{"id":12268,"date":"2026-01-17T19:28:26","date_gmt":"2026-01-17T19:28:26","guid":{"rendered":"https:\/\/csiag.eu\/?p=12268"},"modified":"2026-04-13T15:35:04","modified_gmt":"2026-04-13T15:35:04","slug":"lecba-borreliozy-u-pacientu-s-arla-antibiotiky-rezistentni-lymska-artritida","status":"publish","type":"post","link":"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/","title":{"rendered":"Lymsk\u00e1 boreli\u00f3za - Huaier\u016fv p\u0159\u00edstup pro pacienty s ARLA (Antibioticky rezistentn\u00ed lymsk\u00e1 artritida)"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_83 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Obsah<\/p>\n<span class=\"ez-toc-title-toggle\"><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Pathogenese\" >Patogeneze<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Herkommliche_Therapieformen\" >Konven\u010dn\u00ed formy terapie<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#NSAR\" >NSAIDS<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#DMARD\" >DMARD<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Beispiel_ARLA-Patient_%E2%80%93_NSARs_und_DMARD\" >P\u0159\u00edklad pacienta ARLA - NSAID a DMARDs<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Biologika\" >Biologick\u00e1 l\u00e9\u010diva<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Huaier-Pilz_%E2%80%93_eine_Alternative\" >Houba Huaier - alternativa?<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#NF-%CE%BAB-Pathway-Hemmung_Plasma-Membran-Signalisierung\" >Inhibice dr\u00e1hy NF-\u03baB (signalizace plazmatick\u00e9 membr\u00e1ny)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#JAKSTAT-Pathway-Modulation_Endosomal-Signalisierung_IL-6-Feedback\" >Modulace dr\u00e1hy JAK\/STAT (endozom\u00e1ln\u00ed signalizace + zp\u011btn\u00e1 vazba IL-6)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Vergleich_JAK1i_wie_Upadacitinib_vs_Huaier\" >Srovn\u00e1n\u00ed: JAK1i (jako upadacitinib) vs Huaier:<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-11\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#PI3KAKT-Aktivierung_Mitochondriale_Restoration_Treg-Support\" >Aktivace PI3K\/AKT (obnova mitochondri\u00ed + podpora Treg)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-12\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Spezifische_Effekte_bei_ARLA\" >Specifick\u00e9 \u00fa\u010dinky s ARLA:<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-13\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Ribosomale_Homoostase_Tanaka-Hauptfund\" >Ribosom\u00e1ln\u00ed homeost\u00e1za (hlavn\u00ed n\u00e1lez Tanaka)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-14\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Mechanistischer_Vergleich_Huaier_zu_Biologika\" >Mechanistick\u00e9 srovn\u00e1n\u00ed Huaiera s biologick\u00fdmi l\u00e1tkami<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-15\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Dosierungsempfehlung_bei_ARLA_im_fortgeschrittenen_Stadium\" >Dosierungsempfehlung bei ARLA im fortgeschrittenen Stadium<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-16\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Vorschlag_fur_ARLA-Dosierung\" >N\u00e1vrh d\u00e1vkov\u00e1n\u00ed ARLA<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-17\" href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Weitere_relevante_Beitrage_zum_Anwendungsbereich_des_Huaier-Pilzes\" >Dal\u0161\u00ed relevantn\u00ed \u010dl\u00e1nky o oblasti p\u016fsobnosti houby Huaier<\/a><\/li><\/ul><\/nav><\/div>\n<span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Doba \u010dten\u00ed<\/span> <span class=\"rt-time\"> 18<\/span> <span class=\"rt-label rt-postfix\">minuty<\/span><\/span>\n<p>Lymskou boreli\u00f3zu zp\u016fsobuje <em>Borrelia burgdorferi<\/em>, spir\u00e1lovit\u00e1 bakterie, kter\u00e1 dok\u00e1\u017ee <em>Lymsk\u00e1 boreli\u00f3za <\/em>(zn\u00e1m\u00e1 tak\u00e9 jako boreli\u00f3za).<\/p>\n\n\n\n<p>Je to jeden z m\u00e1la patogen\u016f, kter\u00e9 jsou tak v\u011bdecky fascinuj\u00edc\u00ed a z\u00e1rove\u0148 p\u0159edstavuj\u00ed nejobt\u00ed\u017en\u011bj\u0161\u00ed bakteri\u00e1ln\u00ed infekce v imunologii a klinick\u00e9 praxi:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Neobvykl\u00e1 genetika:<\/strong> Line\u00e1rn\u00ed chromozom a komplexn\u00ed plazmidov\u00fd syst\u00e9m<\/li>\n\n\n\n<li><strong>Mistr imunitn\u00ed invaze:<\/strong> antigenn\u00ed variace VlsE, inhibice komplementu, biofilm<\/li>\n\n\n\n<li><strong>Multiorg\u00e1nov\u00e9 patogeny:<\/strong> M\u016f\u017ee ovlivnit t\u00e9m\u011b\u0159 v\u0161echny org\u00e1nov\u00e9 syst\u00e9my<\/li>\n\n\n\n<li><strong>Specialista na vytrvalost:<\/strong> M\u016f\u017ee zp\u016fsobit chronick\u00e9 infekce, kter\u00e9 trvaj\u00ed roky<\/li>\n\n\n\n<li><strong>TLR2 dominance:<\/strong> Spou\u0161t\u00ed masivn\u00ed z\u00e1n\u011bt (v\u00edce ne\u017e Toll-like receptor 4)<\/li>\n\n\n\n<li><strong>Autoimunitn\u00ed potenci\u00e1l:<\/strong> Vede k postinfek\u010dn\u00ed autoimunit\u011b (ARLA).<\/li>\n<\/ul>\n\n\n\n<p>V\u011bt\u0161ina lid\u00ed s boreliovou artritidou se po l\u00e9\u010db\u011b antibiotiky vyl\u00e9\u010d\u00ed. P\u0159ibli\u017en\u011b 10% v\u0161ak na tuto l\u00e9\u010dbu nereaguje a vyvine se u nich tzv. boreliov\u00e1 artritida. <strong>lymesk\u00e1 artritida rezistentn\u00ed na antibiotika<\/strong> (<em>ARLA<\/em>).<\/p>\n\n\n\n<p>Tyto 10% se d\u011bl\u00ed na<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>50% se spont\u00e1nn\u00ed remis\u00ed (do\u010dasn\u00fd nebo trval\u00fd \u00fastup p\u0159\u00edznak\u016f onemocn\u011bn\u00ed) za x let<\/li>\n\n\n\n<li>30% do <strong>DMARD<\/strong> (L\u00e9ky modifikuj\u00edc\u00ed onemocn\u011bn\u00ed) \/ <strong>Biologick\u00e1 l\u00e9\u010diva<\/strong> (<strong>p\u016fsob\u00ed proti specifick\u00fdm c\u00edlov\u00fdm struktur\u00e1m<\/strong> imunitn\u00edho syst\u00e9mu)<\/li>\n\n\n\n<li>20% chronick\u00fd a rezistentn\u00ed k l\u00e9\u010db\u011b<\/li>\n<\/ul>\n\n\n\n<p>Nejprve je vysv\u011btlena patogeneze (p\u0159\u00ed\u010dina onemocn\u011bn\u00ed), konven\u010dn\u00ed mo\u017enosti terapie a pot\u00e9 p\u0159\u00edstup k terapii pomoc\u00ed \u00fa\u010dinn\u00fdch l\u00e1tek houby Huaier.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Pathogenese\"><\/span>Patogeneze<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p><strong>P\u0159\u00edm\u00e1 invaze:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Vazba kolagenu\/dekorinu prost\u0159ednictv\u00edm DbpA\/B - (umo\u017e\u0148uje patogenu p\u0159ichytit se na struktury bohat\u00e9 na kolagen, co\u017e je d\u016fle\u017eit\u00e9 pro vlastn\u00ed invazi do hostitele a kolonizaci patogenu v hostiteli).<\/li>\n\n\n\n<li>Vazba fibronektinu prost\u0159ednictv\u00edm BBK32 - (umo\u017e\u0148uje dynamick\u00e9 posilov\u00e1n\u00ed vazebn\u00e9 schopnosti patogenu prost\u0159ednictv\u00edm tvorby polymerizovan\u00e9ho fibronektinu v z\u00e1vislosti na mechanick\u00e9 z\u00e1t\u011b\u017ei (nap\u0159. v krevn\u00edm \u0159e\u010di\u0161ti): \u010d\u00edm vy\u0161\u0161\u00ed, t\u00edm siln\u011bj\u0161\u00ed). <\/li>\n\n\n\n<li>Nep\u0159\u00edm\u00e9 po\u0161kozen\u00ed tk\u00e1n\u00ed v d\u016fsledku vyvolan\u00e9 imunitn\u00ed reakce<\/li>\n<\/ul>\n\n\n\n<p><strong>Spou\u0161t\u011bn\u00ed imunitn\u00edho syst\u00e9mu (dominantn\u00ed TLR2):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Povrchov\u00e9 lipoproteiny (OspA, OspC, OspE)<\/strong> \u2192 aktivace TLR2\/6 (\u010dasn\u00e1 imunitn\u00ed odpov\u011b\u010f, ale tak\u00e9 pro patogenezi, proto\u017ee mohou vyvolat nadm\u011brn\u00e9 z\u00e1n\u011btliv\u00e9 reakce).<\/li>\n\n\n\n<li><strong>Peptidoglykany<\/strong> \u2192 aktivace TLR2 (vede k siln\u00e9 z\u00e1n\u011btliv\u00e9 reakci a aktivaci vrozen\u00e9ho a adaptivn\u00edho imunitn\u00edho syst\u00e9mu)<\/li>\n\n\n\n<li>Vede k masivn\u00edmu <strong>Aktivace NF-\u03baB\/MAPK<\/strong> (vede k siln\u00e9mu uvoln\u011bn\u00ed&nbsp;<strong>proz\u00e1n\u011btliv\u00e9 cytokiny<\/strong>&nbsp;jako <strong>TNF-\u03b1, IL-6 a IL-1\u03b2<\/strong>, kter\u00fd zesiluje z\u00e1n\u011btlivou reakci p\u0159i boreli\u00f3ze).<\/li>\n\n\n\n<li>Masivn\u00ed <strong>produkce proz\u00e1n\u011btliv\u00fdch cytokin\u016f<\/strong><\/li>\n<\/ul>\n\n\n\n<p><strong>Imunitn\u00ed invaze:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inhibice komplementu<\/strong><br><em>OspE, OspF<\/em> - Povrchov\u00e9 proteiny bakterie se v\u00e1\u017eou na regula\u010dn\u00ed protein H komplementov\u00e9ho syst\u00e9mu a br\u00e1n\u00ed tak aktivaci komplementu, kter\u00fd by jinak bakterii zni\u010dil.