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Host-microbiota, pro-inflammatory immunity and physiological senescence in wild birds
Těšický, Martin
Triggered by microbial ligands, inflammation serves as a "double-edged sword" to fight infections on the one hand, but on the other hand causing tissue damage due to oxidative stress if it is dysregulated. For example, chronic inflammation can contribute to inflammaging, which is now widely regarded as one of the causes of ageing. In my interdisciplinary dissertation, my colleagues and I investigated three interrelated aspects of inflammation, using an evolutionary framework and various free-living birds as models: (1) ecological and evolutionary determinants of gut microbiota (GM) composition and diversity, a driver of wild bird immunity, (2) diversity in immune genes affecting inflammatory responses in wild birds and (3) inflammation-related physiological senescence in a free-living passerine bird, the great tit (Parus major). Firstly, using 16S rRNA gene metabarcoding, we revealed high intra- and interspecific variation in passerine gut microbiota (GM) dominated by the major phyla Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Although in mammals GM depends strongly on host phylogeny and diet, in birds we found only moderate effects of phylogeny and very limited effects of host geography and ecology on GM composition. While microbiota diverged between the upper and lower...
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Analýza nejčastějších onemocnění u dojnic českého strakatého skotu ve vybraném chovu
Müller, Tomáš
This bachelor thesis deals with the most common diseases in dairy cows of Fleckvieh cattle on selected farm. Literary part informs about the basic properties of the disease, symptoms, etiology but also about the possibilities of diagnosis and therapy. The described diseases were selected on the basis of an annual analysis of a specific farm, for the purposes of which the medical documentation of dairy cows was inspected. The analysis included 4 categories of diseases and 3 of them were evaluated throughout the year 2021. Inflammation of the mammary gland was evaluated during individual months. The annual analysis shows that inflammation of the mammary gland was the most frequently recorded disease. Other commonly observed illnesses were inflammation of the hoofs, uterus and decreased rumen activity.
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Host-microbiota, pro-inflammatory immunity and physiological senescence in wild birds
Těšický, Martin ; Vinkler, Michal (advisor) ; Tschirren, Barbara (referee) ; Štěpánek, Ondřej (referee)
Triggered by microbial ligands, inflammation serves as a "double-edged sword" to fight infections on the one hand, but on the other hand causing tissue damage due to oxidative stress if it is dysregulated. For example, chronic inflammation can contribute to inflammaging, which is now widely regarded as one of the causes of ageing. In my interdisciplinary dissertation, my colleagues and I investigated three interrelated aspects of inflammation, using an evolutionary framework and various free-living birds as models: (1) ecological and evolutionary determinants of gut microbiota (GM) composition and diversity, a driver of wild bird immunity, (2) diversity in immune genes affecting inflammatory responses in wild birds and (3) inflammation-related physiological senescence in a free-living passerine bird, the great tit (Parus major). Firstly, using 16S rRNA gene metabarcoding, we revealed high intra- and interspecific variation in passerine gut microbiota (GM) dominated by the major phyla Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Although in mammals GM depends strongly on host phylogeny and diet, in birds we found only moderate effects of phylogeny and very limited effects of host geography and ecology on GM composition. While microbiota diverged between the upper and lower...
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Identification of new regulators of proinflammatory signaling pathways
Dráberová, Helena ; Štěpánek, Ondřej (advisor) ; Krulová, Magdaléna (referee) ; Funda, David (referee)
Identification of new regulators of proinflammatory signaling pathways Helena Dráberová Protein 4.1R has been described in immune system as regulator of migration and cell adhesion, but was also shown to play a role in activation of T lymphocytes. Polymorphism in gene ORMDL-3 is associated with asthma risk in children and correlates with increased ORMDL-3 expression. This disertation thesis describes the function of proteins 4.1R and ORMDL-3 in activation of mast cells after stimulation of FcεRI receptor. IL-17 is a proinflammatory cytokine that plays a role in immune response against fungal and yeast infections. IL-17 however also plays a role in the pathology of autoimmune diseases such as reumatoid arthritis, psoriasis and multiple sclerosis. IL-17 signaling is tightly regulated, however the exact mechanism has not been described. This disertation thesis describes the IL-17R complex by mass spectrometry and analyze the function of its known and newly discovered components in cells deficient in individual proteins by method CRISPR-Cas9. Last part focuses on the discovery of new subunit of IL-17RC protein CMTM4, which role in IL-17 signaling has not been described so far. CMTM4 stabilizes IL-17RC and is required for its surface expression. In vitro data are supported by data from autoimmune model of...
