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The article deals with the Chinese global strategy the Silk Road Economic Belt and the possibility of involving Ukraine in it. The authors pay special attention to the implementation of the China-Ukraine-EU High-Speed Railway Project within the framework of the Silk Road Strategy. The geopolitical position of Ukraine allows the authors to state that Ukraine may represent a special interest for the Celestial Empire as a logistical hub and a kind of “window” to Europe, as the central axis of the international transport corridors passes through Ukraine. The authors analyze the direct economic, as well as external economic and social effects of the construction of High-Speed Railways in Ukraine.

The studies are devoted to the transformational processes associated with digitalization, which takes place in the Ukrainian economy. Economic development is impossible without widespread introduction and full use of the digital technologies. The rate of digital innovation is growing every year. The transformation of the landscape of interpersonal connections and economic relations leads to the digitalization of the operational processes and the change in business models, which generally results in large-scale digital transformation of companies. Meanwhile, it should be noted that the digitization and transformation processes of business models, taking place mainly at the level of private and state enterprises, are expanding to the level of government and have a significant impact on the competitiveness of the economy. Today, there is a significant number of projects of digital transformation in Ukraine. The general idea is to create a unified digital communication system. It is nice to note that not only private companies but also state structures have joined this system, which testifies to their interest in self-development and the desire to keep up with the modern technologies, focusing on clients.

Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy.Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor.Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color-coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer.Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+/ISH±); and 15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15 000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression.Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2-enriched molecular class and the response to anti-HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.

Background: Natural antimicrobial peptides are used in the fight against pathogens resistant to existing synthetic antibiotics. The non-specific mechanism of cytostatic action of antimicrobial peptides, in particular gramicidin S, against bacteria is also effective for damaging the cells of neoplasms. The existence of such a property in a registered antibiotic will indicate its antineoplastic potential and can be used to expand the spectrum of its therapeutic application. Aim of work is to clarify the possible antitumor effect of the antimicrobial peptide gramicidin S. Materials and Methods: Using the methods of confocal laser microscopy and light microscopy, the morphological and functional features of connective tissue cells under the influence of gramicidin S in the concentration range 0.5–50 μg/ml were studied using L929 fibroblasts cell culture. The cell area, nucleus area, and nucleus-to-cytoplasm ratio were determined. To study the migratory and proliferative activity of cells in vitro, the “scratch assay” was used, the confluency of the monolayer of cells was evaluated, morphometric studies were performed, and the relative area of the scratch was measured after 24, 48, and 72 hours. Results: The lytic effect of gramicidin S in a concentration of 50 μg/ml on L929 cells was established, in concentrations of 0.5 μg/ml and 5.0 μg/ml, the antibiotic increases the synthetic activity of cells and stimulates the proliferation of fibroblasts in a monolayer. Cell anisomorphism is more pronounced in the presence of 5.0 μg/ml gramicidin S added to the culturing medium during monolayer formation, while a one-third of the cells in the sample form a population that is morphologically different from other cells in the culture. The addition of gramicidin S at non-lytic concentrations of 0.5 and 5.0 μg/ml to unattached fibroblasts reliably inhibits monolayer formation. Under the influence of 5.0 μg/ml gramicidin S, the rate of monolayer formation is low, even despite the significant content of cells with a high nuclear-cytoplasmic ratio. The kinetics of filling the cell monolayer defect using the “scratch assay” shows that GS in concentrations of 0.5 and 5.0 μg/ml can control the migratory and proliferative properties of L929 cells. Conclusions: The effect of gramicidin S on the morphometric parameters of cells depends on the concentration of the peptide and the cell status in the culture. GS corrupts the adhesive properties of L929 fibroblasts in monolayer cell culture and the rate of cell monolayer formation. Cells at the stage of attachment and monolayer formation were most sensitive to non-lytic concentrations of GS. Inhibition of the adhesive properties of connective tissue cells by gramicidin S is a new non-canonical effect of a known antimicrobial drug, which may indicate the possibility of using gramicidin S as an anti-neoplasm agent.

