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Background: Osteopontin is a protein expressed by various cell types, such as endothelial and epithelial cells, osteoclasts, hepatocytes, smooth muscle cells, activated macrophages, and T-cells. Cardiomyocytes, heart fibroblasts, endothelial cells of coronary arteries express osteopontin in response to hypoxia, inflammation, toxic factors, mechanical strain, and other stimuli. Aim: To study osteopontin levels in patients with chronic obstructive pulmonary disease (COPD) depending on concomitant ischemic heart disease (IHD), to identify an association between osteopontin levels with severity of COPD and functional lung test parameters. Materials and methods: This open-label, prospective, non-randomized comparative study with parallel groups included 99 patients with COPD grades AD by GOLD, with 49 of them having confirmed comorbid stable IHD. Serum osteopontin levels were measured by immunoenzyme assay (Human Osteopontin Platinum ELISA; Bender MedSystems, Austria). The data is given as medians and quartiles (Me [Q1; Q3]). In all patients we performed functional lung tests with bronchodilation, a 6-minute walking test, BODE index assessment, as well as CAT and mMRC questionnaires were used. Results: In the patients with COPD and IHD, the osteopontin levels were higher than in the patients with COPD without IHD (85.55 [46.86; 110.91] vs 55.43 [20.76; 89.64] ng/mL, respectively; p = 0.027). Osteopontin levels in the patients with all COPD grades and IHD were higher than in those without IHD, but the difference was significant only in GOLD grade B patients (91.28 [73.04; 110.91] vs 37.81 [22.54; 82.95] ng/mL, respectively, р = 0.028) and GOLD grade D patients (80.79 [34.65; 111.11] vs 37.46 [13.32; 109.5] ng/mL, respectively, р = 0.027). Conclusion: A significant increase of osteopontin levels in comorbid patients with COPD and stable IHD found in this study has not been previously known. It is necessary to perform further studies to identify a threshold level of osteopontin predictive of the risk of COPD exacerbations or cardiovascular events. This would help to improve medical treatment of COPD patients, as well as to identify the risk groups.

Introduction. Over the past decade, tongue cancer has maintained a leading position in the overall structure of the incidence of head and neck malignant tumors. Squamous cell carcinoma of the tongue is an aggressive form and has a clinically unpredictable prognosis. Currently, there are several histological subtypes of this disease. And the search for new prognostic factors that could reflect the actual state of tumor progression and give an objective prognosis of disease development is an important research area in molecular oncology. Such factors may be certain transcriptomic characteristics of tumors, which determine the features of pathogenesis in each specific case.Aim. To research genes transcriptional activity features in various histological subtypes of tongue squamous cell carcinoma using bioinformatic and molecular approaches.Materials and methods. The stage of screening bioinformatics analysis was performed using an interactive web server for analyzing data on messenger RNA expression of 9736 tumors and 8587 normal samples from the The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects using a standard processing pipeline (GEPIA). The main (validation) stage of the study was performed on 300 patients with locally advanced malignant tumors of the tongue. The quantitative real-time polymerase chain reaction method was used to determine the values of the relative expression of genes identified at the stage of bioinformatic analysis.Results. Bioinformatic analysis identified 1488 genes that increase expression and 589 genes that decrease expression in tongue squamous cell carcinoma. Of these 2077 genes, 23 genetic loci were selected that most strongly alter expression in tumor tissue relative to normal tissue of the tongue. Of these, when validated by polymerase chain reaction, only 14 changed their transcriptional profile in tumor tissue relative to normal: MMP1, MMP11, CA9, PTHLH, MMP9, LAMC2, MMP3, ANXA1, MT-ND6, CRNN, MAL, TGM3, IL1RN and CLU. The analysis of polymerase chain reaction data revealed significant heterogeneity in a number of biological samples studied. Cluster analysis made it possible to divide the total sample of 300 patients into 3 groups differing in gene expression: cluster 1 (n = 90), cluster 2 (n = 101) and cluster 3 (n = 109), corresponding to the basaloid, acantholytic and usual histological subtypes. Thus, the study made it possible to identify a number of molecular markers of tongue squamous cell carcinoma (MMP1, MMP11, CA9, PTHLH, MMP9, LAMC2, MMP3, ANXA1, MT-ND6, CRNN, MAL, TGM3, IL1RN and CLU), as well as to reveal the transcriptional features of various histological subtypes of this disease.

