|
|
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
|
|
| |
|
|
Immunogenic cell death in tumor specimens in the clinics
Fejfarová, Adéla ; Drbal, Karel (advisor) ; Büchler, Tomáš (referee)
Tumor development and growth are under the control of the immune system in the human body. Danger-associated molecular pattern (DAMP) molecules trigger the anti-tumor response by binding to pattern recognition receptor (PRR) on myeloid cells which in turn activate an adaptive immune system. DAMP molecules are released from cancer cells during a process of immunogenic cell death (ICD) which is a form of regulated cell death (RCD). ICD is induced by a variety of treatments in experimental settings as well as by therapeutic modalities commonly used in medicine. A typical DAMP marker of ICD is calreticulin which is translocated from the endoplasmatic reticulum to the plasma membrane attached to the CD91 receptor. Another marker is the nuclear protein HMGB1 which is released into the tumor environment at the later stage of ICD. This bachelor thesis describes a variety of detection methods and the results of DAMP externalization after ICD induction in vitro in cancer cell lines and in tumor specimens from cancer patiens. Moreover, the link between DAMP molecules and cancer patient survival is discussed. Last, it also summarizes the current status of clinical trials concerning ICD. Keywords tumor, antitumor immunity, cell death, adjuvans, DAMP, chemotherapeutics, immunogenic cell death, clinical trials
|
|
|
Study of Cellular Toxicity of Representative Nanoparticles in Tissue Cultures.
Filipová, Marcela ; Holada, Karel (advisor) ; Benson, Veronika (referee) ; Hubálek Kalbáčová, Marie (referee)
Safety concerns arising from cytotoxic behavior of nanoparticles (NPs) in complex biological environment remain the main problem limiting NPs application in biomedicine. In this study, we have investigated cytotoxicity of NPs with different composition, shape and size, namely SiO2 NPs (SiNPs, 7-14 nm), superparamagnetic iron oxide NPs (SPIONs, 8 nm) and carboxylated multiwalled carbon nanotubes (CNTCOOHs, diameter: 60-100 nm, length: 1-2 μm). Cytotoxicity was evaluated with newly designed screening assay capable to simultaneously assess activity of cell dehydrogenases, activity of lactate dehydrogenase (LDH) released from cells into environment and number of intact cell nuclei and apoptotic bodies in human umbilical vein endothelial cell (HUVEC) culture growing in the very same well of the 96-well plate. Aforementioned attributes were subsequently utilized to obtain information about cell viability and necrotic and apoptotic aspects of cell death. Results from this "three-in-one" cell death screening (CDS) assay showed that SiNPs and CNTCOOHs evoked pronounced cytotoxic effect demonstrated as decrease of cell viability and development of apoptotic bodies formation. In contrast to this, SPIONs induced only mild cytotoxicity. Moreover, SiNPs impaired cell membrane leading to increased LDH release...
|
|
|
Structural changes in model of hypoxic-ischemic encephalopathy in rat
Slotta, Michal ; Otáhal, Jakub (advisor) ; Riljak, Vladimír (referee)
Title: Structural changes in model of hypoxic-ischemic encephalopathy in rat Objectives: The aim of the research is to develop a model of hypoxic-ischemic encephalopathy in a rat that would represent perinatal injury in a human and then histologically differentiate the most commonly damaged cerebral structures. Methods: This is an experimental study. Five laboratory rats underwent hypoxic-ischemic conditions causing encephalopathy according to the Rice-Vannucci model. The control group representing the other five rats underwent hypoxia for 1.5 hours. Subsequently, the animals were returned to their mother. 48 hours later, cerebral perfusion, paraffinisation, slicing the brain into sections and followed by applying these sections onto slides. Sections to represent morphological changes and degeneration of neurons were stained with Hematoxylin-Eosin, Fluoro Jade B and immunohistochemically. The sections were then observed and evaluated under a light microscope. Results: Following the onset of hypoxic-ischemic encephalopathy in 7-day-old rat pups, damage to the investigated structures was observed in two animals. Other animals in the experimental group exhibited only minor morphological changes in neurons observable in H&E staining. Brains of the control group were intact. Keywords: necrosis,...
