{"id":297,"date":"2022-08-02T09:37:24","date_gmt":"2022-08-02T07:37:24","guid":{"rendered":"http:\/\/apitoxin.sk\/?p=297"},"modified":"2022-08-11T08:12:34","modified_gmt":"2022-08-11T06:12:34","slug":"vceli-jed-od-jedu-k-lieku","status":"publish","type":"post","link":"http:\/\/d.r5.wbsprt.com\/apitoxin.sk\/2022\/08\/02\/vceli-jed-od-jedu-k-lieku\/","title":{"rendered":"V\u010del\u00ed jed: Od jedu k lieku"},"content":{"rendered":"\n
  1. Entomologick\u00e1 div\u00edzia, Katedra zool\u00f3gie, Pr\u00edrodovedeck\u00e1 fakulta, Univerzita Beni-Suef, Beni-Suef 62521, Egypt
    2. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudsk\u00e1 Ar\u00e1bia
    3. \u00dastav patol\u00f3gie, Lek\u00e1rska fakulta, Univerzita Mansoura, Mansoura 35516, Egypt
    4. Katedra fyziol\u00f3gie, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudsk\u00e1 Ar\u00e1bia
    5. \u00dastav fyziol\u00f3gie, Lek\u00e1rska fakulta, Univerzita Beni-Suef, Beni-Suef 62521, Egypt
    6. Fyziologick\u00e1 div\u00edzia, Katedra zool\u00f3gie, Pr\u00edrodovedeck\u00e1 fakulta, Univerzita Beni-Suef, Beni-Suef 62521, Egypt
    *
    Autor, ktor\u00e9mu treba adresova\u0165 kore\u0161pondenciu.
    Akademick\u00ed redaktori: Nada Orsolic a Maja Jazvin\u0161\u0107ak Jembrek
    Molecules 2021, 26(16), 4941; https:\/\/doi.org\/10.3390\/molecules26164941
    Prijat\u00e9: 17. j\u00fana 2021 \/ Upraven\u00e9: 10. augusta 2021 \/ Prijat\u00e9: 11. augusta 2021 \/ Zverejnen\u00e9: 15. augusta 2021
    (Tento \u010dl\u00e1nok patr\u00ed do \u0161peci\u00e1lneho vydania v\u010del\u00edch produktov: Ned\u00e1vny pokrok v \u0161t\u00fadi\u00e1ch zdravotn\u00fdch v\u00fdhod)<\/li><\/ol>\n\n\n\n

    Abstraktn\u00e9
    Hmyz z radu Hymenoptera m\u00e1 obrann\u00fa l\u00e1tku, ktor\u00e1 obsahuje mnoho biologicky akt\u00edvnych zl\u00fa\u010den\u00edn. Konkr\u00e9tne, jed v\u010diel medonosn\u00fdch (Apis mellifera) obsahuje mno\u017estvo enz\u00fdmov a peptidov, ktor\u00e9 s\u00fa \u00fa\u010dinn\u00e9 proti r\u00f4znym chorob\u00e1m. R\u00f4zne v\u00fdskumn\u00e9 pr\u00e1ce uviedli mo\u017enos\u0165 pou\u017eitia v\u010delieho jedu (priame v\u010delie bodnutie alebo v injek\u010dnej forme) pri lie\u010dbe nieko\u013ek\u00fdch komplik\u00e1ci\u00ed; bu\u010f in vivo alebo in vitro. In\u00e9 spr\u00e1vy pou\u017e\u00edvali akt\u00edvne frakcie v\u010delieho jedu klinicky alebo v laborat\u00f3rnom meradle. Mnoho spr\u00e1v a publik\u00e1ci\u00ed uv\u00e1dza, \u017ee v\u010del\u00ed jed a jeho zlo\u017eky maj\u00fa viacero biologick\u00fdch \u00fa\u010dinkov vr\u00e1tane antimikrobi\u00e1lnych, antiprotozo\u00e1lnych, protirakovinov\u00fdch, protiz\u00e1palov\u00fdch a antiartritick\u00fdch vlastnost\u00ed. Cie\u013eom tohto preh\u013eadu je pouk\u00e1za\u0165 na pou\u017eitie samotn\u00e9ho v\u010delieho jedu alebo jeho frakci\u00ed pri lie\u010dbe nieko\u013ek\u00fdch chor\u00f4b a proti toxicite liekov ako alternat\u00edvneho protokolu terapie. Aktualizovan\u00e9 molekul\u00e1rne mechanizmy p\u00f4sobenia v\u010delieho jedu a jeho zlo\u017eiek s\u00fa diskutovan\u00e9 vo svetle predch\u00e1dzaj\u00facich aktualizovan\u00fdch publik\u00e1ci\u00ed. Preh\u013ead tie\u017e sumarizuje potenci\u00e1l jedu nalo\u017een\u00e9ho na nano\u010dastice ako nosi\u010da lie\u010diva a jeho molekul\u00e1rne mechanizmy. Nakoniec s\u00fa predveden\u00e9 aj produkty v\u010delieho jedu dostupn\u00e9 na trhoch.
    K\u013e\u00fa\u010dov\u00e9 slov\u00e1: v\u010del\u00ed jed; z\u00e1palov\u00e9 a chronick\u00e9 ochorenia; nano\u010dastice; produkty v\u010delieho jedu<\/p>\n\n\n\n

    1. \u00davod
      Apiterapia je alternat\u00edvna terapia, ktor\u00e1 sa opiera o pou\u017eitie produktov v\u010diel, predov\u0161etk\u00fdm v\u010delieho jedu, na lie\u010dbu mnoh\u00fdch \u013eudsk\u00fdch chor\u00f4b [1,2,3,4]. Lie\u010div\u00e9 \u00fa\u010dinky medu a in\u00fdch v\u010del\u00edch produktov s\u00fa uveden\u00e9 v r\u00f4znych n\u00e1bo\u017eensk\u00fdch knih\u00e1ch ako Veda, Biblia a Sv\u00e4t\u00fd Kor\u00e1n [5,6]. V\u0161emoh\u00faci Boh potvrdil pravdu, ke\u010f vo sv\u00e4tom Kor\u00e1ne povedal nasledovn\u00e9:
      \u201eA tvoj P\u00e1n vd\u00fdchol v\u010dele,\u201c vezmi si pre seba medzi hory, domy a medzi stromy a [v] tom, \u010do stavaj\u00fa (68). Potom jedzte zo v\u0161etk\u00fdch plodov a nasledujte cesty svojho P\u00e1na, ktor\u00e9 v\u00e1m ur\u010dil. z ich \u00fatrob vytek\u00e1 n\u00e1poj r\u00f4znej farby, v ktorom je pre \u013eud\u00ed lie\u010div\u00fd \u00fa\u010dinok. V skuto\u010dnosti je to znamenie pre \u013eud\u00ed, ktor\u00ed rozm\u00fd\u0161\u013eaj\u00fa (69). Surat Al-Nahl.
      Po tis\u00edce rokov \u013eudia pou\u017e\u00edvali v\u010delie produkty vr\u00e1tane medu, propolisu a jedu z eur\u00f3pskej v\u010dely medonosnej Apis mellifera ako lieky; pou\u017eitie t\u00fdchto produktov v\u010diel na lie\u010dbu chor\u00f4b je zn\u00e1me ako apiterapia. Lie\u010debn\u00e9 vyu\u017eitie v\u010delieho jedu sa datuje do starovek\u00e9ho Egypta a Gr\u00e9cka a v \u010c\u00edne sa praktizuje u\u017e 3000\u20135000 rokov [7]. Starovek\u00fd gr\u00e9cky lek\u00e1r Hippokrates pou\u017e\u00edval v\u010del\u00ed jed na terapeutick\u00e9 \u00fa\u010dely [8]. V modernej\u0161ej dobe z\u00e1ujem o \u00fa\u010dinky v\u010delieho jedu obnovili v roku 1868 Rusi Lokumski a Lubarski, ktor\u00ed publikovali pr\u00e1cu s n\u00e1zvom \u201eV\u010del\u00ed jed, liek\u201c [9]. V poslednej dobe lek\u00e1ri a licencovan\u00ed apiterapeuti pou\u017e\u00edvaj\u00fa v\u010del\u00ed jed na lie\u010dbu pacientov, ktor\u00ed trpia chronick\u00fdmi alebo autoimunitn\u00fdmi ochoreniami. Klinick\u00e9 \u0161t\u00fadie aj laborat\u00f3rne testy potvrdili, \u017ee v\u010del\u00ed jed je vynikaj\u00facou formou bioterapie. V\u010del\u00ed jed bu\u010f bojuje proti z\u00e1palu a de\u0161trukcii spojivov\u00fdch tkan\u00edv (ako v pr\u00edpade reumatizmu a artrit\u00eddy), alebo vracia aktivitu a pohyblivos\u0165 podporou prirodzenej obranyschopnosti organizmu (ako v pr\u00edpade roztr\u00fasenej skler\u00f3zy a lupusu) [1,10,11 ]. V poslednej dobe bol jed hodnoten\u00fd aj na lie\u010dbu r\u00f4znych typov rakoviny [12,13,14]. Okrem terapeutick\u00fdch \u00fa\u010dinkov sa v literat\u00fare uv\u00e1dza, \u017ee v\u010del\u00ed jed m\u00f4\u017ee zni\u017eova\u0165 ne\u017eiaduce \u00fa\u010dinky in\u00fdch typov liekov a konven\u010dn\u00fdch liekov [15,16,17].
      Cie\u013eom tohto preh\u013eadu je poskytn\u00fa\u0165 komplexn\u00fd aktualizovan\u00fd preh\u013ead zlo\u017eenia v\u010delieho jedu, v\u00fdhod a aplik\u00e1ci\u00ed v experiment\u00e1lnych a klinick\u00fdch liekoch. Preh\u013ead tie\u017e vysvetl\u00ed, ako m\u00f4\u017ee tento jed pom\u00f4c\u0165 pri lie\u010dbe mnoh\u00fdch \u013eudsk\u00fdch chor\u00f4b a p\u00f4sobi\u0165 proti nepriazniv\u00fdm ved\u013eaj\u0161\u00edm \u00fa\u010dinkom r\u00f4znych liekov. Okrem toho sa v preh\u013eade diskutuje aj o d\u00f4le\u017eitosti pou\u017eitia polym\u00e9rov a ich nanoforiem ako nosi\u010dov v\u010delieho jedu.<\/li><\/ol>\n\n\n\n
      1. Hymenoptera Hmyz
        V\u010dely, mravce a osy patriace do entomologick\u00e9ho poriadku: Hymenoptera m\u00f4\u017ee sp\u00f4sobi\u0165 toxicitu pre \u013eud\u00ed prostredn\u00edctvom envenom\u00e1cie. Niektor\u00e9 blanokr\u00eddlovce s\u00fa samot\u00e1rske, ale in\u00e9 s\u00fa prospe\u0161n\u00e9, ako napr\u00edklad ope\u013euj\u00face v\u010dely a parazitoidy. Druhy blanokr\u00eddlovcov, ktor\u00e9 m\u00f4\u017eu postihn\u00fa\u0165 \u013eud\u00ed, s\u00fa bodav\u00fd hmyz, ktor\u00fd m\u00f4\u017ee pou\u017ei\u0165 svoj bodav\u00fd n\u00e1stroj ako pomstu alebo agres\u00edvnu ruku. Tie, ktor\u00e9 koexistuj\u00fa v koloniz\u00e1cii, sp\u00f4sobuj\u00fa nebezpe\u010dn\u00e9 u\u0161tipnutia. Ich tox\u00edny \u010dasto sp\u00f4sobuj\u00fa boles\u0165 pred\u00e1torom. Jedn\u00fdm zo zauj\u00edmav\u00fdch vzorov blanokr\u00eddlovcov je bodav\u00fd. Reakciu bodnutia vyvol\u00e1vaj\u00fa r\u00f4zne faktory, ako s\u00fa vizu\u00e1lne sign\u00e1ly a vibr\u00e1cie. Okrem toho, vibr\u00e1cie hniezd alebo ob\u0165a\u017eovanie robotn\u00edkov s\u00fa faktory, ktor\u00e9 vyvol\u00e1vaj\u00fa \u0161t\u00edpanie alebo otravu [18].
        Jedy blanokr\u00eddlovcov s\u00fa vysoko komplexn\u00e9 kombin\u00e1cie sol\u00ed, organick\u00fdch prvkov (t.j. aminokysel\u00edn, alkaloidov) a neurotransmiterov [19,20]. Zlo\u017eenie jedov sa ve\u013emi l\u00ed\u0161i medzi blanokr\u00eddlymi druhmi a koncentr\u00e1ciou niektor\u00fdch zlo\u017eiek a l\u00ed\u0161i sa aj u druhov rovnak\u00e9ho rodu [21,22]. V\u010del\u00ed jed obsahuje niektor\u00e9 z rovnak\u00fdch zl\u00fa\u010den\u00edn ako osie jedy, ako je adrenal\u00edn, noradrenal\u00edn, dopam\u00edn, seroton\u00edn, histam\u00edn, hyaluronid\u00e1za, fosfolip\u00e1zy B (PLB) a fosfolip\u00e1zy A2 (PLA2), zatia\u013e \u010do apam\u00edn, melitt\u00edn a masti obsahuj\u00fa iba v\u010delie jedy. bunkov\u00fd degranula\u010dn\u00fd peptid (MCD) [23].<\/li>
      2. V\u010del\u00ed jed
        V\u010del\u00ed jed (api-tox\u00edn) vylu\u010duje \u017e\u013eaza umiestnen\u00e1 v bru\u0161nej dutine v\u010diel (Apis mellifera L.). Je to prieh\u013eadn\u00e1 kysl\u00e1 kvapalina bez z\u00e1pachu, ktor\u00fa v\u010dely \u010dasto pou\u017e\u00edvaj\u00fa ako obrann\u00fd n\u00e1stroj proti pred\u00e1torom. V\u010del\u00ed jed (komer\u010dne zn\u00e1my ako Apitox alebo Apitox\u00edn) je kombin\u00e1ciou r\u00f4znych zl\u00fa\u010den\u00edn. Ako uv\u00e1dzaj\u00fa mnoh\u00e9 publik\u00e1cie, v\u010del\u00ed jed obsahuje nieko\u013eko akt\u00edvnych molek\u00fal, ako s\u00fa peptidy a enz\u00fdmy vr\u00e1tane melit\u00ednu (hlavn\u00e1 zlo\u017eka v\u010delieho jedu), apam\u00ednu, adolap\u00ednu, peptidu degranuluj\u00faceho \u017e\u00edrne bunky a enz\u00fdmov (fosfolip\u00e1za A2 a hyaluronid\u00e1za), ako aj in\u00e9 -peptidov\u00e9 zlo\u017eky, ako je histam\u00edn, dopam\u00edn a norepinefr\u00edn [3,24,25]. Hlavn\u00fdmi zlo\u017ekami s\u00fa melit\u00edn, ktor\u00fd tvor\u00ed asi 50 percent such\u00e9ho jedu, a fosfolip\u00e1za A2 (PLA2), ktor\u00e1 tvor\u00ed asi 12 percent [26].
        V klasickej medic\u00edne sa v\u010del\u00ed jed a tox\u00edny z\u00edskan\u00e9 z v\u010diel pou\u017e\u00edvali na lie\u010dbu chronick\u00fdch z\u00e1palov\u00fdch por\u00fach, preto\u017ee maj\u00fa r\u00f4zne \u00fa\u010dinky, ako s\u00fa antiartritick\u00e9, protirakovinov\u00e9 a bolesti tlmiace \u00fa\u010dinky [24,26,27]. Pri terapii v\u010del\u00edm bodnut\u00edm v\u010dely id\u00fa priamo do cie\u013eov\u00e9ho bodu cez \u017eihadlo, zatia\u013e \u010do pri terapii v\u010del\u00edm jedom sa lyofilizovan\u00fd jed (zozbieran\u00fd od v\u010diel a n\u00e1sledne lyofilizovan\u00fd) vstrekuje priamo v r\u00f4znych d\u00e1vkach in situ [28,29]. Vpichovanie v\u010delieho jedu m\u00e1 schopnos\u0165 lie\u010di\u0165 r\u00f4zne ochorenia, ako s\u00fa autoimunitn\u00e9 poruchy (reumatoidn\u00e1 artrit\u00edda, psori\u00e1za at\u010f.), neurologick\u00e9 poruchy, chronick\u00e9 z\u00e1paly, boles\u0165, ko\u017en\u00e9 ochorenia a mikrobi\u00e1lne infekcie [2,8,29].
        3.1. Fyzik\u00e1lne vlastnosti, ch\u00e9mia a farmakol\u00f3gia v\u010delieho jedu
        V\u010del\u00ed jed je \u010d\u00edra tekutina s horkou chu\u0165ou, vo\u0148av\u00e1, m\u00e1 \u0161pecifick\u00fa hmotnos\u0165 1,13 a pH 4,5\u20135,5 [30,31]. Ke\u010f sa v\u010del\u00ed jed dostane do kontaktu so vzduchom, r\u00fdchlo vyschne a skry\u0161talizuje [32]. Su\u0161en\u00fd jed z\u00edska svetlo\u017elt\u00fa farbu a niektor\u00e9 komer\u010dn\u00e9 pr\u00edpravky s\u00fa hned\u00e9, o \u010dom sa predpoklad\u00e1, \u017ee je to kv\u00f4li oxid\u00e1cii niektor\u00fdch prote\u00ednov jedu. Je rozpustn\u00fd vo vode a nerozpustn\u00fd v alkohole a s\u00edrane am\u00f3nnom. V\u010del\u00ed jed obsahuje mno\u017estvo ve\u013emi prchav\u00fdch zl\u00fa\u010den\u00edn, ktor\u00e9 sa pri zbere \u013eahko str\u00e1caj\u00fa [28].
        Uv\u00e1dza sa, \u017ee v\u010del\u00ed jed obsahuje zmes mnoh\u00fdch zlo\u017eiek. Kateg\u00f3ria tak\u00fdchto zlo\u017eiek zah\u0155\u0148a prote\u00edny p\u00f4sobiace ako enz\u00fdmy, ako je fosfolip\u00e1za A2, fosfolip\u00e1za B, kysl\u00e1 fosfomonoester\u00e1za, hyaluronid\u00e1za, fosfat\u00e1za a lyzofosfolip\u00e1za, ako aj men\u0161ie prote\u00edny a peptidy, ako je melit\u00edn, apam\u00edn, adolap\u00edn, tertiap\u00edn a sekap\u00edn. \u010eal\u0161ie zlo\u017eky zah\u0155\u0148aj\u00fa fosfolipidy a fyziologicky akt\u00edvne am\u00edny, ako je histam\u00edn, dopam\u00edn a noradrenal\u00edn. \u010eal\u0161\u00edmi zlo\u017ekami s\u00fa aminokyseliny, cukry ako gluk\u00f3za a frukt\u00f3za, ferom\u00f3ny a miner\u00e1ly ako v\u00e1pnik a hor\u010d\u00edk. Hlavnou zlo\u017ekou v\u010delieho jedu je melit\u00edn, ktor\u00fd sa sklad\u00e1 z 26 aminokysel\u00edn a predstavuje 40\u201350 % such\u00e9ho jedu [8,12,33].
        Farmakol\u00f3gia v\u010delieho jedu bola \u0161tudovan\u00e1 prostredn\u00edctvom \u0161t\u00fadi\u00ed in vivo a in vitro [1,4,12,17,34,35,36,37]. V\u010del\u00ed jed m\u00e1 viacero r\u00f4znych farmakologick\u00fdch \u00fa\u010dinkov, ako s\u00fa antimutag\u00e9nne [37], antinocicept\u00edvne [37], r\u00e1dioprotekt\u00edvne [37], antihepatotoxick\u00e9 [17], cytoprotekt\u00edvne [17], antioxida\u010dn\u00e9 [4,17], antimikrobi\u00e1lne [4], antiv\u00edrusov\u00e9 [4], protiz\u00e1palov\u00e9 [4,17], neuroprotekt\u00edvne [4], antiartritick\u00e9 [1], antimetastatick\u00e9 [12] a protin\u00e1dorov\u00e9 [12] \u00fa\u010dinky (Postava 1).<\/li><\/ol>\n\n\n\n
        \"\"
        Obr\u00e1zok 1. Farmakologick\u00e9 aktivity v\u010delieho jedu.<\/figcaption><\/figure>\n\n\n\n

