{"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":"borreliozes-arstesana-arla-pacientiem-antibiotiku-rezistentu-laima-artrits","status":"publish","type":"post","link":"https:\/\/csiag.eu\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/","title":{"rendered":"Laima slim\u012bba - Huaier pieeja ARLA pacientiem (Antibiotiku rezistents Laima artr\u012bts)"},"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\">Satura r\u0101d\u012bt\u0101js<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Pathogenese\" >Pato\u0123en\u0113ze<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Herkommliche_Therapieformen\" >Tradicion\u0101lie terapijas veidi<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#NSAR\" >NPL<\/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\/lv\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Beispiel_ARLA-Patient_%E2%80%93_NSARs_und_DMARD\" >ARLA pacienta piem\u0113rs - NPL un 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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Biologika\" >Biolo\u0123isk\u0101s z\u0101les<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Huaier-Pilz_%E2%80%93_eine_Alternative\" >Huaier s\u0113ne - alternat\u012bva?<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#NF-%CE%BAB-Pathway-Hemmung_Plasma-Membran-Signalisierung\" >NF-\u03baB ce\u013ca inhib\u012bcija (plazmas membr\u0101nas signaliz\u0101cija)<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#JAKSTAT-Pathway-Modulation_Endosomal-Signalisierung_IL-6-Feedback\" >JAK\/STAT ce\u013ca modul\u0101cija (endosom\u0101l\u0101 signaliz\u0101cija + IL-6 atgriezenisk\u0101 saite)<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Vergleich_JAK1i_wie_Upadacitinib_vs_Huaier\" >Sal\u012bdzin\u0101jums: JAK1i (piem\u0113ram, upadacitinibs) 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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#PI3KAKT-Aktivierung_Mitochondriale_Restoration_Treg-Support\" >PI3K\/AKT aktiviz\u0113\u0161ana (mitohondriju atjauno\u0161ana + Treg atbalsts)<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Spezifische_Effekte_bei_ARLA\" >\u012apa\u0161a ietekme ar 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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Ribosomale_Homoostase_Tanaka-Hauptfund\" >Ribosomu homeost\u0101ze (Tanaka galvenais atkl\u0101jums)<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Mechanistischer_Vergleich_Huaier_zu_Biologika\" >Huaier meh\u0101nisma sal\u012bdzin\u0101jums ar biolo\u0123iskajiem l\u012bdzek\u013ciem<\/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\/lv\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Vorschlag_fur_ARLA-Dosierung\" >ARLA doz\u0113\u0161anas priek\u0161likums<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Weitere_relevante_Beitrage_zum_Anwendungsbereich_des_Huaier-Pilzes\" >Citi attiec\u012bgie raksti par Huaier s\u0113nes piem\u0113ro\u0161anas jomu<\/a><\/li><\/ul><\/nav><\/div>\n<span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Las\u012b\u0161anas laiks<\/span> <span class=\"rt-time\"> 18<\/span> <span class=\"rt-label rt-postfix\">protokols<\/span><\/span>\n<p>Laima slim\u012bbu izraisa <em>Borrelia burgdorferi<\/em>, spir\u0101les formas bakt\u0113rija, kas var <em>Laima borelioze <\/em>(paz\u012bstama ar\u012b k\u0101 Laima slim\u012bba).<\/p>\n\n\n\n<p>Tas ir viens no nedaudzajiem patog\u0113niem, kas ir tik zin\u0101tniski aizraujo\u0161i un vienlaikus ir visgr\u016bt\u0101k izplat\u012bt\u0101s bakteri\u0101l\u0101s infekcijas imunolo\u0123ij\u0101 un kl\u012bniskaj\u0101 praks\u0113:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Neparasta \u0123en\u0113tika:<\/strong> Line\u0101r\u0101 hromosomu un kompleks\u0101 plazm\u012bdu sist\u0113ma<\/li>\n\n\n\n<li><strong>Im\u016bnsist\u0113mas iebrukuma meistars:<\/strong> VlsE antig\u0113nu vari\u0101cijas, komplementa inhib\u012bcija, biofilma<\/li>\n\n\n\n<li><strong>Multiorg\u0101nu patog\u0113ni:<\/strong> Var ietekm\u0113t gandr\u012bz visas org\u0101nu sist\u0113mas<\/li>\n\n\n\n<li><strong>Notur\u012bbas speci\u0101lists:<\/strong> Var izrais\u012bt hroniskas infekcijas, kas ilgst gadiem.<\/li>\n\n\n\n<li><strong>TLR2 dominance:<\/strong> Izraisa masveida iekaisumu (vair\u0101k nek\u0101 Toll l\u012bdz\u012bgs receptoram 4).<\/li>\n\n\n\n<li><strong>Autoim\u016bn\u0101s sist\u0113mas potenci\u0101ls:<\/strong> izraisa p\u0113cinfekcijas autoimunit\u0101ti (ARLA).<\/li>\n<\/ul>\n\n\n\n<p>Liel\u0101k\u0101 da\u013ca cilv\u0113ku ar Laima artr\u012btu tiek iz\u0101rst\u0113ti p\u0113c antibiotiku terapijas. Tom\u0113r aptuveni 10% cilv\u0113ku nerea\u0123\u0113 uz \u0161o \u0101rst\u0113\u0161anu un vi\u0146iem att\u012bst\u0101s t\u0101 sauktais Laimas artr\u012bts. <strong>pret antibiotik\u0101m rezistents Laima artr\u012bts.<\/strong> (<em>ARLA<\/em>).<\/p>\n\n\n\n<p>\u0160ie 10% ir iedal\u012bti<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>50% ar spont\u0101nu remisiju (slim\u012bbas simptomu pagaidu vai past\u0101v\u012bga remisija) x gadu laik\u0101<\/li>\n\n\n\n<li>30% l\u012bdz <strong>DMARD<\/strong> (slim\u012bbu modific\u0113jo\u0161ie pretreimatiskie l\u012bdzek\u013ci) \/ <strong>Biolo\u0123isk\u0101s z\u0101les<\/strong> (<strong>iedarbojas uz konkr\u0113t\u0101m m\u0113r\u0137a strukt\u016br\u0101m.<\/strong> im\u016bnsist\u0113mu)<\/li>\n\n\n\n<li>20% hronisks un pret terapiju rezistents<\/li>\n<\/ul>\n\n\n\n<p>Vispirms tiek izskaidrota slim\u012bbas pato\u0123en\u0113ze (slim\u012bbas c\u0113lonis), tradicion\u0101l\u0101s terapijas iesp\u0113jas un p\u0113c tam terapijas pieeja ar Huaier s\u0113nes akt\u012bvaj\u0101m viel\u0101m.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Pathogenese\"><\/span>Pato\u0123en\u0113ze<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p><strong>Tie\u0161s iebrukums:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Kolag\u0113na\/dekor\u012bna saist\u012b\u0161an\u0101s ar DbpA\/B - (\u013cauj patog\u0113nam piestiprin\u0101ties pie ar kolag\u0113nu bag\u0101t\u0101m strukt\u016br\u0101m, kas ir svar\u012bgi faktiskai saimnieka inv\u0101zijai un patog\u0113na koloniz\u0101cijai saimniek\u0101).<\/li>\n\n\n\n<li>Fibronekt\u012bna saist\u012b\u0161an\u0101s ar BBK32 - (\u013cauj dinamiski stiprin\u0101t patog\u0113na saist\u012b\u0161an\u0101s sp\u0113ju, veidojot polimeriz\u0113tu fibronekt\u012bnu atkar\u012bb\u0101 no meh\u0101nisk\u0101s slodzes (piem\u0113ram, asinsrit\u0113): jo liel\u0101ka, jo stipr\u0101ka). <\/li>\n\n\n\n<li>Netie\u0161s audu boj\u0101jums, ko izraisa izrais\u012bta im\u016bn\u0101 reakcija.<\/li>\n<\/ul>\n\n\n\n<p><strong>Im\u016bnsist\u0113mas aktiviz\u0113\u0161ana (TLR2 domin\u0113jo\u0161ais):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Virsmas lipoprote\u012bni (OspA, OspC, OspE)<\/strong> \u2192 TLR2\/6 aktiviz\u0101cija (agr\u012bna im\u016bnreakcija, bet ar\u012b pato\u0123en\u0113ze, jo tie var izrais\u012bt p\u0101rm\u0113r\u012bgas iekaisuma reakcijas).<\/li>\n\n\n\n<li><strong>Peptidoglik\u0101ni<\/strong> \u2192 TLR2 aktiv\u0101cija (izraisa sp\u0113c\u012bgu iekaisuma reakciju un iedzimt\u0101s un adapt\u012bv\u0101s im\u016bnsist\u0113mas aktiv\u0101ciju).<\/li>\n\n\n\n<li>Noved pie masveida <strong>NF-\u03baB\/MAPK aktiv\u0101cija<\/strong> (izraisa sp\u0113c\u012bgu izdal\u012b\u0161anos&nbsp;<strong>proiekaisuma citok\u012bni<\/strong>&nbsp;piem\u0113ram, <strong>TNF-\u03b1, IL-6 un IL-1\u03b2.<\/strong>, kas pastiprina iekaisuma reakciju Laima slim\u012bbas gad\u012bjum\u0101).<\/li>\n\n\n\n<li>Massive <strong>pro-iekaisuma citok\u012bnu ra\u017eo\u0161ana<\/strong><\/li>\n<\/ul>\n\n\n\n<p><strong>Im\u016bn\u0101 invazija:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Komplementa inhib\u012bcija<\/strong><br><em>OspE, OspF<\/em> - Bakt\u0113rijas virsmas olbaltumvielas saist\u0101s ar komplementa sist\u0113mas regul\u0113jo\u0161o olbaltumvielu H faktoru un t\u0101d\u0113j\u0101di nov\u0113r\u0161 komplementa aktiviz\u0101ciju, kas cit\u0101di izn\u012bcin\u0101tu bakt\u0113riju.