Background. Breast cancer is one of the most common female malignancies. Molecular diagnostic methods of tumor profiling allow us to analyze individual tumor characteristics, identify new prognostic and predictive markers. Aim. To increase the efficacy of systemic therapy for breast cancer and reduce inappropriate prescriptions using the data on individual molecular tumor characteristics; to develop a polygenic panel to ensure a tailored approach to systemic therapy for breast cancer. Materials and methods. We analyzed 84 tumor tissue samples from pre- and postmenopausal women with metastatic breast cancer who were treated and followed-up in 6 healthcare institutions. We assessed expression of genes involved in breast cancer. In a pilot study, we analyzed archived paraffin-embedded tumor specimens form 12 out of 1,216 patients with T1–2N0M0 breast cancer included into retrospective analysis. Gene expression was assessed using the nCounter technology based on direct digital detection of targets using fluorescent barcodes (nCounter Analysis System; NanoString Technologies, USA). Tumor tissue (biopsy and surgical specimens) was analyzed. The choice of genes was based on the literature data and experience in the development of other polygenic panels, as well as clinical significance of markers of prognostic scales. Gene mutations were confirmed by next generation sequencing and reverse transcription-polymerase chain reaction. Results. We analyzed the expression of 28 genes with a high predictive value that have been substantially studied (including ESR1, PGR, PIK3CA, BCAR4, BCAS2, CCND1, CCND2, CCND3, FOXA1, Erb2, EGFR, CDH3, FOXC1, KRT14, KRT5, CD274, CDK4, CDK6, P53, PTEN, BRCA1, BRCA2, CHEK2, CLDN3, CLDN7, AR, TOP2a, TUBBIII). We identified 29 cases of discrepancy (29 / 84; 34.5 %) in tumor subtype, including 11 cases of luminal A and B breast cancer, which might potentially affect the choice of the treatment regimen. In 18 cases, there were some principal discrepancies in the tumor subtype that implied totally different treatment regimens. The proposed polygenic signature allows accurate identification of the tumor subtype in patients with metastatic breast cancer and choice of an optimal treatment strategy. Conclusion. We have developed a 100-gene signature including molecular subtypes of breast cancer (luminal A, luminal B, basal, claudin-like) and treatment-oriented clusters. Molecular tumor profiling using this polygenic signature is an accurate method for determining tumor subtype in patients with breast cancer, which enables a tailored approach to therapy.

In this work, fragments of isophthalic and terephthalic acids are proposed as a structural scaffold to develop potential inhibitors of protein kinases. Novel isophthalic and terephthalic acid derivatives were designed as type-2 protein kinase inhibitors, synthesized and subjected to physicochemical characterization. The screening of their cytotoxic actions against a panel of cell lines derived from different types of tumors (liver, renal, breast and lung carcinomas, as well as chronic myelogenous and promyelocytic leukemia) and normal human B lymphocyte, for the sake of comparison, was performed. Compound 5 showed the highest inhibitory activity against four cancer cell lines, K562, HL-60, MCF-7 and HepG2 (IC50 = 3.42, 7.04, 4.91 and 8.84 µM, respectively). Isophthalic derivative 9 revealed a high potency against EGFR and HER2, at the levels of 90% and 64%, respectively, being comparable to lapatinib at 10 µM. In general, tumor cell cultures were more sensitive to isophthalic acid derivatives than to terephthalic acid ones. In cell cycle studies, isophthalic analogue 5 showed a pronounced dose-dependent effect, and with the increase in its concentration up to 10.0 µM, the number of living cells decreased to 38.66%, while necrosis reached 16.38%. The considered isophthalic compounds had a similar docking performance to that of sorafenib against the VEGFR-2 (PDB id: 4asd, 3wze). The correct binding of compounds 11 and 14 with VEGFR-2 was validated using MD simulations and MM-GPSA calculations.

