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Mechanisms responsible for sex bias in the prevalence of autoimmune diseases
Ráček, Vojtěch ; Daňková, Pavlína (advisor) ; Ciferská, Hana (referee)
Studies have shown that women typically have stronger immune responses than men. This can also make them more susceptible to autoimmune diseases, with females comprising 80% of autoimmune patients. In women, one X chromosome is epigenetically silenced through a process called X chromosome inactivation. However, some immune-related genes located on the X chromosome, such as TLR7 and CD40L, may escape this silencing process in certain cells or tissues. This can result in a sex-biased expression that contributes to the development and susceptibility of autoimmune diseases like lupus, rheumatoid arthritis, and Sjögren's syndrome. Another interesting factor that explains this sex bias is lncRNA XIST, which is a primary regulator of the inactivation process. It plays a crucial role in lupus development and creates an XIST ribonucleoprotein complex with proteins that help establish a repressed chromatin state on the inactivated chromosome. Importantly, many of these proteins are autoantigens in various autoimmune diseases and may serve as clinical markers for the diagnosis of these conditions. While microbiome and sexual hormones also play important roles, the focus remains primarily on XIST RNA and escape genes. Keywords: autoimmune disease, sex bias, X chromosome, escape genes, lncRNA XIST, sexual...
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Amylase gene variability in human populations
Vosmíková, Veronika ; Černý, Viktor (advisor) ; Daňková, Pavlína (referee)
Amylase is a starch-digesting enzyme produced by the pancreas and salivary glands in humans. Genes for the salivary isoenzyme (AMY1), located on chromosome 1p21.1, show remarkable variability in their copy numbers (CNV). Their count is positively correlated with the final amount of the produced enzyme. This variability could be the result of positive selection during human evolution, depending on the amount of starch consumed by various populations. Starch pre-digested by salivary α-amylase is absorbed more effectively, resulting in a greater gain of energy in later stages of the metabolizing process. Thus, it could have been one of the factors for rapid brain growth in humans and, significantly later, even for the agricultural transition. It could belong to a group of other known subsistence-based evolutionary changes in the human genome, such as those resulting in lactase persistence or slow acetylation of xenobiotics. Nowadays, the number of copies and the amount of produced α-amylase can influence the glucose level in the blood and insulin production after consumption, as well as the incidence of certain civilization diseases, such as obesity or type II diabetes. The influence of salivary α-amylase on the composition of the microbiome, cardiovascular diseases, and the pro-inflammatory profile...
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The effect of specific dietary intervention on inflammatory activation of innate immunity in patients with stabilized celiac disease
Selková, Katarína ; Daňková, Pavlína (advisor) ; Černá, Marie (referee)
Introduction: Celiac disease is a complex autoimmune disease induced in genetically predisposed individuals after ingestion of cereals containing gluten. Monocytes, as the main effector cells of innate immunity, play a non-negligible role in the development of the immune response in response to pathogenic and foreign agents as well as in the pathogenesis of celiac disease. The only effective treatment for celiac disease is strict and lifelong adherence to a gluten-free diet, while dietary choices are of key importance in the regulation of this disease. Oats have emerged as a controversial but nutritionally rich option to supplement a gluten-free diet with a source rich in fiber, micro- and macronutrients. Therefore, in this thesis, we focused on how the innate immune system, specifically monocytes, interact with the avenin peptides of a selected gluten-free oat cultivar and whether an immune reaction detectable at the molecular level occurs in response to its consumption. Materials and methods: 39 patients with stabilized celiac disease were included in the study, who consumed 50 g of raw oatmeal of the selected cultivar daily for 14 days. CD14+ monocytes were isolated from whole blood before the start of the study and after its completion using immunomagnetic separation, in which TLR2, TLR4, TNFα,...
