National Repository of Grey Literature 22 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
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...
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...
Cell response to genotoxic stress-based anti-cancer therapies
Imrichová, Terezie ; Hodný, Zdeněk (advisor) ; Rossmeislová, Lenka (referee) ; Rotrekl, Vladimír (referee)
The dissertation deals with a cell response to genotoxic stress, specifically to anti-cancer treatments with a genotoxic mechanism of action. In principle, cells can respond to these perturbing stimuli in several ways: in case of severe DNA damage, they usually undergo apoptosis or enter senescence. In case of minor DNA damage, or upon defective checkpoint mechanisms, they may continue the cell cycle, either with successfully repaired DNA or with mutations of various kind. Thanks to selection pressure, the mutations that provide cells with a certain growth advantage under conditions of continuing genotoxic stress, gradually accumulate and render the tumor treatment-resistant. In my thesis, I focus on several aspects of this whole process. First, I participated in a characterization of a radioresistant and anoikis-resistant population of prostate cancer cells. This population was generated by irradiating cells 35 times by 2 Gy, a regime used in clinics. After this treatment, a population of low-adherent cells emerged that demonstrated increased expression of EMT- and stem cell markers. The low-adherent state of these cells was maintained by Snail signaling and their anoikis resistance by ERK1/2 signaling. Interestingly, after a protracted period of time, these cells were able to re-adhere and...
Impact of weight loss in obese subjects on the sensitivity of adipose tissue cells in relation to stress of endoplasmatic reticulum.
Karlická, Michaela ; Rossmeislová, Lenka (advisor) ; Koc, Michal (referee)
Adipocytokines released by the adipose tissue play an important role in the regulation of immune and inflammatory responses. In case of obesity their production is badly regulated, which is one of the major factors contributing to the onset of a chronic low-grade overall inflammatory response. This response represents a risk factor for the progression of other diseases, such as atherosclerosis or type-2 diabetes. The main goal of this thesis consisted in comparing the secretion of selected adipocytokines (adiponectin, IL6 and MCP1), isolated from the adipose tissue prior to and after a dietary intervention, and this under basal conditions and during stimulated lipolysis. Based on the same profile, the secretion of the isoforms of adiponectin was compared subsequently. The concentration of adiponectin, IL6 and MCP1 was determined by the ELISA method, the Western Blot method was used to determine the distribution of the adiponectin isoforms. The thesis also concentrates on the gene expression of ATF3, ATF4 and HSPA5, factors engaged in the ER stress in the course of the differentiation of adipocytes. The changes in the gene expression were measured by the quantitative Real Time PCR method. To prove the correct process of the differentiation the genes aP2 and PPARg were used. Within the framework of...
Promyelocytic leukemia protein function in normal, tumor and senescent human cells
Rossmeislová, Lenka ; Hozák, Pavel (advisor) ; Forstová, Jitka (referee) ; Anděra, Ladislav (referee)
Promyelocytic leukemia protein (PML) gene encodes a nuclear protein localizing into the nucleoplasm and distinct nuclear bodies, referred to as PML nuclear bodies (PML NBs). PML is now considered as a gene with tumor-suppressive properties since it is implicated in many nuclear functions affecting cellular proliferation, apoptosis and senescence. The presented work is a part of a larger project that aims to clarify the regulation of promyelocytic leukemia protein expression and investigates the role of PML protein in cellular senescence. The specific goals of my PhD project were to evaluate new in vitro models for the study of PML, to elucidate the effects of histone deacetylase inhibitors on PML gene expression, and to investigate the association of PML with the nucleolus.
Importance of adipose tissue metabolism for whole-body energy balance
Zouhar, Petr ; Flachs, Pavel (advisor) ; Rossmeislová, Lenka (referee) ; Kazdová, Ludmila (referee)
Adipose tissue plays a crucial role in nutrient and energy homeostasis. At the time of worldwide pandemy of obesity and consequent metabolic syndrome, a great effort is made to find new treatments with potential to preserve insulin sensitivity, or even counteract development of obesity and type 2 diabetes. There are three principal possibilities how the adipose tissue biology can contribute to this goal: 1) induction of UCP1-dependent energy dissipation in brown adipose tissue; 2) conversion of white adipose depots to brown-like tissue (i.e. "browning"); and 3) stimulation of UCP1-independent thermogenesis in white adipose tissue. This thesis is based on two published works and one article under preparation. Generaly, it is focused on three different approaches targeting the above mentioned processes in adipose tissue of laboratory mouse: 1) diet supplementation with bile acids; 2) combination treatment of ω-3 polyunsaturated fatty acids and calorie restriction; and 3) cold exposure. In the experiments with administration of bile (specifically chenodeoxycholic) acid to mice, we confirm specific induction of UCP1 in both brown and subcutaneous white adipose tissue, as well as reversion of obesity in the response to the treatment. Nevertheless, most of the acute beneficial effects are mediated by...