Objective To investigate the relationship between calcium metabolism disorders, stone formation inhibitor levels and stone density in primary and recurrent calcium-oxalate nephrolithiasis.Material and Methods Sixty nine patients with urolithiasis were examined, their average age was 41,4 ± 9,5 years. Two main groups were distinguished: Group 1 – primary calcium-oxalate nephrolithiasis (PN), Group 2 – recurrent calcium-oxalate nephrolithiasis (RN). Then each group was divided into two subgroups – A and B according to stone density: 500–1000 HU and from 1000–1500 HU, respectively. Stone density was determined by computed tomography (CT). PTH (parathormone), PTHrP (parathyroid hormone related protein), vitamin D, total blood calcium (Ca), ionized blood Ca, total blood protein, Ca and urine pH were also examined. After the examination, patients underwent surgical removal of the stones.Results It was found that 41.9% of group 1 and 46.9% of group 2 patients had grade I obesity. Average creatinine level in group 2 was 9.7% higher than in group 1 (p < 0.05). Urea level in both groups was not statistically significantly different. Glomerular filtration rate (GFR) was comparable. Groups 2A and 2B had higher PTHrP values (77.61 and 76.98 pg/mL, respectively) combined with relatively high PTH levels (2A – 4.4 pg/mL and 2B – 5.1 pg/mL), relatively low osteopontin concentration (2A – 0.044 pg/ mL, 2B – 1.106 pg/mL), compared to those in group 1 (p < 0.05). Pairwise unidirectional differences between groups 1A and 2A, 1B and 2B were found to correlate positively with density values: for osteopontin: r = 0.992 (p < 0.05); for vitamin D: r = 0.831 (p < 0.05); for blood Ca2+ ions: r = 0.836 (p < 0.05); for urine pH: r = 0.863 (p < 0.05). There was a negative correlation with the daily concentration of urinary calcium ions with the density of concrements: r = -0.663; p < 0.05. The concentration of osteopontin was significantly higher in Group 1B and 2B patients, and it was significantly lower in patients with stones of < 1000 HU density. Higher values of osteopontin concentration were noted in groups 1B and 2B in relation to groups 1A (p < 0.05) and 2A (p < 0.05). The increase of blood Ca2+ ions in patients in groups 1B and 2B in relation to groups 1A (p < 0.05) and 2A (p < 0.05) was also accompanied by higher values of vitamin D.Conclusion Patients with denser stones showed high values of osteopontin and PTHrP in serum and low values of urinary calcium ions, which may lead to the formation of concrements on the matrix with an organic base. Determination of calcium metabolism makes it possible to predict recurrence of KSD in primary calcium oxalate nephrolithiasis and assess the severity of mineral metabolism disorders in recurrent calcium oxalate nephrolithiasis.

Osteopontin is an extracellular matrix protein which is produced by different types of cells and plays an important functional role in many biological processes. This review discusses the main functions of osteopontin, its role in the progression and chemoresistance of malignant neoplasms, in the regulation of epithelial-mesenchymal transition, angiogenesis, and the body’s immune response to the tumor. The article considers the currently known mechanisms by which osteopontin affects to the survival, mobility and invasion of tumor cells, to tumor sensitivity to drug treatment, as well as the prospects for a integrated study of the predictive significance of osteopontin, markers of hypoxia, angiogenesis, epithelial- mesenchymal transition, and immunological tolerance.

The literature review highlights the results of the most recent foreign and Russian studies on topical problems of vascular calcification with an emphasis on the relationship between some biochemical markers of vascular calcification (in priority osteoprotegerin and osteopontin) with cardiovascular disease and other associated conditions. Including some provisions of the reviewed studies help to clarify the pathophysiology mechanisms of vascular calcification. And it should also be noted that many aspects of the reviewed studies are directly related to a clinical practice. The purpose of this review is to generalize and systematize current knowledge about the contribution of vascular calcification biochemical markers to vascular tunic pathology, which finally leads to cardiovascular events. To prepare it, the databases PubMed, Google Scholar, ScienceDirect, MDPI, Hindawi, Oxford Academic were used.

