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Non-malignant breast diseases (NMBD) may increase the risk of developing a malignant neoplasm. Therefore, it seems relevant to search for criteria for cell malignancy in NMBD. Aim of the study was to investigate the relationship between expression of proliferation and epithelial-mesenchymal transition (EMT) markers and histidine-rich glycoprotein (HRG) mRNA in breast diseases. Material and methods. In breast biopsy specimens of 37 patients with invasive carcinoma of a non-specific type (ICNT) and 17 patients with NMBD expression of proliferation markers (Ki-67, cyclin D1 (CCND1)) and EMT markers (E-cadherin (CDH1), type II collagen (CII) and β1-integrin (CD29)) was determined immunohistochemically. HRG mRNA expression was estimated using real time PCR. Results. HRG mRNA expression was detected in 91.9 % cases (34 of 37) in ICNT, 82.4 % (14 of 17) in NMBD and in the latter case was inversely related to the expression of CDH1, CD29 and Ki-67. A direct relationship has been established between the presence of Ki-67 and CCND1, CII, between CCND1 and CD29 in NMBD. In patients with ICNT, a direct correlation was found between the HRG mRNA expression and the presence of CII, and an inverse correlation between the number of cells containing CII and CD29. It was found that in ICNT and NMBD with the presence of HRG mRNA expression, the CDH1 expression is less than in its absence. Conclusions. Indicators of HRG mRNA expression in NMBD, combined with the assessment of proliferation and EMT markers, can be useful in developing criteria for cell malignancy in benign breast diseases.

Metastasis is the leading cause of death in patients with breast cancer (BC). It is known that the lesion of regional lymph nodes by tumor cells is more common in tumors with higher proliferative activity. Moreover, there is literature evidence on effects of cytokines and proteins upon the migration potential of the tumor. The aim of our work was to study the correlation between the concentrations of cytokines, proteins, and expression of Ki-67 proliferation marker in breast cancer with histology of non-specific invasive carcinoma.On the basis of pathological findings, 16 patients had metastases in regional lymph nodes (group I), and 18 patients had no detectable metastases (group II). Solid-phase enzyme immunoassay was used to determine concentrations of 14 cytokines in the supernatants of immunocompetent blood cells, i.e., IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF and MCP-1, and concentrations of 6 proteins were determined in blood serum: estrogen and progesterone receptors, cadherin-E (CDH1), plasminogen activator type 1 (PAI-1), mucin 1 (MUC1), heat shock protein 90αA1 (HSP90αA1). Immunohistochemical study of Ki-67 expression was performed in paraffin sections of tumors using monoclonal antibodies.The study showed that Ki-67 expression in tumor tissues and blood concentrations of IL-6, IL-8, IL-1β and TNFα were higher in group I patients. On the contrary, blood concentrations of CDH1 and PAI-1 were higher in group II patients. It was found that Ki-67 showed both inverse correlations with CDH1 and PAI1, and direct correlations with IL-8 and TNFα. CDH1 had a direct correlation with PAI1, and inverse correlations with IL-6, IL-1β and TNFα. The studied cytokines showed direct correlations with each other. The analysis of ROC curves showed good quality and optimal values of the cut-off points for Ki-67 expression, cytokine and protein concentrations, thus allowing best prediction for detectable lymphatic metastasis.On the basis of these results, a quotient was proposed, which represents a ratio of CDH1 contents to the sum of IL-1β and TNFα concentrations in blood samples, which can help identification of the patients with breast cancer at risk for lymphatic metastasis.

A lot of attention is paid to distance learning today, as, probably, none of the many ways of learning using technology. Modern research in education, and in particular in ICT, tends to use technological resources to the maximum and use them effectively in pedagogy. In the field of foreign language teaching, much has been done to cover various languages of the world, but attempts are constantly being made to find new solutions, taking into account the specific needs of language learners. The purpose of the article is to present the technological aspect of the DE system common to all courses, to identify the main features of teaching a foreign language in distance learning, to consider the process of developing and implementing online English courses from the point of view of the overall design of the course, the choice of teaching materials, technological and pedagogical processing of course materials, the role of the teacher, support and motivation of students.