<br>Zd\u00e1 se, \u017ee OspF hraje roli v sebeobran\u011b proti vlastn\u00edmu patogenu u kl\u00ed\u0161\u0165at: my\u0161i imunizovan\u00e9 OspF vykazovaly sn\u00ed\u017een\u00ed po\u010dtu spirochet a\u017e o 90%. Zdroj:<a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC186469\/\" target=\"_blank\" rel=\"noreferrer noopener\">\u010c\u00e1ste\u010dn\u00e9 zni\u010den\u00ed Borrelia burgdorferi v kl\u00ed\u0161\u0165atech, kter\u00e1 se p\u0159is\u00e1la na my\u0161i imunizovan\u00e9 OspE nebo OspF<\/a>)<\/li>\n\n\n\n<li><strong>Antigenn\u00ed variace<\/strong><br><em>VlsE - variabiln\u00ed hlavn\u00ed sekvence podobn\u00e1 proteinu Expresn\u00ed<\/em> &#8211; verhindert Erkennung durch das Immunsystem<\/li>\n\n\n\n<li><strong>Tvorba biofilmu<\/strong><br>selbst produzierte <em>extracelul\u00e1rn\u00ed polymern\u00ed l\u00e1tka<\/em> zum Eigenschutz des Erregers<\/li>\n\n\n\n<li><strong>Intracelul\u00e1rn\u00ed perzistence<\/strong><br>in Spiroch\u00e4ten-Form-Varianten (Gruppe gramnegativer, schraubenf\u00f6rmiger, anaerob oder fakultativ anaerob lebender Bakterien, u.a. auch Syphilis- und Leptospirose-Erreger) m\u00f6glich, verstecken sich innerhalb der infizierten Zelle und k\u00f6nnen dort symptomlos \u00fcber Monate und Jahre verweilen<\/li>\n<\/ul>\n\n\n\n<p><strong>Autoimunita (postinfek\u010dn\u00ed):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Zk\u0159\u00ed\u017een\u00e1 reaktivita mezi OspA a lidsk\u00fdmi proteiny (nap\u0159. LFA-1)<\/strong><br>molekulares Mimicry: f\u00fchrt zu einer&nbsp;autoimmunologisch aufrechterhaltenen Entz\u00fcndung, auch wenn der Erreger bereits eliminiert ist.<br>Siln\u00e1 odpov\u011b\u010f T-bun\u011bk u geneticky predisponovan\u00fdch pacient\u016f je spojena s nadm\u011brnou produkc\u00ed proz\u00e1n\u011btliv\u00fdch cytokin\u016f (nap\u0159.&nbsp;<strong>TNF\u03b1, IFN\u03b3<\/strong>) verbunden, die den Entz\u00fcndungsprozess aufrecht erh\u00e4lt<\/li>\n\n\n\n<li><strong>\u0160\u00ed\u0159en\u00ed epitop\u016f<\/strong><br>Nach anf\u00e4nglicher Immunreaktion gegen Borrelien-Antigene wie&nbsp;<strong>OspA<\/strong>&nbsp;p\u0159etrv\u00e1vaj\u00edc\u00ed z\u00e1n\u011bt vede k rozpadu tk\u00e1n\u00ed a uvol\u0148ov\u00e1n\u00ed t\u011blu vlastn\u00edch b\u00edlkovin.<br>Ty jsou pak rovn\u011b\u017e rozpozn\u00e1ny a prezentov\u00e1ny imunitn\u00edm syst\u00e9mem, \u010d\u00edm\u017e se imunitn\u00ed odpov\u011b\u010f roz\u0161\u00ed\u0159\u00ed na nov\u00e9, p\u016fvodn\u011b ciz\u00ed epitopy nez\u00e1visl\u00e9 na antigenu. Tento proces je charakterizov\u00e1n nedostatkem regula\u010dn\u00edch l\u00e1tek.&nbsp;<strong>IL-10<\/strong>&nbsp;verst\u00e4rkt, was zu einer unkontrollierten Autoimmunit\u00e4t f\u00fchren kann.<\/li>\n\n\n\n<li><strong>Perzistentn\u00ed peptidoglykany spou\u0161t\u011bj\u00ed autoreaktivn\u00ed T-bu\u0148ky<\/strong><br>Bestandteile der bakteriellen Zellwand des Erregers k\u00f6nnen, auch nach erfolgreicher Antibiotikatherapie, in Geweben wie Leber oder in Gelenken vereilen und stimulieren weiterhin das Immunsystem. Zudem beeinflussen sie den&nbsp;Energiestoffwechsel von Immunzellen&nbsp;und f\u00f6rdern die Produktion entz\u00fcndungsf\u00f6rdernder Proteine, was wiederum die Autoimmunit\u00e4t verst\u00e4rkt<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Herkommliche_Therapieformen\"><\/span>Konven\u010dn\u00ed formy terapie<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NSAR\"><\/span>NSAIDS<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Nesteroidn\u00ed protiz\u00e1n\u011btliv\u00e9 l\u00e9ky (NSAID) jsou l\u00e9ky, kter\u00e9 tlum\u00ed z\u00e1n\u011bt, zm\u00edr\u0148uj\u00ed bolest a sni\u017euj\u00ed hore\u010dku, ale na rozd\u00edl od kortikosteroid\u016f nejsou steroidy.<br>Na rozd\u00edl od steroid\u016f nezvy\u0161uj\u00ed NSAID m\u00edru infekce.<\/p>\n\n\n\n<p>Neselektivn\u011b inhibuj\u00ed enzymy COX (cyklooxygen\u00e1za)-1 a COX-2 produkuj\u00edc\u00ed prostaglandiny a tromboxan.<br>Zat\u00edmco COX-1 je v\u017edy aktivn\u00ed (pokud je neaktivn\u00ed nebo inhibovan\u00e1, zp\u016fsobuje nap\u0159. \u017ealude\u010dn\u00ed v\u0159edy, probl\u00e9my s ledvinami a sklon ke krv\u00e1cen\u00ed), COX-2 je p\u0159i z\u00e1n\u011btu regulov\u00e1na.<br>Blokov\u00e1n\u00ed COX-2 vede k po\u017eadovan\u00fdm \u00fa\u010dink\u016fm, nap\u0159. ke sn\u00ed\u017een\u00ed z\u00e1n\u011btu a bolesti, sn\u00ed\u017een\u00ed hore\u010dky.<\/p>\n\n\n\n<p>Proto\u017ee neselektivn\u00ed NSA inhibuj\u00ed oba enzymy stejn\u011b, maj\u00ed tak\u00e9 v\u00fd\u0161e uveden\u00e9 ne\u017e\u00e1douc\u00ed (vedlej\u0161\u00ed) \u00fa\u010dinky.<\/p>\n\n\n\n<p><strong>NSAID maj\u00ed pouze symptomatick\u00fd \u00fa\u010dinek<\/strong>. Patogen je st\u00e1le p\u0159\u00edtomen a aktivn\u00ed, z\u00e1n\u011btliv\u00e9 medi\u00e1tory (proz\u00e1n\u011btliv\u00e9 cytokiny) se nad\u00e1le neru\u0161en\u011b produkuj\u00ed a eroze chrupavky pokra\u010duje.<\/p>\n\n\n\n<p>Nej\u010dast\u011bj\u0161\u00edmi \u00fa\u010dinn\u00fdmi l\u00e1tkami neselektivn\u00edch NSAID jsou<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Kyselina acetysalicylov\u00e1<\/li>\n\n\n\n<li>Diklofenak<\/li>\n\n\n\n<li>Ibuprofen<\/li>\n\n\n\n<li>Indometacin<\/li>\n\n\n\n<li>Ketoprofen<\/li>\n\n\n\n<li>Meloxikam<\/li>\n\n\n\n<li>Naproxen<\/li>\n\n\n\n<li>Piroxicam<\/li>\n<\/ul>\n\n\n\n<p>Nejb\u011b\u017en\u011bj\u0161\u00edmi selektivn\u00edmi \u00fa\u010dinn\u00fdmi l\u00e1tkami inhibitor\u016f (COX-2) jsou<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Celekoxib<\/li>\n\n\n\n<li>Etorikoxib<\/li>\n<\/ul>\n\n\n\n<p>Rofekoxib (z d\u016fvodu zv\u00fd\u0161en\u00e9ho rizika srde\u010dn\u00edho infarktu) a valdekoxib byly sta\u017eeny z trhu.<\/p>\n\n\n\n<p>COX-2 selektivn\u00ed NSAID se nesm\u00ed pod\u00e1vat pacient\u016fm s ischemickou chorobou srde\u010dn\u00ed (ICHS) nebo po srde\u010dn\u00edm infarktu, proto\u017ee tato onemocn\u011bn\u00ed zv\u00fdhod\u0148uj\u00ed.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"DMARD\"><\/span>DMARD<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Kategorie DMARD zahrnuje l\u00e1tky, kter\u00e9 nejen zm\u00edr\u0148uj\u00ed p\u0159\u00edznaky (nap\u0159. NSAID), ale tak\u00e9 <strong>aktivn\u011b zpomalit nebo zastavit progresi onemocn\u011bn\u00ed.<\/strong> a imunitn\u00edho syst\u00e9mu z dlouhodob\u00e9ho hlediska.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Beispiel_ARLA-Patient_%E2%80%93_NSARs_und_DMARD\"><\/span>P\u0159\u00edklad pacienta ARLA - NSAID a DMARDs<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>Pacient: 42let\u00fd mu\u017e s ARLA (monartritida kolene po boreli\u00f3ze)<\/p>\n\n\n\n<p><strong>Po\u010d\u00e1te\u010dn\u00ed:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Naproxen 500 mg 2x denn\u011b<\/li>\n\n\n\n<li>Omeprazol 20 mg jednou denn\u011b (ochrana \u017ealudku)<\/li>\n<\/ul>\n\n\n\n<p>Bolest 7\/10<br>Kloubn\u00ed v\u00fdpotek 200 ml<\/p>\n\n\n\n<p><strong>Po 2 t\u00fddnech<\/strong>:<\/p>\n\n\n\n<p>Bolest 4\/10 (lep\u0161\u00ed \u201epohoda\u201c)<br>Kloubn\u00ed v\u00fdpotek st\u00e1le 180 ml <br>Otok se sotva zlep\u0161\u00ed<\/p>\n\n\n\n<p><strong>Eskalace na DMARD:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>+ methotrex\u00e1t 15 mg\/t\u00fdden<\/li>\n<\/ul>\n\n\n\n<p>nebo <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>+ biologika (TNFi nebo JAKi)<\/li>\n<\/ul>\n\n\n\n<p><strong>Po 8-12 t\u00fddnech kombinovan\u00e9 l\u00e9\u010dby:<\/strong><\/p>\n\n\n\n<p>Bolest 0-1\/10<br>Kloubn\u00ed v\u00fdpotek &lt; 50 ml<br>Obnoven\u00ed mobility<br>Dosa\u017een\u00ed remise!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Biologika\"><\/span>Biologick\u00e1 l\u00e9\u010diva<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Biologika jsou biotechnologicky vyr\u00e1b\u011bn\u00e9 v\u011bt\u0161\u00ed molekuly podle vzoru lidsk\u00fdch protein\u016f, nukleov\u00fdch kyselin nebo protil\u00e1tek, kter\u00e9 nelze pod\u00e1vat ve form\u011b tablet z d\u016fvodu p\u0159ed\u010dasn\u00e9ho rozkladu \u017ealude\u010dn\u00ed kyselinou, ale pouze ve form\u011b podko\u017en\u00edch injekc\u00ed nebo infuz\u00ed. Peror\u00e1ln\u011b se u\u017e\u00edvaj\u00ed pouze inhibitory JAK.<br>Mohou m\u00edt regula\u010dn\u00ed \u00fa\u010dinek na cytokiny, receptory nebo imunitn\u00ed bu\u0148ky. Inzul\u00edn je tak\u00e9 (prvn\u00ed z roku 1982) biologikum.<\/p>\n\n\n\n<p>V kontextu ARLA se d\u011bl\u00ed do \u010dty\u0159 hierarchi\u00ed<\/p>\n\n\n\n<p>1. volba - <strong>Inhibitory TNF-\u03b1 (TNFi)<\/strong> - Odpov\u011b\u010f s 50-70% po 4-8 t\u00fddnech<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Adalimumab<\/li>\n\n\n\n<li>Infliximab<\/li>\n\n\n\n<li>Etanercept<\/li>\n<\/ul>\n\n\n\n<p>2. volba - <strong>Inhibitory IL-6 (IL-6i)<\/strong> - Odpov\u011b\u010f p\u0159i 50-60% po 4-12 t\u00fddnech<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Tocilizumab<\/li>\n\n\n\n<li>Sarilumab<\/li>\n<\/ul>\n\n\n\n<p>\u00da\u010dinn\u00fd tak\u00e9 u pacient\u016f nereaguj\u00edc\u00edch na TNFi (~30-50% pacient\u016f).<\/p>\n\n\n\n<p>3. volba - <strong>Inhibitory JAK (JAKi) <\/strong>- Reakce ji\u017e po 2-4 t\u00fddnech - st\u00e1le ve v\u00fdvoji<br>Blokuj\u00ed JAK1 (prim\u00e1rn\u011b, siln\u011b), JAK2 (sekund\u00e1rn\u011b, slab\u011b) a TYK2 (sekund\u00e1rn\u011b, slab\u011b), proto nem\u016f\u017ee b\u00fdt STAT3 fosforylov\u00e1n, a proto z\u016fst\u00e1v\u00e1 neaktivn\u00ed a geny z\u00e1visl\u00e9 na IL-6 nejsou transkribov\u00e1ny. JAK3 naopak blokov\u00e1n nen\u00ed, co\u017e je pozitivn\u00ed pro lep\u0161\u00ed obranu proti infekci (zdroj - pln\u00fd text s n\u00e1klady): <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/312615\/\" target=\"_blank\" rel=\"noreferrer noopener\">Chronick\u00e1 lymsk\u00e1 artritida. Klinick\u00e9 a imunogenetick\u00e9 odli\u0161en\u00ed od revmatoidn\u00ed artritidy<\/a>).