Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor CD34+ cells

ABSTRACT Etoposide is a widely used anticancer drug successfully utilized for treatment of many types of cancer in children and adults. Its use, however, is associated with an increased risk of development of secondary acute myelogenous leukemia (t-AML) involving MLL gene MOL #68718

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries

Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control

The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity. As oxidative intermediates, these peroxidases produce not only active heme compounds, but also protein-based tyrosyl radicals. Hemoglobin, myoglobin, cytochrome c/cardiolipin complexes and cytoglobin are considered as pseudo-peroxidases. Рeroxidases play an important role in innate immunity and in a number of physiologically important processes like apoptosis and cell signaling. Unfavorable excessive peroxidase activity is implicated in oxidative damage of cells and tissues, thereby initiating the variety of human diseases. Hence, regulation of peroxidase activity is of considerable importance. Since peroxidases differ in structure, properties and location, the mechanisms controlling peroxidase activity and the biological effects of peroxidase products are specific for each hemoprotein. This review summarizes the knowledge about the properties, activities, regulations and biological effects of true and pseudo-peroxidases in order to better understand the mechanisms underlying beneficial and adverse effects of this class of enzymes

New Approach for Specific Determination of Antibiotics by Use of Luminescent Escherichia coli and Immune Serum

This paper describes a possible application of luminescent Escherichia coli activated by blood serum for high-sensitivity and high-specificity assays of antibiotics in solutions. Antibiotics inhibited luminescence of a genetically engineered E. coli strain; the system sensitivity to some antibiotics grew notably after the cells had been preactivated by blood serum. The highest level of sensitivity (2.8 ± 0.6 ng/ml) of luminescent cells was obtained for aminoglycoside antibiotics (gentamicin and streptomycin). It is feasible to create the specific biosensor for antibiotics on the basis of bioluminescent E. coli strains by applying sera containing antibodies against the antibiotic under assay. The presence of antibodies specific for gentamicin in serum affects inhibition of luminescent cells by gentamicin but not inhibition by other antibiotics

MSCs’ conditioned media cytokine and growth factor profiles and their impact on macrophage polarization

Abstract Background There is a growing body of evidence that multipotent mesenchymal stromal cells’ (MSCs’) remarkable therapeutic potential is attributed not only to their differentiation and regenerative capacity, but also to the paracrine effect, underlying their immunomodulatory properties. MSCs’ secretome (i.e., cytokines, growth factors, and extracellular vesicles) is therefore increasingly discussed in the context of their ability to modulate inflammatory response and promote regeneration. There is evidence that 2D or 3D culturing conditions have an impact on the cells’ secretome, and here we aimed to compare the secretion of cytokines and growth factors in human MSCs from different sources cultured in 2D and 3D conditions and assess their effect on human macrophages polarization in vitro. Methods MSCs were derived from human adipose tissue, bone marrow, gingiva, placenta, and umbilical cord, cultured as monolayers or as cell spheroids. Their cytokine profiles were analyzed, and data standardization was carried out using a z-score. Human peripheral blood mononuclear cells-derived macrophages were then treated with umbilical cord-derived MSCs’ conditioned media and their effect on macrophages polarization was assessed. Results Our findings suggest that umbilical cord-derived MSCs’ conditioned media demonstrated the highest cytokine and growth factor levels and despite mostly pro-inflammatory cytokine profile were able to promote anti-inflammatory macrophage polarization. Conclusions Umbilical cord-derived MSCs’ conditioned media hold great potential for therapeutic use, demonstrating significant anti-inflammatory effect on human macrophages

Перевод в сфере профессиональной и научной коммуникации (конференции, официальные встречи, деловые переговоры)

