{"id":271,"date":"2022-07-28T12:03:55","date_gmt":"2022-07-28T10:03:55","guid":{"rendered":"http:\/\/apitoxin.sk\/?p=271"},"modified":"2022-07-28T12:27:25","modified_gmt":"2022-07-28T10:27:25","slug":"vceli-jed-prehlad-hlavnych-zlucenin-a-bio-aktivit-pre-terapeuticke-zaujmy","status":"publish","type":"post","link":"http:\/\/d.r5.wbsprt.com\/apitoxin.sk\/2022\/07\/28\/vceli-jed-prehlad-hlavnych-zlucenin-a-bio-aktivit-pre-terapeuticke-zaujmy\/","title":{"rendered":"V\u010del\u00ed jed: Preh\u013ead hlavn\u00fdch zl\u00fa\u010den\u00edn a bio aktiv\u00edt pre terapeutick\u00e9 z\u00e1ujmy"},"content":{"rendered":"\n


Apiterapia je alternat\u00edvna terapia, ktor\u00e1 sa opiera o vyu\u017eitie produktov v\u010dely medonosnej, predov\u0161etk\u00fdm v\u010delieho jedu na lie\u010dbu mnoh\u00fdch \u013eudsk\u00fdch chor\u00f4b. Jed sa m\u00f4\u017ee dosta\u0165 do \u013eudsk\u00e9ho tela manu\u00e1lnou injekciou alebo priamym v\u010del\u00edm bodnut\u00edm. V\u010del\u00ed jed obsahuje nieko\u013eko akt\u00edvnych molek\u00fal, ako s\u00fa peptidy a enz\u00fdmy, ktor\u00e9 maj\u00fa v\u00fdhodn\u00fd potenci\u00e1l pri lie\u010dbe z\u00e1palov a ochoren\u00ed centr\u00e1lneho nervov\u00e9ho syst\u00e9mu, ako je Parkinsonova choroba, Alzheimerova choroba a amyotrofick\u00e1 later\u00e1lna skler\u00f3za. Okrem toho v\u010del\u00ed jed preuk\u00e1zal s\u013eubn\u00e9 v\u00fdhody proti r\u00f4znym typom rakoviny, ako aj antiv\u00edrusov\u00fa aktivitu, dokonca aj proti n\u00e1ro\u010dn\u00e9mu v\u00edrusu \u013eudskej imunodeficiencie (HIV). Mnoh\u00e9 \u0161t\u00fadie op\u00edsali biologick\u00e9 aktivity zlo\u017eiek v\u010delieho jedu a spustili predklinick\u00e9 \u0161t\u00fadie na zlep\u0161enie potenci\u00e1lneho vyu\u017eitia apitox\u00ednu a jeho zlo\u017eiek ako \u010fal\u0161ej gener\u00e1cie liekov. Cie\u013eom tohto preh\u013eadu je zhrn\u00fa\u0165 hlavn\u00e9 zl\u00fa\u010deniny v\u010delieho jedu, ich prim\u00e1rne biologick\u00e9 vlastnosti, mechanizmy \u00fa\u010dinku a ich terapeutick\u00e9 hodnoty v alternat\u00edvnych terapeutick\u00fdch strat\u00e9gi\u00e1ch.<\/p>\n\n\n\n

Medzi v\u010delami medonosn\u00fdmi je Apis mellifera (obr\u00e1zok 1) hlavn\u00fdm druhom pou\u017e\u00edvan\u00fdm na ope\u013eovanie plod\u00edn na svete [1]. Pou\u017e\u00edvanie v\u0161etk\u00fdch v\u010del\u00edch produktov, vr\u00e1tane v\u010delieho jedu a medu, sa datuje tis\u00edce rokov sp\u00e4\u0165, ke\u010f\u017ee ich lie\u010div\u00e9 vlastnosti boli citovan\u00e9 v n\u00e1bo\u017eensk\u00fdch knih\u00e1ch, ako je Biblia a Kor\u00e1n [2,3,4]. Apiterapia je odvetvie alternat\u00edvnej medic\u00edny, ktor\u00e9 sa opiera o pou\u017e\u00edvanie v\u010del\u00edch produktov, ktor\u00e9 pozost\u00e1vaj\u00fa z medu, pe\u013eu, propolisu, materskej ka\u0161i\u010dky a hlavne v\u010delieho jedu (BV), ktor\u00fd je zn\u00e1my aj ako apitox\u00edn [5,6].<\/p>\n\n\n\n

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Apis mellifera (autorsk\u00e9 pr\u00e1vo Dany El Obeid).<\/figcaption><\/figure>\n\n\n\n

Terapia v\u010del\u00edm jedom (BVT) je medic\u00ednska aplik\u00e1cia BV z v\u010diel medonosn\u00fdch do \u013eudsk\u00e9ho tela na lie\u010dbu niektor\u00fdch chor\u00f4b, ako je reumatizmus artrit\u00edda [7]. T\u00e1to strat\u00e9gia sa pou\u017e\u00edva v alternat\u00edvnej medic\u00edne u\u017e viac ako 5000 rokov. Pozost\u00e1va bu\u010f z nepriamej aplik\u00e1cie, extrakciou BV elektrick\u00fdm stimulom s n\u00e1slednou injekciou do tela alebo priamo cez v\u010delie bodnutie [8] (obr\u00e1zok 2). My\u0161lienka vyu\u017eitia BV v medic\u00edne vznikla z presved\u010denia, \u017ee v\u010del\u00e1ri takmer netrpia reumatizmom alebo probl\u00e9mami s k\u013abmi.<\/p>\n\n\n\n

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Aplik\u00e1cia v\u010delieho jedu priamym v\u010del\u00edm bodnut\u00edm do tela.<\/figcaption><\/figure>\n\n\n\n

BV je produkovan\u00fd samicami v\u010diel a je zn\u00e1me, \u017ee obsahuje mnoho akt\u00edvnych zlo\u017eiek vr\u00e1tane: (i) peptidov, ako je melitt\u00edn, apam\u00edn, peptid degranuluj\u00faci \u017e\u00edrne bunky (MCD) a adolap\u00edn, (ii) enz\u00fdmy, ako je fosfolip\u00e1za A2 (PLA2) a hyaluronid\u00e1za a (iii) aminokyseliny a prchav\u00e9 zl\u00fa\u010deniny. Nieko\u013eko \u0161t\u00fadi\u00ed hodnotilo terapeutick\u00fd potenci\u00e1l t\u00fdchto zlo\u017eiek pri lie\u010dbe z\u00e1palov\u00fdch ochoren\u00ed u \u013eud\u00ed, ako aj ochoren\u00ed centr\u00e1lneho nervov\u00e9ho syst\u00e9mu, ako je Parkinsonova choroba (PD), Alzheimerova choroba (AD) a amyotrofick\u00e1 later\u00e1lna skler\u00f3za (ALS), ako aj mnoh\u00e9 \u010fal\u0161ie stavy. [9,10]. Zauj\u00edmav\u00e9 je, \u017ee v\u010del\u00ed jed, podobne ako in\u00e9 zvieracie jedy, tie\u017e preuk\u00e1zal priazniv\u00fd protirakovinov\u00fd a antiv\u00edrusov\u00fd potenci\u00e1l proti rakovine vaje\u010dn\u00edkov a prostaty, ako aj HIV [11,12,13,14].<\/p>\n\n\n\n

