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Preparation and evaluation of nanoparticles for targeted treatment of inflammatory diseases
Wurzel, Natalie ; Holas, Ondřej (advisor) ; Smékalová, Monika (referee)
Charles University, Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, PhD Consultant: Mgr. Barbora Boltnarová Student: Natalie Wurzel Title of Thesis: Preparation and evaluation of nanoparticles for targeted treatment of inflammatory diseases Nanoparticles are used in the health sciences for, among other things, targeted drug delivery. This is used for the therapy of cancer and chronic inflammatory diseases. The aim of this diploma thesis was to prepare nanoparticles suitable for targeted treatment of inflammatory diseases. The task was to determine the ideal concentration of the active substance, which would ensure high encapsulation efficiency and drug loading. The difference between nanoparticles prepared from PLGA 5/5E and PLGA 7/3A was also investigated. Nanoparticles were prepared by the nanoprecipitation method. The matrix of the nanoparticles was composed of PLGA with different ratios of lactic acid and glycolic acid. Acetone was used as the organic solvent. The encapsulated active substance was the anti-inflammatory dexamethasone acetate. The aqueous phase was consisted of a 0.1% aqueous solution of Pluronic F-127. The evaluated parameters of the resulting nanoparticles included size, polydispersity index, zeta potential,...
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Precision-cut placental slices as a model to study inflammatory response
Bolboli, Bahareh ; Štaud, František (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bahareh Bolboli Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: Kasin Yadunandam Anandam, Ph.D. Title of the diploma thesis: Precision-cut placental slices as a model to study inflammatory response. Maternal inflammation during pregnancy is a recognized factor linked to an array of complications and potential neurodevelopmental and neuropsychiatric risks for offspring. Placenta isthe crucial interface between maternal and fetal domains. This organ not only shapes fetal development but also possesses the ability to respond to inflammatory stimulations, potentially in a sex-specific manner. Nonetheless, the fundamental immunoregulatory mechanisms orchestrating such responses remain unclear. To bridge this knowledge gap, our study harnessed an innovative approach: the ex vivo precision-cut placental slice model using rat placentas. This experimental design was tailored to probe acute inflammatory responses. Precision-cut placental slices, precisely 200 µm thick, were meticulously generated from both male and female rat placentas. These slices were subjected to varying concentrations of Lipopolysaccharide (LPS) or Polyinosinic: polycytidylic acid (Poly I:C) for discrete periods of 4...
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The effect of methamphetamine on the neuroimmune system
Petrášová, Blanka ; Hejnová, Lucie (advisor) ; Lapka, Marek (referee)
Metamphetamine is worldwide problem and in the Czech republic is 2-3 % of people older than 15 years exposed to it. There are 34,7 thousand long-term users in Czech republic and 19 methamphetamine-related deaths in 2022. The impact on the neuroimmune system has only started to be studied in recent years. Understanding its effect on the neuroimmune system may outline new treatment options, as there is no cure for methamphetamine addiction to date. This paper summarizes its effects on the different components of the neuroimmune system and outlines some substances that could be used in treatment. Key words: methamphetamine, neuroimmune system, inflammation, microglia, astrocytes
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Effects of peripheral inflammation on gene expression modulation in passerines and parrots
Kuttiyarthu Veetil, Nithya ; Vinkler, Michal (advisor) ; Hyršl, Pavel (referee) ; Harazim, Markéta (referee)
(English) Birds have well-defined roles in maintaining the ecological balance as predators, seed dispersers, nutrient cyclers, and pollinators making them an integral part of many ecosystems. Birds are often the flag-ship species and are important for wildlife preservation. Some of the avian populations are very well connected across the globe through their annual migration, increasing risks of epidemics of infections. Birds also face different levels of existence encounters in challenging living conditions like deserts and cold mountains. To cope with these diverse environments not only need physiological adaptations, but also a very well-equipped immune system, optimised to challenges common to the environment they inhabit. How well a host immune system responds to pathogens determines the overall fitness of the organism and its survival. Insight into the avian immune system functions is of great significance as birds are reservoirs of innumerable pathogens. They have been the primary source of several major epidemics' onset leading to worldwide human and animal fatalities (e.g., COVID-19, Avian influenza, or West Nile virus outbreaks). Similar to all living beings, avian hosts and pathogens are always in a continuous adaptational arms race. This coevolution of hosts and their pathogens forms the...