<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Upadacitinib<\/li>\n\n\n\n<li>Baricitinib<\/li>\n\n\n\n<li>Tofacitinib<\/li>\n<\/ul>\n\n\n\n<p>4. volba - <strong>Depletory B-bun\u011bk<\/strong> - Odpov\u011b\u010f p\u0159i 40-50% - pouze pro non-respond\u00e9ry TNFi + IL-6i + JAKi<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Rituximab<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Huaier-Pilz_%E2%80%93_eine_Alternative\"><\/span>Houba Huaier - alternativa?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <a href=\"https:\/\/aditum.org\/journals\/international-journal-of-medical-case-reports-and-medical-research\/archive\/967\" target=\"_blank\" rel=\"noreferrer noopener\">Studie Tanaka<\/a> osv\u011btluje \u00fa\u010dinek \u00fa\u010dinn\u00fdch l\u00e1tek spole\u010dnosti Huaier p\u0159edev\u0161\u00edm ve vztahu k rakovin\u011b v\u0161eho p\u016fvodu (s v\u00fdjimkou n\u00e1dor\u016f mozku, proto\u017ee velk\u00e9 molekuly \u00fa\u010dinn\u00fdch l\u00e1tek nejsou schopny proj\u00edt hematoencefalickou bari\u00e9rou).<br>K dispozici je samostatn\u00e1 <a href=\"https:\/\/csiag.eu\/cs\/houba-huaier-v-terapii-rakoviny\/\" target=\"_blank\" rel=\"noreferrer noopener\">P\u0159\u00edsp\u011bvek<\/a>, tak\u00e9 s <a href=\"https:\/\/csiag.eu\/cs\/houba-huaier-v-terapii-rakoviny\/#Dosierungsempfehlung\" target=\"_blank\" rel=\"noreferrer noopener\">Pokyny pro d\u00e1vkov\u00e1n\u00ed<\/a> a <a href=\"https:\/\/nutrimentas-shop.de\/products\/vitalpilz-huaier-trametes-robiniophila-fur-wissenschaftliche-zwecke\" target=\"_blank\" rel=\"noreferrer noopener\">Zdroj dod\u00e1vek<\/a> granul\u00ed pou\u017eit\u00fdch ve studii s 32 polysacharidy %.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p><strong>Pozor<\/strong>:<br>Dosierungsempfehlungen basieren ausschlie\u00dflich auf dem unter dem o.g. Link &#8222;Bezugsquelle&#8220; aufgef\u00fchrten Produkt, da, Stand 04.2026, nur dieses \u00fcber die nachgewiesenen 32% Polysaccahride und 58% \u03b2-<mark>Glukane<\/mark> verf\u00fcgt, die auch durch unabh\u00e4ngige Analyse-Daten (siehe die Links auf der Produktseite weiter unten) best\u00e4tigt sind.<\/p>\n<\/blockquote>\n\n\n\n<p>Studie prok\u00e1zaly, \u017ee \u00fa\u010dinn\u00e9 l\u00e1tky houby Huaier maj\u00ed \u0161irokou \u0161k\u00e1lu \u010dist\u011b regula\u010dn\u00edch a programov\u00fdch vlastnost\u00ed. Jsou schopny obnovit chybn\u011b nasm\u011brovan\u00e9 geny do jejich p\u016fvodn\u00edho rozsahu funkc\u00ed a dokonce je p\u0159eprogramovat sm\u011brem k norm\u00e1ln\u00ed funkci.<\/p>\n\n\n\n<p>Geny mohou b\u00fdt zapnuty nebo vypnuty a regulov\u00e1ny nahoru nebo dol\u016f. V\u0161echny stavy, kter\u00e9 nejsou v norm\u00e1ln\u00edm rozmez\u00ed, maj\u00ed za n\u00e1sledek odpov\u00eddaj\u00edc\u00ed nadm\u011brn\u00e9 nebo potla\u010den\u00e9 reakce na sign\u00e1ly. \u00da\u010dinn\u00e9 l\u00e1tky Huaier jsou schopny selektivn\u011b obnovit individu\u00e1ln\u011b spr\u00e1vn\u00e9 regula\u010dn\u00ed chov\u00e1n\u00ed.<\/p>\n\n\n\n<p>Existuj\u00ed mechanistick\u00e9 paralely s ARLA, a proto existuj\u00ed \u010dty\u0159i kritick\u00e9 body molekul\u00e1rn\u00edho z\u00e1sahu, ve kter\u00fdch m\u016f\u017ee Huaier p\u016fsobit v patogenezi ARLA:<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NF-%CE%BAB-Pathway-Hemmung_Plasma-Membran-Signalisierung\"><\/span>Inhibice dr\u00e1hy NF-\u03baB (signalizace plazmatick\u00e9 membr\u00e1ny)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>U postinfek\u010dn\u00ed boreliov\u00e9 artritidy se po \u00fasp\u011b\u0161n\u00e9 antibiotick\u00e9 l\u00e9\u010db\u011b bor\u00e9li\u00ed tzv. <em>perzistentn\u00ed peptidoglykany<\/em>, slo\u017eky bun\u011b\u010dn\u00e9 st\u011bny mrtv\u00fdch bor\u00e9li\u00ed, v synovi\u00e1ln\u00ed tekutin\u011b a v kloubn\u00ed tk\u00e1ni. Tyto peptidoglykany jsou pr\u016fb\u011b\u017en\u011b rozpozn\u00e1v\u00e1ny imunitn\u00edm syst\u00e9mem, a to zejm\u00e9na pomoc\u00ed <em>Toll-like receptor 2<\/em> (TLR2), kter\u00fd je lokalizov\u00e1n na povrchu makrof\u00e1g\u016f, dendritick\u00fdch bun\u011bk a dal\u0161\u00edch bun\u011bk vrozen\u00e9 imunity.<\/p>\n\n\n\n<p>Kdy\u017e TLR2 rozpozn\u00e1 perzistentn\u00ed peptidoglykany, spust\u00ed se signaliza\u010dn\u00ed kask\u00e1da, kter\u00e1 vede k aktivaci klasick\u00fdch peptidoglykan\u016f. <em>sign\u00e1ln\u00ed dr\u00e1ha NF-\u03baB<\/em> vede. K tomu doch\u00e1z\u00ed prost\u0159ednictv\u00edm n\u00e1boru adaptorov\u00fdch protein\u016f, jako jsou nap\u0159. <em>TIRAP<\/em> a <em>MyD88<\/em> na aktivovan\u00fd receptor TLR2.<br>Tyto adaptorov\u00e9 proteiny pak rekrutuj\u00ed komplex kin\u00e1z, v\u010detn\u011b kin\u00e1zy. <em>Komplex IKK<\/em> (Inhibitor \u03baB kin\u00e1zy), co\u017e je inhibi\u010dn\u00ed b\u00edlkovina. <em>I\u03baB\u03b1<\/em> fosforylov\u00e1ny, a t\u00edm ozna\u010deny pro proteazom\u00e1ln\u00ed degradaci. Po degradaci I\u03baB\u03b1 se z n\u011bj st\u00e1v\u00e1 <em>Dimer transkrip\u010dn\u00edho faktoru p50\/p65<\/em> se uvoln\u00ed z NF-\u03baB a m\u016f\u017ee se p\u0159em\u00edstit do bun\u011b\u010dn\u00e9ho j\u00e1dra.<\/p>\n\n\n\n<p>Jakmile se NF-\u03baB objev\u00ed v bun\u011b\u010dn\u00e9m j\u00e1d\u0159e, nav\u00e1\u017ee se na vazebn\u00e1 m\u00edsta \u03baB DNA v promotorov\u00fdch oblastech proz\u00e1n\u011btliv\u00fdch cytokin\u016f a zah\u00e1j\u00ed jejich masivn\u00ed transkripci. To vede k nep\u0159etr\u017eit\u00e9, trval\u00e9 produkci <em>TNF-\u03b1, IL-6, IL-1\u03b2, IL-8<\/em> a dal\u0161\u00ed chemokiny, jako jsou nap\u0159. <em>MCP-1<\/em> a <em>KC<\/em>.<br>U pacient\u016f s ARLA nen\u00ed tento proces samovoln\u00fd. Pokra\u010duje t\u00fddny, m\u011bs\u00edce i roky, dokud jsou p\u0159\u00edtomny peptidoglykany. To je hlavn\u00ed probl\u00e9m: neexistuje nov\u00e1 infekce, se kterou by bylo t\u0159eba bojovat, ale imunitn\u00ed syst\u00e9m z\u016fst\u00e1v\u00e1 zaseknut\u00fd v z\u00e1n\u011btliv\u00e9m re\u017eimu.<\/p>\n\n\n\n<p><strong>Jak m\u016f\u017ee Huaier tento proces p\u0159eru\u0161it:<\/strong><\/p>\n\n\n\n<p>Huaier je bohat\u00fd na <em>\u03b2-glukany<\/em> a dal\u0161\u00ed <em>Polysacharidy<\/em>, kter\u00e9 se v\u00e1\u017eou na jin\u00fd receptor ne\u017e TLR2, a to na tzv. <em>Receptor Dectin-1<\/em> (Dectin-1 je <em>Receptor pro lektin typu C<\/em>, kter\u00fd je exprimov\u00e1n p\u0159edev\u0161\u00edm na makrof\u00e1z\u00edch a dendritick\u00fdch bu\u0148k\u00e1ch). Kdy\u017e se \u03b2-glukany z Huaier nav\u00e1\u017e\u00ed na Dectin-1, aktivuj\u00ed tak\u00e9 NF-\u03baB, ale alternativn\u00ed, m\u00e9n\u011b proz\u00e1n\u011btlivou sign\u00e1ln\u00ed cestou.<br>M\u00edsto klasick\u00e9ho <em>Trasa TIRAP\/MyD88<\/em> Stejn\u011b jako u signalizace TLR2 je signalizace prov\u00e1d\u011bna pomoc\u00ed <em>Syk kin\u00e1za<\/em> a <em>Card9<\/em>, co\u017e vede k \u201eregulovan\u00e9mu\u201c sign\u00e1lu NF-\u03baB.<\/p>\n\n\n\n<p>Krom\u011b toho Huaier pracuje prost\u0159ednictv\u00edm <em>miRNA zprost\u0159edkovan\u00e1<\/em> Mechanismy, kter\u00e9 vedou k redukci samotn\u00fdch slo\u017eek NF-\u03baB. Specifick\u00e9 mikroRNA, kter\u00e9 jsou regulov\u00e1ny Huaierem (jako nap\u0159. <em>miRNA-223, miRNA-146a<\/em> a dal\u0161\u00ed), mohou p\u0159\u00edmo degradovat mRNA podjednotek IKK a RelA (podjednotka p65 NF-\u03baB). To znamen\u00e1, \u017ee v bu\u0148k\u00e1ch je m\u00e9n\u011b celkov\u00e9ho komplexu NF-\u03baB, kter\u00fd m\u016f\u017ee b\u00fdt aktivov\u00e1n, i kdy\u017e jsou st\u00e1le p\u0159\u00edtomny p\u0159etrv\u00e1vaj\u00edc\u00ed peptidoglykany a stimuluj\u00ed TLR2.<\/p>\n\n\n\n<p>Praktick\u00fdm v\u00fdsledkem tohoto Huaierova dvoj\u00edho z\u00e1sahu je, \u017ee kontinu\u00e1ln\u00ed aktivace NF-\u03baB peptidoglykany je v\u00fdrazn\u011b omezena. Sn\u00ed\u017e\u00ed se produkce TNF-\u03b1, sn\u00ed\u017e\u00ed se produkce IL-6 a sn\u00ed\u017e\u00ed se produkce IL-1\u03b2. Klinicky to vede k rychl\u00e9mu sn\u00ed\u017een\u00ed C-reaktivn\u00edho proteinu (CRP), co\u017e je protein akutn\u00ed f\u00e1ze indukovan\u00fd NF-\u03baB.<br>P\u0159i men\u0161\u00edm mno\u017estv\u00ed TNF-\u03b1 a IL-6, kter\u00e9 p\u016fsob\u00ed jako chemokiny, se kloubn\u00ed v\u00fdpotek tak\u00e9 rychleji vst\u0159eb\u00e1v\u00e1, proto\u017ee se sni\u017euje n\u00e1bor leukocyt\u016f do kloubu. Pacienti uv\u00e1d\u011bj\u00ed rychl\u00e9 sn\u00ed\u017een\u00ed otoku a bolesti v prvn\u00edch 1-2 t\u00fddnech po zah\u00e1jen\u00ed l\u00e9\u010dby p\u0159\u00edpravkem Huaier. To je v souladu s potla\u010den\u00edm NF-\u03baB.