Концептуально-фреймовий аналіз квазісинонімічного ряду кіберсету ПОРУШНИК СИСТЕМИ. (THE CONCEPTUAL FRAME ANALYSIS OF QUASISYNONYMIC GROUP OF CYBERSET SYSTEM BURGLAR.)

У статті висвітлено дослідження аналізу квазісинонімічного ряду кіберсету ПОРУШНИК СИСТЕМИ (hacker, cracker, phreaker). Звернуто увагу на аналіз значення зазначених комп’ютерних неологізмів та порівнювання їх лексико-семантичних варіантів (ЛСВ). Сконструйовано слоти предметного та акціонального фреймів в межах даного кіберсету. Представлено таблицю кількісних параметрів слотової подібності та розбіжності комп’ютерних неологізмів hacker, cracker та phreaker, які входять до складу кіберсету ПОРУШНИК СИСТЕМИ. Визначено слоти у яких виявляється точна та неточна синонімія. Окреслено та досліджено явище квазісинонімії в межах представленого кіберсету. Визначено домінанту цього кіберсету, яка може замінити будь-який із комп’ютерних неологізмів у широкому лінгвістичному контексті) (The article deals with the research of analysis of quasisynonymic group of cyberset SYSTEM BURGLAR (hacker, cracker, phreaker). Attention has been devoted to the analysis of the above mentioned computer neologisms definitions and the comparison of their lexico-semantic variants. Slots of objected and actional frames have been constructed in the given cyberset. The table of similarity and difference of slots parameters of the computer neologisms hacker, cracker and phreaker make up the cyberset SYSTEM BURGLAR has also been presented. Slots with the exact and non-exact synonymy have been defined. It has also been described and studied the phenomenon of quasisynonymy in the given cyberset. The dominant of the given cyberset has been identified and it can substitute any of the computer neologisms in the wide linguistic context.

Последствия фиктивного банкротства для кредиторов

Ясинская Д. В. Последствия фиктивного банкротства для кредиторов / Д. В. Ясинская // Римське право як підґрунтя сучасного права Європи : матеріали Міжнар. наук.-практ. конф. (м. Одеса, 27 травня 2016 р.) / за заг. ред. Є. О. Харитонова ; НУ "ОЮА". Півд. регіон. центр НАПрН України. - Одеса : Фенікс, 2016. - С. 258-260

Interaction between diabetes-associated disorders of the salivary glands and oral mucosa (literature review)

The aim of the study: to analyze literature sources concerning interaction between pathogenesis of lesions of the salivary glands and oral mucous membrane in patients suffering from diabetes mellitus (DM).  Conclusion. Analysis of the current literature is quite explicit on the point concerning interdependence of lesions of the salivary glands and morphofunctional changes of the oral mucosa with diabetes mellitus

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells

Activation of immune evasion machinery is a part of the process of malignant transformation of human cells.

Malignant transformation of human cells is associated with their re-programming which results in uncontrolled proliferation and in the same time biochemical activation of immunosuppressive pathways which form cancer immune evasion machinery. However, there is no conceptual understanding of whether immune evasion machinery pathways and expression of immune checkpoint proteins form a part of the process of malignant transformation or if they are triggered by T lymphocytes and natural killers (NK) attempting to attack cells which are undergoing or already underwent malignant transformation. To address this fundamental question, we performed experimental malignant transformation of BEAS-2B human bronchial epithelium cells and RC-124 non-malignant human kidney epithelial cells using bracken extracts containing carcinogenic alkaloid called ptaquiloside. This transformation led to a significant upregulation of cell proliferation velocity and in the same time led to a significant upregulation in expression of key immune checkpoint proteins - galectin-9, programmed death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO1). Their increased expression levels were in line with upregulation of the levels and activities of HIF-1 transcription complex and transforming growth factor beta type 1 (TGF-β)-Smad3 signalling pathway. When co-cultured with T cells, transformed epithelial cells displayed much higher and more efficient immune evasion activity compared to original non-transformed cells. Therefore, this work resolved a very important scientific and clinical question and suggested that cancer immune evasion machinery is activated during malignant transformation of human cells regardless the presence of immune cells in microenvironment

T lymphocytes induce human cancer cells derived from solid malignant tumors to secrete galectin-9 which facilitates immunosuppression in cooperation with other immune checkpoint proteins.

