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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...
Alcohol intake of athletic university students
HRDLIČKOVÁ, Vanda
The topic of my bachelor's thesis is "alcohol intake of athletic university students." The rate at which alcohol is broken down depends on a number of physiological differences, such as gender or the proportion of muscle and fat tissue. Despite its certain protective effects, consumption cannot be recommended - especially in combination with sport. In the practical part, a quantitative method of data collection was used. The research group consisted of 128 university students aged 18-30. The aim was to compare the different alcohol consumption of athletic and non-athletic students. The results of both groups were very similar. The most frequently chosen option was "I consume alcohol only occasionally (about twice a month)", as it was chosen by 40% of sports and 33.3% of non-sports respondents. This was followed by consumption 3-5 times a month, which was chosen by 36% of athletes and 41% of non-athletes. There was a higher frequency of consumption (several times a week) in the case of 18% of athletes and 16.7% of non-athletes. The last 6% of sports and 9% of non-sports respondents consume alcohol every day. Another aim was to examine the degradation of alcohol from the system. I tested 20 students (10 athletes, 10 non-athletes) by using an alcohol tester. Athletic men eliminated a dose of 40 ml of 34% distillate within 30 minutes. Non-athletes in double time, i. e. 60 minutes. All women eliminated the same dose of alcohol within a similar period of time (60-105 minutes), regardless of the level of their physical activity. All participants also provided a weekly dietary record, including alcohol consummation. After entering dietary records into the Nutriservis program, I came to an average energy intake and the representation of individual nutrients, which can also affect the degradation itself.
Rekonstrukce metabolických drah bakterií Legionella polyplacis a Candidatus Riesia pediculischaeffi, symbiontů vší
ZADINOVÁ, Zuzana
The genomes of two bacteria, Legionella polyplacis and Candidatus Riesia pediculischaeffi, lice endosymbionts, were examined and compared. Preserved genes were identified, assigned to appropriate metabolic pathways, and listed in an electronic attachment table. Completeness and functionality were assessed for individual metabolic pathways. Based on the results, metabolic maps were created for both bacteria
Imunoterapie metastazujícího pankreatického adenokarcinomu řešená na dvounádorovém modelu
SKALIČKOVÁ, Markéta
This master's thesis studies the efficacy of cancer immunotherapy based on TLR agonists and ligands stimulating phagocytosis, abbreviated as MBTA therapy, using a mouse model of pancreatic adenocarcinoma. The main goals are: (1) to enhance the efficacy of MBTA in the case of large tumors, (2) to enhance the efficacy of MBTA using a bilateral pancreatic adenocarcinoma mouse model, (3) to examine the potential of lipoteichoic acid to opsonize cancer cells and stimulate phagocytic cells.
The role of mTOR complexes in immunophenotype of leukemia cells
Kořánová, Tereza ; Kuželová, Kateřina (advisor) ; Krulová, Magdaléna (referee)
Acute myeloid leukemia (AML) is a cancerous disease of hematopoiesis characterised by accumulation of immature cells (blasts) of the myeloid lineage. AML blasts utilise a range of mechanisms to escape the immune system including alteration of their metabolism or expression of inhibitory molecules. Activation of these mechanisms is not yet fully understood. One of the pathways used to regulate a great number of cellular processes is the mammalian target of rapamycin (mTOR) pathway. mTOR kinase forms two complexes, mTORC1 and mTORC2, each regulating different substrates and cellular functions. The aim of this thesis was to analyze the influence of inhibition of each of the mTOR complexes on the metabolism (oxidative phosphorylation and glycolysis) and expression of immune escape markers (HLA-I, HLA-DR, CLIP, PD-L1, TIM-3) was analysed. The inhibitor JR-AB2-011 (an mTORC2 inhibitor) reduced the mitochondrial respiration rate in the majority of the cell lines, but its impact on the cell immunophenotype was only weak. Importantly, we found that the effect on the cell metabolism did not stem from the inhibition of mTORC2. Rapamycin (an mTORC1 inhibitor) decreased both metabolic rates, as well as glucose uptake. At the same time, CLIP, PD-L1, and TIM-3 expression was reduced in all the studied cell lines,...
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.
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...
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...
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
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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