца (ИБС) занимает лидирующую позицию среди причин смертности во всем мире. Сохраняется необходимость поиска новых эпигенетических маркеров, определяющих риск и прогноз ИБС. Цель Оценить уровень экспрессии микроРНК-21 в крови и в миокарде правого предсердия у больных ИБС, перенесших коронарное шунтирование (КШ). Материал и методы В исследование включено 98 больных ИБС, перенесших КШ, и 40 пациентов без ИБС (группа сравнения) сопоставимого возраста, перенесших операцию по поводу клапанных пороков сердца. Уровни экспрессии микроРНК-21 в крови и в миокарде предсердий оценивали с помощью полимеразной цепной реакции в реальном времени. Уровень глюкозы в крови определяли энзиматическим глюкозооксидативным методом, показатели липидного спектра сыворотки крови определяли ферментативным методом на биохимическом анализаторе «ARCHITECT 8000 C» (Россия, группа компаний “Ниармедик”). Оценку уровня инсулина сыворотки крови проводили методом иммуноферментного анализа (DRG, США). Для оценки степени резистентности к инсулину использовали малую модель гомеостаза (Homeostasis Model Assesment – HOMA) с определением показателя НОМА-ИР. Результаты Уровень экспрессии микроРНК-21 в кардиомиоцитах выше, чем в крови как у больных ИБС, так и в группе сравнения. У больных ИБС уровень экспрессии микроРНК-21 в крови, а также в миокарде выше, чем у пациентов группы сравнения. Установлено, что уровень экспрессии микроРНК-21 в крови более 3,61 УЕЭ ассоциируется с увеличением риска ИБС в 2,7 раза. Уровень экспрессии микроРНК-21 в крови ниже у больных ИБС с ИМТ≥30 кг/м2, чем при нормальной и избыточной массе тела. Аналогичные закономерности выявлены при оценке уровня экспрессии микроРНК-21 в миокарде у больных ИБС и в группе сравнения. Заключение У больных ИБС уровень экспрессии микроРНК-21 в крови и в миокарде выше, чем в группе сравнения. Уровень экспрессии микроРНК-21 в крови более 3,61 УЕЭ ассоциируется с увеличением риска ИБС в 2,7 раза.

The management of cerebral glioma (CG) remains challenging. Recently, methods based on the study of the expression levels of miRNAs in blood plasma have proven to be promising. The volume of tumor tissue is known to correlate with increased expression levels of microRNA-21 and -210. MicroRNA-15, -16, -34, -126 and -342 are involved in the regulation of tumor proliferative potential, and microRNA-128 is involved in the regulation of metabolic activity.The aim of the study was to evaluate the extended protocol for assessing the expression of microRNA-15, -16, -21, -34, -126, -128, -210, and -342 in the plasma and saliva of CG patients.Material and Methods. The study group consisted of 24 patients with supratentorial glioma (8 men and 16 women aged 41 to 71 years, mean age: 56 years). The control group consisted of 30 volunteers. MicroRNA expression was studied in plasma and saliva according to the StemLoop-RealTime protocol, using fluorescently labeled samples with small miRNA U6 as a reference gene. Statistical analysis was carried out using nonparametric methods.Results. The lack of CG stabilization and the most probable progression of the tumor with a poor prognosis was related to an increase in microRNA-21 and -210 expression levels and decrease in microRNA-128 expression and at least four of microRNA 15, -16, -34, -126, and -342. Stabilization of CG with a high probability of progression was associated with an increase in microRNA-21 or microRNA210 expression levels, decrease in no more than three of microRNA-15, -16, -34, -126, -342 expression levels as well as decrease in microRNA-128 expression. Stabilization of the tumor with a low probability of progression was associated with a decrease in the expression of microRNA-21 and -210 and in no more than one of miRNA-15, -16, -34, -126, -342 below the reference level, with a simultaneous increase in miRNA-128 expression.Conclusion. The determination of microRNA expression in blood plasma and saliva can be one of the important criteria for assessing the prognosis of CG.

The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.

Introduction . Fibroblast growth factor type 23 (FGF-23) inhibits phosphate reabsorption and vitamin D hormone synthesis in the kidneys. There is a known relationship between FGF-23 levels and serum phosphate, as well as a direct correlation between hyperphosphatemia and the risk of cardiovascular events. Aim . To evaluate associations between serum FGF-23 levels and bone and mineral metabolism in patients on renal replacement therapy (RRT) with hemo- and peritoneal dialysis, receiving and not receiving phosphate binders. Materials and methods . The study included 65 patients, of which 43 received maintenance hemodialysis tratment (HD), and 22 – peritoneal dialysis (PD). The control group consisted of 28 healthy volunteers. Results . The increase in the concentration of FGF-23 in the blood serum in patients on maintenance HD correlated with the vintage of dialysis treatment (rs = 0,765; p = 0,04). The positive correlation was found between the serum concentrations of FGF-23 and inorganic phosphorus (rs = 0,54; p = 0,03). The serum level of FGF-23 positively correlated with the serum PTH level (rs = 0,5; p = 0,01). In patients receiving sevelamer carbonate levels of FGF-23 was lower, than in control group (12.4 ± 5.9, and 23 ± 7.3, respectively; p = 0.003), as well as PTH (110 ± 27 ng/mL, and 340 ± 15, respectively; p = 0.01). Conclusions . The level of FGF-23 in dialysis patients directly correlated with the serum level of PTH and “dialysis vintage”. The use of phosphate binders, in particular sevelamer carbonate, positively affects the expression of FGF-23 and PTH in dialysis patients.

