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Interaction of selected natural substances used in food industry with DNA and its structural motifs
Gardošová, Zuzana ; Pernicová, Iva (referee) ; Brázda, Václav (advisor)
G-quadruplexes represent secondary DNA structures formed in guanine-rich nucleic acid regions. These structures are involved in many biological processes, including DNA replication, transcription, and telomere maintenance. Several natural substances interacting with G-quadruplex structures have been described. Many of them can be used in the treatment of cancer or other areas of therapeutic practice. G-quadruplexes are dynamic structures whose stability can be affected by a variety of different factors, including chemical modifications to DNA. One of these modifications is DNA methylation, which is an important epigenetic mechanism regulating gene expression. DNA methylation can affect the function and stability of G-quadruplex structures. The theoretical part of the present work focuses on DNA secondary structures, characterization of G-quadruplexes and their ligands and describes the relationship between DNA methylation and G-quadruplex structures. In the experimental part, the binding ability of the natural substances quercetin, berberine, piperine, and caffeine to G-quadruplex structures formed in telomeric oligonucleotide sequences and sequences derived from the proto- oncogene c-Myc was confirmed. Furthermore, the ability of berberine and quercetin was proven to stabilize G-quadruplexes in the aforementioned sequences. Bioinformatics analysis showed that the frequency of G4 is higher in CpG regions than in their surroundings, and the highest frequency of G4 within CpG regions was observed on chromosome 19. Global methylation assays demonstrated that the breast cancer cell line exhibited hypomethylation compared to the non-tumor human dermal fibroblast cell line. After treatment with berberine, the analyzed DNA of both cell lines showed hypermethylation, whereas DNA after interaction with quercetin showed hypomethylation.
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Impact of plant alkaloids on viral infection
Šnejdarová, Aneta ; Horníková, Lenka (advisor) ; Váňová, Jana (referee)
Plant products have been used to treat various diseases since ancient times thanks to the many active substances they contain. One such group of substances are alkaloids. Alkaloids are biologically active substances which, in addition to antimicrobial, anti-inflammatory, antioxidant and many other properties, also possess antiviral properties. As a result, they can help treat viral infections, which are still a major medical problem today. Alkaloids affect all steps of virus replication, both viral components but especially cellular processes, without which a successful progress of viral cycle is not possible. In connection with the treatment of viral infections, the tropane, troponol, purine and isoquinoline alkaloids have been best investigated, which are also the subject of this work. The tropane alkaloid atropine acts mainly on enveloped viruses due to its ability to change the properties of biological membranes. Purine alkaloid caffeine, thanks to its ability to inhibit the cellular enzyme phosphodiestrase, causes an increase in intracellular cAMP levels and it has an impact on viral replication. Its antioxidant and immunomodulatory properties are also beneficial for the treatment. The anti-inflammatory effects of the tropane alkaloid colchicine stem from its ability to inhibit the dynamics of...
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