Paclitaxel (PTX) is a chemotherapeutic agent affecting microtubule polymerization. The efficacy of PTX depends on the type of tumor, and its improvement would be beneficial in patients' treatment. Therefore, we tested the effect of slow sulfide donor GYY4137 on paclitaxel sensitivity in two different breast cancer cell lines, MDA-MB-231, derived from a triple negative cell line, and JIMT1, which overexpresses HER2 and is resistant to trastuzumab. In JIMT1 and MDA-MB-231 cells, we compared IC50 and some metabolic (apoptosis induction, lactate/pyruvate conversion, production of reactive oxygen species, etc.), morphologic (changes in cytoskeleton), and functional (migration, angiogenesis) parameters for PTX and PTX/GYY4137, aiming to determine the mechanism of the sensitization of PTX. We observed improved sensitivity to paclitaxel in the presence of GYY4137 in both cell lines, but also some differences in apoptosis induction and pyruvate/lactate conversion between these cells. In MDA-MB-231 cells, GYY4137 increased apoptosis without affecting the IP3R1 protein, changing the morphology of the cytoskeleton. A mechanism of PTX sensitization by GYY4137 in JIMT1 cells is distinct from MDA-MB-231, and remains to be further elucidated. We suggest different mechanisms of action for H2S on the paclitaxel treatment of MDA-MB-231 and JIMT1 breast cancer cell lines.
- MeSH
- apoptóza * účinky léků MeSH
- chemorezistence účinky léků MeSH
- lidé MeSH
- morfoliny * farmakologie MeSH
- nádorové buněčné linie MeSH
- nádory prsu * farmakoterapie patologie metabolismus MeSH
- organothiofosforové sloučeniny * farmakologie MeSH
- paclitaxel * farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sulfidy farmakologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cannabidiol (CBD) and cannabigerol (CBG) are the two main non-psychotropic phytocannabinoids with high application potential in drug development. Both substances are redox-active and are intensively investigated for their cytoprotective and antioxidant action in vitro. In this study, we focused on an in vivo safety evaluation and the effect of CBD and CBG on the redox status in rats in a 90-d experiment. The substances were administered orogastrically in a dose of 0.66 mg synthetic CBD or 0.66 mg/1.33 mg CBG/kg/day. CBD produced no changes in the red or white blood count or biochemical blood parameters in comparison to the control. No deviations in the morphology or histology of the gastrointestinal tract and liver were observed. After 90 d of CBD exposure, a significant improvement in redox status was found in the blood plasma and liver. The concentration of malondialdehyde and carbonylated proteins was reduced compared to the control. In contrast to CBD, total oxidative stress was significantly increased and this was accompanied by an elevated level of malondialdehyde and carbonylated proteins in CBG-treated animals. Hepatotoxic (regressive changes) manifestations, disruption in white cell count, and alterations in the ALT activity, level of creatinine and ionized calcium were also found in CBG-treated animals. Based on liquid chromatography-mass spectrometry analysis, CBD/CBG accumulated in rat tissues (in the liver, brain, muscle, heart, kidney and skin) at a low ng level per gram. Both CBD and CBG molecular structures include a resorcinol moiety. In CBG, there is an extra dimethyloctadienyl structural pattern, which is most likely responsible for the disruption to the redox status and hepatic environment. The results are valuable to further investigation of the effects of CBD on redox status and should contribute towards opening up critical discussion on the applicability of other non-psychotropic cannabinoids.
- MeSH
- kanabidiol * toxicita MeSH
- kanabinoidy * toxicita MeSH
- krysa rodu rattus MeSH
- oxidace-redukce MeSH
- vápník MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- tisková chyba MeSH
Titanium-based alloys have established a crucial role in implantology. As material deteriorates overtime, nanoparticles of TiO2 and Ni are released. This study is focused on the impact of TiO2 and Ni nanoparticles with size of 100 nm on cytoskeletal and adhesive changes in human physiological and osteoarthritic osteoblasts. The impact of nanoparticles with concentration of 1.5 ng/mL on actin and tubulin expression and gene expression of FAK and ICAM-1 was studied. The cell size and actin expression of physiological osteoblasts decreased in presence of Ni nanoparticles, while TiO2 nanoparticles caused increase in cell size and actin expression. Both cell lines expressed more FAK as a response to TiO2 nanoparticles. ICAM-1 gene was overexpressed in both cell lines as a reaction to both types of nanoparticles. The presented study shows a crucial role of Ni and TiO2 nanoparticles in human osteoblast cytoskeletal and adhesive changes, especially connected with the osteoarthritic cells. Graphical abstract.
- MeSH
- buněčná adheze MeSH
- cytoskelet MeSH
- lidé MeSH
- nanočástice * MeSH
- osteoblasty MeSH
- titan * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The performance of ECG signals compression is influenced by many things. However, there is not a single study primarily focused on the possible effects of ECG pathologies on the performance of compression algorithms. This study evaluates whether the pathologies present in ECG signals affect the efficiency and quality of compression. Single-cycle fractal-based compression algorithm and compression algorithm based on combination of wavelet transform and set partitioning in hierarchical trees are used to compress 125 15-leads ECG signals from CSE database. Rhythm and morphology of these signals are newly annotated as physiological or pathological. The compression performance results are statistically evaluated. Using both compression algorithms, physiological signals are compressed with better quality than pathological signals according to 8 and 9 out of 12 quality metrics, respectively. Moreover, it was statistically proven that pathological signals were compressed with lower efficiency than physiological signals. Signals with physiological rhythm and physiological morphology were compressed with the best quality. The worst results reported the group of signals with pathological rhythm and pathological morphology. This study is the first one which deals with effects of ECG pathologies on the performance of compression algorithms. Signal-by-signal rhythm and morphology annotations (physiological/pathological) for the CSE database are newly published.