        3.2. In vitro a predklinick\u00e9 \u0161t\u00fadie
        V\u010del\u00ed jed bol sk\u00faman\u00fd nieko\u013ek\u00fdmi in vitro a predklinick\u00fdmi \u0161t\u00fadiami, ktor\u00e9 preuk\u00e1zali cel\u00fd rad jeho rozmanit\u00fdch biologick\u00fdch aktiv\u00edt.
        Uk\u00e1zalo sa, \u017ee v\u010del\u00ed jed m\u00e1 antioxida\u010dn\u00fa \u00fa\u010dinnos\u0165 in vitro aj in vivo. \u010co sa t\u00fdka \u0161t\u00fadi\u00ed in vitro, antioxida\u010dn\u00e1 aktivita v\u010delieho jedu bola hodnoten\u00e1 r\u00f4znymi met\u00f3dami, vr\u00e1tane schopnosti zachyt\u00e1va\u0165 2,2-difenyl-1-pikrylhydrazyl (DPPH), redukova\u0165 \u017eelezo\/antioxida\u010dn\u00fa silu (FRAP), 2,20-azinobis 3- etylbenzotiazol\u00edn-6-sulf\u00f3nov\u00e1 kyselina (ABTS) schopnos\u0165 zachyt\u00e1va\u0165 vo\u013en\u00e9 radik\u00e1ly, inhib\u00edcia l\u00e1tok reakt\u00edvnych na kyselinu tiobarbiturov\u00fa (TBARS) a inhib\u00edcia \u03b2-karot\u00e9nov\u00e9ho bielenia [4,38,39]. V\u00fdsledky t\u00fdchto \u0161t\u00fadi\u00ed odhalili antioxida\u010dn\u00fd potenci\u00e1l v\u010delieho jedu, hoci nebol spojen\u00fd s ur\u010ditou individu\u00e1lnou zl\u00fa\u010deninou. Somwongin a kol. [39] porovnali antioxida\u010dn\u00e9 \u00fa\u010dinky r\u00f4znych druhov Apis a zistili, \u017ee v\u0161etky extrakty z jedu vykazovali inhib\u00edciu DPPH, pri\u010dom najvy\u0161\u0161iu aktivitu vykazoval Apis dorsata nasledovan\u00fd Apis mellifera. <\/p>\n\n\n\n

        \u010co sa t\u00fdka \u0161t\u00fadi\u00ed in vivo, El-Hanoun a kol. [40] injek\u010dne pod\u00e1vali kr\u00e1likom 0,1, 0,2 a 0,3 mg na kr\u00e1lika subkut\u00e1nnou aplik\u00e1ciou dvakr\u00e1t t\u00fd\u017edenne po\u010das 20 t\u00fd\u017ed\u0148ov. V\u00fdsledky uk\u00e1zali zv\u00fd\u0161enie aktivity glutati\u00f3n-S-transfer\u00e1zy (GST) a obsahu glutati\u00f3nu (GSH) a zn\u00ed\u017eenie hlad\u00edn malondialdehydu (MDA) a TBARS u lie\u010den\u00fdch kr\u00e1likov, \u010do potvrdilo antioxida\u010dn\u00fd \u00fa\u010dinok v\u010delieho jedu. Okrem toho Mohamed a kol. [41] zistili, \u017ee u potkanov s indukovan\u00fdm \u017eal\u00fado\u010dn\u00fdm vredom lie\u010den\u00fdm v\u010del\u00edm jedom a kyselinou acetylsalicylovou do\u0161lo k oslabeniu peroxid\u00e1cie lipidov. Ahmed a kol. [1] uviedli, \u017ee zhor\u0161enie antioxida\u010dn\u00e9ho obrann\u00e9ho syst\u00e9mu u artritick\u00fdch potkanov vyvolan\u00fdch kompletn\u00fdm Freundov\u00fdm adjuvans (CFA) sa v\u00fdrazne zlep\u0161ilo v d\u00f4sledku pod\u00e1vania v\u010delieho jedu. Zlep\u0161enie antioxida\u010dn\u00e9ho obrann\u00e9ho syst\u00e9mu sa prejavilo zn\u00ed\u017een\u00edm peroxid\u00e1cie pe\u010de\u0148ov\u00fdch lipidov a zv\u00fd\u0161en\u00edm obsahu glutati\u00f3nu a aktivity antioxida\u010dn\u00fdch enz\u00fdmov vr\u00e1tane glutati\u00f3nperoxid\u00e1zy a GST.
        V\u010del\u00ed jed m\u00e1 okrem antioxida\u010dnej aktivity aj protiz\u00e1palov\u00e9 vlastnosti. Protiz\u00e1palov\u00fd \u00fa\u010dinok v\u010delieho jedu bol zaznamenan\u00fd pri artrit\u00edde vyvolanej CFA u potkanov [1] a na zvieracom modeli atopickej dermatit\u00eddy vyvolanej anhydridom kyseliny ftalovej [42]. Protiz\u00e1palov\u00e9 \u00fa\u010dinky sa prejavili zn\u00ed\u017een\u00edm zv\u00fd\u0161en\u00fdch hlad\u00edn interleuk\u00ednu-2 (IL-2) a interleuk\u00ednu-12 (IL-12) v s\u00e9re a zv\u00fd\u0161en\u00edm hladiny interleuk\u00ednu-10 (IL-10) pri artritike vyvolanej CFA. potkanov v d\u00f4sledku lie\u010dby v\u010del\u00edm jedom [1]. Protiz\u00e1palov\u00fa aktivitu v\u010delieho jedu mo\u017eno prip\u00edsa\u0165 jeho hlavnej zlo\u017eke, melit\u00ednu. Uv\u00e1dza sa, \u017ee t\u00e1to zl\u00fa\u010denina m\u00e1 protiz\u00e1palov\u00e9 \u00fa\u010dinky proti acne vulgaris, neuroz\u00e1palom, amyotrofickej later\u00e1lnej skler\u00f3ze, artrit\u00edde a z\u00e1palu pe\u010dene [43]. Lie\u010dba melit\u00ednom moduluje aktiv\u00e1ciu dr\u00e1h Toll-like receptorov (TLR) a inhibuje expresiu z\u00e1palov\u00fdch cytok\u00ednov. Zistilo sa, \u017ee melit\u00edn potl\u00e1\u010da aktiv\u00e1ciu jadrov\u00e9ho faktora kappa B (NF-\u03baB) p65 a inhibuje sign\u00e1l prote\u00ednkin\u00e1zy aktivovanej mitog\u00e9nom prote\u00edn 38 (p38 MAPK) in vitro [44]. Preto m\u00f4\u017ee by\u0165 protiz\u00e1palov\u00e1 aktivita sprostredkovan\u00e1 sign\u00e1lnymi dr\u00e1hami NF-KB a p38. In vivo melit\u00edn tie\u017e vykazoval protiz\u00e1palov\u00e9 vlastnosti modul\u00e1ciou transkrip\u010dn\u00fdch faktorov NF-\u03baB a aktiva\u010dn\u00e9ho prote\u00ednu 1 (AP-1) (obr\u00e1zok 2) [44]. Uv\u00e1dza sa, \u017ee melit\u00edn potl\u00e1\u010da sign\u00e1lne dr\u00e1hy Toll-like receptora typu 2 (TLR2), Toll-like receptora typu 4 (TLR4), klastrovej diferenci\u00e1cie 14 (CD14), NF-KB esenci\u00e1lneho modul\u00e1tora (NEMO) a rastu odvoden\u00e9ho od krvn\u00fdch do\u0161ti\u010diek faktor receptora beta (PDGFRp). Ovplyvnen\u00edm t\u00fdchto sign\u00e1lnych dr\u00e1h melit\u00edn zni\u017euje aktiv\u00e1ciu NF-\u03baB prote\u00ednu 38 (p38), extracelul\u00e1rneho sign\u00e1lom regulovanej kin\u00e1zy 1\/2 (ERK1\/2), prote\u00ednovej kin\u00e1zy B (PKB), Akt alebo fosfolip\u00e1zy C\u03b31 (PLC\u03b31). ako aj translok\u00e1ciu NF-KB do jadra (obr\u00e1zok 2). T\u00e1to deaktiv\u00e1cia vedie k zn\u00ed\u017eeniu z\u00e1palu ko\u017ee, aroty, k\u013abov, pe\u010dene a neur\u00f3nov\u00e9ho tkaniva (obr\u00e1zok 2) [45]. V \u010fal\u0161ej sign\u00e1lnej dr\u00e1he v\u010del\u00ed jed (alebo melit\u00edn) inhibuje uvo\u013e\u0148ovanie inhib\u00edtora NF-KB (IkB) prostredn\u00edctvom inhib\u00edcie IkB kin\u00e1z (IKK). Tak\u00e1to inhib\u00edcia by mohla by\u0165 sp\u00f4soben\u00e1 interakciou medzi SH skupinou I\u03baB kin\u00e1zy \u03b1 (IKK\u03b1) a I\u03baB kin\u00e1zy \u03b2 (IKK\u03b2) s v\u010del\u00edm jedom alebo molekulou melit\u00ednu, \u010do vedie k deaktiv\u00e1cii NF-\u03baB, a t\u00fdm zni\u017euje tvorbu z\u00e1palov\u00fdch medi\u00e1torov. V\u010del\u00ed jed, ako aj melit\u00edn m\u00f4\u017eu tie\u017e priamo interagova\u0165 s p50 NF-\u03baB, a t\u00fdm potla\u010di\u0165 translok\u00e1ciu p50 do jadra (obr\u00e1zok 2) [46]. R\u00f4zne extracelul\u00e1rne sign\u00e1ly vr\u00e1tane TNF-a (kanonick\u00e1 dr\u00e1ha) m\u00f4\u017eu aktivova\u0165 enz\u00fdm IkB kin\u00e1zu (IKK), \u010do vedie k aktiv\u00e1cii NF-KB a uvo\u013eneniu heterodim\u00e9rov p65\/p50. Translok\u00e1cia heterodim\u00e9rov NF-\u03baB p65\/p50 do jadra im umo\u017e\u0148uje viaza\u0165 sa na ich \u0161pecifick\u00e9 sekvencie DNA a podporuje cie\u013eov\u00e9 g\u00e9ny NF-\u03baB zapojen\u00e9 do z\u00e1palov\u00fdch reakci\u00ed [47]. V\u010del\u00ed jed a melit\u00edn m\u00f4\u017eu produkova\u0165 svoje protiz\u00e1palov\u00e9 \u00fa\u010dinky ovplyvnen\u00edm kanonickej dr\u00e1hy NF-\u03baB prostredn\u00edctvom inhib\u00edcie TNF-\u03b1 receptorov 1 a 2 (TNFR1 a TNFR2) (obr\u00e1zok 2) [48].<\/p>\n\n\n\n

