{"id":13511,"date":"2024-05-10T10:58:49","date_gmt":"2024-05-10T08:58:49","guid":{"rendered":"https:\/\/semmelweis.hu\/pharmacology\/?page_id=13511"},"modified":"2024-10-11T19:41:46","modified_gmt":"2024-10-11T17:41:46","slug":"kardioprotekcio-munkacsoport","status":"publish","type":"page","link":"https:\/\/semmelweis.hu\/pharmacology\/kutatas\/kardiovaszkularis-es-metabolizmus\/kardioprotekcio-munkacsoport\/","title":{"rendered":"Kardioprotekci\u00f3 munkacsoport"},"content":{"rendered":"<p>&nbsp;<\/p>\n<p><iframe loading=\"lazy\" title=\"Cardiovascular And Metabolic Research Group\" width=\"753\" height=\"424\" src=\"https:\/\/www.youtube.com\/embed\/F89VrbDg4B4?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><\/p>\n<div class=\"responsive-tabs\">\n<h2 class=\"tabtitle\">Projektek<\/h2>\n<div class=\"tabcontent\">\n\n<p><strong>A kissejtes t\u00fcd\u0151r\u00e1k Immunoter\u00e1pia rezisztenci\u00e1j\u00e1nak \u00e9s v\u00e1laszk\u00e9szs\u00e9g\u00e9nek vizsg\u00e1lata<\/strong><\/p>\n<p>Projektvezet\u0151: G\u00f6rbe Anik\u00f3<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-13292\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Gorbe-Aniko_SOTE_web004.jpg\" alt=\"\" width=\"210\" height=\"315\" \/><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>Projektfelel\u0151s: Pa\u00e1l \u00c1gnes<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-12783 alignnone\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/2.jpg\" alt=\"\" width=\"148\" height=\"222\" \/><\/p>\n<p style=\"text-align: justify\">A kissejtes t\u00fcd\u0151r\u00e1k (SCLC) a legrosszabb progn\u00f3zis\u00fa rosszindulat\u00fa daganatok egyike, amelynek ter\u00e1pi\u00e1j\u00e1ban az elm\u00falt h\u00e1rom \u00e9vtizedben nem t\u00f6rt\u00e9nt jelent\u0151s el\u0151rel\u00e9p\u00e9s. Az els\u0151 \u00edg\u00e9retes eredm\u00e9nyeket az immunellen\u0151rz\u00e9si pont g\u00e1tl\u00f3k (ICI-k) alkalmaz\u00e1sa hozta, de a siker messze elmarad a nem kissejtes t\u00fcd\u0151r\u00e1kn\u00e1l tapasztaltakt\u00f3l, ahol az ICI-k alkalmaz\u00e1sa \u00e1tt\u00f6r\u00e9st jelentett a ter\u00e1pi\u00e1ban. Az SCLC-ben a kiterjedt st\u00e1dium\u00fa betegs\u00e9gben szenved\u0151 betegekn\u00e9l esetenk\u00e9nt a t\u00fal\u00e9l\u00e9s 1-2 h\u00f3nappal hosszabb lehet.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-12784 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/3-400x300.jpg\" alt=\"\" width=\"400\" height=\"300\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/3-400x300.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/3.jpg 542w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/p>\n<p style=\"text-align: center\">A kissejtes t\u00fcd\u0151r\u00e1k sz\u00f6vettani k\u00e9pe<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-12785 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-400x300.png\" alt=\"SCLC cells in culture\" width=\"400\" height=\"300\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-400x300.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-1024x768.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-768x576.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-1536x1152.png 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-753x565.png 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4.png 1600w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/p>\n<p style=\"text-align: center\">Kissejtes t\u00fcd\u0151r\u00e1k sejtek kult\u00far\u00e1ban<\/p>\n<p style=\"text-align: justify\">Ezek arra utalnak, hogy \u00faj megk\u00f6zel\u00edt\u00e9sekre van sz\u00fcks\u00e9g az SCLC immunter\u00e1pi\u00e1ra adott v\u00e1lasz\u00e1nak \u00e9s rezisztenci\u00e1j\u00e1nak meg\u00e9rt\u00e9s\u00e9hez. Sz\u00e1mos kutat\u00f3csoport azonos\u00edtotta az SCLC molekul\u00e1ris alt\u00edpusait, amelyek r\u00e9szben megfelelnek egym\u00e1snak. P\u00e9ld\u00e1ul a gyeng\u00e9bb neuroendokrin marker-expresszi\u00f3 gyakran er\u0151sebb immuninfiltr\u00e1ci\u00f3val j\u00e1r egy\u00fctt (neuroendokrin-alacsony, immuno\u00e1zis tumorok), ami az ilyen tumorok jobb immunter\u00e1pi\u00e1s \u00e9rz\u00e9kenys\u00e9get felt\u00e9telezheti.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-12786 size-large\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-1024x503.png\" alt=\"A possible road to improved therapy: evolving subclassificiation of SCLC\" width=\"753\" height=\"370\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-1024x503.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-400x197.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-768x377.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-753x370.png 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5.png 1264w\" sizes=\"auto, (max-width: 753px) 100vw, 753px\" \/><\/p>\n<p style=\"text-align: center\">Egy lehets\u00e9ges \u00fat a hat\u00e9konyabb ter\u00e1pia fel\u00e9: az SCLC fejl\u0151d\u0151 aloszt\u00e1lyoz\u00e1sa<\/p>\n<p style=\"text-align: justify\">Az er\u0151sebb immun infiltr\u00e1ci\u00f3 ellen\u00e9re a tumorok nem mindig reag\u00e1lnak az ICI-kre, \u00e9s immunszuppressz\u00edv molekul\u00e1k helyi fokozott expresszi\u00f3j\u00e1t is kimutatt\u00e1k.<\/p>\n<p style=\"text-align: justify\">Vizsg\u00e1ljuk az egyik ilyen immunszuppressz\u00edv molekula, az annexin A1 expresszi\u00f3j\u00e1nak csendes\u00edt\u00e9s\u00e9t neuroendokrin-alacsony SCLC-sejtvonalak kult\u00far\u00e1iban. Felt\u00e9telez\u00e9s\u00fcnk szerint a malignus fenot\u00edpus egyes jellemz\u0151it befoly\u00e1solhatja az annexin A1 csendes\u00edt\u00e9se, mint p\u00e9ld\u00e1ul a n\u00f6veked\u00e9si sebess\u00e9get, az epithelio-mesenchym\u00e1lis \u00e1tmenetet, a metabolikus eltol\u00f3d\u00e1st, a domin\u00e1ns transzkripci\u00f3s drivereket \u00e9s a klasszikus kemoter\u00e1pi\u00e1s szerekkel, ciszplatinnal \u00e9s etopoziddal szembeni \u00e9rz\u00e9kenys\u00e9get.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-12787 size-large aligncenter\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-768x1024.png\" alt=\"\" width=\"753\" height=\"1004\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-768x1024.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-300x400.png 300w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-1152x1536.png 1152w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-1536x2048.png 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-753x1004.png 753w\" sizes=\"auto, (max-width: 753px) 100vw, 753px\" \/><\/p>\n<p style=\"text-align: center\">Fluoreszcens viabilit\u00e1s essz\u00e9<\/p>\n<p style=\"text-align: justify\">\u00dagy gondoljuk, hogy az annexin A1 csendes\u00edt\u00e9s hat\u00e1sainak vizsg\u00e1lata seg\u00edthet meg\u00e9rteni a kissejtes t\u00fcd\u0151r\u00e1k \u00faj, a ter\u00e1pia szempontj\u00e1b\u00f3l fontos aspektusait.<\/p>\n<p>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/p>\n<ul>\n<li>kissejtes t\u00fcd\u0151r\u00e1k sejtvonalak teny\u00e9szt\u00e9se, fenntart\u00e1sa<\/li>\n<li>n\u00f6veked\u00e9si r\u00e1ta vizsg\u00e1lata sejtsz\u00e1mol\u00e1ssal \u00e9s fluoreszcens viabilit\u00e1s essz\u00e9kkel<\/li>\n<li>sejtek kezel\u00e9se, kemoszenzitivit\u00e1s m\u00e9r\u00e9se fluoreszcens vibabilit\u00e1s essz\u00e9kkel<\/li>\n<li>western blot<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13839 size-large\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-1024x717.png\" alt=\"\" width=\"753\" height=\"527\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-1024x717.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-400x280.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-768x538.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-1536x1075.png 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-2048x1434.png 2048w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/SCLC_sejtek_vmi_magyar-753x527.png 753w\" sizes=\"auto, (max-width: 753px) 100vw, 753px\" \/><\/p>\n<p>(BioRender.com)<\/p>\n<p>&nbsp;<\/p>\n<p>Kapcsol\u00f3d\u00f3 k\u00f6zlem\u00e9nyek:<\/p>\n<ul>\n<li>Dora, David et al. \u201cNeuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution.\u201d\u00a0<em>Molecular oncology<\/em> 14,9 (2020): 1947-1965. doi:10.1002\/1878-0261.12741<\/li>\n<li>Dora, David et al. \u201cCharacterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer.\u201d\u00a0<em>Biology<\/em> 10,6 502. 4 Jun. 2021, doi:10.3390\/biology10060502<\/li>\n<li>Dora, David et al. \u201cProtein Expression of immune checkpoints STING and MHCII in small cell lung cancer.