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Effect of soluble endoglin on bile acids metabolism in the liver of high-fat diet-fed transgenic mice.
Jiroušková, Barbora ; Nachtigal, Petr (advisor) ; Schreiberová, Jolana (referee)
Barbora Jiroušková Effect of soluble endoglin on bile acids metabolism in the liver of high-fat diet-fed transgenic mice. Diploma thesis Charles University, Faculty of Pharmacy in Hradci Králové Pharmacy Background: Increased plasma concentrations of soluble endoglin (sEng) have been demonstrated in metabolic disorders such as hypercholesterolemia or insulin resistance. Metabolic diseases and inappropriate diet are the basis for the development of NASH (Non-alcoholic steatohepatitis). The aim of this diploma thesis was to determine how high plasma concentrations of sEng affect the bile acids metabolism in the liver of mice fed with high-fat diet, which induced NASH. Methods: Three-month-old male mice with CBAxC57BL/6J base (n = 8, in each group) were used in experiment: 1) "wild-type", which were fed a standard diet (WTchow) for 6 months; 2) "wild-type" male mice fed a high fat diet (cholesterol, glucose and fructose) (WTHFD); 3) males expressing human sEng (sENGHFD) which were fed a high fat diet, glucose and fructose. In vivo kinetic study was performed to determine bile flow. Expression of transport proteins responsible for bile acids transport was performed at mRNA and protein level by qRT-PCR and Western blot. Results: High levels of soluble endoglin did not significantly affect BA homeostasis...
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Study of Novel FXR Ligands
Jeřábková, Jana ; Pávek, Petr (advisor) ; Schreiberová, Jolana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Mgr. Jana Jeřábková Consultant: prof. PharmDr. Petr Pávek, Ph.D. Title of Thesis: Study of Novel FXR Ligands Human farnesoid X receptor (FXR) is ligand-activated transcription factor that belongs to the nuclear receptor superfamily. FXR binds to its response element (FXRE) as monomer or heterodimer with retinoid X receptor (RXR) resulting to activation of transcription of target genes. FXR positively or negatively regulates a wide range of target genes involved in maintaining the homeostasis of bile acids, cholesterol, lipid and glucose metabolism. Furthermore, FXR transcriptionally regulates genes involved in regulation of the immune response, in the development of inflammation and maintaining the intestinal barrier function and genes controlling coagulation and remodeling of the vessel wall. The interest of current scientific studies is to find the new ligands of FXR, which would be suitable for therapeutic use. Besides the natural bile acids, the first medicinal product containing semi- synthetic FXR ligand, obeticholic acid (6-ECDCA) as active substance was registered last year for the treatment of primary biliary cholangitis. In this experimental rigorosum thesis we focused on...
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Effect of soluble endoglin on bile acids metabolism in the liver of high-fat diet-fed transgenic mice.
Jiroušková, Barbora ; Nachtigal, Petr (advisor) ; Schreiberová, Jolana (referee)
Barbora Jiroušková Effect of soluble endoglin on bile acids metabolism in the liver of high-fat diet-fed transgenic mice. Diploma thesis Charles University, Faculty of Pharmacy in Hradci Králové Pharmacy Background: Increased plasma concentrations of soluble endoglin (sEng) have been demonstrated in metabolic disorders such as hypercholesterolemia or insulin resistance. Metabolic diseases and inappropriate diet are the basis for the development of NASH (Non-alcoholic steatohepatitis). The aim of this diploma thesis was to determine how high plasma concentrations of sEng affect the bile acids metabolism in the liver of mice fed with high-fat diet, which induced NASH. Methods: Three-month-old male mice with CBAxC57BL/6J base (n = 8, in each group) were used in experiment: 1) "wild-type", which were fed a standard diet (WTchow) for 6 months; 2) "wild-type" male mice fed a high fat diet (cholesterol, glucose and fructose) (WTHFD); 3) males expressing human sEng (sENGHFD) which were fed a high fat diet, glucose and fructose. In vivo kinetic study was performed to determine bile flow. Expression of transport proteins responsible for bile acids transport was performed at mRNA and protein level by qRT-PCR and Western blot. Results: High levels of soluble endoglin did not significantly affect BA homeostasis...
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Effect of soluble endoglin on bile acids metabolism in the liver of high-fat diet-fed transgenic mice.
Jiroušková, Barbora ; Nachtigal, Petr (advisor) ; Schreiberová, Jolana (referee)
Barbora Jiroušková Effect of soluble endoglin on bile acids metabolism in the liver of high-fat diet-fed transgenic mice. Diploma thesis Charles University, Faculty of Pharmacy in Hradci Králové Pharmacy Background: Increased plasma concentrations of soluble endoglin (sEng) have been demonstrated in metabolic disorders such as hypercholesterolemia or insulin resistance. Metabolic diseases and inappropriate diet are the basis for the development of NASH (Non-alcoholic steatohepatitis). The aim of this diploma thesis was to determine how high plasma concentrations of sEng affect the bile acids metabolism in the liver of mice fed with high-fat diet, which induced NASH. Methods: Three-month-old male mice with CBAxC57BL/6J base (n = 8, in each group) were used in experiment: 1) "wild-type", which were fed a standard diet (WTchow) for 6 months; 2) "wild-type" male mice fed a high fat diet (cholesterol, glucose and fructose) (WTHFD); 3) males expressing human sEng (sENGHFD) which were fed a high fat diet, glucose and fructose. In vivo kinetic study was performed to determine bile flow. Expression of transport proteins responsible for bile acids transport was performed at mRNA and protein level by qRT-PCR and Western blot. Results: High levels of soluble endoglin did not significantly affect BA homeostasis...
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Study of Novel FXR Ligands
Jeřábková, Jana ; Pávek, Petr (advisor) ; Schreiberová, Jolana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Mgr. Jana Jeřábková Consultant: prof. PharmDr. Petr Pávek, Ph.D. Title of Thesis: Study of Novel FXR Ligands Human farnesoid X receptor (FXR) is ligand-activated transcription factor that belongs to the nuclear receptor superfamily. FXR binds to its response element (FXRE) as monomer or heterodimer with retinoid X receptor (RXR) resulting to activation of transcription of target genes. FXR positively or negatively regulates a wide range of target genes involved in maintaining the homeostasis of bile acids, cholesterol, lipid and glucose metabolism. Furthermore, FXR transcriptionally regulates genes involved in regulation of the immune response, in the development of inflammation and maintaining the intestinal barrier function and genes controlling coagulation and remodeling of the vessel wall. The interest of current scientific studies is to find the new ligands of FXR, which would be suitable for therapeutic use. Besides the natural bile acids, the first medicinal product containing semi- synthetic FXR ligand, obeticholic acid (6-ECDCA) as active substance was registered last year for the treatment of primary biliary cholangitis. In this experimental rigorosum thesis we focused on...
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