The study objective is to improve results of treatment of patients with low-risk prostate cancer (PC).Materials and methods. In the study, comparative analysis of data from 84 patients with low-risk PC was performed: 40 patients were included in the active observation group (group 1) and 44 patients underwent radical prostatectomy (group 2). For evaluation of functional responses the following questionnaires were used: Short Form 36 Health Quality Survey (SF-36), International Index of Erectile Function (IIEF-5), International Prostate Symptom Score (IPSS), Expanded Prostate Cancer Index Composite (EPIC-26). For control of oncological results, tests for prostate-specific antigen, digital rectal examination, magnetic resonance imaging of the pelvic organs with intravenous contrast, and confirmation biopsy of the prostate were preformed.Results. Mean score for the SF-36 questionnaire in the group 1 (active observation) at the beginning of the study was 63.2 ± 11.5 for mental health (MH) and 57.1 ± 9.8 for physical health (PH), while in the group 2 MH score was 63.1± 6.8, PH score was 56.2 ± 8.6. However, 18 months later in the group 1 mean MH score increased to 68.2 ± 10.1, mean PH score to 62.4 ± 7.8; in the group 2 PH score increased insignificantly to 64.2 ± 7.4 and PH score decreased to 54.8 ± 5.4 (p

Introduction. An original research work was performed to assess split kidney function by glomerular filtration rate (GFR) with mathematical analysis of the kidneys computed tomography (CT) data in patients with kidney stone disease (KSD). Objective was to evaluate the GFR and the parenchyma structure of each kidney and identify the possible patterns of contrast medium intrarenal transport with mathematical analysis of the kidneys CT data in patients with KSD.Materials and methods. Data of 27 patients of both genders with KSD were retrospectively analyzed. To evaluate GFR separately for each kidney we analyzed the data of contrast-enhanced CT (GFR reference values are 0.55 % of contrast medium per second). Inclusion criteria are as follows: 1) newly diagnosed SKD; 2) stone size ≤1,5-2,0 cm, no obstruction of the urine flow registered; 3) no kidney or upper urinary tract surgical history; 4) age - ≤45 years; 5) no severe chronic diseases. All of these allowed to minimize influence of any other disorders on split renal function except for SKD and conduct per se research.Results. The mathematic analysis of the contrast-enhanced CT data revealed GFR changes in 26 (96.3 %) out of 27 patients. Hyperfiltration was found in 12 (44.4 %) patients: right kidney GFR - 0.6-0.77 %, mean value - 0.65 %; left kidney GFR - 0.59-0.79 %, mean value - 0.67 %. Hypofiltration was found in 13 (48.1 %) patients: right kidney GFR - 0.2-0.54 %, mean value - 0.37 %; left kidney GFR - 0.2-0.53 %, mean value - 0.4 %. The GFR values significantly differed between the groups both for the right (p = 0.000014) and left (p = 0.000045) kidneys. We found no significant age-related difference between the groups (p = 0.895). As well as that no significant differences in Resistance Index both in magistral (right kidney: p = 0.221; left kidney: p = 0.850) and segmental (right kidney: p = 0.306; left kidney: p = 0.957) arteries between the groups with hyperfiltration and hypofiltration were observed. One patient demonstrated no changes in GFR, and the other one had hyperfiltration (0,62 %) in one kidney and hypofiltration (0,48 %) in another.Conclusion. Most of the patients (92.6 %) with SKD demonstrate GFR changes (either hyperfiltration or hypofiltration) that may indicate the disturbed intrarenal blood and urine flow through the kidney.

