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The effect of opioids on the immune system
Miniariková, Nina ; Novotný, Jiří (advisor) ; Cimermanová, Veronika (referee)
The use of opioids in medicine is necessary as they serve to suppress pain as a part of anesthesia notably during surgical procedures. After that, they help suppress pain during postoperative care and they are also prescribed to patients with chronic pain, for example in the final stages of cancer. However, opioids are among the most abused substances worldwide. The United States of America is facing an opioid epidemic, also called the opioid crisis, which began mainly with the excessive prescription of opioids and their subsequent misuse. It is clear that opioids affect the immune system which has been the subject of many recent studies. Different opioids have variable effects on the immune system. The understanding of their impact on the immune system could mean improvement of health care, and at the same time could present a basis for proposals of new treatment methods for some of the diseases. This bachelor thesis summarizes the available studies dealing with the influence and effects of various opioids on the cells of the immune system in order to better understand their importance and their use in practice. Keywords: opioids, immune system, inhibition, immunomodulation, phagocytes, lymphocytes
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Immunomodulatory properties of microbial components
Pavličová, Anna ; Kverka, Miloslav (advisor) ; Prokešová, Ludmila (referee)
The human body is inhabited by a complex composition of microorganisms. Particularly significant is the intestinal microbiota due to its profound effect on the development and function of the immune system. The ability of the host to defend against pathogens is kept by two important, interrelated components - the mucosal barrier and immune system. The barrier is composed of several layers (gut microbiota, mucus, epithelium, and immune cells) joined into one functional unit. Through its diverse array of structural components and metabolites, the gut microbiota interacts with the epithelium and mucosal immune system, confers to its induction, and modulates immune responses. Disruption of this interplay can contribute to pathogenesis of several diseases.
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Comparison of immunomodulatory properties of mesenchymal stem cells and Sertoli cells
Porubská, Bianka ; Krulová, Magdaléna (advisor) ; Komrsková, Kateřina (referee) ; Filipp, Dominik (referee)
Cell therapies are increasingly considered in preclinical studies and in the future of medicine. The main cell type investigated in this manner is mesenchymal stem cells (MSCs), because of their strong immunomodulatory properties. The efficacy of the therapy depends on various aspects, such as the viability and source of MSCs, the purity of the cell suspension and many more. There is a need for more tailored therapy and the use of cell type better fitting for the specific pathology. Sertoli cells (SCs) are deemed by some authors to be a kind of MSCs, namely because of their similar immunomodulatory properties. Because they reside in the seminiferous tubules in the testes, they are a promising candidate for the treatment of inflammatory pathologies of testicular tissue, such as bacterial infection-induced infertility. In vitro comparison of the ability of MSCs and SCs to differentiate into mesenchymal cell lineages such as osteocyte, chondrocyte, and adipocyte showed success in the case of SCs, providing evidence for their mesenchymal origin. The effect of MSCs or SCs on activated immune cells in vitro showed immunosuppression in both cases with distinct features. MSCs suppressed Th17 cell activation and IL-17 production by CD4+ T cells and SCs down-regulated TNFα and IL-2 production by these cells,...
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Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine
Klusová, Natálie ; Beránek, Martin (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Natálie Klusová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultant: RNDr. Milada Šírová, Ph.D. Title of diploma thesis: Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine The diploma thesis is focused on the anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine (Gem). We investigated the effects of four polymer conjugates (P-Gem1-P-Gem4), which had similar molecular weight and carried approximately the same amount of the drug. The only difference were the used spacers for Gem linkage. We used the following spacers: β-Alanin (P-Gem1); glycyl-phenylalanyl- leucyl-glycyl (P-Gem2); aminocaproic acid (P-Gem3); valeric acid (P-Gem4). Based on the assessed IC50 values for tumor cell lines 4T1, LL2, Panc02, MiaPaca2 and Panc1 the samples were divided into two groups: a) samples with quick rate of Gem release (P- Gem1, P-Gem2); b) samples with slow rate of Gem release (P-Gem3, P-Gem4). The in vivo stability of the conjugate affects systemic toxicity and anti-tumor activity, which was proven by the experiment performed on BALB/c mice bearing murine mammary carcinoma cells (4T1). We enrolled significant...
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Functional characterization of selected Kunitz proteins of Eudiplozoon nipponicum
Tymich, Alexandr ; Mikeš, Libor (advisor) ; Kašný, Martin (referee)
Proteins containing the Kunitz domain are mostly 6-10 kDa inhibitors of serine proteases, but in exceptional cases they can also inhibit cysteine and aspartic proteases. The main characteristic is the presence of six cysteine residues forming three disulfide bridges creating a typical active loop, which is complementary to the active site of various proteases. The specificity of this binding is largely determined by the amino acid in the P1 position. Their functions include the regulation of a number of physiological events based on proteolysis, e.g. the blood coagulation cascade or immune reactions. However, due to their nature, they have also become a powerful tool for parasitic organisms to interact with their host, where they again target proteases involved in the host's physiological events and thus allow the parasite to survive the interaction with the host. Until recently, representatives of the class Monogenea were a neglected group from the point of view of molecular parasite-host interactions, and only a few works were devoted to their biochemistry and the description of biologically active molecules. In this work, I focused on two selected Kunitz proteins in Eudiplozoon nipponicum, a blood-sucking ectoparasite from the Monogenea class, which has become a fairly common parasite of common...
