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Liver cells regeneration in mammals
Ťažký, Timotej ; Tlapáková, Tereza (advisor) ; Onhajzer, Jakub (referee)
Liver cell regeneration is an important biological process that allows mammals to maintain liver function while recovering from liver damage. Liver cell proliferation serves as the primary mode of liver regeneration, which in hepatocytes is activated by the transition from the G0 to G1 phase of the cell cycle. Proliferation is also promoted by non-parenchymal liver cells among which include Ito cells, Kupffer cells, and endothelial cells of hepatic sinusoids. In a comprehensive analysis of key signaling pathways, it was clearly demonstrated that the Wnt/β catenin, Notch, Hippo, NF-κB, and Hedgehog signaling pathways play a key role in the regulation of liver cell proliferation and differentiation during regeneration. The regenerative potential of the liver is influenced by various factors such as age, extent of damage and health conditions. Additionally, the remarkable regenerative capacity of the liver has clinical implications in the context of liver transplantation, partial hepatectomy and the treatment of liver diseases such as cirrhosis, hepatitis and hepatocellular or cholangiocellular carcinoma. Modulation of key signaling pathways and identification of novel molecular targets can improve the clinical outcomes of patients with liver diseases or even accelerate the entire process of liver...
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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
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Molecular mechanisms of vertebrate limb regeneration
Onhajzer, Jakub ; Krylov, Vladimír (advisor) ; Soukup, Vladimír (referee)
Limb regeneration fascinates innumerable scientists for decades. Urodele amphibians can regenerate their limbs perfectly. This ability is preserved for a whole lifetime. However, they are not the only ones who regenerate their limbs. Second species are anuran amphibians, but their ability to promote limb regeneration take place only throughout a larval stage. Both groups belong to amphibians. Limbs are regeneated by the process called epimorphosis. The primary process is formation of blastema, mass of heterogeneous dedifferetiated cells, which are unipotent with the capacity to redifferentiate into only one cell type. Essential factor is the regulation of limb regeneration by numerous molecular mechanisms in order to achieve the perfect limb shape, without unwanted tumors. Mechanisms allowing limb regeneration in lower vertebrates would be applied via regenerative medicine in higher vertebrates in the future. Keywords: regeneration, limb, epimorphosis, dedifferentiation, vertebrates
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Regenerative potential of Sertoli cell progenitors regarding heart injury in Xenopus tropicalis
Onhajzer, Jakub ; Krylov, Vladimír (advisor) ; Procházka, Jan (referee)
Cardiac failure is one of the leading cause of deaths worldwide. Potential therapeutic approach, which overcome invasive organ transplantation and delivery of immunosuppressive drugs, is lacking nowadays. However, research of mesenchymal stem cells (MSCs) therapy displays immunomodulation potential, which can further promote variety of organ regeneration without need of drug treatment. Xenopus tropicalis immature Sertoli cells (XtiSCs) culture was established in our laboratory from juvenile Xenopus tropicalis male. XtiSCs possess immunomodulatory capacity and differentiation to cardiomyocytes after the treatment with the inhibitor of glycogen synthase kinase-3 (GSK-3) CHIR99021. To test the survival rate of transplanted XtiSCs we firstly microinjected treated cells directly inside tadpole's heart. XtiSCs proliferated there for the whole tested time period (30 days). However, after direct heart XtiSCs injection and subsequent cardiac injury in adult frog, no cells were localized in wound area. Thus, we focused on remote control of cardiac regeneration using XtiSCs without CHIR99021 treatment. We injected cells inside skeletal muscle bed and confirmed their survival and proliferation. Moreover, if cells were transplanted 3 days before heart injury, it resulted in significant reduction of fibronectin...
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Molecular mechanisms of vertebrate limb regeneration
Onhajzer, Jakub ; Krylov, Vladimír (advisor) ; Soukup, Vladimír (referee)
Limb regeneration fascinates innumerable scientists for decades. Urodele amphibians can regenerate their limbs perfectly. This ability is preserved for a whole lifetime. However, they are not the only ones who regenerate their limbs. Second species are anuran amphibians, but their ability to promote limb regeneration take place only throughout a larval stage. Both groups belong to amphibians. Limbs are regeneated by the process called epimorphosis. The primary process is formation of blastema, mass of heterogeneous dedifferetiated cells, which are unipotent with the capacity to redifferentiate into only one cell type. Essential factor is the regulation of limb regeneration by numerous molecular mechanisms in order to achieve the perfect limb shape, without unwanted tumors. Mechanisms allowing limb regeneration in lower vertebrates would be applied via regenerative medicine in higher vertebrates in the future. Keywords: regeneration, limb, epimorphosis, dedifferentiation, vertebrates
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