Background: MicroRNA (miRNAs) participate in the pathogenesis of coronary artery disease (CAD). Objective: To evaluate the expressions of myocardial and serum miRNA-27a, miRNA-133a, and miRNA-203 in CAD patients. Method: This cross-sectional observational study comprised 100 subjects (60.9 +/- 1.0 years; 67% men). The right atrial and serum expressions of miRNA-27a, miRNA-133a, and miRNA-203 in 80 patients referred for elective coronary artery bypass graft surgery (CABG) and 20 control patients scheduled for heart valve surgery were analyzed using real-time polymerase chain reaction. Results: There was a positive correlation between the SYNTAX score I index and serum miRNA-203 expression level (r = 0.693; p < .001). Patients with >= 3 coronary artery lesions had significantly higher myocardial expressions of miRNA-27a, miRNA-133a, and miRNA-203 than patients with 1-2 vessel disease in the atrial myocardium (miRNA-27a: 234.62 +/- 29.51 vs. 182.39 +/- 19.62 relative expression unit (REU); miRNA-133a: 127.53 +/- 13.41 vs. 111.35 +/- 12.31 REU; and miRNA-203: 5.25 +/- 0.96 vs. 4.71 +/- 0.67 REU; p < 0.05); the same association was found for serum miRNA expressions (miRNA-27a: 11.41 +/- 3.85 vs. 4.82 +/- 1.82 REU; miRNA-133a: 8.42 +/- 2.43 vs. 4.35 +/- 1.23 REU; and miRNA-203: 145.71 +/- 15.73 vs. 43.70 +/- 9.67 REU; p 0.05). The decision tree method established that the risk of multivessel lesions was increased five-fold if the miRNA-203 serum expression was 101.00 REU (OR, 5.90; 95% CI, 2.34-9.46; p < .001). Conclusions: Both myocardial and serum miRNA-27a, miRNA-133a, and miRNA-203 expressions are higher in CABG patients than in non-CAD subjects. The serum miRNA-203 expression level corresponds to myocardial expression and is strongly correlated with the extent of coronary atherosclerosis. (C) 2020 Published by Elsevier B.V.

Background and objective. Currently, the role of miRNA‑21 in the development of heart and kidney damage and their interaction remains unclear. Therefore, the aim of this work is to assess the impact of changes in the expression of microRNA‑21 in myocardial tissue in the development of cardiac remodeling with chronic reduction in the mass of active nephrons in the experiment. Design and methods. Wistar drain rats were divided into two groups. The first (control) group included nine falsely operated animals. The second (n = 9) group included rats with step-by-step resection of 5/6 renal tissue. After 4 months after surgery, blood pressure (BP) was measured, heart ultrasound (echocardiography, EchoCG) was performed and the level of relative expression of microRNA‑21 in myocardial tissue was determined. Results . The rats with an experimental decrease in the mass of functioning nephrons, showed significantly higher levels of BP, microRNA‑21 expression in the myocardium and the thickness of the interventricular septum (according to EchoCG). They also demonstrated smaller end-systolic dimension of the left ventricle and systolic motion of the mitral valve ring. Conclusions . Our data indicate the potential role of miRNA‑21 in the development of concentric left ventricular remodeling while reducing the number of functioning nephrons. This remodeling is characterized by the prevalence of myocardial hypertrophy over fibrosis. However, the specific mechanisms linking microRNA in the pathogenesis of heart remodeling require further research.