V\u010del\u00ed jed sa vyzna\u010duje t\u00fdm, \u017ee po u\u0161tipnut\u00ed vyvol\u00e1va alergick\u00e9 reakcie. Tieto reakcie sa m\u00f4\u017eu vyskytn\u00fa\u0165 v ko\u017ei, d\u00fdchacom syst\u00e9me, kardiovaskul\u00e1rnom syst\u00e9me a gastrointestin\u00e1lnom syst\u00e9me. N\u00e1sledne by \u0165a\u017ek\u00fd anafylaktick\u00fd \u0161ok mohol vies\u0165 k cerebr\u00e1lnej alebo myokardi\u00e1lnej isch\u00e9mii [15,16]. Tieto alergick\u00e9 reakcie s\u00fa sp\u00f4soben\u00e9 pr\u00edtomnos\u0165ou viacer\u00fdch prote\u00ednov\u00fdch alerg\u00e9nov v jede, z ktor\u00fdch v\u00e4\u010d\u0161ina m\u00e1 enzymatick\u00fa aktivitu [9]. Hlavn\u00e9 BV alerg\u00e9ny a \u0161pecifick\u00e9 induktory imunoglobul\u00ednu E (IgE) s\u00fa PLA2, melit\u00edn a hyaluronid\u00e1za. Okrem mechanizmov sprostredkovan\u00fdch IgE \u0161t\u00fadie nazna\u010duj\u00fa, \u017ee alerg\u00e9ny m\u00f4\u017eu zah\u0155\u0148a\u0165 aj reakcie nez\u00e1visl\u00e9 od IgE, ako je medi\u00e1tor bradykin\u00ednu (BK), \u010do vedie k r\u00f4znym anafylaktick\u00fdm sympt\u00f3mom [17,18]. Produkcia tohto neimunitn\u00e9ho medi\u00e1tora m\u00f4\u017ee by\u0165 indukovan\u00e1 melit\u00ednom, zn\u00e1mym ako aktiv\u00e1tor PLA2, ktor\u00fd m\u00f4\u017ee napodob\u0148ova\u0165 \u00fa\u010dinky BK na trache\u00e1lny tonus [17,19]. Okrem toho je MCD-peptid alebo peptid 401 schopn\u00fd vyvola\u0165 anafylaktoidn\u00fa reakciu degranul\u00e1ciou mastocytov [9,20].<\/p>\n\n\n\n

Okrem molekul\u00e1rnych \u0161t\u00fadi\u00ed, ktor\u00e9 sk\u00famaj\u00fa mo\u017en\u00e9 mechanizmy za reakciou z\u00e1palov\u00fdch bodnut\u00ed v\u010delou, mnoh\u00e9 klinick\u00e9 \u0161t\u00fadie hlboko sk\u00famaj\u00fa potenci\u00e1lne vyu\u017eitie BV na lie\u010dbu chronick\u00fdch ochoren\u00ed. Preto je cie\u013eom nasleduj\u00facich \u010dast\u00ed preh\u013eadu zd\u00f4razni\u0165 prim\u00e1rne biologick\u00e9 vlastnosti BV a jeho bioakt\u00edvnych molek\u00fal, ktor\u00e9 maj\u00fa potenci\u00e1l pri v\u00fdvoji terapeutick\u00fdch strat\u00e9gi\u00ed.<\/p>\n\n\n\n

Hlavn\u00e9 zl\u00fa\u010deniny v\u010delieho jedu<\/p>\n\n\n\n

BV je prieh\u013eadn\u00e1 kvapalina bez z\u00e1pachu obsahuj\u00faca hydrolytick\u00fa zmes bielkov\u00edn s kysl\u00fdm pH (4,5 a\u017e 5,5), ktor\u00fa v\u010dely \u010dasto pou\u017e\u00edvaj\u00fa ako obrann\u00fd n\u00e1stroj proti pred\u00e1torom. Jedna kvapka BV pozost\u00e1va z 88 % vody a len 0,1 \u00b5g such\u00e9ho jedu [10]. Ten je mimoriadne komplexnou zmesou peptidov vr\u00e1tane melitt\u00ednu, adolap\u00ednu, apam\u00ednu a MCD-peptidu. Obsahuje tie\u017e enz\u00fdmy, predov\u0161etk\u00fdm PLA2, a zl\u00fa\u010deniny s n\u00edzkou molekulovou hmotnos\u0165ou, ako s\u00fa bioakt\u00edvne am\u00edny (napr. histam\u00edn a epinefr\u00edn) a miner\u00e1ly [9].<\/p>\n\n\n\n

2.1. Melittin
Melitt\u00edn, 26-zvy\u0161kov\u00fd peptid, je hlavnou zlo\u017ekou BV a tvor\u00ed 40\u201360 % jeho zlo\u017eenia [21]. Karboxylov\u00e1 koncov\u00e1 oblas\u0165 peptidu je hydrofiln\u00e1 a zodpovedn\u00e1 za lytick\u00fd \u00fa\u010dinok, zatia\u013e \u010do aminokoncov\u00e1 oblas\u0165 jeho sekvencie je preva\u017ene hydrof\u00f3bna bez lytickej aktivity [22]. Amfipatick\u00e1 vlastnos\u0165 melitt\u00ednu ho rob\u00ed rozpustn\u00fdm vo vode v monom\u00e9rnej aj tetram\u00e9rnej forme. Umo\u017e\u0148uje tie\u017e \u013eahk\u00e9 vlo\u017eenie melit\u00ednu do membr\u00e1n naru\u0161en\u00edm prirodzen\u00fdch aj syntetick\u00fdch fosfolipidov\u00fdch dvojvrstiev. Predch\u00e1dzaj\u00face \u0161t\u00fadie uk\u00e1zali, \u017ee mechanizmus \u00fa\u010dinku melitt\u00ednu pri rozru\u0161ovan\u00ed membr\u00e1n je sprostredkovan\u00fd tvorbou p\u00f3rov l\u00fdzuj\u00facich prokaryotick\u00e9 aj eukaryotick\u00e9 bunky v neselekt\u00edvnej hmote. V skuto\u010dnosti sa melit\u00edn via\u017ee na membr\u00e1ny ako monom\u00e9ry, ale p\u00f4sob\u00ed na membr\u00e1nu inkluz\u00edvne. V z\u00e1vislosti od koncentr\u00e1cie m\u00f4\u017ee tento biopeptid indukova\u0165 prechodn\u00e9 alebo stabiln\u00e9 p\u00f3ry [23]. Ke\u010f sa vytvor\u00ed prechodn\u00fd p\u00f3r, cez membr\u00e1nu s\u00fa schopn\u00e9 difundova\u0165 iba i\u00f3ny. V pr\u00edpade stabilnej tvorby p\u00f3rov sa v\u0161ak membr\u00e1na st\u00e1va priepustnou pre relat\u00edvne ve\u013ek\u00e9 molekuly, ako je gluk\u00f3za [24]. Tvorba p\u00f3rov vyvolan\u00e1 melit\u00ednom je zodpovedn\u00e1 za jeho hemolytick\u00e9, antimikrobi\u00e1lne, antifung\u00e1lne a protin\u00e1dorov\u00e9 aktivity [12,25]. Ned\u00e1vno sa uk\u00e1zalo, \u017ee melit\u00edn sp\u00f4sobuje nervov\u00e9 plastick\u00e9 zmeny pozd\u013a\u017e dr\u00e1h signaliz\u00e1cie bolesti aktiv\u00e1ciou a senzibiliz\u00e1ciou nociceptorov\u00fdch buniek. Mechanizmus zah\u0155\u0148a fosforyl\u00e1ciu mitog\u00e9nom aktivovan\u00fdch prote\u00ednkin\u00e1z (MAPK), ako aj aktiv\u00e1ciu tepeln\u00fdch nocicept\u00edvnych kan\u00e1lov, ako je TRPV1 (prechodn\u00fd receptorov\u00fd potenci\u00e1l vaniloidn\u00e9ho receptora 1), ATP-gated P2X a P2Y purinergn\u00e9 receptory. Podobne m\u00f4\u017ee melit\u00edn p\u00f4sobi\u0165 ako aktiv\u00e1tor PLA2 [26]. Je to tie\u017e hlavn\u00e1 biologicky akt\u00edvna l\u00e1tka BV, ktor\u00e1 po podan\u00ed do akupunkt\u00fary pacienta vyvol\u00e1va antinocicept\u00edvne, protiz\u00e1palov\u00e9 a antiartritick\u00e9 \u00fa\u010dinky [27].<\/p>\n\n\n\n

