{"id":530,"date":"2020-05-09T17:24:43","date_gmt":"2020-05-09T15:24:43","guid":{"rendered":"https:\/\/covid.si\/?page_id=530"},"modified":"2020-05-11T23:06:00","modified_gmt":"2020-05-11T21:06:00","slug":"misija-projekta-covid-si","status":"publish","type":"page","link":"https:\/\/covid.si\/misija-projekta-covid-si\/","title":{"rendered":"Misije projekta COVID.SI"},"content":{"rendered":"\t\t
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Na tej strani so predstavljene trenutne in kon\u010dane misije projekta COVID.SI, skupaj z osnovnimi podatki, statistiko in rezultati.<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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\r\n\r\n \r\n\r\n \r\n <\/i> <\/span>\r\n \r\n \r\n <\/i> <\/span>\r\n \r\n <\/span>\r\n \r\n \r\n\r\n Misija #1: Iskanje inhibitorjev glavne proteaze virusa CoV-SARS-2 <\/span>\r\n\r\n <\/div>\r\n
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Status misije: KON\u010cANA<\/strong><\/p>

\"\"<\/p>

Design misije: dr. Marko Juki\u0107<\/strong><\/p>

\u0160tevilo tar\u010d: 21<\/strong><\/p>

Tar\u010de: #1…#21<\/span>
<\/strong><\/p>

\u0160tevilo spojin: 10.000.000<\/strong><\/p>

Skupno \u0161tevilo sidranih spojin: 210.000.000<\/strong><\/p>

Za\u010detek misije: ??????<\/strong><\/p>

Konec misije: \u00a07\/5\/2020<\/strong><\/p>

Rezultati: v obdelavi<\/strong><\/p>

\u00a0<\/p> <\/div>\r\n <\/div>\r\n

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\r\n\r\n \r\n\r\n \r\n <\/i> <\/span>\r\n \r\n \r\n <\/i> <\/span>\r\n \r\n <\/span>\r\n \r\n \r\n\r\n Misija #2: Iskanje selektivnih modulatorjev PPAR\u03b3 <\/span>\r\n\r\n <\/div>\r\n
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Status misije: AKTIVNA<\/strong><\/p>

\"\"<\/strong><\/p>

Design misije:\u00a0Filip Cernati\u010d in dr. \u010crtomir Podlipnik\u00a0<\/strong><\/p>

\u0160tevilo tar\u010d: 4<\/strong><\/p>

Tar\u010de: #22-#25<\/strong><\/p>

\u0160tevilo spojin: 10.000.000<\/strong><\/p>

Skupno \u0161tevilo sidranih spojin: 40.000.000<\/b><\/p>

Za\u010detek misije: 7\/5\/2020<\/strong><\/p>

Konec misije:\u00a011\/5\/2020<\/strong><\/p>

Rezultati: xxxxxxxx<\/strong><\/p>

\u00a0<\/strong><\/p>

OPIS:<\/strong><\/p>

PPAR\u03b3 je jedrni receptor, ki igra osrednjo vlogo pri promociji rasti in diferenciacije adipocitov ter regulaciji nivoja glukoze in trigliceridov v krvi. PPAR\u03b3 obstaja v dveh izoformah, PPAR\u03b31 in PPAR\u03b32, od katerih je PPAR\u03b31 vseprisotna, PPAR\u03b32 pa se izra\u017ea ve\u010dinoma v ma\u0161\u010dobnem tkivu. Pri normalnih fiziolo\u0161kih pogojih je PPAR\u03b3 tar\u010da \u0161tevilnih post-translacijskih modifikacij, ki uravnavajo transkripcijsko aktivnost tega receptorja. Post-translacijska modifikacija PPAR\u03b3 s strani od ciklina odvisne kinaze 5 (CDK5) vodi v supresijo specifi\u010dnih genov, ki pove\u010dujejo inzulinsko ob\u010dutljivost. Pri posameznikih, obremenjenih z debelostjo pride do vdora proinflamatornih citokinov, kot so TNF-\u03b1, IL-6, in IL-1\u03b2, v ma\u0161\u010dobno tkivo. Tovrstni citokini pospe\u0161ijo cepitev proteina p35, vezavnega partnerja CDK5, v stabilnej\u0161o in biolo\u0161ko aktivnej\u0161o podenoto p25, katera pove\u010da aktivnost CDK5, kar vodi do prekomernega obsega fosforilacije PPAR\u03b3 na mestu Ser245 (Ser273 v PPAR\u03b32). Kon\u010dna posledica opisanega poteka dogodkov je inzulinska rezistenca posameznika – stanje, ki precej pove\u010da verjetnost pojava sladkorne bolezni tipa 2 in sr\u010dno-\u017eilnih bolezni. Inhibicija fosforilacije PPAR\u03b3 s strani CDK5, z vezavo liganda v aktivno mesto PPAR\u03b3 povrne bazalni nivo transkripcije in ponovno pove\u010da inzulinski ob\u010dutljivost [1,2].
<\/strong><\/p>

V prej\u0161njih desetletjih je bilo za zdravljenje bolezni, povezanih z debelostjo, razvitih in odobrenih \u017ee ve\u010d skupin zdravilnih u\u010dinkovinod katerih je verjetno najpomembnej\u0161a skupina tiazolodindionov (TZD), polnih agonistov PPAR\u03b3. Zaradi \u0161tevilnih stranskih u\u010dinkov zdravil is skupine TZD, kot so pove\u010danje telesne te\u017ee, prekomerno zadr\u017eevanje vode v telesu, izguba kostne mase in slabokrvnost, je bila pozornost pri razvoju tovrstnih zdravilnih u\u010dinkovin preusmerjena k skupini selektivnih modulatorjev PPAR\u03b3 (angl. selective PPAR\u03b3 modulators, SPPARMs), ki izra\u017eajo manj\u0161i obseg \u0161kodljivih stranskih u\u010diknov, a kljub temu \u0161e vedno ohranjajo mo\u010dne antidiabeti\u010dne lastnosti [1,2,3].<\/p>

References:<\/p>

[1] Choi JH, Banks AS, Estall JL, et al. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature. 2010;466(7305):451\u2010456. doi:10.1038\/nature09291<\/p>

[2] Zieleniak, A., W\u00f3jcik, M. & Wo\u017aniak, L.A. Structure and physiological functions of the human peroxisome proliferator-activated receptor \u03b3. Arch. Immunol. Ther. Exp. 56, 331 (2008). https:\/\/doi.org\/10.1007\/s00005-008-0037-y<\/p>

[2] Zhang F, Lavan BE, Gregoire FM. Selective Modulators of PPAR-gamma Activity: Molecular Aspects Related to Obesity and Side-Effects. PPAR Res. 2007;2007:32696. doi:10.1155\/2007\/32696<\/p> <\/div>\r\n <\/div>\r\n <\/div>\r\n <\/div>\r\n \t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Na tej strani so predstavljene trenutne in kon\u010dane misije projekta COVID.SI, skupaj z osnovnimi podatki, statistiko in rezultati. Misija #1: […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"yoast_head":"\nMisije projekta COVID.SI - COVID.SI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/covid.si\/misija-projekta-covid-si\/\" \/>\n<meta property=\"og:locale\" content=\"ru_RU\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Misije projekta COVID.SI - COVID.SI\" \/>\n<meta property=\"og:description\" content=\"Na tej strani so predstavljene trenutne in kon\u010dane misije projekta COVID.SI, skupaj z osnovnimi podatki, statistiko in rezultati. 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