\u201d\u00a0<em>Cancer immunology, Immunotherapy : CII<\/em> 72,3 (2023): 561-578. doi:10.1007\/s00262-022-03270-w<\/li>\n<\/ul>\n<p><strong>A miRNS-ek fejleszt\u00e9se, mint \u00faj ter\u00e1pi\u00e1s eszk\u00f6z a sz\u00edv- \u00e9s \u00e9rrendszeri betegs\u00e9gek kezel\u00e9s\u00e9ben<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-12849\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/1-3.png\" alt=\"\" width=\"310\" height=\"163\" \/><\/p>\n<p>Projektvezet\u0151k: Prof. Dr. Ferdinandy P\u00e9ter, Dr. G\u00f6rbe Anik\u00f3<\/p>\n<table style=\"border-collapse: collapse;width: 100%\">\n<tbody>\n<tr>\n<td style=\"width: 50%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13291\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-scaled.jpg\" alt=\"\" width=\"210\" height=\"315\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-scaled.jpg 1707w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-267x400.jpg 267w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-683x1024.jpg 683w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-768x1152.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-1024x1536.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-1365x2048.jpg 1365w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-753x1130.jpg 753w\" sizes=\"auto, (max-width: 210px) 100vw, 210px\" \/><\/td>\n<td style=\"width: 50%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13292\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Gorbe-Aniko_SOTE_web004.jpg\" alt=\"\" width=\"210\" height=\"315\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-12852 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-4-393x400.png\" alt=\"\" width=\"393\" height=\"400\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-4-393x400.png 393w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/4-4.png 477w\" sizes=\"auto, (max-width: 393px) 100vw, 393px\" \/>Az iszk\u00e9mi\u00e1s sz\u00edvbetegs\u00e9gek \u00e9s k\u00f3ros k\u00f6vetkezm\u00e9nyeik vil\u00e1gszerte a vezet\u0151 hal\u00e1lokok k\u00f6z\u00e9 tartoznak. A myocardialis ischaemia akut kezel\u00e9s\u00e9ben az egyik legfontosabb feladat a sz\u00f6veti perf\u00fazi\u00f3 helyre\u00e1ll\u00edt\u00e1sa.<\/p>\n<p style=\"text-align: justify\">Sajnos a reperf\u00fazi\u00f3 a sz\u00edvizom tov\u00e1bbi k\u00e1rosod\u00e1s\u00e1t is okozza, amit \u00e1ltal\u00e1ban reperf\u00fazi\u00f3s s\u00e9r\u00fcl\u00e9snek neveznek. Bizonyos esetekben ez felel\u0151s a teljes sz\u00edvizomk\u00e1rosod\u00e1s fel\u00e9\u00e9rt.<\/p>\n<p style=\"text-align: justify\">Annak ellen\u00e9re, hogy preklinikai k\u00f6r\u00fclm\u00e9nyek k\u00f6z\u00f6tt sz\u00e1mos kis molekul\u00e1j\u00fa gy\u00f3gyszerr\u0151l meg\u00e1llap\u00edtott\u00e1k, hogy cs\u00f6kkenti az infarktus m\u00e9ret\u00e9t, egyiket sem siker\u00fclt hum\u00e1n ter\u00e1pi\u00e1ba alkalmazni. Ez\u00e9rt \u00faj megk\u00f6zel\u00edt\u00e9seket \u00e9s hat\u00e9kony kardioprotekt\u00edv molekulajel\u00f6lteket kell tal\u00e1lni a j\u00f6v\u0151beli gy\u00f3gyszerfejleszt\u00e9shez.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-12853\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-3.png\" alt=\"\" width=\"745\" height=\"439\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-3.png 745w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/5-3-400x236.png 400w\" sizes=\"auto, (max-width: 745px) 100vw, 745px\" \/><\/p>\n<p style=\"text-align: center\">Paolo Severino, Andrea D\u2019Amato et al., 2020, Int J Mol Sci., 10.3390\/ijms21218118<\/p>\n<p style=\"text-align: justify\">Az elm\u00falt \u00e9vtizedekben az oligonukleotid molekul\u00e1k, p\u00e9ld\u00e1ul a miRNS-ek potenci\u00e1lis alkalmaz\u00e1sa vonz\u00f3 \u00e9s innovat\u00edv megk\u00f6zel\u00edt\u00e9sk\u00e9nt jelent meg a k\u00fcl\u00f6nb\u00f6z\u0151 k\u00f3rk\u00e9pek, k\u00f6zt\u00fck a r\u00e1kos megbeteged\u00e9sek, s\u0151t a sz\u00edv- \u00e9s \u00e9rrendszeri betegs\u00e9gek kezel\u00e9s\u00e9ben.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-12854 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-3-336x400.png\" alt=\"\" width=\"336\" height=\"400\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-3-336x400.png 336w, https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/6-3.png 533w\" sizes=\"auto, (max-width: 336px) 100vw, 336px\" \/>Meg\u00e1llap\u00edtott\u00e1k, hogy a miRNS-ek diszregul\u00e1ci\u00f3ja fontos szerepet j\u00e1tszik a sz\u00edvinfarktus patomechanizmus\u00e1ban. A mikroRNS-ek r\u00f6vid, ~18-25 nukleotid hossz\u00fas\u00e1g\u00fa nem k\u00f3dol\u00f3 RNS-szekvenci\u00e1k, amelyek a transzkripci\u00f3 ut\u00e1n a g\u00e9nexpresszi\u00f3t negat\u00edvan szab\u00e1lyozz\u00e1k poszt-transzkripci\u00f3s szinten vagy a transzl\u00e1ci\u00f3 g\u00e1tl\u00e1s\u00e1val, vagy a c\u00e9l mRNS degrad\u00e1ci\u00f3j\u00e1nak el\u0151seg\u00edt\u00e9s\u00e9vel. Egyetlen mikroRNS ak\u00e1r egy eg\u00e9sz \u00fatvonalat is szab\u00e1lyozhat, ez\u00e9rt a miRNS-ek nagy potenci\u00e1llal rendelkeznek abban, hogy multi-target gy\u00f3gyszerekk\u00e9 v\u00e1ljanak a multifaktori\u00e1lis eredet\u0171 betegs\u00e9gek kezel\u00e9s\u00e9ben. A mikroRNS-ter\u00e1pi\u00e1k k\u00e9t k\u00fcl\u00f6nb\u00f6z\u0151 t\u00edpusa a mikroRNS-mimics \u00e9s az antagomiRs (Varga ZV et al., Am J Physiol Heart Circ Physiol, 10.1152\/ajpheart.00812.2013). A mikroRNS mimics k\u00e9tsz\u00e1l\u00fa szekvenci\u00e1k, bele\u00e9rtve a \u201evezet\u0151\u201d sz\u00e1lat, amelynek szekvenci\u00e1ja megegyezik az endog\u00e9n megfelel\u0151j\u00e9vel, \u00e9s egy nem teljesen komplementer k\u00eds\u00e9r\u0151sz\u00e1lat, amely a lev\u00e1laszt\u00e1s ut\u00e1n lebomlik. Az antagomiR-ek l\u00e9nyeg\u00e9ben egysz\u00e1l\u00fa oligonukleotidok, amelyek komplementerek az endog\u00e9n miRNS-hez, ez\u00e1ltal blokkolva annak m\u0171k\u00f6d\u00e9s\u00e9t.<\/p>\n<p>1. A miRNS-ek felt\u00e1r\u00e1sa farmakokinetikai profilalkot\u00e1sa eg\u00e9rmodellekben<\/p>\n<p>Projekt felel\u0151s\u00f6k: Dr. Makkos Andr\u00e1s, Szab\u00f3 M\u00e1rta<\/p>\n<table style=\"border-collapse: collapse;width: 100%;height: 327px\">\n<tbody>\n<tr style=\"height: 327px\">\n<td style=\"width: 50%;height: 327px\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-12855\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/7-1.png\" alt=\"\" width=\"210\" height=\"315\" \/><\/td>\n<td style=\"width: 50%;height: 327px\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13634\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/marta_szabo.jpg\" alt=\"\" width=\"210\" height=\"315\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-13635 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles-400x208.png\" alt=\"\" width=\"400\" height=\"208\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles-400x208.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles-1024x532.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles-768x399.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles-1536x798.png 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles-753x391.png 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/06\/egeres_mirna_leveles.png 1573w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/>B\u00e1r a miRNS-ek alkalmaz\u00e1s\u00e1t akt\u00edvan vizsg\u00e1lj\u00e1k k\u00fcl\u00f6nb\u00f6z\u0151 indik\u00e1ci\u00f3kban, kev\u00e9ss\u00e9 ismertek farmakokinetikai tulajdons\u00e1gaik \u00e9s a k\u00fcl\u00f6nb\u00f6z\u0151 miRNS-ek jellemz\u0151inek k\u00fcl\u00f6nbs\u00e9gei. Ez\u00e9rt c\u00e9lunk a miRNS-mimic-ek \u00e9s az antagomiR-ek farmakokinetikai profilj\u00e1nak felt\u00e1r\u00e1sa eg\u00e9szs\u00e9ges \u00e1llatokban.<\/p>\n<p>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13797\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvobe_3askep_1_pont_utan.png\" alt=\"\" width=\"1366\" height=\"380\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvobe_3askep_1_pont_utan.png 1366w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvobe_3askep_1_pont_utan-400x111.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvobe_3askep_1_pont_utan-1024x285.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvobe_3askep_1_pont_utan-768x214.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvobe_3askep_1_pont_utan-753x209.png 753w\" sizes=\"auto, (max-width: 1366px) 100vw, 1366px\" \/><\/p>\n<ul>\n<li><em> In vivo <\/em>k\u00eds\u00e9rleti m\u00f3dszerek (pl. miRNS-ekkel val\u00f3 kezel\u00e9s, plazma\/sz\u00f6vetmintav\u00e9tel)<\/li>\n<li><em> In vitro <\/em>m\u00f3dszerek (pl. western blot, RNS-izol\u00e1l\u00e1s, qRT-PCR)<\/li>\n<li>sz\u00f6vettani m\u00f3dszerek (pl. fix\u00e1l\u00e1s, metsz\u00e9s, fest\u00e9si m\u00f3dszerek<em>,<\/em> RNAscope)<\/li>\n<\/ul>\n<p>2. A protectomiRs koncepci\u00f3j\u00e1nak <em>in vivo<\/em> bizony\u00edt\u00e1si vizsg\u00e1latai<\/p>\n<p>Projekt vezet\u0151k: Dr. Makkos Andr\u00e1s, Szab\u00f3 M\u00e1rt<\/p>\n<p style=\"text-align: justify\">Ezekben a vizsg\u00e1latokban \u00faj vagy kor\u00e1bban azonos\u00edtott protektomiR-ek (miRNS-ek) kardioprotekt\u00edv hat\u00e1s\u00e1t k\u00edv\u00e1njuk felt\u00e1rni \u00e9s bizony\u00edtani a sz\u00edvinfarktus \u00e9s sz\u00edvel\u00e9gtelens\u00e9g eg\u00e9rmodellj\u00e9ben. Emellett c\u00e9lunk a sz\u00f6vetspecifikus c\u00e9lg\u00e9n-expresszi\u00f3s profil v\u00e1ltoz\u00e1sainak jellemz\u00e9se is mind a sz\u00edvben, mind a k\u00fcl\u00f6nb\u00f6z\u0151 sz\u00f6vett\u00edpusokban.