Glioma-associated protein CHI3L2 suppresses cells viability and induces G1/S transition arrest

Aim. To analyze the effect of the CHI3L2 protein on malignant and non-malignant cell viability, and determined the CHI3L2 impact on the cell cycle and signaling pathways involved in the cell cycle regulation. Methods. MTT-based cell proliferation assay, FACS, western blot analysis. Results. The CHI3L2 protein inhibits the glioma cells viability and potentiates the effect of anti-cancer cytotoxic agents. The CHI3L2 treatment results in the G1/S transition arrest. CHI3L2 provoked a dramatic reduction of pRB phosphorylation and a significant decrease in the cyclin D1 expression, whereas the p53 and p21 expression levels were substantially increased. Conclusions. The CHI3L2 protein, which is overexpressed in human gliomas, is a negative regulator of the glioma cells viability. The reduced cell viability after the CHI3L2 treatment could be due to the activation of pRB and p53 and the downregulation of cyclin D.Мета. Проаналізувати життєздатність злоякісних та незлоякісних клітин за дії протеїна CHI3L2, а також визначити вплив CHI3L2 на клітинний цикл і сигнальні шляхи, залучені до його регуляції. Методи. МТТ–тест, проточна цитофлуориметрія, вестерн блот аналіз. Результати. CHI3L2 пригнічує життєздатність клітин гліоми людини і підсилює дію протиракових цитотоксичних агентів. CHI3L2 інгібує перехід клітин із G1- до S-фази клітинного циклу. CHI3L2 зумовлює зниження кількості фосфорильованої форми pRB, зменшення вмісту цикліну D1 та зростання вмісту p53 і p21. Висновки. CHI3L2, що надекспресується в гліомах людини, є негативним регулятором життєздатності клітин гліоми. Цитотоксичний вплив CHI3L2 може бути пов'язаним з активацією pRB та р53, а також зниженням вмісту цикліну D.Цель. Проанализировать жизнеспособность злокачественных и незлокачественных клеток при воздействии протеина CHI3L2, а также определить влияние CHI3L2 на клеточный цикл и сигнальные пути, вовлеченные в его регуляцию. Методы. МТТ-тест, проточная цитофлуориметрия, вестерн блот анализ. Результаты. CHI3L2 подавляет жизнеспособность клеток глиомы человека и усиливает действие противораковых цитотоксических агентов. CHI3L2 ингибирует переход клеток с G1- в S-фазу клеточного цикла. Влияние CHI3L2 приводит к снижению количества фосфорилированной формы pRB, уменьшению содержания циклина D1 и увеличению содержания p53 и p21. Выводы. CHI3L2, оверэкспрессия которого характерна для глиом человека, является негативным регулятором жизнеспособности клеток глиомы. Цито­ток­си­чес­кое влияние CHI3L2 может быть связано с активацией pRB и р53, а также снижением содержания циклина D

Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Проблематика. Програми доклінічного вивчення безпеки продуктів у системі охорони здоров’я залежать від регуляторного статусу досліджуваних продуктів. Класифікування таких продуктів, зокрема супозиторіїв для ректального та вагінального застосування, є критичним етапом для розробки тактики їх біологічного оцінювання. Актуальними для біомедицини залишаються питання адаптації методів біологічного оцінювання медичних виробів на основі комбінації біологічно активних речовин, а також оцінки результатів такого оцінювання. Мета. Здійснити обґрунтування регуляторного статусу та біологічне оцінювання медичних виробів у формі вагінальних супозиторіїв на основі октенідину дигідрохлориду (“Продексин”) та у формі ректальних супозиторіїв на основі екстрактів рослин Saw palmetto, Levisticum officinale і Calendula officinalis (“Правенор”). Методика реалізації. Біологічне оцінювання проводили згідно з вимогами стандартів серії ISO 10993 за допомогою біологічних тест-систем in vitro та in vivo (цитотоксичність у культурі клітин та у МТТ-тесті, сенсибілізуюча та подразнювальна дія на мурчаків). Результати. Цитотоксичність (СС50) екстракту медичного виробу “Продексин” на культурі клітин Vero становила 8,35 мкг/мл у перерахунку на октенідину дигідрохлорид та 416,65 мкг/мл у перерахунку на декспантенол. Медичній виріб “Правенор” виявився нетоксичним на культурі клітин Vero. За результатами МТТ-тесту СС50 для октенідину дигідрохлориду становила 1,67 мкг/мл, декспантенолу – 83,33 мкг/мл. СС50 у перерахунку на активні інгредієнти медичного виробу “Правенор” становила 50 мг/мл для екстракту ягід карликової пальми (Saw palmetto), 16,67 мг/мл для екстракту коренів любистку лікарського (Levisticum officinale), 16,67 мг/мл для екстракту квіток нагідок лікарських (Calendula officinalis). Для медичних виробів не було виявлено сенсибілі­зуючої та шкіроподразнювальної дії на мурчаків. Висновки. Біологічне оцінювання медичних виробів у формі ректальних супозиторіїв “Правенор” і вагінальних супозиторіїв “Продексин”, проведене із використанням біологічних систем in vitro та in vivo, засвідчило прийнятний рівень безпечності цієї продукції. При визначенні цитотоксичності МТТ-тест виявився у 5 разів чутливішим порівняно з методом на основі культури клітин Vero.Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity