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"JAKSTAT-Pathway-Modulation_Endosomal-Signalisierung_IL-6-Feedback\"><\/span>Modulace dr\u00e1hy JAK\/STAT (endozom\u00e1ln\u00ed signalizace + zp\u011btn\u00e1 vazba IL-6)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>ARLA je nadprodukce <em>Interferony typu I<\/em> (interferon-\u03b1 a interferon-\u03b2), kter\u00fd je zn\u00e1m\u00fd jako \u201e<em>Amplifika\u010dn\u00ed smy\u010dka IFN<\/em>\u201c je ozna\u010den. Nejedn\u00e1 se o klasickou signalizaci TLR2, o kter\u00e9 jsme pr\u00e1v\u011b hovo\u0159ili v souvislosti s NF-\u03baB. M\u00edsto toho k n\u00ed doch\u00e1z\u00ed jinou cestou: perzistentn\u00ed bor\u00e9lie jsou signalizov\u00e1ny prost\u0159ednictv\u00edm <em>Makrof\u00e1gy<\/em> a <em>dendritick\u00e9 bu\u0148ky<\/em> fagocytov\u00e1ny. Kdy\u017e jsou zachyceny ve fagozomu, jsou rozpozn\u00e1ny endozom\u00e1ln\u00edmi receptory podobn\u00fdmi Toll, a to zejm\u00e9na <em>TLR7, TLR8<\/em> a <em>TLR9<\/em>. Tyto receptory se nach\u00e1zej\u00ed na vnit\u0159n\u00edm povrchu <em>endozom\u00e1ln\u00ed\/fagozom\u00e1ln\u00ed vezikuly<\/em> a rozpozn\u00e1vaj\u00ed RNA a DNA bor\u00e9li\u00ed.<\/p>\n\n\n\n<p>Kdy\u017e jsou TLR7\/8\/9 stimulov\u00e1ny bakteri\u00e1ln\u00edmi nukleov\u00fdmi kyselinami, rekrutuj\u00ed adaptorov\u00fd protein. <em>MyD88<\/em> a\/nebo <em>TRIF<\/em> a vedou k aktivaci interferon-reguluj\u00edc\u00edch faktor\u016f, zejm\u00e9na <em>IRF3<\/em> a <em>IRF7<\/em>. Tyto transkrip\u010dn\u00ed faktory IRF pak vstupuj\u00ed do j\u00e1dra a iniciuj\u00ed transkripci interferonov\u00fdch gen\u016f typu I: zpo\u010d\u00e1tku <em>Interferon-\u03b2<\/em> a po n\u00ed n\u00e1sleduje sekund\u00e1rn\u00ed vlna <em>Interferon-\u03b1<\/em>.<\/p>\n\n\n\n<p>Jakmile se IFN-\u03b1 a IFN-\u03b2 uvoln\u00ed do synovi\u00e1ln\u00ed tekutiny a krve, nav\u00e1\u017e\u00ed se na receptor pro interferon-\u03b1\/\u03b2 (IFNAR), kter\u00fd je p\u0159\u00edtomen prakticky na v\u0161ech bu\u0148k\u00e1ch, v\u010detn\u011b t\u011bch, kter\u00e9 se nach\u00e1zej\u00ed v k\u016f\u017ei. <em>T-lymfocyty, makrof\u00e1gy<\/em> a <em>synovi\u00e1ln\u00ed fibroblasty<\/em>.<br>Vazba IFNAR rekrutuje k receptoru dv\u011b kin\u00e1zy: <em>JAK1<\/em> a <em>TYK2<\/em>. Tyto kin\u00e1zy pak fosforyluj\u00ed proteiny STAT. <em>STAT1<\/em> a <em>STAT2<\/em> (<strong>ne<\/strong> <em>STAT3<\/em> v t\u00e9to konkr\u00e9tn\u00ed cest\u011b). Fosforylovan\u00fd STAT1\/STAT2 spolu s fosforylovan\u00fdm <em>IRF9<\/em> komplex transkrip\u010dn\u00edch faktor\u016f, kter\u00fd <em>ISGF3<\/em> a p\u0159ech\u00e1z\u00ed do bun\u011b\u010dn\u00e9ho j\u00e1dra.<\/p>\n\n\n\n<p>V bun\u011b\u010dn\u00e9m j\u00e1d\u0159e se ISGF3 v\u00e1\u017ee na <em>Prvky odpov\u011bdi stimulovan\u00e9 interferonem<\/em> (ISRE) v promotorov\u00fdch oblastech <em>Interferonem stimulovan\u00e9 geny<\/em> (ISG). Mezi tyto ISG pat\u0159\u00ed geny jako nap\u0159. <em>OAS<\/em> (2\u2032,5\u2032-oligoadenyl\u00e1t syntet\u00e1za), <em>MxA<\/em> (Myxovirus Resistance Protein A), <em>PBR<\/em> (proteinkin\u00e1za R) a mnoho dal\u0161\u00edch. Tyto geny jsou masivn\u011b regulov\u00e1ny a vytv\u00e1\u0159ej\u00ed v bu\u0148k\u00e1ch \u201eantivirov\u00fd stav\u201c. To je norm\u00e1ln\u00ed a adaptivn\u00ed u skute\u010dn\u00e9 virov\u00e9 infekce, ale u ARLA je to maladaptivn\u00ed, proto\u017ee zde nen\u00ed aktivn\u00ed virov\u00e1 infekce. Jedn\u00e1 se o jak\u00fdsi \u201efale\u0161n\u00fd poplach\u201c.<\/p>\n\n\n\n<p>Probl\u00e9m zhor\u0161uje mechanismus zp\u011btn\u00e9 vazby: bu\u0148ky produkuj\u00edc\u00ed interferon produkuj\u00ed v\u00edce interferonu, co\u017e vyvol\u00e1v\u00e1 je\u0161t\u011b siln\u011bj\u0161\u00ed signalizaci IFNAR v jin\u00fdch bu\u0148k\u00e1ch, co\u017e zase vede k v\u011bt\u0161\u00ed transkripci ISG, kter\u00e1 zase zvy\u0161uje pravd\u011bpodobnost v\u011bt\u0161\u00ed produkce IFN. To je tzv.\u201e<em>Amplifika\u010dn\u00ed smy\u010dka IFN<\/em>\u201e, kter\u00e1 je charakteristick\u00e1 pro postinfek\u010dn\u00ed ARLA. Tato smy\u010dka je samospou\u0161t\u011bc\u00ed: i po usmrcen\u00ed v\u0161ech \u017eiv\u00fdch bor\u00e9li\u00ed tato cesta pokra\u010duje, proto\u017ee mrtv\u00e9 bakterie a jejich nukleov\u00e9 kyseliny jsou st\u00e1le fagocytov\u00e1ny.<\/p>\n\n\n\n<p>Sou\u010dasn\u011b tento stav IFN typu I vede k aktivaci a expanzi T bun\u011bk, zejm\u00e9na T lymfocyt\u016f. <em>bu\u0148ky Th1<\/em> a pozd\u011bji tak\u00e9 <em>bu\u0148ky Th17<\/em>. Bu\u0148ky Th17 se aktivuj\u00ed jin\u00fdm mechanismem: pot\u0159ebuj\u00ed... <em>IL-6<\/em> v kombinaci s <em>TGF-\u03b2<\/em>. IL-6 je tak\u00e9 produkov\u00e1n NF-\u03baB, ale tak\u00e9 geny stimulovan\u00fdmi interferonem. Existuje tedy n\u011bkolik cest, kter\u00e9 vedou ke vzniku IL-6.<\/p>\n\n\n\n<p>Jakmile je IL-6 p\u0159\u00edtomen ve v\u00fdznamn\u00e9m mno\u017estv\u00ed, stane se n\u011bco zaj\u00edmav\u00e9ho: IL-6 se v\u00e1\u017ee na sv\u016fj receptor (<em>IL-6R<\/em>) spolu s ko-receptorem, kter\u00fd se naz\u00fdv\u00e1 <em>gp130<\/em> na povrchu T-bun\u011bk, synovi\u00e1ln\u00edch fibroblast\u016f a dal\u0161\u00edch bun\u011bk. Tato vazba rekrutuje JAK1 a JAK2 k receptoru. JAK1 a JAK2 pak fosforyluj\u00ed protein STAT STAT3. Touto fosforylac\u00ed se STAT3 aktivuje a vstupuje do bun\u011b\u010dn\u00e9ho j\u00e1dra, kde se v\u00e1\u017ee na vazebn\u00e1 m\u00edsta DNA a iniciuje transkripci IL-17 a transkrip\u010dn\u00edho faktoru ROR\u03b3t.<\/p>\n\n\n\n<p>To vede k masivn\u00ed expanzi bun\u011bk Th17, kter\u00e9 n\u00e1sledn\u011b produkuj\u00ed v\u00edce IL-17. IL-17 je vysoce proz\u00e1n\u011btliv\u00fd a p\u016fsob\u00ed na synovi\u00e1ln\u00ed fibroblasty (tzv. FLS - fibroblast\u016fm podobn\u00e9 synoviocyty), kter\u00e9 produkuj\u00ed je\u0161t\u011b v\u00edce IL-6. Vznik\u00e1 tak druh\u00fd syst\u00e9m zp\u011btn\u00e9 vazby: IL-6 \u2192 expanze Th17 \u2192 produkce IL-17 \u2192 v\u00edce IL-6 z FLS \u2192 je\u0161t\u011b v\u00edce Th17 \u2192 je\u0161t\u011b v\u00edce IL-17. Stejn\u011b jako v p\u0159\u00edpad\u011b smy\u010dky amplifikace IFN se tato smy\u010dka sama opakuje a d\u00e1v\u00e1 ARLA jej\u00ed chronick\u00fd, obt\u00ed\u017en\u011b kontrolovateln\u00fd charakter.<\/p>\n\n\n\n<p><strong>Jak m\u016f\u017ee Huaier tento proces p\u0159eru\u0161it:<\/strong><\/p>\n\n\n\n<p>Huaier zasahuje do t\u00e9to dr\u00e1hy JAK\/STAT na z\u00e1sadn\u011bj\u0161\u00ed \u00farovni, ne\u017e je p\u0159\u00edm\u00e9 blokov\u00e1n\u00ed JAK1 nebo JAK2 (proto\u017ee blokuje JAK1 nebo JAK2). <em>Inhibitory JAK<\/em> jako <em>Upadacitinib<\/em> do). <strong>M\u00edsto toho Huaier p\u016fsob\u00ed prost\u0159ednictv\u00edm transkrip\u010dn\u00ed regulace zprost\u0159edkovan\u00e9 miRNA.<\/strong>. Specifick\u00e9 mikroRNA, kter\u00e9 jsou regulov\u00e1ny Huaierov\u00fdmi polysacharidy, samy ni\u010d\u00ed nebo degraduj\u00ed mRNA protein\u016f JAK.<\/p>\n\n\n\n<p>K tomu doch\u00e1z\u00ed d\u00edky elegantn\u00edmu regula\u010dn\u00edmu mechanismu: kdy\u017e se Huaierovy polysacharidy nav\u00e1\u017e\u00ed na Dectin-1 a stimuluj\u00ed bu\u0148ku sign\u00e1ly, aktivuje se nejen jedna sign\u00e1ln\u00ed dr\u00e1ha, ale tak\u00e9 se zv\u00fd\u0161\u00ed po\u010det enzym\u016f zpracov\u00e1vaj\u00edc\u00edch miRNA. Ty vedou k biogenezi n\u011bkolika kanonick\u00fdch i nekanonick\u00fdch miRNA. N\u011bkter\u00e9 z t\u011bchto miRNA, jako nap\u0159. <strong>miR-223, miR-146a<\/strong> a <strong>miR-34a<\/strong>, maj\u00ed vazebn\u00e1 m\u00edsta v nep\u0159ekl\u00e1dan\u00e9 oblasti 3' (<strong>3\u2032-UTR<\/strong>) od <em>JAK1, JAK2<\/em> a <em>STAT3 mRNA<\/em>.<br>Kdy\u017e tyto miRNA hybridizuj\u00ed s t\u011bmito sekvencemi, ozna\u010d\u00ed mRNA pro rozklad RNA interferenc\u00ed pomoc\u00ed <strong>Komplex RISC<\/strong> (RNA-Induced Silencing Complex). V\u00fdsledkem je, \u017ee mRNA je degradov\u00e1na a tyto proteiny ji\u017e nejsou produkov\u00e1ny tak efektivn\u011b.<\/p>\n\n\n\n<p>B\u011bhem n\u011bkolika dn\u016f a\u017e t\u00fddne po vystaven\u00ed Huaierov\u011b p\u016fsoben\u00ed se bu\u0148ky jednodu\u0161e <strong>m\u00e9n\u011b JAK1-, JAK2-<\/strong> a <strong>Protein STAT3<\/strong>. To je z\u00e1sadn\u011bj\u0161\u00ed ne\u017e pouh\u00e9 blokov\u00e1n\u00ed kin\u00e1zov\u00e9 aktivity. Znamen\u00e1 to, \u017ee i kdy\u017e je receptor aktivov\u00e1n a sna\u017e\u00ed se fosforylovat JAK, je k dispozici m\u00e9n\u011b molekul JAK k fosforylaci. Na adrese <strong>Reakce na signalizaci cytokin\u016f z\u00e1vislou na JAK<\/strong> je proto <strong>v\u00fdrazn\u011b sn\u00ed\u017eena<\/strong>.<\/p>\n\n\n\n<p>Toto sn\u00ed\u017een\u00ed exprese JAK p\u0159eru\u0161\u00ed smy\u010dku amplifikace IFN typu I. I kdy\u017e se TLR7\/8\/9 nad\u00e1le pokou\u0161\u00ed o produkci interferonu, bu\u0148ky produkuj\u00edc\u00ed IFN-\u03b1\/\u03b2 maj\u00ed m\u00e9n\u011b JAK1\/TYK2, tak\u017ee STAT1\/STAT2 m\u016f\u017ee b\u00fdt fosforylov\u00e1n m\u00e9n\u011b \u00fa\u010dinn\u011b. To vede k men\u0161\u00ed aktivaci ISGF3, men\u0161\u00ed transkripci ISG, a t\u00edm i k men\u0161\u00edmu <strong>m\u00e9n\u011b \u201eantivirov\u00e9ho stavu\u201c<\/strong>.