<br>\u0160\u0137iet, ka OspF ir svar\u012bga loma \u0113r\u010du pa\u0161aizsardz\u012bb\u0101 pret savu patog\u0113nu: ar OspF imuniz\u0113t\u0101m pel\u0113m spirohetu daudzums samazin\u0101j\u0101s l\u012bdz 90%. Avots:<a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC186469\/\" target=\"_blank\" rel=\"noreferrer noopener\">Borrelia burgdorferi da\u013c\u0113ja izn\u012bcin\u0101\u0161ana \u0113rc\u0113s, kas pies\u016bku\u0161\u0101s OspE vai OspF imuniz\u0113t\u0101m pel\u0113m<\/a>)<\/li>\n\n\n\n<li><strong>Antig\u0113nu vari\u0101cijas<\/strong><br><em>VlsE - main\u012bga galven\u0101 olbaltumvielai l\u012bdz\u012bga sekvence Expressed<\/em> &#8211; verhindert Erkennung durch das Immunsystem<\/li>\n\n\n\n<li><strong>Biofilmu veido\u0161an\u0101s<\/strong><br>selbst produzierte <em>ekstracelul\u0101r\u0101 polim\u0113ra viela<\/em> zum Eigenschutz des Erregers<\/li>\n\n\n\n<li><strong>Intracelul\u0101r\u0101 notur\u012bba<\/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>Autoimunit\u0101te (p\u0113c infekcijas):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>OspA un cilv\u0113ka olbaltumvielu (piem\u0113ram, LFA-1) savstarp\u0113j\u0101 reaktivit\u0101te.<\/strong><br>molekulares Mimicry: f\u00fchrt zu einer&nbsp;autoimmunologisch aufrechterhaltenen Entz\u00fcndung, auch wenn der Erreger bereits eliminiert ist.<br>Sp\u0113c\u012bga T-\u0161\u016bnu reakcija \u0123en\u0113tiski predispon\u0113tiem pacientiem ir saist\u012bta ar p\u0101rm\u0113r\u012bgu proiekaisuma citok\u012bnu (piem., T-\u0137ermen\u012b\u0161u) veido\u0161anos.&nbsp;<strong>TNF\u03b1, IFN\u03b3<\/strong>) verbunden, die den Entz\u00fcndungsprozess aufrecht erh\u00e4lt<\/li>\n\n\n\n<li><strong>Epitopa izplat\u012b\u0161an\u0101s<\/strong><br>Nach anf\u00e4nglicher Immunreaktion gegen Borrelien-Antigene wie&nbsp;<strong>OspA<\/strong>&nbsp;ilgsto\u0161s iekaisums izraisa audu boj\u0101\u0161anos un organisma olbaltumvielu izdal\u012b\u0161anos.<br>P\u0113c tam im\u016bnsist\u0113ma tos ar\u012b atpaz\u012bst un uzr\u0101da, t\u0101d\u0113j\u0101di im\u016bn\u0101 atbilde papla\u0161in\u0101s, aptverot jaunus, no sve\u0161zemju antig\u0113na neatkar\u012bgus epitopus. \u0160im procesam rakstur\u012bgs regul\u0113jo\u0161o faktoru tr\u016bkums.&nbsp;<strong>IL-10<\/strong>&nbsp;verst\u00e4rkt, was zu einer unkontrollierten Autoimmunit\u00e4t f\u00fchren kann.<\/li>\n\n\n\n<li><strong>Notur\u012bgi peptoglik\u0101ni izraisa autoreakt\u012bv\u0101s T \u0161\u016bnas<\/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>Tradicion\u0101lie terapijas veidi<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>NPL<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Nestero\u012bdie pretiekaisuma l\u012bdzek\u013ci (NPL) ir z\u0101les, kas mazina iekaisumu, atvieglo s\u0101pes un samazina drudzi, bet at\u0161\u0137ir\u012bb\u0101 no kortikostero\u012bdiem tie nav stero\u012bdi.<br>At\u0161\u0137ir\u012bb\u0101 no stero\u012bdiem NPL nepalielina infekciju bie\u017eumu.<\/p>\n\n\n\n<p>T\u0101s neselekt\u012bvi inhib\u0113 prostagland\u012bnus un tromboks\u0101nu produc\u0113jo\u0161os enz\u012bmus COX (ciklooksigen\u0101zi)-1 un COX-2.<br>COX-1 vienm\u0113r ir akt\u012bva (ja t\u0101 ir neakt\u012bva vai inhib\u0113ta, t\u0101 izraisa, piem\u0113ram, ku\u0146\u0123a \u010d\u016blas, nieru darb\u012bbas trauc\u0113jumus un tendenci asi\u0146ot), bet COX-2 iekaisuma laik\u0101 tiek regul\u0113ta.<br>COX-2 blo\u0137\u0113\u0161ana izraisa v\u0113lamo iedarb\u012bbu, piem\u0113ram, iekaisuma un s\u0101pju mazin\u0101\u0161anos, drud\u017ea samazin\u0101\u0161anos.<\/p>\n\n\n\n<p>T\u0101 k\u0101 neselekt\u012bvie NPL abus enz\u012bmus inhib\u0113 vien\u0101di, tiem ir ar\u012b iepriek\u0161 min\u0113t\u0101s nev\u0113lam\u0101s (blakus) blakuspar\u0101d\u012bbas.<\/p>\n\n\n\n<p><strong>NPL ir tikai simptom\u0101tiska iedarb\u012bba<\/strong>. Patog\u0113ns joproj\u0101m ir kl\u0101teso\u0161s un akt\u012bvs, iekaisuma mediatori (proiekaisuma citok\u012bni) turpina netrauc\u0113ti izdal\u012bties, un skrim\u0161\u013ca erozija nemazin\u0101s.<\/p>\n\n\n\n<p>Visbie\u017e\u0101k sastopam\u0101s neselekt\u012bvas NPL akt\u012bv\u0101s vielas ir \u0161\u0101das.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Acetizalicilsk\u0101be<\/li>\n\n\n\n<li>Diklofenaks<\/li>\n\n\n\n<li>Ibuprof\u0113ns<\/li>\n\n\n\n<li>Indometac\u012bns<\/li>\n\n\n\n<li>Ketoprof\u0113ns<\/li>\n\n\n\n<li>Meloksik\u0101ms<\/li>\n\n\n\n<li>Naproks\u0113ns<\/li>\n\n\n\n<li>Piroksik\u0101ms<\/li>\n<\/ul>\n\n\n\n<p>Visbie\u017e\u0101k sastopam\u0101s selekt\u012bv\u0101s akt\u012bv\u0101s (COX-2) inhibitoru vielas ir \u0161\u0101das.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Celekoksibs<\/li>\n\n\n\n<li>Etorikoksibs<\/li>\n<\/ul>\n\n\n\n<p>Rofekoksibs (sakar\u0101 ar paaugstin\u0101tu sirdsl\u0113kmju risku) un valdekoksibs tika iz\u0146emti no tirgus.<\/p>\n\n\n\n<p>COX-2 selekt\u012bvos NPL nedr\u012bkst lietot pacientiem ar koron\u0101ro sirds slim\u012bbu (KSS) vai p\u0113c sirdsl\u0113kmes, jo tie veicina \u0161o slim\u012bbu att\u012bst\u012bbu.<\/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>DMARD kategorij\u0101 ietilpst vielas, kas ne tikai atvieglo simptomus (piem\u0113ram, NPL), bet ar\u012b. <strong>akt\u012bvi pal\u0113nin\u0101t vai aptur\u0113t slim\u012bbas progres\u0113\u0161anu.<\/strong> un im\u016bnsist\u0113mu ilgtermi\u0146\u0101.<\/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>ARLA pacienta piem\u0113rs - NPL un DMARDs<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>Pacients: 42 gadus vecs v\u012brietis ar ARLA (ce\u013cgala monartr\u012bts p\u0113c Laimas slim\u012bbas).<\/p>\n\n\n\n<p><strong>S\u0101kotn\u0113jais:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Naproks\u0113ns 500 mg 2x dien\u0101<\/li>\n\n\n\n<li>Omeprazols 20 mg vienu reizi dien\u0101 (ku\u0146\u0123a aizsardz\u012bba)<\/li>\n<\/ul>\n\n\n\n<p>S\u0101pes 7\/10<br>Loc\u012btavu izsv\u012bdums 200 ml<\/p>\n\n\n\n<p><strong>P\u0113c 2 ned\u0113\u013c\u0101m<\/strong>:<\/p>\n\n\n\n<p>S\u0101pes 4\/10 (lab\u0101ka \u201elabsaj\u016bta\u201c)<br>Loc\u012btavu izsv\u012bdums joproj\u0101m 180 ml <br>Piet\u016bkums diez vai lab\u0101k<\/p>\n\n\n\n<p><strong>P\u0101reja uz DMARD:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>+ metotreks\u0101ts 15 mg ned\u0113\u013c\u0101<\/li>\n<\/ul>\n\n\n\n<p>vai <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>+ biolo\u0123iskie l\u012bdzek\u013ci (TNFi vai JAKi)<\/li>\n<\/ul>\n\n\n\n<p><strong>P\u0113c 8-12 ned\u0113\u013cu ilgas kombin\u0113t\u0101s terapijas:<\/strong><\/p>\n\n\n\n<p>S\u0101pes 0-1\/10<br>Loc\u012btavu izsv\u012bdums &lt; 50 ml<br>Atjaunota mobilit\u0101te<br>Sasniegta remisija!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Biologika\"><\/span>Biolo\u0123isk\u0101s z\u0101les<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Biolo\u0123iskie medikamenti ir biotehnolo\u0123iski ra\u017eotas liel\u0101kas molekulas, kas veidotas p\u0113c cilv\u0113ka olbaltumvielu, nukle\u012bnsk\u0101bju vai antivielu parauga un kuras nevar ievad\u012bt table\u0161u veid\u0101, jo t\u0101s priek\u0161laic\u012bgi sadal\u0101s ku\u0146\u0123a sk\u0101bes ietekm\u0113, bet tikai zem\u0101das injekciju vai inf\u016bziju veid\u0101. Tikai JAK inhibitorus lieto iek\u0161\u0137\u012bgi.<br>T\u0101s var regul\u0113t citok\u012bnus, receptorus vai im\u016bn\u0161\u016bnas. Insul\u012bns ar\u012b ir (1982. gad\u0101 pirmais) biolo\u0123iskais l\u012bdzeklis.<\/p>\n\n\n\n<p>ARLA kontekst\u0101 t\u0101s iedala \u010detr\u0101s hierarhij\u0101s.<\/p>\n\n\n\n<p>1. izv\u0113le - <strong>TNF-\u03b1 inhibitori (TNFi)<\/strong> - Atbilde ar 50-70% p\u0113c 4-8 ned\u0113\u013c\u0101m<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Adalimumabs<\/li>\n\n\n\n<li>Infliksimabs<\/li>\n\n\n\n<li>Etanercept<\/li>\n<\/ul>\n\n\n\n<p>2. izv\u0113le - <strong>IL-6 inhibitori (IL-6i)<\/strong> - Atbilde pie 50-60% p\u0113c 4-12 ned\u0113\u013c\u0101m<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Tocilizumabs<\/li>\n\n\n\n<li>Sarilumabs<\/li>\n<\/ul>\n\n\n\n<p>Efekt\u012bvs ar\u012b pacientiem, kas nerea\u0123\u0113 uz TNFi (~30-50% pacientu).