2.2. Apamin
Apam\u00edn je 18-aminokyselinov\u00fd peptid obsahuj\u00faci dva disulfidov\u00e9 most\u00edky. Je to najmen\u0161\u00ed neurotox\u00edn v BV [28]. Tento polypeptid je schopn\u00fd prejs\u0165 hematoencefalickou bari\u00e9rou, a preto ovplyv\u0148uje fungovanie centr\u00e1lneho nervov\u00e9ho syst\u00e9mu r\u00f4znymi sp\u00f4sobmi \u00fa\u010dinku. Sp\u00f4sobuje napr\u00edklad neurotoxick\u00e9 \u00fa\u010dinky v mieche cicavcov, \u010do m\u00e1 za n\u00e1sledok hyperaktivitu a z\u00e1chvaty, ako sa to dok\u00e1zalo u potkanov. Blokovan\u00edm v\u00e1pnikom aktivovan\u00fdch K+ kan\u00e1lov je apam\u00edn tie\u017e schopn\u00fd ovplyvni\u0165 priepustnos\u0165 bunkovej membr\u00e1ny vo\u010di draseln\u00fdm i\u00f3nom (K+). V hladkom svalstve ciev je tox\u00edn schopn\u00fd inhibova\u0165 prolifer\u00e1ciu a migr\u00e1ciu buniek hladk\u00e9ho svalstva ciev prostredn\u00edctvom sign\u00e1lnych dr\u00e1h Akt a Erk [29]. Toto zistenie poukazuje na potenci\u00e1l apam\u00ednu v strat\u00e9gi\u00e1ch lie\u010dby ateroskler\u00f3zy. \u010eal\u0161ia \u0161t\u00fadia hodnotila d\u00f4sledky citlivosti K+ kan\u00e1lov na apam\u00edn a uk\u00e1zala, \u017ee neurotox\u00edn m\u00f4\u017ee inhibova\u0165 NO-indukovan\u00fa relax\u00e1ciu spont\u00e1nnej kontraktilnej aktivity myometria u netehotn\u00fdch \u017eien [30].<\/p>\n\n\n\n

2.3. Peptid degranuluj\u00faci \u017e\u00edrne bunky (MCD).
MCD peptid, tie\u017e zn\u00e1my ako peptid 401, je BV polypeptid obsahuj\u00faci 22 aminokysel\u00edn s podobnou \u0161trukt\u00farou ako apam\u00edn, preto\u017ee oba obsahuj\u00fa dve disulfidov\u00e9 v\u00e4zby. Tvor\u00ed 2\u20133 % su\u0161iny BV. N\u00e1zov MCD odr\u00e1\u017ea biologick\u00fd \u00fa\u010dinok pri uvo\u013e\u0148ovan\u00ed histam\u00ednu zo \u017e\u00edrnych buniek. Je to epileptog\u00e9nny neurotox\u00edn, d\u00f4le\u017eit\u00fd inhib\u00edtor K+ kan\u00e1lov a m\u00f4\u017ee sp\u00f4sobi\u0165 v\u00fdznamn\u00e9 zn\u00ed\u017eenie krvn\u00e9ho tlaku potkanov [31]. Zd\u00e1 sa, \u017ee niektor\u00e9 biologick\u00e9 aktivity MCD maj\u00fa odli\u0161n\u00e9 mechanizmy a m\u00f4\u017eu predstavova\u0165 dobr\u00fa ilustr\u00e1ciu vz\u0165ahu medzi \u0161trukt\u00farou a funkciou. \u0160t\u00fadie opisuj\u00fa MCD ako siln\u00e9 protiz\u00e1palov\u00e9 \u010dinidlo a m\u00f4\u017ee sl\u00fa\u017ei\u0165 ako potenci\u00e1lny kandid\u00e1t na \u0161t\u00fadium sekre\u010dn\u00fdch mechanizmov z\u00e1palov\u00fdch buniek, ako s\u00fa mastocyty, bazofily a leukocyty, \u010do vedie k n\u00e1vrhu zl\u00fa\u010den\u00edn s terapeutick\u00fdmi aplik\u00e1ciami [32].<\/p>\n\n\n\n

2.4. Adolapin
Adolap\u00edn je b\u00e1zick\u00fd polypeptid so 103 aminokyselinov\u00fdmi zvy\u0161kami. Zodpoved\u00e1 1 % suchej hmotnosti BV. V\u00fdskumn\u00edci uk\u00e1zali, \u017ee adolap\u00edn m\u00e1 protiz\u00e1palov\u00e9, antinocicept\u00edvne a antipyretick\u00e9 \u00fa\u010dinky t\u00fdm, \u017ee blokuje synt\u00e9zu prostagland\u00ednov a inhibuje aktivitu cyklooxygen\u00e1zy [33]. Polypeptid m\u00f4\u017ee inhibova\u0165 lipoxygen\u00e1zu z \u013eudsk\u00fdch krvn\u00fdch do\u0161ti\u010diek a m\u00f4\u017ee ma\u0165 analgetick\u00fd \u00fa\u010dinok pod\u013ea Jung et al. [34].<\/p>\n\n\n\n

