|
|
Cardioprotective effects of sodium-glucose cotransporter SGLT2 inhibitors.
Thořová, Markéta ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Cardiovascular diseases are one of the most common causes of death in both non-diabetic and diabetic patients. Nowadays, a large number of drugs target cardiovascular problems. One of the very promising therapies is the use of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. SGLT2 inhibitors have gained a wide interest in the treatment of type 2 diabetes (DM2) due to their ability to lower blood glucose levels independently of insulin action. However, in addition to their main effect on glycemic control, there is increasing evidence of their beneficial effects on the cardiovascular system beyond their hypoglycaemic effects. These drugs reduce hyperglycemia, hypertension, and improve diabetic retinopathy through multiple mechanisms, many of which have not been fully explained. The main focus has been on identifying the mechanisms through which these drugs affect the heart and blood vessels, whether by reducing blood pressure, affecting cardiac cells, or improving metabolic processes in blood vessels. Key words: SGLT2, inhibitors of SGLT2, cardioprotective effect, diabetes mellitus, heart
|
|
|
Cardiotoxic effects of anthracyclines in oncological treatment
Tekáčová, Kateřina ; Horníková, Daniela (advisor) ; Vávra, Jiří (referee)
Anthracyclines are antitumor antibiotics used during chemotherapy in cancer patients. Treatment with anthracyclines has good results but a side effect is significant cardiotoxicity. This bachelor thesis describes the mechanisms of action of anthracyclines which are essential in cancer therapy and may be risky for patients. The thesis also defines the term of cardiotoxicity and summarizes factors that may increase the risk of cardiotoxicity. The most commonly used agents in the anthracycline series are briefly described. Cardiotoxicity can be detected by cardiac markers, especially particular troponin and diagnostic methods. The last chapter describes the groups of substances that reduce the cardiotoxic effects of anthracyclines. Key words: heart, anthracyclines, cardiotoxicity, chemotherapy, onkology treatment
|
|
|
Tcf4 transcription factor in the intestinal epithelium renewal and pathology
Müllerová, Tereza ; Janečková, Lucie (advisor) ; Vávra, Jiří (referee)
TCF4 (T-Cell Factor 4, sometimes also TCF7L2) is an important effector of the canonical Wnt signalling pathway. The transcription factor is produced in many different isoforms with tissue-specific expressionand diametricallyopposing functions.In the intestine,TCF4 is a key factor in epithelial regenerationandmaintenance of stem cell homeostasis. Its depletion causes loss of the proliferatingcrypt compartment and complete breakdown of the intestinal mucosal architecture. The processes in which it acts are therefore vital and must be strongly regulated by the Wnt signalling pathway. Disturbances in TCF4 expression or alternative splicing often lead to a wide range of complex pathologies such as colon cancer, ileal Crohn's disease and type 2 diabetes mellitus.
|
|
|
Structure and function of ubiquitin-activating enzyme UBA1
Pánska, Dominika ; Vávra, Jiří (advisor) ; Onhajzer, Jakub (referee)
Ubiquitin-activating enzyme, also known as UBA1, is an essential enzyme in the process of ubiquitin activation in all eukaryotic cells, and its loss, as well as complete disfunction, leads inevitably to death of an organism. In humans, nuclear (UBA1a) and cytoplasmic (UBA1b) isoforms are known. Ubiquitination, the process at the beginning of which UBA1 stands as a key player, is important for proteasomal degradation of proteins, cell cycle progression, DNA damage repairs, fertilisation, as well as antiviral response of an organism. Its impaired function is the cause of many oncological and neurodegenerative diseases or just recently discovered autoinflammatory syndrome VEXAS. This thesis includes basic and current knowledge about UBA1, its structure, functions in cells and pathologies. Key words: UBA1, ubiquitin, catalytic cysteine, proteasomal degradation, VEXAS
|
|
|
Molecular mechanism of animal cells adaptation on hyperosmotic induced stress
Novotná, Jana ; Vávra, Jiří (advisor) ; Převorovský, Martin (referee)
Various types of cells animal tissues consist of need to adapt to intracellular as well as extracellular osmotic changes in order to maintain homeostasis. Hypertonicity (increased osmolarity) is one of the factors activating complex cellular reactions. In order to manage such stress, a cell needs to incorporate regulation pathways that can either regulate ion transporters through WNK kinases or activate gene expression of transporters of compatible osmolytes through the transcription factor TonEBP/NFAT5. Physiologically exposed to hypertonic conditions are cells in renal medulla, cartilage, inner ear tissues, in specialised neurons or buccal epithelium. This work includes basic and current knowledge about the adaption of cells to increased osmolarity of outer environment. Key words: Hyperosmolarity, osmotic stress, TonEBP/NFAT5, WNK kinases, NF-κB, HSP70
|
|
|
Electronically Configurable Transfer Structures
Langhammer, Lukáš ; Hospodka, Jiří (referee) ; Vávra, Jiří (referee) ; Šotner, Roman (advisor)
Práce se zaměřuje na vývoj a výzkum v oblasti elektronicky rekonfigurovatelných přenosových struktur. Primárním cílem je návrh těchto struktur za užití moderních elektronicky řiditelných aktivních prvků. V práci je prezentováno množství elektronicky rekonfigurovatelných filtračních struktur, jež byly vytvořeny za užití různých návrhových metod. Důraz je dále kladen na možnost řídit některý z typických parametrů filtru pomocí řiditelných aktivních prvků. Práce dále obsahuje několik obvodových návrhů aktivních prvků či stavebních bloků s vhodně řešenou elektronickou řiditelností, tak, aby tyto prvky/bloky mohly být dále použity pro návrh elektronicky rekonfigurovatelných filtrů. Správnost návrhu jednotlivých zapojení je podpořena PSpice a Cadence simulacemi s modely na tranzistorové úrovni. Vybraná zapojení jsou dále realizována za pomocí dostupných aktivních prvků a podrobena experimentálnímu měření.
