Huntington's disease (HD) is a neurodegenerative disorder characterized by a progressive motor and cognitive decline and the development of psychiatric symptoms.
Introduction: The mechanism of the cytotoxicity of anthracyclines is pleiotropic and its significance in cell growth inhibition seems to be highly specific and dependent on cell type and anthracycline drug. Resistance and the high cardiotoxicity of anthracyclines have stimulated many studies aimed at identifying critical substituents required for optimal activity. Many authors point to the fact that the double-strand breaks, the consequence of the activity of topoisomerase II poisons, and the inability of cells to repair the DNA lesions are the signal for apoptosis. The aim of this study was to define the influence of 4-demetoxy 2'-halogenated analogs with altered basicity at the 3'-position on topoisomerase II and the relationship of that interaction with apoptosis and the cytotoxicity of these novel anthracyclines. Parental human ME18 melanoma cells and the ME18/R subline, obtained experimentally, resistant to doxorubicin (DOX), exposed to 1.7 and 8.6 µM DOX or its analogs, annamycin and WP903 (both 0.3 and 3.0 µM) were studied. Materials and Methods: The MTT test was used to assay cytotoxicity. Interaction of the drugs with topoisomerase II and apoptosis were done by Western blot and fluorescence microscopy using Hoechst 33342. Results: The structural changes at positions 4, 2', and 3' can influence topoisomerase II interaction and apoptotic activity, although correlation between these events and cytotoxic consequences has not been proved. Conclusions: The biological response of the cells to the structurally similar anthracyclines may be variable and probably depends on the cell type which seems to be an additional problem in the multifactorial resistance of tumor cells to anthracyclines.
Background. Oxidative stress accompanies neurodegeneration and also causes abnormalities in thiamine-dependent processes. These processes have been reported to be diminished in the brains of patients with several neurodegenerative diseases.
Unique phytochemical profile of plants belonging to Boraginaceae family provides a prolific resource of lipophilic pigments from the group of naphthoquinone derivatives. To overcome low compound content, the major obstacle of plant-based production, immobilization of Rindera graeca roots in in vitro cultures was implemented for efficient production of rinderol, novel furanonaphthoquinone derivative with anticancer properties. Chromatographic procedures revealed rinderol presence in extracts of all investigated root lines, derived both from root biomass and post-culture medium. Unexpectedly, in the second stage of the experiment, rinderol production was ceased in control, unmodified culture systems. On the contrary, roots immobilized on PUF rafts uniformly and stably produced rinderol, and its highest amount was noted for transformed root lines after 42 days of cultivation (222.98 ± 10.47 µg/flask). PUF occurred to be the main place of compound accumulation. Moreover, investigation of rinderol biological activity revealed its fast-acting cell death induction in HeLa cervical cancer cells at relatively low concentrations. Presented results revealed successful application of R. graeca roots immobilization on PUF rafts for production and in situ product removal of rinderol, novel lipophilic furanonaphthoquinone with suggested proapoptotic activity.
Background. Alloplastic biomaterials are an alternative for autologous transplants and xenografts in oral surgery and dental implantology. These non-immunogenic and resorbable materials are becoming the basis for complete and predictable guided bone regeneration in many cases. The chemical composition of a great majority of them is based on calcium phosphate salts. In vivo performance is often variable. Objectives. The objective was to evaluate the biological and chemical properties of an experimental bone substitute material. Material and Methods. The present research focuses on the cytotoxicity comparison and physiochemical characterization of two biomaterials: a novel chitosan/tricalcium phosphate/alginate composite (CH/TCP/Ag) and a commercially available synthetic bone graft made of HA (60%) and βTCP (40%) (HA/TCP). The materials were evaluated according to PN-EN ISO 10993 Biological evaluation of medical devices i.e. cytotoxicity on mouse fibroblasts (L929) and, in addition, tests on human osteoblasts (hFOB1.19) and human osteosarcoma (MG-63) were conducted. The crystallochemical analysis was performed using the X-ray powder diffraction method. The Bruker--AXS D8 Advance diffractometer (Karlsruhe, Germany) was used to collect diffractograms. Results. The tested materials showed a close resemblance in chemical composition and a considerable differentiation in cytotoxic response.
Conclusions.The novel composite demonstrated a high degree of cytocompatibility, which is promising in future clinical trials (Adv Clin Exp Med 2015, 24, 3, 511-516).
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