Introduction. Colorectal cancer is one of the most common cancers worldwide. In the Republic of Kazakhstan, over the past decade, the incidence rates of colon and rectal cancers have increased by 23 % and 17 %, respectively. Although colorectal cancer screening rates have increased over time, it is necessary to identify new serum markers for early detection and prognosis of this cancer. The aim of the study was to evaluate the diagnostic value of serum biomarkers for colorectal cancer. Material and Methods. Biomarkers were studied by immunofluorescence method using xMap technology, which included simultaneous immunofluorescence determination on magnetic spheres CA125, CA15–3, CA19–9, CEA, CYFRA21–1, sFAS, sFasL, HE4, Osteopontin, VEGF-A, pd-L1. Results. The study showed no significant differences in the levels of markersbetween healthy subjects (control group) and patients with bowel diseases. In cancer patients, СEA and OpN markers increased with increasing tumor stage, and were significantly higher than those observed in patients with bowel diseases and controls. The CA125 marker was significantly higher in patients with stage IV cancer then in patients with I–III stages. Conclusion. Our study revealed that the new pd-L1 marker can serve as a significant biomarker for colorectal cancer.

The literature review highlights the results of foreign and Russian studies of recent years, devoted to the study of biochemical factors and potential biomarkers of calcification of the vascular wall, as well as atherosclerotic plaques of the coronary and carotid arteries. The results of the studies allow to clarify and to supplement the known mechanisms of calcification of the vascular wall. To date, the four most studied biomarkers of vascular calcification are most studied osteoprotegerin, osteopontin, osteonectin and osteocalcin.

The development of atherosclerosis is a complex multifactorial process, in which the markers of bone formation and resorption play an important role and which is closely related to the calcification of the vessel intima and fibrous plaques.Objective: to assess the relationship between bone remodeling markers (cathepsin K, C-terminal telopeptide of type I collagen (CTX-I) and osteopontin), bone mineral density (BMD), and severity of coronary atherosclerosis in men with stable coronary heart disease (CHD).Patients and methods. The investigation enrolled 102 male patients with verified stable CHD. Coronary angiographic and densitometric findings and blood cathepsin K, osteopontin, and CTX-I concentrations were assessed.Results.The concentration of cathepsin K and CTX-I was significantly higher and that of osteopontin was significantly lower in patients with CHD than in men without CHD. There was no association of the level of bone remodeling markers with the type of coronary artery lesion and the severity of coronary atherosclerosis. Cathepsin K concentrations in patients with a high SYNTAX score of coronary atherosclerosis were shown to be 5.5 times lower in the presence of osteopenic syndrome (OPS) than in those with the similar severity of atherosclerosis and normal BMD. Analysis of osteopontin and CTX-I levels from the standpoint of the presence of OPS suggests that there are no differences in relation to both the type of coronary vessel lesion and its severity. Conclusion. Current data suggest that there are common mechanisms for the development of two socially significant conditions: atherosclerosis and osteoporosis (OP). The phenomenon of concomitant development of these diseases has been studied mainly in postmenopausal women. Today, however, OP is also increasingly found in men, associating with more severe manifestations of coronary atherosclerosis than in patients with no signs of osteopenia.

