Antitumor activity of the novel pyridine derivative

The study aim was to explore a toxicological property and antitumor action of the novel pyridine derivative LHT-17-19 in cell culture and on experimental models of lung cancer in mic

Comparative nature of an emotional burnout syndrome in students 3rd and 5th course of pediatric faculty in the medical university

The article presents the results of the study of the level of emotional burnout syndrome by the method of diagnosis of V.V. Boyko on the basis of the degree of severity in students of the three main phases (tension, resistance, exhaustion) and it´s comparison in students of 3rd and 5th year of pediatrics at the Ural State Medical University.В статье представлены результаты исследования уровня синдрома эмоционального выгорания по методике диагностики В.В. Бойко на основании степени выраженности у студентов трех основных фаз (напряжение, резистенция, истощение) и сравнение полученных результатов у студентов 3-го и 5-го курсов педиатрического факультета Уральского государственного медицинского университет

Spontaneous formation of spheroids in human umbilical cord matrix derived cells culture

The possibility of formation of spontaneous spheroids („mesenspheres”) in some samples of human umbilical cord matrix mesenchymal cell cultures are shown. The cellular composition of these formations and some of their properties are analyzed. Presence of undifferentiated cells in the spheroids is shown. Apparently, spheroids are the kind of cell state in culture

Monitoring of transplanted human Mesenchymal Stem Cells from Wharton’s Jelly in xenogeneic systems in vivo

Mesenchymal stem cells (MSCs) are ideal candidates for cell-based therapy aimed at tissue repair and immunomodulation. Aim. to study the survival of transplanted human MSCs from umbilical cord Wharton’s Jelly (hWJ-MSCs) in the animal model of experimental osteoarthritis (OA) in rats after injecting cells into a knee joint and to explore the effect of collagen scaffold on the cell survival in vivo. Methods. MSC isolation and cultivation in vitro. Immunological phenotyping of propagated hWJ-MSCs was performed by flow cytometry. The retention of transplanted cells was studied by the PCR revealing of human specific sequences in genomic DNA extracted from animal tissues. Results. hWJ-MSCs, both individual and grown on scaffold, were used and it was shown by PCR that human alpha-satellite DNA was detected on the first day in the immunocompetent OA animals inside the injured knee joint. In the collagen matrix (in the model of subcutaneous implantation) human alpha-satellite DNA was detected on the 5th day but was not detected on the 12th day. Conclusions. According to the PCR results, hWJ-MSCs survived in the OA animal model for a short period. Collagenic scaffold increased the residence time of donor cells in the recipients. hWJ-MSCs may be considered as a perspective cell source for the treatment of OA in human

Хондрогенне диференціювання мезенхімальних стовбурових клітин кроля, залежно від типу культуральної системи