|
|
|
Caspase-8 - a multifunctional protease at the intersection of apoptosis and necrosis
Davídková, Daniela ; Anděra, Ladislav (advisor) ; Doubravská, Lenka (referee)
Caspase-8 is classified as an initiator caspase especially of death receptors-induced apoptosis. It is expressed in all tissues and depending on its regulatory circuits it plays an important role not only in the signalization of apoptosis but also in necroptosis, cell survival and other cellular processes. Its proper function is irreplaceable in general proliferation, differentiation and development, in the function of immune responses and thus maintenance of homeostasis. Its malfunction or absence is manifested by defects in both cells and organisms and it is connected with serious diseases such as cancer. This thesis summarizes the knowledge of ways of regulation and function of caspase-8 in these processes. Key words: caspases, apoptosis, necrosis, necroptosis, DISC, activation complex
|
|
|
Vliv vybraných druhů probiotik na životnost monocytů prasete a člověka
Vejrychová, Šárka
Many studies describe the beneficial effect of probiotic bacteria of the gastrointestinal tract and their immunomodulatory effects. The aim of this diploma thesis was to evaluate the effect of probiotics, which are commonly used in human and animal nutrition, on the viability of the cells of the immune system. For the experiment were selected blood monocytes, which were isolated from porcine and human blood by dextran sedimentation. Monocyte population was co-cultivated in vitro with probiotic strains Bifidobacterium bifidum, Lactobacillus rhamnosus and Enterococcus faecium for 2 and 4 hours. The percentage of apoptosis and necrosis of monocytes was analysed by flow cytometry. The results showed statistically significant differences in the proportion of apoptotic and necrotic of porcine and human monocytes. It is obvious that the selected strains of probiotics have immunomodulatory effect on immune cells. Enterococcus faecium and Lactobacillus rhamnosus induce cell death of porcine and human monocytes during short-term cultivation in vitro.
|
|
|
Programovaná buněčná smrt makrofágů v mléčné žláze u skotu
Skřipská, Iva
This bachelor is thesis provides a general overview of the anatomy and physiology of bovine mammary gland and its defence mechanisms with the focus on macrophages, their characteristic features, activation and functions. The second part describes apoptosis of macrophages at the end of their life cycle, their transformation from monocytes and their influence on the surrounding mammary gland tissue. The thesis also summarises methods of detection of apoptotic macrophages and depicts the advantages and disadvantages of each method.
|
|
|
Knowledge of nurses about posibilities of using moist wound healing in neonatology.
Konečná, Veronika ; Kulhavá, Miluše (advisor) ; Novák, Ivan (referee)
This thesis deals with nursing care of skin defects using a wet therapy in neonatology. The first section summarizes information related to preterm infants, the development of the individual layers of the skin in the embryonic period. It lists the types of skin defects which the neonatolgy nurse may frequently encounter at the department with including a list of modern therapeutic coverage that can be used. It lists a brief history of wound healing too, focusing just on the development of the wet therapy . Furthermore is marginally discussed the evaluation and documentation of damage to the skin wound. For interest, the thesis mentions a case reportof the preterm newborn with the necrosis of the lower limb, accompanied by commentaries of the alternative treatment for this type of skin damage from my own experience. The second part is assessing the awareness of the nurses in the modern methods of the healing. The priority is the mapping of the experience in using the wet therapy through the quantitative research, which is mediated by an anonymous questionnaire. The main goal of the research is to determine the awareness of the nurses from the neonatology intensive care unit, resuscitation and intermediate care in the nursing of the skin defects using a wet therapy. For this purpose the chosen method...
|
|
|
Phytopathogenic fungi causing necrosis of Acer pseudoplatanus bark
Kelnarová, Ivana ; Koukol, Ondřej (advisor) ; Černý, Karel (referee)
Bark necrosis is a symptom of variously serious diseases caused by various pathogens. Sycamore is relatively susceptible to bark necrosis, especially trees weakened by stress such as climatic extremes or anthropogenic pollution. Causal agents are Ascomycetes and also Peronosporomycetes of the genus Phytophthora. Degree of pathogenicity is variable, ranging from local necrosis to cankers invading cambium resulting in death of the host. Pathogens can be classified as opportunistic (Cryptostroma corticale), weak (Prosthecium pyriforme) or obligate (Eutypella parasitica). Saprophytes decomposing dead tissue can also be isolated from necroses. To prove non-pathogenicity of these species inoculation experiments on the host are needed. Mycophagous fungi may grow in necroses as hyperparasites (Acremonium sp.). Various species of invertebrates search for necroses as a source of food and shelter. Several small mammals were observed feeding on bark necroses. Their role in spreading spores and initiating a gateway for infection is also considered.
|
guest ::