        \"\"<\/figure>\n\n\n\n

        Obr\u00e1zok 2. Schematick\u00fd obr\u00e1zok zn\u00e1zor\u0148uj\u00faci navrhovan\u00e9 protiz\u00e1palov\u00e9 mechanizmy \u00fa\u010dinku v\u010delieho jedu a melit\u00ednu. NF-KB, jadrov\u00fd faktor-KB; IKB, inhib\u00edtor NF-KB; IkB\/NF-KB, IKB-NF-KB komplex; IKKa, IKB kin\u00e1za a; IKKp, IKB kin\u00e1za p; NEMO, esenci\u00e1lny modul\u00e1tor NF-\u03baB; TLR, Toll-like receptor; CD, zhluk diferenci\u00e1cie; PDGFRp, receptor beta rastov\u00e9ho faktora odvoden\u00e9ho od krvn\u00fdch do\u0161ti\u010diek; AP-1, aktiva\u010dn\u00fd prote\u00edn 1.<\/p>\n\n\n\n

        V\u010del\u00ed jed a jeho hlavn\u00e1 zlo\u017eka melit\u00edn maj\u00fa inhibi\u010dn\u00e9 \u00fa\u010dinky na rast rakovinov\u00fdch buniek pri rakovine prostaty. Down-regul\u00e1cia antiapoptotick\u00fdch g\u00e9nov\u00fdch produktov, ako je B-bunkov\u00fd lymf\u00f3m 2 (Bcl-2) (obr\u00e1zok 3), X-viazan\u00fd inhib\u00edtor apopt\u00f3zy (XIAP), indukovate\u013en\u00e1 synt\u00e1za oxidu dusnat\u00e9ho (iNOS) a cyklooxygen\u00e1za-2 ( COX-2) sa m\u00f4\u017ee podie\u013ea\u0165 na sprostredkovan\u00ed protirakovinov\u00fdch \u00fa\u010dinkov [49,50]. Je pozoruhodn\u00e9, \u017ee surov\u00fd v\u010del\u00ed jed a melit\u00edn odhalili protin\u00e1dorov\u00e9 aktivity proti r\u00f4znym rakovinov\u00fdm bunkov\u00fdm l\u00edni\u00e1m vr\u00e1tane bunkov\u00fdch l\u00edni\u00ed rakoviny prsn\u00edka, pe\u010dene, leuk\u00e9mie, p\u013e\u00fac, melan\u00f3mu a prostaty [51,52,53,54]. Protirakovinov\u00e9 \u00fa\u010dinky v\u010delieho jedu a jeho hlavnej zlo\u017eky melitt\u00edn mo\u017eno vysvetli\u0165 nieko\u013ek\u00fdmi sp\u00f4sobmi. Po prv\u00e9, protin\u00e1dorov\u00fd \u00fa\u010dinok m\u00f4\u017ee by\u0165 sprostredkovan\u00fd indukciou vonkaj\u0161\u00edch a vn\u00fatorn\u00fdch dr\u00e1h apopt\u00f3zy (obr\u00e1zok 3). Bolo hl\u00e1sen\u00e9, \u017ee v\u010del\u00ed jed a melit\u00edn zv\u00fd\u0161ili expresiu a hladiny r\u00f4znych proapoptotick\u00fdch a apoptotick\u00fdch medi\u00e1torov, ako s\u00fa cytochr\u00f3m C (Cyt C), prote\u00edn 53 (p53), prote\u00edn X asociovan\u00fd s Bcl-2 (Bax), homol\u00f3gy Bcl-2 antagonista\/killer (Bak), kasp\u00e1za-3, kasp\u00e1za-9 a r\u00f4zne typy receptorov smrti a redukovali antiapoptotick\u00fd medi\u00e1tor Bcl-2 [12,50,55]. Protin\u00e1dorov\u00e9 \u00fa\u010dinky v\u010delieho jedu a melit\u00ednu m\u00f4\u017eu by\u0165 tie\u017e sprostredkovan\u00e9 inhib\u00edciou sign\u00e1lnych dr\u00e1h NF-KB a komplexu v\u00e1pnik-kalmodul\u00edn (Ca2+\/CaM). T\u00e1to inhib\u00edcia n\u00e1sledne vedie k zn\u00ed\u017eeniu rastu a pre\u017eitia n\u00e1doru prostredn\u00edctvom potla\u010denia bunkovej prolifer\u00e1cie, angiogen\u00e9zy, antiapopt\u00f3zy, inv\u00e1zie a metast\u00e1z (obr\u00e1zok 3) [12]. Uv\u00e1dza sa, \u017ee v\u010del\u00ed jed zvy\u0161uje produkciu ROS z mitochondri\u00ed, ktor\u00e9 vyvol\u00e1vaj\u00fa vn\u00fatorn\u00fa apopt\u00f3zu. Okrem toho v\u010del\u00ed jed a melit\u00edn zv\u00fd\u0161ili produkciu faktora indukovan\u00e9ho apopt\u00f3zou (AIF) a endonukle\u00e1zy G (EndoG), \u010do s\u00fa mitochondri\u00e1lne prote\u00edny, ktor\u00e9 aktivuj\u00fa apopt\u00f3zu nez\u00e1visl\u00fa od kasp\u00e1zy [56,57].<\/p>\n\n\n\n

        \"\"
        Obr\u00e1zok 3. Schematick\u00fd obr\u00e1zok zn\u00e1zor\u0148uj\u00faci navrhovan\u00e9 protirakovinov\u00e9 mechanizmy \u00fa\u010dinku v\u010delieho jedu a melit\u00ednu. DR, receptor smrti; Cyt C, cytochr\u00f3m C; ROS, reakt\u00edvne formy kysl\u00edka; DNA, deoxynukleov\u00e1 kyselina; p53, prote\u00edn 53; Bcl-2, B-bunkov\u00fd lymf\u00f3m 2; Bax, Bcl-2-asociovan\u00fd Xprote\u00edn; Bak, antagonista\/zabijak homol\u00f3gov Bcl-2; NF-KB, jadrov\u00fd faktor-KB; Ca2+\/CaM, komplex v\u00e1pnik-kalmodul\u00edn; VEGF, vaskul\u00e1rny endotelov\u00fd rastov\u00fd faktor; VCAM1 vaskul\u00e1rna bunkov\u00e1 adh\u00e9zna molekula 1; ICAM1, intercelul\u00e1rna adh\u00e9zna molekula 1; MMP2\/9, matricov\u00e1 metaloprotein\u00e1za 2 a 9; cMyc, c- myelocytomat\u00f3za; Bcl-xL, B-bunkov\u00fd lymf\u00f3m extra ve\u013ek\u00fd; AIF, faktor indukovan\u00fd apopt\u00f3zou; EndoG, endonukle\u00e1za G; TRAILR, receptor ligandu indukuj\u00faceho apopt\u00f3zu s\u00favisiaci s TNF; FasR, fasreceptor.<\/figcaption><\/figure>\n\n\n\n

        Uv\u00e1dza sa, \u017ee v\u010del\u00ed jed m\u00e1 antimikrobi\u00e1lnu aktivitu, ktor\u00e1 sa pripisuje dvom jeho hlavn\u00fdm zlo\u017ek\u00e1m, melit\u00ednu a PLA2. Tak\u00e9to zl\u00fa\u010deniny m\u00f4\u017eu uplatni\u0165 svoje antimikrobi\u00e1lne \u00fa\u010dinky proti bakt\u00e9ri\u00e1m produkovan\u00edm p\u00f3rov cez ich membr\u00e1ny, \u010do vedie k ich po\u0161kodeniu a n\u00e1sledne k l\u00fdze [3,4,58]. Pod\u013ea Pucca et al. [59], tieto tox\u00edny v\u010delieho jedu m\u00f4\u017eu odvodi\u0165 synergicky zv\u00fd\u0161en\u00fa toxicitu prostredn\u00edctvom tvorby tox\u00ednov\u00fdch komplexov heterooligomeriz\u00e1ciou. Zv\u00fd\u0161en\u00e1 bakteri\u00e1lna l\u00fdza m\u00f4\u017ee by\u0165 sprostredkovan\u00e1 tvorbou heterooligom\u00e9rov melitt\u00edn-PLA2 na fosfolipidov\u00fdch dvojvrstvov\u00fdch membr\u00e1nach. Ke\u010f sa melit\u00edn kombinuje s PLA2, melit\u00edn sa s v\u00e4\u010d\u0161ou pravdepodobnos\u0165ou \u013eahko via\u017ee na neutr\u00e1lnu vonkaj\u0161iu membr\u00e1nu na povrchu molekuly via\u017eucej lipidy, \u010do vedie k synergicky zv\u00fd\u0161enej l\u00fdze. T\u00e1to v\u00e4zba je pravdepodobne sprostredkovan\u00e1 elektrostatickou pr\u00ed\u0165a\u017elivos\u0165ou medzi z\u00e1sadit\u00fdmi aminokyselinov\u00fdmi zvy\u0161kami melit\u00ednu a fosf\u00e1tovou skupinou fosfatidylchol\u00ednu (hlavn\u00e1 zlo\u017eka bunkov\u00fdch membr\u00e1n). V\u00e4zba melitt\u00edn-fosfolipid umo\u017e\u0148uje oligomeriz\u00e1ciu melitt\u00ednu, tvorbu membr\u00e1nov\u00fdch p\u00f3rov a l\u00fdzu [23,60]. Antiv\u00edrusov\u00fd \u00fa\u010dinok v\u010delieho jedu bol zaznamenan\u00fd so zauj\u00edmav\u00fdmi zisteniami in vivo aj in vitro. Pri v\u00fdskumoch in vitro maj\u00fa v\u010del\u00ed jed a melitt\u00edn v\u00fdznamn\u00e9 antiv\u00edrusov\u00e9 \u00fa\u010dinky proti neobalen\u00fdm v\u00edrusom (v\u00edrus coxsackie a enterov\u00edrus-71) \u200b\u200ba nieko\u013ek\u00fdm obalen\u00fdm v\u00edrusom (v\u00edrus vezikul\u00e1rnej stomatit\u00eddy, v\u00edrus chr\u00edpky A, v\u00edrus herpes simplex at\u010f.) [61]. In vivo 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 v\u010del\u00ed jed a melit\u00edn p\u00f4sobia ako antiv\u00edrusov\u00e9 l\u00e1tky, zost\u00e1va nejasn\u00fd, potvrdilo sa, \u017ee v\u010del\u00ed jed interaguje priamo s v\u00edrusov\u00fdm povrchom. Okrem toho v\u010del\u00ed jed a jeho zlo\u017eky m\u00f4\u017eu stimulova\u0165 interfer\u00f3n typu I (IFN), a teda potla\u010di\u0165 replik\u00e1ciu v\u00edrusu v hostite\u013eskej bunke [62].
        Okrem predch\u00e1dzaj\u00facej literat\u00fary Sig et al. [63], Bogdanov [8], Zhang a kol. [2] a Or\u0161oli\u0107 [12] uviedli, \u017ee v\u010del\u00ed jed m\u00e1 siln\u00e9 in vivo \u00fa\u010dinky proti artrit\u00edde, Parkinsonovej a Alzheimerovej chorobe a rakovine.<\/p>\n\n\n\n