<\/p>\n\n\n\n<p>3. izv\u0113le - <strong>JAK inhibitori (JAKi) <\/strong>- Reakcija jau p\u0113c 2-4 ned\u0113\u013c\u0101m - v\u0113l izstr\u0101des stadij\u0101<br>T\u0101s blo\u0137\u0113 JAK1 (prim\u0101ro, sp\u0113c\u012bgo), JAK2 (sekund\u0101ro, v\u0101jo) un TYK2 (sekund\u0101ro, v\u0101jo), t\u0101p\u0113c STAT3 nevar tikt fosforil\u0113ts un t\u0101p\u0113c paliek neakt\u012bvs, un IL-6 atkar\u012bgie g\u0113ni netiek transkrib\u0113ti. Savuk\u0101rt JAK3 netiek blo\u0137\u0113ts, kas pozit\u012bvi ietekm\u0113 uzlabotu aizsardz\u012bbu pret infekciju (avots - pilns teksts ar izmaks\u0101m): <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/312615\/\" target=\"_blank\" rel=\"noreferrer noopener\">Hronisks Laima artr\u012bts. Kl\u012bnisk\u0101 un im\u016bn\u0123en\u0113tisk\u0101 at\u0161\u0137ir\u012bba no reimato\u012bd\u0101 artr\u012bta<\/a>).<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Upadacitinibs<\/li>\n\n\n\n<li>Baricitinibs<\/li>\n\n\n\n<li>Tofacitinibs<\/li>\n<\/ul>\n\n\n\n<p>4. izv\u0113le - <strong>B \u0161\u016bnu depletori<\/strong> - Atbilde pie 40-50% - tikai TNFi + IL-6i + JAKi nerea\u0123\u0113jo\u0161iem pacientiem<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Rituksimabs<\/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>Huaier s\u0113ne - alternat\u012bva?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Port\u0101ls <a href=\"https:\/\/aditum.org\/journals\/international-journal-of-medical-case-reports-and-medical-research\/archive\/967\" target=\"_blank\" rel=\"noreferrer noopener\">Tanakas p\u0113t\u012bjums<\/a> atkl\u0101j Huaier akt\u012bvo sast\u0101vda\u013cu iedarb\u012bbu galvenok\u0101rt attiec\u012bb\u0101 uz visu veidu v\u0113zi (iz\u0146emot smadze\u0146u audz\u0113jus, jo liel\u0101s akt\u012bvo sast\u0101vda\u013cu molekulas nesp\u0113j izk\u013c\u016bt cauri hematoencefaliskajai barjerai).<br>Ir atsevi\u0161\u0137s <a href=\"https:\/\/csiag.eu\/lv\/huaier-senes-veza-terapija\/\" target=\"_blank\" rel=\"noreferrer noopener\">Iemaksas<\/a>, ar\u012b ar <a href=\"https:\/\/csiag.eu\/lv\/huaier-senes-veza-terapija\/#Dosierungsempfehlung\" target=\"_blank\" rel=\"noreferrer noopener\">Doz\u0113\u0161anas instrukcijas<\/a> un <a href=\"https:\/\/nutrimentas-shop.de\/products\/vitalpilz-huaier-trametes-robiniophila-fur-wissenschaftliche-zwecke\" target=\"_blank\" rel=\"noreferrer noopener\">Pieg\u0101des avots<\/a> p\u0113t\u012bjum\u0101 izmantoto granulu ar 32 % polisahar\u012bdiem.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p><strong>Uzman\u012bbu<\/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>P\u0113t\u012bjumi liecina, ka Huaier s\u0113nes akt\u012bvaj\u0101m sast\u0101vda\u013c\u0101m piem\u012bt pla\u0161a spektra t\u012bri regul\u0113jo\u0161as un programmatiskas \u012bpa\u0161\u012bbas. T\u0101s sp\u0113j atjaunot nepareizi novirz\u012btus g\u0113nus to s\u0101kotn\u0113j\u0101 funkciju diapazon\u0101 un pat p\u0101rprogramm\u0113t tos uz norm\u0101lu darb\u012bbu.<\/p>\n\n\n\n<p>G\u0113nus var iesl\u0113gt vai izsl\u0113gt un regul\u0113t vai samazin\u0101t to darb\u012bbu. Visi apst\u0101k\u013ci, kas nav normas robe\u017e\u0101s, rada attiec\u012bgi p\u0101rm\u0113r\u012bgas vai nom\u0101ktas reakcijas uz sign\u0101liem. Huaier akt\u012bv\u0101s sast\u0101vda\u013cas sp\u0113j selekt\u012bvi atjaunot individu\u0101li pareizu regulat\u012bvo darb\u012bbu.<\/p>\n\n\n\n<p>ARLA ir meh\u0101niski l\u012bdz\u012bgi, t\u0101p\u0113c ir \u010detri kritiski molekul\u0101r\u0101s iejauk\u0161an\u0101s punkti, kuros Huaier var ietekm\u0113t ARLA pato\u0123en\u0113zi:<\/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>NF-\u03baB ce\u013ca inhib\u012bcija (plazmas membr\u0101nas signaliz\u0101cija)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Laimas artr\u012bta p\u0113cinfekcijas gad\u012bjum\u0101, p\u0113c veiksm\u012bgas bor\u0113lijas \u0101rst\u0113\u0161anas ar antibiotik\u0101m, t\u0101 sauktais. <em>notur\u012bgi peptoglik\u0101ni<\/em>, boj\u0101 g\u0101ju\u0161o boreliju \u0161\u016bnu sieni\u0146u komponenti sinovi\u0101laj\u0101 \u0161\u0137idrum\u0101 un loc\u012btavas audos. \u0160os peptodoglik\u0101nus nep\u0101rtraukti atpaz\u012bst im\u016bnsist\u0113ma, jo \u012bpa\u0161i im\u016bnsist\u0113ma <em>Toll l\u012bdz\u012bgs receptoru 2<\/em> (TLR2), kas lokaliz\u0113ts uz makrof\u0101gu, dendr\u012bt\u0161\u016bnu un citu iedzimto im\u016bn\u0161\u016bnu virsmas.<\/p>\n\n\n\n<p>Kad TLR2 atpaz\u012bst notur\u012bgos peptoglik\u0101nus, iedarbojas signaliz\u0101cijas kask\u0101de, kas izraisa klasisk\u0101s <em>NF-\u03baB signaliz\u0101cijas ce\u013c\u0161<\/em> vadi. Tas notiek, piesaistot adaptorprote\u012bnus, piem. <em>TIRAP<\/em> un <em>MyD88<\/em> aktiv\u0113tajam TLR2 receptoram.<br>P\u0113c tam \u0161ie adapterprote\u012bni piesaista kin\u0101\u017eu kompleksu, tostarp ar\u012b <em>IKK komplekss<\/em> (\u03baB kin\u0101zes inhibitors), kas ir inhib\u0113jo\u0161ais prote\u012bns. <em>I\u03baB\u03b1<\/em> fosforil\u0113ti un t\u0101d\u0113j\u0101di mar\u0137\u0113ti proteazom\u0101lai no\u0101rd\u012b\u0161anai. L\u012bdz ar I\u03baB\u03b1 no\u0101rd\u012b\u0161anos. <em>Transkripcijas faktoru dim\u0113rs p50\/p65<\/em> atbr\u012bvojas no NF-\u03baB un var p\u0101rvietoties \u0161\u016bnas kodol\u0101.<\/p>\n\n\n\n<p>Tikl\u012bdz NF-\u03baB atrodas \u0161\u016bnas kodol\u0101, t\u0101 saist\u0101s ar \u03baB DNS saist\u012b\u0161anas viet\u0101m proiekaisuma citok\u012bnu promotoru apgabalos un uzs\u0101k to masveida transkripciju. Tas izraisa nep\u0101rtrauktu, past\u0101v\u012bgu un ilgsto\u0161u <em>TNF-\u03b1, IL-6, IL-1\u03b2, IL-8.<\/em> un citiem hemok\u012bniem, piem\u0113ram. <em>MCP-1<\/em> un <em>KC<\/em>.<br>Pacientiem ar ARLA \u0161is process nav pa\u0161saprotams. Tas turpin\u0101s ned\u0113\u013c\u0101m, m\u0113ne\u0161iem un gadiem ilgi, kam\u0113r saglab\u0101jas peptidoglik\u0101ni. T\u0101 ir galven\u0101 probl\u0113ma: nav jaunas infekcijas, ar kuru b\u016btu j\u0101c\u012bn\u0101s, bet im\u016bnsist\u0113ma paliek iespr\u016bdusi iekaisuma re\u017e\u012bm\u0101.<\/p>\n\n\n\n<p><strong>K\u0101 Huaier var p\u0101rtraukt \u0161o procesu:<\/strong><\/p>\n\n\n\n<p>Huaier ir bag\u0101ts ar <em>\u03b2-glik\u0101ni<\/em> un citi <em>Polisahar\u012bdi<\/em>, kas saist\u0101s ar receptoru, kas nav TLR2, proti, ar t. s. <em>Dekt\u012bna-1 receptors<\/em> (Dekt\u012bns-1 ir <em>C tipa lekt\u012bna receptoru<\/em>, kas galvenok\u0101rt ir izteikta makrof\u0101gos un dendr\u012bt\u0161\u016bn\u0101s). Kad Huaier \u03b2-glik\u0101ni saist\u0101s ar dekt\u012bnu-1, tie ar\u012b aktiviz\u0113 NF-\u03baB, ta\u010du izmantojot alternat\u012bvu, maz\u0101k proiekaisuma signaliz\u0101cijas ce\u013cu.<br>T\u0101 viet\u0101, lai izmantotu klasisko <em>TIRAP\/MyD88 mar\u0161ruts<\/em> T\u0101pat k\u0101 TLR2 signaliz\u0101cijas gad\u012bjum\u0101, signaliz\u0101ciju veic <em>Syk kin\u0101ze<\/em> un <em>Karte9<\/em>, kas rada sava veida \u201eregul\u0113tu\u201c NF-\u03baB sign\u0101lu.<\/p>\n\n\n\n<p>Turkl\u0101t Huaier darbojas ar <em>ar miRNA starpniec\u012bbu<\/em> Meh\u0101nismi, kas izraisa pa\u0161u NF-\u03baB komponentu samazin\u0101\u0161anos. \u012apa\u0161as mikroRNS, kuras Huaier regul\u0113 (piem\u0113ram, mikroRNS, kas ir <em>miRNA-223, miRNA-146a<\/em> un citi), var tie\u0161i no\u0101rd\u012bt IKK apak\u0161vien\u012bbu un RelA (NF-\u03baB p65 apak\u0161vien\u012bba) mRNS. Tas noz\u012bm\u0113, ka \u0161\u016bn\u0101s ir maz\u0101k kop\u0113j\u0101 NF-\u03baB kompleksa, ko var aktiviz\u0113t, pat ja joproj\u0101m ir notur\u012bgi peptoglik\u0101ni un tie stimul\u0113 TLR2.<\/p>\n\n\n\n<p>\u0160\u012bs Huaier veikt\u0101s dubult\u0101s iejauk\u0161an\u0101s praktiskais rezult\u0101ts ir t\u0101ds, ka nep\u0101rtraukt\u0101 NF-\u03baB aktiv\u0101cija ar peptoglik\u0101niem ir iev\u0113rojami samazin\u0101ta. Samazin\u0101s TNF-\u03b1, IL-6 un IL-1\u03b2 ra\u017eo\u0161ana. Kl\u012bniski tas izraisa strauju C-reakt\u012bv\u0101 prote\u012bna (CRP), kas ir NF-\u03baB induc\u0113ts ak\u016bt\u0101s f\u0101zes prote\u012bns, samazin\u0101\u0161anos.<br>Ja ir maz\u0101k TNF-\u03b1 un IL-6, kas darbojas k\u0101 hemok\u012bni, loc\u012btavu izpl\u016bdums ar\u012b \u0101tr\u0101k uzs\u016bcas, jo samazin\u0101s leikoc\u012btu iepl\u016b\u0161ana loc\u012btav\u0101. Pacienti zi\u0146o par strauju piet\u016bkuma un s\u0101pju samazin\u0101\u0161anos pirmaj\u0101s 1-2 ned\u0113\u013c\u0101s p\u0113c Huaier uzs\u0101k\u0161anas. Tas atbilst NF-\u03baB nom\u0101kumam.