Aortic stenosis (AS) is of the most prevalent acquired heart valve defects; the role calcium is serious in its development. One of the key mediators of calcium metabolism is vitamin D.Aim. To reveal the relation of the sufficiency of vitamin D with mineral bone density (MBD) and other biomarkers of calcification in AS patients.Material and methods. Totally, 89 patients studied, with severe AS (aortic valve flow velocity more than 4 m/s) at the age 40-76 year old. The controls were almost healthy participants, blood donors (n=31). All patients underwent 25(OH)D in serum measurement, of osteopontin, C-reactive protein and lipid profile, as bienergetic x-ray absorptiometry of lumbar spine and of proximal femur.Results. According to the data of absorptiometry, there was no osteoporosis or osteopenia in AS patients. However, the pressure gradient on aortic valve was related with MBD and T-criteria value. Vitamin D deficiency was found in 46% of patients. Content of 25(OH)D in serum of AS patients was lower and did not differ between bi- and tricuspid aortic valve patients. There was higher level of osteopontin in AS patients comparing to the controls. Decrease of 25(OH)D was associated with the decrease of osteopontin and atherogenety coefficient. There was no relation of the gradient on aortic valve and the level of vitamin D sufficiency.Conclusion. Vitamin D deficiency might impact pathogenesis of AS regardless the anatomic specifics of aortic valve. Its action probably is mediated by the regulation with proinflammatory cytokines, such as osteopontin.

Aim. To examine the cardiovascular remodeling parameters and osteopontin plasma level in dynamics of the candesartan therapy in patients with chronic kidney disease on the stage before dialysis Methods and results. Peculiarities of the cardiovascular remodeling were studied in 52 patients with chronic kidney disease III, IV, and V stage. Echocardiography, carotid dopplerography, and immunoassay detection of the osteopontin level were done. The predominant type of pathological left ventricular geometry was concentric hypertrophy, its prevalence increased with worsening of the renal function. The maximum level of IMT was observed at stage V of the CKD. The chronic kidney disease progression was accompanied by increased plasma levels of the osteopontin. Conclusion. Direct correlation between the concentration of the protein and the index of left ventricular mass and the intima-media thickness were detected. The therapy with candesartan during 12 weeks leads to the significant reduction of osteopontin, which can be considered as a marker of cardiovascular remodeling in patients with CKD.

The article presents results of the study which includes 41 children with chronic viral hepatitis B (CHB) and acute lymphoblastic leukemia (ALL), aged 3 to 17 years and all were at dispensary observation in the Vinnytsia Regional Infectious Disease Hospital, Ukraine from January 2016 to February 2017. The aim of this study was to determine the plasma osteopontin level (OPN) in children, depending on sex, viral load, and degree of fibrosis. It was found that the level of this glycoprotein in children with chronic hepatitis B with ALL was significantly higher (275.66 ± 22.32 ng / ml) than in control group children (92.65 ± 7.31 ng / ml) (p

Aim. Large population-based studies acknowledge that patients with chronic kidney disease have a high risk of cardiovascular diseases regardless of etiology, especially in its late stages. The aim of this study was to investigate the features of arterial hypertension, cardiovascular remodeling and plasma level of osteopontin in dynamics of candesartan therapy, as well as to identify the relationships between studied parameters in patients with chronic kidney disease treated by hemodialysis. Methods and results. 50 patients were performed ambulatory blood pressure monitoring, the plasma level of osteopontin was determined by ELISA method, standard echocardiography and ultrasonography of common carotid after treatment of candesartan during 12 weeks. Conclusion. The results indicate that the use of candesartan cilexetil in hemodialysis populations promotes regression of left ventricular hypertrophy and vascular remodeling indices, has antihypertensive effect.

Aim. To examine vascular calcification and plasma levels of osteopontin in patients with chronic kidney disease who are treated by program hemodyalisis Methods and results. 53 patients were treated by renal hemodialysis. In this population the prevalence of abdominal aortic calcification was established using X-ray radiography. In 20 of them multislice computer tomography was conducted. There was a positive correlation between vascular calcification and phosphate levels, phosphate - calcium product. Plasma level of osteopontin in hemodialysis patients was significantly higher than in patients with predialysis stages of chronic kidney disease. Conclusion. Positive correlation between plasma levels of citokine and abdominal aortic calcification may indicate that osteopontin is a marker of vascular calcification in patients, who are treated by program hemodialysis.

