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The role of galectins in skin wound healing
Přitasilová, Adriena ; Sedlář, Antonín (advisor) ; Zimolová, Miluše (referee)
Galectins are proteins that bind β-galactosides through their Carbohydrate Recogni- tion Domain (CRD). There have been 16 types discovered in mammals, with only 4 not found in humans. They are present in various cell types and tissues and are involved in numerous physiological functions, such as apoptosis and cell proliferation, as well as in several pathological conditions, including inflammatory skin diseases. For example, anti- bodies against galectin-3 cause skin inflammation in lupus erythematosus. During wound healing in a pig model experiment, an upregulation of galectin-1 in the dermis and its neo-expression in the epidermis were observed, along with an increased level of galectin- 7. Galectin-1 plays a significant role especially in the formation of hypertrophic scars (HTS), which result from excessive collagen deposition during wound healing. HTS are erythematous and thick, causing cosmetic defects that could be addressed by modulating galectin activity during healing. Therefore, the aim of this bachelor thesis is to conduct a systematic literature review on the role of galectins in wound healing, considering both their positive and negative effects, with particular emphasis on the role of galectins and their ligands in the formation and regression of hypertrophic and keloid scars.
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The cross-talk between opioid and TLR4 receptor signaling systems
Hrdličková, Daniela ; Drastichová, Zdeňka (advisor) ; Březina, Jiří (referee)
Opioids are commonly used in clinical practice to treat acute and chronic pain. They stereoselectively bind to opioid receptors and trigger a signal cascade through inhibitory Gi/o- proteins, resulting in analgetic effects. However, their use can lead to various adverse effects, such as the development of addiction, analgetic tolerance, allodynia, hyperalgesia, constipation, and peripheral immunosuppression. Recent studies have found that opioids also bind non- stereoselectively to Toll-like receptor which belongs to innate immune system receptors recognizing lipopolysacharide. Findings suggest that some of these adverse effects may be a result of this interaction. It induces the expression of proinflammatory mediators in the central nervous system, but under certain conditions, it may also suppress inflammation. Communication between these different receptor systems occurs at multiple levels. Understanding these mechanisms could greatly benefit the development of new therapeutic approaches in opioid analgetic treatment, aiming to minimize their adverse effects, it could also lead to the therapeutic use of the antiinflammatory potential of opioids. Keywords: Opioids, Toll-like receptor 4, cellular signaling, inflammation, lipopolysaccharide, cytokine
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The role of SGIP1 protein interaction with cannabinoid receptor 1 in nociception under pathological conditions.
Dresslerová, Denisa ; Špicarová, Diana (advisor) ; Zímová, Lucie (referee)
The cannabinoid receptor type 1 (CB1) is a component of the endocannabinoid system and is abundantly expressed in the central nervous system. CB1 receptor has been extensively studied primarily due to its inhibitory role in neurotransmitter release from presynaptic terminals, and this process subsequently modulates postsynaptic currents and postsynaptic neuron excitation. Its interaction with the Src homology domain 3 growth factor 2 receptor binding protein (SGIP1) has recently been investigated in the context of nociception modulation (Hájková et al., 2016b). However, the role of this CB1 regulatory protein, SGIP1, in pathological pain conditions has not yet been described. Clarification of the role of SGIP1 interaction with CB1 receptor may help future research based on the use of cannabinoids as potential therapeutics. The thesis is structured into two parts, theoretical and practical. In the theoretical part of the thesis, knowledge of the given topic is summarized. First, pain is described from an anatomical-physiological perspective, followed by a description of the endocannabinoid system, where a part is dedicated to the CB1 cannabinoid receptor itself, and then another part is dedicated to the SGIP1 protein and its interaction with the CB1 receptor. In the practical part, the role of SGIP1...
