Cellular signaling responses show substantial cell-to-cell heterogeneity, which is often ascribed to the inherent randomness of biochemical reactions, termed molecular noise, wherein high noise implies low signaling fidelity. Alternatively, heterogeneity could arise from differences in molecular content between cells, termed molecular phenotypic variability, which does not necessarily imply imprecise signaling. The contribution of these two processes to signaling heterogeneity is unclear.
View Article and Find Full Text PDFAlthough we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose-response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels.
View Article and Find Full Text PDFDiseases leading to terminal hepatic failure are among the most common causes of death worldwide. Transplant of the whole organ is the only effective method to cure liver failure. Unfortunately, this treatment option is not available universally due to the serious shortage of donors.
View Article and Find Full Text PDFCell-based therapies that could provide an alternative treatment for the end-stage liver disease require an adequate source of functional hepatocytes. There is little scientific evidence for the influence of patient's age, sex, and chemotherapy on the cell isolation efficiency and metabolic activity of the harvested hepatocytes. The purpose of this study was to investigate whether hepatocytes derived from different sources display differential viability and biosynthetic capacity.
View Article and Find Full Text PDFThe primary hepatocytes culture is still one of the main challenges in toxicology studies in the drug discovery process, development of in vitro models to study liver function, and cell-based therapies. Isolated hepatocytes display a rapid decline in viability and liver-specific functions including albumin production, conversion of ammonia to urea, and activity of the drug metabolizing enzymes. A number of methods have been developed in order to maintain hepatocytes in their highly differentiated state in vitro.
View Article and Find Full Text PDFNanoparticles have attracted a great deal of attention as carriers for drug delivery to cancer cells. However, reports on their potential cytotoxicity raise questions of their safety and this matter needs attentive consideration. In this paper, for the first time, the cytotoxic effects of two carbon based nanoparticles, diamond and graphite, on glioblastoma and hepatoma cells were compared.
View Article and Find Full Text PDFThe use of fluorescent markers has proven to be an attractive tool in biological imaging. However, its usefulness may be confined by the cytotoxicity of the fluorescent proteins. In this article, for the first time, we have examined an influence of the antibiotics present in culture medium on cytotoxicity of the EGFP and DsRed2 markers used for whole-cell labeling.
View Article and Find Full Text PDFHepatic/nonhepatic cell cocultures are widely used in studies on the role of homo- and heterotypic interactions in liver physiology and pathophysiology. In this article, for the first time, establishment of the coculture model employing hepatoma C3A cells and human skin fibroblasts, stably expressing fluorescent markers, is described. Suitability of the model in studying coculture conditions using fluorescence microscopy and flow cytometry was examined.
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