National Repository of Grey Literature 21 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
The role of new profibrotic molecules in the pathogenesis of systemic sclerosis.
Šumová, Barbora ; Šenolt, Ladislav (advisor) ; Funda, David (referee) ; Soukup, Tomáš (referee)
Systemic sclerosis (SSc) is immune-mediated fibrotic disease of unknown aetiology. Among the dominant pathogenic manifestations of SSc belong vascular changes, production of autoantibodies, activation of innate and adaptive immune responses and fibrotic processes. Transforming growth factor beta (TGF-β) has been identified as a central profibrotic factor stimulating fibroblasts to produce collagen. There are, however, a number of other mediators involved in the pathogenesis of SSc. Mutual activation and amplification of these molecules and their cascades may be a central mechanism of the SSc pathogenesis. Hedgehog (Hh) canonical signalling pathway plays an important role in the development and progression of fibrotic diseases. Expression of Hh target genes can be regulated through a canonical or non-canonical signalling cascade. The non-canonical activation of GLI transcription factors by TGF-β has not yet been investigated in SSc. The substantial part of this thesis is focused on the study of the mutual interaction of TGF-β and Hh signalling pathway. In vitro analysis confirmed TGF- β/SMAD3 dependent activation of GLI2 in dermal fibroblasts. Fibroblasts specific knockout of GLI2 prevented the development of experimental fibrosis in vivo. Combined targeting of canonical and non-canonical Hh...
Immunopathology aspects and new treatment options for rheumatoid arthritis
Bartoňová, Michaela ; Šenolt, Ladislav (advisor) ; Drbal, Karel (referee)
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, which affects joints. It significantly affects the quality of life and is associated with increased mortality. Although its etiology is not fully known, it is believed that both genetic and environmental risk factors are involved in its outbreak. Knowledge of these risk factors helps us to determine the risk of RA outbreaks in vulnerable populations and provides us with knowledge about possible prevention. Pathogenesis of RA is caused by activated mesenchymal cells and cells of the innate and adaptive immune system, such as endothelial cells, synovial fibroblasts, monocytes, macrophages, dendritic cells, T and B lymphocytes. It is an incurable disease, but there are several medications, which improve disease activity or can even cause remission. Great success has been observed in biological treatment and inhibitors of Janus kinases. In some cases, the response to this relatively new therapy is not sufficient, and new drugs based on other mechanism should be developed. Examples include inhibition of granulocyte and macrophage colony stimulating factor, inhibition of interleukin 6 or interleukin 17 and bispecific antibodies. There is a growing importance of biosimilar drugs, which would make treatment, thanks to a lower price,...
Molecular mechanisms of metabolic syndrome with focus on new hormones produced by adipose tissue, liver and skeletal muscle
Kloučková, Jana ; Haluzík, Martin (advisor) ; Šenolt, Ladislav (referee) ; Bužga, Marek (referee)
1 Abstract The cluster of obesity, insulin resistance and other associated comorbidities represents a significant health risk for the affected individuals as well as the whole population. Chronic low-grade inflammation of adipose tissue is considered one of the main mechanisms respon- sible for the progression from simple obesity to a fully developed metabolic syndrome. The aim of our study was to explore two different approaches that could potentially ameliorate adipose tissue inflammation - therapeutic hypothermia and the adipocytokine clusterin. In the first part, we showed that a period of deep hypothermia associated with the an- oxic phase of cardiac surgery significantly delayed the onset of systemic inflammatory re- sponse induced by surgery. The relative gene expression of the studied genes was not altered during the hypothermic period, but was significantly increased in five out of ten studied genes (IL-6, MCP-1, TNF-α, HIF1-α, GLUT1) and decreased in two genes (IRS1, GPX1) at the end of surgery. We conclude that deep hypothermia delays the onset of local adipose tissue hy- poxia and inflammation. These results could partially explain the positive effects of therapeu- tic deep hypothermia on postoperative morbidity and mortality in cardiac surgery patients. In the second part, we examined plasma...
Study of interleukin 37 and its role in rheumatoid arthritis
Jandová, Romana ; Šenolt, Ladislav (advisor) ; Krulová, Magdaléna (referee)
Dysregulation between pro- and anti-inflammatory cytokines activity in rheumatoid arthritis (RA) contributes to immune dysregulation, chronic inflammation and subsequent joint destruction. Interleukin-37 (IL-37) has been described as an anti-inflammatory cytokine in several autoimmune diseases. The main aim of this work was to determine the levels of IL-37 in serum and synovial fluid (SF) of RA patients and to compare them with the levels in patients with osteoarthritis (OA) and further explore the association of IL-37 with disease activity and other clinical parameters. Subsequent goal was to study its anti-inflammatory function on RA synovial fibroblasts and describe other cells types of synovial tissue contributing to its production. IL-37 levels were detected using enzyme-linked immunosorbent assay (ELISA). Synovial fibroblasts were stimulated by lipopolysaccharide (LPS) and recombinant IL-37 (rIL-37). The levels of studied genes were detected by PCR. Synovial tissues and immune cells were visualized by immunohistochemical and by immunofluorescence staining. We found increased levels of IL-37 in SF of patients with RA in comparison to OA patients. There was a significant correlation between serum and SF levels of IL-37. RA as well as OA patients showed increased levels of IL-37 in serum than in...
The role of biomarkers in erosive osteoarthritis of the hands
Lennerová, Tereza ; Šenolt, Ladislav (advisor) ; Tachezy, Ruth (referee)
Hand osteoarthritis (OA) is a degenerative joint disease that causes pain, functional limitation and negatively affects the patients' quality of life. The most severe subtype of this disease is erosive OA. Erosive hand OA is characterized by an abrupt onset, inflammation and is linked to worse outcomes than non-erosive hand OA. Current methods do not allow early diagnosis or to distinguish between patients with different forms at disease onset. This could be changed by the utilization of biomarkers in clinical practice. Biomarkers are molecules released into circulation that reflect biological processes. The main goal of this study was to analyze the levels of circulating biomarkers with the aim to differentiate patients from healthy subjects and patients with erosive OA from patients with non-erosive disease. Serum concentrations of seven biomarkers and the expression of plasma microRNAs were determined. Patients with hand OA showed altered cartilage metabolism, increased levels of adiponectin, decreased levels of clusterin and a dysregulated expression of several microRNAs in comparison to the healthy population. Patients with erosive OA had lower levels of clusterin and decreased expression of miR-151-3p than those with the non-erosive form of the disease. These findings suggest the potential...

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