Global Determinants of the International Movement of Production Factors: Economic-legal and Institutional Context

Scientific research is devoted to current problems of the influence of globalization on changes in the international movement of production factors in the 21st century. Considerable attention is focused on the economic, legal and institutional aspects of the transformation of the international movement of capital and labor in modern conditions, taking into account the need to apply an integrated interdisciplinary approach to identify new phenomena and processes that occur in the global economic environment The state and trends of development in the organization of global production, investment and marketing in the context of destabilizing phenomena in the global economy, the strengthening of non-protectionist appeals in the world avant-garde countries to return production to the national territory and the exacerbation of social and economic problems caused by international migration are revealed. The authors are looking for answers to difficult questions about the opportunities for small open economies to be attracted to global value chains through the format of investment and contractual relations, to increase the level of localization of international and national production through import substitution, to optimize the taxation of entrepreneurial activities in a liberalized international capital transfer, transform the national regulatory policy as a mechanism that ensures the possibility of taking into account the imperatives of globalization and contributes to the protection of national economic interests, ensure the development of fair competition as a prerequisite for the country’s integration into world economic processes

Research the influence of excipients on the technological properties of captopril fast dissolving films

Drug-loaded films are of great interest among fast-dissolving drug-delivery systems. The creation of fast-dissolving films for the treatment of cardiovascular diseases is important.The first inhibitor of angiotensin-converting enzyme to appear on the world market was captopril, which is used to treat hypertension, chronic heart failure and others. Captopril has an antihypertensive effect, which manifests itself within 5–15 minutes after sublingual administration. The aim of our study was to develop the technology of captopril fast dissolving films by solvent casting method and analyze the influence of groups of excipients on technological properties of the films. The influence of the character of polymers, plasticizers, disintegrants and sweeteners on the technological properties of experimental batches of captopril fast dissolving films was studied. Such technological indicators as uniformity of weight, thickness, swelling index,tensile strength, elongationand disintegration time were studied. The influence of excipients' composition on the technological indicators of captopril fast dissolving films has been researched. It was found out that the effect of the type of polymer had the decisive influence on all parameters of films.The selected plasticizer determined the elasticity (films' elongation), film thickness and weight variation. Optimal values of the average weight and thickness of captopril films are provided by the use of a polymer in the combination of HPMC with PEG 4000 or a combination of HPMC with PEG 6000, as a plasticizer – glycerin or PEG 400. The best results of films' swelling were obtained with the introduction of HPMC brands Metolose® 90 SH 100 000 or Metolose® 65 SH 50, Polyplasdone XL-10 crospovidone, propylene glycol and sorbitol. The disintegration time less than 3 min was observed in all investigated film compositions, except those containing PVA. The highest value of tensile strength for captopril films was obtained using HPMC brand Metolose® 65 SH 50 or Metolose®90 SH 100 000. Using the desirability function, the optimal excipients within the studied groups were selected.It has been established that the optimal values of the technological parameters of captopril films can be achieved using Hydroxypropyl MethylcelluloseVivapharm® E15, polyethylene glycol 400, sodium starch glycolate and sorbitol

Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia.

N6-methyladenosine (m6A) is an abundant internal RNA modification1,2 that is catalysed predominantly by the METTL3-METTL14 methyltransferase complex3,4. The m6A methyltransferase METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but the potential of therapeutic applications targeting this enzyme remains unknown5-7. Here we present the identification and characterization of STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3-METTL14. Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. We demonstrate that pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML. Collectively, these results reveal the inhibition of METTL3 as a potential therapeutic strategy against AML, and provide proof of concept that the targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

підручник

Трудове право України : підручник / [автор. кол.: С. М. Бортник, К. Ю. Мельник, Л. В. Могілевський та ін.]; МВС України, Харків. нац. ун-т внутр. справ. – Харків, 2019. – 408 с. – ISBN 978-966-610-165-8.У підручнику висвітлено основні положення сучасного трудового права України та порядку проходження служби в Національній поліції України. Підручник підготовлено на підставі норм чинного національного законодавства й сучасних напрацювань науки трудового права. Авторський колектив підручника становлять учені Харківського національного університету внутрішніх справ. Видання присвячено 25-річчю Харківського національного університету внутрішніх справ. Для студентів, курсантів і науково-педагогічних працівників закладів вищої освіти та закладів вищої освіти із специфічними умовами навчання. Видання також буде корисним для юристів-практиків та усіх тих, хто цікавиться трудовим правом.The textbook contains the main provisions of modern labor law of Ukraine and the procedure for serving in the National Police of Ukraine. The textbook is prepared on the basis of the norms of existing national legislation and modern developments in the science of labor law. For students, cadets and scientific and pedagogical workers of higher educational institutions and higher educational institutions with specific educational conditions, as well as all those interested in labor law.В учебнике освещены основные положения современного трудового права Украины и порядка прохождения службы в Национальной полиции Украины. Учебник подготовлен на основании норм действующего национального законодательства и современных наработок науки трудового права. Для студентов, курсантов и научно-педагогических работников высших учебных заведений и высших учебных заведений со специфическими условиями обучения, а также всех интересующихся трудовым правом

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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