As a consequence of the advances in systemic neoadjuvant therapy of breast cancer is the de-escalation of surgical treatment. The study of a limited number of axillary lymph nodes after neoadjuvant therapy and refusal of lymphadenectomy in the absence of metastatic lesions is becoming more common. The published studies have proven the informativeness and safety of standard techniques of sentinel lymph node biopsy after neoadjuvant treatment for cN0 patients. For group cN1 and regression of metastases after neoadjuvant treatment, standard sentinel lymph node biopsy techniques have failed. The use of combined methods of double detection and an increase in the number of examined lymph nodes to 3 and more increased the detection rate of sentinel node biopsy after neoadjuvant therapy and reduced false-negative rate. Long-term results, questions of methodology lymph nodes evaluation, radiation therapy in this group of patients require further investigation.

At the first stage of studying the pharmacological properties of substances, the general cytotoxic effect is determined based on the assessment of viability, morphological integrity and functional activity of cells. One of the standard cell lines often used in cytotoxicity tests is the L929 line. Studying the ability of a combined lipid-lowering agent based on dense carrot root extract and quercetin to influence the morphological and functional properties of fibroblasts of the L929 line in cell culture was the aim of this study. Materials and methods. Determination of the cytotoxicity of the drug under study was carried out in a cell culture of the L929 line at a concentration of 40, 100, and 200 mg/ml. The safety of cells in the resulting suspension was assessed using staining with a 0.4 % trypan blue solution. Cell morphology and nuclear-cytoplasmic ratio were assessed in fixed culture preparations stained with hematoxylin-eosin. To assess the migration and proliferative activity of a monolayer culture, the "scratch" test was used. Results. When L929 cells were incubated in a nutrient medium with the addition of the product, their viability and morphological properties were preserved; images of a monolayer of the culture of these cells under phase-contrast microscopy coincided with the quantitative analysis data. The absence of changes in the nuclear-cytoplasmic ratio was further evidence of the absence of toxic effects of the studied drug in relation to fibroblast culture. According to the experiment results, the migration and proliferative activity of L929 cells under the influence of the drug did not differ significantly from intact cells. Conclusions. The results of the toxicological study showed that the combined product based on dense carrot root extract and quercetin does not have a cytotoxic effect on the L929 cell line culture and can be recommended for further preclinical research. [ABSTRACT FROM AUTHOR]

Abstract. The research aimed to study the morphological characteristics of kidneys after intraperitoneal administration of biologically active compositions (BACs) in rats with infravesical obstruction (IVO). Methods. IVO was reproduced by surgical ligation. BACs were injected intraperitoneally for 10 days. The morphometric parameters of the kidneys were determined by examining their structure (the areas of renal corpuscle, glomerulus, the cavity of the glomerular capsule, outer and inner diameters of the tubules, the tubular index, the outer diameter and area of the vascular lumen). The experimental animals were divided into the following groups: Group 1 was saved as an intact control group, Group 2 received “Cortexin”, Group 3 was given CMCNMG, Group 4 received BCM, and Group 5 was not treated (U). Results. BACs obtained from a culture of native mantle gliocytes (MG) and BCM were involved in the remodeling of the kidneys’ structure being changed during IVO. The renal corpuscle area was found to be increased in groups 2, 4, and 5 by 42.3%, 193.9%, and 72.3%, respectively, compared with the control group. At the same time, the extent of renal corpuscle hypertrophy in group 3 was minimal and approached the control values. The glomerulus area expanded by 35.4%, 181.1%, and 34% in animals of groups 3, 4, and 5, respectively, compared with the control group. However, the difference in the index between group 5 and BAC-treated animals was not significant, except for group 4. The Bowman's capsule area increased by 117.6%, 235.8%, and 186%, in groups 2, 4 and 5, respectively, compared with the control group. Interestingly, the values in groups 1 and 3 were in agreement but differed from group 5. The lowest values of outer and inner diameters of renal tubules were determined in group 3, which were close to those in the control group but significantly different from those of other groups. An increased tubular index (by 1.35 and 1.4 times) was revealed in groups 3 and 4, compared with other groups. The lowest values were found in groups 2 and 5. The maximum values of the average diameter and area of the vessel lumen were determined in groups 3 and 4, and the minimum values were obtained in group 5. It is noteworthy that the indices of these groups were significantly different from those of group 5. Conclusions. The research results suggest that the phenomena of glomerulosclerosis, tubular atrophy, and renal interstitial fibrosis in rats can be alleviated, as well as the morphological structure of rat kidneys can be partially restored against the background of IVO after administration of CMCNMG and, to a lesser extent, BCM due to the multidirectional action of neurotrophic factors.

