{"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":"arla-hastalari-i%cc%87ci%cc%87n-borreli%cc%87oz-tedavi%cc%87si%cc%87-anti%cc%87bi%cc%87yoti%cc%87ge-di%cc%87rencli%cc%87-lyme-artri%cc%87ti%cc%87","status":"publish","type":"post","link":"https:\/\/csiag.eu\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/","title":{"rendered":"Lyme hastal\u0131\u011f\u0131 - ARLA hastalar\u0131 i\u00e7in Huaier yakla\u015f\u0131m\u0131 (Antibiyoti\u011fe Diren\u00e7li Lyme Artriti)"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_87_1 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\">\u0130\u00e7indekiler tablosu<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Pathogenese\" >Patogenez<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Herkommliche_Therapieformen\" >Geleneksel terapi bi\u00e7imleri<\/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\/tr\/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\/tr\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Beispiel_ARLA-Patient_%E2%80%93_NSARs_und_DMARD\" >\u00d6rnek ARLA hastas\u0131 - NSA\u0130\u0130'ler ve DMARD'lar<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Biologika\" >Biyolojikler<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Huaier-Pilz_%E2%80%93_eine_Alternative\" >Huaier mantar\u0131 - bir alternatif mi?<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#NF-%CE%BAB-Pathway-Hemmung_Plasma-Membran-Signalisierung\" >NF-\u03baB yola\u011f\u0131 inhibisyonu (plazma membran sinyalizasyonu)<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#JAKSTAT-Pathway-Modulation_Endosomal-Signalisierung_IL-6-Feedback\" >JAK\/STAT yola\u011f\u0131 mod\u00fclasyonu (endosomal sinyalizasyon + IL-6 geri bildirimi)<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Vergleich_JAK1i_wie_Upadacitinib_vs_Huaier\" >Kar\u015f\u0131la\u015ft\u0131rma: JAK1i (upadacitinib gibi) 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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#PI3KAKT-Aktivierung_Mitochondriale_Restoration_Treg-Support\" >PI3K\/AKT aktivasyonu (mitokondriyal restorasyon + Treg deste\u011fi)<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Spezifische_Effekte_bei_ARLA\" >ARLA ile spesifik etkiler:<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Ribosomale_Homoostase_Tanaka-Hauptfund\" >Ribozomal homeostaz (Tanaka ana bulgusu)<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Mechanistischer_Vergleich_Huaier_zu_Biologika\" >Huaier ile biyolojik ila\u00e7lar\u0131n mekanistik kar\u015f\u0131la\u015ft\u0131rmas\u0131<\/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\/tr\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Vorschlag_fur_ARLA-Dosierung\" >ARLA dozaj\u0131 i\u00e7in \u00f6neri<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/#Weitere_relevante_Beitrage_zum_Anwendungsbereich_des_Huaier-Pilzes\" >Huaier mantar\u0131n\u0131n uygulama kapsam\u0131na ili\u015fkin di\u011fer ilgili maddeler<\/a><\/li><\/ul><\/nav><\/div>\n<span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Okuma s\u00fcresi<\/span> <span class=\"rt-time\"> 18<\/span> <span class=\"rt-label rt-postfix\">dakika<\/span><\/span>\n<p class=\"wp-block-paragraph\">Lyme hastal\u0131\u011f\u0131na \u015funlar neden olur <em>Borrelia burgdorferi<\/em>, spiral \u015feklinde bir bakteri olan <em>Lyme borreliosis <\/em>(Lyme hastal\u0131\u011f\u0131 olarak da bilinir).