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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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Dietary habits of patients in the schizophrenic spectrum
Krůčková, Dominika ; Kalinová, Nelly (advisor) ; Pehr, Martin (referee)
The thesis deals with the dietary habits of schizophrenic patients and the effect of anti- inflammatory food on the levels of inflammatory markers in the blood. Patients suffering from schizophrenia are observed to have poorer eating habits compared to healthy controls. These patients are more likely to consume saturated and trans unsaturated fatty acids and less likely to include fruit and vegetables, unsaturated fatty acids or fibre in their diet. At the same time these patients have a higher consumption of foods involved in promoting chronic inflammation and thus possibly worsening the symptoms of the disease. The aim of this study is to evaluate the dietary habits of schizophrenic patients using a semi-quantitative frequency questionnaire and to compare them with a control group without a psychiatric diagnosis. Furthermore, based on the findings from the DII to select foods from the questionnaire that contain components of or are themselves included in the anti-inflammatory food index and to determine whether the frequency of consumption of these foods correlates with blood levels of inflammatory markers. According to the results of this work the diet of schizophrenic patients can be considered less healthy compared to the control group due to lower consumption of fresh fruits and vegetables,...
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Evaluation of gene expression of selected ABC and SLC transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines
Pokorná, Petra ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petra Pokorná Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Dudičová Title of diploma thesis: Evaluation of gene expression of selected ABC and OATP transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines Placenta is the first and the largest fetal organ that gradually develops during pregnancy and plays an essential role in the development of the fetus. It fulfills the entire spectrum of functions, ensures the transport of nutrients to the fetus and the removal of waste substances back into the maternal circulation, protects the fetus from toxins, and at the same time fulfills a certain mechanical and especially immunological barrier between mother and fetus. One of the main functions of the placenta is the transport function which is made possible by membrane transporters present mainly in the syncytiotrophoblast layer of the placenta. Transporters in the human placenta can be divided into two families, SLC and ABC which are further divided into several subfamilies. The expression of transporters changes physiologically during pregnancy, but pathological conditions such as inflammation can also influence the expression....
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Role of the serotonin receptor type 7 (5-HT7) in autoimmune disease
NUßBAUMER, Mia
Serotonin receptor type 7 (5-HT7) displays immunomodulatory functions and is overexpressed in individuals with Crohn's disease. Here, we set out to determine 5-HT7 mode of interaction with its cognate proteins Gs and G12. A unique type of coupling, termed 'inverse coupling' is known to occur between the 5-HT7 receptor and the Gs protein. The aim of our research was to determine whether G12 can also undergo this kind of coupling. We found that the G12 protein has a surprisingly lower mobility than Gs implying a specific interaction with a membrane domain or another membrane-localized protein. For both G proteins, we were unable to detect their inverse coupling with the 5-HT7 receptor at room temperature. Our findings indicate peculiar differences in G protein mobility and emphasize the importance of temperature for studies of interactions between G proteins and G protein-coupled receptors.
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Atherosclerosis risk factors and macrophage polarization in adipose tissue
Králová, Anna ; Poledne, Rudolf (advisor) ; Vrablík, Michal (referee) ; Zicha, Josef (referee)
Atherosclerosis is a major cause of cardiovascular disease, and the pro-inflammatory state stimulates the process of atherogenesis. Since the 1990s, it has become clear that adipose tissue has not only an endocrine function, but it is also a very important immune organ due to the presence of various immunocytes with high cytokine secretion. Local resident macrophages represent a major component in the development of this inflammation. Due to our inclusion in the unique transplantation program at IKEM, which ensured availability of peroperatively harvested adipose tissue and its subsequent and immediate analysis, we were able to characterize the different subpopulations of monocytes/macrophages and classify macrophages into pro- and anti-inflammatory populations based on the differential expression of surface markers. From subcutaneous (SCAT), perivascular (PVAT), and visceral (VAT) adipose tissue samples from healthy living kidney donors (LKD), we analyzed the macrophage phenotype after obtaining the stromal fraction by flow cytometry. At the beginning of the experiments, we chose the calprotectin molecule as a proinflammatory marker. However, in subsequent experiments described herein, we chose a different route and selected the CD16 receptor to determine the proinflammatory phenotype. This...
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