<\/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>JAK\/STAT ce\u013ca modul\u0101cija (endosom\u0101l\u0101 signaliz\u0101cija + IL-6 atgriezenisk\u0101 saite)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>ARLA ir p\u0101rprodukcija <em>I tipa interferoni<\/em> (interferons-\u03b1 un interferons-\u03b2), kas ir paz\u012bstams k\u0101 \u201e<em>IFN amplifik\u0101cijas cilpa<\/em>\u201c ir mar\u0137\u0113ts. T\u0101 nav klasisk\u0101 TLR2 signaliz\u0101cija, par kuru m\u0113s tikko run\u0101j\u0101m saist\u012bb\u0101 ar NF-\u03baB. T\u0101 viet\u0101 tas notiek pa citu ce\u013cu: notur\u012bg\u0101s bor\u0113lijas signaliz\u0113 ar <em>Makrof\u0101gi<\/em> un <em>dendr\u012bt\u0161\u016bnas<\/em> fagocitiz\u0113ti. Kad t\u0101s tiek uz\u0146emtas fagosom\u0101, t\u0101s atpaz\u012bst endosomu Toll l\u012bdz\u012bgie receptori, jo \u012bpa\u0161i Toll l\u012bdz\u012bgie receptori. <em>TLR7, TLR8<\/em> un <em>TLR9<\/em>. \u0160ie receptori atrodas uz iek\u0161\u0113j\u0101s virsmas. <em>endosomu\/fagosomu vezikulas.<\/em> un atpaz\u012bt Borrelia RNS un DNS.<\/p>\n\n\n\n<p>Kad TLR7\/8\/9 tiek stimul\u0113ti ar bakt\u0113riju nukle\u012bnsk\u0101b\u0113m, tie piesaista adaptorprote\u012bnu. <em>MyD88<\/em> un\/vai <em>TRIF<\/em> un izraisa interferonu regul\u0113jo\u0161o faktoru aktiviz\u0101ciju, jo \u012bpa\u0161i interferonu regul\u0113jo\u0161o faktoru aktiviz\u0101ciju. <em>IRF3<\/em> un <em>IRF7<\/em>. P\u0113c tam \u0161ie IRF transkripcijas faktori non\u0101k kodol\u0101 un inici\u0113 I tipa interferona g\u0113nu transkripciju: s\u0101kotn\u0113ji <em>Interferons-\u03b2<\/em> un tam seko sekund\u0101rais vilnis <em>Interferons-\u03b1<\/em>.<\/p>\n\n\n\n<p>Kad IFN-\u03b1 un IFN-\u03b2 non\u0101k sinovi\u0101laj\u0101 \u0161\u0137idrum\u0101 un asin\u012bs, tie saist\u0101s ar interferona-\u03b1\/\u03b2 receptoru (IFNAR), kas atrodas praktiski uz vis\u0101m \u0161\u016bn\u0101m, ieskaitot <em>T \u0161\u016bnas, makrof\u0101gi<\/em> un <em>sinovi\u0101lie fibroblasti<\/em>.<br>IFNAR saist\u012b\u0161an\u0101s piesaista receptoru div\u0101m kin\u0101z\u0113m: <em>JAK1<\/em> un <em>TYK2<\/em>. P\u0113c tam \u0161\u012bs kin\u0101zes fosforil\u0113 STAT olbaltumvielas. <em>STAT1<\/em> un <em>STAT2<\/em> (<strong>ne<\/strong> <em>STAT3<\/em> \u0161aj\u0101 konkr\u0113taj\u0101 ce\u013c\u0101). Fosforil\u0113tais STAT1\/STAT2 kop\u0101 ar <em>IRF9<\/em> transkripcijas faktoru komplekss, kas <em>ISGF3<\/em> un non\u0101k \u0161\u016bnas kodol\u0101.<\/p>\n\n\n\n<p>\u0160\u016bnas kodol\u0101 ISGF3 saist\u0101s ar <em>Interferona stimul\u0113tas atbildes reakcijas elementi<\/em> (ISRE) promotoru apgabalos. <em>Interferona stimul\u0113tie g\u0113ni<\/em> (ISG). \u0160ie ISG ietver t\u0101dus g\u0113nus k\u0101 <em>OAS<\/em> (2\u2032,5\u2032-oligoadenil\u0101ta sintet\u0101ze), <em>MxA<\/em> (Myxovirus Resistance Protein A), <em>PBR<\/em> (prote\u012bnkin\u0101ze R) un daudzi citi. \u0160ie g\u0113ni masveid\u0101 tiek regul\u0113ti un \u0161\u016bn\u0101s rada \u201epretv\u012brusu st\u0101vokli\u201c. Tas ir norm\u0101li un adapt\u012bvi \u012bstas v\u012brusu infekcijas gad\u012bjum\u0101, bet ARLA gad\u012bjum\u0101 tas ir neadapt\u012bvs, jo nav akt\u012bvas v\u012brusu infekcijas. T\u0101 ir sava veida \u201eviltus trauksme\u201c.<\/p>\n\n\n\n<p>Probl\u0113mu pasliktina atgriezenisk\u0101s saites meh\u0101nisms: interferonu ra\u017eojo\u0161\u0101s \u0161\u016bnas ra\u017eo vair\u0101k interferona, kas izraisa v\u0113l sp\u0113c\u012bg\u0101ku IFNAR signaliz\u0101ciju cit\u0101s \u0161\u016bn\u0101s, kas savuk\u0101rt izraisa liel\u0101ku ISG transkripciju, kas savuk\u0101rt palielina IFN ra\u017eo\u0161anas varb\u016bt\u012bbu. Tas ir \u201e<em>IFN amplifik\u0101cijas cilpa<\/em>\u201e, kas rakstur\u012bga p\u0113cinfekcijas ARLA. \u0160\u012b cilpa ir pa\u0161pietiekama: pat p\u0113c tam, kad visas dz\u012bv\u0101s bor\u0113lijas ir nogalin\u0101tas, \u0161is ce\u013c\u0161 turpin\u0101s, jo miru\u0161\u0101s bakt\u0113rijas un to nukle\u012bnsk\u0101bes joproj\u0101m tiek fagocit\u0113tas.<\/p>\n\n\n\n<p>Vienlaikus \u0161is I tipa IFN st\u0101voklis izraisa ar\u012b T \u0161\u016bnu aktiviz\u0101ciju un papla\u0161in\u0101\u0161anos, jo \u012bpa\u0161i T \u0161\u016bnu aktiviz\u0101ciju un papla\u0161in\u0101\u0161anos. <em>Th1 \u0161\u016bnas<\/em> un v\u0113l\u0101k ar\u012b <em>Th17 \u0161\u016bnas<\/em>. Th17 \u0161\u016bnas aktiviz\u0113jas ar at\u0161\u0137ir\u012bgu meh\u0101nismu: t\u0101m ir nepiecie\u0161ams <em>IL-6<\/em> kop\u0101 ar <em>TGF-\u03b2<\/em>. Un IL-6 ra\u017eo ar\u012b NF-\u03baB, k\u0101 ar\u012b interferona stimul\u0113tie g\u0113ni. T\u0101p\u0113c ir vair\u0101ki ce\u013ci, kas noved pie IL-6.<\/p>\n\n\n\n<p>Tikl\u012bdz IL-6 par\u0101d\u0101s iev\u0113rojam\u0101 daudzum\u0101, notiek kaut kas interesants: IL-6 saist\u0101s ar savu receptoru (<em>IL-6R<\/em>) kop\u0101 ar l\u012bdzreceptoru, ko sauc par <em>gp130<\/em> uz T \u0161\u016bnu, sinovi\u0101lo fibroblastu un citu \u0161\u016bnu virsmas. \u0160\u012b saist\u012b\u0161an\u0101s piesaista JAK1 un JAK2 receptoram. JAK1 un JAK2 p\u0113c tam fosforil\u0113 STAT prote\u012bnu STAT3. P\u0113c \u0161\u012bs fosforil\u0113\u0161anas STAT3 aktiviz\u0113jas un non\u0101k \u0161\u016bnas kodol\u0101, kur tas saist\u0101s ar DNS saist\u012b\u0161an\u0101s viet\u0101m un inici\u0113 IL-17 un transkripcijas faktora ROR\u03b3t transkripciju.<\/p>\n\n\n\n<p>Tas izraisa masveida Th17 \u0161\u016bnu skaita palielin\u0101\u0161anos, kas, savuk\u0101rt, ra\u017eo vair\u0101k IL-17. IL-17 ir sp\u0113c\u012bgi proiekaislisks un iedarbojas uz sinovi\u0101lajiem fibroblastiem (t\u0101 sauktajiem FLS - fibroblastiem l\u012bdz\u012bgajiem sinovioc\u012btiem), lai tie ra\u017eotu v\u0113l vair\u0101k IL-6. Tas rada otru atgriezenisk\u0101s saites sist\u0113mu: IL-6 \u2192 Th17 papla\u0161in\u0101\u0161an\u0101s \u2192 IL-17 ra\u017eo\u0161ana \u2192 v\u0113l vair\u0101k IL-6 no FLS \u2192 v\u0113l vair\u0101k Th17 \u2192 v\u0113l vair\u0101k IL-17. T\u0101pat k\u0101 IFN pastiprin\u0101\u0161an\u0101s cilpa, t\u0101 ir pa\u0161pietiekama un pie\u0161\u0137ir ARLA hronisku, gr\u016bti kontrol\u0113jamu raksturu.<\/p>\n\n\n\n<p><strong>K\u0101 Huaier var p\u0101rtraukt \u0161o procesu:<\/strong><\/p>\n\n\n\n<p>Huaier iejaucas \u0161aj\u0101 JAK\/STAT ce\u013c\u0101 daudz fundament\u0101l\u0101k\u0101 l\u012bmen\u012b nek\u0101 tie\u0161i blo\u0137\u0113jot JAK1 vai JAK2 (jo tas <em>JAK inhibitori<\/em> piem\u0113ram, <em>Upadacitinibs<\/em> dar\u012bt). <strong>T\u0101 viet\u0101 Huaier darbojas ar miRNA medi\u0113tu transkripcijas regul\u0101ciju.<\/strong>. \u012apa\u0161as mikroRNS, ko regul\u0113 Huaier polisahar\u012bdi, pa\u0161as izn\u012bcina vai no\u0101rda JAK olbaltumvielu mRNS.<\/p>\n\n\n\n<p>Tas notiek, izmantojot elegantu regul\u0113\u0161anas meh\u0101nismu: kad Huaier polisahar\u012bdi saist\u0101s ar Dectin-1 un stimul\u0113 \u0161\u016bnu ar sign\u0101liem, tiek aktiviz\u0113ts ne tikai viens signaliz\u0101cijas ce\u013c\u0161, bet ar\u012b tiek aktiviz\u0113ti miRNA apstr\u0101d\u0101jo\u0161ie fermenti. To rezult\u0101t\u0101 notiek vair\u0101ku kanonisko un nekanonisko miRNS biog\u0113ze. Da\u017eas no \u0161\u012bm miRNA, piem. <strong>miR-223, miR-146a<\/strong> un <strong>miR-34a<\/strong>, ir saisto\u0161as vietas 3\u2032 nep\u0101rrakst\u012btaj\u0101 apgabal\u0101 (<strong>3\u2032-UTR<\/strong>) no <em>JAK1, JAK2<\/em> un <em>STAT3 mRNS<\/em>.<br>Kad \u0161\u012bs miRNA hibridiz\u0113jas ar \u0161\u012bm sekvenc\u0113m, t\u0101s mar\u0137\u0113 mRNS, lai RNS interferences proces\u0101 to no\u0101rd\u012btu. <strong>RISC komplekss<\/strong> (RNS induc\u0113t\u0101s sl\u0101p\u0113\u0161anas komplekss). Rezult\u0101t\u0101 mRNS tiek no\u0101rd\u012bta un \u0161ie prote\u012bni vairs netiek ra\u017eoti tik efekt\u012bvi.<\/p>\n\n\n\n<p>Da\u017eu dienu l\u012bdz ned\u0113\u013cas laik\u0101 p\u0113c Huaier iedarb\u012bbas \u0161\u016bnas vienk\u0101r\u0161i <strong>maz\u0101k JAK1-, JAK2-<\/strong> un <strong>STAT3 prote\u012bns<\/strong>. Tas ir daudz b\u016btisk\u0101k nek\u0101 vienk\u0101r\u0161i blo\u0137\u0113t kin\u0101\u017eu aktivit\u0101ti. Tas noz\u012bm\u0113, ka pat tad, kad receptori ir aktiviz\u0113ti un cen\u0161as fosforil\u0113t JAK, ir maz\u0101k JAK molekulu, ko fosforil\u0113t. Uz <strong>Reakcija uz JAK atkar\u012bgo citok\u012bnu signaliz\u0101ciju<\/strong> t\u0101p\u0113c ir <strong>iev\u0113rojami samazin\u0101ts<\/strong>.