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Macrophages selectively sense mechanical cell death in CLASP-depleted melanoma cells to trigger CXCL10 response
Otruba, Matúš ; Labzin, Larisa (advisor) ; Filipp, Dominik (referee)
Melanoma represents a significant and often fatal form of cancer, with metastasis being a primary cause of cancer-related deaths. Immunotherapy aims to stimulate the immune system to eliminate tumors, but even when used together with traditional chemotherapy, still only has <50% success rate. Chemotherapeutic drugs induce tumor cell death, primarily through apoptosis, which is 'silent' and does not incite inflammation or immune cell infiltration into the tumor. During metastasis, tumor cells migrate through confined spaces. CLASP proteins protect organelles and cellular integrity during tumor cell metastasis; when CLASP proteins are depleted, tumor cells migrating through tissue die through a mechanical cell death. The immunological impact of CLASP depletion-induced cell death remains unknown. This study aims to explore whether macrophages, innate immune cells that sense neighboring dying cells, trigger inflammatory cytokine responses specifically to mechanical, as opposed to chemotherapeutic, melanoma cell death. To model mechanical cell death during metastatic migration, CLASP1, a microtubule stabilizing protein, was depleted, and cells were physically compressed to simulate forces encountered during metastasis. Chemotherapy was simulated using a B-Raf inhibitor and the apoptosis inducer...
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The effect of cold exposure on regeneration in skeletal muscle
Novotná, Veronika ; Kašík, Petr (advisor) ; Vašek, Daniel (referee)
Cold is a stressful stimulus to which the body responds with an extensive physiological response, making it important to understand its complex effects. Skeletal muscle is an important thermoregulatory organ and helps maintain a constant body temperature by both shivering and non-shivering thermogenesis. At the same time, it has a considerable regenerative capacity that is modulated by the inflammatory immune response. This paper summarizes the effects of cold on skeletal muscle regeneration and the inflammatory response that is triggered after intense exercise or skeletal muscle injury. The inflammatory response is essential for the successful completion of skeletal muscle regeneration, and if it is impaired, it can have a negative effect on muscle tissue recovery. The balance between the pro-inflammatory and anti-inflammatory phases of the immune response, which is determined by the presence of specific immune cell populations and cytokine release, is crucial. Cold exposure is generally accepted as an effective strategy to improve skeletal muscle regeneration, but the molecular basis of this effect is not fully understood, and thus the observation of the effect of cold on skeletal muscle regeneration is still a actual topic. Keywords: cold exposure, inflammation, skeletal muscle, regeneration,...
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Lipid emulsions in lonf-term parenteral nutition
Ševela, Stanislav ; Novák, František (advisor) ; Cahová, Monika (referee) ; Lahoda Brodská, Helena (referee)
The combination of intestinal failure and parenteral nutrition is a condition associated with mild chronic inflammation and organ injury, the most significant of which is hepatic injury. This crossover-controlled trial investigated the effects of different intravenous lipid emulsions (IVLE) enriched with increased doses of omega-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) in patients on home parenteral nutrition (HPNP) for chronic intestinal failure. Twelve patients were consecutively given three different IVLEs, with an FO emulsion added after each IVLE. The study also included twelve paired healthy controls for comparison. The aim of this study was to investigate how long-term administration of these IVLEs affected primarily the erythrocyte and plasma fatty acid (FA) spectrum, as well as the inflammatory response, antioxidant status, markers of liver function and bile acid spectrum in HPNP, and how these changes differed from healthy subjects. We demonstrated successful incorporation of n-3 PUFA into erythrocyte phospholipids and corresponding changes in the plasma FA spectrum, characterized in particular by significant increases in n-3 versus n-6 PUFA, with a decrease in the n-6/n-3 PUFA ratio. We also found a more prolonged effect on these changes with high dose FO...
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Host-microbe interactions and its consequences for intestinal inflammation and carcinogenesis
Kejzlarová, Leona ; Kverka, Miloslav (advisor) ; Smrž, Daniel (referee)
A number of physiological and pathological processes, including the transition from chronic inflammation to cancer, are affected by commensal microbes. However, abundance of microbes and ability to produce active metabolites in the intestine depend on environmental factors, particularly diet. Microbes can influence this process in two ways, by producing genotoxic substances that directly damage the epithelium or by stimulating the inflammatory response. The aim of my thesis was to study the interaction among gut microbiota, diet and the immune system with the subsequent influence on the development of colorectal cancer (CRC) in an experimental mouse model. Animals were fed synthetic diets containing either normal amounts of animal protein (17%; KD) or elevated amounts of animal protein (51%; HPD) throughout the experiments. Two weeks after the diets were introduced, intestinal tumors were induced by administering azoxymethane (AOM) and inducing acute inflammation with 2% sodium dextran sulfate one week after AOM injection. At the end of the experiment I evaluated the number of tumors in the colon and the status of the immune response in the intestine, mesenteric lymph nodes and spleen. To study the effect of macrophages, a similar experiment was performed in animals with depleted macrophages using...
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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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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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