        3.3. Klinick\u00e9 aplik\u00e1cie
        Vzh\u013eadom na \u0161irok\u00e9 spektrum biologick\u00fdch vlastnost\u00ed v\u010delieho jedu by nebolo prekvapuj\u00face, \u017ee jeho pou\u017eitie by mohlo dosiahnu\u0165 terapeutick\u00e9 \u00fa\u010dely pri \u013eudsk\u00fdch ochoreniach. Terapia v\u010del\u00edm jedom, podobne ako mnoh\u00e9 in\u00e9 pr\u00edstupy komplement\u00e1rnej a alternat\u00edvnej medic\u00edny, sa pou\u017e\u00edva na lie\u010dbu mnoh\u00fdch chor\u00f4b [4,28].
        Pred aplik\u00e1ciou injekci\u00ed injek\u010dn\u00fdmi strieka\u010dkami bol v\u010del\u00ed jed v\u017edy dod\u00e1van\u00fd priamo od v\u010diel medonosn\u00fdmi \u017eihadlami [64,65]. V s\u00fa\u010dasnosti sa v niektor\u00fdch podmienkach jed v\u010diel st\u00e1le dop\u013a\u0148a takouto tradi\u010dnou met\u00f3dou. \u017div\u00fa v\u010delu hladko pridr\u017e\u00ed pinzetou alebo in\u00fdmi n\u00e1strojmi osoba pod\u00e1vaj\u00faca v\u010del\u00ed jed, ktor\u00e1 potom prilo\u017e\u00ed v\u010delu na t\u00fa \u010das\u0165 tela pacienta, ktor\u00e1 sa m\u00e1 lie\u010di\u0165, a vtedy v\u010dela reflexne bodne. Tu stoj\u00ed za zmienku, \u017ee ke\u010f v\u010dely bodn\u00fa in\u00fd hmyz, nezomr\u00fa. Napriek tomu v\u010dela v\u00e4\u010d\u0161inou uhynie pri bodnut\u00ed do \u013eudsk\u00e9ho tela. Po bodnut\u00ed do \u013eudsk\u00e9ho tela v\u010dela nedok\u00e1\u017ee \u017eihadlo vytiahnu\u0165 sp\u00e4\u0165. Zanech\u00e1va za sebou nielen \u017eihadlo, ale aj \u010das\u0165 tr\u00e1viaceho traktu, plus svaly a nervy. Toto mas\u00edvne pretrhnutie brucha zabije v\u010delu [66].
        V z\u00e1vislosti od stavu sa sch\u00e9ma lie\u010dby m\u00f4\u017ee l\u00ed\u0161i\u0165. V tomto oh\u013eade m\u00f4\u017ee by\u0165 v\u010del\u00ed jed pod\u00e1van\u00fd r\u00f4znymi terapeutick\u00fdmi met\u00f3dami, ktor\u00e9 zah\u0155\u0148aj\u00fa priame bodnutie v\u010delou, injekciu v\u010delieho jedu alebo akupunkt\u00faru v\u010delieho jedu (tie\u017e naz\u00fdvan\u00fa apiterapia). Hoci sa odpor\u00fa\u010da pod\u00e1vanie v\u010delieho jedu injek\u010dnou strieka\u010dkou a nie priamo od v\u010diel, v\u00e4\u010d\u0161ina \u0161t\u00fadi\u00ed a prakt\u00edk vyu\u017e\u00edva akupunkt\u00faru v\u010delieho jedu vzh\u013eadom na bioaktivitu spojen\u00fa s mechanickou stimul\u00e1ciou akupunkt\u00fary [2,4,65].
        V klinickom prostred\u00ed sa uv\u00e1dza, \u017ee injekcia v\u010delieho jedu v akutn\u00fdch bodoch je \u00fa\u010dinn\u00e1 pri lie\u010dbe klinick\u00fdch por\u00fach, ako je Parkinsonova choroba, neuropatick\u00e1 boles\u0165, Alzheimerova choroba, ochorenie medzistavcov\u00fdch platni\u010diek, poranenie miechy, muskuloskelet\u00e1lna boles\u0165, artrit\u00edda, roztr\u00fasen\u00e1 skler\u00f3za, ko\u017ea choroba a rakovina [67]. \u00da\u010dinnos\u0165 injekcie v\u010delieho jedu v akupunkt\u00farnych bodoch mo\u017eno vypl\u00fdva z jeho protiz\u00e1palov\u00fdch, antinocicept\u00edvnych a antiapopt\u00f3znych \u00fa\u010dinkov.
        Pokia\u013e ide o terapeutick\u00fd potenci\u00e1l v\u010diel, \u0161t\u00fadia vykonan\u00e1 na \u013eu\u010foch preuk\u00e1zala, \u017ee akupunkt\u00fara v\u010del\u00edm jedom preuk\u00e1zala \u00fa\u010dinnos\u0165 ako adjuvans pri lie\u010dbe Parkinsonovej choroby, ke\u010f boli dospel\u00ed stimulovan\u00ed na 10 akupunkt\u00farnych bodoch dvakr\u00e1t t\u00fd\u017edenne po\u010das 8 t\u00fd\u017ed\u0148ov [68].
        Pod\u013ea klinickej \u0161t\u00fadie Hausera et al. [10] sa zistilo, \u017ee terapeutick\u00e9 injekcie v\u010delieho jedu pacientom so skler\u00f3zou multiplex s\u00fa \u00fa\u010dinn\u00e9 pri zni\u017eovan\u00ed funk\u010dnej slabosti pacienta sp\u00f4sobenej chorobou. Po\u010das 12-mesa\u010dn\u00e9ho sk\u00fa\u0161ania s pou\u017eit\u00edm lie\u010dby v\u010del\u00edm jedom pacienti vykazovali v\u00fdznamn\u00e9 zlep\u0161enie rovnov\u00e1hy, koordin\u00e1cie, kontroly mo\u010dov\u00e9ho mech\u00fara a \u010driev, sily horn\u00fdch a doln\u00fdch kon\u010dat\u00edn, \u00fanavy, vytrvalosti, spasticity a necitlivosti. \u0160tatisticky boli zaznamenan\u00e9 v\u00fdrazn\u00e9 zlep\u0161enia pri ch\u00f4dzi, st\u00fapan\u00ed po schodoch, presunoch autom, presunoch na l\u00f4\u017eko, presunoch na toaletu, presunoch vo vani a polohovan\u00ed postele. V inej klinickej \u0161t\u00fadii Wesselius a spol. [69] odhalili, \u017ee lie\u010dba v\u010del\u00edm jedom u pacientov s recidivuj\u00facou skler\u00f3zou multiplex nezn\u00ed\u017eila aktivitu ochorenia, invaliditu alebo \u00fanavu a nezlep\u0161ila kvalitu \u017eivota.
        Liu a kol. [70] uviedli, \u017ee aplik\u00e1cia kombinovanej terapie v\u010del\u00edm jedom s in\u00fdmi liekmi je pri lie\u010dbe reumatoidnej artrit\u00eddy \u00fa\u010dinnej\u0161ia ako jednoduch\u00e9 pou\u017eitie liekov. Tie\u017e uviedli, \u017ee ke\u010f bola aplikovan\u00e1 terapia v\u010del\u00edm bodnut\u00edm, d\u00e1vky z\u00e1padn\u00fdch liekov sa m\u00f4\u017eu zn\u00ed\u017ei\u0165 a miera relapsov sa zn\u00ed\u017ei.
        Obr\u00e1zok 4 [71,72,73,74,75,76,77,78,79,80,81,82,83,84] sumarizuje terapeutick\u00e9 \u00fa\u010dinky a sp\u00f4sob p\u00f4sobenia v\u010delieho jedu pri r\u00f4znych chorob\u00e1ch a stavoch. \u00da\u010dinky a akcie na obr\u00e1zkoch s\u00fa podporen\u00e9 odkazmi.<\/p>\n\n\n\n

        \"\"
        Obr\u00e1zok 4. Terapeutick\u00e9 \u00fa\u010dinky a sp\u00f4sob p\u00f4sobenia v\u010delieho jedu. Skratky: CNS, centr\u00e1lny nervov\u00fd syst\u00e9m; PNS, perif\u00e9rny nervov\u00fd syst\u00e9m; MS, roztr\u00fasen\u00e1 skler\u00f3za; BPH, ben\u00edgna hyperpl\u00e1zia prostaty; TNF-a, tumor nekrotizuj\u00faci faktor-a; Hepatocyty o\u0161etren\u00e9 Act D, hepatocyty o\u0161etren\u00e9 aktinomyc\u00ednom D.<\/figcaption><\/figure>\n\n\n\n

        Hoci existuje ve\u013ea presved\u010div\u00fdch v\u00fdsledkov t\u00fdkaj\u00facich sa potenci\u00e1lneho pou\u017eitia v\u010delieho jedu, konkr\u00e9tnej\u0161ie melit\u00ednu, proti r\u00f4znym typom rakoviny, jeho pou\u017eite\u013enos\u0165 u \u013eud\u00ed zost\u00e1va ve\u013emi n\u00e1ro\u010dn\u00e1 vzh\u013eadom na jeho ne\u0161pecifick\u00fa cytotoxicitu [85].
        Napriek \u0161irok\u00e9mu spektru terapeutick\u00e9ho potenci\u00e1lu v\u010delieho jedu existuje paraleln\u00e1 realita potenci\u00e1lnych ved\u013eaj\u0161\u00edch \u00fa\u010dinkov alebo alergick\u00fdch reakci\u00ed spojen\u00fdch s pod\u00e1van\u00edm v\u010delieho jedu [86].
        3.3.1. Testovanie alergi\u00ed, pokyny pre pacientov a kontraindik\u00e1cie
        Syst\u00e9movo-alergick\u00e9 reakcie na v\u010delie bodnutie boli preuk\u00e1zan\u00e9 a\u017e u 3,4 % det\u00ed a a\u017e u 7,5 % dospel\u00fdch. Tieto alergick\u00e9 reakcie mo\u017eno kategorizova\u0165 ako mierne a obmedzen\u00e9 na ko\u017eu alebo stredne z\u00e1va\u017en\u00e9 a\u017e z\u00e1va\u017en\u00e9 s rizikom \u017eivot ohrozuj\u00facej anafylaxie. Preto pred aplik\u00e1ciou terapie v\u010del\u00edm jedom by sa mal vykona\u0165 test na alergiu. Jedinou lie\u010dbou na elimin\u00e1ciu \u010fal\u0161\u00edch syst\u00e9mov\u00fdch reakci\u00ed na bodnutie jedom je imunoterapia jedom, ktor\u00e1 je indikovan\u00e1 na prevenciu \u010fal\u0161\u00edch stredne \u0165a\u017ek\u00fdch a\u017e \u0165a\u017ek\u00fdch syst\u00e9mov\u00fdch reakci\u00ed na bodnutie u det\u00ed a dospel\u00fdch alergick\u00fdch na jed [87].
        Na testovanie alergie sa asi 0,05 ml (1,0 mg \u010dist\u00e9ho lyofilizovan\u00e9ho jedu rozpusten\u00e9ho v 1,0 ml fyziologick\u00e9ho roztoku) vstrekne do flexorov\u00e9ho povrchu predlaktia pacienta. Pomaly sa vstrekuje, aby sa vytvorila mal\u00e1 pologu\u013eov\u00e1 kvap\u00f4\u010dka. Ak sa do 15\u201330 min\u00fat po intraderm\u00e1lnej injekcii v\u010delieho jedu neobjavia \u017eiadne syst\u00e9mov\u00e9 reakcie, pacient sa v teste pova\u017euje za negat\u00edvneho. V pr\u00edpade anafylaxie m\u00e1 pacient dosta\u0165 intenz\u00edvnu lek\u00e1rsku starostlivos\u0165, ktor\u00e1 zah\u0155\u0148a injekciu adrenal\u00ednu a\/alebo dexametaz\u00f3nu. Preto\u017ee citlivos\u0165 na v\u010del\u00ed jed sa u jednotliv\u00fdch os\u00f4b l\u00ed\u0161i, neexistuje v\u0161eobecn\u00fd protokol pre v\u0161etk\u00fdch pacientov, ktor\u00ed s\u00fa lie\u010den\u00ed v\u010del\u00edm jedom. Pre citliv\u00e9 osoby by sa mal pou\u017ei\u0165 \u0161pecializovan\u00fd protokol. V pr\u00edpade chronick\u00fdch z\u00e1palov\u00fdch por\u00fach by sa na dosiahnutie najlep\u0161\u00edch v\u00fdsledkov malo vykona\u0165 pribli\u017ene 12\u201320 seden\u00ed. Niektor\u00e9 pr\u00edpady vy\u017eaduj\u00fa dlh\u00e9 obdobia lie\u010dby, ako napr\u00edklad reumatoidn\u00e1 artrit\u00edda, psori\u00e1za, roztr\u00fasen\u00e1 skler\u00f3za a lupus. Pacientom sa odpor\u00fa\u010da, aby dodr\u017eiavali nasleduj\u00face pokyny, aby dosiahli \u010do najlep\u0161ie v\u00fdsledky [88].
        a. 2\u20133 mg vitam\u00ednu C denne sa odpor\u00fa\u010da celoplo\u0161n\u00e1 lie\u010dba v\u010del\u00edm jedom;
        b. 650 mg acetaminof\u00e9nu sa m\u00f4\u017ee u\u017e\u00edva\u0165 v pr\u00edpade hor\u00fa\u010dky a zimnice;
        c. Po\u010das terapie v\u010del\u00edm jedom je pr\u00edsne zak\u00e1zan\u00fd alkohol;
        d. \u013dadov\u00fd obklad mo\u017eno aplikova\u0165 na miesto vpichu, ak sa vyskytla lok\u00e1lna syst\u00e9mov\u00e1 reakcia (ako je opuch a\/alebo \u0161krabanie);
        e. Ak sa vyskytli lok\u00e1lne reakcie (anafylaxia), pacient by mal okam\u017eite dosta\u0165 subkut\u00e1nnu injekciu adrenal\u00ednu (adrenal\u00edn) a potom by mal by\u0165 prevezen\u00fd do nemocnice.<\/p>\n\n\n\n

        Aplik\u00e1cia v\u010delieho jedu pri lie\u010dbe \u013eud\u00ed je kontraindikovan\u00e1 pri mnoh\u00fdch stavoch, ako s\u00fa deti do 5 rokov, tehotenstvo, doj\u010denie, ak\u00fatne a chronick\u00e9 infekcie, po o\u010dkovan\u00ed, zlyhanie obli\u010diek a pe\u010dene, srdcov\u00e9 a respira\u010dn\u00e9 probl\u00e9my, chronick\u00e1 tuberkul\u00f3za, hepatit\u00edda, ak\u00fatna rakovina a diabetes mellitus 1. typu [88].
        3.3.2. Cesta pod\u00e1vania v\u010delieho jedu
        Vzh\u013eadom na bielkovinov\u00fa povahu v\u010delieho jedu je pod\u00e1vanie or\u00e1lnou cestou \u0165a\u017ek\u00e9, preto\u017ee ho tr\u00e1viace enz\u00fdmy m\u00f4\u017eu str\u00e1vi\u0165 [4]. Terapia v\u010del\u00edm jedom sa m\u00f4\u017ee pod\u00e1va\u0165 r\u00f4znymi sp\u00f4sobmi, ako je priame bodnutie v\u010delami do \u0161pecifick\u00fdch bodov, injekcia vy\u010disten\u00e9ho a steriln\u00e9ho v\u010delieho jedu, masti, kr\u00e9my, pilulky, kvapky, homeopatick\u00e9 pr\u00edpravky Apis, elektrofor\u00e9za a fonofor\u00e9za (obr\u00e1zok 5). Za tradi\u010dn\u00fa met\u00f3du lie\u010dby sa pova\u017euje terapia priamym bodnut\u00edm v\u010diel medonosnou. M\u00e1 viacero nev\u00fdhod, ako je boles\u0165 a z\u00e1pal sp\u00f4soben\u00fd bodnut\u00edm, \u0165a\u017ekosti s udr\u017eiavan\u00edm jeho pravideln\u00fdch koncentr\u00e1ci\u00ed v krvi, potreba dlhodob\u00e9ho pod\u00e1vania s\u00e9rie bodnut\u00ed alebo injekci\u00ed z d\u00f4vodu kr\u00e1tkeho pol\u010dasu melit\u00ednu a \u0165a\u017ekosti s pacientov [89]. Relat\u00edvne kr\u00e1tky plazmatick\u00fd pol\u010das v\u010delieho jedu a problematick\u00e1 povaha stanovenia jeho definit\u00edvnej d\u00e1vky viedli v\u00fdskumn\u00edkov a odborn\u00edkov k podpore a v\u00fdvoju in\u00fdch alternat\u00edv, ako je kombin\u00e1cia s polym\u00e9rmi alebo nano\u010dasticami (NP) [90].<\/p>\n\n\n\n

