20.500.12556/RUL-147201 Vpliv okužbe s SARS-CoV-2 na energijsko presnovo monocitov, izoliranih iz krvi odraslih bolnikov z akutnim ali dolgotrajnim potekom COVID-19 The effect of SARS-CoV-2 infection on energy metabolism of monocytes isolated from adult patients with acute or long COVID-19 Decembra 2019 je bil v Wuhanu na Kitajskem potrjen novi koronavirus SARS-CoV-2, ki povzroča novo koronarno bolezen 19, krajše covid-19. Je visokonalezljiva virusna bolezen, ki je do danes imela hude posledice na svetovno demografsko sliko, z več kot 6 milijoni žrtev po celem svetu in predstavlja najhujšo svetovno zdravstveno krizo po pandemiji gripe leta 1918. Nekateri bolezen prebolijo asimptomatsko, nekateri imajo lahek potek bolezni, nekatere pa virus hudo prizadene in potrebujejo hospitalizacijo. Pri nekaterih posameznikih se pojavljajo težave še po več mesecih od prebolelega covid-19. Najpogostejše težave so nevrološki simptomi, simptomi respiratornega sistema ter palpitacije in bolečine v mišicah. Do sedaj še niso ugotovili dejanskega vzroka teh težav in jih zdravimo zgolj simptomatsko. Monociti so ena od treh skupin belih krvnih celic in predstavljajo 3–8 % vseh belih krvnih celic. Bele krvne celice ali levkociti so raznolika skupina celic, ki skrbijo za imunski odgovor človeka. V času cirkulacije po krvnem obtoku monociti konstantno oprezajo za prisotnostjo mikroorganizmov v telesu. Ko pride do dejanskega vnetja, monociti migrirajo iz krvi na mesto vnetja. Kot imunske celice imajo v telesu tri glavne funkcije. To so fagocitoza, predstavitev antigena ter proizvodnja citokinov. V magistrski nalogi smo preverili vpliv SARS-CoV-2 na energijsko presnovo monocitov. Nova metoda merjenja z analizatorjem izvenceličnega pretoka Agilent Seahorse XFe24 nam je omogočila spremljanje hitrosti porabe kisika (mitohondrijskega dihanja) in hitrosti izvencelične acidifikacije (glikolize) v realnem času. Analizirali smo kri 46 posameznikov, ki so bili razdeljeni na zdrave prostovoljce (n = 16), akutne bolnike (n = 16) ter bolnike z dolgotrajnim potekom covid-19 (n = 14). Na podlagi izvedenih poskusov in rezultatov smo ugotovili vpliv SARS-CoV-2 na energijsko presnovo monocitov. Ugotovili smo, da je prišlo do manjše oksidativne fosforilacije v bazalnih pogojih in manjše hitrosti porabe kisika za zadostitev celičnih potreb po ATP v stresnih situacijah. Sklepamo, da je SARS-CoV-2 okvaril delovanje in strukturo mitohondrijev v monocitih. In December 2019 in Wuhan, China was confirmed a novel coronavirus SARS-CoV-2 which causes a novel Coronavirus disease 2019, covid-19. It is highly contagious viral disease that has had severe consequences on the global demographics with more than 6 million deaths worldwide and represents the worst global health crisis since the influenza pandemic in 1918. While many infected with SARS-CoV-2 are asymptomatic or develop mild disease, for others, covid-19 have severe impact and can require hospitalization. In some individuals, however, problems appear even after several months of recovering from covid-19. The most common problems are neurological, respiratory system symptoms, palpitations and muscle pain. So far, the actual cause of these problems has not been discovered and those problems are being treated only symptomatically. Monocytes are one of the three groups of white blood cells and they represent 3-8% of all white blood cells. White blood cells or leukocytes are a diverse group of cells which are responsible for the human immune response. During circulation in the blood circulatory system, monocytes constantly watch for the presence of microorganisms in the body. When the actual inflammation takes place monocytes migrate from blood to an inflammatory site to perform their functions. They serve three main functions in the immune system. These are phagocytosis, antigen presentation and cytokine production. In this master thesis, we looked for the potential impact of SARS-CoV-2 on the energy metabolism of monocytes. A new measurement method with the Agilent Seahorse XFe24 extracellular flux analyzer enables us to observe the oxygen consumption rate (mitochondrial respiration) and extracellular acidification rate (glycolysis) in real-time. We analyzed 46 individuals who were divided into three groups – healthy controls (n=16), acute covid-19 patients (n=16) and long covid-19 patients (n=14). Based on our experiments and results we can conclude that SARS-CoV-2 has an impact on the energy metabolism of monocytes. We discovered decreased oxidative phosphorylation in basal conditions and decreased oxygen consumption rate in order to meet the cellular needs for ATP production in stress situations. We conclude that SARS-CoV-2 damaged function and structure of mitochondria in monocytes. Covid-19 energijska presnova glikoliza monocit oksidativna fosforilacija SARS-CoV-2 Covid-19 energy metabolism glycolysis monocytes oxidative phosphorylation SARS-CoV-2 true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2023-06-25 07:45:29 2023-06-25 07:45:39 2023-06-26 03:59:59 0000-00-00 00:00:00 2023 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 96282 14328.pdf 14328.pdf 1 40A6F13A156A72BA53610A928DFC88AA dbddda650416c57c2ba22a5cbbee1312c96a50a40637bae1c7da8d4a5d110c85 273e6f36-131b-11ee-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=170678 Fakulteta za farmacijo 0 0 0