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13798\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_2es_pont_utan.png\" alt=\"\" width=\"1472\" height=\"565\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_2es_pont_utan.png 1472w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_2es_pont_utan-400x154.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_2es_pont_utan-1024x393.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_2es_pont_utan-768x295.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_2es_pont_utan-753x289.png 753w\" sizes=\"auto, (max-width: 1472px) 100vw, 1472px\" \/><\/p>\n<p>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/p>\n<ul>\n<li><em>In vivo <\/em>k\u00eds\u00e9rleti m\u00f3dszerek (pl. miRNS-ekkel val\u00f3 kezel\u00e9s, plazma\/sz\u00f6vetmintav\u00e9tel)<\/li>\n<li><em>In vitro <\/em>m\u00f3dszerek (pl. western blot, RNS-izol\u00e1l\u00e1s, qRT-PCR)<\/li>\n<li>sz\u00f6vettani m\u00f3dszerek (pl. fix\u00e1l\u00e1s, metsz\u00e9s, fest\u00e9si m\u00f3dszerek<em>,<\/em> RNAscope.<\/li>\n<\/ul>\n<p>3. K\u00e9miailag m\u00f3dos\u00edtott miRNS mimik\u00e1k\/AntagomiR-ek kifejleszt\u00e9se<\/p>\n<p>Projekt felel\u0151s\u00f6k: Dr. Makkos Andr\u00e1s, Szab\u00f3 M\u00e1rt<\/p>\n<p style=\"text-align: justify\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-13799 alignleft\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_3as_pont_1.png\" alt=\"\" width=\"221\" height=\"189\" \/>A miRNS-alap\u00fa farmakoter\u00e1pi\u00e1k fejleszt\u00e9se sor\u00e1n kulcsfontoss\u00e1g\u00fa k\u00e9rd\u00e9s a megfelel\u0151 biol\u00f3giai hozz\u00e1f\u00e9rhet\u0151s\u00e9g \u00e9s sz\u00f6vetspecifikuss\u00e1g biztos\u00edt\u00e1sa, mik\u00f6zben minimaliz\u00e1ljuk a gy\u00f3gyszer potenci\u00e1lis toxicit\u00e1s\u00e1t. Ennek megfelel\u0151en akt\u00edvan dolgozunk a szabadalmaztatott kardioprotekt\u00edv miRNS-szekvenci\u00e1ink k\u00e9miai m\u00f3dos\u00edt\u00e1son alapul\u00f3 jav\u00edt\u00e1s\u00e1n, hogy jav\u00edtsuk farmakokinetikai tulajdons\u00e1gaikat \u00e9s biztons\u00e1goss\u00e1gukat.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13800\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_3as_pont_2.png\" alt=\"\" width=\"415\" height=\"252\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_3as_pont_2.png 415w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_3as_pont_2-400x243.png 400w\" sizes=\"auto, (max-width: 415px) 100vw, 415px\" \/><\/p>\n<p>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/p>\n<ul>\n<li><em>In vivo<\/em> k\u00eds\u00e9rleti m\u00f3dszerek (miRNS-kezel\u00e9s, plazma\/sz\u00f6vetmintav\u00e9tel)<\/li>\n<li><em>In silico<\/em> modellez\u00e9s, preparat\u00edv k\u00e9mia<\/li>\n<li>Sejtteny\u00e9szt\u00e9s, sejtkult\u00fara-alap\u00fa k\u00eds\u00e9rleti modellek (pl. miRNS-transzfekci\u00f3, szimul\u00e1lt iszk\u00e9mi\u00e1s reperf\u00fazi\u00f3s modell, \u00e9letk\u00e9pess\u00e9gi vizsg\u00e1latok, fluoreszcenciajel-m\u00e9r\u00e9s).<\/li>\n<li>konfok\u00e1lis mikroszk\u00f3pos k\u00e9palkot\u00e1s<\/li>\n<li>sz\u00f6vettani m\u00f3dszerek (pl. fix\u00e1l\u00e1s, metsz\u00e9s, fest\u00e9si m\u00f3dszerek, RNAscope)<\/li>\n<li><em>In vitro<\/em> m\u00f3dszerek (pl. Western blot, RNS-izol\u00e1l\u00e1s, qRT-PCR)<\/li>\n<\/ul>\n<p>4. \u00dajszer\u0171, miRNS mimik\u00e1kat\/AntagomiR-eket tartalmaz\u00f3 viv\u0151anyag-formul\u00e1k kifejleszt\u00e9se<\/p>\n<p>Projekt felel\u0151s: Dr. Makkos Andr\u00e1s<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-13802 alignleft\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_1.jpg\" alt=\"\" width=\"416\" height=\"327\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_1.jpg 416w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_1-400x314.jpg 400w\" sizes=\"auto, (max-width: 416px) 100vw, 416px\" \/>Amint azt kor\u00e1bban eml\u00edtett\u00fck, az oligonukleotid-alap\u00fa ter\u00e1pi\u00e1k megfelel\u0151 sz\u00f6vetspecifikuss\u00e1ga \u00e9s plazma\/sz\u00f6vet felez\u00e9si ideje nagy kih\u00edv\u00e1st jelent. A k\u00e9miai m\u00f3dos\u00edt\u00e1sokon t\u00falmen\u0151en az innovat\u00edv hordoz\u00f3k alkalmaz\u00e1sa jelent\u0151sen jav\u00edthatja a kardioprotekt\u00edv miRNS-ek farmakokinetikai tulajdons\u00e1gait (pl. sz\u00f6veti specifit\u00e1s, sejtfelv\u00e9tel).<img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13803\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_egyben.png\" alt=\"\" width=\"1416\" height=\"701\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_egyben.png 1416w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_egyben-400x198.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_egyben-1024x507.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_egyben-768x380.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/mirvivo_4es_pont_egyben-753x373.png 753w\" sizes=\"auto, (max-width: 1416px) 100vw, 1416px\" \/><\/p>\n<p>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/p>\n<ul>\n<li>Sejtteny\u00e9szt\u00e9s, sejtkult\u00fara-alap\u00fa k\u00eds\u00e9rleti modellek (pl. miRNS transzfekci\u00f3, szimul\u00e1lt iszk\u00e9mi\u00e1s reperf\u00fazi\u00f3s modell, \u00e9letk\u00e9pess\u00e9gi vizsg\u00e1latok, fluoreszcens jelek m\u00e9r\u00e9se).<\/li>\n<li>Konfok\u00e1lis mikroszk\u00f3pos k\u00e9palkot\u00e1s<\/li>\n<li><em>In vivo<\/em> k\u00eds\u00e9rleti m\u00f3dszerek (oligonukleotidokkal t\u00f6rt\u00e9n\u0151 kezel\u00e9s, plazma\/sz\u00f6vetmintav\u00e9tel, sz\u00edvinfarktus vagy sz\u00edvel\u00e9gtelens\u00e9g eg\u00e9rmodelljei).<\/li>\n<li>sz\u00f6vettani m\u00f3dszerek (pl. fix\u00e1l\u00e1s, metsz\u00e9s, fest\u00e9si m\u00f3dszerek, RNAscope)<\/li>\n<\/ul>\n<p>Publik\u00e1ci\u00f3k:<\/p>\n<ul>\n<li style=\"text-align: justify\">Makkos, A., \u00c1gg, B., Petrovich, B., Varga, Z. V., G\u00f6rbe, A., &amp; Ferdinandy, P. (2021). Systematic review and network analysis of microRNAs involved in cardioprotection against myocardial ischemia\/reperfusion injury and infarction: Involvement of redox signalling.\u00a0<em>Free radical biology &amp; medicine<\/em>,\u00a0<em>172<\/em>, 237\u2013251. <a href=\"https:\/\/doi.org\/10.1016\/j.freeradbiomed.2021.04.034\">https:\/\/doi.org\/10.1016\/j.freeradbiomed.2021.04.034<\/a><\/li>\n<li style=\"text-align: justify\">Makkos, A., \u00c1gg, B., Varga, Z. V., Giricz, Z., Gy\u00f6ngy\u00f6si, M., Lukovic, D., Schulz, R., Bartekov\u00e1, M., G\u00f6rbe, A., &amp; Ferdinandy, P. (2021). Molecular Network Approach Reveals\u00a0<em>Rictor<\/em>as a Central Target of Cardiac ProtectomiRs.\u00a0<em>International journal of molecular sciences<\/em>,\u00a0<em>22<\/em>(17), 9539. <a href=\"https:\/\/doi.org\/10.3390\/ijms22179539\">https:\/\/doi.org\/10.3390\/ijms22179539<\/a><\/li>\n<li style=\"text-align: justify\">Varga, Z. V., Zvara, A., Farag\u00f3, N., Kocsis, G. F., Pipicz, M., G\u00e1sp\u00e1r, R., Bencsik, P., G\u00f6rbe, A., Csonka, C., Pusk\u00e1s, L. G., Thum, T., Csont, T., &amp; Ferdinandy, P. (2014). MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs.\u00a0<em>American journal of physiology. Heart and circulatory physiology<\/em>,\u00a0<em>307<\/em>(2), H216\u2013H227. <a href=\"https:\/\/doi.org\/10.1152\/ajpheart.00812.2013\">https:\/\/doi.org\/10.1152\/ajpheart.00812.2013<\/a><\/li>\n<li style=\"text-align: justify\">Ferdinandy, P., Andreadou, I., Baxter, G. F., B\u00f8tker, H. E., Davidson, S. M., Dobrev, D., Gersh, B. J., Heusch, G., Lecour, S., Ruiz-Meana, M., Zuurbier, C. J., Hausenloy, D. J., &amp; Schulz, R. (2023). Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia\/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.\u00a0<em>Pharmacological reviews<\/em>,\u00a0<em>75<\/em>(1), 159\u2013216. <a href=\"https:\/\/doi.org\/10.1124\/pharmrev.121.000348\">https:\/\/doi.org\/10.1124\/pharmrev.121.000348<\/a><\/li>\n<li style=\"text-align: justify\">On\u00f3di, Z., Visnovitz, T., Kiss, B., Hambalk\u00f3, S., Koncz, A., \u00c1gg, B., V\u00e1radi, B., T\u00f3th, V. \u00c9., Nagy, R. N., Gergely, T. G., Gerg\u0151, D., Makkos, A., Pelyhe, C., Varga, N., Re\u00e9, D., Ap\u00e1ti, \u00c1., Leszek, P., Kov\u00e1cs, T., Nagy, N., Ferdinandy, P., \u2026 Varga, Z. V. (2022). Systematic transcriptomic and phenotypic characterization of human and murine cardiac myocyte cell lines and primary cardiomyocytes reveals serious limitations and low resemblances to adult cardiac phenotype.\u00a0<em>Journal of molecular and cellular cardiology<\/em>,\u00a0<em>165<\/em>, 19\u201330. <a href=\"https:\/\/doi.org\/10.1016\/j.yjmcc.2021.12.007\">https:\/\/doi.org\/10.1016\/j.yjmcc.2021.12.007<\/a><\/li>\n<li style=\"text-align: justify\">Schreckenberg, R., Klein, J., Kutsche, H. S., Schulz, R., G\u00f6m\u00f6ri, K., Bencsik, P., Benczik, B., \u00c1gg, B., S\u00e1ghy, \u00c9., Ferdinandy, P., &amp; Schl\u00fcter, K. D. (2020). Ischaemic post-conditioning in rats: Responder and non-responder differ in transcriptome of mitochondrial proteins.