2.5. Fosfolip\u00e1za A2
PLA2, najsmrte\u013enej\u0161\u00ed enz\u00fdm v BV, je jeden polypeptidov\u00fd re\u0165azec 128 aminokysel\u00edn obsahuj\u00faci \u0161tyri disulfidov\u00e9 most\u00edky. Fosfolip\u00e1za A2 z v\u010delieho jedu (bvPLA2) patr\u00ed do skupiny III enz\u00fdmov sPLA2 a m\u00f4\u017ee p\u00f4sobi\u0165 ako ligand pre \u0161pecifick\u00e9 receptory. BvPLA2 predstavuje 12\u201315 % su\u0161iny BV a je extr\u00e9mne z\u00e1sadit\u00fd. BvPLA2 je hydrolytick\u00fd enz\u00fdm, schopn\u00fd \u0161pecificky \u0161tiepi\u0165 sn-2 acylov\u00fa v\u00e4zbu fosfolipidov na rozhran\u00ed voda\/lipid [35]. Je zauj\u00edmav\u00e9, \u017ee jeho \u010dinnos\u0165 m\u00f4\u017ee by\u0165 zlep\u0161en\u00e1 melitt\u00ednom. Uk\u00e1zalo sa, \u017ee k tomu doch\u00e1dza po\u010das procesu l\u00fdzy erytrocytov, \u010do dokazuje pr\u00edtomnos\u0165 synergick\u00e9ho \u00fa\u010dinku medzi bvPLA2 a melit\u00ednom [36,37]. V skuto\u010dnosti sa preuk\u00e1zalo, \u017ee melit\u00edn pom\u00e1ha pri vystavovan\u00ed membr\u00e1nov\u00fdch fosfolipidov katalytick\u00e9mu miestu enz\u00fdmov prostredn\u00edctvom otv\u00e1rania melit\u00ednom indukovan\u00fdch kan\u00e1lov [38]. Okrem toho nov\u00e9 experiment\u00e1lne \u00fadaje preuk\u00e1zali ochrann\u00e9 imunitn\u00e9 reakcie bvPLA2 proti \u0161irok\u00e9mu spektru chor\u00f4b, ako je astma, Alzheimerova choroba a Parkinsonova choroba [39,40,41]. BvPLA2 hr\u00e1 neuroprotekt\u00edvnu \u00falohu t\u00fdm, \u017ee indukuje mikrogli\u00e1lnu deaktiv\u00e1ciu a zni\u017euje infiltr\u00e1ciu CD4+ T buniek v MPTP-indukovanom my\u0161om modeli PD (MPTP: 1-metyl-4-fenyl-1,2,3,6-tetrahydropyrid\u00edn) [42].<\/p>\n\n\n\n

2.6. Hyaluronid\u00e1za
Hyaluronid\u00e1za predstavuje 1,5\u20132 % su\u0161iny BV a je zn\u00e1me, \u017ee rozklad\u00e1 kyselinu hyalur\u00f3nov\u00fa v tkaniv\u00e1ch, ako napr\u00edklad v synovi\u00e1lnej burze pri reumatoidnej artrit\u00edde. BV hyaluronid\u00e1za umo\u017e\u0148uje akt\u00edvnym zlo\u017ek\u00e1m BV \u00fa\u010dinne difundova\u0165 do tkaniva obete ovplyvnen\u00edm jeho \u0161truktur\u00e1lnej integrity a zv\u00fd\u0161en\u00edm prietoku krvi v danej oblasti. Tieto dve akcie sa kombinuj\u00fa, aby zintenz\u00edvnili \u0161irok\u00e9 roz\u0161\u00edrenie jedu [43,44].<\/p>\n\n\n\n

Bioaktivity a terapeutick\u00e9 aplik\u00e1cie v\u010delieho jedu a jeho hlavn\u00fdch zl\u00fa\u010den\u00edn<\/p>\n\n\n\n

3.1. Protiz\u00e1palov\u00fd potenci\u00e1l
Z\u00e1pal je ochrann\u00fd proces pre telo v reakcii na \u0161kodliv\u00e9 podnety. Chronick\u00fd z\u00e1pal m\u00f4\u017ee vies\u0165 k rozvoju nieko\u013ek\u00fdch chor\u00f4b, ako je reumatoidn\u00e1 artrit\u00edda (RA), cukrovka, kardiovaskul\u00e1rne choroby, obezita, astma, ko\u017en\u00e9 choroby a choroby s\u00favisiace s CNS, ako s\u00fa PD, AD a ALS [45].<\/p>\n\n\n\n

Melittin, ke\u010f sa pod\u00e1va vo vysok\u00fdch d\u00e1vkach, sp\u00f4sobuje lok\u00e1lnu boles\u0165, svrbenie a z\u00e1pal. Av\u0161ak n\u00edzke d\u00e1vky tejto BV zl\u00fa\u010deniny m\u00f4\u017eu vyvola\u0165 \u0161irok\u00e9 protiz\u00e1palov\u00e9 \u00fa\u010dinky. Mnoh\u00e9 spr\u00e1vy sk\u00famali protiz\u00e1palov\u00e9 mechanizmy melit\u00ednu pri r\u00f4znych ochoreniach, ako je RA a ALS [46,47]. V skuto\u010dnosti p\u00f4sob\u00ed inhib\u00edciou z\u00e1palov\u00fdch cytok\u00ednov, ako je interleuk\u00edn-6 (IL-6), IL-8, tumor nekrotizuj\u00faci faktor-a (TNF-a) a interfer\u00f3n-y (IFN-y). Okrem toho melit\u00edn zni\u017euje sign\u00e1lne dr\u00e1hy, ktor\u00e9 aktivuj\u00fa z\u00e1palov\u00e9 cytok\u00edny, vr\u00e1tane nukle\u00e1rneho faktora-kappa B (NF-KB), prote\u00ednkin\u00e1zy Akt a kin\u00e1z regulovan\u00fdch extracelul\u00e1rnym sign\u00e1lom (ERK1\/2) v \u013eudsk\u00fdch keratinocytoch o\u0161etren\u00fdch lipopolysacharidom porfyromonas gingivalis (PgLPS). Tieto zistenia nazna\u010duj\u00fa, \u017ee blokovan\u00edm ich prim\u00e1rnych sign\u00e1lnych dr\u00e1h melit\u00edn inhibuje z\u00e1palov\u00e9 cytok\u00edny, \u010do vedie k zn\u00ed\u017eeniu z\u00e1palu v ko\u017ei, pe\u010deni, k\u013aboch \u200b\u200ba neur\u00f3novom tkanive [48].<\/p>\n\n\n\n

\u010co sa t\u00fdka ko\u017en\u00fdch ochoren\u00ed, ned\u00e1vna \u0161t\u00fadia Kim et al. uk\u00e1zali, \u017ee BV zni\u017euje atopick\u00fa dermatit\u00eddu, naj\u010dastej\u0161ie alergick\u00e9 chronick\u00e9 z\u00e1palov\u00e9 ochorenie ko\u017ee [49]. V skuto\u010dnosti jed stimuluje produkciu CD55 spusten\u00edm dr\u00e1h ERK1\/2, \u010do vedie k zmierneniu sympt\u00f3mov ochorenia [50]. Je zauj\u00edmav\u00e9, \u017ee predch\u00e1dzaj\u00faca \u0161t\u00fadia Shina a kol. op\u00edsali protiz\u00e1palov\u00fd potenci\u00e1l bvPLA2 pri ko\u017en\u00fdch ochoreniach t\u00fdm, \u017ee uk\u00e1zali, \u017ee enz\u00fdm tlm\u00ed atopick\u00fd z\u00e1pal ko\u017ee prostredn\u00edctvom interakcie s CD206 [51].<\/p>\n\n\n\n