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The role of mitochondrial DNA in reproduction
Svobodová, Mariana ; Daňková, Pavlína (advisor) ; Jelínková, Ladislava (referee)
The bachelor's thesis focuses on the role of mitochondrial DNA (mtDNA) in human reproduction, especially describing the differences in mtDNA dynamics in oogenesis, spermatogenesis and early embryo development. The physiological function of mtDNA is complemented by its pathologies and their effect on fertility and the ability of the embryo to implant successfully. Furthermore, mtDNA is discussed as a possible diagnostic marker in the evaluation of the quality of sperm, eggs and embryos. These findings of these studies are especially significant for assisted reproduction, where the goal is to select the highest quality embryo with the greatest implantation potential. The work also briefly mentions the presence of cell free mtDNA in the mother's blood and its connection with the development of preeclampsia. Key words: mtDNA, mitochondria, reproduction, (in)fertility
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Effect of biological treatment and body constitution on in vitro osteoclastogenesis from peripheral precursors in axial spondylarthritisis
Beránková, Martina ; Daňková, Pavlína (advisor) ; Rossmeislová, Lenka (referee)
Introduction: Biological therapy is becoming a common approach to stop disease progression and suppress symptoms of axial spondyloarthritis, an inflammatory rheumatic disease characterized by bone loss due to dysregulation of bone turnover and increased osteoclast differentiation. Obesity likely affects bone metabolism through multiple mechanisms. It can promote adipocyte differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Additionally, obesity is closely associated with chronic inflammation, which can enhance osteoclast activity and bone resorption. This master's thesis aims to examine the potential influence of excessive adiposity on the osteoclastogenesis process among patients receiving biological therapy for axial spondyloarthritis. Materials and methods: Monocytes isolated from the peripheral blood of patients with axial spondyloarthritis undergoing biological therapy and healthy donors were stimulated in vitro with pooled sera from patients receiving biological treatment, patients with different type of treatment, and healthy controls for a duration of 7-14 days. Osteoclasts were evaluated as multinucleated, TRAP-positive cells, and their numbers were subjected to statistical analysis. Markers of bone metabolism and inflammation were assessed...
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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
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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.
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Interaction between nurses and family members and their view of patients admitted to the anaesthesia-resuscitation department
DAŇKOVÁ, Pavlína
The present Master's thesis examines the topic of anaesthesia-resuscitation ward visits, interactions, and communication, seen from the perspective and views of nurses and family members of the patients. The primary objective was to examine the interaction between nurses and family members of patients admitted to the anaesthesia-resuscitation wards; the second objective was to investigate the nurses' and family members' perceptions of these patients. The author has achieved the goals mentioned above through qualitative research using two methods: semi-structured interviews with family members of patients and questionnaires involving nurses working in the anaesthesiology-resuscitation wards. The research has established the following: nurses keep an open, positive attitude towards supporting the patient's family; nurses' cooperation with the family members does not depend on their shift difficulty; however, the demandingness of the shift can be influenced by the amount of time the nurse spends with the patient's family; and the nurse's view of the patient is not subject to their education or length of work experience. It is hard for families to see their relatives admitted to the anaesthetic and resuscitation ward; such experiences are associated with very negative feelings; moreover, the family members expect the nurse to behave and act in a role-defined manner. Families usually want to be involved in their loved one's care and appreciate when the nurse is helpful, proactive, supportive and does not shun them; on the other hand, the unfamiliar and strange environment of the ward, and their loved one fighting for life, impacts negatively on families. The present thesis has resulted in drafting an information leaflet that nurses can use for the education of anaesthesia-resuscitation ward visits, containing basic information about the ward, general instructions and a description of the patient, accompanied by illustrations.
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Functional crosstalk between human adipose tissue and lymphatic system
Varaliová, Zuzana ; Rossmeislová, Lenka (advisor) ; Daňková, Pavlína (referee) ; Horáková, Olga (referee)
Both adipose tissue (AT) and lymphatic system (LS) are organs with a great influence on whole-body homeostasis and metabolism. Although the first evidence of a link between the AT and LS was provided already in the 19th century when immune clusters called "milk spots" were found in the omental AT, their functional crosstalk remained unexplored and therefore unappreciated for a long time. However, research in recent years has begun to clearly demonstrate the relationship between the two organs, thanks to the development of new tools for studying and visualizing the LS. Nevertheless, many questions about this crosstalk remain unanswered. This doctoral thesis therefore aimed to answer some of them: How do AT and adipocytes change in response to LS dysfunction ranging from worsened lymphatic drainage to chronic lymphedema? What is the trigger of massive AT expansion in lymphedema? Do adipocytes support lymphangiogenesis, and how? Do lymphatic endothelial cells (LECs) affect the metabolic activities of adipocytes? Although our experiments to answer these questions are ongoing, this work demonstrates several new facts. We showed that the lack of effective lymphatic drainage affects lipolytic reactivity in femoral AT and leads to significant differences in the distribution of AT metabolites between the...
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