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bilimsel a\u00e7\u0131dan bu kadar b\u00fcy\u00fcleyici olan ve ayn\u0131 zamanda imm\u00fcnoloji ve klinik uygulamada en zor bakteriyel enfeksiyonlar\u0131 temsil eden birka\u00e7 patojenden biridir:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>S\u0131rad\u0131\u015f\u0131 genetik:<\/strong> Do\u011frusal kromozom ve karma\u015f\u0131k plazmid sistemi<\/li>\n\n\n\n<li><strong>Ba\u011f\u0131\u015f\u0131kl\u0131k istilas\u0131n\u0131n efendisi:<\/strong> VlsE antijenik varyasyonu, kompleman inhibisyonu, biyofilm<\/li>\n\n\n\n<li><strong>\u00c7oklu organ patojenleri:<\/strong> Neredeyse t\u00fcm organ sistemlerini etkileyebilir<\/li>\n\n\n\n<li><strong>Israr uzman\u0131:<\/strong> Y\u0131llarca s\u00fcren kronik enfeksiyonlara neden olabilir<\/li>\n\n\n\n<li><strong>TLR2 bask\u0131nl\u0131\u011f\u0131:<\/strong> Kitlesel enflamasyonu tetikler (Toll benzeri Resept\u00f6r 4'ten daha fazla)<\/li>\n\n\n\n<li><strong>Otoimm\u00fcn potansiyel:<\/strong> Enfeksiyon sonras\u0131 otoimm\u00fcniteye yol a\u00e7ar (ARLA)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Lyme artriti olan \u00e7o\u011fu insan antibiyotik tedavisinden sonra iyile\u015fir. Bununla birlikte, yakla\u015f\u0131k 10% bu tedaviye yan\u0131t vermez ve Lyme artriti olarak bilinen durum geli\u015fir. <strong>antibiyoti\u011fe diren\u00e7li Lyme artriti<\/strong> (<em>ARLA<\/em>).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu 10% a\u015fa\u011f\u0131dakilere ayr\u0131lm\u0131\u015ft\u0131r<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>x y\u0131l i\u00e7inde spontan remisyon (hastal\u0131k semptomlar\u0131n\u0131n ge\u00e7ici veya kal\u0131c\u0131 olarak gerilemesi) ile 50%<\/li>\n\n\n\n<li>30% ila <strong>DMARD<\/strong> (Hastal\u0131k Modifiye Edici Antiromatizmal \u0130la\u00e7lar) \/ <strong>Biyolojikler<\/strong> (<strong>belirli hedef yap\u0131lara kar\u015f\u0131 hareket eder<\/strong> ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin)<\/li>\n\n\n\n<li>20% kronik ve tedaviye diren\u00e7li<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130lk olarak patogenez (hastal\u0131\u011f\u0131n nedeni), geleneksel tedavi se\u00e7enekleri ve ard\u0131ndan Huaier mantar\u0131n\u0131n etken maddeleri ile tedavi yakla\u015f\u0131m\u0131 a\u00e7\u0131klanmaktad\u0131r.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Pathogenese\"><\/span>Patogenez<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Do\u011frudan istila:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>DbpA\/B arac\u0131l\u0131\u011f\u0131yla kolajen\/dekorin ba\u011flanmas\u0131 - (patojenin kolajen bak\u0131m\u0131ndan zengin yap\u0131lara ba\u011flanmas\u0131n\u0131 sa\u011flar, bu da kona\u011f\u0131n ger\u00e7ek istilas\u0131 ve patojenin konakta kolonizasyonu i\u00e7in \u00f6nemlidir)<\/li>\n\n\n\n<li>BBK32 arac\u0131l\u0131\u011f\u0131yla fibronektin ba\u011flanmas\u0131 - (mekanik y\u00fcke ba\u011fl\u0131 olarak (\u00f6rn. kan dola\u015f\u0131m\u0131nda) polimerize fibronektin olu\u015fumu yoluyla patojenin ba\u011flanma kapasitesinin dinamik olarak g\u00fc\u00e7lendirilmesini sa\u011flar: ne kadar y\u00fcksek, o kadar g\u00fc\u00e7l\u00fc) <\/li>\n\n\n\n<li>Tetiklenen ba\u011f\u0131\u015f\u0131kl\u0131k tepkisi nedeniyle dolayl\u0131 doku hasar\u0131<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Ba\u011f\u0131\u015f\u0131kl\u0131k tetikleyici (TLR2 