3.2. Aplik\u00e1cia BV na lie\u010dbu neurodegenerat\u00edvnych chor\u00f4b
3.2.1. Parkinsonova choroba PD je degenerat\u00edvna pohybov\u00e1 porucha, ktor\u00e1 vedie u pacientov k progres\u00edvnej invalidite. Patologick\u00fdmi znakmi ochorenia s\u00fa progres\u00edvna strata dopaminergn\u00fdch neur\u00f3nov v substantia nigra (\u0161trukt\u00fara baz\u00e1lnych gangli\u00ed nach\u00e1dzaj\u00faca sa v \u013eudskom mozgu) a pr\u00edtomnos\u0165 Lewyho teliesok, ktor\u00e9 obsahuj\u00fa agreg\u00e1ty alfa-synukle\u00ednu, \u0161iroko distribuovan\u00e9ho prote\u00ednu v mozgu. [52,53]. Abnorm\u00e1lna mikrogli\u00e1lna aktiv\u00e1cia je tie\u017e patologick\u00fdm znakom pri r\u00f4znych neurodegenerat\u00edvnych ochoreniach vr\u00e1tane PD [54]. Mnoho predklinick\u00fdch \u0161t\u00fadi\u00ed sk\u00famalo \u00fa\u010dinok BV na migr\u00e1ciu leukocytov alebo mikrogli\u00e1lnu aktiv\u00e1ciu na zvierac\u00edch a bunkov\u00fdch modeloch. \u010eal\u0161ie testy hodnotili neuroprotekt\u00edvny potenci\u00e1l BV akupunkt\u00farnej terapie (BVA) proti roten\u00f3nom indukovan\u00e9mu oxida\u010dn\u00e9mu stresu, neuroz\u00e1palu a apopt\u00f3ze na modeloch my\u0161\u00ed s PD [55]. Roten\u00f3n je pestic\u00edd, ktor\u00fd m\u00f4\u017ee ovplyvni\u0165 patofyziologick\u00e9 mechanizmy, ktor\u00e9 sa podie\u013eaj\u00fa na PD [55]. Je zauj\u00edmav\u00e9, \u017ee BV preuk\u00e1zal svoju schopnos\u0165 zabr\u00e1ni\u0165 depl\u00e9cii dopam\u00ednu po podan\u00ed roten\u00f3nu. Okrem toho sa lokomotorick\u00e1 aktivita znovu obnovila po o\u0161etren\u00ed modelov my\u0161\u00ed PD pomocou BV. Lie\u010dba \u00fa\u010dinne potla\u010dila po\u0161kodenie DNA a inhibovala expresiu apoptotick\u00fdch g\u00e9nov Bax, Bcl-2 a kasp\u00e1zy-3 v mozgu PD my\u0161\u00ed. Tieto zistenia ukazuj\u00fa, \u017ee BV normalizovala v\u0161etky apoptotick\u00e9 a neuroz\u00e1palov\u00e9 markery a obnovila neuroch\u00e9miu mozgu po poranen\u00ed roten\u00f3nom [56]. Tie\u017e sa uk\u00e1zalo, \u017ee BV m\u00f4\u017ee chr\u00e1ni\u0165 doparminergn\u00e9 neur\u00f3ny pred degener\u00e1ciou v experiment\u00e1lnych modeloch PD. Spolu s t\u00fdmto zisten\u00edm sa zistilo, \u017ee akupunkt\u00farna stimul\u00e1cia doln\u00fdch zadn\u00fdch kon\u010dat\u00edn BV m\u00e1 ochrann\u00fd \u00fa\u010dinok na MPTP (1-metyl-4-fenyl-1,2,3,6-tetrahydropyrid\u00edn) my\u0161om modeli PD [57].
3.2.2. Alzheimerova choroba AD je naj\u010dastej\u0161\u00edm neurodegenerat\u00edvnym ochoren\u00edm a na jeho vzniku sa podie\u013ea mnoho patologick\u00fdch procesov [58]. Hypot\u00e9za amyloidnej kask\u00e1dy a toxicita amyloidn\u00fdch beta (A\u03b2) peptidov v\u0161ak doteraz dominovala v\u00fdskumu v\u010faka pokro\u010dil\u00fdm \u0161t\u00fadi\u00e1m, ktor\u00e9 ukazuj\u00fa, \u017ee agreg\u00e1ty tohto peptidu s\u00fa charakteristick\u00e9 znaky ochorenia [59,60,61]. Hoci etiol\u00f3gia AD zost\u00e1va nezn\u00e1ma, d\u00f4kazy nazna\u010duj\u00fa, \u017ee z\u00e1palov\u00e9 odpovede m\u00f4\u017eu hra\u0165 k\u013e\u00fa\u010dov\u00fa \u00falohu v jej patogen\u00e9ze [62,63]. S\u00fa\u010dasn\u00e9 lie\u010dby kognit\u00edvnej straty s\u00favisiacej s AD sa spoliehaj\u00fa na pou\u017eitie muskar\u00ednov\u00fdch alebo nikot\u00ednov\u00fdch receptorov\u00fdch ligandov a inhib\u00edtora acetylchol\u00ednester\u00e1zy (AChE) [64]. Ako alternat\u00edvnu strat\u00e9giu Ye et al. uk\u00e1zali, \u017ee bvPLA2 mo\u017eno pou\u017ei\u0165 ako lie\u010dbu na blokovanie progresie AD u transg\u00e9nnych my\u0161\u00ed [40]. Je to kv\u00f4li schopnosti bvPLA2 zni\u017eova\u0165 akumul\u00e1ciu Ap a zlep\u0161ova\u0165 kognit\u00edvne funkcie v mozgoch my\u0161\u00ed. Rovnak\u00e1 \u0161t\u00fadia podobne ukazuje, \u017ee bvPLA2 m\u00f4\u017ee zv\u00fd\u0161i\u0165 metabolizmus gluk\u00f3zy v mozgu a zn\u00ed\u017ei\u0165 neuroz\u00e1palov\u00e9 reakcie v hipokampe, \u010do m\u00f4\u017ee obmedzi\u0165 patogen\u00e9zu AD [40]. Ned\u00e1vna \u0161t\u00fadia tie\u017e uk\u00e1zala, \u017ee popul\u00e1cie regula\u010dn\u00fdch T-buniek by mohli by\u0165 modulovan\u00e9 lie\u010dbou bvPLA2 v my\u0161om modeli 3xTg-AD. Preto autori navrhli nov\u00fd terapeutick\u00fd pr\u00edstup na zn\u00ed\u017eenie progresie AD kombin\u00e1ciou lie\u010dby bvPLA2 spolu s vakcina\u010dnou terapiou A\u03b2, aby sa zabr\u00e1nilo jej ne\u017eiaducej z\u00e1palovej odpovedi [60].
3.2.3. Amyotrofick\u00e1 later\u00e1lna skler\u00f3za ALS je ochorenie CNS, ktor\u00e9 sp\u00f4sobuje smr\u0165 motorick\u00fdch neur\u00f3nov [65]. V\u00fdznamnou \u010drtou ALS je abnorm\u00e1lna akumul\u00e1cia mutantn\u00fdch prote\u00ednov\u00fdch agreg\u00e1tov SOD1 (mtSOD1) [66]. My\u0161\u00ed model ALS nes\u00faci mutovan\u00fd g\u00e9n mtSOD1 so substit\u00faciou glyc\u00ednu za alan\u00edn (SOD1G93A) charakterizoval Jaarsma et al., \u010d\u00edm sa u\u013eah\u010dilo pochopenie etiol\u00f3gie ALS [67]. \u0160t\u00fadie in vitro aj in vivo s pou\u017eit\u00edm mutantn\u00fdch transg\u00e9nnych my\u0161\u00ed SOD1 preuk\u00e1zali r\u00f4zne bunkov\u00e9 patog\u00e9nne udalosti v motorick\u00fdch neur\u00f3noch, ako je nespr\u00e1vne poskladanie prote\u00ednov, dysfunkcia mitochondri\u00ed a akumul\u00e1cia neurofilamentov [67]. Je zauj\u00edmav\u00e9, \u017ee BV preuk\u00e1zal ur\u010dit\u00fd potenci\u00e1l na p\u00f4sobenie proti tejto chorobe. V skuto\u010dnosti pod\u00e1vanie BV v presnom a symptomatickom \u0161t\u00e1diu progresie ALS vedie k zv\u00fd\u0161eniu motorickej aktivity u my\u0161\u00ed s mutantom SOD1G93A a k pred\u013a\u017eeniu o\u010dak\u00e1vanej d\u013a\u017eky \u017eivota v porovnan\u00ed s kontroln\u00fdmi my\u0161ami rovnak\u00e9ho veku. Mohlo by to by\u0165 sp\u00f4soben\u00e9 zablokovan\u00edm aktivovanej mikroglie, ktor\u00e1 sa zvy\u010dajne nach\u00e1dza v my\u0161ac\u00edch modeloch ALS [68]. \u010eal\u0161ia \u0161t\u00fadia preuk\u00e1zala, \u017ee akupunkt\u00fara v\u010delieho jedu (BVA) na ST36 inhibuje neuroz\u00e1pal v mieche my\u0161\u00ed so symptomatickou ALS signifikantn\u00fdm zn\u00ed\u017een\u00edm hlad\u00edn z\u00e1palov\u00fdch prote\u00ednov ako TLR4, CD14 a TNF-\u03b1 [69].<\/p>\n\n\n\n

