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Effect of maternal obesity on postnatal development of circadian clocks
Sejrková, Veronika ; Sumová, Alena (advisor) ; Spišská, Veronika (referee)
This thesis focuses on the synchronizing effect of obesity in mothers on ontogenesis of the circadian system in their offspring during gestation and postnatal life. Additionally, the work summarizes its impact on health of offspring in adulthood. During postnatal life, the central clock oscillator (SCN) is synchronized with external conditions through alternating period of light and darkness, but during prenatal ontogenesis of the main oscillator and peripheral oscillators, the SCN is synchronized with maternal signals, both behavioral, metabolic and hormonal. In the event of disruption of the maternal circadian and metabolic systems due to obesity, the circadian clocks of the offspring are incorrectly synchronized during gestation and breastfeeding, which may have a long-term effect on their health later during postnatal life. Maternal obesity is considered the main trigger for obesity occurring later.
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Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on Farnesoid X receptor and the G protein-coupled bile acid receptor 1
Hutníková, Miriama ; Pávek, Petr (advisor) ; Chlebek, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Miriama Hutníková Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of diploma thesis: Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on the farnesoid X receptor and the G protein coupled receptor 1 Farnesoid X receptor (FXR) and bile acid receptor associated with G protein 1 (TGR5) significantly affect metabolic processes in the human body. The role of FXR in neuronal apoptosis in Alzheimer's disease (AD) has also been discovered. The possible structural similarity of the small lipophilic molecules binding to these receptors and the alkaloids found in the plants Corydalis cava and Narcissus pseudonarcissus, as well as the richoften use of these plants in traditional medicine, represent a potential therapeutic intervention for these molecules. In our screening methods, we performed tests using a luciferase gene reporter assay to determine the ability of the alkaloids to interact with FXR and TGR5 in the HepG2 cell line. Many derivatives have shown a strong ability to antagonize FXR and TGR5 activated by obethicholic (OCA) or litocholic (LCA) acids in this assay. Some of the compounds also demonstrated the ability to potentiate the effects of OCA or LCA. Cytotoxicity...
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Mitochondrial transfer-mediated modulatory action of stem cells on immune cells
Somova, Veronika ; Krulová, Magdaléna (advisor) ; Balounová, Jana (referee)
Stem cells use different mechanisms of intercellular communication to modulate an immune response. Mitochondrial transfer is one of the mechanisms which induce metabolic changes, support cell survival, and change the phenotype of immune cells. Nevertheless, little is known about the mechanism used for transfer of mitochondria between different cell populations and the faith of mitochondria inside the acceptor cell. This thesis aims to describe the mechanism of transfer and the provided modulation. Factors that could affect mitochondrial transfer including reactive oxygen species production, apoptosis and mitochondria function were analyzed. And the impact of mitochondrial transfer on cell survival and mitophagy was described. The next aim was to compare the ability of mesenchymal stem cells (MSC) and Sertoli cells (SC) to transfer mitochondria, with MSC being more productive in the transfer of mitochondria than SC. Significant differences in the presence of mitochondria from donor MSC or SC in individual populations of immune cells were also detected. To explain these findings, the impact of reactive oxygen species on the transfer of mitochondria was analyzed in detail, although it wasn't confirmed. However, it needs to be highlighted that mitophagy plays an important role before and after...
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High grade serous ovarian carcinoma: molecular background and platinum-based chemotherapy challenges
Ivančinová, Jana ; Heneberg, Petr (advisor) ; Brábek, Jan (referee)
Ovarian carcinoma (O.C.) represent a group of various disease entities derived from ovaries. The most common malignant gynaecological cancer is high-grade serous ovarian carcinoma (HGSOC). HGSOC is associated with a high mortality rate due to its aggressive behaviour and insufficient early-stage detection. The survival rate has not been significantly improved since 1970s. The most effective treatment of HGSOC patients is by cytoreductive surgery (for early stages I/II) and followed by platinum-based chemotherapy (HGSOC presented in advanced stage III/IV) combined with taxane or potentially with PARP inhibitors (for BRCA1/2 mutation carriers). Multiple factors affect the patient's outcome and prognosis. Chemoresistance, molecular mutational patterns, stage at presentation of HGSOC are one of the clinical challenges contributing to common relapses even though patients often initially respond well to the HGSOC chemotherapy. This thesis overviews the fundamental biology of HGSOC, the major obstacles in clinical management and its improvements by implementing of multitherapy approaches. Key words: CA-125; platinum−based chemotherapy treatment; homologous recombination deficiency; ovarian carcinoma; resistance; Tp53; mortality; survival rate
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Importance of glycolysis and oxidative phosphorylation in the metabolism of mesenchymal stem cells
Fráňová, Markéta ; Krulová, Magdaléna (advisor) ; Rohlenová, Kateřina (referee)
Mesenchymal stem cells (MSCs) are classified as multipotent stem cells. They possess the ability to differentiate into many cell types, promote angiogenesis, increase cell survival in damaged tissue and modulate the immune response. These functions of MSCs are used in the treatment of various injuries and some diseases. This work characterizes MSCs, with a focus on their energy metabolism, specifically on the switch in their metabolic phenotype between glycolysis and oxidative phosphorylation in different states of MSCs, during cell culture and after transplantation. Finally, two modulations of MSC metabolism are presented, including cultivation in a hypoxic environment and quiescence induced by serum deprivation, which increase cell survival under the ischemic conditions that MSCs enter after transplantation. Key words: mesenchymal stem cells, metabolism, glycolysis, oxidative phosphorylation
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Factors influencing intraspecific scaling of metabolic rate
Trubelová, Zuzana ; Starostová, Zuzana (advisor) ; Storch, David (referee)
The relationship between metabolic rate and animal body size of the animal has been studied for more than hundred years. Recently, attention of scientists moved from the interspecific to the intraspecific level. The work focuses on the intraspecific scaling of metabolism. When plotting the metabolic rate against body mass during ontogeny the resulting line often exhibits one or more breaks. Why these breaks (and thus reduction the metabolic rate) occur hasn't been fully explained. It is assumed that can be due to certain factors that affect an individual during development. Some of these factors came from the most famous of several hypotheses attempting to explain the scaling of metabolic rate. These hypotheses include the Metabolic Theory of Ecology (MTE), the Metabolic Level Boundaries (MLB), the Cell model and the Dynamic Energy Budget (DEB) hypothesis. There are several factors that could affect individuals during ontogeny. These include internal factors, which result from the internal processes within the body. These factors are often interrelated with each other in different ways; therefore, it is unlikely to choose only one particular factor which affects metabolic rate. The most frequently studied factors are changes of cell size and changes in the proportion of metabolically active...