<\/p>\n\n\n\n<p>Sn\u00ed\u017een\u00ed JAK1 a JAK2 z\u00e1rove\u0148 p\u0159eru\u0161\u00ed zp\u011btnovazebn\u00ed smy\u010dku IL-6. I kdy\u017e je IL-6 p\u0159\u00edtomen a v\u00e1\u017ee se na IL-6R na T bu\u0148k\u00e1ch, je m\u00e9n\u011b JAK1 a JAK2, kter\u00e9 se fosforyluj\u00ed, a proto je STAT3 m\u00e9n\u011b fosforylov\u00e1n. S m\u00e9n\u011b aktivn\u00edm STAT3 se produkuje m\u00e9n\u011b ROR\u03b3t a IL-17, a proto bu\u0148ky Th17 neexpanduj\u00ed tak agresivn\u011b. To znamen\u00e1 men\u0161\u00ed produkci IL-17, men\u0161\u00ed stimulaci FLS k produkci IL-6, - a smy\u010dka je p\u0159eru\u0161ena.<\/p>\n\n\n\n<p>Z laboratorn\u00edho hlediska to vn\u00edm\u00e1me jako <strong>Sn\u00ed\u017een\u00ed hladiny IFN-\u03b3<\/strong> (marker aktivity Th1, kter\u00fd je rovn\u011b\u017e regulov\u00e1n IFN typu I), <strong>Sn\u00ed\u017een\u00ed hladiny IL-6 <\/strong>(marker pro zp\u011btnovazebn\u00ed syst\u00e9m IL-6) a <strong>Sn\u00ed\u017een\u00ed hladiny IL-17<\/strong> (marker pro Th17). K tomu doch\u00e1z\u00ed pomaleji ne\u017e k potla\u010den\u00ed NF-\u03baB (k n\u011bmu\u017e doch\u00e1z\u00ed b\u011bhem n\u011bkolika dn\u00ed) - trv\u00e1 p\u0159ibli\u017en\u011b 2-4 t\u00fddny, ne\u017e se \u00fa\u010dinky zalo\u017een\u00e9 na miRNA pln\u011b projev\u00ed, ale jakmile se tak stane, jsou trvalej\u0161\u00ed.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Vergleich_JAK1i_wie_Upadacitinib_vs_Huaier\"><\/span><br><strong>Srovn\u00e1n\u00ed: JAK1i (jako upadacitinib) vs Huaier:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>A <strong>Inhibitor JAK1<\/strong> jako <em>Upadacitinib<\/em> (obchodn\u00ed n\u00e1zev Rinvoq) p\u016fsob\u00ed zcela jin\u00fdm mechanismem ne\u017e Huaier, i kdy\u017e oba nakonec moduluj\u00ed sign\u00e1ln\u00ed dr\u00e1hy JAK\/STAT. Upadacitinib je mal\u00e1 molekula, kter\u00e1 m\u016f\u017ee b\u00fdt p\u0159\u00edmo <em>Kapsa pro vazbu ATP<\/em> na <em>Kin\u00e1za JAK1<\/em> a fyzicky je blokuje. Jedn\u00e1 se o jak\u00fdsi \u201emechanick\u00fd inhibitor\u201c.<br>Kdy\u017e je JAK1 zablokov\u00e1n, nem\u016f\u017ee ji\u017e fosforylovat aminokyselinu tyrozin na proteinech STAT bez ohledu na to, jak moc se receptor sna\u017e\u00ed JAK aktivovat. \u00da\u010dinek je rychl\u00fd: jakmile se upadacitinib vst\u0159eb\u00e1 do krevn\u00edho ob\u011bhu a dostane se do bun\u011bk, JAK1 je inhibov\u00e1n. To je d\u016fvod, pro\u010d maj\u00ed inhibitory JAK rychl\u00fd n\u00e1stup, obvykle za 2-4 t\u00fddny dojde ke znateln\u00e9mu klinick\u00e9mu zlep\u0161en\u00ed.<\/p>\n\n\n\n<p>Tato p\u0159\u00edm\u00e1 blok\u00e1da m\u00e1 v\u0161ak i sv\u00e9 nev\u00fdhody. Inhibitory JAK1 neinhibuj\u00ed pouze JAK1, ale v r\u016fzn\u00e9 m\u00ed\u0159e i ostatn\u00ed kin\u00e1zy JAK, v z\u00e1vislosti na jejich selektivit\u011b. Dokonce i \u201eJAK1-selektivn\u00ed\u201c inhibitory do ur\u010dit\u00e9 m\u00edry slab\u011b inhibuj\u00ed JAK2 a TYK2. To vede k <strong>Ne\u017e\u00e1douc\u00ed \u00fa\u010dinky<\/strong>, zejm\u00e9na zv\u00fd\u0161en\u00e9 riziko <strong>Herpes zoster<\/strong> (p\u00e1sov\u00fd opar), proto\u017ee blok\u00e1da JAK3 naru\u0161uje proliferaci T-bun\u011bk, a t\u00edm i kontrolu latentn\u00edch vir\u016f, jako jsou nap\u0159. <em>Varicella zoster<\/em> oslabuje. Celkov\u011b vede blok\u00e1da JAK2 k. <strong>Aktivace tromboembolie<\/strong> m\u00edsto inhibice (zejm\u00e9na baricitinibu, kter\u00fd blokuje JAK2 siln\u011bji).<\/p>\n\n\n\n<p><strong>Huaier<\/strong> funguje na zcela jin\u00e9 \u00farovni. Neblokuje p\u0159\u00edmo protein JAK. M\u00edsto toho <strong>sn\u00ed\u017een\u00fd<\/strong> to <strong>mno\u017estv\u00ed proteinu JAK<\/strong>, kter\u00e9 bu\u0148ka v\u016fbec produkuje. K tomu doch\u00e1z\u00ed prost\u0159ednictv\u00edm miRNA zprost\u0159edkovan\u00e9 degradace mRNA JAK. V\u00fdhodou je, \u017ee tento mechanismus je jemn\u011bj\u0161\u00ed a mo\u017en\u00e1 i fyziologi\u010dt\u011bj\u0161\u00ed. Bu\u0148ky jednodu\u0161e sn\u00ed\u017e\u00ed mno\u017estv\u00ed JAK, kter\u00e9 produkuj\u00ed, nam\u00edsto toho, aby l\u00e9k n\u00e1siln\u011b blokoval tento protein. Nev\u00fdhodou je, \u017ee tento proces je pomalej\u0161\u00ed. Trv\u00e1 n\u011bkolik dn\u00ed a\u017e t\u00fdden, ne\u017e dojde k regulaci miRNA v dostate\u010dn\u00e9m mno\u017estv\u00ed, a pak trv\u00e1 dal\u0161\u00edch n\u011bkolik dn\u00ed, ne\u017e se rozlo\u017e\u00ed dostate\u010dn\u00e9 mno\u017estv\u00ed mRNA JAK, aby hladina proteinu JAK znateln\u011b klesla. To je d\u016fvod, pro\u010d m\u00e1 Huaier pomalej\u0161\u00ed n\u00e1stup, pravd\u011bpodobn\u011b 4-8 t\u00fddn\u016f do znateln\u00e9ho \u00fa\u010dinku na procesy z\u00e1visl\u00e9 na JAK\/STAT.<\/p>\n\n\n\n<p>Dal\u0161\u00edm d\u016fle\u017eit\u00fdm rozd\u00edlem je reverzibilita. Kdy\u017e pacient p\u0159estane u\u017e\u00edvat upadacitinib, blok\u00e1da JAK skon\u010d\u00ed b\u011bhem 24-48 hodin, proto\u017ee polo\u010das upadacitinibu je kr\u00e1tk\u00fd. JAK1 se op\u011bt st\u00e1v\u00e1 aktivn\u00edm a m\u016f\u017ee fosforylovat STAT. To je u\u017eite\u010dn\u00e9, pokud pacient trp\u00ed infekcemi a pot\u0159ebuje l\u00e9\u010dbu p\u0159eru\u0161it, ale tak\u00e9 to znamen\u00e1, \u017ee je nutn\u00e9 st\u00e1l\u00e9 denn\u00ed pod\u00e1v\u00e1n\u00ed. Huaier m\u016f\u017ee m\u00edt dlouhodob\u011bj\u0161\u00ed \u00fa\u010dinek, proto\u017ee regulace na b\u00e1zi miRNA trv\u00e1 d\u00e9le. Samotn\u00e9 miRNA maj\u00ed del\u0161\u00ed polo\u010das rozpadu ne\u017e mal\u00e9 molekuly a obnova JAK proteinu trv\u00e1 d\u00e9le, kdy\u017e se expozice p\u0159\u00edpravku Huaier ukon\u010d\u00ed.<\/p>\n\n\n\n<p>Je\u0161t\u011b jemn\u011bj\u0161\u00ed rozd\u00edl spo\u010d\u00edv\u00e1 ve specifi\u010dnosti. Upadacitinib je JAK1-selektivn\u00ed, co\u017e znamen\u00e1, \u017ee siln\u011b blokuje JAK1, slab\u011b blokuje JAK2 a sotva blokuje JAK3. To je vlastn\u011b c\u00edlem selektivity JAK1, toti\u017e vyhnout se blokov\u00e1n\u00ed JAK3, aby byly l\u00e9pe zachov\u00e1ny funkce T-bun\u011bk.<br>Huaier pravd\u011bpodobn\u011b sni\u017euje JAK1, JAK2 a mo\u017en\u00e1 i TYK2 v\u00edce \u010di m\u00e9n\u011b proporcion\u00e1ln\u011b v z\u00e1vislosti na tom, kter\u00e9 miRNA jsou regulov\u00e1ny. To by mohlo znamenat, \u017ee Huaier m\u00e1 <strong>\u0161ir\u0161\u00ed suprese JAK<\/strong> co\u017e by mohlo b\u00fdt dobr\u00e9 nap\u0159\u00edklad pro signalizaci IFN typu I (kter\u00e1 pot\u0159ebuje TYK2), ale tak\u00e9 by to mohlo v\u00e9st k v\u011bt\u0161\u00edmu vlivu JAK2 (teoreticky riziko tromboembolie).<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"PI3KAKT-Aktivierung_Mitochondriale_Restoration_Treg-Support\"><\/span>Aktivace PI3K\/AKT (obnova mitochondri\u00ed + podpora Treg)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>T\u0159et\u00edm z\u00e1va\u017en\u00fdm probl\u00e9mem ARLA je nejen p\u0159etrv\u00e1vaj\u00edc\u00ed produkce proz\u00e1n\u011btliv\u00fdch cytokin\u016f, ale tak\u00e9 rozpad syst\u00e9m\u016f, kter\u00e9 by za norm\u00e1ln\u00edch okolnost\u00ed tento z\u00e1n\u011bt omezovaly. Nejd\u016fle\u017eit\u011bj\u0161\u00edm syst\u00e9mem, kter\u00fd kontroluje z\u00e1n\u011bt, je populace regula\u010dn\u00edch T bun\u011bk (<em>Tregs<\/em>), zejm\u00e9na <em>CD4+CD25+Foxp3+ <\/em>Tregs.<\/p>\n\n\n\n<p>U zdrav\u00fdch lid\u00ed jsou Tregs ned\u00edlnou sou\u010d\u00e1st\u00ed imunitn\u00edho syst\u00e9mu a p\u016fsob\u00ed prost\u0159ednictv\u00edm produkce protiz\u00e1n\u011btliv\u00fdch cytokin\u016f, jako jsou nap\u0159. <em>IL-10<\/em> a <em>TGF-\u03b2<\/em>, a tak\u00e9 p\u0159\u00edm\u00fdm kontaktem mezi bu\u0148kami, aby se indukovaly proz\u00e1n\u011btliv\u00e9 T-bu\u0148ky (<em>Efektorov\u00e9 T-bu\u0148ky<\/em>), kter\u00e9 maj\u00ed b\u00fdt potla\u010deny.<br>Tregs jsou metabolicky velmi aktivn\u00ed a spol\u00e9haj\u00ed se na oxidativn\u00ed fosforylaci. <em>Mitochondrie<\/em> To znamen\u00e1, \u017ee pot\u0159ebuj\u00ed funk\u010dn\u00ed mitochondrie a st\u00e1l\u00fd p\u0159\u00edsun energie. <em>ATP<\/em>. Pot\u0159ebuj\u00ed tak\u00e9 schopnost syntetizovat b\u00edlkoviny, zejm\u00e9na k v\u00fdrob\u011b b\u00edlkovin. <em>P\u0159epis Regula\u010dn\u00ed <\/em>protein Foxp3 a supresivn\u00ed cytokiny IL-10 a TGF-\u03b2.<\/p>\n\n\n\n<p>U pacient\u016f ARLA se pokazilo n\u011bkolik v\u011bc\u00ed. Zaprv\u00e9, v d\u016fsledku kontinu\u00e1ln\u00ed stimulace TLR2 a TLR7\/8. <strong>Chronicky zat\u00ed\u017een\u00e9 mitochondrie<\/strong>. Pr\u016fb\u011b\u017en\u00e1 v\u00fdroba <em>ROS<\/em> (reaktivn\u00ed formy kysl\u00edku) aktivovan\u00fdmi z\u00e1n\u011btliv\u00fdmi bu\u0148kami oxiduje vnit\u0159n\u00ed mitochondri\u00e1ln\u00ed membr\u00e1nu a po\u0161kozuje komplexy v elektronov\u00e9m transportn\u00edm \u0159et\u011bzci. Mitochondri\u00e1ln\u00ed DNA m\u016f\u017ee b\u00fdt oxidov\u00e1na, co\u017e vede k defektn\u00ed transkripci. Mitochondrie jednodu\u0161e nemohou produkovat dostatek ATP, aby z\u00e1sobovaly v\u0161echny bu\u0148ky v chronick\u00e9m z\u00e1n\u011btliv\u00e9m stavu.