3.3. Aplik\u00e1cie BV a\/alebo Melittinu pri rakovine
Pou\u017eitie apitox\u00ednu, najm\u00e4 jeho hlavnej zl\u00fa\u010deniny melitt\u00ednu, ako novej strat\u00e9gie lie\u010dby rakoviny nadobudlo v poslednej dobe ve\u013ek\u00fd v\u00fdznam [70,71]. V skuto\u010dnosti je zn\u00e1me, \u017ee melit\u00edn je ne\u0161pecifick\u00fd cytolytick\u00fd peptid, ktor\u00fd m\u00f4\u017ee atakova\u0165 lipidov\u00fa dvojvrstvu, \u010do vedie k v\u00fdznamnej toxicite pri intraven\u00f3znej injekcii [72]. Napriek tomu sa vyu\u017eilo mnoho optimaliza\u010dn\u00fdch pr\u00edstupov, vr\u00e1tane pou\u017eitia dod\u00e1vania melit\u00ednu na b\u00e1ze nano\u010dast\u00edc. Je pozoruhodn\u00e9, \u017ee surov\u00fd BV, ako aj melit\u00edn preuk\u00e1zali protin\u00e1dorov\u00e9 aktivity proti r\u00f4znym typom rakovinov\u00fdch buniek vr\u00e1tane buniek rakoviny prsn\u00edka, pe\u010dene, leuk\u00e9mie, p\u013e\u00fac, melan\u00f3mu a prostaty [70,72,73,74,75]. Wang a kol. [76] sk\u00famali mechanizmus protin\u00e1dorovej aktivity melit\u00ednu a uk\u00e1zali, \u017ee melit\u00edn m\u00f4\u017ee indukova\u0165 apopt\u00f3zu buniek hepatocelul\u00e1rneho karcin\u00f3mu (HCC) prostredn\u00edctvom aktiv\u00e1cie sign\u00e1lnej dr\u00e1hy CAMKII-TAK1-JNK\/p38 (CAMKII: Ca2+\/kalmodul\u00edn-dependentn\u00e1 prote\u00ednkin\u00e1za; TAK1 : Transformuj\u00faci rastov\u00fd faktor-beta-aktivovan\u00e1 kin\u00e1za 1; JNK\/p38: Mitog\u00e9nom-aktivovan\u00e9 prote\u00ednkin\u00e1zy). Okrem toho m\u00f4\u017ee melit\u00edn senzibilizova\u0165 TRAIL-rezistentn\u00e9 bunky HCC (TRAIL: ligand indukuj\u00faci apopt\u00f3zu s\u00favisiaci s faktorom nekrotizuj\u00facim n\u00e1dory) na apopt\u00f3zu indukovan\u00fa TRAIL, pravdepodobne prostredn\u00edctvom aktiv\u00e1cie dr\u00e1hy CAMKII-TAK1-JNK\/p38 a inhib\u00edcie dr\u00e1hy IKK-NF\u03baB (obr\u00e1zok 3). Tieto zistenia s\u00fa v s\u00falade s aktiv\u00e1ciou v\u00e1pnikov\u00fdch kan\u00e1lov melit\u00ednom, ktor\u00e1 vedie k zv\u00fd\u0161eniu intracelul\u00e1rnej koncentr\u00e1cie Ca2+ a aktiv\u00e1cii CaMKII citliv\u00e9ho na v\u00e1pnik, ako je vidie\u0165 aj na obr\u00e1zku 3 [76].<\/p>\n\n\n\n

\"\"
Schematick\u00fd n\u00e1kres hlavn\u00fdch mechanizmov \u00fa\u010dinku melit\u00ednu ako protirakovinov\u00e9ho \u010dinidla.<\/figcaption><\/figure>\n\n\n\n