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Ultrafine particles and their possible role in etiology and development of neurodegenerative diseases
Topinka, Jan ; Závodná, Táňa ; Rössnerová, Andrea ; Rössner ml., Pavel
Air pollutants have been shown to cause a vast amount of different adverse health effects. These effects include impairment of many respiratory (e.g. asthma, chronic obstructive pulmonary disease) and cardiovascular (ischemic heart disease, infarction, stroke) diseases. However, in recent years, the evidence showing effects beyond the lungs and circulatory system are becoming more evident. Neurological diseases, namely Alzheimer's disease (AD) has shown to be associated with living near traffic. However, reason for this has remained unresolved until today. Our new H2020 project TUBE aims on revealing the mechanisms of action of ultrafine particles involved in neurological diseases. The TUBE consortium includes experts in areas of aerosol technology, emission research, engine and fuel research, human clinical studies, epidemiology, emission inventories, inhalation toxicology, neurotoxicology and disease mechanism studies. This enables research of resolving the effects of nanoparticles from different traffic modes for both air quality and concomitant toxic effect of these air pollutants. We will investigate adverse effects of air pollutants using cell cultures, animal exposures and volunteered human exposures as well as the material from epidemiological cohort study. These are going to be compared according to inflammatory, cytotoxic and genotoxic changes and furthermore beyond the current state of the art to neurotoxic and brain health effects. With this approach, we are aiming to a comprehensive understanding of the adverse brain effects of nanoparticles from traffic.
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Pathology of adnex
BARANCOVÁ, Iveta
The term adnex comes from the latin word nexus or connection and i tis used in gynecology and dermatology. Gynecological adnexa involves the internal genitals of woman without uterus, so it involves the fallopian tubes and ovaries. In every woman´s life, there can be conditions when the woman feels abdominal pain. These abdominal pain can´t be serious, however if the pain persists, it needs to be examinated their origin. During diagnostics, it is also important to keep in mind that the woman is prone to various diseases associated with gynecological adnexa. This bachleor thesis deals with pathological conditions od gynecological adnexa, therefore inflammation of the fallopian tubes and ovaries, ovarian cysts, adnexal endometriosis and benign but also malignant neoplasms located in the fallopian tubes and ovaries. Because every woman is at risk of an ectopic pregnancy when she is of childbearin age, this type of pregnancy is considered as pathological, so it is included in this bachleor thesis as well. Forty samples of gynecological adnexa are processed for this thesis. A selected part of the adnex sample is documented in this thesis. Samples are processed in all sections of the histological laboratory. After that histological preparations are made and the diagnosis is made too. Histological preparations are stained with basic histological staining Hematoxylin-eosin, but also with special methods Hematoxylin-van Gieson and Goldner´s trichrome. The thesis also contains a statistical evaluation of the incidence of gynecological adnexa for the period from 2015-2019, which were diagnosed at the pathological department. Female sterilization is included in this evaluation too, because its number has increased over the period. The sterilization included in the evaluation was always performed with the patient´s consent and at her own reques, for example it is performed during the planned caesarean section.
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Anti-inflammatory and immunomodulatory activities of Ixodes ricinus salivary proteins
CHLASTÁKOVÁ, Adéla
Ticks are highly specialized obligate ectoparasites whose life cycle is fully dependent on obtaining a blood meal from a host. To prevent blood clotting and counteract the host's immune and wound healing responses, ticks secrete saliva, containing hundreds to thousands of proteins and non-proteins, into the feeding cavity. This thesis focuses on deciphering the function of three serpins (inhibitors of serine proteases) expressed in the salivary glands of the European tick Ixodes ricinus. Iripin-1, Iripin-3, and Iripin-8 were produced in the Escherichia coli expression system, and their effects on the immune response were evaluated using various in vitro assays and a mouse model of acute inflammation. Furthermore, the thesis involves one review article that summarizes the role of serpins in tick physiology and tick-host interaction.