<\/p>\n\n\n\n<p>JAK ekspresijas samazin\u0101\u0161an\u0101s p\u0101rtrauc I tipa IFN pastiprin\u0101\u0161an\u0101s cilpu. Pat ja TLR7\/8\/9 turpina m\u0113\u0123in\u0101t ra\u017eot interferonu, \u0161\u016bn\u0101s, kas ra\u017eo IFN-\u03b1\/\u03b2, ir maz\u0101k JAK1\/TYK2, t\u0101p\u0113c STAT1\/STAT2 var tikt fosforil\u0113ts maz\u0101k efekt\u012bvi. Tas izraisa maz\u0101ku ISGF3 aktiviz\u0101ciju, maz\u0101ku ISG transkripciju un l\u012bdz ar to ar\u012b maz\u0101ku ISG3 aktiviz\u0101ciju. <strong>maz\u0101k \u201epretv\u012brusu st\u0101voklis\u201c<\/strong>.<\/p>\n\n\n\n<p>Vienlaikus JAK1 un JAK2 samazin\u0101\u0161ana p\u0101rtrauc ar\u012b IL-6 atgriezenisk\u0101s saites cilpu. Pat ja IL-6 ir kl\u0101teso\u0161s un saist\u0101s ar IL-6R T \u0161\u016bn\u0101s, JAK1 un JAK2 fosforil\u0113 maz\u0101k, t\u0101p\u0113c STAT3 tiek maz\u0101k fosforil\u0113ts. Ja STAT3 ir maz\u0101k akt\u012bvs, tiek sara\u017eots maz\u0101k ROR\u03b3t un IL-17, un t\u0101p\u0113c Th17 \u0161\u016bnas neizple\u0161as tik agres\u012bvi. Tas noz\u012bm\u0113 maz\u0101ku IL-17 ra\u017eo\u0161anu, maz\u0101ku FLS stimul\u0101ciju IL-6 ra\u017eo\u0161anai, - un cilpa tiek p\u0101rtraukta.<\/p>\n\n\n\n<p>Laboratorijas terminolo\u0123ij\u0101 m\u0113s to uzskat\u0101m par <strong>IFN-\u03b3 l\u012bme\u0146a samazin\u0101\u0161an\u0101s<\/strong> (Th1 aktivit\u0101tes mar\u0137ieris, kas ar\u012b tiek regul\u0113ts ar I tipa IFN), <strong>IL-6 l\u012bme\u0146a samazin\u0101\u0161an\u0101s <\/strong>(IL-6 atgriezenisk\u0101s saites sist\u0113mas mar\u0137ieris) un <strong>IL-17 l\u012bme\u0146a samazin\u0101\u0161an\u0101s<\/strong> (Th17 mar\u0137ieris). Tas notiek l\u0113n\u0101k nek\u0101 NF-\u03baB nom\u0101k\u0161ana (kas notiek da\u017eu dienu laik\u0101) - ir nepiecie\u0161amas aptuveni 2-4 ned\u0113\u013cas, lai miRNS balst\u012bt\u0101 ietekme piln\u012bb\u0101 izpaustos, bet, kad t\u0101 izpau\u017eas, t\u0101 ir notur\u012bg\u0101ka.<\/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>Sal\u012bdzin\u0101jums: JAK1i (piem\u0113ram, upadacitinibs) vs Huaier:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>A <strong>JAK1 inhibitors<\/strong> piem\u0113ram, <em>Upadacitinibs<\/em> (tirdzniec\u012bbas nosaukums Rinvoq) darbojas p\u0113c piln\u012bgi at\u0161\u0137ir\u012bga meh\u0101nisma nek\u0101 Huaier, lai gan abi galu gal\u0101 modul\u0113 JAK\/STAT signaliz\u0101cijas ce\u013cus. Upadacitinibs ir maza molekula, ko var tie\u0161i <em>ATP saist\u012b\u0161anas kabata<\/em> . <em>JAK1 kin\u0101ze<\/em> un fiziski tos blo\u0137\u0113. Tas ir sava veida \u201emeh\u0101niskais inhibitors\u201c.<br>Kad JAK1 ir blo\u0137\u0113ts, tas vairs nevar fosforil\u0113t STAT olbaltumvielu aminosk\u0101bi tiroz\u012bnu, neatkar\u012bgi no t\u0101, cik \u013coti receptors cen\u0161as aktiviz\u0113t JAK. Efekts ir \u0101trs: tikl\u012bdz upadacitinibs uzs\u016bcas asinsrit\u0113 un sasniedz \u0161\u016bnas, JAK1 tiek inhib\u0113ts. T\u0101p\u0113c JAK inhibitoriem ir \u0101tra iedarb\u012bba, parasti 2-4 ned\u0113\u013cas l\u012bdz paman\u0101miem kl\u012bniskiem uzlabojumiem.<\/p>\n\n\n\n<p>Tom\u0113r \u0161ai tie\u0161ajai blok\u0101dei ir ar\u012b tr\u016bkumi. JAK1 inhibitori inhib\u0113 ne tikai JAK1, bet ar\u012b citas JAK kin\u0101zes atkar\u012bb\u0101 no to selektivit\u0101tes. Pat \u201eJAK1-selekt\u012bvie\u201c inhibitori zin\u0101m\u0101 m\u0113r\u0101 v\u0101ji inhib\u0113 JAK2 un TYK2. Tas noved pie <strong>Blakuspar\u0101d\u012bbas<\/strong>, \u012bpa\u0161i paaugstin\u0101ts risks <strong>Herpes zoster<\/strong> (\u0161indeles), jo JAK3 blok\u0101de trauc\u0113 T-\u0161\u016bnu prolifer\u0101ciju un t\u0101d\u0113j\u0101di ar\u012b latento v\u012brusu, piem\u0113ram, T-\u0161\u016bnu, kontroli. <em>Varicella zoster<\/em> v\u0101jina. Kopum\u0101 JAK2 blok\u0101de izraisa <strong>Trombembolijas aktiviz\u0113\u0161ana<\/strong> inhib\u012bcijas viet\u0101 (\u012bpa\u0161i baricitinibs, kas sp\u0113c\u012bg\u0101k blo\u0137\u0113 JAK2).<\/p>\n\n\n\n<p><strong>Huaier<\/strong> darbojas pavisam cit\u0101 l\u012bmen\u012b. Tas tie\u0161i neblo\u0137\u0113 JAK prote\u012bnu. T\u0101 viet\u0101 <strong>samazin\u0101ts<\/strong> t\u0101 <strong>JAK olbaltumvielu daudzumu<\/strong>, ka \u0161\u016bna visp\u0101r ra\u017eo. Tas notiek ar miRNA medi\u0113tu JAK mRNS degrad\u0101ciju. Priek\u0161roc\u012bba ir t\u0101, ka \u0161is meh\u0101nisms ir smalk\u0101ks un, iesp\u0113jams, fiziolo\u0123isk\u0101ks. \u0160\u016bnas vienk\u0101r\u0161i samazina JAK produkcijas daudzumu, nevis z\u0101les piespiedu k\u0101rt\u0101 blo\u0137\u0113 olbaltumvielu. Tr\u016bkums ir tas, ka \u0161is process ir l\u0113n\u0101ks. Ir nepiecie\u0161amas vair\u0101kas dienas l\u012bdz ned\u0113\u013ca, lai miRNA tiktu regul\u0113ta pietiekam\u0101 daudzum\u0101, un p\u0113c tam ir nepiecie\u0161amas v\u0113l vair\u0101kas dienas, lai JAK mRNA sadal\u012btos pietiekami daudz, lai JAK prote\u012bna l\u012bmenis iev\u0113rojami samazin\u0101tos. Tas ir iemesls, k\u0101d\u0113\u013c Huaier iedarb\u012bbas s\u0101kums ir l\u0113n\u0101ks, iesp\u0113jams, 4-8 ned\u0113\u013cas, l\u012bdz j\u016btama ietekme uz JAK\/STAT atkar\u012bgajiem procesiem.<\/p>\n\n\n\n<p>V\u0113l viena svar\u012bga at\u0161\u0137ir\u012bba ir atgriezeniskums. Kad pacients p\u0101rtrauc lietot upadacitinibu, JAK blok\u0101de beidzas 24-48 stundu laik\u0101, jo upadacitiniba pusperiods ir \u012bss. JAK1 atkal k\u013c\u016bst akt\u012bvs un var fosforil\u0113t STAT. Tas ir noder\u012bgi, ja pacients slimo ar infekcij\u0101m un vi\u0146am nepiecie\u0161ams p\u0101rtraukt z\u0101\u013cu lieto\u0161anu, bet tas noz\u012bm\u0113 ar\u012b to, ka nepiecie\u0161ama past\u0101v\u012bga dienas deva. Huaier var b\u016bt ilgsto\u0161\u0101ka iedarb\u012bba, jo uz miRNA balst\u012bt\u0101 regul\u0101cija ilg\u0101k saglab\u0101jas. Pa\u0161\u0101m miRNA ir gar\u0101ks pussabruk\u0161anas periods nek\u0101 maz\u0101m molekul\u0101m, un JAK prote\u012bna atjauno\u0161an\u0101s ilg\u0101k notiek, kad Huaier iedarb\u012bba tiek p\u0101rtraukta.<\/p>\n\n\n\n<p>V\u0113l smalk\u0101ka at\u0161\u0137ir\u012bba ir specifiskums. Upadacitinibs ir JAK1 selekt\u012bvs, kas noz\u012bm\u0113, ka tas sp\u0113c\u012bgi blo\u0137\u0113 JAK1, v\u0101ji blo\u0137\u0113 JAK2 un gandr\u012bz nemaz JAK3. Tas faktiski ir JAK1 selektivit\u0101tes m\u0113r\u0137is, proti, izvair\u012bties no JAK3 blo\u0137\u0113\u0161anas, lai lab\u0101k saglab\u0101tu T \u0161\u016bnu funkcijas.<br>Huaier, iesp\u0113jams, vair\u0101k vai maz\u0101k proporcion\u0101li samazina JAK1, JAK2 un, iesp\u0113jams, TYK2, atkar\u012bb\u0101 no t\u0101, kuras miRNS tiek regul\u0113tas. Tas var\u0113tu noz\u012bm\u0113t, ka Huaier <strong>pla\u0161\u0101ka JAK nom\u0101k\u0161ana<\/strong> kas var\u0113tu b\u016bt labi t\u0101d\u0101m liet\u0101m k\u0101 I tipa IFN signaliz\u0101cija (kam nepiecie\u0161ams TYK2), bet, iesp\u0113jams, var izrais\u012bt ar\u012b liel\u0101ku JAK2 ietekmi (teor\u0113tiski - trombembolijas risku).<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"PI3KAKT-Aktivierung_Mitochondriale_Restoration_Treg-Support\"><\/span>PI3K\/AKT aktiviz\u0113\u0161ana (mitohondriju atjauno\u0161ana + Treg atbalsts)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>Tre\u0161\u0101 b\u016btisk\u0101k\u0101 ARLA probl\u0113ma ir ne tikai past\u0101v\u012bga proiekaisuma cito\u0137\u012bnu veido\u0161an\u0101s, bet ar\u012b sist\u0113mu, kas parasti ierobe\u017eo \u0161o iekaisumu, darb\u012bbas trauc\u0113jumi. Vissvar\u012bg\u0101k\u0101 sist\u0113ma, kas kontrol\u0113 iekaisumu, ir regulat\u012bvo T \u0161\u016bnu popul\u0101cija (<em>Tregs<\/em>), jo \u012bpa\u0161i <em>CD4+CD25+Foxp3+ <\/em>Tregs.<\/p>\n\n\n\n<p>Veseliem cilv\u0113kiem Tregs ir neat\u0146emama im\u016bnsist\u0113mas sast\u0101vda\u013ca un darbojas, produc\u0113jot pretiekaisuma citok\u012bnus, piem\u0113ram. <em>IL-10<\/em> un <em>TGF-\u03b2<\/em>, k\u0101 ar\u012b tie\u0161\u0101 kontakt\u0101 starp \u0161\u016bn\u0101m, lai aktiviz\u0113tu proiekaisuma T \u0161\u016bnas (<em>Efektoru T \u0161\u016bnas<\/em>), kas j\u0101aizliedz.