Park a kol. [13] tie\u017e uviedli, \u017ee BV a jeho hlavn\u00e1 zlo\u017eka, melit\u00edn, indukuj\u00fa inhib\u00edciu rastu rakovinov\u00fdch buniek in vitro aj in vivo prostredn\u00edctvom aktiv\u00e1cie kasp\u00e1zov\u00fdch dr\u00e1h (3 a 9) a inhib\u00edciou signaliz\u00e1cie NF-\u03baB a jej downstream prolifer\u00e1cie a antiapoptotick\u00e9 g\u00e9nov\u00e9 produkty ako Bcl-2, cIAP-2, iNOS, COX-2 a cPLA2 (obr\u00e1zok 3) [13]. Podobne Zheng a kol. [77] preuk\u00e1zali, \u017ee BV m\u00e1 antiproliferat\u00edvny \u00fa\u010dinok a indukuje apopt\u00f3zu prostredn\u00edctvom aktiv\u00e1cie receptorov smrti (DR4 a DR5). \u010eal\u0161ie zauj\u00edmav\u00e9 zistenie sa objavilo o melit\u00edne zd\u00f4raznen\u00edm jeho antimetastatick\u00fdch a protirastov\u00fdch vlastnost\u00ed [73]. Pri rakovine s\u00fa metast\u00e1zy a inv\u00e1zia mal\u00edgnych buniek hlavn\u00fdmi pr\u00ed\u010dinami progresie ochorenia. Preto sa v\u00fdskumn\u00edci v oblasti rakoviny zameriavaj\u00fa na pochopenie molekul\u00e1rnych mechanizmov, ktor\u00e9 reguluj\u00fa migr\u00e1ciu mal\u00edgnych buniek a mo\u017en\u00fd sp\u00f4sob, ako tomu zabr\u00e1ni\u0165, ako rozhoduj\u00faci krok v ich boji proti rakovine [78,79]. V tejto s\u00favislosti sa zistilo, \u017ee melit\u00edn inhibuje in vitro a in vivo motilitu buniek HCC potla\u010den\u00edm dr\u00e1h z\u00e1visl\u00fdch od Rac1 [73]. Na druhej strane ned\u00e1vna \u0161t\u00fadia dok\u00e1zala, \u017ee kombin\u00e1cia melitt\u00ednu s chemoterapeutikom, ako je temozolomid, v\u00fdrazne zni\u017euje rast spolu s inv\u00e1ziou buniek melan\u00f3mu v porovnan\u00ed so stavmi, ke\u010f sa TMZ alebo melit\u00edn pou\u017e\u00edvali samostatne [71].<\/p>\n\n\n\n

Tieto zistenia poukazuj\u00fa na ve\u013ek\u00fd potenci\u00e1l melitt\u00ednu pri lie\u010dbe rakoviny p\u00f4soben\u00edm na r\u00f4zne k\u013e\u00fa\u010dov\u00e9 body choroby a mali by sa \u010falej rozobera\u0165.<\/p>\n\n\n\n

Napriek presved\u010div\u00fdm \u00fadajom t\u00fdkaj\u00facim sa potenci\u00e1lneho pou\u017eitia BV, konkr\u00e9tnej\u0161ie melitt\u00ednu, proti r\u00f4znym typom rakoviny, jeho pou\u017eite\u013enos\u0165 u \u013eud\u00ed zost\u00e1va ve\u013emi n\u00e1ro\u010dn\u00e1 z d\u00f4vodu jeho ne\u0161pecifickej cytotoxicity [80]. S\u00fa\u010dasn\u00e9 optimaliza\u010dn\u00e9 met\u00f3dy sa zameriavaj\u00fa na dod\u00e1vanie melitt\u00ednu na b\u00e1ze nano\u010dast\u00edc, aby sa predi\u0161lo tak\u00fdmto probl\u00e9mom. V\u010faka nanotechnol\u00f3gii bolo mo\u017en\u00e9 vyvin\u00fa\u0165 a efekt\u00edvne otestova\u0165 konjug\u00e1ty melitt\u00ednu proti \u0161irok\u00e9mu spektru \u013eudsk\u00fdch typov rakoviny v predklinick\u00fdch modeloch [81]. Cheng a kol. zameran\u00e9 na v\u00fdvoj \u00fa\u010dinn\u00e9ho a z\u00e1rove\u0148 bezpe\u010dn\u00e9ho syst\u00e9mu dod\u00e1vania melitt\u00ednu, ktor\u00fd m\u00f4\u017ee zn\u00ed\u017ei\u0165 jeho hemolytick\u00fa aktivitu pri zachovan\u00ed jeho cytotoxick\u00fdch v\u00fdhod. Preto bol navrhnut\u00fd du\u00e1lny zabezpe\u010den\u00fd nano-\u017eihadlo (DSNS) prostredn\u00edctvom kombin\u00e1cie zwitteri\u00f3nov\u00e9ho glykolchitosanu a disulfidov\u00fdch v\u00e4zieb. DSNS nabit\u00fd melitt\u00ednom vykazoval takmer \u00fapln\u00fd cytotoxick\u00fd \u00fa\u010dinok na mnoh\u00e9 typy rakovinov\u00fdch buniek pri ve\u013emi n\u00edzkych koncentr\u00e1ci\u00e1ch, pri\u010dom \u010derven\u00e9 krvinky zostali nepo\u0161koden\u00e9 [82]. Okrem toho sa uk\u00e1zalo, \u017ee intraven\u00f3zne podanie nano\u010dast\u00edc s prekurzorom melitt\u00ednu s pou\u017eit\u00edm nano\u010dast\u00edc per fluorouhl\u00edk v modeli my\u0161\u00ed s melan\u00f3mom \u00fa\u010dinne zn\u00ed\u017eilo r\u00fdchlos\u0165 rastu n\u00e1doru v porovnan\u00ed s lie\u010dbou fyziologick\u00fdm roztokom a slep\u00fdmi nano\u010dasticami [83].<\/p>\n\n\n\n

3.4. Antiv\u00edrusov\u00e9 a antibakteri\u00e1lne vlastnosti<\/p>\n\n\n\n

Je dobre zn\u00e1me, \u017ee BV a jej dve hlavn\u00e9 zlo\u017eky (melit\u00edn a PLA2) vykazuj\u00fa antimikrobi\u00e1lne aktivity, a preto sa m\u00f4\u017eu pou\u017ei\u0165 ako doplnkov\u00e9 antibakteri\u00e1lne l\u00e1tky [84,85,86,87]. Tieto zl\u00fa\u010deniny uplat\u0148uj\u00fa svoje \u00fa\u010dinky proti bakt\u00e9ri\u00e1m indukciou p\u00f3rov cez ich membr\u00e1ny, \u010do vedie k ich \u0161tiepeniu a n\u00e1sledne l\u00fdze [36].<\/p>\n\n\n\n