BACKGROUND Galectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. Recent evidence demonstrated that galectin-9 is highly expressed in a wide range of human malignancies including the most aggressive tumors, such as high-grade glioblastomas and pancreatic ductal adenocarcinomas, as well as common malignancies such as breast, lung and colorectal cancers. However, solid tumor cells at rest are known to secrete either very low amounts of galectin-9 or, in most of the cases, do not secrete it at all. Our aims were to elucidate whether T cells can induce galectin-9 secretion in human cancer cells derived from solid malignant tumors and whether this soluble form displays higher systemic immunosuppressive activity compared with the cell surface-based protein. METHODS A wide range of human cancer cell lines derived from solid tumours, keratinocytes and primary embryonic cells were employed, together with helper and cytotoxic T cell lines and human as well as mouse primary T cells. Western blot analysis, ELISA, quantitative reverse transcriptase-PCR, on-cell Western and other measurement techniques were used to conduct the study. Results were validated using in vivo mouse model. RESULTS We discovered that T lymphocytes induce galectin-9 secretion in various types of human cancer cells derived from solid malignant tumors. This was demonstrated to occur via two differential mechanisms: first by translocation of galectin-9 onto the cell surface followed by its proteolytic shedding and second due to autophagy followed by lysosomal secretion. For both mechanisms a protein carrier/trafficker was required, since galectin-9 lacks a secretion sequence. Secreted galectin-9 pre-opsonised T cells and, following interaction with other immune checkpoint proteins, their activity was completely attenuated. As an example, we studied the cooperation of galectin-9 and V-domain Ig-containing suppressor of T cell activation (VISTA) proteins in human cancer cells. CONCLUSION Our results underline a crucial role of galectin-9 in anticancer immune evasion. As such, galectin-9 and regulatory pathways controlling its production should be considered as key targets for immunotherapy in a large number of cancers

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 - Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes.

Immune checkpoint proteins play crucial roles in human embryonic development but are also used by cancer cells to escape immune surveillance. These proteins and biochemical pathways associated with them form a complex machinery capable of blocking the ability of cytotoxic immune lymphoid cells to attack cancer cells and, ultimately, to fully suppress anti-tumor immunity. One of the more recently discovered immune checkpoint proteins is V-domain Ig-containing suppressor of T cell activation (VISTA), which plays a crucial role in anti-cancer immune evasion pathways. The biochemical mechanisms underlying regulation of VISTA expression remain unknown. Here, we report for the first time that VISTA expression is controlled by the transforming growth factor beta type 1 (TGF-β)-Smad3 signaling pathway. However, in T lymphocytes, we found that VISTA expression was differentially regulated by TGF-β depending on their immune profile. Taken together, our results demonstrate the differential biochemical control of VISTA expression in human T cells and various types of rapidly proliferating cells, including cancer cells, fetal cells and keratinocytes

Content of protein oxidative modification products and nitrogen monoxide metabolites in the kidneys and myocardium of rats with streptozotocin-induced diabetes in dynamics of cerebral ischemia-reperfusion

Introduction. Acute disorders of cerebral circulation similar to diabetes mellitus (DM) cause long-term multiple organ effects, although pathogenesis of internal organs injury in association with DM and cerebral ischemia-reperfusion has not been investigated completely. The aim of the study. To study the dynamics of the content of protein oxidative modification and metabolites in the myocardium and kidneys of rats with DM complicated by cerebral ischemia-reperfusion. Results. The content of protein oxidative modification products in the tissues of the kidneys and myocardium and the content of nitrogen monoxide metabolites in the cortical and medullary substance of the kidneys were found to decrease in the early ischemic-reperfusion period in rats without DM. In rats with DM early post-ischemic changes are restricted by the increase of nitrogen oxide metabolites content in the renal medullary substance. Total remote changes of the examined parameters are found in the myocardium of rats without DM and the medullary substance of the kidneys in rats with DM. Conclusions. Diabetes mellitus eliminates or restricts the reaction of the examined indices peculiar for control animals in both periods of observation in all the examined tissues except the medullary substance of the kidneys on the 12th day of the post-ischemic period

Functional role of galectin-9 in directing human innate immune reactions to Gram-negative bacteria and T cell apoptosis

Galectin-9 is a member of the galectin family of proteins, which were first identified to specifically bind to carbohydrates containing β-galactosides. Galectin-9 is conserved through evolution and recent evidence demonstrated its involvement in innate immune reactions to bacterial infections as well as the suppression of cytotoxic immune responses of T and natural killer cells. However, the molecular mechanisms underlying such differential immunological functions of galectin-9 remain largely unknown. In this work we confirmed that soluble galectin-9 derived from macrophages binds to Gram-negative bacteria by interacting with lipopolysaccharide (LPS), which forms their cell wall. This opsonisation effect most likely interferes with the mobility of bacteria leading to their phagocytosis by innate immune cells. Galectin-9-dependent opsonisation also promotes the innate immune reactions of macrophages to these bacteria and significantly enhances the production of proinflammatory cytokines – interleukin (IL) 6, IL-1β and tumour necrosis factor alpha (TNF-α). In contrast, galectin9 did not bind peptidoglycan (PGN), which forms the cell wall of Gram-positive bacteria. Moreover, galectin-9 associated with cellular surfaces (studied in primary human embryonic cells) was not involved in the interaction with bacteria or bacterial colonisation. However, galectin-9 expressed on the surface of primary human embryonic cells, as well as soluble forms of galectin-9, were able to target T lymphocytes and caused apoptosis in T cells expressing granzyme B. Furthermore, “opsonisation” of T cells by galectin-9 led to the translocation of phosphatidylserine onto the cell surface and subsequent phagocytosis by macrophages through Tim-3, the receptor, which recognises both galectin-9 and phosphatidylserine as ligands