Background.Cardiovascular disease, including coronary artery disease (CAD), remains a leading cause of mortality. The results of recent studies demonstrate that microRNA engages in pathogenesis of different pathological states, including coronary atherosclerosis and its clinical manifestation — CAD.Objective.To evaluate microRNA-27а, microRNA-133а and microRNA-203 expression in cardiomyocytes and blood serum of CAD patients with different degrees of coronary artery lesion.Design and methods. 100 patients were included in the study, they formed 3 groups: 40 patients with CAD and significant atherosclerosis of 1-2 coronary arteries; 40 patients with multi arterial coronary disease and 20 persons without CAD and significant comorbidity. The microRNA-27a, microRNA-133а and microRNA-203 expression was determined in cardiomyocytes and blood serum of these patients by real-time polymerase chain reaction.Results.Level of microRNA-27a, microRNA-133а and microRNA-203 expression in left atrium cardiomyocytes of CAD patients with significant stenosis of 3 or more coronary arteries was higher, then their expression in the patients with 1-2-vessel and in group without coronary atherosclerosis. Examination of the microRNA expression level in blood serum and in left atrium cardiomyocytes revealed a significant difference. The expression of microRNA-27a and microRNA-133а in cardiomyocytes is above than in blood serum, while the expression of microRNA-203 in the myocardium is lower, than in the blood serum. Level of microRNA-27a, microRNA-133а and microRNA-203 expression in blood serum in CAD patients with significant stenosis of 3 or more coronary arteries was significantly higher, than in patients with 1-2 stenosis of coronary arteries. Furthermore, classification tree method established that risk of atherosclerotic heart disease increases five-fold if microRNA-203 expression in blood serum is more than 100 REU.Conclusion.MicroRNA-27а and microRNA-133а expression in cardiomyocytes of left atrium is higher than in blood serum in CAD patients. MicroRNA-203 expression level in blood serum may be a new predictive marker of coronary artery degree atherosclerotic stenosis in CAD patients.

THE AIM.To evaluate the effect of the sodium-glucose cotransporter SGLT-2 inhibitor - empagliflozin on the kidney in nondiabetic Wistar rats with experimental heart failure (HF).MATERIAL AND METHODS. Cronic heart failure (CHF) was induced by ligation the left coronary artery. Animals with CHF in the first group (n=11) received empagliflozin (Jardiance®, Boehringer Ingelheim) orally (1 mg / kg/day) for 1 month. In the second group of rats with CHF (n = 10) the drug is not administered. Systolic blood pressure, heart rate, concentrations and daily urinary excretion of glucose, albumin, creatinine, urea and essential ions were measured. The relative level of microRNA-21 urinary expression was established.RESULTS.Empagliflozin administration led to an increase in glycosuria, albuminuria, and the expression of microRNA-21 in urine. However in this conditions inorganic phosphorus excretion decreased. Empagliflozin did not influence on blood pressure, heart rate or levels of investigated substances excretion including sodium.CONCLUSION. The findings suggest that the SGLT-2 inhibitors may have some negative direct effects on the kidneys. However, in diabetes, such effects of these drugs can be masked by powerful nephroprotective actions associated with the ability of SGLT-2 inhibitors to counteract hyperglycemia and glomerular hyperfiltration.

THE AIM: to estimate the level of expression miRNA-21 inthe urine and renal tissue in rats with unilateral ureteral obstruction (UUO). MATHERIAL AND METHODS. UUO was induced by ligation of the left ureter in male Wistar rats (n=10). Follow-up period was 14 days after UUO modeling. Urine was collected one day before the operation (UmiRNA21C), and one day before the end of experiment (UmiRNA21I ) during 24 hours. Before releasing animal out of experiment collected urine from left kidney pelvis (UmiRNA21O) and tissue of left kidney (KmiRNA21O) and right kidney (KmiRNA21I). MiRNA-21 expression in kidney tissues and urine was carried out with reaction amplification (RealTime PCR-protocol). Calculation was realized by 2-deltaCtmethod. Statistical analysis was performed with Wilcoxon test and Spearman correlation coefficient. Results are demonstrated as median [low – upper quartile]. RESULTS. UmiRNA21I(3.78[2.0-5.28]) and UmiRNA21O(3.78[3.25-3.82]) were significantly higher than UmiRNA21C (1.15[0.71-1.74]; P=0.0125 and P=0.0069, respectively). UmiRNA21I and UmiRNA21O values were practically equal. In kidneys with UUO the tissue levels of miRNA21 expression was a higher than in contralateral organ (P=0,0926). Revealed direct correlation between KmiRNAIand KmiRNAO(RS=0,770, P=0,0092). CONCLUSION. UOO can cause specific changes in the expression, distribution and excretion of micro RNA-21 and its role in the development of renal tubulointestitsial fibrosis requires further studies. Key words: miRNA-21, tubulointerstitial fibrosis, unilateral ureteral obstruction