To improve early detection of cancer, search for tumor markers in biological fluids is of great importance. A significant portion of exosomes is associated with the surface of blood cells, however, the protein spectrum of such exosomes has not been previously studied. The use of total blood exosomes (plasma exosomes and exosomes associated with the surface of blood cells) can not only significantly increase the specificity and sensitivity of existing methods, but also suggest new tumor markers for liquid biopsy.Objective. Search for candidate protein tumor markers of breast cancer by comparing 2D-proteomic maps of total blood exosomes of healthy females (HFs) and breast cancer patients (BCPs).Methods. Exosomes were isolated from plasma and total blood of HFs and BCPs by ultrafiltration followed by ultracentrifugation and were characterized using transmission electron microscopy (TEM) and immunocytochemistry. Protein concentration in exosomes was determined using the NanoOrange Protein Quantitation kit (Invitrogen) commercial kit. Proteomes of exosomes were studied using 2d electrophoresis followed by protein identification by mass spectrometry.Results. Highly purified samples of vesicles from plasma and total blood of no more than 100 nm in size were obtained, on the surface of which markers specific for exosomes were detected by monoclonal antibodies CD9. A comparative analysis of the proteomic maps of exosomal proteins of the HFs and BCPs obtained by 2D-electrophoresis allowed us to establish significant differences in the expression level and protein set in normal and pathological conditions. The 11 proteomic markers of breast cancer were identified by the peptide fingerprint method, of which LRG и у-chain FGB were detected in the composition of exosomes for the first time (according to the Exocarta database). Using MALDI-TOF mass spectrometry, 99 proteins were identified in the exosome preparations of the blood of HFs and BCPs, of which 35% were detected in the composition of the exosomes for the first time (according to the Exocarta database). 17 (53%) proteins associated with breast cancer were detected in total blood exosomes of cancer patients.Conclusion. The results obtained indicate that total blood exosomes are a promising source of diagnostic material for the search for proteomic markers of breast cancer. The identified proteomic tumor markers require further validation.

The aim of this study was to evaluate production of cytokines by the blood immune cells in patients of different age groups with invasive non-specified type mammary ductal carcinoma, with or without metastases. Production of cytokines by periphery blood immunocompetent cells, either spontaneous and stimulated with polyclonal activators, was assessed in 82 patients with invasive mammary ductal carcinoma. The concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1p, IL-1ra, TNFa, IFNy, G-CSF, GM-CSF, VEGF и MCP-1 were determined by solid-phase enzyme-linked immunosorbent assay. The patients were divided into 2 age groups: the first group consisted of 48 patients from 45 to 60 years old; the second group consisted of 34 older patients (61 to 75 years old). Metastases in local lymph nodes were documented in twenty patients from the first group and nine patients from the second group. The younger patients (45-60 years old) with metastases in local lymph nodes showed higher polyclonal activation index of IL-4 and IL-1ra production, when compared to the patients without lymphatic metastases. As for the older patients (61 to 75 years old), their polyclonal activation index of IL-6, IL-8, IL-1ra, G-CFS, GM-CSF production was significantly lower in cases of local lymph nodes metastases. The latter was due to higher level of spontaneous production, which suppressed the influence of polyclonal activators. The index of polyclonal activation upon production of cytokines in patients with lymphatic metastases was shown to be significantly higher for the age group of 45 to 60 years than in the age group of 61 to 75 years old. This fact suggested a highly stimulating effect of polyclonal activators in patients younger than 60 years. It was found that correlation between the index of polyclonal activation of cytokine production, and the indexes of ER, PR, HER2/NEU and Ki-67 receptor expression, which are used for the determination of molecular genetic subtype of the tumor, differ significantly for the distinct age groups.

The demand for low- and non-fat products has recently increased due to the health problems, such as obesity, diabetes, and cardiovascular diseases, that have resulted from high-fat products. However, the reduction in fat can affect the quality of products adversely. The objective of this work was to explore the potential of whey protein isolate (WPI) in improving the quality of non-fat yogurt prepared using skim milk powder (SMP). Yogurt mixes (standardized at 14% total solids) were formulated using SMP as a milk base enriched with WPI. The SMP was replaced by WPI in the yogurt mixes at a rate of 3, 5, 7, and 9%. Full-fat and non-fat set-style yogurts were prepared from whole milk and skim milk, respectively, as controls. Yogurts were fermented at 43 °C to get a pH of 4.6 and stored at 4 °C for the next day. The texture, microstructure, rheological characteristics, and sensory properties of the yogurt samples were studied. The incorporation of WPI increased the water holding capacity to 50% as compared to the non-fat control. This improved the rheological properties while the yogurt viscosity increased in direct proportion with increasing the WPI. The firmness of yogurt was inversely proportional to the increase in WPI, which resulted in 180 g firmness when 9% WPI was added to the non-fat yogurt formulations. Yogurts’ microstructure improved by the addition of WPI. The non-fat yogurt incorporated with 3 and 7% WPI had comparable sensory and textural characteristics to the full-fat yogurt. WPI can be used as a fat replacer to develop low-fat yogurt with desired features. WPI may be a natural and economical ingredient for producing low- and non-fat fermented dairy food products.