|
|
Novel bile acid derivatives as a promising therapeutic approach for liver and metabolic disorders
Štefela, Alžbeta ; Pávek, Petr (advisor) ; Vítek, Libor (referee) ; Juřica, Jan (referee)
IN ENGLISH LANGUAGE Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology Candidate: Mgr. Alžbeta Štefela Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Novel bile acid derivatives as promising therapeutic approach Bile acids (BAs) are amphipathic steroidal molecules that are traditionally known to facilitate intestinal digestion and absorption of lipids and fat-soluble substances. On top, the recent findings have revealed that they represent important signaling agents involved in the orchestration of lipid, glucose and energy metabolism and immune response. BAs exhibit these roles by activating intracellular nuclear receptors such as farnesoid X (FXR), pregnane X (PXR) vitamin D receptors. Furthermore, BAs act as endocrine signaling molecules and activate numerous biological cascades via a membrane G-protein-coupled receptor, termed TGR5. Therefore, the extensive modulation of BA scaffold underwent to identify compounds with specific targeting of above-mentioned receptors as a promising therapeutic approach for the treatment of various liver and metabolic disorders including cholestasis, biliary cirrhosis, nonalcoholic steatohepatitis or diabetes. The principal aim of this doctoral thesis was to investigate the structure...
|
|
|
Novel bile acid derivatives as a promising therapeutic approach for liver and metabolic disorders
Štefela, Alžbeta ; Pávek, Petr (advisor) ; Vítek, Libor (referee) ; Juřica, Jan (referee)
IN ENGLISH LANGUAGE Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology Candidate: Mgr. Alžbeta Štefela Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Novel bile acid derivatives as promising therapeutic approach Bile acids (BAs) are amphipathic steroidal molecules that are traditionally known to facilitate intestinal digestion and absorption of lipids and fat-soluble substances. On top, the recent findings have revealed that they represent important signaling agents involved in the orchestration of lipid, glucose and energy metabolism and immune response. BAs exhibit these roles by activating intracellular nuclear receptors such as farnesoid X (FXR), pregnane X (PXR) vitamin D receptors. Furthermore, BAs act as endocrine signaling molecules and activate numerous biological cascades via a membrane G-protein-coupled receptor, termed TGR5. Therefore, the extensive modulation of BA scaffold underwent to identify compounds with specific targeting of above-mentioned receptors as a promising therapeutic approach for the treatment of various liver and metabolic disorders including cholestasis, biliary cirrhosis, nonalcoholic steatohepatitis or diabetes. The principal aim of this doctoral thesis was to investigate the structure...
|
|
|
miRNAs as diagnostic markers after treatment with glucocorticoids in rheumatology
Tripská, Katarína ; Pávek, Petr (advisor) ; Doseděl, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Katarína Tripská Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: miRNAs as diagnostic markers after treatment with glucocorticoids in rheumatology MicroRNAs are important class of non-coding RNAs that play important role in modulation of expression of multiple genes at a post-transcriptional level. Their deregulation contributes to many immune disorders including rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. This thesis represents the most recent knowledge about functions of microRNAs in pathogenesis of these disorders and results were obtained by review of scientific literature published on PubMed database. The most perspective microRNAs in rheumatoid arthritis seem to be miR-16, miR-21, miR- 146a, miR-150 a miR-223. In lupus miR-148, miR-126, miR-21, miR-155, miR-125a a miR- 146 will probably find their useage as biomarkers. Systemic sclerosis is less examined diseases and we know most about miR-29 in the disease. Since the research of microRNA as diagnostic biomarkers is only at the beginning, it is most likely, that with the time there will be more and more of new microRNAs helping us clarify pathogenesis of each disorder. We can suppose...
|
|
|
Pharmacogenetics in rheumatology - role of miRNAs
Vicherková, Petra ; Pávek, Petr (advisor) ; Doseděl, Martin (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Bc. Petra Vicherková Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of master thesis: Pharmacogenetics in rheumatology - role of miRNA Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that causes progressive joint damage and can result in to life-long depreciation of life. The influence on the onset and course of the disease is not only genetic, but due to the heterogeneous character of the disease, it is also strongly influenced by lifestyle. This disease, based on the malfunction of our immune system in RA, is still incurable. The treatment of RA uses conventional synthetic drugs as well as biological treatment. To diagnose the effect of anti-rheumatic therapy, monitoring and evaluating the response to treatment is necessary. Important indicators of RA activity, functional status, quality of life, and structural progression of the disease are important. In clinical practice, we use DAS 28 composite system according to recommendation of ČRS. Recent discoveries in the area of diagnostics raise the question of whether some miRNAs could be appropriate biomarkers of RA progression. In my diploma thesis, I summarize available knowledge in this field, obtained from...
|
guest ::