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Aim: To evaluate the dynamics of plasma and urine level of osteopontin in the early postoperative period after percutaneous nephrolithotomy (PCNL) in patients with pelvic stones., Materials and Methods: A total of 110 patients with pelvic stones up to 20 mm in size without urinary tract obstruction were included in the study. The patients were divided into two groups based on the results of intraoperative monitoring of intrarenal pressure. In each of the groups, PCNL or mini-PCNL were performed in same proportions. Intraoperative monitoring of intrarenal pressure was done in all cases according to the authors method. Sampling of plasma and urine for enzyme immunoassay was performed on the 0, 7 and 30 days after the procedure. Plasma and urine osteopontin level was measured using a commercial Human Osteopontin ELISA Kit for enzyme immunoassay., Results: In patients with increased intraoperative intrarenal pressure pyelonephritis developed, accompanied by hyperthermia from 3 to 7 days in 70% of cases, and leukocytosis and leukocyturia in 100% of cases. The number of hemorrhagic complications did not differ in both groups. An increase in serum osteopontin level was seen, which was significantly more pronounced in the group with increased intraoperative intrarenal pressure. Urinary osteopontin level, on the contrary, tends to decrease, more pronouncedly in patients with normal intraoperative intrarenal pressure., Conclusion: The rate of decrease in urinary osteopontin level indicates the stabilization of injury and the restoration of renal function after PCNL. An increase in serum osteopontin level is associated with the development of postoperative inflammatory complications, which demonstrates the immune functions of serum osteopontin.

Objective: To analyse a role of BP (blood pressure) variability in shaping neuroplasticity in patients with type 2 diabetes mellitus (DM)., Material and Methods: The study enrolled 100 patients with type 2 DM divided according to the presence of cognitive impairment (CI) and 25 control subjects. Biochemical blood count, plasma osteopontin, 24-hour self-blood pressure monitoring (SBPM) and brain MRI were assessed., Results: Patients with type 2 DM and CI had higher body mass index as well as glycated hemoglobin (HbA1c), glucose, alanine aminotransferase, osteopontin and hyperlipidemia ( p ≤0.05). There was a significant difference in all standard indices, patients with type 2 DM were classified as «non-dipper», and there were significantly higher values of the index of time and area of stay in the state of suprathreshold BP and BP variability at night, as well as the risk of latent arterial hypertension in CI. Neuroimaging assessment revealed decreased blood flow according to contrast and non-contrast perfusion in all parameters in cortical (especially the frontal lobe) and subcortical structures (predominantly in the shell region), and was associated with SMAD parameters. Mean systolic and diastolic BP during the day and night, as well as the variability index, also influenced the integrity between cortico-spinal tract, hook, inferior longitudinal and arcuate fascicles. The same parameters altered hippocampal metabolism in terms of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr ratios., Conclusion: In patients with type 2 DM, BP variability contributes to CI through a proinflammatory mechanism (osteopontin) leading to brain neuroimaging abnormalities.

Objective: Analysis of the role of blood pressure (BP) variability in the formation of neuroplasticity in patients with type 2 diabetes mellitus (DM)., Material and Methods: 100 patients with type 2 DM were examined, which were divided into groups depending on the presence of cognitive impairment (CI), the control group consisted of 25 people. All examined patients underwent a clinical examination, a standard set of biochemical blood tests, plasma osteopontin levels, 24-hour blood pressure monitoring (ABPM) for 24-26 h MRI of the brain (dynamic contrast and arterial spin marks, proton spectroscopy, tractography)., Results: Patients with type 2 diabetes and CI had higher body mass index, blood levels of glycated hemoglobin, glucose, alanine aminotransferase, low-density lipoprotein, triglycerides, total cholesterol, osteopontin, and lower levels of high-density lipoprotein ( p ≤0.05). The level of osteopontin was higher in patients with overweight, hyperglycemia, dyslipidemia, and in patients with CI in patients with BP variability. When assessing 24-hour blood pressure monitoring (ABPM), a significant difference was found in all standard indicators, while patients with type 2 diabetes were referred to as «non-dipper», in the presence of CI they noted significantly higher values of the index of time and area of stay in the suprathreshold state. BP and variability in SBP and DBP at night, as well as the risk of occult hypertension. A decrease in cerebral blood flow was revealed according to the data of contrast and non-contrast assessment of perfusion in cortical (especially in the frontal lobe) and subcortical (mainly in the putamen) structures, associated with changes in ABPM parameters. Mean SBP and DBP day and night, as well as the index of BP variability, also affect the integrity of the corticospinal, uncinate, lower longitudinal tracts, and arcuate fasciculus. The same parameters change the metabolism of the hippocampus in terms of choline (Cho), creatine (Cr), creatine phosphate (Cr2), as well as the ratio of N-acetylaspartate (NAA)/Cho, NAA/Cr, Cho/Cr., Conclusion: In patients with type 2 diabetes, BP variability contributes to the formation of CI through a pro-inflammatory mechanism (osteopontin), leading to impaired brain vascularization in general, white matter structure, and hippocampal metabolism.