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Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine
Klusová, Natálie ; Beránek, Martin (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Natálie Klusová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultant: RNDr. Milada Šírová, Ph.D. Title of diploma thesis: Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine The diploma thesis is focused on the anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine (Gem). We investigated the effects of four polymer conjugates (P-Gem1-P-Gem4), which had similar molecular weight and carried approximately the same amount of the drug. The only difference were the used spacers for Gem linkage. We used the following spacers: β-Alanin (P-Gem1); glycyl-phenylalanyl- leucyl-glycyl (P-Gem2); aminocaproic acid (P-Gem3); valeric acid (P-Gem4). Based on the assessed IC50 values for tumor cell lines 4T1, LL2, Panc02, MiaPaca2 and Panc1 the samples were divided into two groups: a) samples with quick rate of Gem release (P- Gem1, P-Gem2); b) samples with slow rate of Gem release (P-Gem3, P-Gem4). The in vivo stability of the conjugate affects systemic toxicity and anti-tumor activity, which was proven by the experiment performed on BALB/c mice bearing murine mammary carcinoma cells (4T1). We enrolled significant...
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Immunomodulatory effect of tumor targeted polymer drugs
Mervartová, Ivana ; Šírová, Milada (advisor) ; Palich Fučíková, Jitka (referee)
5 Abstract Myeloid-derived suppressor cells (MDSC) are a very heterogeneous population of immature, activated myeloid progenitors of neutrophils, monocytes/macrophages and dendritic cells that have not differentiated into mature forms. A common feature of these cells is the ability to suppress immune responses of T cells, NK cells, and dendritic cells. It is known that MDSC accumulate under various pathological conditions, such as chronic inflammation or cancer. In breast cancer patients, the highest MDSC counts correlate with the occurrence of metastatic foci in lung tissue. The suppressive effects of MDSCs are associated with resistance to chemotherapy, reduced effectiveness of immunotherapy and overall poor prognosis of the disease. Therefore, many studies focus on MDSC. One possibility is the differentiation of MDSC into mature populations that lose their suppressive phenotype. In this work, we focused on modulation of MDSC activity by all-trans retinoic acid (ATRA), bound to a polymer conjugate based on N-(2-hydroxypropyl)methacrylamide (HPMA). ATRA is used in clinical practice for the treatment of acute promyelocytic leukemia, where the mechanism of action is the differentiation of pathological cells into more mature forms and thus the cessation of their proliferation. The binding of ATRA to the...
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Analysis of trypsin inhibitor-like cysteine-rich domain-containing peptides (TIL-domain inhibitors) from the tick Ixodes ricinus
PECHOVÁ, Hana
The master thesis deals with the analysis of trypsin inhibitor-like cysteine-rich domain-containing peptides (TIL-domain inhibitors) extracted from salivary glands of a tick Ixodes ricinus. It comprises the initial bioinformatical analysis of TIL-domain containing peptide family from I. ricinus, molecular cloning of the representative protein into expression vector, followed by production of recombinant TIL-domain inhibitor in bacteria. A representative TIL-domain gene is proved for their structure, biochemical properties as well as immunomodulatory and anticoagulation features.
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Immunomodulatory potential of Sertoli cell progenitors in Xenopus tadpoles during the healing of amputated tail
Mertová, Irem ; Krylov, Vladimír (advisor) ; Procházka, Jan (referee)
A cell culture of common Sertoli and peritubular myoid cells progenitors derived from the testes of male X. tropicalis, called XtiSC, was established in the Laboratory of Developmental Biology. XtiSCs exhibit similar properties as more well-known mesenchymal stem cells that are used in cell therapy for their immunomodulatory and proregenerative properties. Microinjection of XtiSC into the dorsal vein of the tail of the tadpoles has increased macrophage numbers 7 days after tail amputation (dpa), both in controls and in tadpoles after depletion of macrophages by the application of clodrosomes. Macrophage depletion also reduces the migratory ability of XtiSC to the site of tail amputation. Macrophage depletion also led to a reduction in the number of satellite cells 1 dpa. On the seventh day after tail amputation and XtiSC injection, there was a significant increase in their number compared to the control group without XtiSC injection. Using DAF-2DA probe, nitric oxide production was confirmed by injected XtiSC and at the injury site. For future research of the proliferation, differentiation and migration of satellite cells in vivo, a vector expressing EGFP under endogenous Pax7 promoter and Katushka-RFP under gama-crystalline promoter was created and integrated into the X. tropicalis genome using...
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Immunomodulatory properties of mesenchymal stem cells - use in therapy
Pavlíková, Michaela ; Krulová, Magdaléna (advisor) ; Stříž, Ilja (referee)
Mesenchymal stem cells (MSC) are extensively studied mainly due to their feasible clinical application. Therapeutic potential of MSC consists not only of the ability to differentiate into mesenchymal cells, ectodermal and endodermal cell lines, but primarily in their immunomodulatory functions. Due to their effect on immune cells, MSC promote the shift of the inflammatory immune response to antiinflammatory. The ability to suppress inflammation, together with their differentiation potential and antiapoptotic potential on the surrounding cells makes MSC a promising tool for treating serious diseases. This work discusses the effect of MSC on the individual cells of the immune system. It focuses on the description of the effect of MSC in four model cases. These are an experimental autoimmune encephalomyelitis, myocardial infarction, diabetes mellitus and skin graft transplantation. The knowledge of the mechanisms of the interactions between MSC and the cells of the immune system, together with the understanding the effect of specific conditions on MSC is essential for their use in clinical therapy. Keywords: mesenchymal stem cells, immunomodulation, autoimmune diseases, transplantation
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