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Comparison of methods of basal metabolism determination
Kosková, Martina ; Coufalová, Klára (advisor) ; Hráský, Pavel (referee)
Title: Comparison of individual methods of basal metabolism determination Objectives: The aim of the work is to compare the individual methods of basal metabolism. These values were measured by indirect calorimetry, plethysmography, bioelectric impedance and predictive equations. Methods: The research was attended by 31 people, including eight men and twenty-three women. All participants of my research were aged 21-30 years. None of the participants was a professional athlete, they were all healthy and none of the women were pregnant or had menstruation. The indirect calorimetry, bioelectronics impedance device Tanita MC - 980 and BOD POD were used to collect the data. Basal metabolic rates were calculated from the prediction equations by Harris & Benedict, Fleisch's equation and Schofield's equation using measured anthropometric values. Results: The results of the methods that have been used for this group of people vary, but the difference is not significant. If we choose as a reference method indirect calorimetry, we can't replace it by any other method. The results for other methods are not significantly different, so we can replace one method with another, except indirect calorimetry. From calculations, we also found out that fat free mass greatly influences the results of basal metabolic rate...
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Metabolism of uric acid during mammalian evolution
Mančíková, Andrea ; Krylov, Vladimír (advisor) ; Stibůrková, Blanka (referee)
Uric acid is the end product of purine metabolism of humans and some higher primates. In other mammals enzyme urate oxidase is capable to further convert uric acid to allantoin. During evolution of primates several mutations in urate oxidase gene had occured, led the enzyme to decrease its activity or to complete loss of function. What was the initial impetus for the utilization of uric acid and what biochemical traits of uric acid led to a tendency to retain a major of this metabolite production in the bloodstream? Uric acid has antioxidant capabilities and it is scavanger of free radicals. Increased levels of uric acid in blood has an effect on acute and chronic elevations of blood pressure. It is possible that hyperuricemia helped to maintain blood pressure under low-salt dietary conditions of primates during the Miocene. This mechanism probably have allowed to stabilize bipedalism our ancestors. Uric acid has an important role as a neuroprotector. As inhibitor the permeability blood-brain barrier, uric acid limits the infiltration of undesirable substances to the neurons and prevents central nervous system against the formation of inflammatory diseases. Such as neurodegenerative diseases may be caused by reduced serum uric acid levels. Uric acid protects against peroxinitrite damage tissues in the...
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Lipid composition of biological membranes and life-histories in songbirds
Šimonová, Kateřina ; Tomášek, Oldřich (advisor) ; Sam, Kateřina (referee)
Differences in the composition of cell membranes are considered to be the physiological mechanism responsible for different metabolic rates, life span and consequently, different life-histories. The membrane pacemaker theory suggests that higher membrane unsaturation may be an important factor responsible for higher metabolic rate and shorter life span of organisms. The alternative hypothesis, on the other hand, assumes that membranes can function as structural antioxidants, and thus that higher membrane unsaturation may be associated with longer life span. The aim of this work was to test how changes in the fatty acid composition of membranes depends on body size, latitude and altitude, within which different life-histories and metabolic rate were observed. Temperate and tropical lowland songbird species were chosen for the models testing the effect of latitude, and only tropical species of songbirds were chosen for the models testing the effect of altitude. Part of the work was molecular sex determination. Using gas chromatography and mass spectrometry, the amount of individual fatty acids contained in red blood cell phospholipids was obtained from blood samples. The results showed that the composition of the membranes in most cases correlates with body size, which also correlates with almost all...
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Effect of cholinesterase inhibitors on monoaminergic system and energic metabolism
Kalinová, Tereza ; Mladěnka, Přemysl (advisor) ; Štěpánková, Šárka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tereza Kalinová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Mentor: Assoc. Prof. Jana Hroudová, Pharm.D., Ph.D. Title of diploma thesis: Effect of cholinesterase inhibitors on monoaminergic system and energy metabolism Cholinesterase (ChE) inhibitors play an essential role in the treatment of Alzheimer's disease (AD). They effect positively cognitive, functional and behavior symptoms of AD. Up to date, donepezil, rivastigmine and galantamine represent the only ChE inhibitors approved for AD treatment. The first ChE inhibitor was tacrine, which was withdrawn from market due to its toxicity and adverse effects. Recently, novel tacrine and 7-methoxytacrine (7-MEOTA) derivatives were synthetized and extensively investigated to find less toxic compounds affecting pathological mechanisms associated with development of AD. There is less known about effects of these drugs on mitochondrial functions and cellular energy metabolism. The aim of this project is to examine in vitro effects of ChE inhibitors on energy metabolism and cellular respiration, specifically on mitochondrial electron transport chain complexes and an enzyme of the citric acid cycle - citrate synthase. Inhibitory effects...
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