<br>Tregs ir metaboliski \u013coti akt\u012bvi un pa\u013caujas uz oksidat\u012bvo fosforil\u0113\u0161anu. <em>Mitohondriji<\/em> Tas noz\u012bm\u0113, ka vi\u0146iem ir nepiecie\u0161ami funkcion\u0113jo\u0161i mitohondriji un past\u0101v\u012bga pieg\u0101de <em>ATP<\/em>. Vi\u0146iem ir nepiecie\u0161ama ar\u012b sp\u0113ja sintez\u0113t olbaltumvielas, jo \u012bpa\u0161i, lai ra\u017eotu <em>Transkripcijas regul\u0113\u0161ana <\/em>Foxp3 prote\u012bnu un nom\u0101co\u0161os citok\u012bnus IL-10 un TGF-\u03b2.<\/p>\n\n\n\n<p>Vair\u0101kas lietas ARLA pacientiem ir biju\u0161as nepareizas. Pirmk\u0101rt, nep\u0101rtrauktas TLR2 un TLR7\/8 stimul\u0101cijas d\u0113\u013c. <strong>Mitohondriji hronisk\u0101 stres\u0101<\/strong>. Nep\u0101rtraukta ra\u017eo\u0161ana <em>ROS<\/em> (reakt\u012bv\u0101s sk\u0101bek\u013ca sugas), ko izraisa aktiviz\u0113tas iekaisuma \u0161\u016bnas, oksid\u0113 iek\u0161\u0113jo mitohondriju membr\u0101nu un boj\u0101 elektronu transporta \u0137\u0113des kompleksus. Mitohondriju DNS var oksid\u0113ties, izraisot boj\u0101tu transkripciju. Mitohondriji vienk\u0101r\u0161i nesp\u0113j sara\u017eot pietiekami daudz ATP, lai apg\u0101d\u0101tu visas hroniska iekaisuma st\u0101vokl\u012b eso\u0161\u0101s \u0161\u016bnas.<\/p>\n\n\n\n<p>Otrk\u0101rt, izmantojot <strong>hronisks <em>ER stresa situ\u0101cija<\/em><\/strong> (jo iekaisuma \u0161\u016bnas past\u0101v\u012bgi ra\u017eo lielu daudzumu citok\u012bnu un <em>Olbaltumvielu loc\u012b\u0161anas sp\u0113ja<\/em> no <em>endoplazmas retikuls<\/em> ir p\u0101rslogota), tad <em>Olbaltumvielu sint\u0113zes jauda<\/em> \u0161\u016bn\u0101s ir glob\u0101li samazin\u0101ts.<br>Ribosomas ir olbaltumvielu ra\u017eo\u0161anas r\u012bks, un, kad ER ir pak\u013cauta stresam, ar\u012b ribosomas ir pak\u013cautas stresam. Rezult\u0101t\u0101 nevar optim\u0101li ra\u017eot t\u0101dus svar\u012bgus prote\u012bnus k\u0101 Foxp3, IL-10 un TGF-\u03b2.<\/p>\n\n\n\n<p>Tre\u0161k\u0101rt, caur vis\u0101m \u0161\u012bm vielmai\u0146as probl\u0113m\u0101m ir <strong>Tregs<\/strong> vienk\u0101r\u0161s <strong>disfunkcion\u0101ls<\/strong>. Lai gan Tregs joproj\u0101m var konstat\u0113t (to skaits bie\u017ei vien ir pat palielin\u0101jies), to nom\u0101co\u0161\u0101 iedarb\u012bba ir iev\u0113rojami maz\u0101ka. Tie nesp\u0113j sara\u017eot pietiekami daudz IL-10. T\u0101p\u0113c Tregs nesp\u0113j pien\u0101c\u012bgi nom\u0101kt Th17 un Th1 \u0161\u016bnas. Ja vid\u0113 ir maz\u0101k IL-10, im\u016bnsist\u0113mas pretiekaisuma \u201ebremz\u0113\u0161ana\u201c nevar notikt, un im\u016bnsist\u0113mas <strong>Pro-iekaisuma \u201epa\u0101trin\u0101jums\u201c paliek aktiviz\u0113ts<\/strong>.<\/p>\n\n\n\n<p><strong>K\u0101 Huaier aktiviz\u0113\/atjauno \u0161o procesu:<\/strong><\/p>\n\n\n\n<p>Huaier \u0161o probl\u0113mu risina, izmantojot <em>PI3K\/AKT signaliz\u0101cijas ce\u013c\u0161<\/em> par. Kad Huaier polisahar\u012bdi saist\u0101s ar dekt\u012bna-1 receptoru, tie aktiviz\u0113 ne tikai NF-\u03baB un interferona ce\u013cus, bet ar\u012b PI3K (fosfoinosit\u012bda 3-kin\u0101zi). PI3K kataliz\u0113 fosfatidilinozitol-(4,5)-bisfosf\u0101ta fosforil\u0113\u0161anu (<em>PIP2<\/em>) uz fosfatidilinozitol-(3,4,5)-trisfosf\u0101tu (<em>PIP3<\/em>). PIP3 ir \u201eotrais v\u0113stnesis\u201c - intracelul\u0101ra sign\u0101lmolekula, kas piesaista citas olbaltumvielas.<\/p>\n\n\n\n<p>Prote\u012bns, ko piesaista PIP3, ir <em>ACT<\/em> (saukta ar\u012b par prote\u012bnkin\u0101zi B). AKT veido no 3-fosfoinozit\u012bda atkar\u012bg\u0101 prote\u012bnkin\u0101ze 1 (<em>PDK1<\/em>) tiek fosforil\u0113ts un aktiviz\u0113ts. P\u0113c aktiviz\u0113\u0161anas AKT ir daudzu \u0161\u016bnu procesu \u201egalvenais regulators\u201c. ARLA kontekst\u0101 \u012bpa\u0161i svar\u012bgas ir divas AKT funkcijas:<\/p>\n\n\n\n<p>Pirmk\u0101rt, <strong>AKT aktiviz\u0113 mTOR<\/strong> (Mechanistic Target Of Rapamycin) - liels olbaltumvielu komplekss, kas kontrol\u0113 mRNS transl\u0101ciju un ribosomu biog\u0113nozi.<br>Kad AKT aktiviz\u0113 mTOR, notiek divas lietas: (1) mTOR fosforil\u0113 <em>S6K<\/em> (ribosom\u0101l\u0101 S6 kin\u0101ze), kas fosforil\u0113 S6 olbaltumvielas ribosom\u0101s, t\u0101d\u0113j\u0101di palielinot tulko\u0161anas efektivit\u0101ti. (2) mTOR ar\u012b fosforil\u0113 <em>4E-BP1<\/em> (4E-saisto\u0161ais prote\u012bns 1), kas nodro\u0161ina 4E-BP1 saist\u012b\u0161anos ar 4E-BP1. <em>eIF4E<\/em> un t\u0101d\u0113j\u0101di palielina eIF4E atkar\u012bgo mRNS transl\u0101ciju.<br>Rezult\u0101t\u0101 \u0161\u016bna var sara\u017eot vair\u0101k olbaltumvielu \u012bs\u0101k\u0101 laik\u0101. Par <strong>Tregs<\/strong> tas noz\u012bm\u0113, ka tagad vi\u0146i var <strong>var optim\u0101li produc\u0113t IL-10 un Foxp3.<\/strong>, nepiecie\u0161am\u0101s olbaltumvielas, <strong>ar nom\u0101co\u0161u iedarb\u012bbu<\/strong>.<\/p>\n\n\n\n<p>Otrk\u0101rt, <strong>AKT aktiviz\u0113 jaunu mitohondriju biog\u0113nozi<\/strong>. Da\u013c\u0113ji tas ir saist\u012bts ar PGC1\u03b1 g\u0113na aktiviz\u0101ciju, ko veic AKT.<br>PGC1\u03b1 ir t\u0101 sauktais mitohondri\u0101l\u0101s biog\u0113nozes \u201egalvenais regulators\u201c. Tas ir koaktivators, kas darbojas kop\u0101 ar vair\u0101kiem transkripcijas faktoriem, lai aktiviz\u0113tu g\u0113nus, kuri kod\u0113 mitohondriju olbaltumvielas. <br>Ar akt\u012bvu <em>PGC1\u03b1<\/em> \u0161\u016bn\u0101s veidojas jauni mitohondriji. Vair\u0101ku ned\u0113\u013cu laik\u0101 tas noz\u012bm\u0113, ka Tregs var atjaunot mitohondriju popul\u0101ciju, vecie, boj\u0101tie mitohondriji tiek aizst\u0101ti ar jauniem, funkcion\u0101liem, un mitohondriji tiek atjaunoti. <strong>tiek atjaunota Tregs sp\u0113ja ra\u017eot ATP.<\/strong>.<\/p>\n\n\n\n<p>Uzlabojoties mitohondriju funkcijai un uzlabojoties olbaltumvielu sint\u0113zei, Tregs atg\u016bst sp\u0113ju efekt\u012bvi darboties. Tie atkal var ra\u017eot iev\u0113rojamu daudzumu IL-10. Ar IL-10 sinovi\u0101laj\u0101 \u0161\u0137idrum\u0101 var nom\u0101kt Th17 \u0161\u016bnas, nom\u0101kt Th1 \u0161\u016bnas un nov\u0113rst hronisku autoimunit\u0101ti.<\/p>\n\n\n\n<p>Tas ir l\u0113ns process, jaunu mitohondriju biog\u0113noze aiz\u0146em ned\u0113\u013cas, bet tas ir ilgtsp\u0113j\u012bgs. Huaier veikt\u0101 NF-\u03baB nom\u0101k\u0161ana darbojas \u0101tri (dienas), bet JAK\/STAT modul\u0101cija darbojas vid\u0113j\u0101 termi\u0146\u0101 (ned\u0113\u013cas), bet Huaier veikt\u0101 NF-\u03baB nom\u0101k\u0161ana darbojas \u0101tri (dienas) un JAK\/STAT modul\u0101cija darbojas vid\u0113j\u0101 termi\u0146\u0101 (ned\u0113\u013cas). <em>PI3K\/AKT aktiviz\u0101cija<\/em> ilga iejauk\u0161an\u0101s, kas nemain\u012bs b\u016btisko <strong>atjauno vielmai\u0146as apst\u0101k\u013cus im\u016bn\u0101s tolerances nodro\u0161in\u0101\u0161anai.<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Spezifische_Effekte_bei_ARLA\"><\/span><br><strong>\u012apa\u0161a ietekme ar ARLA:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p>ARLA pacientam pamatst\u0101vokl\u012b pirms Huaier terapijas ir vair\u0101kas patolo\u0123iskas paz\u012bmes. Pirmk\u0101rt, sinovi\u0101lo \u0161\u016bnu, makrof\u0101gu un T \u0161\u016bnu mitohondriji ir hroniski boj\u0101ti. Elektronu transporta \u0137\u0113de nedarbojas optim\u0101li, un ATP sint\u0113ze ir samazin\u0101ta. To var pier\u0101d\u012bt ar metabolisma testiem, piem. <em>J\u016bras zirdzi\u0146a anal\u012bze<\/em> (kas m\u0113ra re\u0101lo ATP ra\u017eo\u0161anas \u0101trumu). ARLA pacientiem OXPHOS r\u0101d\u012bt\u0101ji bija zem\u0101ki nek\u0101 kontroles person\u0101m.<\/p>\n\n\n\n<p>Otrk\u0101rt, regulat\u012bvo T \u0161\u016bnu (Tregs) ir daudz. T\u0101s var identific\u0113t, izmantojot <em>Pl\u016bsmas citometrija<\/em> CD4+CD25+Foxp3+ mar\u0137ieri. ARLA pacientiem bie\u017ei ir palielin\u0101ts absol\u016btais Tregs skaits, da\u017ek\u0101rt pat liel\u0101ks nek\u0101 veseliem cilv\u0113kiem. Var\u0113tu sagaid\u012bt, ka liel\u0101ks Tregs skaits nodro\u0161in\u0101s lab\u0101ku supresiju, ta\u010du ir tie\u0161i pret\u0113ji, jo \u0161ie Tregs ir disfunkcion\u0101li. Tie ra\u017eo maz\u0101k IL-10 uz vienu \u0161\u016bnu, to supres\u012bv\u0101 aktivit\u0101te ir zema, t\u0101p\u0113c tie nesp\u0113j efekt\u012bvi kontrol\u0113t autoreakt\u012bv\u0101s T \u0161\u016bnas.