Власова, Т. І. Переклад у сфері професійної та наукової комунікації (конференції, офіційні зустрічі, ділові перемовини) : навчальний посібник / Т. І. Власова. — Дніпропетровськ : Вид-во Дніпропетр. нац. ун-т залізн. трансп. ім. акад. В. Лазаряна, 2016. — 131 с. Наводиться фрагмент тексту.UK: Навчальний посібник «Переклад у сфері професійної та наукової комунікації (конференції, офіційні зустрічі, ділові перемовини)» представляє собою практичний посібник з розвитку навичок володіння лексичним матеріалом, необхідним для проведення конференцій та ділових зустрічей англійською мовою, з акцентом на проблемах перекладу наукового вокабулярія та професійного тезауруса. Посібник розрахований на широке коло тих, хто удосконалює свої знання з англійської мови.RU: Учебное пособие «Перевод в сфере профессиональной и научной коммуникации (конференции, официальные встречи, деловые переговоры)» представляет собой практическое пособие по развитию навыков владения лексическим материалом, необходимым для проведение конференций и деловых встреч на английском языке, с акцентом на проблемах перевода научного вокабулярия и профессионального тезауруса. Пособие рассчитано на широкий круг тех, кто совершенствует свои знания по английскому языку.Міністерство освіти і науки У країни; Дніпропетровський національний університет залізничного транспорту імені академіка В. Лазарян

Legal regulation of the information space as a way of forming modern legal awareness

Purpose: The purpose of this article is to study the problem of improving the legal regulation of the information and legal sphere of the Russian state and its impact on the legal consciousness of the Russian society. The authors efforts are aimed at studying the peculiarities of social development, characterized by the expansion of information processes that permeate the activities of state bodies, institutions, enterprises and citizens, which have a huge impact on the formation of legal awareness and legal culture of the entire society. Design/Methodology/Approach: The problems of expanding the information sphere of public life are investigated as a new direction of scientific knowledge, which is complex and diverse, due to the dynamism and instability of this category. Such fundamental concepts as personality, freedom, information, law, and civil society are considered as the fundamental standards of modern life, as the most important ideas which can be applied for the formation of an information society. Findings: Modern legal science in the context of informatization of public life should preserve the moral foundations of law, its adherence to universal values and spiritual guidelines. Currently, the processes of informatization and digitalization of real legal reality are increasing, which contribute to the formation of new civilizational phenomena and processes, the emergence of a new legal understanding, worldview, legal awareness, and legal culture. The new digital reality imposes requirements on legal science and practice related to improving the mechanisms of legal regulation of various spheres of public life based on modern digital technologies. Further development of communication and information technologies provides a new round of development of scientific and technological progress and transformation of society at a new stage of development, defined by the postmodern era. Practical Implications: In connection with the ongoing processes of informatization, the analysis of current legislation that determines the development of the information sphere of public life, which affects the formation of legal awareness, education of the legal culture of society and each individual, is of general particular practical importance. It is legal awareness as the most important legal institution that is one of the main conditions for the development and improvement of legislation, ensuring law and order in public relations Originality/Value: Informatization of social life has led to the emergence of new forms of legal consciousness, has had a significant impact on the formation of the legal culture of society, in which there were previously unknown, so-called digital rights of the individual that define modern life. The development of legislation in the information sphere is of particular importance, since it has a significant impact on the processes of regulating public relations in all areas of modern life, contributes to the formation of a developed legal consciousness and legal culture.peer-reviewe

Redox-Activation of Neutrophils Induced by Pericardium Scaffolds

Implantation of scaffolds causes a local inflammatory response whereby the early recruitment of neutrophils is of great importance not only for fighting the infection, but also for facilitating effective regeneration. We used luminol-dependent chemiluminescence, flow cytometry, ELISA, and confocal microscopy to assess the responses of neutrophils after the exposure to the scaffold-decellularized bovine pericardium (collagen type I) crosslinked with genipin (DBPG). We demonstrated that DBPG activated neutrophils in whole blood causing respiratory burst, myeloperoxidase (MPO) secretion, and formation of neutrophil extracellular trap-like structures (NETs). In addition, we studied platelets, another important player of the immediate immune host response. We found that platelets triggered redox-activation of isolated neutrophils by the pericardium scaffold, and likely participate in the NETs formation. Free radicals generated by neutrophils and hypochlorous acid produced by MPO are potent oxidizing agents which can oxidatively degrade biological structures. Understanding the mechanisms and consequences of redox activation of neutrophils by pericardium scaffolds is important for the development of new approaches to increase the efficiency of tissue regeneration