Napriek tomu sa antiv\u00edrusov\u00fd \u00fa\u010dinok BV v literat\u00fare pr\u00edli\u0161 nespom\u00edna. Ned\u00e1vna \u0161t\u00fadia sk\u00famala BV antiv\u00edrusov\u00fd potenci\u00e1l a priniesla zauj\u00edmav\u00e9 zistenia in vivo aj in vitro. T\u00e1to \u0161t\u00fadia uk\u00e1zala, \u017ee BV a melit\u00edn maj\u00fa v\u00fdznamn\u00e9 antiv\u00edrusov\u00e9 \u00fa\u010dinky proti mnoh\u00fdm obalen\u00fdm v\u00edrusom (v\u00edrus vezikul\u00e1rnej stomatit\u00eddy, v\u00edrus chr\u00edpky A, v\u00edrus herpes simplex at\u010f.) a neobalen\u00fdm v\u00edrusom (enterov\u00edrus-71 a v\u00edrus coxsackie) in vitro [88]. \u0160t\u00fadia tie\u017e uk\u00e1zala, \u017ee melit\u00edn chr\u00e1nil my\u0161i, ktor\u00e9 boli vystaven\u00e9 smrte\u013en\u00fdm d\u00e1vkam v\u00edrusu chr\u00edpky A H1N1. Hoci presn\u00fd mechanizmus \u00fa\u010dinku, ktor\u00fdm BV a melit\u00edn p\u00f4sobia ako antiv\u00edrusov\u00e9 \u010dinidl\u00e1, zost\u00e1va nejasn\u00fd, potvrdilo sa, \u017ee BV interaguje priamo s v\u00edrusov\u00fdm povrchom. Okrem toho m\u00f4\u017ee BV a jeho zlo\u017eky stimulova\u0165 interfer\u00f3n typu I (IFN), a teda potla\u010di\u0165 replik\u00e1ciu v\u00edrusu v hostite\u013eskej bunke [89].<\/p>\n\n\n\n

Okrem toho v\u00fdskumn\u00edci z Washington University School of Medicine v St. Louis ozn\u00e1mili mo\u017en\u00fa aplik\u00e1ciu nano\u010dast\u00edc naplnen\u00fdch melitt\u00ednom pri ni\u010den\u00ed v\u00edrusu \u013eudskej imunodeficiencie, pri\u010dom neinfikovan\u00e9 bunky zost\u00e1vaj\u00fa bez po\u0161kodenia. V tomto pr\u00edstupe autori navrhuj\u00fa prevent\u00edvnu strat\u00e9giu, v ktorej sa tieto nano\u010dastice pou\u017e\u00edvaj\u00fa pri v\u00fdvoji vagin\u00e1lneho g\u00e9lu, ktor\u00fd inhibuje \u0161\u00edrenie HIV. Jeho teoretick\u00fd princ\u00edp je nasledovn\u00fd: Molekuly melitt\u00ednu pr\u00edtomn\u00e9 na nano\u010dasticiach sa sp\u00e1jaj\u00fa s v\u00edrusov\u00fdm obalom a vytv\u00e1raj\u00fa p\u00f3rovit\u00e9 \u00fato\u010dn\u00e9 komplexy, \u010d\u00edm sa v\u00edrusov\u00fd obal rozb\u00edja [14]. \u010eal\u0161ia \u0161t\u00fadia uk\u00e1zala, \u017ee bvPLA2 m\u00f4\u017ee tie\u017e blokova\u0165 replik\u00e1ciu v\u00edrusu. Ten ist\u00fd t\u00edm \u010falej identifikoval peptidov\u00fa sekvenciu bvPLA2 zodpovedn\u00fa za inhib\u00edciu replik\u00e1cie HIV [89,90,91,92].<\/p>\n\n\n\n

  1. Z\u00e1very
    Pou\u017eitie BV na lek\u00e1rske \u00fa\u010dely mo\u017eno vysledova\u0165 tis\u00edce rokov sp\u00e4\u0165. Tu sa diskutuje o terapeutickom z\u00e1ujme surov\u00e9ho v\u010delieho jedu a\/alebo jeho hlavn\u00fdch zl\u00fa\u010den\u00edn, najm\u00e4 melit\u00ednu. Ten poskytuje \u0161irok\u00e9 protiz\u00e1palov\u00e9 vlastnosti t\u00fdm, \u017ee ovplyv\u0148uje sign\u00e1lne dr\u00e1hy prim\u00e1rneho z\u00e1palu a indukuje inhib\u00edciu expresie proz\u00e1palov\u00fdch g\u00e9nov. BV m\u00e1 tie\u017e neuroprotekt\u00edvny potenci\u00e1l pri neurodegenerat\u00edvnych ochoreniach, ako s\u00fa PD, AD a ALS t\u00fdm, \u017ee v\u00fdznamne blokuje ich progresiu a zlep\u0161uje kognit\u00edvne fungovanie na my\u0161ac\u00edch modeloch. Pokia\u013e ide o protin\u00e1dorov\u00fa aktivitu, melit\u00edn aj BV maj\u00fa cytotoxick\u00fd \u00fa\u010dinok na rakovinov\u00e9 bunky a v\u00fdznamn\u00fa antimetastatick\u00fa aktivitu. Optimaliza\u010dn\u00e9 pr\u00edstupy sa v s\u00fa\u010dasnosti zameriavaj\u00fa na mo\u017en\u00e9 vyu\u017eitie nano\u010dasticov\u00e9ho dod\u00e1vania melitt\u00ednu alebo dokonca BV, aby sa predi\u0161lo ich ne\u0161pecifick\u00e9mu cytotoxick\u00e9mu \u00fa\u010dinku. Antiv\u00edrusov\u00e1 aktivita BV je tie\u017e s\u013eubn\u00e1, preto\u017ee BV a melit\u00edn maj\u00fa pozoruhodn\u00e9 toxick\u00e9 \u00fa\u010dinky proti \u0161irok\u00e9mu spektru obalen\u00fdch v\u00edrusov, vr\u00e1tane n\u00e1ro\u010dn\u00e9ho HIV, a nieko\u013ek\u00fdch neobalen\u00fdch v\u00edrusov. Napokon, klinick\u00e1 aplik\u00e1cia terapie BV je e\u0161te dlh\u00e1 cesta, ale v\u00fdskumn\u00edci veria, \u017ee prebiehaj\u00faca pr\u00e1ca na tejto t\u00e9me nakoniec umo\u017en\u00ed, aby sa BV a jej zl\u00fa\u010deniny v nadch\u00e1dzaj\u00facich rokoch pova\u017eovali za kone\u010dn\u00fdch kandid\u00e1tov na r\u00f4zne terapie.<\/li><\/ol>\n\n\n\n

    Po\u010fakovanie
    Autori by sa chceli po\u010fakova\u0165 Eliemu N. Mahfoudovi za usilovn\u00fa korekt\u00faru pr\u00edspevku. Za u\u017eito\u010dn\u00fa diskusiu \u010fakuj\u00fa aj Cesarovi Matteiovi a Christianovi Legrosovi.<\/p>\n\n\n\n

    Autorsk\u00e9 pr\u00edspevky
    Konceptualiz\u00e1cia, Z.F. a J.-M.S.; z\u00edskavanie financi\u00ed, Z.F. a D.E.O.; p\u00edsanie \u2013 pr\u00edprava p\u00f4vodn\u00e9ho n\u00e1vrhu, R.W.; p\u00edsanie \u2013 recenzia a \u00faprava, J.F., R.W., M.R. a Z.F.<\/p>\n\n\n\n

    Financovanie
    Tento v\u00fdskum financovala Libanonsk\u00e1 univerzita.<\/p>\n\n\n\n

    Konflikt z\u00e1ujmov
    Autori nedeklaruj\u00fa \u017eiadny konflikt z\u00e1ujmov.<\/p>\n\n\n\n

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