<\/p>\n\n\n\n<p>Tre\u0161k\u0101rt, IL-10\/IFN-\u03b3 attiec\u012bba ir \u013coti nel\u012bdzsvarota. Veseliem cilv\u0113kiem IL-10 parasti ir vismaz tikpat liels k\u0101 IFN-\u03b3, ja ne liel\u0101ks. ARLA pacientiem IFN-\u03b3 ir \u013coti paaugstin\u0101ts (simtiem rei\u017eu augst\u0101ks sinovi\u0101laj\u0101 \u0161\u0137idrum\u0101 nek\u0101 veseliem cilv\u0113kiem), bet IL-10 ir zems. \u0160\u012b nel\u012bdzsvarot\u012bba, iesp\u0113jams, ir viens no lab\u0101kajiem ARLA smaguma pak\u0101pes biolo\u0123iskajiem mar\u0137ieriem.<\/p>\n\n\n\n<p>Ceturtk\u0101rt, ir paaugstin\u0101ts autoantivielu titrs. Tie var b\u016bt <em>Anti-OspA antivielas<\/em> (pret bor\u0113lijas antig\u0113nu, bet reakcija saglab\u0101jas), antivielas pret pa\u0161a organisma skrim\u0161\u013cu olbaltumviel\u0101m, piem. <em>II tipa kolag\u0113ns<\/em> un <em>Aggrecan<\/em>, da\u017ereiz ar\u012b <em>Reimato\u012bdais faktors<\/em> un <em>Anti-CCP antivielas<\/em>.<\/p>\n\n\n\n<p>P\u0113c Huaier terapijas uzs\u0101k\u0161anas ar 20 g\/dien\u0101 un vair\u0101ku ned\u0113\u013cu l\u012bdz m\u0113ne\u0161u laik\u0101 m\u0113s nov\u0113rojam \u0161\u0101das izmai\u0146as:<\/p>\n\n\n\n<p>Port\u0101ls <strong>normaliz\u0113jas mitohondri\u0101l\u0101 elpo\u0161ana.<\/strong>. To var izm\u0113r\u012bt, veicot j\u016bras zirdzi\u0146u anal\u012bzi. . <strong><em>Baz\u0101l\u0101 elpo\u0161ana<\/em> un ATP ra\u017eo\u0161anas \u0101trums palielin\u0101s l\u012bdz norm\u0101l\u0101m v\u0113rt\u012bb\u0101m<\/strong>. Tas ir izm\u0113r\u0101ms un reproduc\u0113jams. Meh\u0101nisms ir PI3K\/AKT medi\u0113ta mitohondriju biog\u0113noze, induc\u0113jot PGC1\u03b1, k\u0101 aprakst\u012bts iepriek\u0161.<\/p>\n\n\n\n<p>Port\u0101ls <strong>Tregs k\u013c\u016bst funkcion\u0101li<\/strong>. To izm\u0113r\u012bt ir smalk\u0101ks, bet ir vair\u0101ki ce\u013ci: palielin\u0101s IL-10 ra\u017eo\u0161ana uz vienu Treg (var izm\u0113r\u012bt ar intracelul\u0101ro citok\u012bnu kr\u0101so\u0161anu un pl\u016bsmas citometriju). Palielin\u0101s Foxp3 ekspresija (vair\u0101k Foxp3 prote\u012bna uz \u0161\u016bnu). Supres\u012bvo funkciju in vitro var izm\u0113r\u012bt ar supresijas testiem. Ja ARLA pacientu Tregs tiek kop\u012bgi kultiv\u0113ti ar autoreakt\u012bvaj\u0101m T \u0161\u016bn\u0101m, Tregs lab\u0101k nom\u0101c T \u0161\u016bnu prolifer\u0101ciju p\u0113c Huaier terapijas.<\/p>\n\n\n\n<p>Port\u0101ls <strong>IL-10\/IFN-\u03b3 attiec\u012bba krasi normaliz\u0113jas<\/strong>. IFN-\u03b3 l\u012bmenis bie\u017ei samazin\u0101s par 50-70%, bet IL-10 l\u012bmenis palielin\u0101s par 100-200%. T\u0101 rezult\u0101t\u0101 attiec\u012bba atkal izskat\u0101s norm\u0101la, vairs nav patolo\u0123isk\u0101 attiec\u012bba 1:100, bet gan tuv\u0101k 1:1 vai pat IL-10 domin\u0113.<\/p>\n\n\n\n<p>Port\u0101ls <strong>Samazin\u0101s autoantivielu titrs<\/strong>. Tas prasa ilg\u0101ku laiku, bie\u017ei vien 8-12 ned\u0113\u013cas, bet titri past\u0101v\u012bgi samazin\u0101s. Anti-OspA antivielas samazin\u0101s vispirms, bet antivielas pret organisma skrim\u0161\u013ca prote\u012bniem samazin\u0101s v\u0113l\u0101k. T\u0101 ir z\u012bme, ka B \u0161\u016bnu atbildes reakcija samazin\u0101s, jo normaliz\u0113jas T \u0161\u016bnu kontrole (Tregs nom\u0101c B \u0161\u016bnu atbildes reakciju).<\/p>\n\n\n\n<p>Port\u0101ls <strong>Samazin\u0101s loc\u012btavu izsv\u012bdums<\/strong>. T\u0101 ir visredzam\u0101k\u0101 paz\u012bme, un to var izm\u0113r\u012bt, veicot kl\u012bnisko izmekl\u0113\u0161anu, apk\u0101rtm\u0113ra m\u0113r\u012bjumus vai ultraska\u0146u. Ja ir vair\u0101k IL-10 un maz\u0101k TNF-\u03b1\/IL-6, samazin\u0101s leikoc\u012btu \u0137\u012bmotaksis loc\u012btav\u0101 un eso\u0161ais izpl\u016bdums tiek reabsorb\u0113ts. Izpl\u016bdums 200-300 ml apjom\u0101 var samazin\u0101ties l\u012bdz 50-100 ml vai piln\u012bb\u0101 izzust.<\/p>\n\n\n\n<p>Port\u0101ls <strong>attiec\u012bgi uzlabojas kl\u012bniskie simptomi.<\/strong>Samazin\u0101s s\u0101pes, palielin\u0101s mobilit\u0101te, pacienti atkal var izmantot loc\u012btavas. Dz\u012bves kvalit\u0101te iev\u0113rojami uzlabojas. Daudzi ARLA pacienti apraksta, ka pirmo reizi vair\u0101ku gadu laik\u0101 vi\u0146i atkal var veikt parastas ikdienas aktivit\u0101tes (k\u0101pt pa k\u0101pn\u0113m, iepirkties, sportot).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ribosomale_Homoostase_Tanaka-Hauptfund\"><\/span>Ribosomu homeost\u0101ze (Tanaka galvenais atkl\u0101jums)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p>Ceturtais intervences punkts ir smalks, bet, pamatojoties uz Tanaka p\u0113t\u012bjumiem par ribosom\u0101lo disfunkciju, ir potenci\u0101li iz\u0161\u0137iro\u0161s. \u0160\u012b ir hipot\u0113ze: ARLA hroniska, notur\u012bga TLR2 un TLR7\/8 signaliz\u0101cija izraisa hronisku ER stresu. Endoplazmatiskajam retikul\u0101m (ER) ir past\u0101v\u012bgi j\u0101salok\u0101s un j\u0101atbr\u012bvo liels daudzums jaunu citok\u012bnu un hemok\u012bnu, t\u0101p\u0113c t\u0101 proteostat\u0101zes sist\u0113mas ir past\u0101v\u012bgi p\u0101rslogotas.<\/p>\n\n\n\n<p>Kad ER ir pak\u013cauta hroniskam stresam, \u0161\u016bna rea\u0123\u0113 ar t\u0101 saukto \u201enesaloc\u012bto olbaltumvielu reakciju\u201c (<em>UPR<\/em>). UPR ir izdz\u012bvo\u0161anas meh\u0101nisms, bet, ja tas tiek hroniski aktiviz\u0113ts, tas var k\u013c\u016bt problem\u0101tisks.<br>Viena no UPR sast\u0101vda\u013c\u0101m ir fosforil\u0113\u0161ana. <em>eIF2\u03b1<\/em> (eikariotiskais inici\u0101cijas faktors 2 alfa) ar <em>HRI<\/em> (H\u0113mregul\u0113ta inhibitoru kin\u0101ze) vai cit\u0101m kin\u0101z\u0113m. Fosforil\u0113jot eIF2\u03b1, samazin\u0101s prote\u012bnu sint\u0113zes \u0101trums. Tas ir adapt\u012bvi, jo \u0161\u016bnai nevajadz\u0113tu salikt v\u0113l vair\u0101k olbaltumvielu, ja ER jau ir p\u0101rslogota.<\/p>\n\n\n\n<p>Kad <em>Olbaltumvielu sint\u0113zes \u0101trums<\/em> Kopum\u0101 ir samazin\u0101ts, optim\u0101li netiek ra\u017eoti ar\u012b prote\u012bni, kas parasti ir j\u0101ra\u017eo nep\u0101rtraukti, lai uztur\u0113tu im\u016bno toleranci. Tie ir IL-10, TGF-\u03b2 un Foxp3. T\u0101s ir relat\u012bvi lielas un struktur\u0101li sare\u017e\u0123\u012btas olbaltumvielas, kuru optim\u0101lai saloc\u012b\u0161anai nepiecie\u0161ama \u012bpa\u0161a ribosomu kvalit\u0101te.<\/p>\n\n\n\n<p>Turkl\u0101t ER stresa ietekm\u0113 var tikt boj\u0101tas ar\u012b pa\u0161as ribosomas. Liel\u0101s ribosomu apak\u0161vien\u012bbas (<em>60S<\/em>) un maz\u0101s ribosom\u0101l\u0101s apak\u0161vien\u012bbas (<em>40S<\/em>) ir sare\u017e\u0123\u012bta strukt\u016bra un sast\u0101vs.<br>Ja ER ir pak\u013cauta stresam un \u0161\u016bn\u0101 rodas p\u0101r\u0101k daudz nepareizi saliktu olbaltumvielu, t\u0101s var mijiedarboties ar ribosom\u0101liem prote\u012bniem un boj\u0101t tos, kas, savuk\u0101rt, noved pie nenorm\u0101las ribosom\u0101l\u0101s RNS strukt\u016bras, k\u0101 Tanaka aprakst\u012bja sav\u0101 mRNS vakcin\u0101cijas p\u0113t\u012bjum\u0101.<\/p>\n\n\n\n<p>Ja ribosomas ir boj\u0101tas struktur\u0101l\u0101 l\u012bmen\u012b, t\u0101s joproj\u0101m var darboties, bet ne optim\u0101li. Tas var izrais\u012bt<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Tulko\u0161anas k\u013c\u016bdas<\/li>\n\n\n\n<li>neefekt\u012bva olbaltumvielu sint\u0113ze<\/li>\n\n\n\n<li>boj\u0101ti prote\u012bni, \u012bpa\u0161i struktur\u0101li sare\u017e\u0123\u012bti prote\u012bni, piem\u0113ram, IL-10.<\/li>\n<\/ul>\n\n\n\n<p>T\u0101d\u0113j\u0101di probl\u0113ma k\u013c\u016bst pa\u0161pietiekama: v\u0101jas ribosomas \u2192 v\u0101ja IL-10 sint\u0113ze \u2192 maz\u0101k IL-10 vid\u0113 \u2192 maz\u0101ka im\u016bn\u0101 tolerance \u2192 liel\u0101ks iekaisums.<\/p>\n\n\n\n<p><strong>K\u0101 Huaier nov\u0113r\u0161 \u0161o procesu:<\/strong><\/p>\n\n\n\n<p>Huaier piev\u0113r\u0161as ribosom\u0101l\u0101s homeost\u0101zes jaut\u0101jumiem, izmantojot miRNS medi\u0113tu regul\u0101ciju. Tanaka aprakst\u012bja, ka <strong>Huaier<\/strong> ar specifisku miRNA regul\u0113\u0161anu. <strong>normaliz\u0113ts ribosom\u0101l\u0101s RNS sast\u0101vs un strukt\u016bra<\/strong>. Tas darbojas, izmantojot \u0161\u0101dus meh\u0101nismus:<\/p>\n\n\n\n<p>Pirmk\u0101rt, Huaier induc\u0113 specifiskas miRNS, kas kav\u0113 to olbaltumvielu ekspresiju, kuras ir saist\u012btas ar ribosomu disfunkciju. Piem\u0113ram, miRNS var samazin\u0101t to olbaltumvielu ekspresiju, kas ribosom\u0101s uzkr\u0101j nepareizi saliktas olbaltumvielas.