        \"\"
        Obr\u00e1zok 5. Met\u00f3dy terapi\u00ed v\u010del\u00edm jedom.<\/figcaption><\/figure>\n\n\n\n

        3.3.3. Terapia v\u010del\u00edm jedom v nemocniciach
        Najzn\u00e1mej\u0161ia sk\u00fasenos\u0165 s terapiou v\u010del\u00edm jedom bola v rusk\u00fdch nemocniciach. Tabu\u013eka 1 ukazuje sk\u00fasenosti Dr. Krylova a jeho kolegov [91] s pou\u017eit\u00edm terapie v\u010del\u00edm jedom pri lie\u010dbe roztr\u00fasenej skler\u00f3zy v \u010ce\u013eabinskom centre pre skler\u00f3zu multiplex v Rusku. Okrem toho rusk\u00fd apiterapeut Dr. Ludyanski lie\u010dil r\u00f4zne ochorenia [73] v ruskej nemocnici pomocou v\u010delieho jedu (tabu\u013eka 2).<\/p>\n\n\n\n

        \"\"
        Tabu\u013eka 1. Experiment s lie\u010dbou v\u010del\u00edm jedom na pacientoch so skler\u00f3zou multiplex v ruskom centre \u010ce\u013eabinsk [91].<\/figcaption><\/figure>\n\n\n\n
        \"\"
        Tabu\u013eka 2. Sk\u00fasenosti Dr. Ludjansk\u00e9ho s v\u010del\u00edm jedom pri lie\u010dbe r\u00f4znych ochoren\u00ed v ruskej nemocnici [72].<\/figcaption><\/figure>\n\n\n\n

        3.3.4. Ne\u017eiaduce \u00fa\u010dinky v\u010delieho jedu
        <\/strong>Hoci boli preuk\u00e1zan\u00e9 terapeutick\u00e9 \u00fa\u010dinky v\u010delieho jedu, jeho bezpe\u010dnos\u0165 je st\u00e1le silne limituj\u00facim faktorom [2]. Ne\u017eiaduce \u00fa\u010dinky v\u010delieho jedu siahaj\u00fa od miernych ko\u017en\u00fdch reakci\u00ed, ktor\u00e9 sa po nieko\u013ek\u00fdch d\u0148och zotavia, a\u017e po \u017eivot ohrozuj\u00face \u0165a\u017ek\u00e9 alebo smrte\u013en\u00e9 anafylaktick\u00e9 reakcie. V roku 2015 systematick\u00fd preh\u013ead a metaanal\u00fdza hodnotili ne\u017eiaduce \u00fa\u010dinky lie\u010dby v\u010del\u00edm jedom. Spomedzi 145 \u0161t\u00fadi\u00ed sa ne\u017eiaduce udalosti vyskytli v 58 \u0161t\u00fadi\u00e1ch [64]. Tieto ne\u017eiaduce udalosti zah\u0155\u0148aj\u00fa imunologick\u00e9 syst\u00e9mov\u00e9 reakcie, lok\u00e1lne svrbenie alebo opuch, alergiu, boles\u0165, ko\u017en\u00e9 probl\u00e9my a ne\u0161pecifick\u00e9 reakcie [64]. Okrem toho sa m\u00f4\u017ee vyskytn\u00fa\u0165 ak\u00fatny anafylaktick\u00fd \u0161ok, hemol\u00fdza, Guillaume-Barreov syndr\u00f3m a ireverzibiln\u00e9 po\u0161kodenie uln\u00e1rneho nervu [86]. Ne\u017eiaduce \u00fa\u010dinky v\u010delieho jedu mo\u017eno prip\u00edsa\u0165 precitlivenosti [92,93], pretrv\u00e1vaj\u00facemu lok\u00e1lnemu z\u00e1palu [94], frekvencii pod\u00e1vania v\u010delieho jedu a koncentr\u00e1cii jedu [2].
        Naproti tomu Kim a spol. [95] zistili, \u017ee subkut\u00e1nna injekcia v\u010delieho jedu a jeho frakci\u00ed nemala pri najvy\u0161\u0161ej testovanej d\u00e1vke (200-kr\u00e1t a 100-kr\u00e1t vy\u0161\u0161ej) \u017eiadne v\u00fdznamn\u00e9 ved\u013eaj\u0161ie \u00fa\u010dinky na celkov\u00e9 fyziologick\u00e9 funkcie centr\u00e1lnych nervov, ako aj kardiovaskul\u00e1rne respira\u010dn\u00e9 a gastrointestin\u00e1lne funkcie d\u00e1vky, ne\u017e ak\u00e9 sa pou\u017e\u00edvaj\u00fa klinicky). Pod\u013ea v\u00fdsledkov takejto \u0161t\u00fadie s\u00fa d\u00e1vky v\u010delieho jedu v terapeutickom rozsahu alebo vy\u0161\u0161ie v klinick\u00fdch \u0161t\u00fadi\u00e1ch bezpe\u010dn\u00e9 a m\u00f4\u017eu sa pou\u017ei\u0165 ako bezpe\u010dn\u00e9 antinocicept\u00edvne a protiz\u00e1palov\u00e9 \u010dinidl\u00e1.
        Je dobre zn\u00e1me, \u017ee u\u0161tipnutie v\u010delou a injekcia v\u010delieho jedu sp\u00f4sobuj\u00fa okrem z\u00e1palu aj boles\u0165 [96]. Ve\u013ea hromadiacich sa d\u00f4kazov podporuje hypot\u00e9zu, \u017ee melit\u00edn je hlavnou zlo\u017ekou v\u010delieho jedu, ktor\u00e1 sp\u00f4sobuje boles\u0165 [97]. Chen a kol. [97] odhalili, \u017ee subkut\u00e1nna injekcia melitt\u00ednu sp\u00f4sobuje pocit tonickej bolesti u zvierat aj u \u013eud\u00ed. T\u00e1to schopnos\u0165 vyvola\u0165 boles\u0165 m\u00f4\u017ee by\u0165 sprostredkovan\u00e1 priamou alebo nepriamou aktiv\u00e1ciou prim\u00e1rnych nociceptorov\u00fdch buniek melit\u00ednom.
        Medzi \u010fal\u0161ie nepriazniv\u00e9 \u00fa\u010dinky v\u010delieho jedu a melit\u00ednu patr\u00ed hemol\u00fdza kv\u00f4li ich vysokej lytickej aktivite na \u013eudsk\u00e9 erytrocytov\u00e9 bunky [45,98]. Okrem toho je melit\u00edn cytotoxick\u00fd pre \u013eudsk\u00e9 lymfocyty perif\u00e9rnej krvi sp\u00f4sobom z\u00e1visl\u00fdm od d\u00e1vky a \u010dasu. Vedie ku granul\u00e1cii, morfologick\u00fdm zmen\u00e1m a nakoniec k l\u00fdze buniek [45,99].<\/p>\n\n\n\n

        3.4. Produkty v\u010delieho jedu
        V z\u00e1padn\u00fdch krajin\u00e1ch s\u00fa injek\u010dn\u00e9 formy v\u010delieho jedu alternat\u00edvou k niektor\u00fdm liekom, ktor\u00e9 maj\u00fa ved\u013eaj\u0161ie \u00fa\u010dinky. To plat\u00ed najm\u00e4 pre reumatoidn\u00fa artrit\u00eddu. V z\u00e1vislosti od typu ochorenia mo\u017eno v\u010del\u00ed jed pou\u017ei\u0165 vo forme kr\u00e9mov\u00fdch [73, 100] tabliet alebo mast\u00ed [101]. In\u00e9 liekov\u00e9 formy pozost\u00e1vaj\u00fa zo zmesi v\u010delieho jedu so steriln\u00fdmi injek\u010dn\u00fdmi tekutinami a ich plnen\u00edm do sklenen\u00fdch liekoviek alebo strieka\u010diek. Okrem toho sa such\u00fd jed udr\u017eiava lyofilizovan\u00fd a potom sa zmie\u0161a s rozp\u00fa\u0161\u0165adlom v \u010dase injekcie [102]. V Eur\u00f3pe a \u010c\u00edne sa roztoky v\u010delieho jedu pou\u017e\u00edvaj\u00fa aj s elektrofor\u00e9zou alebo ultrasonofor\u00e9zou. Niektor\u00ed v\u00fdrobcovia prid\u00e1vali do v\u010delieho jedu niektor\u00e9 \u010fal\u0161ie v\u010delie produkty (ako je pe\u013eov\u00fd propolis, med a matersk\u00e1 ka\u0161i\u010dka), aby dosiahli v\u00fdrazn\u00e9 \u00fa\u010dinky. Tabu\u013eka 3 zobrazuje niektor\u00e9 produkty dostupn\u00e9 na trhoch, ako aj ich d\u00e1vkov\u00fa formu, indik\u00e1cie a v\u00fdrobcov.<\/p>\n\n\n\n

        \"\"
        Tabu\u013eka 3. Niektor\u00e9 produkty v\u010delieho jedu dostupn\u00e9 na trhoch.<\/figcaption><\/figure>\n\n\n\n

        3.5. Licencovanie v\u010delieho jedu ako lieku
        V z\u00e1padoeur\u00f3pskych a severoamerick\u00fdch krajin\u00e1ch existuje len jedna leg\u00e1lne schv\u00e1len\u00e1 injek\u010dn\u00e1 forma v\u010diel na znecitlivenie os\u00f4b, ktor\u00e9 s\u00fa hyperalergick\u00e9 na v\u010del\u00ed jed [102]. Injekcia v\u010delieho jedu bola schv\u00e1len\u00e1 ako bioterapeutick\u00fd liek juhok\u00f3rejskou spr\u00e1vou potrav\u00edn a liekov (Juhok\u00f3rejsk\u00fd FDA), ale v Spojen\u00fdch \u0161t\u00e1toch (USA) \u010dak\u00e1 na schv\u00e1lenie FDA. V Spojen\u00fdch \u0161t\u00e1toch a na celom svete je ve\u013ea zn\u00e1mych apiterapeutov, ktor\u00ed aplikuj\u00fa apiterapiu, ako napr\u00edklad Bodog F. Beck, M.D. (New York); Raymond Carey, M.D. (Kalifornia); Stephan Stangaciu, M.D. (Rumunsko); H. O’Connell, M.D. (Connecticut); Joseph Broadman, M.D. (New York); L. A. Doyle, M. D. (Iowa); Christopher M-H Kim, M.D. (Ju\u017en\u00e1 K\u00f3rea); Joseph Saine, M.D. (Montreal); a Charles Mraz, majster v\u010del\u00e1r (Vermont).<\/p>\n\n\n\n