<\/p>\n\n\n\n<p>Za druh\u00e9, prost\u0159ednictv\u00edm <strong>chronick\u00e9 <em>Stresov\u00e1 situace ER<\/em><\/strong> (proto\u017ee z\u00e1n\u011btliv\u00e9 bu\u0148ky nep\u0159etr\u017eit\u011b produkuj\u00ed velk\u00e9 mno\u017estv\u00ed cytokin\u016f a <em>Schopnost skl\u00e1d\u00e1n\u00ed b\u00edlkovin<\/em> o <em>endoplazmatick\u00e9 retikulum<\/em> je p\u0159et\u00ed\u017een\u00e1), je <em>Kapacita synt\u00e9zy b\u00edlkovin<\/em> bun\u011bk se glob\u00e1ln\u011b sni\u017euje.<br>Ribosomy jsou n\u00e1strojem pro v\u00fdrobu b\u00edlkovin, a kdy\u017e je ER ve stresu, jsou ve stresu i ribosomy. V d\u016fsledku toho nemohou b\u00fdt optim\u00e1ln\u011b produkov\u00e1ny d\u016fle\u017eit\u00e9 proteiny, jako jsou Foxp3, IL-10 a TGF-\u03b2.<\/p>\n\n\n\n<p>Za t\u0159et\u00ed, v\u0161echny tyto metabolick\u00e9 probl\u00e9my jsou <strong>Tregs<\/strong> jednoduch\u00fd <strong>nefunk\u010dn\u00ed<\/strong>. A\u010dkoli Tregs lze st\u00e1le detekovat (\u010dasto se jejich po\u010det dokonce zv\u00fd\u0161\u00ed), jejich schopnost p\u016fsobit supresivn\u011b je zna\u010dn\u011b sn\u00ed\u017eena. Nedok\u00e1\u017eou produkovat dostate\u010dn\u00e9 mno\u017estv\u00ed IL-10. Tregs proto nejsou schopny dostate\u010dn\u011b potla\u010dit bu\u0148ky Th17 a Th1. S men\u0161\u00edm mno\u017estv\u00edm IL-10 v prost\u0159ed\u00ed nem\u016f\u017ee doch\u00e1zet k protiz\u00e1n\u011btliv\u00e9mu \u201ebrzd\u011bn\u00ed\u201c imunitn\u00edho syst\u00e9mu a <strong>Proz\u00e1n\u011btliv\u00e1 \u201eakcelerace\u201c z\u016fst\u00e1v\u00e1 aktivov\u00e1na<\/strong>.<\/p>\n\n\n\n<p><strong>Jak Huaier tento proces aktivuje\/obnovuje:<\/strong><\/p>\n\n\n\n<p>Huaier \u0159e\u0161\u00ed tento probl\u00e9m prost\u0159ednictv\u00edm <em>Sign\u00e1ln\u00ed dr\u00e1ha PI3K\/AKT<\/em> na. Kdy\u017e se Huaierovy polysacharidy nav\u00e1\u017e\u00ed na receptor Dectin-1, aktivuj\u00ed nejen dr\u00e1hy NF-\u03baB a interferonu, ale tak\u00e9 PI3K (fosfoinositid 3-kin\u00e1zu). PI3K katalyzuje fosforylaci fosfatidylinositol-(4,5)-bisfosf\u00e1tu (<em>PIP2<\/em>) na fosfatidylinositol-(3,4,5)-trisfosf\u00e1t (<em>PIP3<\/em>). PIP3 je \u201edruh\u00fd posel\u201c - intracelul\u00e1rn\u00ed sign\u00e1ln\u00ed molekula, kter\u00e1 p\u0159itahuje dal\u0161\u00ed proteiny.<\/p>\n\n\n\n<p>Protein, kter\u00fd je p\u0159itahov\u00e1n PIP3, je <em>ACT<\/em> (naz\u00fdvan\u00e1 tak\u00e9 proteinkin\u00e1za B). AKT je produkov\u00e1n 3-fosfoinositid-dependentn\u00ed proteinkin\u00e1zou 1 (<em>PDK1<\/em>) je fosforylov\u00e1n a aktivov\u00e1n. Po aktivaci je AKT \u201ehlavn\u00edm regul\u00e1torem\u201c mnoha bun\u011b\u010dn\u00fdch proces\u016f. V souvislosti s ARLA jsou obzvl\u00e1\u0161t\u011b d\u016fle\u017eit\u00e9 dv\u011b funkce AKT:<\/p>\n\n\n\n<p>Za prv\u00e9, <strong>AKT aktivuje mTOR<\/strong> (mechanistic Target Of Rapamycin), velk\u00fd proteinov\u00fd komplex, kter\u00fd \u0159\u00edd\u00ed translaci mRNA a biogenezi ribozom\u016f.<br>Kdy\u017e AKT aktivuje mTOR, doch\u00e1z\u00ed ke dv\u011bma ud\u00e1lostem: (1) mTOR fosforyluje <em>S6K<\/em> (ribozom\u00e1ln\u00ed S6 kin\u00e1za), kter\u00e1 fosforyluje proteiny S6 v ribozomech, co\u017e vede ke zv\u00fd\u0161en\u00ed \u00fa\u010dinnosti translace. (2) mTOR tak\u00e9 fosforyluje <em>4E-BP1<\/em> (4E-Binding Protein 1), kter\u00fd umo\u017e\u0148uje vazbu 4E-BP1 na 4E-BP1. <em>eIF4E<\/em> a t\u00edm zvy\u0161uje translaci mRNA z\u00e1visl\u00fdch na eIF4E.<br>V\u00fdsledkem je, \u017ee bu\u0148ka m\u016f\u017ee produkovat v\u00edce b\u00edlkovin za krat\u0161\u00ed dobu. Pro <strong>Tregs<\/strong> to znamen\u00e1, \u017ee nyn\u00ed mohou <strong>mohou optim\u00e1ln\u011b produkovat IL-10 a Foxp3.<\/strong>, pot\u0159ebn\u00e9 b\u00edlkoviny, <strong>m\u00edt tlumiv\u00fd \u00fa\u010dinek<\/strong>.<\/p>\n\n\n\n<p>Za druh\u00e9, <strong>AKT aktivuje biogenezi nov\u00fdch mitochondri\u00ed<\/strong>. To je \u010d\u00e1ste\u010dn\u011b zp\u016fsobeno aktivac\u00ed genu PGC1\u03b1 prost\u0159ednictv\u00edm AKT.<br>PGC1\u03b1 je takzvan\u00fd \u201ehlavn\u00ed regul\u00e1tor\u201c biogeneze mitochondri\u00ed. Jedn\u00e1 se o koaktiv\u00e1tor, kter\u00fd spolupracuje s n\u011bkolika transkrip\u010dn\u00edmi faktory p\u0159i aktivaci gen\u016f, kter\u00e9 k\u00f3duj\u00ed mitochondri\u00e1ln\u00ed proteiny. <br>S aktivn\u00edm <em>PGC1\u03b1<\/em> v bu\u0148k\u00e1ch vznikaj\u00ed nov\u00e9 mitochondrie. V pr\u016fb\u011bhu n\u011bkolika t\u00fddn\u016f tak mohou Tregs obnovovat sv\u00e9 mitochondrie, star\u00e9, po\u0161kozen\u00e9 mitochondrie jsou nahrazov\u00e1ny nov\u00fdmi, funk\u010dn\u00edmi a <strong>schopnost Tregs produkovat ATP je obnovena.<\/strong>.<\/p>\n\n\n\n<p>D\u00edky zlep\u0161en\u00ed funkce mitochondri\u00ed a lep\u0161\u00ed synt\u00e9ze b\u00edlkovin z\u00edsk\u00e1vaj\u00ed Tregs schopnost efektivn\u011b pracovat. Mohou op\u011bt produkovat v\u00fdznamn\u00e9 mno\u017estv\u00ed IL-10. D\u00edky IL-10 v synovi\u00e1ln\u00ed tekutin\u011b lze potla\u010dit bu\u0148ky Th17, potla\u010dit bu\u0148ky Th1 a vy\u0159e\u0161it chronickou autoimunitu.<\/p>\n\n\n\n<p>Jedn\u00e1 se o pomal\u00fd proces, biogeneze nov\u00fdch mitochondri\u00ed trv\u00e1 t\u00fddny, ale je udr\u017eiteln\u00e1. Zat\u00edmco potla\u010den\u00ed NF-\u03baB podle Huaiera funguje rychle (dny) a modulace JAK\/STAT funguje ve st\u0159edn\u011bdob\u00e9m horizontu (t\u00fddny). <em>Aktivace PI3K\/AKT<\/em> dlouh\u00fd z\u00e1sah, kter\u00fd nezm\u011bn\u00ed z\u00e1sadn\u00ed <strong>obnovuje metabolick\u00e9 podm\u00ednky pro imunitn\u00ed toleranci.<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Spezifische_Effekte_bei_ARLA\"><\/span><br><strong>Specifick\u00e9 \u00fa\u010dinky s ARLA:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>U pacienta s ARLA v baz\u00e1ln\u00edm stavu p\u0159ed Huaierovou terapi\u00ed existuje n\u011bkolik patologick\u00fdch rys\u016f. Za prv\u00e9, mitochondrie v synovi\u00e1ln\u00edch bu\u0148k\u00e1ch, makrof\u00e1z\u00edch a T-lymfocytech jsou chronicky napadeny. Elektronov\u00fd transportn\u00ed \u0159et\u011bzec nefunguje optim\u00e1ln\u011b a synt\u00e9za ATP je sn\u00ed\u017eena. To lze prok\u00e1zat metabolick\u00fdmi testy, nap\u0159. <em>Anal\u00fdzy mo\u0159sk\u00fdch kon\u00edk\u016f<\/em> (kter\u00e9 m\u011b\u0159\u00ed skute\u010dnou m\u00edru produkce ATP). Pacienti s ARLA m\u011bli ni\u017e\u0161\u00ed m\u00edru OXPHOS ne\u017e kontroln\u00ed subjekty.<\/p>\n\n\n\n<p>Za druh\u00e9, regula\u010dn\u00ed T-lymfocyty (Tregs) jsou po\u010detn\u00e9. Lze je identifikovat pomoc\u00ed <em>Pr\u016ftokov\u00e1 cytometrie<\/em> pomoc\u00ed marker\u016f CD4+CD25+Foxp3+. Pacienti s ARLA maj\u00ed \u010dasto zv\u00fd\u0161en\u00fd absolutn\u00ed po\u010det Tregs, n\u011bkdy dokonce vy\u0161\u0161\u00ed ne\u017e u zdrav\u00fdch jedinc\u016f. Dalo by se o\u010dek\u00e1vat, \u017ee v\u00edce Tregs povede k lep\u0161\u00ed supresi, ale opak je pravdou, proto\u017ee tyto Tregs jsou dysfunk\u010dn\u00ed. Produkuj\u00ed m\u00e9n\u011b IL-10 na bu\u0148ku, jejich supresivn\u00ed aktivita je n\u00edzk\u00e1, a proto nemohou \u00fa\u010dinn\u011b kontrolovat autoreaktivn\u00ed T-lymfocyty.<\/p>\n\n\n\n<p>Za t\u0159et\u00ed, pom\u011br IL-10\/IFN-\u03b3 je velmi nevyv\u00e1\u017een\u00fd. U zdrav\u00fdch lid\u00ed je IL-10 obvykle nejm\u00e9n\u011b stejn\u011b vysok\u00fd jako IFN-\u03b3, ne-li vy\u0161\u0161\u00ed. U pacient\u016f s ARLA je IFN-\u03b3 vysoce zv\u00fd\u0161en\u00fd (stokr\u00e1t vy\u0161\u0161\u00ed v synovi\u00e1ln\u00ed tekutin\u011b ne\u017e u zdrav\u00fdch lid\u00ed) a IL-10 je n\u00edzk\u00fd. Tato nerovnov\u00e1ha je pravd\u011bpodobn\u011b jedn\u00edm z nejlep\u0161\u00edch biologick\u00fdch marker\u016f z\u00e1va\u017enosti ARLA.<\/p>\n\n\n\n<p>Za \u010dtvrt\u00e9, titry autoprotil\u00e1tek jsou zv\u00fd\u0161en\u00e9. Ty mohou b\u00fdt <em>Protil\u00e1tky proti OspA<\/em> (proti antigenu bor\u00e9li\u00ed, ale reakce p\u0159etrv\u00e1v\u00e1), protil\u00e1tky proti t\u011blu vlastn\u00edm protein\u016fm chrupavky, jako jsou nap\u0159. <em>Kolagen typu II<\/em> a <em>Aggrecan<\/em>, n\u011bkdy tak\u00e9 <em>Revmatoidn\u00ed faktor<\/em> a <em>Protil\u00e1tky anti-CCP<\/em>.<\/p>\n\n\n\n<p>Po zah\u00e1jen\u00ed l\u00e9\u010dby p\u0159\u00edpravkem Huaier v d\u00e1vce 20 g\/den a n\u011bkolika t\u00fddnech a\u017e m\u011bs\u00edc\u00edch pozorujeme n\u00e1sleduj\u00edc\u00ed zm\u011bny:<\/p>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <strong>mitochondri\u00e1ln\u00ed d\u00fdch\u00e1n\u00ed se normalizuje.<\/strong>. To lze m\u011b\u0159it pomoc\u00ed anal\u00fdzy mo\u0159sk\u00fdch kon\u00edk\u016f. Na str\u00e1nk\u00e1ch <strong><em>Z\u00e1kladn\u00ed d\u00fdch\u00e1n\u00ed<\/em> a rychlost produkce ATP se zv\u00fd\u0161\u00ed na norm\u00e1ln\u00ed hodnoty<\/strong>. To je m\u011b\u0159iteln\u00e9 a reprodukovateln\u00e9. Mechanismem je PI3K\/AKT zprost\u0159edkovan\u00e1 mitochondri\u00e1ln\u00ed biogeneze prost\u0159ednictv\u00edm indukce PGC1\u03b1, jak je pops\u00e1no v\u00fd\u0161e.