THE AIM OF THE RESEARCH: to reveal the relationship of various markers of calcium metabolism (osteopontin (OPN), parathyroid hormone-related protein (PTHrP), vitamin D, parathyroid hormone (PTH)) on the course of urolithiasis (Urolithiasis) in patients with calcium oxalate nephrolithiasis., Materials and Methods: 100 people were examined, the following groups were included: group 1 - patients with calcium oxalate primary nephrolithiasis (n=41), group 2 - with calcium oxalate recurrent nephrolithiasis (n=39). Group 3 included conditionally healthy volunteers (n=20). The studies were carried out by the immunoenzymometric ELIZA and biochemical methods using appropriate test systems., Results: in patients with recurrent nephrolithiasis, the serum PTHrP level is 54.6 (25.4-78.2) pg / ml, which is 3.7 times higher than in conventionally healthy individuals; the level of osteopontin is more than 1.5 times higher and amounts to 1.820 (0.991-2.212) pg / ml. In the group of primary nephrolithiasis, the level of PTHrP is 2-2.5 times higher than in conventionally healthy people. In patients with primary nephrolithiasis, the blood calcium level does not correlate with the level of PTHrP in the blood (r=- 0.0173, p> 0.05), as in the group with recurrent nephrolithiasis (r=0.0223, p>0.05)., Discussion: in patients with recurrent nephrolithiasis in the preoperative period, the serum levels of osteopontin and PTHrP in the blood serum were higher than in patients who were first diagnosed with urolithiasis, the data obtained can be used as a criterion for predicting the risk of recurrence of urolithiasis in the postoperative period. The blood calcium level does not have a statistically significant relationship with PTHrP, which allows us to assume that PTHrP has other mechanisms of influence on the development of urolithiasis, given the data obtained that the PTHrP level in patients with primary and recurrent nephrolithiasis is higher than in conditionally healthy people., Conclusion: Determination of the level of PTHrP and osteopontin in patients with urolithiasis allows predicting the risk of recurrence of urolithiasis at the stage of primary calcium oxalate nephrolithiasis. Determination of the level of PTHrP makes it possible to predict the risks of developing urolithiasis in conventionally healthy individuals, which can be used for targeted prevention of an unfavorable course of urolithiasis by prescribing timely adequate rational therapy and correcting the patients diet. At the same time, no correlation was found between the level of PTHrP and the level of blood calcium in patients with calcium oxalate nephrolithiasis; therefore, further studies of the role of this protein in the pathogenesis of urolithiasis are needed.