        3.6. Potenci\u00e1l v\u010delieho jedu nalo\u017een\u00e9ho na polym\u00e9roch a nano\u010dasticiach (NP)
        Preto\u017ee bodnutie v\u010delou a injekcie v\u010delieho jedu maj\u00fa mnoho nev\u00fdhod, bol by potrebn\u00fd n\u00e1vrh vhodn\u00e9ho syst\u00e9mu s postupn\u00fdm uvo\u013e\u0148ovan\u00edm, ktor\u00fd poskytuje dlhodob\u00fd a kon\u0161tantn\u00fd terapeutick\u00fd \u00fa\u010dinok. Ned\u00e1vno boli NP pripraven\u00e9 z biodegradovate\u013en\u00fdch polym\u00e9rov, ako je poly-D, kyselina L-mlie\u010dna-ko-glykolov\u00e1 (PLGA), algin\u00e1t a chitosan. Tieto polym\u00e9ry a ich NP s\u00fa vynikaj\u00facimi a \u00fa\u010dinn\u00fdmi nosi\u010dmi pre bioakt\u00edvne zl\u00fa\u010deniny. V\u010del\u00ed jed tak m\u00f4\u017ee by\u0165 nanesen\u00fd na tieto polym\u00e9ry a ich NP, aby sa zlep\u0161ilo jeho dod\u00e1vanie a uvo\u013e\u0148ovanie, \u010do vedie k zlep\u0161enej kompliancii pacienta odstr\u00e1nen\u00edm potreby \u010dast\u00fdch injekci\u00ed. \u010cas degrad\u00e1cie pre NP m\u00f4\u017ee by\u0165 kontrolovan\u00fd z dn\u00ed na roky zmenou typu a mno\u017estva polym\u00e9rov, molekulov\u00fdch hmotnost\u00ed polym\u00e9rov alebo \u0161trukt\u00far NP. V\u010del\u00ed jed si m\u00f4\u017ee udr\u017ea\u0165 pred\u013a\u017een\u00e9 uvo\u013e\u0148ovanie a \u00fa\u010dinnos\u0165 po dlh\u00fa dobu pomocou tak\u00fdchto polym\u00e9rnych NP, \u010do zni\u017euje interval pod\u00e1vania a komplianciu pacienta [89,103].
        V rovnakom oh\u013eade Qiao a kol. [104] sk\u00famali interakcie medzi v\u010del\u00edm jedom a kopolym\u00e9rom poly(dl-laktid-ko-glykolid-b-etyl\u00e9nglykol-b-dl-laktid-ko-glykolid) (PLGA\u2013PEG\u2013PLGA). V\u0161imli si, \u017ee uvo\u013e\u0148ovanie v\u010delieho jedu bolo zn\u00ed\u017een\u00e9 a hydrog\u00e9l bol slabo degradovan\u00fd, zatia\u013e \u010do vyvinut\u00e9 biologick\u00e9 aktivity boli zachovan\u00e9 [104].
        V inom sp\u00f4sobe pod\u00e1vania lie\u010diva Xing a kol. [90] navrhli nov\u00fa formul\u00e1ciu na peror\u00e1lne pod\u00e1vanie s pou\u017eit\u00edm potiahnut\u00fdch lipoz\u00f3mov a peptidov v\u010delieho jedu potiahnut\u00fdch g\u00e9lov\u00fdmi gu\u013e\u00f4\u010dkami z algin\u00e1tu v\u00e1penat\u00e9ho ako modelov\u00e9ho lieku na dod\u00e1vanie lieku \u0161pecifick\u00e9ho pre hrub\u00e9 \u010drevo. V tak\u00fdchto podmienkach bol v\u010del\u00ed jed chr\u00e1nen\u00fd pred \u00fapln\u00fdm uvo\u013enen\u00edm v \u017eal\u00fadku a tenkom \u010dreve. Zistilo sa, \u017ee \u010das pr\u00edchodu tabliet do hrub\u00e9ho \u010dreva je 4\u20135 hod\u00edn. V\u00fdsledky jasne uk\u00e1zali, \u017ee potiahnut\u00fd lipoz\u00f3m zachyten\u00fd g\u00e9lov\u00fdmi gu\u013e\u00f4\u010dkami z algin\u00e1tu v\u00e1penat\u00e9ho je potenci\u00e1lnym syst\u00e9mom na dod\u00e1vanie lie\u010diva \u0161pecifick\u00e9ho pre hrub\u00e9 \u010drevo.
        V roku 2018 Lee a jeho kolegovia [105] vyhodnotili \u00fa\u010dinnos\u0165 chitosanov\u00fdch\/algin\u00e1tov\u00fdch NP na zapuzdrenie v\u010delieho jedu a ich \u00fa\u010dinnos\u0165 proti v\u00edrusu reproduk\u010dn\u00e9ho a respira\u010dn\u00e9ho syndr\u00f3mu o\u0161\u00edpan\u00fdch. Vo svojej \u0161t\u00fadii Lee a jeho kolegovia zistili, \u017ee NP odvoden\u00e9 z nosa boli schopn\u00e9 vyvola\u0165 imunitn\u00fa odpove\u010f pomocn\u00fdch T buniek typu 1 (Th1) a zv\u00fd\u0161i\u0165 produkciu klastrovej diferenci\u00e1cie (CD4+), T lymfocyty, popul\u00e1cie pam\u00e4\u0165ov\u00fdch T buniek, cytok\u00edny (interfer\u00f3n – y (IFN-y) a IL-12) a transkrip\u010dn\u00e9 faktory, ako je prevodn\u00edk sign\u00e1lu a aktiv\u00e1tor transkripcie 4 (STAT4) a T-box exprimovan\u00fd v T bunk\u00e1ch (T-bet). Podobne tieto naz\u00e1lne odvoden\u00e9 NP sp\u00f4sobili zn\u00ed\u017eenie T regula\u010dn\u00fdch buniek, cytok\u00ednov (IL-10 a transformuj\u00faci rastov\u00fd faktor-\u03b2 (TGF-\u03b2)) a transkrip\u010dn\u00fdch faktorov (prevodn\u00edk sign\u00e1lu a aktiv\u00e1tor transkripcie 5 (STAT5) a Forkhead box prote\u00edn P3 (Foxp3)).
        Alalawy a kol. [103] zistili, \u017ee nanesenie v\u010delieho jedu na nano-hubov\u00fd chitosan zv\u00fd\u0161ilo protirakovinov\u00fa biologick\u00fa aktivitu proti bunk\u00e1m karcin\u00f3mu kr\u010dka maternice (HeLa) a mohlo by vyvola\u0165 v\u00e1\u017ene pr\u00edznaky apopt\u00f3zy v bunk\u00e1ch HeLa sp\u00f4sobom z\u00e1visl\u00fdm od \u010dasu a d\u00e1vky.
        V\u00fdskumn\u00edci z Washingtonskej univerzity v St. Louis uk\u00e1zali, \u017ee NP pren\u00e1\u0161aj\u00face v\u010del\u00ed jed \u00fa\u010dinne ni\u010dia HIV, pri\u010dom okolit\u00e9 bunky nech\u00e1vaj\u00fa nepo\u0161koden\u00e9 [106]. Navy\u0161e nanovl\u00e1kna naplnen\u00e9 v\u010del\u00edm jedom a propolisom vykazovali \u0161irok\u00e9 spektrum antibakteri\u00e1lnych aktiv\u00edt [45].<\/p>\n\n\n\n

        1. Z\u00e1very a perspekt\u00edvy do bud\u00facnosti
          V\u010del\u00ed jed a jeho zlo\u017eky maj\u00fa \u0161irok\u00e9 spektrum biologick\u00fdch a farmakologick\u00fdch aktiv\u00edt. Bol podroben\u00fd klinick\u00fdm aplik\u00e1ci\u00e1m apiterapeutov na lie\u010dbu mnoh\u00fdch chor\u00f4b. Bola licencovan\u00e1 na hum\u00e1nnu terapiu v r\u00f4znych krajin\u00e1ch a teraz je dostupn\u00e1 na trhoch v r\u00f4znych form\u00e1ch. Plnenie v\u010delieho jedu a jeho zlo\u017eky melitt\u00edn polym\u00e9rmi a ich nanoformami udr\u017euje dlhodob\u00e9 uvo\u013e\u0148ovanie a zvy\u0161uje \u00fa\u010dinnos\u0165 v\u010delieho jedu. Vyu\u017eitie v\u010delieho jedu nalo\u017een\u00e9ho na NP je v\u0161ak zatia\u013e na \u00farovni experiment\u00e1lnych a predklinick\u00fdch \u0161t\u00fadi\u00ed. T\u00e1to \u0161t\u00fadia teda vy\u017eaduje spolupr\u00e1cu medzi v\u00fdskumn\u00edkmi a klinick\u00fdmi lek\u00e1rmi s cie\u013eom pos\u00fadi\u0165 bezpe\u010dnos\u0165 a \u00fa\u010dinnos\u0165 v\u010delieho jedu a ich zlo\u017ekov\u00fdch peptidov nalo\u017een\u00fdch na NP pri lie\u010dbe \u013eudsk\u00fdch chor\u00f4b.<\/li>
        2. Materi\u00e1ly a met\u00f3dy
          \u010cl\u00e1nky publikovan\u00e9 do j\u00fana 2021 sme v PubMed, Scopus, Google Scholar a Web of Science h\u013eadali s pou\u017eit\u00edm nasleduj\u00facich nadpisov a k\u013e\u00fa\u010dov\u00fdch slov samostatne alebo v r\u00f4znych kombin\u00e1ci\u00e1ch: \u201eV\u010del\u00ed jed\u201c, \u201e\u0160t\u00fadie in vitro\u201c, \u201e\u0160t\u00fadie in vivo\u201c , \u201eFarmakologick\u00e9 \u00fa\u010dinky\u201c, \u201eKlinick\u00e1 aplik\u00e1cia\u201c, \u201eAkupunkt\u00farne body\u201c, \u201eAkupunkt\u00fara\u201c a \u201eApiterapia\u201c. \u010cl\u00e1nky vybran\u00e9 na zahrnutie na zhroma\u017e\u010fovanie a zhroma\u017e\u010fovanie inform\u00e1ci\u00ed do preh\u013eadov\u00e9ho \u010dl\u00e1nku zah\u0155\u0148aj\u00fa recenzovan\u00e9 \u010dl\u00e1nky, ktor\u00e9 maj\u00fa identifik\u00e1tor digit\u00e1lneho objektu (DOI) a medzin\u00e1rodn\u00e9 \u0161tandardn\u00e9 s\u00e9riov\u00e9 \u010d\u00edslo (ISSN), ako aj kapitoly kn\u00edh s medzin\u00e1rodn\u00fdm \u0161tandardn\u00fdm \u010d\u00edslom knihy (ISBN). . Krit\u00e9ri\u00e1 vyl\u00fa\u010denia zah\u0155\u0148aj\u00fa nerecenzovan\u00fa literat\u00faru, \u010dl\u00e1nky, ktor\u00fdch \u00fapln\u00fd text nebol dostupn\u00fd, \u010dl\u00e1nky nes\u00favisiace so v\u010del\u00edm jedom, \u010dl\u00e1nky s obmedzen\u00fdmi inform\u00e1ciami, \u010dl\u00e1nky duplikovan\u00e9 medzi datab\u00e1zami, abstrakty z konferenci\u00ed a stiahnut\u00e9 \u010dl\u00e1nky.
          Autorsk\u00e9 pr\u00edspevky
          A.K., B.H.E., T.M.A. a O.M.A. podie\u013eal sa na pr\u00edprave n\u00e1vrhu verzie rukopisu. A.K., B.H.E., T.M.A. a O.M.A. zrevidovali kone\u010dn\u00fa verziu rukopisu, ktor\u00fd sa predklad\u00e1 \u010dasopisu. V\u0161etci autori si pre\u010d\u00edtali publikovan\u00fa verziu rukopisu a s\u00fahlasili s \u0148ou.<\/li><\/ol>\n\n\n\n

          <\/p>\n\n\n\n

          Financovanie:
          Tento v\u00fdskum nez\u00edskal \u017eiadne extern\u00e9 financovanie.
          Vyhl\u00e1senie in\u0161titucion\u00e1lnej rev\u00edznej rady:
          Nepou\u017eite\u013en\u00e9.
          Vyhl\u00e1senie informovan\u00e9ho s\u00fahlasu:
          Nepou\u017eite\u013en\u00e9.
          Vyhl\u00e1senie o dostupnosti \u00fadajov:
          \u00dadaje uveden\u00e9 v tejto \u0161t\u00fadii s\u00fa k dispoz\u00edcii na po\u017eiadanie od pr\u00edslu\u0161n\u00e9ho autora.
          Konflikt z\u00e1ujmov:
          Autori nedeklaruj\u00fa \u017eiadny konflikt z\u00e1ujmov.<\/p>\n\n\n\n