Cadmium (Cd) is a widespread and non-biodegradable pollutant of great concern to human health. This element can affect cellular signal transduction and cell-to-cell interaction in the testis. Immune tolerance towards auto- and alloantigens is an important component of testis immunity. It is involved in spermatogenesis and hormone secretion. Plus, the immune tolerance may help to reveal the changes in testis immunity over a long period after Cd exposure. The current research was aimed at investigating the long-term effects of acute Cd exposure on testis immunity by means of elicitation of testicular immune cell composition shift induced by Cd. Cadmium chloride was intraperitoneally injected at 3 mg Cd/kg to mice. After that testis interstitial cells were stained with surface markers for leukocyte and lymphocyte subpopulations (CD45, CD11b, CD3, CD4, CD8, CD25) and analyzed cytofluorimetrically by week 4, 6, 8 and 12 after Cd administration (Cd group). To identify the delayed effects of cadmium on immune tolerance two groups of animals were subjected to intratesticular allotransplantation of neonatal testis (groups ITT and Cd+ ITT). One of the groups was administered with Cd four weeks before the transplantation (Cd+ITT group). I group served as a control that did not undergo any transplantation or Cd injection. For a better demonstration of the phenomenon of immunological tolerance of the testicles, an additional group (UKT group) was used which got grafts under the kidney capsule (non-immune privileged site).Investigation of the cell population showed that CD45+, CD11b+, CD4+, CD8+ cells were permanently present in testicular interstitial tissue in I group. Intratesticular testis transplantation increased the proportion of CD11b+ but did not have such a pronounced effect on CD8+ cells in ITT group. Moreover, the transplantation elevated CD4+ CD25+ cells known for their immunosuppressive property and promoted graft development by week 2 (histological data). Cd injection resulted in severe inflammation that quenched by week 4 (Cd and Cd+ ITT groups). This time point was chosen for transplantation in Cd+ ITT group. Such Cd pretreatment led to a high CD8+ cell proportion and to the delayed appearance of CD4+ CD25+ cells by week 2 (Cd+ ITTgroup). The finding is consistent with the impairment of graft development in Cd+ ITTgroup pretreated with Cd. Observation suggest that Cd pretreatment was associated with disproportion of interstitial immune cell populations which resulted in the impairment of immunoprotective function of the testis. The impairment of testis immunity showed itself only after several weeks of Cd administration, and only when the recipient testis immunity was provoked by alloantigens of donor testes.

Interest in adjuvant endocrine therapy in the treatment of women with breast cancer does not fade for many years. In recent decades, more and more attention has been paid to the role of ovarian suppression. Recent publications and data from international congresses confirm the necessity of prescribing predominantly medicamentous ovarian suppression to women with breast cancer and preserved menstrual function not only as a therapy but also for fertility preservation.

The article presents a literature review on late radiation injury (RI) of skin and subcutaneous fat after surgical treatment and radiation therapy (RT) in patients with breast cancer (BC). In Russia, the rate of radiation injuries in patients after RT exceeds 10–15 %. Combination treatment of BC (surgery and radiation) carries a risk of RI of skin and subcutaneous fat which might lead to dystrophic changes in the form of prominent radiation-induced fibrosis of the irradiated area, lower the quality of life, cause suffering and even death. Most of BC patients are of working age, so the problem of local RI is of social importance, and it requires effective methods of treatment and rehabilitation allowing for favorable conditions for patients’ social adaptation. Currently, there’s no consensus on the mechanisms of development of skin and subcutaneous fat late RI, and it’s being considered from several angles. Therefore, problems of determination of individual sensitivity to ionizing radiation and further study of local RI of skin and subcutaneous fat after surgical treatment and RT in BC patients are of utmost importance.