Abstract. Our general purpose was to investigate bcl–2 gene expression in patients treated by allogeneic unrelated haematopoietic stem cells transplantation (aUHSCT) for the evaluation of aGvHD. Total RNA from the leukocytes of 19 oncohaematological patients was collected before starting the conditioning regimen (D–T), at the day of hematological recovery (D–R) and at the D+30. An original RT–PCR protocol was developed, by quantifying the signals from the target genes, as compared to beta–actin as a reference gene. We have shown that the levels of bcl–2 expression in aGVHD patients were higher, as compared to aGVHD–free patients at D–T (Р=0,011), like as D–R (Р=0,012) time–points. The patients at the D–R and D+30 were divided into two groups, either with or without clinical signs of aGvHD at these observation terms (resp., groups I and II). At D–R point, bcl–2 expression in the 1st group was two–fold higher, than in the patients of second group (P=0,05). By the contrary, bcl–2 expression by the D+30 in group I was two–fold lower, as compared to the patients of second group (Р=0,016). Thus, we suggest the monitoring of bcl–2 expression to be of certain clinical significance. This criterion could be used as additional approach to prediction of aGVHD development and adjustment of immunosuppressive therapy. We also suppose that the role of the bcl–2 in the pathogenesis of aGvHD should be analyzed in more details. (Med. Immunol., 2005, vol.7, № 4, pp. 381–384)

THE AIM: to estimate the level of expression miRNA-21 inthe urine and renal tissue in rats with unilateral ureteral obstruction (UUO). MATHERIAL AND METHODS. UUO was induced by ligation of the left ureter in male Wistar rats (n=10). Follow-up period was 14 days after UUO modeling. Urine was collected one day before the operation (UmiRNA21 C ), and one day before the end of experiment (UmiRNA21I ) during 24 hours. Before releasing animal out of experiment collected urine from left kidney pelvis (UmiRNA21O) and tissue of left kidney (KmiRNA21 O ) and right kidney (KmiRNA21 I ). MiRNA-21 expression in kidney tissues and urine was carried out with reaction amplification (RealTime PCR-protocol). Calculation was realized by 2- deltaCt method. Statistical analysis was performed with Wilcoxon test and Spearman correlation coefficient. Results are demonstrated as median [low – upper quartile]. RESULTS. UmiRNA21 I (3.78[2.0-5.28]) and UmiRNA21 O (3.78[3.25-3.82]) were significantly higher than UmiRNA21C (1.15[0.71-1.74]; P=0.0125 and P=0.0069, respectively). UmiRNA21I and UmiRNA21O values were practically equal. In kidneys with UUO the tissue levels of miRNA21 expression was a higher than in contralateral organ (P=0,0926). Revealed direct correlation between KmiRNA I and KmiRNA O (RS=0,770, P=0,0092). CONCLUSION. UOO can cause specific changes in the expression, distribution and excretion of micro RNA-21 and its role in the development of renal tubulointestitsial fibrosis requires further studies. Key words: miRNA-21, tubulointerstitial fibrosis, unilateral ureteral obstruction

A possibility of detection of BRAF mutation has been studied by means of polymerase chain reaction in punctate from the thyroid node with the aim of diagnostics of high-differentiated cancer on pre-operative stage. A study includes 94 patients with nodal lesions of the thyroid. According to cytological investigation of material, received by fine-needle aspiration biopsy, papillary thyroid cancer was revealed in 47 patients, follicular tumor-in 35 and nodal colloid goiter in 12 patients. In case of papillary thyroid cancer data of genetic analysis showed the following indices of sensitivity, specificity and diagnostic accuracy: 86%, 100% and 92% correspondingly. Detection of BRAF mutation could be used in pre-operative differential diagnostics of high-differentiated cancer and benign nodal lesions of the thyroid.

Silver staining for nucleolar proteins was used to evaluate the ribosomal genes activity in cardiomyocytes (Cm) and fibroblast-like cells (FBS) of intraventricular septum, and other regions of the left ventricle. Specimens to be analysed were taken from 7 patients with idiopathic obstructive hypertrophic cardiomyopathy (OHCM). In this group the quantity of nucleoli and AgNORs, reflecting the transcriptional and processing level of pre-ribosomal RNA in all type of cells, was at least 2 and 3 times higher than in patients with essential hypertension and in healthy control, respectively. We suggest that nucleolar hypertrophy in patients with hypertrophic cardiomyopathies, inappropriate to hypertrophy in other pathological conditions, may be most probably of compensatory character, and this may be in part explained by nuclear hyperploidy and chromosomal endoreduplication. We have noted a marked heterogeneity in shape, size and quantity of nucleoli, and in AgNORs of FBC. Nuclei with modulated phenotype containing nucleoli of high activity were revealed. This article presents the first data on p53 mutation identification in patients with advanced OHCM.

Cytological screening is essential for adequate diagnosis of gynecological cancer. Moreover, every effort should be made to identify such risks of cancer as viruses (HPV, Herpes simplex, cytomegalovirus, Epstein-Barr virus, etc.). When high risk HPV-16 and HPV-18 are detected, diagnostic strategies should include assay of blood prolactin and prolactin/TTH ratio. Virus-related tumors and various risk groups may be studied using HPV genotyping detection of high-risk alleles of certain genes. Hence, some HPV gene variants and gene polymorphism can be investigated as potential risk factors in women.