\u00a0<em>Journal of cellular and molecular medicine<\/em>,\u00a0<em>24<\/em>(10), 5528\u20135541. <a href=\"https:\/\/doi.org\/10.1111\/jcmm.15209\">https:\/\/doi.org\/10.1111\/jcmm.15209<\/a><\/li>\n<li style=\"text-align: justify\">Tamargo, J., Agewall, S., Borghi, C., Ceconi, C., Cerbai, E., Dan, G. A., Ferdinandy, P., Grove, E. L., Rocca, B., Sulzgruber, P., Semb, A. G., Sossalla, S., Niessner, A., Kaski, J. C., &amp; Dobrev, D. (2023). New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.\u00a0<em>European heart journal. Cardiovascular pharmacotherapy<\/em>,\u00a0<em>9<\/em>(4), 353\u2013370. Advance online publication. <a href=\"https:\/\/doi.org\/10.1093\/ehjcvp\/pvad034\">https:\/\/doi.org\/10.1093\/ehjcvp\/pvad034<\/a><\/li>\n<li style=\"text-align: justify\">Weber, B. Y., Brenner, G. B., Kiss, B., Gergely, T. G., Sayour, N. V., Tian, H., Makkos, A., G\u00f6rbe, A., Ferdinandy, P., &amp; Giricz, Z. (2022). Rosiglitazone Does Not Show Major Hidden Cardiotoxicity in Models of Ischemia\/Reperfusion but Abolishes Ischemic Preconditioning-Induced Antiarrhythmic Effects in Rats In Vivo.\u00a0<em>Pharmaceuticals (Basel, Switzerland)<\/em>,\u00a0<em>15<\/em>(9), 1055. <a href=\"https:\/\/doi.org\/10.3390\/ph15091055\">https:\/\/doi.org\/10.3390\/ph15091055<\/a><\/li>\n<li style=\"text-align: justify\">S\u00e1ghy, \u00c9., V\u00f6r\u00f6s, I., \u00c1gg, B., Kiss, B., Koncsos, G., Varga, Z. V., G\u00f6rbe, A., Giricz, Z., Schulz, R., &amp; Ferdinandy, P. (2020). Cardiac miRNA Expression and their mRNA Targets in a Rat Model of Prediabetes.\u00a0<em>International journal of molecular sciences<\/em>,\u00a0<em>21<\/em>(6), 2128. <a href=\"https:\/\/doi.org\/10.3390\/ijms21062128\">https:\/\/doi.org\/10.3390\/ijms21062128<\/a><\/li>\n<li style=\"text-align: justify\">V\u00f6r\u00f6s, I., S\u00e1ghy, \u00c9., Poh\u00f3czky, K., Makkos, A., On\u00f3di, Z., Brenner, G. B., Baranyai, T., \u00c1gg, B., V\u00e1radi, B., Kem\u00e9ny, \u00c1., Leszek, P., G\u00f6rbe, A., Varga, Z. V., Giricz, Z., Schulz, R., Helyes, Z., &amp; Ferdinandy, P. (2021). Somatostatin and Its Receptors in Myocardial Ischemia\/Reperfusion Injury and Cardioprotection.\u00a0<em>Frontiers in pharmacology<\/em>,\u00a0<em>12<\/em>, 663655. <a href=\"https:\/\/doi.org\/10.3389\/fphar.2021.663655\">https:\/\/doi.org\/10.3389\/fphar.2021.663655<\/a><\/li>\n<li style=\"text-align: justify\">Brenner, G. B., Makkos, A., Nagy, C. T., On\u00f3di, Z., Sayour, N. V., Gergely, T. G., Kiss, B., G\u00f6rbe, A., S\u00e1ghy, \u00c9., Z\u00e1dori, Z. S., L\u00e1z\u00e1r, B., Baranyai, T., Varga, R. S., Husti, Z., Varr\u00f3, A., T\u00f3thfalusi, L., Schulz, R., Baczk\u00f3, I., Giricz, Z., &amp; Ferdinandy, P. (2020). Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia\/Reperfusion.\u00a0<em>Cells<\/em>,\u00a0<em>9<\/em>(3), 551. <a href=\"https:\/\/doi.org\/10.3390\/cells9030551\">https:\/\/doi.org\/10.3390\/cells9030551<\/a><\/li>\n<li style=\"text-align: justify\">Spannbauer, A., Traxler, D., Lukovic, D., Zlabinger, K., Winkler, J., Gugerell, A., Ferdinandy, P., Hausenloy, D. J., Pavo, N., Emmert, M. Y., Hoerstrup, S. P., Jakab, A., Gy\u00f6ngy\u00f6si, M., &amp; Riesenhuber, M. (2019). Effect of Ischemic Preconditioning and Postconditioning on Exosome-Rich Fraction microRNA Levels, in Relation with Electrophysiological Parameters and Ventricular Arrhythmia in Experimental Closed-Chest Reperfused Myocardial Infarction.\u00a0<em>International journal of molecular sciences<\/em>,\u00a0<em>20<\/em>(9), 2140. <a href=\"https:\/\/doi.org\/10.3390\/ijms20092140\">https:\/\/doi.org\/10.3390\/ijms20092140<\/a><\/li>\n<li style=\"text-align: justify\">Sayour, N. V., Brenner, G. B., Makkos, A., Kiss, B., Kov\u00e1csh\u00e1zi, C., Gergely, T. G., Aukrust, S. G., Tian, H., Zenkl, V., G\u00f6m\u00f6ri, K., Szabados, T., Bencsik, P., Heinen, A., Schulz, R., Baxter, G. F., Zuurbier, C. J., Vok\u00f3, Z., Ferdinandy, P., &amp; Giricz, Z. (2023). Cardioprotective efficacy of limb remote ischaemic preconditioning in rats: discrepancy between a meta-analysis and a three-centre in vivo study.\u00a0<em>Cardiovascular research<\/em>,\u00a0<em>119<\/em>(6), 1336\u20131351. <a href=\"https:\/\/doi.org\/10.1093\/cvr\/cvad024\">https:\/\/doi.org\/10.1093\/cvr\/cvad024<\/a><\/li>\n<li style=\"text-align: justify\">Schreckenberg, R., Wolf, A., Szabados, T., G\u00f6m\u00f6ri, K., Szab\u00f3, I. A., \u00c1goston, G., Brenner, G., Bencsik, P., Ferdinandy, P., Schulz, R., &amp; Schl\u00fcter, K. D. (2022). Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Deletion but Not Inhibition of Extracellular PCSK9 Reduces Infarct Sizes Ex Vivo but Not In Vivo.\u00a0<em>International journal of molecular sciences<\/em>,\u00a0<em>23<\/em>(12), 6512. <a href=\"https:\/\/doi.org\/10.3390\/ijms23126512\">https:\/\/doi.org\/10.3390\/ijms23126512<\/a><\/li>\n<\/ul>\n<p><strong>GY\u00d3GYSZER HAT\u00d3ANYAGOK REJTETT KARDIOTOXIKUS VAGY KARDIOPROTEKT\u00cdV HAT\u00c1S\u00c1NAK VIZSG\u00c1LATA<\/strong><\/p>\n<p>A sz\u00edvizomzat v\u00e9rell\u00e1t\u00e1s\u00e1nak akut megsz\u0171n\u00e9se az infarktus sor\u00e1n visszaford\u00edthatatlan sz\u00f6veti k\u00e1rosod\u00e1shoz \u00e9s nekr\u00f3zishoz vezet. Napjainkban a sz\u00edvizom megment\u00e9s\u00e9re a leghat\u00e9konyabb ter\u00e1pia a revaszkulariz\u00e1ci\u00f3, amelyet vagy trombol\u00edzissel, vagy perkut\u00e1n koron\u00e1ria intervenci\u00f3val (PCI), vagy koron\u00e1ria bypass (CABG) m\u0171t\u00e9ttel v\u00e9geznek. A v\u00e9r\u00e1raml\u00e1s helyre\u00e1ll\u00edt\u00e1sa azonban tov\u00e1bbi sz\u00f6vetk\u00e1rosod\u00e1shoz vezethet. Ezt a jelens\u00e9get iszk\u00e9mia\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1snak nevezz\u00fck, amely 4 m\u00f3don jelentkezhet: az infarktusos sz\u00f6vet ter\u00fclet\u00e9nek n\u00f6veked\u00e9se (l\u00e1sd az 1. \u00e1br\u00e1t), megn\u00f6vekedett m\u00e9rt\u00e9k\u0171 mikrovaszkul\u00e1ris obstrukci\u00f3, ritmuszavarok nagyobb val\u00f3sz\u00edn\u0171s\u00e9ge, cs\u00f6kkent sz\u00edvkontraktilit\u00e1s.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13805 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_1-400x168.png\" alt=\"\" width=\"400\" height=\"168\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_1-400x168.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_1-1024x430.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_1-768x323.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_1-753x316.png 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_1.png 1052w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>1. \u00e1bra: <\/em><\/strong><em>Patk\u00e1nysz\u00edv iszk\u00e9mia\/reperf\u00fazi\u00f3n \u00e1tesett, Evan-k\u00e9kkel \u00e9s TTC-vel festett szelete. A bal oldali szeleten a halv\u00e1ny ter\u00fclet az infarktusos sz\u00f6vetet jel\u00f6li. Az infarktusos sz\u00f6vet ter\u00fclete egy kardioprotekt\u00edv gy\u00f3gyszer alkalmaz\u00e1s\u00e1val cs\u00f6kkent.<\/em><\/p>\n<p>Az iszk\u00e9mia\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1s kezel\u00e9s\u00e9re m\u00e9g nem \u00e1ll rendelkez\u00e9sre enged\u00e9lyezett gy\u00f3gyszer, annak ellen\u00e9re, hogy a ter\u00fcleten nagyon intenz\u00edv kutat\u00e1s folyik, azonban jelent\u0151s sz\u00fcks\u00e9g lenne erre az infarktusos betegek akut \u00e9s hossz\u00fa t\u00e1v\u00fa t\u00fal\u00e9l\u00e9s\u00e9nek \u00e9s\/vagy \u00e9letmin\u0151s\u00e9g\u00e9nek jav\u00edt\u00e1sa \u00e9rdek\u00e9ben. A projekt\u00fcnkben a sz\u00edv iszk\u00e9mi\u00e1s\/reperf\u00fazi\u00f3s s\u00e9r\u00fcl\u00e9s\u00e9nek molekul\u00e1ris aspektusait vizsg\u00e1ljuk \u00faj farmakol\u00f3giai c\u00e9lpontok azonos\u00edt\u00e1sa \u00e9rdek\u00e9ben. Tov\u00e1bb\u00e1 tanulm\u00e1nyozzuk az egy\u00e9b betegs\u00e9gek eset\u00e9n alkalmazott hat\u00f3anyagok \u00e9s az iszk\u00e9mia\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1s m\u00e9rt\u00e9ke k\u00f6z\u00f6tti k\u00f6lcs\u00f6nhat\u00e1st (a gy\u00f3gyszerek rejtett kardiotoxicit\u00e1sa), valamint a metabolikus betegs\u00e9gek hat\u00e1s\u00e1t a kardioprotekt\u00edv beavatkoz\u00e1sokra \u00e9s kezel\u00e9sekre.<\/p>\n<p><strong>1. A gy\u00f3gyszerek hat\u00e1sa az iszk\u00e9mia\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1sra kis\u00e1llatmodellekben: a rejtett kardiotoxicit\u00e1s jelent\u0151s\u00e9ge<\/strong><\/p>\n<p>\nProjektvezet\u0151k: Prof. Dr. Ferdinandy P\u00e9ter, Dr. G\u00f6rbe Anik\u00f3, Dr. Giricz Zolt\u00e1n<\/p>\n<table style=\"border-collapse: collapse;width: 100%\">\n<tbody>\n<tr>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13291\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-scaled.jpg\" alt=\"\" width=\"210\" height=\"315\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-scaled.jpg 1707w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-267x400.jpg 267w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-683x1024.jpg 683w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-768x1152.