In 11.5 % of breast cancer patients distant metastases are detected at diagnosis. The results of treatment of 608 patients of 5 Russian oncological centers are presented. Removal of the primary tumor in case of newly diagnosed advanced breast cancer increases the mean duration of life from 23 up to 35 months (p < 0.01). Three-year overall survival increases from 47 to 65 % and 5-year survival – from 21 to 45 % (p = 0.001). The most impressive effect of surgical treatment is observed in patients with bone metastases, 1–2 metastatic lesions in one anatomical region, with positive effect after systemic treatment, high expression estrogen/progesterone receptors, possibility of attaining free surgical margins.

The development of inexpensive equipment adapted for the study of a specific biological object is very important for cryobiology. In the presented work, we have proposed a simple system for microscopy utilising open‐source platform Arduino. Testing this system showed that it had sufficient sensitivity to determine the physical processes occurring in a cryopreserved sample such as intra‐ and extracellular water crystallisation and salt eutectic. Utilising this system, we investigated the mechanisms of cryoprotection and cryodamage of testis interstitial cells (ICs) in cryoprotective media, which included cryoprotective agents such as dimethyl sulphoxide (Me2SO), as well as foetal bovine serum or polymers (dextran, hydroxyethyl starch and polyethylene glycol). It was shown that a serum‐/xeno‐free medium that included 0.7 M Me2SO and 100 mg/mL dextran was able to reduce intracellular water crystallisation in cells, change the structure of extracellular ice, and reduce salt eutectic and recrystallisation. All these effects correlated with better IC survival after cryopreservation in the medium. This medium is potentially less toxic as it has lower concentrations of Me2SO compared to serum‐containing media developed for cryopreservation of testicular cells. This would pave a way for the creation of nontoxic serum‐free compositions that does not require removal before use of cryopreserved living cells for laboratory practice or in clinics. LAY DESCRIPTION: Research in the field of cryobiology involves many technics linked with the assessment of cell recovery after cooling/warming as well as quantification, identification and description of physical processes occurring in and out of the cells. These processes can affect the overall outcome of cryopreservation. Thus, the investigation of the mechanisms of cryoprotection and cryodamage is of high importance. In this work, we have developed a system for cryomicroscopy utilising open‐source platform for prototyping electronic devices and systems Arduino. The platform includes hardware and software designed to develop various projects. It also supports a programming language. The language was used to create a code to control cooling rate of the sample undergoing microscopy. The system was able to visualise the structure of the forming ice crystals, recrystallisation, salt eutectic crystallisation/melting and intracellular phase transitions. It can be utilised in combination with other approaches and techniques. The system helped us to solve specific tasks of cryobiological experimentation connected with the establishment of mechanisms of cryoprotection and cryodamage of testis interstitial cells (ICs). The microscopy data allowed us to compare different media developed for cryopreservation of testicular cells. The serum‐containing cryoprotective medium (1.4 M Me2SO and 10% foetal bowine serum) was able to suppress darkening of cell, known as 'flashing' associated with intracellular phase transitions by moderately dehydrating cells, and salt eutectic transitions during cooling/warming. However, the media contains relatively high Me2SO concentration and may be toxic. Additionally, the use of serum in the media can result in transferring infection when cryopreserved cells are used in medicine or veterinary, or lead to instability of the composition of serum‐containing media from batch to batch. In the course of the research, we have shown that using the serum‐/xeno‐free medium supplemented with 0.7 M Me2SO and 100 mg/mL Dex (0.7 Me2SO+Dex) can also reduce cell 'flashing'. The medium influenced the size and shape of extracellular ice crystals in a way that can potentially reduce the risk of mechanical cell damage. This medium promoted amorphous solidification in the space between the extracellular ice crystals, thus, lowering the salt eutectic transitions and recrystallisation that could otherwise cause additional cell damage. Therefore, application of the developed system for cryomicroscopy, which allowed real‐time visualisation of cryobiological processes, made it possible to draw a conclusion about cryoprotecitive properties of medium for ICs. 0.7 Me2SO+Dex can be the basis for the creation of commercial serum‐free media with a defined composition that does not require removal before use. [ABSTRACT FROM AUTHOR]