Role of the FTO gene in the genetic determination of common multifactorial diseases
Dlouhá, Dana ; Hubáček, Jaroslav (advisor) ; Černá, Marie (referee) ; Rossmeislová, Lenka (referee)
Obesity is a risk factor for development of cardiovascular disease, diabetes type 2 and some cancers. Newly detected genetic risk factor for body weight is the FTO gene ("fat mass and obesity associated"). The aim of this thesis was determine 1) whether the presence of risk alleles correlate with BMI in Czech population and to determine 2) whether there is an association between variants in the FTO gene and risk of myocardial infarction/ acute coronary syndrome (MI/ ACS), 3) renal failure (ESRD), or 4) incidence of colorectal cancer (CRC). We analyzed polymorphisms rs17817449 (first intron) and rs17818902 (3rd intron) using by PCR-RFLP and then also RT PCR. We found an association of the first intron variant (but not the 3rd one) and BMI in Czech control population. We have detected an association of 1st intron SNP and BMI changes during the intervention study in obese children, but not in obese females. We found a correlation between the risk allele and increased risk of ACS (OR 1.49) in patients with MI. In patients with ESRD was detected association between the risk allele and the risk of disease (OR 1.37). We didn't confirmed the association between rs17817449 and the development of CRC. Representative selected groups of the Czech populations "MONICA" and "HAPPIE" were used as controls. One...
Interaction between adipocytes and immune cells in pathogenesis of obesity related pro-inflammatory state of adipose tissue
Mališová, Lucia ; Rossmeislová, Lenka (advisor) ; Flachs, Pavel (referee) ; Kazdová, Ludmila (referee)
Obesity is considered to be a worldwide epidemic disease characterized by an accumulation of AT. Increased adiposity can perturb normal metabolic functions and lead to the development of diseases like insulin resistance and other metabolic disorders. A large amount of clinical studies have been shown that changes in inflammatory signaling in adipose tissue cells, increased infiltration of immune cells into AT as well as stress of endoplasmic reticulum belong to the key molecular steps leading to the development of metabolic disturbances associated with this disease. Adverse metabolic effects of AT accumulation can be diminished by calorie restriction resulting in weight loss. In addition, stress of endoplasmic reticulum could be alleviated by chemical chaperones including bile acids. These two approaches for the treatment of obesity or the obesity-associated disturbances were basis for this PhD thesis. In the first part of this work, we studied inflammation status of gluteal in comparison with abdominal AT and differentiation and secretory capacity of adipocytes after weight loss in obese patients. We revealed that inflammatory profile of gluteal AT, estimated by mRNA level of macrophages and cytokines as markers of inflammatory status of the body, did not explain the different clinical impact of...
Role of immune and adipose cells in the development of adipose tissue inflammation induced by stress associated with obesity
Kračmerová, Jana ; Rossmeislová, Lenka (advisor) ; Cahová, Monika (referee) ; Daňková, Pavlína (referee)
1 SUMMARY Obesity and overfeeding are associated not only with increased circulating levels of nutrients and metabolites, but also with increased risk of the development of additional disorders, such as cardiovascular diseases, cancer or insulin resistance. Plausible link between obesity and its comorbidities is inflammatory state, observed on the whole body level as well as in AT. As possible initiators of this inflammation, hypertrophied adipocytes were suggested. Adipocytes per se secrete a spectrum of heterogeneous molecules including cytokines. Under the stress conditions, adipocytes and subsequently AT resident immune cells switch to pro-inflammatory state and via secretory signaling attract additional immune cells. Furthermore, hypertrophic adipocytes release higher levels of metabolites that may also contribute to pro- inflammatory polarization of immune cells, mainly macrophages. General aim of this thesis was to investigate connection between impaired levels of nutrients and pro-inflammatory statue and activation of immune cells in healthy (obese and lean) subjects. In the Part one of this thesis, we analyzed acute reaction of immune cells in circulation and AT on artificially elevated levels of nutrients, imitating its increased values typical for metabolic syndrome. HFM ingestion led to...
Regulation of lipogenesis in human adipose tissue: Effect of metabolic stress, dietary intervention and aging.
Šrámková, Veronika ; Rossmeislová, Lenka (advisor) ; Cahová, Monika (referee) ; Kuda, Ondřej (referee) ; Tanti, Jean-Francois (referee)
Adipose tissue (AT) is a complex organ specialised in safe storage and release of energy as lipids. The adipose organ is therefore essential for the maintenance of energy homeostasis. The prototypical cells of AT are adipocytes, emerging from the precursors in a process called adipogenesis. Adipogenesis itself is tightly connected with lipogenesis, i.e. with the synthesis of fatty acids and triglycerides. Various stimuli can disturb adipocyte differentiation and lipogenesis and thus contribute to AT dysfunction and development of associated metabolic diseases. This thesis was endoplasmicfocused on the investigation of lipogenesis in the context of reticulum stress (ERS), calorie restriction and aging. In Project A, we showed that exposition of adipocytes to high acute ERS inhibits expression of lipogenic genes and glucose incorporation into lipids. Moreover, chronic exposure of preadipocytes to ERS impaired both, lipogenesis and adipogenesis. On the other hand, chronic low ERS had no apparent effect on lipogenesis in adipocytes. These effects of ERS could therefore contribute to the worsening of AT function seen in obesity. The capacity of AT to store lipids decreases in aging, possibly due to the accumulation of senescence cells or higher ERS. In Project B, we investigated lipogenic capacity of...

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