SARS-CoV-2 infects human engineered heart tissues and models COVID-19 myocarditis

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease

Human cardiac pericytes are susceptible to SARS-CoV-2 infection

COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19

The genome of the intracellular bacterium of the coastal bivalve, Solemya velum: a blueprint for thriving in and out of symbiosis

Background: Symbioses between chemoautotrophic bacteria and marine invertebrates are rare examples of living systems that are virtually independent of photosynthetic primary production. These associations have evolved multiple times in marine habitats, such as deep-sea hydrothermal vents and reducing sediments, characterized by steep gradients of oxygen and reduced chemicals. Due to difficulties associated with maintaining these symbioses in the laboratory and culturing the symbiotic bacteria, studies of chemosynthetic symbioses rely heavily on culture independent methods. The symbiosis between the coastal bivalve, Solemya velum, and its intracellular symbiont is a model for chemosynthetic symbioses given its accessibility in intertidal environments and the ability to maintain it under laboratory conditions. To better understand this symbiosis, the genome of the S. velum endosymbiont was sequenced. Results: Relative to the genomes of obligate symbiotic bacteria, which commonly undergo erosion and reduction, the S. velum symbiont genome was large (2.7 Mb), GC-rich (51%), and contained a large number (78) of mobile genetic elements. Comparative genomics identified sets of genes specific to the chemosynthetic lifestyle and necessary to sustain the symbiosis. In addition, a number of inferred metabolic pathways and cellular processes, including heterotrophy, branched electron transport, and motility, suggested that besides the ability to function as an endosymbiont, the bacterium may have the capacity to live outside the host. Conclusions: The physiological dexterity indicated by the genome substantially improves our understanding of the genetic and metabolic capabilities of the S. velum symbiont and the breadth of niches the partners may inhabit during their lifecycle. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-924) contains supplementary material, which is available to authorized users

Evaluation of e-learning of "Orthodontics" specialty in HSEIU “Ukrainian Мedical Stomatological Academy” at the postgraduate stage

Науково-технічний прогрес і широка доступність Інтернет ресурсу та комп’ютерного забезпечення значно розширюють можливість застосування цифрових технологій в навчальному процесі. Для забезпечення високих стандартів післядипломної підготовки на кафедрі післядипломної освіти лікарів-ортодонтів ВДНЗУ «Українська медична стоматологічна академія» широко застосовуються інформаційні, мультимедійні технології та сучасні комп’ютерні діагностичні та тестові програми, що створюють сприятливі умови для оптимізації навчального процесу, формування клінічного мислення, засвоєння практичних навичок і реалізації ідеї самовдосконалення курсантів; Technological progress and the widespread availability of Internet resources and computer software greatly extend the applicability of digital technology in the educational process. To ensure the high standards of postgraduate training at the department of postgraduate studding of orthodontists HSEIU “Ukrainian Medical Stomatological Academy” widely used information, multimedia technology and modern computer diagnostic and test programs that create favorable conditions to optimize the learning process, formation of clinical thinking, learning practical skills and self-realization of the idea of students

Distance learning: opportunities and challenges in quarantine.

The urgent introduction of distance education into the learning process due to the COVID-19 pandemic has become a spontaneous experiment, requiring urgent decisions, effective mechanisms to implement into the educational process and analysis of ongoing educational process. The possibilities of modern digital technologies made it possible to quickly set up the information component of education and to controle student’s knowledge. A detailed analysis of the communication between the faculty members of the department among themselves and analysis of the features of teaching and self-education of students in the field of medical radiology and oncology based on answers and comments with using Google classroom, Socrative, Messenger Telegram, etc. was made. Issues of communicative interaction between faculty members and students, psychological aspects of distance communication, language of instruction, logistics of distance education and methodological problems are described in details. It has been suggested that distance education may be equally effective for theoretical subjects in full-time study form, but when studying clinical disciplines, the priority should be given to traditional methods of teaching, involving student's bedside training. Taking into account technical possibilities and high risk of development of extreme and emergency situations, it is suggested to introduce permanent readiness for distance education, to create all – Ukrainian distance imitation service of patients’ follow-up. The importance of using the state language in training as the basis for mastering the professional Ukrainian and English language as the basis for mastering international medical experience is indicated

SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis.

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease

ADVANCING INTERNATIONAL COMPETITIVENESS AS A FACTOR OF DEVELOPMENT OF INDUSTRIAL ENTERPRISE

In the article the problem of advancing the international competitiveness of industry has been highlighted in the context of the impact on getting out the crises in the country and forming preconditions for economic growth. The study is based on an empirical basis of metallurgical industries of Ukraine, which has traditionally focused largely on international markets. The advancing international competitiveness of these enterprises is particularly topical and important for getting over the crisis and forming a trajectory of economic development of the country. The system of the factors has been represented and analysed, the priorities for advancing the international competitiveness of metallurgical industryJSC "Zaporizhstar.Recommendations to improve the competitiveness of the analysed enterprise have been formulated and common priorities for improving the international competitiveness of steel companies determining the possibility of positive impact on getting over the crisis and economic development at the level of companies, as well as at the level of Ukraine’s economy have been identified