|
|
Molecular mechanisms of cfDNA effects
Hříbková, Natálie ; Daňková, Pavlína (advisor) ; Škubica, Patrik (referee)
The biological role of free circulating DNA is currently being investigated mainly in terms of the etiology of autoimmune conditions and cancer. It appears that the role of cfDNA of nuclear or mitochondrial origin in interacting with receptors of the innate immune system is quite complex and cfDNA is thus involved in a variety of molecular mechanisms such as the spread of cancer metastasis, induction of autophagy and triggering of inflammatory processes. Knowledge of the specific pathways in which cfDNA is involved in the development of these pathologies seems to be crucial, especially in terms of selecting and targeting appropriate therapies. This paper provides a framework for the knowledge on the interaction of cfDNA with receptors of the innate immune system, the induction of immunological signaling pathways and the possible consequences that these molecular pathways may have in the body. Key words: cfDNA, TLR9, cGAS/STING, AIM2, autoimmune disease, biomarker, cancer
|
|
|
The circulating cell-free DNA as a biomarker of civilization diseases
Dyachenko, Yulia ; Daňková, Pavlína (advisor) ; Vaňková, Markéta (referee)
The incidence of civilization diseases in the population is increasing every year due to changing environmental conditions and modern lifestyles. These diseases reduce the quality of life, lead to health complications or even death of patients. This can be prevented by monitoring health status. Circulating free DNA (cfDNA) has the potential to be introduced as a non-invasive biomarker. Possible mechanisms of cfDNA release are apoptosis, necrosis, NETosis, pyroptosis and active secretion. The occurrence of these processes in some civilization diseases allows the use of cfDNA as a biomarker. The aim of this work was to summarize the current knowledge on the possibility of using cfDNA in the diagnosis, monitoring of the development and course of some diseases of civilization, namely obesity, diabetes mellitus, atherosclerosis, hypertension, myocardial infarction and stroke. From the available literature it can be concluded that cfDNA could be used in clinical practice for the purposes described above. Key words: Circulating cell-free DNA (cfDNA), civilization diseases, biomarker, obesity, diabetes mellitus, atherosclerosis, hypertension, myocardial infarction and stroke.
|
|
|
The importance of cell-free HPV DNA detection
Milt, Petr ; Saláková, Martina (advisor) ; Horníková, Lenka (referee)
Human papillomaviruses (HPV) are small, nonenveloped DNA viruses that are abundant in the population. They are sexually transmitted or spread by close contact with mucosa and skin. Papillomaviruses can cause lesions and warts on the skin and mucosa. In addition, high-risk HPV types, especially HPV 16 and 18, are associated with squamous cell carcinomas such as cervical cancer, oropharyngeal cancer and carcinomas of the vulva, anus, penis and vagina. Early detection and the right evaluation of the risk of recurrence are crucial for effective treatment. Cell-free DNA released from cells into body fluids has potential in cancer diagnosis. Cell-free circulating HPV DNA, in the blood of patients with HPV-associated cancers is a promising and highly sensitive biomarker, useful for monitoring treatment efficiency, early detection of the disease and estimation of recurrence risk. Key words: HPV, carcinogenesis, cfDNA, cfHPV DNA, significance of detection, cervical cancer, oropharyngeal cancer
|
|
|
Analysis of cell-free nucleic acids in urine of urological patients.
Šantorová, Šárka ; Korabečná, Marie (advisor) ; Brdička, Radim (referee) ; Drábek, Jiří (referee)
The two studies follow free nucleic acids in urine in search for biomarkers to distinguish urinary bladder cancer patients from controls. Bladder cancer forms 4 % of newly diagnosed oncological diseases in the Czech Republic. Nowadays, there is no accredited non-invasive method for its diagnosis, which is sufficiently accurate. Urine supernatant, which is washing the bladder mucosa and which does not contain cell debris, seems to be an appropriate source of biomarkers for non-invasive diagnosis. miRNAs, as a non-invasive biomarker of urinary bladder cancer, were studied in one of the studies. miRNAs are short noncoding RNA, which block the process of translation. miRNAs occur in all body fluids and are relatively stable. A study with three phases was assessed to find a suitable miRNA marker. 109 individuals were examined in total (36 controls and 73 bladder cancer patients). The analysis of miRNAs was based on RT-PCR (Reverse Transcription Polymerase Chain Reaction). In the first phase, the urine of 59 individuals was analyzed on TaqMan array card with 381 miRNAs. In the second phase, the results of the first phase were confirmed on the same cohort by a single miRNA assay. In the third phase, a new cohort was used (23 controls and 27 bladder cancer patients), analyzed by a single miRNA assay again....
|
|
|
Effect of selected inflammatory agents on the osteoclastogenesis
Škubica, Patrik ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Introduction: Bone is a highly active tissue throughout life and is a subject to constant remodelling. Main cells responsible for continuous resorption and de novo synthesis of bone matrix are osteoclast, osteoblasts and osteocytes. Osteoclasts are the only known type of cells able to resorb bone. These cells are formed by fusion of precursor cells in bone marrow or peripheral blood in a process called osteoclastogenesis. Formation of osteoclasts may be of importance concerning chronic inflammatory diseases that are linked with higher risk of developing osteoporosis during lifespan. Celiac disease is one of those diseases, which is characterized by destruction of intestinal mucosa after ingestion of gluten by susceptible individuals followed by induction of chronic inflammation. In this work, we focused on the potential role of osteoclastogenesis in the development of osteoporosis in patients with celiac disease and we studied roles of selected inflammatory agents (TNF-α, IL-6, IFN-γ a cfDNA) with supposed or hypothesised effects on osteoclastogenesis. Material & Methods: We obtained plasma and serum samples from newly diagnosed patients with celiac disease, patients on gluten free diet and healthy controls and analysed concentrations of cfDNA and inflammatory cytokines TNF-α, IL-6 and IFN-γ in...
|
guest ::