<\/p>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <strong>Tregs se st\u00e1vaj\u00ed funk\u010dn\u00edmi<\/strong>. To je jemn\u011bj\u0161\u00ed m\u011b\u0159it, ale existuje n\u011bkolik cest: zvy\u0161uje se produkce IL-10 na Treg (lze m\u011b\u0159it intracelul\u00e1rn\u00edm barven\u00edm cytokin\u016f a pr\u016ftokovou cytometri\u00ed). Zvy\u0161uje se exprese Foxp3 (v\u00edce proteinu Foxp3 na bu\u0148ku). Supresivn\u00ed funkci in vitro lze m\u011b\u0159it pomoc\u00ed test\u016f suprese. Pokud jsou Tregs pacient\u016f s ARLA kultivov\u00e1ny spole\u010dn\u011b s autoreaktivn\u00edmi T bu\u0148kami, Tregs po terapii Huaierem l\u00e9pe potla\u010duj\u00ed proliferaci T bun\u011bk.<\/p>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <strong>Pom\u011br IL-10\/IFN-\u03b3 se v\u00fdrazn\u011b normalizuje<\/strong>. Hladina IFN-\u03b3 se \u010dasto sni\u017euje o 50-70% a hladina IL-10 se zvy\u0161uje o 100-200%. To vede k pom\u011bru, kter\u00fd op\u011bt vypad\u00e1 norm\u00e1ln\u011b, ji\u017e ne jako patologick\u00fd pom\u011br 1:100, ale bl\u00ed\u017e\u00ed se sp\u00ed\u0161e pom\u011bru 1:1 nebo dokonce IL-10 dominuje.<\/p>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <strong>Sn\u00ed\u017een\u00ed titr\u016f autoprotil\u00e1tek<\/strong>. To trv\u00e1 d\u00e9le, \u010dasto 8-12 t\u00fddn\u016f, ale titry trvale klesaj\u00ed. Nejd\u0159\u00edve kles\u00e1 anti-OspA, pozd\u011bji protil\u00e1tky proti t\u011blu vlastn\u00edm protein\u016fm chrupavky. To je zn\u00e1mka toho, \u017ee B-bun\u011b\u010dn\u00e1 odpov\u011b\u010f kles\u00e1 v d\u016fsledku normalizace kontroly T-bun\u011bk (Tregs inhibuj\u00ed B-bun\u011b\u010dnou odpov\u011b\u010f).<\/p>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <strong>Kloubn\u00ed v\u00fdpotek se sni\u017euje<\/strong>. Jedn\u00e1 se o nejviditeln\u011bj\u0161\u00ed znak a lze jej zm\u011b\u0159it klinick\u00fdm vy\u0161et\u0159en\u00edm, obvodov\u00fdm m\u011b\u0159en\u00edm nebo ultrazvukem. P\u0159i v\u011bt\u0161\u00edm mno\u017estv\u00ed IL-10 a men\u0161\u00edm mno\u017estv\u00ed TNF-\u03b1\/IL-6 se sni\u017euje chemotaxe leukocyt\u016f do kloubu a st\u00e1vaj\u00edc\u00ed v\u00fdpotek se reabsorbuje. V\u00fdpotek o objemu 200-300 ml se m\u016f\u017ee zmen\u0161it na 50-100 ml nebo zcela vymizet.<\/p>\n\n\n\n<p>Na str\u00e1nk\u00e1ch <strong>klinick\u00e9 p\u0159\u00edznaky se odpov\u00eddaj\u00edc\u00edm zp\u016fsobem zlep\u0161uj\u00ed<\/strong>Bolest se sni\u017euje, pohyblivost se zvy\u0161uje, pacienti mohou op\u011bt pou\u017e\u00edvat sv\u00e9 klouby. Kvalita \u017eivota se v\u00fdrazn\u011b zlep\u0161uje. Mnoho pacient\u016f s ARLA popisuje, \u017ee poprv\u00e9 po letech mohou op\u011bt vykon\u00e1vat b\u011b\u017en\u00e9 ka\u017edodenn\u00ed \u010dinnosti (ch\u016fze do schod\u016f, nakupov\u00e1n\u00ed, sport).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ribosomale_Homoostase_Tanaka-Hauptfund\"><\/span>Ribosom\u00e1ln\u00ed homeost\u00e1za (hlavn\u00ed n\u00e1lez Tanaka)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>\u010ctvrt\u00fd bod intervence je nen\u00e1padn\u00fd, ale potenci\u00e1ln\u011b kritick\u00fd, a to na z\u00e1klad\u011b Tanakov\u00fdch studi\u00ed o ribozom\u00e1ln\u00ed dysfunkci. Zde je hypot\u00e9za: u ARLA vede chronick\u00e1, p\u0159etrv\u00e1vaj\u00edc\u00ed signalizace TLR2 a TLR7\/8 k chronick\u00e9mu stresu ER. Endoplazmatick\u00e9 retikulum (ER) mus\u00ed neust\u00e1le skl\u00e1dat a uvol\u0148ovat velk\u00e9 mno\u017estv\u00ed nov\u00fdch cytokin\u016f a chemokin\u016f, tak\u017ee jeho proteostat\u00e1zov\u00e9 syst\u00e9my jsou neust\u00e1le p\u0159et\u011b\u017eov\u00e1ny.<\/p>\n\n\n\n<p>Pokud je ER vystavena chronick\u00e9mu stresu, bu\u0148ka reaguje tzv. \u201eunfolded protein response\u201c (\"reakce na rozlo\u017een\u00fd protein\").<em>UPR<\/em>). UPR je mechanismus p\u0159e\u017eit\u00ed, ale pokud je chronicky aktivov\u00e1n, m\u016f\u017ee se st\u00e1t problematick\u00fdm.<br>Jednou ze sou\u010d\u00e1st\u00ed UPR je fosforylace <em>eIF2\u03b1<\/em> (eukaryotick\u00fd inicia\u010dn\u00ed faktor 2 alfa) o <em>HRI<\/em> (Heme-Regulated Inhibitor Kinase) nebo jin\u00fdch kin\u00e1z. Kdy\u017e je eIF2\u03b1 fosforylov\u00e1n, sn\u00ed\u017e\u00ed se glob\u00e1ln\u00ed rychlost synt\u00e9zy protein\u016f. To je adaptivn\u00ed, proto\u017ee bu\u0148ka by nem\u011bla skl\u00e1dat je\u0161t\u011b v\u00edce protein\u016f, pokud je ER ji\u017e p\u0159et\u00ed\u017eena.<\/p>\n\n\n\n<p>Kdy\u017e se <em>Rychlost synt\u00e9zy b\u00edlkovin<\/em> je celkov\u011b sn\u00ed\u017eena, nejsou optim\u00e1ln\u011b produkov\u00e1ny ani proteiny, kter\u00e9 se za norm\u00e1ln\u00edch okolnost\u00ed mus\u00ed produkovat nep\u0159etr\u017eit\u011b, aby se udr\u017eela imunitn\u00ed tolerance. Pat\u0159\u00ed mezi n\u011b IL-10, TGF-\u03b2 a Foxp3. Jedn\u00e1 se o pom\u011brn\u011b velk\u00e9 a strukturn\u011b slo\u017eit\u00e9 proteiny, kter\u00e9 vy\u017eaduj\u00ed speci\u00e1ln\u00ed ribozom\u00e1ln\u00ed kvalitu, aby byly optim\u00e1ln\u011b slo\u017eeny.<\/p>\n\n\n\n<p>Krom\u011b toho mohou b\u00fdt p\u0159i ER stresu po\u0161kozeny i samotn\u00e9 ribozomy. Velk\u00e9 ribozom\u00e1ln\u00ed podjednotky (<em>60S<\/em>) a mal\u00e9 ribozom\u00e1ln\u00ed podjednotky (<em>40S<\/em>) maj\u00ed slo\u017eitou strukturu a slo\u017een\u00ed.<br>Kdy\u017e je ER ve stresu a bu\u0148ka produkuje p\u0159\u00edli\u0161 mnoho nespr\u00e1vn\u011b slo\u017een\u00fdch protein\u016f, mohou nespr\u00e1vn\u011b slo\u017een\u00e9 proteiny interagovat s ribozom\u00e1ln\u00edmi proteiny a po\u0161kozovat je, co\u017e n\u00e1sledn\u011b vede k abnorm\u00e1ln\u00edm struktur\u00e1m ribozom\u00e1ln\u00ed RNA, jak popsal Tanaka ve sv\u00e9 studii o o\u010dkov\u00e1n\u00ed mRNA.<\/p>\n\n\n\n<p>Pokud jsou ribozomy po\u0161kozeny na struktur\u00e1ln\u00ed \u00farovni, mohou st\u00e1le fungovat, ale ne optim\u00e1ln\u011b. To m\u016f\u017ee m\u00edt za n\u00e1sledek<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Chyby v p\u0159ekladu<\/li>\n\n\n\n<li>neefektivn\u00ed synt\u00e9za b\u00edlkovin<\/li>\n\n\n\n<li>defektn\u00ed proteiny, zejm\u00e9na strukturn\u011b slo\u017eit\u00e9 proteiny, jako je IL-10.<\/li>\n<\/ul>\n\n\n\n<p>Probl\u00e9m se tak s\u00e1m opakuje: \u0161patn\u00e9 ribozomy \u2192 \u0161patn\u00e1 synt\u00e9za IL-10 \u2192 m\u00e9n\u011b IL-10 v prost\u0159ed\u00ed \u2192 men\u0161\u00ed imunitn\u00ed tolerance \u2192 v\u00edce z\u00e1n\u011btu.<\/p>\n\n\n\n<p><strong>Jak Huaier tento proces opravuje:<\/strong><\/p>\n\n\n\n<p>Huaier se zab\u00fdv\u00e1 homeost\u00e1zou ribozom\u016f prost\u0159ednictv\u00edm regulace zprost\u0159edkovan\u00e9 miRNA. Tanaka popsal, \u017ee <strong>Huaier<\/strong> prost\u0159ednictv\u00edm upregulace specifick\u00fdch miRNA. <strong>normalizovan\u00e9 slo\u017een\u00ed a struktura ribozom\u00e1ln\u00ed RNA<\/strong>. Funguje to prost\u0159ednictv\u00edm n\u00e1sleduj\u00edc\u00edch mechanism\u016f:<\/p>\n\n\n\n<p>Za prv\u00e9, Huaier indukuje specifick\u00e9 miRNA, kter\u00e9 inhibuj\u00ed expresi protein\u016f pod\u00edlej\u00edc\u00edch se na dysfunkci ribozom\u016f. Nap\u0159\u00edklad miRNA mohou sn\u00ed\u017eit expresi protein\u016f, kter\u00e9 hromad\u00ed chybn\u011b slo\u017een\u00e9 proteiny v ribosomech.<\/p>\n\n\n\n<p>Za druh\u00e9, Huaier <strong>aktivuje autofagii a proteazom.<\/strong>, k odbour\u00e1v\u00e1n\u00ed po\u0161kozen\u00fdch ribozom\u00e1ln\u00edch protein\u016f a star\u00fdch ribozom\u016f. K tomu \u010d\u00e1ste\u010dn\u011b slou\u017e\u00ed miRNA reguluj\u00edc\u00ed geny autofagie. P\u0159i aktivovan\u00e9 autofagii jsou z bun\u011bk odstra\u0148ov\u00e1ny star\u00e9, po\u0161kozen\u00e9 ribozomy.<\/p>\n\n\n\n<p>Za t\u0159et\u00ed, aktivace PI3K\/AKT Huaierem (o kter\u00e9 jsme hovo\u0159ili v posledn\u00edm bod\u011b). <strong>Aktivuje mTOR<\/strong>, co\u017e nejen stimuluje translaci, ale tak\u00e9 biogenezi nov\u00fdch ribozom\u016f. To znamen\u00e1, \u017ee zat\u00edmco star\u00e9 ribozomy jsou odstra\u0148ov\u00e1ny autofagi\u00ed, <strong>nov\u00e9, funk\u010dn\u00ed ribozomy<\/strong> prost\u0159ednictv\u00edm synt\u00e9zy rRNA a exprese ribozom\u00e1ln\u00edch protein\u016f z\u00e1visl\u00e9 na mTOR. <strong>b\u00fdt vyroben<\/strong>.<\/p>\n\n\n\n<p>V\u00fdsledkem je po n\u011bkolika t\u00fddnech <strong>Normalizace populace ribozom\u016f<\/strong>. Bu\u0148ky nyn\u00ed maj\u00ed funk\u010dn\u00ed ribozomy se spr\u00e1vnou strukturou. To znamen\u00e1, \u017ee IL-10, TGF-\u03b2 a Foxp3 mohou b\u00fdt op\u011bt optim\u00e1ln\u011b syntetizov\u00e1ny. Na str\u00e1nk\u00e1ch <strong>Proteiny<\/strong>, kter\u00e9 se vyr\u00e1b\u011bj\u00ed, jsou <strong>Struktur\u00e1ln\u011b spr\u00e1vn\u00e9 a funk\u010dn\u011b efektivn\u00ed<\/strong>.<\/p>\n\n\n\n<p>Jedn\u00e1 se o Huaier\u016fv nejjemn\u011bj\u0161\u00ed a pravd\u011bpodobn\u011b nejpomalej\u0161\u00ed z\u00e1sah. Pln\u00e9 obnoven\u00ed kvality ribozom\u016f trv\u00e1 4-8 t\u00fddn\u016f nebo d\u00e9le. To je z\u00e1sadn\u00ed, proto\u017ee obnovuje schopnost bun\u011bk produkovat pr\u00e1v\u011b ty proteiny, kter\u00e9 jsou nezbytn\u00e9 pro imunitn\u00ed toleranci.