Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

Creating a Board game based on the book by A. S. Yartsov "Russian mountain history"

В диссертации дана краткая историческая справка о происхождении настольных игр, их видах, существующих на сегодняшний день игровых механиках, представлены данные опроса среди продавцов настольных игр. Проанализированы особенности наиболее популярных настольных игр и создана новая уникальная настольная игра, которая является дополнением книги А. С. Ярцова «Российская горная история».The dissertation provides a brief historical background on the origin of Board games, their types, existing game mechanics, and provides survey data among sellers of Board games. The features of the most popular Board games are analyzed and a new unique Board game is created, which is an addition to the book by A. S. Yartsov "Russian mountain history"

Prognostic Analysis of Human Pluripotent Stem Cells Based on Their Morphological Portrait and Expression of Pluripotent Markers

The ability of human pluripotent stem cells for unlimited proliferation and self-renewal promotes their application in the fields of regenerative medicine. The morphological assessment of growing colonies and cells, as a non-invasive method, allows the best clones for further clinical applications to be safely selected. For this purpose, we analyzed seven morphological parameters of both colonies and cells extracted from the phase-contrast images of human embryonic stem cell line H9, control human induced pluripotent stem cell (hiPSC) line AD3, and hiPSC line HPCASRi002-A (CaSR) in various passages during their growth for 120 h. The morphological phenotype of each colony was classified using a visual analysis and associated with its potential for pluripotency and clonality maintenance, thus defining the colony phenotype as the control parameter. Using the analysis of variance for the morphological parameters of each line, we showed that selected parameters carried information about different cell lines and different phenotypes within each line. We demonstrated that a model of classification of colonies and cells by phenotype, built on the selected parameters as predictors, recognized the phenotype with an accuracy of 70&ndash;75%. In addition, we performed a qRT-PCR analysis of eleven pluripotency markers genes. By analyzing the variance of their expression in samples from different lines and with different phenotypes, we identified group-specific sets of genes that could be used as the most informative ones for the separation of the best clones. Our results indicated the fundamental possibility of constructing a morphological portrait of a colony informative for the automatic identification of the phenotype and for linking this portrait to the expression of pluripotency markers

Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms

Design of Conjugates Based on Sesquiterpene Lactones with Polyalkoxybenzenes by &ldquo;Click&rdquo; Chemistry to Create Potential Anticancer Agents

Using the methodology of &ldquo;click&rdquo; chemistry, a singular method has been developed for the synthesis of unique conjugates based on sesquiterpene lactones: dehydrocostuslactone and alantolactone with polyalkoxybenzenes. To expand the structural range of the resulting conjugates, the length of the 1,2,3-triazole spacer was varied. For all synthesized compounds, the cytotoxic profile was determined on the cell lines of tumor origin (SH-SY5Y, HeLa, Hep-2, A549) and normal Hek 293 cells. It was found that the compounds based on alantolactone 7a&ndash;d with a long spacer and substances containing dehydrocostuslactone 10a&ndash;d with a short spacer have the greatest toxic effect. The decrease in cell survival under the action of these conjugates may be due to their ability to cause dissipation of the transmembrane potential of mitochondria and inhibit the process of glycolysis, leading to cell death. The obtained results confirm the assumption that the development of conjugates based on sesquiterpene lactones and polyalkoxybenzenes can be considered as a promising strategy for the search for potential antitumor agents

Essential Role of Adhesion GPCR, GPR123, for Human Pluripotent Stem Cells and Reprogramming towards Pluripotency

G-protein-coupled receptors (GPCRs) are the largest family of cell surface receptors. They modulate key physiological functions and are required in diverse developmental processes including embryogenesis, but their role in pluripotency maintenance and acquisition during the reprogramming towards hiPSCs draws little attention. Meanwhile, it is known that more than 106 GPCRs are overexpressed in human pluripotent stem cells (hPSCs). Previously, to identify novel effectors of reprogramming, we performed a high-throughput RNA interference (RNAi) screening assay and identified adhesion GPCR, GPR123, as a potential reprogramming effector. Its role has not been explored before. Herein, by employing GPR123 RNAi we addressed the role of GPR123 for hPSCs. The suppression of GPR123 in hPSCs leads to the loss of pluripotency and differentiation, impacted colony morphology, accumulation of cells at the G2 phase of the cell cycle, and absence of the scratch closure. Application of the GPR123 RNAi at the initiation stage of reprogramming leads to a decrease in the percentage of the “true” hiPSC colonies, a drop in E-cadherin expression, a decrease in the percentage of NANOG+ nuclei, and the absence of actin cytoskeleton remodeling. Together this leads to the absence of the alkaline-phosphatase-positive hiPSCs colonies on the 18th day of the reprogramming process. Overall, these data indicate for the first time the essential role of GPR123 in the maintenance and acquisition of pluripotency