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-1024x1536.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-1365x2048.jpg 1365w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-753x1130.jpg 753w\" sizes=\"auto, (max-width: 210px) 100vw, 210px\" \/><\/td>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13292\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Gorbe-Aniko_SOTE_web004.jpg\" alt=\"\" width=\"210\" height=\"315\" \/><\/td>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13806\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GZ.jpg\" alt=\"\" width=\"210\" height=\"315\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>\nProjekt felel\u0151s\u00f6k: Nagy Regina, Bennet Weber, Dr. Gergely Tam\u00e1s<\/p>\n<table style=\"border-collapse: collapse;width: 100%\">\n<tbody>\n<tr>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13811\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/NagyRegina.jpeg\" alt=\"\" width=\"190\" height=\"232\" \/><\/td>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13807\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/WeberBennet.jpg\" alt=\"\" width=\"210\" height=\"283\" \/><\/td>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13809\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas.jpeg\" alt=\"\" width=\"210\" height=\"315\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas.jpeg 1365w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-267x400.jpeg 267w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-683x1024.jpeg 683w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-768x1152.jpeg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-1024x1536.jpeg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-753x1130.jpeg 753w\" sizes=\"auto, (max-width: 210px) 100vw, 210px\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify\"><strong>A nem v\u00e1rt sz\u00edvre gyakorolt mell\u00e9khat\u00e1sok<\/strong> a klinikai vizsg\u00e1latok megszak\u00edt\u00e1s\u00e1nak \u00e9s a gy\u00f3gyszerek forgalomb\u00f3l val\u00f3 kivon\u00e1s\u00e1nak legf\u0151bb okai (l\u00e1sd a 2. \u00e1br\u00e1t). A 90-es \u00e9vek k\u00f6zep\u00e9n v\u00e9gzett els\u0151 megfigyel\u00e9sek \u00f3ta j\u00f3l ismert, hogy a kardiovaszkul\u00e1ris kock\u00e1zati t\u00e9nyez\u0151k \u00e9s t\u00e1rsbetegs\u00e9gek (mint p\u00e9ld\u00e1ul az \u00f6reged\u00e9s, a hyperlipidaemia \u00e9s a cukorbetegs\u00e9g), valamint az ezekre alkalmazott gy\u00f3gyszerek (pl. nitr\u00e1t-tolerancia, adenozin-trifoszf\u00e1t-f\u00fcgg\u0151 k\u00e1liumg\u00e1tl\u00f3 antidiabetikus gy\u00f3gyszerek, sztatinok stb.) befoly\u00e1solhatj\u00e1k a sz\u00edv iszk\u00e9miat\u0171r\u00e9s\u00e9t \u00e9s az endog\u00e9n kardioprotekt\u00edv jel\u00e1tviteli utakat. Ezen fel\u00fcl gy\u00f3gyszerek hat\u00f3anyagai a beteg \u00e9s kezel\u00e9s alatt \u00e1ll\u00f3 sz\u00edvre olyan nemk\u00edv\u00e1natos hat\u00e1sokat gyakorolhatnak, amelyek az eg\u00e9szs\u00e9ges sz\u00edvizomban rejtve maradnak. <strong>A rejtett kardiotoxikus hat\u00e1sok<\/strong> h\u00e1tter\u00e9ben (i) az iszk\u00e9mia\/reperf\u00fazi\u00f3s s\u00e9r\u00fcl\u00e9s \u00e9s\/vagy a rizik\u00f3faktorok jelenl\u00e9te k\u00f6vetkezt\u00e9ben kialakul\u00f3 sz\u00f6vetk\u00e1ros\u00edt\u00f3 jel\u00e1tvitel \u00fatvonalak gy\u00f3gyszerek \u00e1ltal induk\u00e1lt feler\u0151s\u00f6d\u00e9se \u00e9s\/vagy (ii) a kardioprotekt\u00edv t\u00fal\u00e9l\u00e9si jel\u00e1tviteli utak g\u00e1tl\u00e1sa \u00e1llhat, amelyek iszk\u00e9mia okozta sejthal\u00e1lhoz \u00e9s\/vagy pro-aritmi\u00e1s hat\u00e1sokhoz vezethetnek. \u00cdgy hat\u00e1roztuk meg a &#8222;rejtett kardiotoxicit\u00e1s&#8221; \u00faj fogalm\u00e1t, amely egy gy\u00f3gyszer kardiotoxicit\u00e1s\u00e1t jelenti, amely csak a beteg sz\u00edvben jelentkezik, pl. iszk\u00e9mi\u00e1s\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1ssal \u00e9s\/vagy a f\u0151bb t\u00e1rsbetegs\u00e9gek jelenl\u00e9t\u00e9ben. A rejtett kardiotoxicit\u00e1s mechanizmus\u00e1r\u00f3l keveset tudunk, r\u00e1ad\u00e1sul nem mutathat\u00f3 ki a rutinszer\u0171en alkalmazott, preklinikai, eg\u00e9szs\u00e9ges \u00e1llatokon vagy sz\u00f6veteken v\u00e9gzett sz\u00edvbiztons\u00e1gi vizsg\u00e1lati m\u00f3dszerekkel. Ez\u00e9rt c\u00e9lunk a sz\u00edvbetegs\u00e9gek (k\u00fcl\u00f6n\u00f6sen a sz\u00edvizom iszk\u00e9mi\u00e1ja\/reperf\u00fazi\u00f3ja \u00e9s az iszk\u00e9mi\u00e1s kondicion\u00e1l\u00e1s) kombin\u00e1lt k\u00eds\u00e9rleti in vivo \u00e9s in vitro modelljeit tartalmaz\u00f3 \u00faj sz\u00edvbiztons\u00e1gi vizsg\u00e1lati platform kifejleszt\u00e9se a f\u0151bb sz\u00edv- \u00e9s \u00e9rrendszeri t\u00e1rsbetegs\u00e9gek \u00e9s\/vagy t\u00e1rskezel\u00e9sek jelenl\u00e9t\u00e9ben \u00e9s hi\u00e1ny\u00e1ban (Ferdinandy et al, European heart <br \/>\njournal, 2018).<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-13813 size-full aligncenter\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_2.jpg\" alt=\"\" width=\"942\" height=\"545\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_2.jpg 942w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_2-400x231.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_2-768x444.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_2-753x436.jpg 753w\" sizes=\"auto, (max-width: 942px) 100vw, 942px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>2. \u00e1bra:<\/em><\/strong><em> A gy\u00f3gyszerfejleszt\u00e9s k\u00f6lts\u00e9gei annak k\u00fcl\u00f6nb\u00f6z\u0151 f\u00e1zisaiban. (M\u00f3dos\u00edtva: Ferdinandy et al. Eur Heart J, 2018)<\/em><\/p>\n<p><strong>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/strong><\/p>\n<ul>\n<li>irodalomkutat\u00e1si m\u00f3dszerek,<\/li>\n<li>in vivo patk\u00e1nyvizsg\u00e1latok tervez\u00e9se,<\/li>\n<li>kis\u00e1llatok kezel\u00e9se,<\/li>\n<li>sz\u00edvm\u0171t\u00e9tek elv\u00e9gz\u00e9se patk\u00e1nyokon,<\/li>\n<li>kvantitat\u00edv PCR \u00e9s Western blotok elv\u00e9gz\u00e9se,<\/li>\n<li>az adatok ki\u00e9rt\u00e9kel\u00e9se \u00e9s bemutat\u00e1sa.<\/li>\n<\/ul>\n<p><strong>F\u0151bb publik\u00e1ci\u00f3ink a t\u00e9m\u00e1ban:<\/strong><\/p>\n<p>Ferdinandy, P. et al. Definition of hidden drug cardiotoxicity: paradigm change in cardiac safety testing and its clinical implications. Eur Heart J, 2018. (link)<\/p>\n<p>Ferdinandy, P., et al. Interaction of risk factors, comorbidities, and comedications with ischemia\/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev, 2014. 66(4): p. 1142-74. (link)<\/p>\n<p>Brenner GB., et al. Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia\/Reperfusion. Cells. 2020 Feb 26;9(3):551. (link)<\/p>\n<p>Weber BY, et al. Rosiglitazone Does Not Show Major Hidden Cardiotoxicity in Models of Ischemia\/Reperfusion but Abolishes Ischemic Preconditioning-Induced Antiarrhythmic Effects in Rats In Vivo. Pharmaceuticals (Basel). 2022 Aug 26;15(9):1055. (link)<\/p>\n<p>Gergely TG, et al. Effects of Bempedoic Acid in Acute Myocardial Infarction in Rats: No Cardioprotection and No Hidden Cardiotoxicity. Int J Mol Sci. 2023 Jan 13;24(2):1585. (link)<\/p>\n<p><strong>2. Gy\u00f3gyszerek hat\u00e1sa az iszk\u00e9mia\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1sra in vitro sejtkult\u00fara modellekben<\/strong><\/p>\n<p>Projektvezet\u0151: Dr. G\u00f6rbe Anik\u00f3<\/p>\n<p>Projektfelel\u0151s\u00f6k: Bennet Weber, Nagy Regina, Szab\u00f3 M\u00e1rta<\/p>\n<p style=\"text-align: justify\">Kor\u00e1bban bemutattuk, hogy a gy\u00f3gyszerjel\u00f6ltek biztons\u00e1goss\u00e1g\u00e1t \u00e9s rejtett kardiotoxikus hat\u00e1s\u00e1t in vitro sejtkult\u00fara-modellekben lehet vizsg\u00e1lni, amelyekben az iszk\u00e9mia\/reperf\u00fazi\u00f3s (I\/R) k\u00e1rosod\u00e1s \u00e9s a t\u00e1rsbetegs\u00e9gek szimul\u00e1ci\u00f3ja megval\u00f3s\u00edthat\u00f3. A sz\u00edvsejtvonalak \u00e9s a primer izol\u00e1lt sz\u00edvsejtek nagy \u00e1tereszt\u0151k\u00e9pess\u00e9g\u0171 gy\u00f3gyszer-sz\u0171r\u00e9sre haszn\u00e1lhat\u00f3k, \u00e9s alkalmaz\u00e1suk el\u0151ny\u00f6s a gy\u00f3gyszerek sz\u00edvsejtekregyakorolt k\u00f6zvetlen hat\u00e1sainak felm\u00e9r\u00e9s\u00e9re. Projekt\u00fcnkben olyan szereket tesztel\u00fcnk, amelyek csak olyan t\u00e1rsbetegs\u00e9gek, mint a hiperkoleszterin\u00e9mia vagy az I\/R k\u00e1rosod\u00e1s jelenl\u00e9t\u00e9ben mutathatnak k\u00f6zvetlen kardiotoxikus hat\u00e1st a sz\u00edvsejtekre.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13814 size-full\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_csoportkep_1.png\" alt=\"\" width=\"556\" height=\"612\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_csoportkep_1.png 556w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_csoportkep_1-363x400.png 363w\" sizes=\"auto, (max-width: 556px) 100vw, 556px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>3. \u00e1bra: <\/em><\/strong><em>Sejtkezel\u00e9si munk\u00e1latok a sejtlaborban<strong>.