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Mechanistischer_Vergleich_Huaier_zu_Biologika\"><\/span>Mechanistick\u00e9 srovn\u00e1n\u00ed Huaiera s biologick\u00fdmi l\u00e1tkami<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Aspekt<\/th><th>TNFi<\/th><th>IL-6i<\/th><th>JAK1i<\/th><th>HUAIER<\/th><\/tr><\/thead><tbody><tr><td><strong>Blokov\u00e1n\u00ed NF-\u03baB<\/strong><\/td><td>Nep\u0159\u00edm\u00fd (\u2193TNF)<\/td><td>Nep\u0159\u00edm\u00fd (\u2193IL-6)<\/td><td>Nep\u0159\u00edm\u00fd (\u2193JAK1)<\/td><td>P\u0159\u00edm\u00fd (potla\u010den\u00ed NF-\u03baB)<\/td><\/tr><tr><td><strong>Blokov\u00e1n\u00ed JAK\/STAT<\/strong><\/td><td>Ne<\/td><td>\u010c\u00e1ste\u010dn\u011b (cesta IL-6)<\/td><td>ANO (velmi siln\u00e9)<\/td><td>JA (prost\u0159ednictv\u00edm miRNA, slab\u0161\u00ed)<\/td><\/tr><tr><td><strong>Aktivace PI3K\/AKT<\/strong><\/td><td>Ne<\/td><td>Ne<\/td><td>Ne<\/td><td>ANO (SILN\u011a!)<\/td><\/tr><tr><td><strong>Kvalita ribozom\u016f<\/strong><\/td><td>Ne<\/td><td>Ne<\/td><td>Ne<\/td><td>JA (regulace miRNA)<\/td><\/tr><tr><td><strong>Podpora Treg<\/strong><\/td><td>Slab\u00e9<\/td><td>Slab\u00e9<\/td><td>Slab\u00fd (JAK3 nen\u00ed blokov\u00e1n)<\/td><td>STARK (prost\u0159ednictv\u00edm PI3K\/AKT + ribozom\u016f)<\/td><\/tr><tr><td><strong>Zv\u00fd\u0161en\u00ed IL-10<\/strong><\/td><td>Minim\u00e1ln\u00ed<\/td><td>Minim\u00e1ln\u00ed<\/td><td>N\u00edzk\u00e1<\/td><td>STARK (prost\u0159ednictv\u00edm ribozom\u016f + podpora Treg)<\/td><\/tr><tr><td><strong>N\u00e1stup<\/strong><\/td><td>4-8 Wo<\/td><td>4-12 Wo<\/td><td>2-4 Wo<\/td><td>4-8 Wo (odhad)<\/td><\/tr><tr><td><strong>Riziko infekce<\/strong><br><\/td><td>Zv\u00fd\u0161en\u00fd po\u010det str\u00e1nek<\/td><td>M\u00edrn\u00e1<\/td><td>M\u00edrn\u00e1<\/td><td>N\u00cdZK\u00c1 (bez imunosuprese!)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Dosierungsempfehlung_bei_ARLA_im_fortgeschrittenen_Stadium\"><\/span>Dosierungsempfehlung bei ARLA im fortgeschrittenen Stadium<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p><strong>ARLA v pokro\u010dil\u00e9m st\u00e1diu s multiorg\u00e1nov\u00fdm napaden\u00edm<\/strong>&nbsp;z\u00e1va\u017enost\u00ed a syst\u00e9movou z\u00e1t\u011b\u017e\u00ed odpov\u00edd\u00e1 nejt\u011b\u017e\u0161\u00edm p\u0159\u00edpad\u016fm rakoviny:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Chronick\u00fd multiorg\u00e1nov\u00fd z\u00e1n\u011bt<\/li>\n\n\n\n<li>Autoimunitn\u00ed slo\u017eka<\/li>\n\n\n\n<li>V\u00edcen\u00e1sobn\u00e9 samopodporuj\u00edc\u00ed smy\u010dky zp\u011btn\u00e9 vazby<\/li>\n\n\n\n<li>Mitochondri\u00e1ln\u00ed dysfunkce<\/li>\n\n\n\n<li>Po\u0161kozen\u00ed ribozom\u016f<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Vorschlag_fur_ARLA-Dosierung\"><\/span>N\u00e1vrh d\u00e1vkov\u00e1n\u00ed ARLA<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Doporu\u010den\u00ed: 50-60 g\/den<\/strong><br>Rozd\u011bleno na 3 \u00fa\u010dtenky, v\u017edy po 8 hodin\u00e1ch.<br>Stejn\u011b jako u v\u0161ech p\u0159\u00edpravk\u016f je pro dosa\u017een\u00ed zam\u00fd\u0161len\u00e9ho \u00fa\u010dinku nezbytn\u00e1 koncentrace \u00fa\u010dinn\u00fdch l\u00e1tek. Vzhledem k tomu, \u017ee se \u00fa\u010dinn\u00e9 l\u00e1tky v pr\u016fb\u011bhu \u010dasu v t\u011ble v\u00edce \u010di m\u00e9n\u011b rychle odbour\u00e1vaj\u00ed, je nezbytn\u00e9 p\u0159esn\u011b dodr\u017eovat \u010dasov\u00e9 intervaly mezi jednotliv\u00fdmi d\u00e1vkami, aby byla zachov\u00e1na konstantn\u00ed hladina \u00fa\u010dinn\u00fdch l\u00e1tek po cel\u00fd den!<\/p>\n\n\n\n<p><strong>Pro\u010d 50 - 60 g\/d m\u00edsto nap\u0159. 40 g\/d:<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Z\u00e1va\u017enost<\/strong>: Ve studii Tanaka odpov\u00edd\u00e1 posti\u017een\u00ed v\u00edce org\u00e1n\u016f st\u00e1diu IV rakoviny.<\/li>\n\n\n\n<li><strong>V\u00edce mechanism\u016f \u00fa\u010dinku<\/strong>: V\u0161echny 4 mechanismy mus\u00ed b\u00fdt \u0159e\u0161eny sou\u010dasn\u011b<\/li>\n\n\n\n<li><strong>Z\u00e1vislost na d\u00e1vce<\/strong>Tanaka vykazuje jasnou z\u00e1vislost na d\u00e1vce bez toxicity<\/li>\n\n\n\n<li><strong>\u010casov\u00fd faktor<\/strong>: Vy\u0161\u0161\u00ed d\u00e1vky by mohly umo\u017enit rychlej\u0161\u00ed n\u00e1stup \u00fa\u010dinku<\/li>\n<\/ol>\n\n\n\n<p><strong>D\u00e1vkovac\u00ed re\u017eim (n\u00e1vrh):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>F\u00e1ze 1 (t\u00fddny 1-4)<\/strong><br>60 g\/den (rozd\u011bleno na 3x20 g)<br>Zam\u011b\u0159en\u00ed: potla\u010den\u00ed NF-\u03baB, zah\u00e1jen\u00ed modulace JAK\/STAT<br>N\u00e1klady \/ m\u011bs\u00edc (ca.) 568,- Euro<\/li>\n\n\n\n<li><strong>F\u00e1ze 2 (t\u00fddny 5-12)<\/strong><br>50 g\/den (3\u00d716-17 g)<br>Zam\u011b\u0159en\u00ed: pln\u011b prok\u00e1zan\u00e9 \u00fa\u010dinky JAK\/STAT, aktivace PI3K\/AKT<br>N\u00e1klady \/ m\u011bs\u00edc (ca.) 473,- Euro<\/li>\n\n\n\n<li><strong>F\u00e1ze 3 (m\u011bs\u00edce 4-6)<\/strong><br>40 g\/den (3x13 g)<br>Konzervace, obnova ribozom\u016f<br>N\u00e1klady \/ m\u011bs\u00edc (ca.) 379,- Euro<\/li>\n\n\n\n<li><strong>Dlouhodob\u00e9 uchov\u00e1v\u00e1n\u00ed<\/strong><br>20-30 g\/den (3x 7 .. 3x 10 g)<br>N\u00e1klady \/ m\u011bs\u00edc (ca.) 189 ... 284,- Euro<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Weitere_relevante_Beitrage_zum_Anwendungsbereich_des_Huaier-Pilzes\"><\/span>Dal\u0161\u00ed relevantn\u00ed \u010dl\u00e1nky o oblasti p\u016fsobnosti houby Huaier<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Z\u00e1klady a l\u00e9\u010dba rakoviny<\/strong> -&gt; <a href=\"https:\/\/csiag.eu\/cs\/houba-huaier-v-terapii-rakoviny\/\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/csiag.eu\/huaier-pilz-in-der-krebstherapie\/<\/a><\/li>\n\n\n\n<li><strong>Chronick\u00e1 onemocn\u011bn\u00ed<\/strong> -&gt; <a href=\"https:\/\/csiag.eu\/cs\/huaier-houba-pro-chronicka-onemocneni\/\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/csiag.eu\/huaier-pilz-bei-chronischen-erkrankungen\/<\/a><\/li>\n<\/ul>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p>Es gibt vermeintlich &#8222;g\u00fcnstige&#8220; Anbieter von Huaier-Granulat. Unterschied zwischen dem &#8222;teuren&#8220; und &#8222;g\u00fcnstigen&#8220; Produkt ist, dass das teure aus dem Fruchtk\u00f6rper des Huaier-Pilzes gewonen wird, w\u00e4hrend das g\u00fcnstige aus dem Myzel auf z.B. Getreide hergestellt wird, dessen Wirkstoffgehalt z.T. nur ein Zehntel betr\u00e4gt und 90% an, bei der Festk\u00f6rperfermentation, unverdautem F\u00fcllstoff enth\u00e4lt.<\/p>\n\n\n\n<p>Hingegen sind bei Fl\u00fcssigfermentation, bei dem Myzel in n\u00e4hrstoffreichen Fl\u00fcssigmedien kultiviert wird, wiederum Wirkstoffe enthalten, die nicht aus dem Fruchtk\u00f6rper gewonnen werden k\u00f6nnen.<\/p>\n\n\n\n<p>Als &#8222;Fruchtk\u00f6rper&#8220; bezeichnet man den Pilz, wie er optisch wahrgenommen wird, als &#8222;Myzel&#8220; das Innere des Pilzes.<\/p>\n<\/blockquote>","protected":false},"excerpt":{"rendered":"<p><span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Doba \u010dten\u00ed<\/span> <span class=\"rt-time\"> 18<\/span> <span class=\"rt-label rt-postfix\">minuty<\/span><\/span>Borreliose wird durch Borrelia burgdorferi, einem spiralf\u00f6rmigen Bakterium, das die Lyme-Borreliose (auch Lyme-Krankheit genannt) verursacht. Er ist einer der wenigen Erreger, die wissenschaftlich derart faszinierend sind und gleichzeitig die schwierigsten bakteriellen Infektionen in Immunologie und Klinik darstellen: Die meisten Menschen mit Lyme-Arthritis erfahren Heilung nach Antibiotika-Therapie. Doch etwa 10% sprechen nicht auf diese Behandlung an&hellip;&nbsp;<a href=\"https:\/\/csiag.eu\/cs\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/\" rel=\"bookmark\">\u010c\u00edst d\u00e1le \"<span class=\"screen-reader-text\">Lymsk\u00e1 boreli\u00f3za - Huaier\u016fv p\u0159\u00edstup pro pacienty s ARLA (Antibioticky rezistentn\u00ed lymsk\u00e1 artritida)<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_lmt_disableupdate":"","_lmt_disable":"","neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"","neve_meta_content_width":0,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","footnotes":""},"categories":[1078,354],"tags":[],"class_list":["post-12268","post","type-post","status-publish","format-standard","hentry","category-medizin","category-medizin-gesundheit"],"modified_by":"Achim Goerner","_links":{"self":[{"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/posts\/12268","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/comments?post=12268"}],"version-history":[{"count":2,"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/posts\/12268\/revisions"}],"predecessor-version":[{"id":13417,"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/posts\/12268\/revisions\/13417"}],"wp:attachment":[{"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/media?parent=12268"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/categories?post=12268"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.eu\/cs\/wp-json\/wp\/v2\/tags?post=12268"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}