Liver cirrhosis in the outcome of hepatitis C is the leading cause of hepatocellular carcinoma (HCC) in the world. Early diagnosis and timely treatment of HCC are important for reducing mortality and increasing life expectancy of patients with hepatocellular carcinoma. To assess the risk of HCC, the definition of alpha-fetoprotein (AFP) in the blood is most widely used, but low sensitivity limits its diagnostic value. In 2012, a new HCC biomarker - osteopontin (OPN), which is a secreted phosphoprotein that has a high affinity for integrins was proposed. The level of acute renal failure begins to rise in the early stages of malignancy, before the period of HCC detection by imaging methods, and has significantly better sensitivity than AFP. The purpose of this study is to evaluate the diagnostic efficacy of the combined determination of alpha-fetoprotein and osteopontin in prospective monitoring of patients with chronic hepatitis C in the advanced phase of liver fibrosis. Monitoring of 588 patients with hepatitis C was carried out from February 2013 to February 2019. HCC was detected in 55 of them (2.6% per year). The combination of 2 biomarkers showed better diagnostic efficacy than alpha-fetoprotein and osteopontin separately: AUC 0.85 (95% CI 0.80-0.90) versus AUC 0.63 (95% CI 0.57-0, 70) and AUC 0.82 (95% CI 0.77-0.88), respectively. This combination showed a sensitivity of 85.5% and made it possible to diagnose HCC with a prognostic level of a positive result of 72.3% at 19,4±0,8 weeks before the diagnosis was confirmed by instrumental imaging methods (ultrasound, MRI, CT). In the combined variant, ARF made the greatest contribution to the increase in diagnostic efficacy (AUC). At an early and very early stage of HCC development, isolated HCC elevations were found in only 5.4% of patients. Conclusion: the combined use of alphafetoprotein and osteopontin as a diagnostic panel can be recommended for monitoring patients with liver cirrhosis in the outcome of hepatitis C and predicting HCC at an early stage of development., Competing Interests: The authors declare no conflict of interest.

Aim: to evaluate antioxidant properties of dietary supplements Nefradoz, as well as its role in the prevention of calcium oxalate stones., Materials and Methods: Our study consisted of two parts, clinical and experimental. In the clinical trial a total of 80 patients with recurrent calcium oxalate urolithiasis of various localization were included. All patients were divided into 2 groups. In treatment group (n=45) patients received Nefradoz 1 capsule 2 times a day. In control group (n=35) no treatment was prescribed. In all patients a biomarkers level (bikunin, osteopontin, nephrocalcin) in urine was determined by ELISA. In addition, Litos-test was performed. Follow-up duration was 6 months. In the experimental part of the study, the antioxidant properties of Nefradoz were evaluated using chemiluminescence method., Results: The antioxidant activity of resveratrol, which is contained in 300 mg Nefradoz (1 capsule), was 23.66+/-1.18, which corresponds to the moderate activity. After 6 months of therapy a level of bikunin and osteopontin did not significantly changed, which indicates a minimal risk of stone recurrence. According to the Litos-test, the activity of stone formation in Nefradoz group significantly decreased to minimal values in 42 out 45 patients (p<0.05). In the control group an excretion of biomarkers was minimal, which significantly increased the risk of stone formation., Conclusion: Dietary supplement NefraDoz can be used for prevention of calcium oxalate urolithiasis in case of increased stone formation according to the Litos-test. The antispasmodic, uroseptic and diuretic effects allow to maintain the effective level of biomarkers which is required for a recurrence-free course of urolithiasis compared to the control. The antioxidant activity, primarily determined by the resveratrol, can sufficiently compensate for oxidative stress and prevent the development of calcium oxalate stone. Further studies are needed to confirm our results.

The study aimed to investigate the changes in the concentration of bikunin, osteopontin, and nephrocalcin, depending on the changes in the renal stone-forming activity in patients with recurrent urolithiasis., Materials and Methods: The study comprised 152 patients with recurrent calcium oxalate stones at various localizations. Patients of the study group (n=78) were administered complex preventive treatment (water load, Blamaren, thiazide diuretics, oral calcium supplementation) aimed at reducing the activity of urolithiasis. Patients of the control group (n=74) received no treatment. The studied parameters included concentrations of urine bikunin, osteopontin, and nephrocalcin in using ELISA. The follow-up period was six months., Results: By the end of the follow-up, the bikunin concentration in the control group was significantly higher than in the study group (7.0+/-0.81 mg/ml vs. 3.28+/-0.86 mg/ml, respectively, p<0.05) while osteopontin level was significantly lower (2.4+/-0.39 mg/ml vs. 3.4+/-0.36 mg/ml, p<0.05). The nephrocalcin concentrations during the follow-up period did not change significantly (p>0.05). The presence of hypercalciuria did not lead to significant changes in the concentration of stone formation inhibitors., Discussion: The increase in bikunin concentration in control patients is associated with an increase in the expression of this stone formation inhibitor due to the rise in the urolithiasis activity. Reduction in the osteopontin concentration in patients with high urolithiasis activity is a consequence of osteopontin being a constituent of calcium oxalate stones., Conclusion: In patients with calcium oxalate urolithiasis, testing for urine concentrations of bikunin and osteopontin as potential markers can be used to estimate the risk of stone recurrence.