<\/strong><\/em><\/p>\n<p><strong>Tanul\u00e1si lehet\u0151s\u00e9gek:<\/strong><\/p>\n<ul>\n<li>irodalomkutat\u00e1si m\u00f3dszerek,<\/li>\n<li>in vitro sejtkult\u00fara alap\u00fa k\u00eds\u00e9rletek tervez\u00e9se,<\/li>\n<li>primer sz\u00edvsejtek izol\u00e1l\u00e1sa,<\/li>\n<li>sejtkult\u00far\u00e1k fenntart\u00e1sa,<\/li>\n<li>a sejtek kezel\u00e9se k\u00fcl\u00f6nb\u00f6z\u0151 hat\u00f3anyagokkal,<\/li>\n<li>sejt\u00e9letk\u00e9pess\u00e9gi vizsg\u00e1latok elv\u00e9gz\u00e9se,<\/li>\n<li>az adatok ki\u00e9rt\u00e9kel\u00e9se \u00e9s bemutat\u00e1sa.<\/li>\n<\/ul>\n<p><strong>F\u0151bb publik\u00e1ci\u00f3ink a t\u00e9m\u00e1ban:<\/strong><\/p>\n<p>Brenner GB., et al. Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia\/Reperfusion. Cells. 2020 Feb 26;9(3):551. (link)<\/p>\n<p>Weber BY, et al. Rosiglitazone Does Not Show Major Hidden Cardiotoxicity in Models of Ischemia\/Reperfusion but Abolishes Ischemic Preconditioning-Induced Antiarrhythmic Effects in Rats In Vivo. Pharmaceuticals (Basel). 2022 Aug 26;15(9):1055. (link)<\/p>\n<p><strong>3. A sz\u00edvre gyakorolt rejtett hat\u00e1st mutat\u00f3 gy\u00f3gyszerek \u00e1ltal kiv\u00e1ltott transzkriptomikai v\u00e1ltoz\u00e1sok vizsg\u00e1lata<\/strong><\/p>\n<p>Projektvezet\u0151: Dr. G\u00f6rbe Anik\u00f3<\/p>\n<p>Projektfelel\u0151s\u00f6k: Bennet Weber, Nagy Regina<\/p>\n<p>Az endog\u00e9n kardioprotekt\u00edv folyamatok \u00e9s molekul\u00e1k j\u00f3l ismertek a miokardi\u00e1lis iszk\u00e9mia\/reperf\u00fazi\u00f3s (I\/R) k\u00e1rosod\u00e1s cs\u00f6kkent\u00e9s\u00e9ben, amelyek hat\u00e1sai gyakran elvesznek a klinikai transzl\u00e1ci\u00f3 sor\u00e1n, k\u00fcl\u00f6n\u00f6sen t\u00e1rsbetegs\u00e9gek jelenl\u00e9t\u00e9ben. Ezenk\u00edv\u00fcl sz\u00e1mos gy\u00f3gyszer miokardi\u00e1lis mell\u00e9khat\u00e1sokat\/rejtett kardiotoxicit\u00e1st mutathat, amelyre a jelenlegi gy\u00f3gyszerfejleszt\u00e9si gyakorlatban nem der\u00fcl f\u00e9ny. A rejtett kardiotoxicit\u00e1sban a g\u00e9nexpresszi\u00f3 v\u00e1ltoz\u00e1sai is szerepet j\u00e1tszhatnak, de ez jelenleg egy nem teljesen felt\u00e1rt ter\u00fclet, \u00e9s kutat\u00e1suk a biztons\u00e1gi farmakol\u00f3gia \u00faj aspektusa. Projekt\u00fcnkben a sz\u00edvizom mikroRNS \u00e9s mRNS expresszi\u00f3s profilj\u00e1t k\u00edv\u00e1njuk vizsg\u00e1lni egy bizony\u00edtottan kardiotoxikus gy\u00f3gyszerrel kezelt patk\u00e1ny akut I\/R modellben, amely sz\u00e1mos differenci\u00e1lisan expressz\u00e1l\u00f3d\u00f3 c\u00e9lmolekula felfedez\u00e9s\u00e9t teszi lehet\u0151v\u00e9. A felt\u00e1rt expresszi\u00f3s v\u00e1ltoz\u00e1sok alapj\u00e1n azonos\u00edthat\u00f3k a mell\u00e9khat\u00e1sok\u00e9rt felel\u0151s mechanizmusok is. A kiv\u00e1lasztott mikroRNS-ek potenci\u00e1lis toxikus vagy v\u00e9d\u0151 hat\u00e1sa valid\u00e1lhat\u00f3 I\/R rendszerben hum\u00e1n sz\u00edvizomsejt modellben is. A bioinformatikai elemz\u00e9s sor\u00e1n el\u0151re jelzett molekul\u00e1ris c\u00e9lpontok transzkript- \u00e9s feh\u00e9rjeszinten is valid\u00e1lhat\u00f3k.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13815\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_3.jpg\" alt=\"\" width=\"701\" height=\"708\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_3.jpg 701w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_3-396x400.jpg 396w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/hiddentox_3-150x150.jpg 150w\" sizes=\"auto, (max-width: 701px) 100vw, 701px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>4. \u00e1bra: <\/em><\/strong><em>Downregul\u00e1lt (z\u00f6ld) \u00e9s upregul\u00e1lt (piros) miRNS-ek interakci\u00f3s h\u00e1l\u00f3zata \u00e9s kardi\u00e1lis miRNS c\u00e9lpont predikci\u00f3 anal\u00edzise patk\u00e1ny prediab\u00e9tesz modellben.<\/em><\/p>\n<p><strong>Tanul\u00e1si lehet\u0151s\u00e9gek<\/strong>:<\/p>\n<ul>\n<li>irodalomkutat\u00e1si m\u00f3dszerek,<\/li>\n<li>in vitro sejtkult\u00fara alap\u00fa k\u00eds\u00e9rletek tervez\u00e9se,<\/li>\n<li>sejtkult\u00far\u00e1k fenntart\u00e1sa,<\/li>\n<li>a sejtek kezel\u00e9se k\u00fcl\u00f6nb\u00f6z\u0151 hat\u00f3anyagokkal,<\/li>\n<li>miRNS c\u00e9lpont keres\u00e9s \u00e9s valid\u00e1l\u00e1s kvantitat\u00edv PCR-rel \u00e9s Western blottal,<\/li>\n<li>az adatok ki\u00e9rt\u00e9kel\u00e9se \u00e9s bemutat\u00e1sa.<\/li>\n<\/ul>\n<p><strong>F\u0151bb publik\u00e1ci\u00f3ink a t\u00e9m\u00e1ban:<\/strong><\/p>\n<p>S\u00e1ghy \u00c9, et al. Cardiac miRNA Expression and their mRNA Targets in a Rat Model of Prediabetes. Int J Mol Sci. 2020 Mar 20;21(6):2128. (link)<\/p>\n<p><strong>A SZ\u00cdV- \u00c9S \u00c9RRENDSZERI BETEGS\u00c9GEK METABOLIKUS T\u00c1RSBETEGS\u00c9GEI<\/strong><\/p>\n<p><strong>1. A metabolikus betegs\u00e9gek hat\u00e1sa az iszk\u00e9mia\/reperf\u00fazi\u00f3s k\u00e1rosod\u00e1s elleni kardioprotekt\u00edv beavatkoz\u00e1sokra \u00e9s kezel\u00e9sekre<\/strong><\/p>\n<p>Projektvezet\u0151k: Prof. Dr. Ferdinandy P\u00e9ter, Dr. G\u00f6rbe Anik\u00f3<\/p>\n<table style=\"border-collapse: collapse;width: 100%\">\n<tbody>\n<tr>\n<td style=\"width: 50%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13291\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-scaled.jpg\" alt=\"\" width=\"210\" height=\"315\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-scaled.jpg 1707w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-267x400.jpg 267w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-683x1024.jpg 683w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-768x1152.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-1024x1536.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-1365x2048.jpg 1365w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Ferdinandy_Peter-753x1130.jpg 753w\" sizes=\"auto, (max-width: 210px) 100vw, 210px\" \/><\/td>\n<td style=\"width: 50%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13292\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/03\/Gorbe-Aniko_SOTE_web004.jpg\" alt=\"\" width=\"210\" height=\"315\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Projektfelel\u0151s\u00f6k: Dr. Makkos Andr\u00e1s, Dr. Gergely Tam\u00e1s, Nagy Regina<\/p>\n<table style=\"border-collapse: collapse;width: 100%\">\n<tbody>\n<tr>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-12855\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2023\/11\/7-1.png\" alt=\"\" width=\"231\" height=\"347\" \/><\/td>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13809\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas.jpeg\" alt=\"\" width=\"210\" height=\"315\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas.jpeg 1365w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-267x400.jpeg 267w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-683x1024.jpeg 683w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-768x1152.jpeg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-1024x1536.jpeg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/GergelyTamas-753x1130.jpeg 753w\" sizes=\"auto, (max-width: 210px) 100vw, 210px\" \/><\/td>\n<td style=\"width: 33.3333%\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13811\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/NagyRegina.jpeg\" alt=\"\" width=\"190\" height=\"232\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify\">Az anyagcserezavarok, mint p\u00e9ld\u00e1ul az elh\u00edz\u00e1s vagy a cukorbetegs\u00e9g, a sz\u00edv- \u00e9s \u00e9rrendszeri betegs\u00e9gek f\u0151 kock\u00e1zati t\u00e9nyez\u0151i. Az eg\u00e9szs\u00e9ges sz\u00edv k\u00e9pes alkalmazkodni az iszk\u00e9mi\u00e1s k\u00e1rosod\u00e1s\u00e1hoz bizonyos m\u00e9rt\u00e9kben (pl. sz\u00edvinfarktus sor\u00e1n), de az anyagcsere-betegs\u00e9gek, mint p\u00e9ld\u00e1ul a hiperkoleszterin\u00e9mia, negat\u00edvan befoly\u00e1solj\u00e1k a sz\u00edvnek ezt az <strong>iszk\u00e9miatoleranci\u00e1j\u00e1t<\/strong>, \u00e9s n\u00f6velhetik az iszk\u00e9mia\/reperf\u00fazi\u00f3 \u00e1ltal \u00e9rintett k\u00e1rosod\u00e1s m\u00e9rt\u00e9k\u00e9t. A <strong>metabolikus t\u00e1rsbetegs\u00e9gek<\/strong> miatt a sz\u00edvizomban bek\u00f6vetkez\u0151 v\u00e1ltoz\u00e1sok mechanizmusa nem teljesen ismert, r\u00e9szletesebb megismer\u00e9s\u00fck lehet\u0151v\u00e9 tenn\u00e9 \u00faj kardioprotekt\u00edv ter\u00e1pi\u00e1k kifejleszt\u00e9s\u00e9t, ami az iszk\u00e9mi\u00e1s sz\u00edvbetegs\u00e9gek jobb progn\u00f3zis\u00e1hoz vezetne. Tansz\u00e9k\u00fcnk\u00f6n a hiperkoleszterin\u00e9mia modelljek\u00e9nt a <strong>magas zs\u00edrtartalm\u00fa di\u00e9t\u00e1val t\u00e1pl\u00e1lt, altatott patk\u00e1nyokon<\/strong> infarktust okozunk a korszer\u0171 kis\u00e1llat-m\u0171t\u00e9ti l\u00e9tes\u00edtm\u00e9ny\u00fcnkben (1. \u00e1bra) egy olyan seb\u00e9szeti elj\u00e1r\u00e1ssal, ahol a bal oldali lesz\u00e1ll\u00f3 koszor\u00faeret \u00f6lt\u00e9ssel 30-45 percre elz\u00e1rjuk, majd felszabad\u00edtjuk. A m\u0171t\u00e9t alatt monitorozzuk a vit\u00e1lis param\u00e9tereket (pl. v\u00e9rnyom\u00e1s, EKG, h\u0151m\u00e9rs\u00e9klet, l\u00e9gz\u00e9s; 2. \u00e1bra). Egyetemi hallgat\u00f3ink megtanulhatj\u00e1k a m\u0171t\u00e9ti technik\u00e1kat, \u00e9s akt\u00edvan r\u00e9szt vehetnek a folyamatban l\u00e9v\u0151 vizsg\u00e1latainkban.