- MeSH
- algoritmy MeSH
- databáze faktografické MeSH
- elektrokardiografie metody MeSH
- fraktály MeSH
- komprese dat metody MeSH
- lidé MeSH
- vlnková analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Eventual protective action of calcium (Ca, 100 or 1000 μM) against cadmium (Cd, 10 or 100 μM) toxicity in common lichen Hypogymnia physodes after 24 h of exposure was studied. Total Cd reached 482 and 2801 μg/g DW in 10 and 100 μM Cd treatments while Ca content reached over 23 mg/g DW in 1000 μM Ca treatment. Ca suppressed Cd accumulation by 23 and 38% in total fraction and completely in absorbed fraction. Fluorescence microscopy of Cd and Ca ions revealed good correlation with quantitative data. Cd stimulated increase in ROS formation and lipid peroxidation as detected using fluorescent reagents and quantification of H2O2 while co-application of Ca suppressed these effects. Formation of nitric oxide was mainly affected by cadmium. Cd depleted amount of amino acids but proteins or phenols remained unaffected by Cd or Ca. On the contrary, sum of thiols, reduced glutathione and ascorbic acid were depleted by Cd but reversed mainly by higher Ca dose. Among organic acids, only Cd-induced depletion of citric acid content was reversed by Ca. Data indicate that ameliorative effect of Ca under Cd excess in lichens is comparable with effect in plants and metabolic responses in various life lineages are discussed.
Compression of ECG signal is essential especially in the area of signal transmission in telemedicine. There exist many compression algorithms which are described in various details, tested on various datasets and their performance is expressed by different ways. There is a lack of standardization in this area. This study points out these drawbacks and presents new compression algorithm which is properly described, tested and objectively compared with other authors. This study serves as an example how the standardization should look like. Single-cycle fractal-based (SCyF) compression algorithm is introduced and tested on 4 different databases-CSE database, MIT-BIH arrhythmia database, High-frequency signal and Brno University of Technology ECG quality database (BUT QDB). SCyF algorithm is always compared with well-known algorithm based on wavelet transform and set partitioning in hierarchical trees in terms of efficiency (2 methods) and quality/distortion of the signal after compression (12 methods). Detail analysis of the results is provided. The results of SCyF compression algorithm reach up to avL = 0.4460 bps and PRDN = 2.8236%.
Toxicity of glyphosate (G) alone or in combination with cadmium (Cd) was studied in Matricaria chamomilla. Cadmium accumulated in shoots and roots in relation to prolonged exposure while glyphosate and aminomethylphosphonic acid (AMPA) were detected only in roots. After 7 days of exposure, root Cd and G accumulation was similar (56 μg G or 47 μg Cd/g DW in 1 μM treatments and 330 μg G or 321 μg Cd/g DW in 10 μM treatments). Despite this fact, Cd stimulated higher ROS formation and G rather suppressed nitric oxide while H2O2 content was elevated by Cd. Subsequent assay of antioxidative enzymes (SOD, CAT, and APX) showed only the impact of Cd. Non-enzymatic antioxidants revealed more pronounced impact of Cd on ascorbic acid and soluble phenols while non-protein thiols showed synergistic effect of G and Cd in roots. Surprisingly, G alone or in combination with Cd depleted shoot citrate and tartrate accumulation despite no detectable G in shoots. In the roots, Cd evoked expected increase in malate and citrate content while G rather suppressed Cd-induced elevation. These data indicate that glyphosate is less toxic than cadmium but even low G doses are able to induce metabolic changes.
The sodium/calcium exchanger (NCX) is a unique calcium transport system, generally transporting calcium ions out of the cell in exchange for sodium ions. Nevertheless, under special conditions this transporter can also work in a reverse mode, in which direction of the ion transport is inverted-calcium ions are transported inside the cell and sodium ions are transported out of the cell. To date, three isoforms of the NCX have been identified and characterized in humans. Majority of information about the NCX function comes from isoform 1 (NCX1). Although knowledge about NCX function has evolved rapidly in recent years, little is known about these transport systems in cancer cells. This review aims to summarize current knowledge about NCX functions in individual types of cancer cells.
- MeSH
- invazivní růst nádoru MeSH
- iontový transport MeSH
- lidé MeSH
- nádory metabolismus MeSH
- pumpa pro výměnu sodíku a vápníku metabolismus MeSH
- sodík metabolismus MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Antioxidative responses of axenic protonema cultures of the moss Physcomitrella patens exposed to 10 μM Cd over 40 d were studied. Cd treatment suppressed growth by ca. 75% with concomitant browning of some filaments and suppression of chlorophyll autofluorescence but had no impact on tissue water content. Despite this negative growth responses which could be related to enhanced ROS formation (as detected using fluorescence staining reagents for total ROS, hydroperoxides and lipid peroxidation), some metabolites revealed strong elevation by Cd which could contribute to attenuation of long-term Cd stress (elevation of ascorbic, malic and citric acids). Molar ratio of malate to Cd was 12.7 and citrate to Cd 2.5, thus potentially contributing to Cd chelation. Interestingly, GSH/GSSG pool and nitric oxide formation remained unaltered by Cd. Accumulation of Cd reached 82 μg/g DW with bioaccumulation factor of 73. Data indicate that Cd induces elevation of potentially protective metabolites even after prolonged exposure though they do not prevent oxidative stress sufficiently.
- MeSH
- antioxidancia metabolismus MeSH
- chlorofyl metabolismus MeSH
- kadmium analýza toxicita MeSH
- mechy účinky léků metabolismus MeSH
- oxidační stres účinky léků MeSH
- peroxid vodíku metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