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Polymeric particles for targeted drug delivery into mononuclear phagocytic system
Prošková, Denisa ; Holas, Ondřej (advisor) ; Šnejdrová, Eva (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Consultant: Dmytro Iefremenko, M.Sc. Student: Denisa Prošková Title of Thesis: Polymeric paticles for targeted drug delivery into mononuclear fagocytic system Polymeric nanoparticles (NPs) can act as drug nanocarriers. They are frequently used to enhance distribution to a target tissues in which they specifically act. The mononuclear phagocytic system (MPS) represents a target to which NPs could be specifically distributed. It has been found that cells of this system are involved in the development of a number of diseases. Optimal parameters of NPs suitable for MPS targeting are size ranging between 100 nm and 300 nm and negative surface charge. In this work the polymeric nanoparticles with encapsulated cholic acid were prepared by nanoprecipitation method using five selected types of non-ionic surfactants in concentration of 0,1%, 0,5%, 1% and 2%. PLGA was the polymer used for their preparation because of its high biocompatibility and biodegradability. Encapsulation efficiency, size and zeta-potential were selected as critical parameters chosen for prepared nanoparticles. The obtained data were used to characterize the effect of non-ionic surfactants on the...
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Polymeric particles for targeted and enhanced bioavailability
Kozáčková, Daniela ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
7 ABSTRACT Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, Ph.D. Consultant: Mgr. Barbora Boltnarová Student: Daniela Kozáčková Title of thesis: Polymeric particles for targeted and enhanced bioavailability Nanoparticles prepared from biodegradable and biocompatible polymers are useful for targeted therapy of inflammatory diseases and increase the bioavailability of poorly water-soluble anti-inflammatory drugs. Targeted distribution is mainly mediated by the physico-chemical properties of nanoparticles. This can reduce unwanted side effects of encapsulated drug. The ideal properties of nanoparticles for passive targeting to cells of the mononuclear phagocytic system (MPS) are size in the range of 100 nm to 300 nm, hydrophobic character and negative surface charge. Matrix-type polymeric nanoparticles were prepared. Prepared nanoparticles were evaluated for size, polydispersity index, zetapotential and encapsulation efficiency of the drug. Three anti-inflammatory substances with different water solubility - a dexamethasone, a dexamethasone acetate and a curcumin were encapsulated. The matrix of nanoparticles was made of PLGA copolymer, three types of PLGA with different lactide:glycolide ratio were used. Nanoparticles...
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Carotuximab effects on inflammation during liver fibrosis development
Sharif, Navid ; Rathouská, Jana (advisor) ; Němečková, Ivana (referee)
Chronic liver inflammation is a process that results in the distortion of the liver parenchyma. Constant damage caused by inflammation would lead to formation of fibrotic tissue which can impair the normal liver physiology. Liver fibrosis is one of the common causes of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) is a pathological state that is characterised by excessive accumulation of lipid in the hepatocytes (hepatic steatosis) which can trigger the inflammatory response in the liver. Carotuximab (TRC 105) is a monoclonal antibody that has been used for the treatment of a number of cancers, including hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of carotuximab in liver inflammation in a mouse model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis. Eighteen 3-month-old C57BL/6 male mice were recruited in this study. They were divided into three groups: control group (n=6) - fed chow diet for the period of 4 weeks, DDC group (n=6) - fed DDC diet for the period of 4 weeks, DDC group treated with carotuximab (DDC+TRC, n=6) - fed DDC diet for the period of 4 weeks and to that TRC 105 (15mg/kg) was administered. The impact of the diet and TRC 105 on mouse weight, as well as the effect on liver damage (levels...
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