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13818\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_1.jpg\" alt=\"\" width=\"1196\" height=\"672\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_1.jpg 1196w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_1-400x225.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_1-1024x575.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_1-768x432.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_1-753x423.jpg 753w\" sizes=\"auto, (max-width: 1196px) 100vw, 1196px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>1. \u00e1bra: <\/em><\/strong><em>Kis\u00e1llat m\u0171t\u00e9ti eszk\u00f6z\u00f6k a Farmakol\u00f3giai Int\u00e9zetben.<\/em><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13817\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_2.jpg\" alt=\"\" width=\"510\" height=\"141\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_2.jpg 510w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_2-400x111.jpg 400w\" sizes=\"auto, (max-width: 510px) 100vw, 510px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>2. \u00e1bra:<\/em><\/strong><em> Vit\u00e1lis param\u00e9terek az in vivo iszk\u00e9mi\u00e1s\/reperf\u00fazi\u00f3s m\u0171t\u00e9t sor\u00e1n. Fentr\u0151l: testh\u0151m\u00e9rs\u00e9klet, v\u00e9rnyom\u00e1s a k\u00f6zponti art\u00e9ri\u00e1ban, EKG.<\/em><\/p>\n<p><strong>Tanul\u00e1si lehet\u0151s\u00e9gek<\/strong>:<\/p>\n<ul>\n<li>irodalomkutat\u00e1si m\u00f3dszerek,<\/li>\n<li>in vivo patk\u00e1nyvizsg\u00e1latok tervez\u00e9se<\/li>\n<li>anyagcsere-betegs\u00e9gmodellekkel val\u00f3 munka patk\u00e1nyokon,<\/li>\n<li>kis\u00e1llatok kezel\u00e9se,<\/li>\n<li>sz\u00edvm\u0171t\u00e9tek elv\u00e9gz\u00e9se patk\u00e1nyokon,<\/li>\n<li>kvantitat\u00edv PCR \u00e9s Western blotok elv\u00e9gz\u00e9se,<\/li>\n<li>az adatok ki\u00e9rt\u00e9kel\u00e9se \u00e9s bemutat\u00e1sa.<\/li>\n<\/ul>\n<p><strong>F\u0151bb publik\u00e1ci\u00f3ink a t\u00e9m\u00e1ban:<\/strong><\/p>\n<p>Andreadou I, Daiber A, Baxter GF, Brizzi MF, Di Lisa F, Kaludercic N, Lazou A, Varga ZV, Zuurbier CJ, Schulz R, Ferdinandy P. Influence of cardiometabolic comorbidities on myocardial function, infarction, and cardioprotection: Role of cardiac redox signaling. Free Radic Biol Med. 2021 Apr;166:33-52.<\/p>\n<p>Andreadou I, Tsoumani M, Vilahur G, Ikonomidis I, Badimon L, Varga ZV, Ferdinandy P, Schulz R. PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation. Front Physiol. 2020 Nov 12;11:602497. doi: 10.3389\/fphys.2020.602497. PMID: 33262707; PMCID: PMC7688516.<\/p>\n<p>Andreadou I, Schulz R, Badimon L, Adameov\u00e1 A, Kleinbongard P, Lecour S, Nikolaou PE, Falc\u00e3o-Pires I, Vilahur G, Woudberg N, Heusch G, Ferdinandy P. Hyperlipidaemia and cardioprotection: Animal models for translational studies. Br J Pharmacol. 2020 Dec;177(23):5287-5311<\/p>\n<p>Andreadou I, Iliodromitis EK, Lazou A, G\u00f6rbe A, Giricz Z, Schulz R, Ferdinandy P. Effect of hypercholesterolemia on myocardial function, ischemia-reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol. 2017 Jun; 174 (12):1555-1569. (link)<\/p>\n<p>Pavo N, Lukovic D, Zlabinger K, Zimba A, Lorant D, Goliasch G, Winkler J, Pils D, Auer K, Jan Ankersmit H, Giricz Z, Baranyai T, S\u00e1rk\u00f6zy M, Jakab A, Garamv\u00f6lgyi R, Emmert MY, Hoerstrup SP, Hausenloy DJ, Ferdinandy P, Maurer G, Gy\u00f6ngy\u00f6si M. Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling. Sci Rep.2017 Mar 7;7:43958.. (link)<\/p>\n<p>Nagy CT, Koncsos G, Varga ZV, Baranyai T, Tuza S, Kassai F, Ernyey AJ, Gyerty\u00e1n I, Kir\u00e1ly K, Ol\u00e1h A, Radovits T, Merkely B, Bukosza N, Sz\u00e9n\u00e1si G, Hamar P, Math\u00e9 D, Szigeti K, Pelyhe C, Jelemensk\u00fd M, On\u00f3di Z, Helyes Z, Schulz R, Giricz Z, Ferdinandy. Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats. Br J Pharmacol. 2018 Sep;175(18):3713-3726. (link)<\/p>\n<p>Koncsos G, Varga ZV, Baranyai T, Boengler K, Rohrbach S, Li L, Schl\u00fcter KD, Schreckenberg R, Radovits T, Ol\u00e1h A, M\u00e1ty\u00e1s C, Lux \u00c1, Al-Khrasani M, Koml\u00f3di T, Bukosza N, M\u00e1th\u00e9 D, Deres L, Bartekov\u00e1 M, Rajt\u00edk T, Adameov\u00e1 A, Szigeti K, Hamar P, Helyes Z, Tretter L, Pacher P, Merkely B, Giricz Z, Schulz R, Ferdinandy P. Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress. Am J Physiol Heart Circ Physiol. 2016 Oct 1;311(4):H927-H943. (link)<\/p>\n<p>Baranyai, T., et al., Acute hyperglycemia abolishes cardioprotection by remote ischemic perconditioning. Cardiovasc Diabetol, 2015. 14: p. 151.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-13819 aligncenter\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3.jpg\" alt=\"\" width=\"1247\" height=\"831\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3.jpg 1247w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3-400x267.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3-1024x682.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3-768x512.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3-753x502.jpg 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_3-203x135.jpg 203w\" sizes=\"auto, (max-width: 1247px) 100vw, 1247px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>3. \u00e1bra<\/em><\/strong><em>: Sz\u00edv ultrahangvizsg\u00e1lat \u00e9s sz\u00edvnyom\u00e1s-t\u00e9rfogat elemz\u00e9s a kis\u00e1llat m\u0171t\u00e9ti eszk\u00f6z\u00f6kkel.<\/em><\/p>\n<p><em>\u00a0<\/em><\/p>\n<p><strong>2. A hiperkoleszterin\u00e9mia hat\u00e1sa a makrof\u00e1gok inflammasz\u00f3ma-aktiv\u00e1ci\u00f3j\u00e1ra<\/strong><\/p>\n<p>Projektvezet\u0151k: Dr. G\u00f6rbe Anik\u00f3, Dr. Varga Zolt\u00e1n<\/p>\n<p>Projektfelel\u0151s: Nagy Regina<\/p>\n<p style=\"text-align: justify\">A <strong>hiperkoleszterin\u00e9mia<\/strong> koleszterinfelhalmoz\u00f3d\u00e1st induk\u00e1l az immunsejtekben, p\u00e9ld\u00e1ul a makrof\u00e1gokban is, ami a Toll-szer\u0171 receptor (TLR) jel\u00e1tvitel \u00e9s <strong>az inflammasz\u00f3ma aktiv\u00e1ci\u00f3ja<\/strong> r\u00e9v\u00e9n el\u0151seg\u00edti a gyullad\u00e1s kialakul\u00e1s\u00e1t. Az intracellul\u00e1ris koleszterinfelhalmoz\u00f3d\u00e1s \u00e9s az ebb\u0151l k\u00f6vetkez\u0151 gyullad\u00e1sos v\u00e1lasz val\u00f3sz\u00edn\u0171leg el\u0151ny\u00f6s a fert\u0151z\u00e9sekre adott v\u00e1laszreakci\u00f3ban, azonban s\u00falyosb\u00edtja a kr\u00f3nikus gyullad\u00e1ssal j\u00e1r\u00f3 betegs\u00e9geket, p\u00e9ld\u00e1ul az ateroszkler\u00f3zist. A gyullad\u00e1s sz\u00e1mos kardiovaszkul\u00e1ris betegs\u00e9g kialakul\u00e1s\u00e1ban, progresszi\u00f3j\u00e1ban \u00e9s megjelen\u00e9s\u00e9ben is kritikus szerepet j\u00e1tszik. Az inflammasz\u00f3m\u00e1k k\u00f6zvetlen g\u00e1tl\u00e1sa, a proinflammatorikus citokinek sziszt\u00e9m\u00e1s g\u00e1tl\u00e1sa n\u00e9lk\u00fcl, hat\u00e9kony gyullad\u00e1scs\u00f6kkent\u0151 kezel\u00e9s lehet. \u00cdgy az inflammasz\u00f3ma-aktiv\u00e1ci\u00f3 m\u00f6g\u00f6tt \u00e1ll\u00f3 molekul\u00e1ris mechanizmusok felt\u00e1r\u00e1sa \u00faj potenci\u00e1lis gy\u00f3gyszerc\u00e9lpontok felfedez\u00e9s\u00e9hez vezethet a hiperkoleszterin\u00e9mi\u00e1s kardiovaszkul\u00e1ris t\u00e1rsbetegs\u00e9gek eset\u00e9ben. Projekt\u00fcnkben azt vizsg\u00e1ljuk, hogy az <strong>in vitro<\/strong> hiperkoleszterin\u00e9mi\u00e1s kezel\u00e9s milyen hat\u00e1ssal van a hum\u00e1n monocit\u00e1k\/makrof\u00e1gok gyullad\u00e1sos mechanizmusaira.<\/p>\n<p><strong>Tanul\u00e1si lehet\u0151s\u00e9gek<\/strong>:<\/p>\n<ul>\n<li>irodalomkutat\u00e1si m\u00f3dszerek,<\/li>\n<li>metabolikus betegs\u00e9gmodellekkel val\u00f3 munka sejtkult\u00far\u00e1kon,<\/li>\n<li>in vitro sejtkult\u00far\u00e1s k\u00eds\u00e9rletek tervez\u00e9se,<\/li>\n<li>sejtkult\u00far\u00e1k fenntart\u00e1sa,<\/li>\n<li>sejtek kezel\u00e9se gy\u00f3gyszerhat\u00f3anyagokkal,<\/li>\n<li>kvantitat\u00edv PCR \u00e9s Western blotok kivitelez\u00e9se,<\/li>\n<li>\naz adatok ki\u00e9rt\u00e9kel\u00e9se \u00e9s bemutat\u00e1sa<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-13822 size-medium\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_4-335x400.png\" alt=\"\" width=\"335\" height=\"400\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_4-335x400.png 335w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_4.png 509w\" sizes=\"auto, (max-width: 335px) 100vw, 335px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>4. \u00e1bra<\/em><\/strong><em>: Az NLRP3 inflammasz\u00f3ma komplex.