          Referencie<\/h2>\n\n\n\n
          1. Ahmed, O.; Fahim, H.; Mahmoud, A.; Eman Ahmed, E.A. Bee venom and hesperidin effectively mitigate complete Freund\u2019s adjuvant-induced arthritis via immunomodulation and enhancement of antioxidant defense system. Arch. Rheumatol.<\/em> 2017<\/strong>, 33<\/em>, 198\u2013212. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          2. Zhang, S.; Liu, Y.; Ye, Y.; Wang, X.R.; Lin, L.T.; Xiao, L.Y.; Zhou, P.; Shi, G.X.; Liu, C.Z. Bee venom therapy: Potential mechanisms and therapeutic applications. Toxicon<\/em> 2018<\/strong>, 148<\/em>, 64\u201373. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          3. Wehbe, R.; Frangieh, J.; Rima, M.; El Obeid, D.; Sabatier, J.M.; Fajloun, Z. Bee Venom: Overview of Main Compounds and Bioactivities for Therapeutic Interests. Molecules<\/em> 2019<\/strong>, 24<\/em>, 2997. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          4. Carpena, M.; Nu\u00f1ez-Estevez, B.; Soria-Lopez, A.; Simal-Gandara, J. Bee Venom: An Updating Review of Its Bioactive Molecules and Its Health Applications. Nutrients<\/em> 2020<\/strong>, 12<\/em>, 3360. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          5. El-Banby, M.A. Honeybees in the Koran and in Medicine<\/em>; Al-Ahram Centre for Translation and Publication: Cairo, Egypt, 1994; p. 268. (In Arabic) [Google Scholar<\/a>]<\/li>
          6. Mraz, C. Health and the Honeybee<\/em>; Queen City Publications: Burlington, VT, USA, 1995. [Google Scholar<\/a>]<\/li>
          7. Rose, A. Bees in Balance<\/em>; Starboint Enterprises, Ltd.: Bethesda, MD, USA, 1994. [Google Scholar<\/a>]<\/li>
          8. Bogdanov, S. Biological and Therapeutic Properties of Bee Venom. In The Bee Venom Book<\/em>; Bee Product Science: Bern, Switzerland, 2016; pp. 1\u201323. Available online: https:\/\/www.researchgate.net\/publication\/304011827_Biological_and_therapeutic_properties_of_bee_venom<\/a> (accessed on 1 April 2016).<\/li>
          9. Urtubey, N. Apitoxin: From Bee Venom to Apitoxin for Medical Use<\/em>; Termas de Rio Grande Santiago del Estero: Rio Hondo, Argentina, 2005. [Google Scholar<\/a>]<\/li>
          10. Hauser, R.A.; Daguio, M.; Wester, D.; Hauser, M.; Kirchman, A.; Skinkis, C. Bee-venom therapy for treating multiple sclerosis: A clinical trial. Altern. Complementary Ther.<\/em> 2004<\/strong>, 7<\/em>, 37. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          11. Rho, Y.H.; Woo, J.H.; Choi, S.J.; Lee, Y.H.; Ji, J.D.; Song, G.G. A new onset of systemic lupus erythematosus developed after bee venom therapy. Korean J. Intern. Med.<\/em> 2009<\/strong>, 24<\/em>, 283\u2013285. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          12. Or\u0161oli\u0107, N. Bee venom in cancer therapy. Cancer Metastasis Rev.<\/em> 2012<\/strong>, 31<\/em>, 173\u2013194. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          13. Kingsland, J. Honeybee Venom Kills Aggressive Breast Cancer Cells<\/em>; Sherrell, Z., Ed.; MPH; Healthline Media UK Ltd.: Brighton, UK, A Red Ventures Company; 7 September 2020; Available online: https:\/\/www.medicalnewstoday.com\/articles\/honeybee-venom-kills-aggressive-breast-cancer-cells<\/a> (accessed on 7 September 2020).<\/li>
          14. Duffy, C.; Sorolla, A.; Wang, E.; Golden, E.; Woodward, E.; Davern, K.; Ho, D.; Johnstone, E.; Pfleger, K.; Redfern, A.; et al. Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer. NPJ Precis. Oncol.<\/em> 2020<\/strong>, 4<\/em>, 24. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          15. Kim, H.; Keum, D.J.; Kwak, J.W.; Chung, H.-S.; Bae, H. Bee Venom Phospholipase A2 Protects against Acetaminophen-Induced Acute Liver Injury by Modulating Regulatory T Cells and IL-10 in Mice. PLoS ONE<\/em> 2014<\/strong>, 9<\/em>, e114726. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          16. Abd El-Rahim, A.H.; Abd-El-Moneim, O.M.; Abd El-Kader, H.A.; Abd El Raouf, A. Inhibitory effect of bee venom against potassium bromate causing genetic toxicity and biochemical alterations in mice. J. Arab. Soc. Med. Res.<\/em> 2018<\/strong>, 13<\/em>, 89\u201398. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          17. Hassan, S.A.; Alazragi, R.S.; Salem, N.A. Potential Therapeutic effect of Bee Venom on Cisplatin-Induced Hepatotoxicity. J. Pharm. Res. Int.<\/em> 2021<\/strong>, 33<\/em>, 200\u2013210. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          18. Akre, R.D.; Reed, H.C. Ants, Wasps and Bees: In the Textbook of Medical and Veterinary Entomology<\/em>, 2nd ed.; Academic Press: San Diego, CA, USA, 2009; pp. 383\u2013410. [Google Scholar<\/a>]<\/li>
          19. Casewell, N.R.; Wuster, W.; Vonk, F.J.; Harrison, R.A.; Fry, B.G. Complex cocktails: The evolutionary novelty of venoms. Trends Ecol. Evol.<\/em> 2013<\/strong>, 28<\/em>, 219\u2013229. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          20. Moreau, S.J.M.; Asgari, S. Venom proteins from parasitoid wasps and their biological functions. Toxins<\/em> 2015<\/strong>, 7<\/em>, 2385\u20132412. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          21. Danneels, E.L.; van Vaerenbergh, M.; Debyser, G.; Devreese, B.; de Graaf, D.C. Honeybee venom proteome profile of queens and winter bees as determined by a mass spectrometric approach. Toxins<\/em> 2015<\/strong>, 7<\/em>, 4468\u20134483. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          22. Moreau, S.J.M.; Vinchon, S.; Cherqui, A.; Prevost, G. Components of Asobara<\/em> venoms and their effects on hosts. Adv. Parasitol.<\/em> 2009<\/strong>, 70<\/em>, 217\u2013232. [Google Scholar<\/a>] [PubMed<\/a>]<\/li>
          23. Pucca, M.B.; Cerni, F.A.; Janke, R.; Berm\u00fadez-M\u00e9ndez, F.; Ledsgaard, L.; Barbosa, J.E.; Laustsen, A.H. Bee updated: Current knowledge on bee venom and bee envenoming therapy. Front. Immunol.<\/em> 2019<\/strong>, 10<\/em>, 2090. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          24. Raghuraman, H.; Chattopadhyay, A. Melittin: A membrane-active peptide with diverse functions. Biosci. Rep.<\/em> 2007<\/strong>, 27<\/em>, 189S\u2013223S. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          25. Moreno, M.; Giralt, E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: Melittin, apamin and mastoparan. Toxins<\/em> 2015<\/strong>, 7<\/em>, 1126\u20131150. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          26. Gajski, G.; Garaj-Vrhovac, V. Melittin: A lytic peptide with anticancer properties. Environ. Toxicol. Pharmacol.<\/em> 2013<\/strong>, 36<\/em>, 697\u2013705. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          27. Im, E.J.; Kim, S.J.; Hong, S.B.; Park, J.K.; Rhee, M.H. Anti-inflammatory activity of bee venom in BV2 microglial cells: Mediation of MyD88-dependent NF-6B signaling pathway. Evid.-Based Complement. Altern. Med.<\/em> 2016<\/strong>, 2016<\/em>, 3704764. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          28. Ali, M.A.M. Studies on bee venom and its medical uses. Int. J. Adv. Res. Technol.<\/em> 2012<\/strong>, 1<\/em>, 1\u201315. [Google Scholar<\/a>]<\/li>
          29. NIH. Apitherapy, Alternative Medicine: Expanding Medical Horizons<\/em>; NIH Pub.: Bethesda, MD, USA, 1995; pp. 172\u2013175. [Google Scholar<\/a>]<\/li>
          30. Bhalotia, S.; Kumar, N.R.; Kaur, J.; Devi, A. Honey bee venom and its composition: Focusing on different apis species\u2014A review. J. Basic Appl. Eng. Res.<\/em> 2016<\/strong>, 3<\/em>, 96\u201398. [Google Scholar<\/a>]<\/li>
          31. Szabat, P.; Poleszak, J.; Szabat, M.; Bore\u0144ski, G.; W\u00f3jcik, M.; Milanowska, J. Apitherapy\u2014The medical use of bee products. J. Educ. Health Sport<\/em> 2019<\/strong>, 9<\/em>, 384\u2013396. [Google Scholar<\/a>]<\/li>
          32. Kolayli, S.; Keskin, M. Natural bee products and their apitherapeutic applications. Stud. Nat. Prod. Chem.<\/em> 2020<\/strong>, 66<\/em>, 175\u2013196. [Google Scholar<\/a>]<\/li>
          33. Badawi, J.K. Bee Venom Components as Therapeutic Tools against Prostate Cancer. Toxins<\/em> 2021<\/strong>, 13<\/em>, 337. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          34. Meier, J.; White, J. Handbook of Clinical Toxicology of Animal Venoms<\/em>; CRC Press: New York, NY, USA, 1995. [Google Scholar<\/a>]<\/li>
          35. Minton, S.A. Venom Disease<\/em>; Charles C Thomas: Springfield, IL, USA, 1974. [Google Scholar<\/a>]<\/li>
          36. Habermehl, G.G. Venomous Animals and Their Toxins<\/em>; Springer: New York, NY, USA, 1981. [Google Scholar<\/a>]<\/li>
          37. Cornara, L.; Biagi, M.; Xiao, J.; Burlando, B. Therapeutic properties of bioactive compounds from different honeybee products. Front. Pharmacol.<\/em> 2017<\/strong>, 8<\/em>, 412. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          38. Sobral, F.; Sampaio, A.; Falc\u00e3o, S.; Queiroz, M.J.R.P.; Calhelha, R.C.; Vilas-Boas, M.; Ferreira, I.C.F.R. Chemical characterization, antioxidant, anti-inflammatory and cytotoxic properties of bee venom collected in Northeast Portugal. Food Chem. Toxicol.<\/em> 2016<\/strong>, 94<\/em>, 172\u2013177. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          39. Somwongin, S.; Chantawannakul, P.; Chaiyana, W. Antioxidant activity and irritation property of venoms from Apis species. Toxicon<\/em> 2018<\/strong>, 145<\/em>, 32\u201339. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          40. El-Hanoun, A.; El-Komy, A.; El-Sabrout, K.; Abdella, M. Effect of bee venom on reproductive performance and immune response of male rabbits. Physiol. Behav.<\/em> 2020<\/strong>, 223<\/em>, 112987. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          41. Mohamed, W.A.; Abd-Elhakim, Y.M.; Ismail, S.A.A. Involvement of the anti-inflammatory, anti-apoptotic, and anti-secretory activity of bee venom in its therapeutic e_ects on acetylsalicylic acid-induced gastric ulceration in rats. Toxicology<\/em> 2019<\/strong>, 419<\/em>, 11\u201323. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          42. Lee, Y.J.; Oh, M.J.; Lee, D.H.; Lee, Y.S.; Lee, J.; Kim, D.H.; Choi, C.H.; Song, M.J.; Song, H.S.; Hong, J.T. Anti-inflammatory effect of bee venom in phthalic anhydride-induced atopic dermatitis animal model. Inflammopharmacology<\/em> 2020<\/strong>, 28<\/em>, 253\u2013263. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          43. Klocek, G.; Schulthess, T.; Shai, Y.; Seelig, J. Thermodynamics of melittin binding to lipid bilayers. Aggregation and pore formation. Biochemistry<\/em> 2009<\/strong>, 48<\/em>, 2586\u20132596. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          44. Lee, W.R.; Kim, K.H.; An, H.J.; Kim, J.Y.; Chang, Y.C.; Chung, H.; Park, Y.Y.; Lee, M.L.; Park, K.K. The protective effects of melittin on propionibacterium acnes-induced inflammatory responses in vitro and in vivo. J. Investig. Dermatol.<\/em> 2014<\/strong>, 134<\/em>, 1922\u20131930. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          45. Lee, G.; Bae, H. Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects. Molecules<\/em> 2016<\/strong>, 21<\/em>, 616. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          46. Son, D.J.; Lee, J.W.; Lee, Y.H.; Song, H.S.; Lee, C.K.; Hong, J.T. Therapeutic application of antiarthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol. Ther.<\/em> 2007<\/strong>, 115<\/em>, 246\u2013270. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          47. Ahmed, O.M.; Ebaid, H.; El-Nahass, E.-S.; Ragab, M.; Alhazza, I.M. Nephroprotective Effect of Pleurotus ostreatus<\/em> and Agaricus bisporus<\/em> Extracts and Carvedilol on Ethylene Glycol-Induced Urolithiasis: Roles of NF-\u03baB, p53, Bcl-2, Bax and Bak. Biomolecules<\/em> 2020<\/strong>, 10<\/em>, 1317. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          48. Aufschnaiter, A.; Kohler, V.; Khalifa, S.; Abd El-Wahed, A.; Du, M.; El-Seedi, H.; B\u00fcttner, S. Apitoxin and Its Components against Cancer, Neurodegeneration and Rheumatoid Arthritis: Limitations and Possibilities. Toxins<\/em> 2020<\/strong>, 12<\/em>, 66. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          49. Pahl, H.L. Activators and target genes of Rel\/NF-\u03baB transcription factors. Oncogene<\/em> 1999<\/strong>, 18<\/em>, 6853\u20136866. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          50. Park, M.H.; Choi, M.S.; Kwak, D.H.; Oh, K.W.; Yoon, D.Y.; Han, S.B.; Song, H.S.; Song, M.J.; Hong, J.T. Anti-cancer effect of bee venomin prostate cancer cells through activation of caspase pathway via inactivation of NF-\u03baB. Prostate<\/em> 2011<\/strong>, 71<\/em>, 801\u2013812. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          51. Liu, X.; Chen, D.; Xie, L.; Zhang, R. E_ect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in-vitro and growth of murine B16 melanomas in-vivo. J. Pharm. Pharmacol.<\/em> 2002<\/strong>, 54<\/em>, 1083\u20131089. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          52. Saidemberg, D.M.; Baptista-Saidemberg, N.B.; Palma, M.S. Chemometric analysis of Hymenoptera toxins and defensins: A model for predicting the biological activity of novel peptides from venoms and hemolymph. Peptides<\/em> 2011<\/strong>, 32<\/em>, 1924\u20131933. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          53. Jung, G.B.; Huh, J.-E.; Lee, H.J.; Kim, D.; Lee, G.J.; Park, H.K.; Lee, J.D. Anti-cancer effect of bee venom on human MDA-MB-231 breast cancer cells using Raman spectroscopy. Biomed. Opt. Express<\/em> 2018<\/strong>, 9<\/em>, 5703\u20135718. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          54. Hong, J.; Lu, X.; Deng, Z.; Xiao, S.; Yuan, B.; Yang, X. How Melittin inserts into cell membrane: Conformational changes, inter-peptide cooperation, and disturbance on the membrane. Molecules<\/em> 2019<\/strong>, 24<\/em>, 1775. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          55. Zheng, J.; Lee, H.L.; Ham, Y.W.; Song, H.S.; Song, M.J.; Hong, J.T. Anti-cancer e_ect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B. Oncotarget<\/em> 2015<\/strong>, 6<\/em>, 44437\u201344451. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          56. Li, B.; Li, L.Y.; Luo, X.; Wang, X. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature<\/em> 2001<\/strong>, 412<\/em>, 95\u201399. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          57. Kroemer, G.; Martin, S.J. Caspase-independent cell death. Nat. Med.<\/em> 2005<\/strong>, 11<\/em>, 725\u2013730. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          58. Leandro, L.F.; Mendes, C.A.; Casemiro, L.A.; Vinholis, A.H.; Cunha, W.R.; De Almeida, R.; Martins, C.H. Antimicrobial activity of apitoxin, melittin and phospholipase A2 of honey bee (Apis mellifera<\/em>) venom against oral pathogens. An. Acad. Bras. Ci\u00eancias<\/em> 2015<\/strong>, 87<\/em>, 147\u2013155. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          59. Pucca, M.B.; Ahmadi, S.; Cerni, F.A.; Ledsgaard, L.; S\u00f8rensen, C.V.; McGeoghan, F.T.S.; Stewart, T.; Schoof, E.; Lomonte, B.; Auf dem Keller, U.; et al. Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2<\/sub> and Cytotoxins. Front. Pharmacol.<\/em> 2020<\/strong>, 11<\/em>, 611. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          60. Yang, L.; Harroun, T.A.; Weiss, T.M.; Ding, L.; Huang, H.W. Barrel-stave model or toroidal model? A case study on melittin pores. Biophys. J.<\/em> 2001<\/strong>, 81<\/em>, 1475\u20131485. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          61. Uddin, M.B.; Lee, B.H.; Nikapitiya, C.; Kim, J.H.; Kim, T.H.; Lee, H.C.; Kim, C.G.; Lee, J.S.; Kim, C.J. Inhibitory effects of bee venom and its components against viruses in vitro and in vivo. J. Microbiol.<\/em> 2016<\/strong>, 54<\/em>, 853\u2013866. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          62. Bachis, A.; Cruz, M.I.; Mocchetti, I. M-tropic HIV envelope protein gp120 exhibits a different neuropathological profile than T-tropic gp120 in rat striatum. Eur. J. Neurosci.<\/em> 2010<\/strong>, 2<\/em>, 570\u2013578. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          63. Sig, A.; G\u00fcney, M.; \u00d6z Sig, \u00d6.; \u015ean, H. Bee venom: A medical perspective. Turk. J. Clin. Lab.<\/em> 2019<\/strong>, 10<\/em>, 414\u2013421. [Google Scholar<\/a>]<\/li>
          64. Park, J.H.; Yim, B.K.; Lee, J.-H.; Lee, S.; Kim, T.-H. Risk Associated with Bee Venom Therapy: A Systematic Review and Meta-Analysis. PLoS ONE<\/em> 2015<\/strong>, 10<\/em>, e0126971. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          65. Kwon, Y.B.; Lee, J.D.; Lee, H.J.; Han, H.J.; Mar, W.C.; Kang, S.K.; Beitz, A.J.; Lee, J.H. Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. Pain<\/em> 2001<\/strong>, 90<\/em>, 271\u2013280. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          66. Pawelek, J. Urban Bee Gardens Archived 2010-05-01 at the Wayback Machine Urban Bee Legends. Available online: https:\/\/web.archive.org\/web\/20100501141312\/http:\/\/nature.berkeley.edu\/urbanbeegardens\/general_legends.html<\/a> (accessed on 1 May 2010).<\/li>
          67. Lin, T.-Y.; Hsieh, C.-L. Clinical Applications of Bee Venom Acupoint Injection. Toxins<\/em> 2020<\/strong>, 12<\/em>, 618. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          68. Cho, S.Y.; Shim, S.R.; Rhee, H.Y.; Park, H.J.; Jung, W.S.; Moon, S.K.; Park, J.M.; Ko, C.N.; Cho, K.H.; Park, S.U. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson\u2019s disease. Park. Relat. Disord.<\/em> 2012<\/strong>, 18<\/em>, 948\u2013952. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          69. Wesselius, T.; Heersema, D.J.; Mostert, J.P.; Heerings, M.; Admiraal-Behloul, F.; Talebian, A.; van Buchem, A.; De Keyser, J. A randomized crossover study of bee sting therapy for multiple sclerosis. Neurology<\/em> 2005<\/strong>, 65<\/em>, 1764. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          70. Liu, S.; Yu, M.; He, Y.; Xiao, L.; Wang, F.; Song, C.; Sun, S.; Ling, C.; Xu, Z. Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway. Hepatology<\/em> 2008<\/strong>, 47<\/em>, 1964\u20131973. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          71. Asafova, N.; Orlov, B.; Kozin, R. Physiologically Active Bee Products<\/em>; Y.A. Nikolaev: Nijnij Novgorod, Russia, 2001; p. 360. (In Russian) [Google Scholar<\/a>]<\/li>
          72. Krylov, V. Pcelni Yad (Bee Venom in Russian)<\/em>; Nizhny Novgorod University: Nizhny Novgorod, Russia, 1995; p. 221. [Google Scholar<\/a>]<\/li>
          73. Ludyanskil, E.A. Apiterapia<\/em>; Poligrafist: Vologda, Russia, 1994; p. 460. [Google Scholar<\/a>]<\/li>
          74. Shkenderov, S.; Ivanov, T. Pcelni Produkti, The Bee Products (in Bulgarian)<\/em>; Zemizdat: Sofia, Bulgaria, 1983; pp. 1\u2013238. [Google Scholar<\/a>]<\/li>
          75. Kang, S.Y.; Roh, D.H.; Kim, H.W.; Han, H.J.; Beitz, A.J.; Lee, J.H. Blockade of Adrenal Medulla- Derived Epinephrine Potentiates Bee Venom-Induced Antinociception in the Mouse Formalin Test: Involvement of Peripheral beta-Adrenoceptors. Evid. Based Complement. Altern. Med.<\/em> 2013<\/strong>, 2013<\/em>, 809062. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          76. Kang, S.; Roh, D.; Moon, J.; Kim, H.; Lee, H.; Beith, A.; Lee, J. Repetitive Treatment With Diluted Bee Venom Reduces Neuropathic Pain Via Potentiation of Locus Coeruleus Noradrenergic Neuronal Activity and Modulation of Spinal NR1 Phosphorylation in Rats. J. Pain<\/em> 2012<\/strong>, 13<\/em>, 155\u2013166. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          77. Karimi, A.; Parivar, K.; Nabiuni, M.; Haghighi, S.; Imani, S.; Afrouzi, H. Effect of honey bee venom on Lewis rats with experimental allergic encephalomyelitis as regards changes of GABA and glutamate. J. Am. Sci.<\/em> 2011<\/strong>, 7<\/em>, 295\u2013300. [Google Scholar<\/a>]<\/li>
          78. Lim, B.S.; Moon, H.J.; Li, D.X.; Gil, M.; Min, J.K.; Lee, G.; Bae, H.; Kim, S.K.; Min, B.I. Effect of bee venom acupuncture on oxaliplatin-induced cold allodynia in rats. Evid. Based Complement. Altern. Med.<\/em> 2013<\/strong>, 2013<\/em>, 369324. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          79. Chung, K.; An, H.; Cheon, S.; Kwon, K.; Lee, K. Bee venom suppresses testosterone-induced benign prostatic hyperplasia by regulating the inflammatory response and apoptosis. Exp. Biol. Med.<\/em> 2015<\/strong>, 240<\/em>, 656\u20131663. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          80. Park, J.H.; Kim, K.H.; Kim, S.J.; Lee, W.R.; Lee, K.G.; Park, K.K. Bee Venom Protects Hepatocytes from Tumor Necrosis Factor-alpha and Actinomycin D. Arch. Pharmacal Res.<\/em> 2010<\/strong>, 33<\/em>, 215\u2013223. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          81. Han, S.M.; Park, K.K.; Nicholis, Y.M.; Macfarlane, N.; Duncan, G. Effects of honeybee (Apis mellifera<\/em>) venom on keratinocyte migration in vitro. Pharmacogn. Mag.<\/em> 2013<\/strong>, 9<\/em>, 220\u2013226. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          82. Cheon, S.; Chung, K.; Lee, K.; An, H. Bee venom suppresses the differentiation of preadipocytes and high fat diet-induced obesity through inhibiting adipogenesis. Integr. Med. Res.<\/em> 2015<\/strong>, 4<\/em>, 55\u201356. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          83. Mousavi, S.M.; Imani, S.; Haghighi, S.; Mousavi, S.E.; Karimi, A. Effect of Iranian Honey bee (Apis mellifera<\/em>) Venom on Blood Glucose and Insulin in Diabetic Rats. J. Arthropod-Borne Dis.<\/em> 2012<\/strong>, 6<\/em>, 136\u2013143. [Google Scholar<\/a>]<\/li>
          84. Kim, K.H.; Lee, W.R.; An, H.J.; Kim, J.Y.; Chung, H.; Han, S.M.; Lee, M.L.; Lee, K.G.; Pak, S.C.; Park, K.K. Bee venom ameliorates compound 48\/80-induced atopic dermatitis-related symptoms. Int. J. Clin. Exp. Pathol.<\/em> 2013<\/strong>, 6<\/em>, 2896\u20132903. [Google Scholar<\/a>] [PubMed<\/a>]<\/li>
          85. G\u00fclmez, Y.; Ayd\u0131n, A.; Can, I.; Tekin, S.; Cacan, E. Cellular toxicity and biological activities of honey bee (Apis mellifera<\/em> L.) venom. Marmara Pharm. J.<\/em> 2017<\/strong>, 21<\/em>, 51\u2013260. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          86. Cherniack, E.P.; Govorushko, S. To bee or not to bee: The potential efficacy and safety of bee venom acupuncture in humans. Toxicon<\/em> 2018<\/strong>, 154<\/em>, 74\u201378. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          87. Sturm, G.J.; Varga, E.-M.; Roberts, G.; Mosbech, H.; Bil\u00f2, M.B.; Akdis, C.A.; Antol\u00edn-Am\u00e9rigo, D.; Cichocka-Jarosz, E.; Gawlik, R.; Jakob, T.; et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy<\/em> 2018<\/strong>, 73<\/em>, 744\u2013764. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          88. Kim, C.M.H. Apitherapy\u2014Bee Venom Therapy. In Biotherapy-History, Principles and Practice. A Practical Guide to the Diagnosis and Treatment of Disease using Living Organisms<\/em>; Springer: Heidelberg, Germany, 2013; pp. 77\u2013112. [Google Scholar<\/a>]<\/li>
          89. Park, M.-H.; Kim, J.-H.; Jeon, J.-W.; Park, J.-K.; Lee, B.-J.; Suh, G.-H.; Cho, C.-W. Preformulation Studies of Bee Venom for the Preparation of Bee Venom-Loaded PLGA Particles. Molecules<\/em> 2015<\/strong>, 20<\/em>, 15072\u201315083. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>][Green Version<\/a>]<\/li>
          90. Xing, L.; Dawei, C.; Liping, X.; Rongqing, Z. Oral colon-specific drug delivery for bee venom peptide: Development of a coated calcium alginate gel beads-entrapped liposome. J. Control Release<\/em> 2003<\/strong>, 93<\/em>, 293\u2013300. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          91. Krylov, V.; Agafonov, A.; Kriftsov, N.; Lebedev, V.; Burimistrova, L.; Oshevenski, L.; Sokolski, S. Theory and Agents of Apitherapy<\/em>; Chelyabinsk Russian Center: Moscow, Russia, 2007. (In Russian) [Google Scholar<\/a>]<\/li>
          92. Bil\u00f2, B.M.; Bonifazi, F. Hymenoptera venom immunotherapy. Immunotherapy<\/em> 2011<\/strong>, 3<\/em>, 229\u2013246. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          93. Reisman, R.E. Late onset reactions following venom immunotherapy and venom skin tests. Ann. Allergy<\/em> 1988<\/strong>, 61<\/em>, 383\u2013387. [Google Scholar<\/a>]<\/li>
          94. Lee, C.W.; Cho, J.H.; Yu, H.J.; Yang, H.Y.; Park, C.K.; Park, M.H. Bee-sting granulomas in the skin. Dermatology<\/em> 1996<\/strong>, 193<\/em>, 355\u2013356. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          95. Kim, H.W.; Kwon, Y.B.; Ham, T.W.; Roh, D.H.; Yoon, S.Y.; Kang, S.Y.; Yang, I.S.; Han, H.J.; Lee, H.J.; Beitz, A.J.; et al. General pharmacological profiles of bee venom and its water soluble fractions in rodent models. J. Vet. Sci.<\/em> 2004<\/strong>, 5<\/em>, 309\u2013318. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          96. Chen, J.; Lariviere, W.R. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword. Prog. Neurobiol.<\/em> 2010<\/strong>, 92<\/em>, 151\u2013183. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          97. Chen, J.; Guan, S.M.; Sun, W.; Fu, H. Melittin, the Major pain-producing substance of bee venom. Neurosci. Bull.<\/em> 2016<\/strong>, 32<\/em>, 265\u2013272. [Google Scholar<\/a>] [CrossRef<\/a>][Green Version<\/a>]<\/li>
          98. Tosteson, M.T.; Holmes, S.J.; Razin, M.; Tosteson, D.C. Melittin lysis of red cells. J. Membr. Biol.<\/em> 1985<\/strong>, 87<\/em>, 35\u201344. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          99. Gajski, G.; Domijan, A.M.; Zegura, B.; Stern, A.; Geric, M.; Novak Jovanovic, I.; Vrhovac, I.; Madunic, J.; Breljak, D.; Filipic, M.; et al. Melittin induced cytogenetic damage, oxidative stress and changes in gene expression in human peripheral blood lymphocytes. Toxicon<\/em> 2016<\/strong>, 110<\/em>, 56\u201367. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          100. Sharma, H.C.; Singh, O.P. Medicinal properties of some lesser known but important bee products. In Proceedings of the 1980, 1983, 2nd Int. Conf. Apiculture in Trop. Climates<\/em>; IBRA: New Delhi, India, 1983; pp. 694\u2013702. [Google Scholar<\/a>]<\/li>
          101. Singh, D. Bee venom. In Commercial Beekeeping (Production, Processing and Value Addition of Beehive Products for Income and Employment Generation)<\/em>; Scientific Publishers: Jodhpur, india, 2020; pp. 257\u2013262. [Google Scholar<\/a>]<\/li>
          102. Krell, R. Value-Added Products from Beekeeping<\/em>; SAO Agricultural Services Bulletin; Food and Agriculture Organization of the United Nation: Rome, Italy, 1996. [Google Scholar<\/a>]<\/li>
          103. Alalawy, A.I.; El Rabey, H.A.; Almutairi, F.M.; Tayel, A.A.; Al-Duais, M.A.; Zidan, N.S.; Sakran, M.I. Effectual Anticancer Potentiality of Loaded Bee Venom onto Fungal Chitosan Nanoparticles. Int. J. Polym. Sci.<\/em> 2020<\/strong>, 2020<\/em>, 2785304. [Google Scholar<\/a>] [CrossRef<\/a>]<\/li>
          104. Qiao, M.; Chen, D.; Hao, T.; Zhao, X.; Hu, H.; Ma, X. E_ect of bee venom peptide-copolymer interactions on thermosensitive hydrogel delivery systems. Int. J. Pharm.<\/em> 2007<\/strong>, 345<\/em>, 116\u2013124. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          105. Lee, J.; Kim, Y.M.; Kim, J.H.; Cho, C.W.; Jeon, J.W.; Park, J.K.; Lee, S.H.; Jung, B.G.; Lee, B.J. Nasal delivery of chitosan\/alginate nanoparticle encapsulated bee (Apis mellifera<\/em>) venom promotes antibody production and viral clearance during porcine reproductive and respiratory syndrome virus infection by modulating T cell related responses. Vet. Immunol. Immunopathol.<\/em> 2018<\/strong>, 200<\/em>, 40\u201351. [Google Scholar<\/a>] [CrossRef<\/a>] [PubMed<\/a>]<\/li>
          106. Strait, J.E. Nanoparticles Loaded with Bee Venom Kill HIV. Washington NewsRoom, Washington University in St. Louis, Washington, USA. 2013. Available online: https:\/\/source.wustl.edu\/2013\/03\/nanoparticles-loaded-with-bee-venom-kill-hiv\/<\/a> (accessed on 7 March 2013).<\/li><\/ol>\n\n\n\n