Experimental study concerned with the ability of mesenchymal stem cells to chondrogenic differentiation in vitro depending on the type of culture system with a view to their further clinical use in veterinary medicine to restore the lost functions of damaged articular cartilage is one of the priority directions of scientific research. Reparative ability of cartilage tissue is limited, since the level of physiological and reparative regeneration of cartilage tissue is quite low. Given this, the search continues for such therapeutic agents and techniques that most effectively restore the damaged structure and function of the tissues of the articular cartilage. A special place in this search belongs to biotechnology. The bone marrow mesenchymal stem cells are one of the most studied multipotent populations of adult cells, which, due to their ability to proliferate and differentiate in vitro, is of great importance in clinical veterinary practice in treating animals with articular cartilage lesions. It was established that with the used protocol of chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells in the monolayer most of the cultured cells acquire a filamentous form, which leads to a decrease in the area of ​​their adhesion to the surface of the culture plastic and, as a result, detachment into the culture medium. During cultivation the confluence of cell monolayer in experimental cultures decreased and at 18 days of cultivation was about 5%. During cultivation the mesenchymal stem cells in the form of a precipitate in chondrogenic medium, for the 6th day of the study, it was visually discovered that the precipitated mass of cells at the bottom of the test tube became spherical, indicating cell compactification and are important condition for their differentiation in the chondrogenic direction. This form of micromass was maintained throughout the entire period of cultivation. Comparison of chondrogenic differentiation methods of rabbit bone marrow mesenchymal stem cells in monolayer and micromass showed that the method of differentiation of cells in the micromass is more efficient, since as early as 21 days during the study revealed significantly larger depositions of the extracellular matrix by cells compared to monolayer differentiation.Eкспериментальне вивчення здатності мезенхімальних стовбурових клітин до хондрогенного диференціювання in vitro залежно від типу культуральної системи з метою їх подальшого клінічного застосування у ветеринарній медицині для відновлення втрачених функцій пошкодженого суглобового хряща є одним із пріоритетних напрямків наукових досліджень. Репаративна здатність хрящової тканини обмежена, оскільки рівень фізіологічної та репаративної регенерації хрящової тканини досить низький. З огляду на це, триває пошук таких терапевтичних засобів та прийомів, які б дозволяли максимально ефективно відновити порушені структуру і функцію тканин суглобового хряща. Особливе місце у цьому пошуку належить біотехнології. Мезенхімальні стовбурові клітини кісткового мозку – одна з найбільш вивчених мультипотентних популяцій клітин дорослого організму, яка завдяки здатності до проліферації і диференціювання in vitro, має вагоме значення в клінічній ветеринарній практиці у лікуванні тварин з ураженнями суглобового хряща. Встановлено, що за апробованого протоколу хондрогенного диференціювання мезенхімальних стовбурових клітин кісткового мозку кроля у моношарі більшість культивованих клітин набуває ниткоподібної форми, що призводить до зниження площі їх адгезії до поверхні культурального пластику і, як наслідок, відкріплення у культуральне середовище. Порівняння методів хондрогенного диференціювання мезенхімальних стовбурових клітин кісткового мозку кроля у моношарі та мікромасі показало, що ефективнішим є метод диференціювання клітин у мікромасі, - вже на 21 добу дослідження виявлялись значно більші відкладання клітинами позаклітинного матриксу, порівняно з методом диференціювання у моношарі

Relapse-Free Survival and PD-L1 Expression in First High- and Low-Grade Relapsed Luminal, Basal and Double-Negative P53-Mutant Non-Muscular Invasive Bladder Cancer Depending on Previous Chemo- and Immunotherapy

The goal of this study was to assess how PD-L1 expression in tissue specimens of patients with main molecular subtypes of NMIBC (luminal, basal and double-negative p53-mutant) associates with relapsed-free survival in dependence on the tumor grade and prior treatment of primary bladder cancer. PD-L1 expressions on the membrane of neoplastic and CD8+ immune cells were assessed in tumor specimens (n = 240) of primary and relapsed luminal, basal and double-negative p53-mutant NMIBC. Association between relapse-free survival and PD-L1 expression was estimated for high-and low-grade relapsed NMIBC according to previous treatment and their molecular profile, using the Kaplan–Meier method, and assessed by using the log-rank test. Potential confounders were adjusted by Cox regression models. In a group of patients who underwent only TUR without intravesical therapy, there were significant differences in relapse time between high-and low-grade tumors in basal and luminal molecular subtypes; for basal relapsed carcinoma, RFS was shorter in cases where tumors were less malignant. Both intravesical mitomycin and Bacillus Calmette–Guerin (BCG) therapy significantly extended the time of recurrence of low-grade luminal and basal bladder malignancies with no intergroup differences in double-negative NMIBC. PD-L1 expression status was associated with RFS for luminal relapsed NMIBCs in the group without previous frontline intervention, and with RFS in the group of patients with luminal relapsed bladder cancer previously utilized BCG. Obtained results may be considered as a promising approach for further clinical implementation. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Prognostic role of fgfr3 expression status and tumor-related micrornas level in association with pd-l1 expression in primary luminal non-muscular invasive bladder carcinoma

Background: Bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: Twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: High grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03-2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92-1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17-0.42] p = 0.003) were associated with relapse-free survival. Conclusions: Tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression. © 2020 by the authors. Licensee MDPI, Basel, Switzerland