<\/em><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-13821\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_5.png\" alt=\"\" width=\"719\" height=\"313\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_5.png 719w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_5-400x174.png 400w\" sizes=\"auto, (max-width: 719px) 100vw, 719px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>5. \u00e1bra<\/em><\/strong><em>: Fluoreszcens felv\u00e9telek THP1-ASC-GFP monocit\u00e1kr\u00f3l flagellinnel val\u00f3 inflammasz\u00f3ma-stimul\u00e1ci\u00f3t k\u00f6vet\u0151en.<\/em><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-13820 aligncenter\" src=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_6.png\" alt=\"\" width=\"1206\" height=\"293\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_6.png 1206w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_6-400x97.png 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_6-1024x249.png 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_6-768x187.png 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/07\/metab_6-753x183.png 753w\" sizes=\"auto, (max-width: 1206px) 100vw, 1206px\" \/><\/p>\n<p style=\"text-align: center\"><strong><em>6. \u00e1bra<\/em><\/strong><em>: Fluoreszcens felv\u00e9telek THP1-ASC-GFP sejtek koleszterinfelv\u00e9tel\u00e9r\u0151l k\u00fcl\u00f6nb\u00f6z\u0151 koncentr\u00e1ci\u00f3j\u00fa hiperkoleszterin\u00e9mi\u00e1s adal\u00e9kokkal t\u00f6rt\u00e9n\u0151 kezel\u00e9st k\u00f6vet\u0151en.<\/em><\/p>\n\n<\/div><h2 class=\"tabtitle\">Tagok<\/h2>\n<div class=\"tabcontent\">\n\n<p><strong>Munkacsoport vezet\u0151<\/strong>:<\/p>\n<p><a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=11539\">Dr. G\u00f6rbe Anik\u00f3<\/a>, PhD<\/p>\n<p><strong>Kutat\u00f3k \/ posztdoktorok<\/strong>:<\/p>\n<p><a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=21659\">Somogyi Orsolya<\/a><br \/>\n<a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=11976\">Dr. Makkos Andr\u00e1s<\/a>, PhD<br \/>\n<a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=11975\">Dr. S\u00e1ghy \u00c9va<\/a>, PhD<\/p>\n<p><strong>PhD hallgat\u00f3k<\/strong>:<\/p>\n<p><a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=14236\">Nagy Regina<\/a><br \/>\n<a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=20521\">Szab\u00f3 M\u00e1rta<\/a><br \/>\n<a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=21947\">Dr. Weber Bennet<\/a><\/p>\n<p><strong>Asszisztensek<\/strong>:<\/p>\n<p><a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=11044\">Petrovics T\u00fcnde<\/a><br \/>\n<a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=14235\">Horv\u00e1th L\u00e1szl\u00f3<\/a>, PhD<br \/>\n<a href=\"https:\/\/semmelweis.hu\/telefonkonyv\/?emp_id=22985\">Szalai Orsolya<\/a><br \/>\nReyad Ali<\/p>\n\n<\/div><h2 class=\"tabtitle\">Gal\u00e9ria<\/h2>\n<div class=\"tabcontent\">\n\n\r\n        [slb_exclude]\r\n        <div class=\"row galeria-wrapper mx-0 h-auto\">\r\n            <div class=\"col-9 pl-0 pr-2\">\r\n            <span class=\"gallery-item frame\">\r\n\t\t\t\t<div class=\"galeria-left-img\"><a href=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7351-scaled.jpg\"><img src=https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7351-scaled.jpg  \r\n                            alt=\"\" \r\n                    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class=\"galeria-title\">Gal\u00e9ria<\/h3>\r\n\t\t\t\t\t<div class=\"galeria-subtitle\">\r\n\r\n\t\t\t\t\t\t<div class=\"galeria-page-counter\"><span>9<\/span>k\u00e9p<\/div>\r\n                    <\/div> <\/div>\r\n                    <span class=\"gallery-item frame d-none d-md-flex\">\r\n\t\t\t\t\t<div class=\"galeria-small-img mt-0\"><a href=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-scaled.jpg\"><img src=https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-scaled.jpg \r\n                                alt=\"\"  \r\n                                class=\"attachment-sote-gallery-small size-sote-gallery-small\" \r\n                                srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-400x267.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-1024x683.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-768x512.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-1536x1024.jpg 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-2048x1366.jpg 2048w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-753x502.jpg 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7434-203x135.jpg 203w\" ><\/a><\/div>\r\n                    <\/span>\r\n                    <span class=\"gallery-item frame d-none d-md-flex\">\r\n\t\t\t\t\t<div class=\"galeria-small-img mt-0\"><a href=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-scaled.jpg\"><img src=https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-scaled.jpg \r\n                                alt=\"\" \r\n                                class=\"attachment-sote-gallery-small size-sote-gallery-small\" \r\n                                srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-400x267.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-1024x683.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-768x512.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-1536x1024.jpg 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-2048x1366.jpg 2048w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-753x502.jpg 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7470-203x135.jpg 203w\" ><\/a><\/div>\r\n                    <\/span>\r\n\r\n                <\/div>\r\n\r\n            <\/div>\r\n\r\n            <span class=\"gallery-item\"><div class=\"hidden\"><a href=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-scaled.jpg\">\r\n        <img src=https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-scaled.jpg alt=\"\" class=\"attachment-sote-gallery-big size-sote-gallery-big\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-400x267.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-1024x683.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-768x512.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-1536x1024.jpg 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-2048x1366.jpg 2048w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-753x502.jpg 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7409-203x135.jpg 203w\" >\r\n        <\/a><\/div><\/span><span class=\"gallery-item\"><div class=\"hidden\"><a href=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-scaled.jpg\">\r\n        <img src=https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-scaled.jpg alt=\"\" class=\"attachment-sote-gallery-big size-sote-gallery-big\" srcset=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-400x267.jpg 400w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-1024x683.jpg 1024w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-768x512.jpg 768w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-1536x1024.jpg 1536w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-2048x1366.jpg 2048w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-753x502.jpg 753w, https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7488-203x135.jpg 203w\" >\r\n        <\/a><\/div><\/span><span class=\"gallery-item\"><div class=\"hidden\"><a href=\"https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7502-scaled.jpg\">\r\n        <img src=https:\/\/semmelweis.hu\/pharmacology\/files\/2024\/08\/BAL7502-scaled.jpg alt=\"\" class=\"attachment-sote-gallery-big size-sote-gallery-big\" 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Projektfelel\u0151s: Pa\u00e1l \u00c1gnes A kissejtes t\u00fcd\u0151r\u00e1k (SCLC) a legrosszabb progn\u00f3zis\u00fa rosszindulat\u00fa daganatok egyike, amelynek ter\u00e1pi\u00e1j\u00e1ban az elm\u00falt h\u00e1rom \u00e9vtizedben nem t\u00f6rt\u00e9nt jelent\u0151s el\u0151rel\u00e9p\u00e9s. Az els\u0151 \u00edg\u00e9retes eredm\u00e9nyeket az immunellen\u0151rz\u00e9si pont g\u00e1tl\u00f3k (ICI-k) alkalmaz\u00e1sa hozta, de a &hellip;<\/p>\n","protected":false},"author":102374,"featured_media":0,"parent":336,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"categories":[],"tags":[],"class_list":["post-13511","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/pages\/13511","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/users\/102374"}],"replies":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/comments?post=13511"}],"version-history":[{"count":10,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/pages\/13511\/revisions"}],"predecessor-version":[{"id":14191,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/pages\/13511\/revisions\/14191"}],"up":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/pages\/336"}],"wp:attachment":[{"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/media?parent=13511"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/categories?post=13511"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/semmelweis.hu\/pharmacology\/wp-json\/wp\/v2\/tags?post=13511"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}