Hereditary thrombophilias (HT) and undifferentiated connective tissue dysplasia (uCTD) are important causes of female infertility. Moreover, there are signs of their common pathogenesis: a number of proteins, such as PAI-1, play an important role in the pathogenesis of both conditions, as well as in the development of infertility in patients with HT and uCTD OBJECTIVE: To determine the morphological substrate and molecular mechanisms of impaired pregnancy outcomes in women with uCTD and HT. SUBJECT AND METHODS: A study group included 130 reproductive-aged female patients with primary infertility and a control group consisted of 11 patients (surrogate mothers). An endometrial pipelle biopsy sample was taken from each patient on days 6-8 after ovulation according to the ultrasound findings. The study group patients were divided into subgroups: 1A) infertility and HT (n=91); 1B) infertility, NT, and uCTD (n=19); 1C) infertility and uCTD (n=20).

To evaluate the level of U. urealyticum colonization of female urogenital tract, the method of the multiplex polymerase chain reaction (PCR) in the presence of two pairs of primers, corresponding to genes controlling U. urealyticum 16S rRNA and unique human osteopontin was used. The study of 93 clinical specimens showed no correlation between high colonization level and the presence of definite clinical manifestations of U. urealyticum infection. The determination of ureaplasmic biovars was carried out by the method of PCR in the presence of 3 primers corresponding to the multiple-banded antigen (MBA) gene. Biovar parvo was detected in 85% of the specimens, biovar T960 in 11% and both biovars were detected in 4% of the specimens. The biovar distribution in the groups of women with different clinical symptoms was approximately similar. U. urealyticum of biovar T960 occurred more frequently (33% of the specimens) only in a group of women with vaginal discharge characteristic of inflammation.

Conservatism of primary and secondary structure of osteopontin mRNA in vertebrates of various taxes was studied using computer analysis and blot-hybridization procedure. Relatively high rate of evolution of a nucleotide sequence of osteopontin gene was revealed. Formation of hairpin-loop structures by adjacent sequences and a high content of AU-pairs indicate more flexible structure of the mammalian osteopontin mRNA as compared with the avian one. It has been detected some AU-enriched regions in 3'-terminal untranslated sequences, which presence is characteristic for short-lived mRNA. Evolutionary conserved subsequences in 3'- and 5'-terminal regions were suggested to be determinants of RNA-protein interaction in cytoplasm.

DNA transcription and replication are organized by the nuclear matrix. It has been recently shown that the osteocalcin gene promoter binds specifically two proteins, NMP-1 and NMP-2 (nuclear matrix proteins 1 and 2), from cell line ROS 17/2.8 (Bidwell et al., 1993). Osteocalcin in one of the proteins taking part in extracellular matrix mineralization during osteogenic differentiation. Osteopontin gene is also active at the late stages of osteogenesis, so we supposed that its promoter could be bound to the nuclear matrix as well. Among the nuclear matrix proteins of ROS 17/2.8 we have found a protein factor which binds the promoter region of the osteopontin gene specifically with the help of gel shift assay. Two proteins with isoelectric points of pH > 8.0 and mol. masses of 38 and 43 kDa, respectively, have been purified by affinity chromatography with the promoter region of osteopontin attached to cellulose. The mol. masses of the revealed proteins are similar to those of already characterized NMP-2 (38 kDa) and one of subunits of heterodimer NMP-1 (43 kDa). Computer analysis shows that the binding sites for these proteins exist in the osteopontin gene promoter region. So, it is very likely that we dealt with the same proteins. A further investigation could lead to characterization of a group of nuclear matrix attached osteogenic-specific transcriptional factors.