|
|
| |
|
|
Phylogeny of Archamoebae
Ptáčková, Eliška ; Čepička, Ivan (advisor) ; Vávra, Jiří (referee)
Archamoebae is a small group of anaerobic protists belonging to the eukaryotic supergroup Amoebozoa. Historically, they were regarded as primitively amitochondriate. However, a mitochondrial remnant has been found in some archamoebae. Phylogenetic analyses showed that Archamoebae are closely related to the aerobic slime moulds (Mycetozoa). Trophozoites of archamoebae are amoeboflagellates or aflagellated amoebae. The group includes both parasitic (Entamoeba, Endolimax and, possibly, Endamoeba and Iodamoeba) and free-living (Mastigamoeba, Mastigella, Pelomyxa) genera. The genus Mastigina comprises both endozoic and free-living representatives. Flagellated genera Mastigina, Mastigamoeba, Mastigella and Pelomyxa possess a single basal body associated with a microtubular cone which may or may not be associated with nucleus. The cone is a common feature for Archamoebae and mycetozoan slime moulds. The phylogeny of Archamoebae has not been fully elucidated yet and the taxonomy of free-living representatives is confusing. In the present study, we obtained 42 stable isolates of free-living Archamoebae. We sequenced and analyzed SSU rDNA of 15 of them. The Archamoebae split into five lineages. Based on TEM, we were able to recognize genera Mastigamoeba and Mastigella. The isolate IND8 probably represents a new...
|
|
|
Porcelain disease in crayfish: biology, impacts and distribution
Jelínková, Tereza ; Balcarová, Eva (advisor) ; Vávra, Jiří (referee)
The porcelain disease is a disease affecting crayfish caused by the microsporidium Thelohania contejeani. This intracellular parasite attacks muscle cells of the host and fills them with spores. This leads to white or opaque colouration of the abdominal muscle of crayfish, which is characteristic for this disease. The parasite gradually attacks more muscle fibers which probably leads to decrease of locomotor activity of affected crayfish and finally may result in their death. T. contejeani at low prevalences does not represent a real danger to crayfish populations and thus it is not as serious threat as crayfish plague. However, it has been associated with several cases of mass mortalities too. This thesis summarizes essential findings about infection by this parasite, analyzes its impacts to the host and factors that can influence transmission and progress of this disease. It also describes a life cycle of T. contejeani, summarizes records of the occurrence of this parasite and evaluates risks which it poses to crayfish populations. Finally, methods used to detect infection are described. Keywords: Thelohania contejeani, porcelain disease, crayfish, microsporidia, parasite, muscle
|
|
|
Molekulární charakterizace gregarin flebotomů a jejich interakce s hostitelem
Lantová, Lucie ; Volf, Petr (advisor) ; Vávra, Jiří (referee) ; Warburg, Alon (referee)
Gregarines (Apicomplexa: Gregarinasina) are monoxenous parasites of invertebrates. Those found in sand flies (Diptera: Psychodidae) and mosquitoes (Diptera: Culicidae) used to be considered a single eugregarine genus Ascogregarina. Our phylogenetic analyses of the gregarine SSU rDNA, including newly obtained sequences of three species from sand flies, showed that mosquito and sand fly gregarines are closely related to neogregarines, and most importantly, they form two disparate monophyletic groups. Based on these molecular features, accompanied by biological differences, we established a new genus Psychodiella for the gregarines from sand flies, reserving the genus Ascogregarina for the mosquito gregarines. In the new genus, two new species Psychodiella sergenti from Phlebotomus sergenti and Psychodiella tobbi from Phlebotomus tobbi were described. They differ in the life cycles (sexual development of Ps. sergenti is triggered by a blood meal intake) and morphology of their life stages, mainly oocysts. The susceptibility of five sand fly species to both gregarines showed their strict host specificity, as they were able to fully develop and complete the life cycle only in their natural hosts. The life cycle of Ps. sergenti was studied in detail using various microscopical methods. Oocysts are attached to the...
|
guest ::
RSS feed.