            Zdroj: https:\/\/www.mdpi.com\/1420-3049\/26\/16\/4941\/htm<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

            Entomologick\u00e1 div\u00edzia, Katedra zool\u00f3gie, Pr\u00edrodovedeck\u00e1 fakulta, Univerzita Beni-Suef, Beni-Suef 62521, Egypt2. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudsk\u00e1 Ar\u00e1bia3. \u00dastav patol\u00f3gie, Lek\u00e1rska fakulta, Univerzita Mansoura, Mansoura 35516, Egypt4. Katedra fyziol\u00f3gie, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudsk\u00e1 Ar\u00e1bia5. \u00dastav fyziol\u00f3gie, […]<\/p>\n","protected":false},"author":1,"featured_media":298,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"ngg_post_thumbnail":0},"categories":[7],"tags":[],"yoast_head":"\nV\u010del\u00ed jed: Od jedu k lieku - apitoxin.sk<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/apitoxin.sk\/2022\/08\/02\/vceli-jed-od-jedu-k-lieku\/\" \/>\n<meta property=\"og:locale\" content=\"sk_SK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"V\u010del\u00ed jed: Od jedu k lieku - apitoxin.sk\" \/>\n<meta property=\"og:description\" content=\"Entomologick\u00e1 div\u00edzia, Katedra zool\u00f3gie, Pr\u00edrodovedeck\u00e1 fakulta, Univerzita Beni-Suef, Beni-Suef 62521, Egypt2. 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