<\/p>\n\n\n\n<p>Otrk\u0101rt, Huaier <strong>aktiviz\u0113 autof\u0101ziju un proteazomu.<\/strong>, lai no\u0101rd\u012btu boj\u0101tos ribosom\u0101los prote\u012bnus un vec\u0101s ribosomas. Da\u013c\u0113ji tas tiek dar\u012bts, izmantojot miRNS regul\u0101ciju autof\u0101\u0123ijas g\u0113nos. Aktiviz\u0113jot autof\u0101ziju, vec\u0101s, boj\u0101t\u0101s ribosomas tiek izvad\u012btas no \u0161\u016bn\u0101m.<\/p>\n\n\n\n<p>Tre\u0161k\u0101rt, PI3K\/AKT aktiviz\u0101cija ar Huaier (ko m\u0113s apspried\u0101m p\u0113d\u0113j\u0101 punkt\u0101) <strong>Aktiviz\u0113 mTOR<\/strong>, kas ne tikai stimul\u0113 tulko\u0161anu, bet ar\u012b stimul\u0113 jaunu ribosomu biogen\u0113zi. Tas noz\u012bm\u0113, ka, kam\u0113r vec\u0101s ribosomas tiek izvad\u012btas ar autof\u0101\u0123ijas pal\u012bdz\u012bbu, <strong>jaunas, funkcion\u0101las ribosomas<\/strong> ar mTOR atkar\u012bgu rRNS sint\u0113zi un ribosom\u0101lo olbaltumvielu ekspresiju. <strong>tiek ra\u017eots<\/strong>.<\/p>\n\n\n\n<p>Rezult\u0101ts p\u0113c vair\u0101k\u0101m ned\u0113\u013c\u0101m ir <strong>Robosomu popul\u0101cijas normaliz\u0101cija<\/strong>. \u0160\u016bn\u0101m tagad ir funkcion\u0113jo\u0161as ribosomas ar pareizu strukt\u016bru. Tas noz\u012bm\u0113, ka IL-10, TGF-\u03b2 un Foxp3 atkal var tikt optim\u0101li sintez\u0113ti. . <strong>Prote\u012bni<\/strong>, kas tiek ra\u017eoti, ir <strong>Struktur\u0101li pareizi un funkcion\u0101li efekt\u012bvi<\/strong>.<\/p>\n\n\n\n<p>\u0160\u012b ir Huaiera vissmalk\u0101k\u0101 un, iesp\u0113jams, l\u0113n\u0101k\u0101 iejauk\u0161an\u0101s. Lai piln\u012bb\u0101 atjaunotu ribosomu kvalit\u0101ti, ir nepiecie\u0161amas 4-8 ned\u0113\u013cas vai ilg\u0101k. Tas ir b\u016btiski, jo atjauno \u0161\u016bnu sp\u0113ju ra\u017eot olbaltumvielas, kas ir nepiecie\u0161amas im\u016bn\u0101s tolerances nodro\u0161in\u0101\u0161anai.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Mechanistischer_Vergleich_Huaier_zu_Biologika\"><\/span>Huaier meh\u0101nisma sal\u012bdzin\u0101jums ar biolo\u0123iskajiem l\u012bdzek\u013ciem<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>Aspect<\/th><th>TNFi<\/th><th>IL-6i<\/th><th>JAK1i<\/th><th>HUAIER<\/th><\/tr><\/thead><tbody><tr><td><strong>NF-\u03baB blo\u0137\u0113ta<\/strong><\/td><td>Netie\u0161ais (\u2193TNF)<\/td><td>Netie\u0161\u0101 veid\u0101 (\u2193IL-6)<\/td><td>Netie\u0161\u0101 veid\u0101 (\u2193JAK1)<\/td><td>Tie\u0161a (NF-\u03baB nom\u0101k\u0161ana)<\/td><\/tr><tr><td><strong>JAK\/STAT blo\u0137\u0113ts<\/strong><\/td><td>N\u0113<\/td><td>Da\u013c\u0113js (IL-6 ce\u013c\u0161)<\/td><td>J\u0100 (\u013coti sp\u0113c\u012bgs)<\/td><td>JA (izmantojot miRNA, v\u0101j\u0101ka)<\/td><\/tr><tr><td><strong>PI3K\/AKT aktiv\u0101cija<\/strong><\/td><td>N\u0113<\/td><td>N\u0113<\/td><td>N\u0113<\/td><td>J\u0100 (STRONG!)<\/td><\/tr><tr><td><strong>Ribosomu kvalit\u0101te<\/strong><\/td><td>N\u0113<\/td><td>N\u0113<\/td><td>N\u0113<\/td><td>JA (miRNA regul\u0101cija)<\/td><\/tr><tr><td><strong>Treg atbalsts<\/strong><\/td><td>V\u0101j\u0161<\/td><td>V\u0101j\u0161<\/td><td>V\u0101ja (JAK3 nav blo\u0137\u0113ts)<\/td><td>STARK (izmantojot PI3K\/AKT + ribosomas)<\/td><\/tr><tr><td><strong>IL-10 palielin\u0101\u0161an\u0101s<\/strong><\/td><td>Minim\u0101ls<\/td><td>Minim\u0101ls<\/td><td>Zema<\/td><td>STARK (izmantojot ribosomas + Treg atbalstu)<\/td><\/tr><tr><td><strong>S\u0101kums<\/strong><\/td><td>4-8 Wo<\/td><td>4-12 Wo<\/td><td>2-4 Wo<\/td><td>4-8 Wo (aptuveni)<\/td><\/tr><tr><td><strong>Infekcijas risks<\/strong><br><\/td><td>Palielin\u0101ts<\/td><td>M\u0113rens<\/td><td>M\u0113rens<\/td><td>ZEMA (nav im\u016bnsupresijas!)<\/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 progres\u0113jo\u0161\u0101 stadij\u0101 ar vair\u0101ku org\u0101nu inv\u0101ziju<\/strong>&nbsp;smaguma pak\u0101pes un sist\u0113misk\u0101 sloga zi\u0146\u0101 atbilst vissmag\u0101kajiem v\u0113\u017ea gad\u012bjumiem:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Hronisks vair\u0101ku org\u0101nu iekaisums<\/li>\n\n\n\n<li>Autoim\u016bn\u0101 komponente<\/li>\n\n\n\n<li>Vair\u0101kas pa\u0161pietiekamas atgriezenisk\u0101s saites cilpas<\/li>\n\n\n\n<li>Mitohondriju disfunkcija<\/li>\n\n\n\n<li>Ribosomu boj\u0101jumi<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Vorschlag_fur_ARLA-Dosierung\"><\/span>ARLA doz\u0113\u0161anas priek\u0161likums<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p><strong>Ieteikums: 50-60 g dien\u0101<\/strong><br>Sadal\u012bts 3 kv\u012bt\u012bs, katr\u0101 pa 8 stund\u0101m.<br>T\u0101pat k\u0101 visiem prepar\u0101tiem, lai pan\u0101ktu paredz\u0113to efektu, b\u016btiska ir akt\u012bvo sast\u0101vda\u013cu koncentr\u0101cija. T\u0101 k\u0101 akt\u012bv\u0101s vielas laika gait\u0101 organism\u0101 sadal\u0101s vair\u0101k vai maz\u0101k \u0101tri, ir svar\u012bgi prec\u012bzi iev\u0113rot laika interv\u0101lu starp dev\u0101m, lai uztur\u0113tu nemain\u012bgu akt\u012bvo vielu l\u012bmeni visas dienas garum\u0101!<\/p>\n\n\n\n<p><strong>K\u0101p\u0113c 50 - 60 g\/d, nevis, piem\u0113ram, 40 g\/d:<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Smaguma pak\u0101pe<\/strong>: Tanaka p\u0113t\u012bjum\u0101 vair\u0101ku org\u0101nu iesaist\u012b\u0161ana atbilst IV stadijas v\u0113zim.<\/li>\n\n\n\n<li><strong>Vair\u0101ki darb\u012bbas meh\u0101nismi<\/strong>: Visi 4 meh\u0101nismi ir j\u0101risina vienlaic\u012bgi<\/li>\n\n\n\n<li><strong>Atkar\u012bba no devas<\/strong>Tanaka par\u0101da skaidru atkar\u012bbu no devas bez toksicit\u0101tes<\/li>\n\n\n\n<li><strong>Laika faktors<\/strong>: Liel\u0101kas devas var\u0113tu nodro\u0161in\u0101t \u0101tr\u0101ku s\u0101kumu<\/li>\n<\/ol>\n\n\n\n<p><strong>Devu re\u017e\u012bms (ieteikums):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>1. posms (1.-4. ned\u0113\u013ca)<\/strong><br>60 g\/dien\u0101 (sadal\u012bts 3x20 g)<br>Fokuss: NF-\u03baB nom\u0101k\u0161ana, JAK\/STAT modul\u0101cijas s\u0101kums<br>Izmaksas \/ m\u0113nes\u012b (aptuveni) 568,- Euro<\/li>\n\n\n\n<li><strong>2. posms (5.-12. ned\u0113\u013ca)<\/strong><br>50 g\/dien\u0101 (3\u00d716-17 g)<br>Fokuss: JAK\/STAT ietekme ir piln\u012bb\u0101 noteikta, PI3K\/AKT aktiviz\u0101cija<br>Izmaksas \/ m\u0113nes\u012b (aptuveni) 473,- Euro<\/li>\n\n\n\n<li><strong>3. posms (4.-6. m\u0113nesis)<\/strong><br>40 g dien\u0101 (3x13 g)<br>Konserv\u0113\u0161ana, ribosomu atjauno\u0161ana<br>Izmaksas \/ m\u0113nes\u012b (aptuveni) 379,- Euro<\/li>\n\n\n\n<li><strong>Ilgtermi\u0146a saglab\u0101\u0161ana<\/strong><br>20-30 g\/dien\u0101 (3x 7 .. 3x 10 g)<br>Izmaksas m\u0113nes\u012b (aptuveni) 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>Citi attiec\u012bgie raksti par Huaier s\u0113nes piem\u0113ro\u0161anas jomu<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pamati un v\u0113\u017ea terapija<\/strong> -&gt; <a href=\"https:\/\/csiag.eu\/lv\/huaier-senes-veza-terapija\/\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/csiag.eu\/huaier-pilz-in-der-krebstherapie\/<\/a><\/li>\n\n\n\n<li><strong>Hroniskas slim\u012bbas<\/strong> -&gt; <a href=\"https:\/\/csiag.eu\/lv\/huaier-sene-hroniskam-slimibam\/\" 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\">Las\u012b\u0161anas laiks<\/span> <span class=\"rt-time\"> 18<\/span> <span class=\"rt-label rt-postfix\">protokols<\/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\/lv\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/\" rel=\"bookmark\">Las\u012bt vair\u0101k \"<span class=\"screen-reader-text\">Laima slim\u012bba - Huaier pieeja ARLA pacientiem (Antibiotiku rezistents Laima artr\u012bts)<\/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\/lv\/wp-json\/wp\/v2\/posts\/12268","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/comments?post=12268"}],"version-history":[{"count":2,"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/posts\/12268\/revisions"}],"predecessor-version":[{"id":13417,"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/posts\/12268\/revisions\/13417"}],"wp:attachment":[{"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/media?parent=12268"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/categories?post=12268"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.eu\/lv\/wp-json\/wp\/v2\/tags?post=12268"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}