bask\u0131n):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Y\u00fczey lipoproteinleri (OspA, OspC, OspE)<\/strong> \u2192 TLR2\/6 aktivasyonu (erken ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131t\u0131, ayn\u0131 zamanda a\u015f\u0131r\u0131 inflamatuar reaksiyonlar\u0131 tetikleyebildikleri i\u00e7in patogenez i\u00e7in)<\/li>\n\n\n\n<li><strong>Peptidoglikanlar<\/strong> \u2192 TLR2 aktivasyonu (g\u00fc\u00e7l\u00fc bir enflamatuar yan\u0131ta ve do\u011fal ve adaptif ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin aktivasyonuna yol a\u00e7ar)<\/li>\n\n\n\n<li>B\u00fcy\u00fck \u00e7apl\u0131 <strong>NF-\u03baB\/MAPK aktivasyonu<\/strong> (g\u00fc\u00e7l\u00fc bir \u015fekilde sal\u0131nmas\u0131na neden olur&nbsp;<strong>proinflamatuvar sitokinler<\/strong>&nbsp;gibi <strong>TNF-\u03b1, IL-6 ve IL-1\u03b2<\/strong>, Lyme hastal\u0131\u011f\u0131nda enflamatuar reaksiyonu yo\u011funla\u015ft\u0131r\u0131r)<\/li>\n\n\n\n<li>Massive <strong>pro-enflamatuar sitokin \u00fcretimi<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Ba\u011f\u0131\u015f\u0131kl\u0131k istilas\u0131:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Kompleman inhibisyonu<\/strong><br><em>OspE, OspF<\/em> - Bakterinin y\u00fczey proteinleri kompleman sisteminin d\u00fczenleyici protein fakt\u00f6r\u00fc H'ye ba\u011flan\u0131r ve b\u00f6ylece aksi takdirde bakteriyi yok edecek olan kompleman aktivasyonunu \u00f6nler.<br>OspF, kenelerde kendi patojenine kar\u015f\u0131 kendini korumada bir rol oynuyor gibi g\u00f6r\u00fcnmektedir: OspF ile a\u015f\u0131lanm\u0131\u015f fareler spiroketlerde 90%'ye kadar bir azalma g\u00f6stermi\u015ftir. Kaynak:<a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC186469\/\" target=\"_blank\" rel=\"noreferrer noopener\">OspE veya OspF ile a\u015f\u0131lanm\u0131\u015f farelere yap\u0131\u015fan kenelerdeki Borrelia burgdorferi'nin k\u0131smen yok edilmesi<\/a>)<\/li>\n\n\n\n<li><strong>Antijenik varyasyon<\/strong><br><em>VlsE - de\u011fi\u015fken maj\u00f6r protein benzeri sekans \u0130fade edilen<\/em> &#8211; verhindert Erkennung durch das Immunsystem<\/li>\n\n\n\n<li><strong>Biyofilm olu\u015fumu<\/strong><br>selbst produzierte <em>h\u00fccre d\u0131\u015f\u0131 polimerik madde<\/em> zum Eigenschutz des Erregers<\/li>\n\n\n\n<li><strong>H\u00fccre i\u00e7i kal\u0131c\u0131l\u0131k<\/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 class=\"wp-block-paragraph\"><strong>Otoimm\u00fcnite (enfeksiyon sonras\u0131):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>OspA ve insan proteinleri aras\u0131nda \u00e7apraz reaktivite (\u00f6rn. LFA-1)<\/strong><br>molekulares Mimicry: f\u00fchrt zu einer&nbsp;autoimmunologisch aufrechterhaltenen Entz\u00fcndung, auch wenn der Erreger bereits eliminiert ist.<br>Genetik olarak yatk\u0131n hastalarda g\u00fc\u00e7l\u00fc T-h\u00fccresi yan\u0131t\u0131, pro-enflamatuar sitokinlerin a\u015f\u0131r\u0131 \u00fcretimi ile ili\u015fkilidir (\u00f6rn.&nbsp;<strong>TNF\u03b1, IFN\u03b3<\/strong>) verbunden, die den Entz\u00fcndungsprozess aufrecht erh\u00e4lt<\/li>\n\n\n\n<li><strong>Epitop Yay\u0131l\u0131m\u0131<\/strong><br>Nach anf\u00e4nglicher Immunreaktion gegen Borrelien-Antigene wie&nbsp;<strong>OspA<\/strong>&nbsp;Kal\u0131c\u0131 iltihap doku \u00e7\u00fcr\u00fcmesine ve v\u00fccudun kendi proteinlerinin sal\u0131nmas\u0131na yol a\u00e7ar.<br>Daha sonra bunlar da ba\u011f\u0131\u015f\u0131kl\u0131k sistemi taraf\u0131ndan tan\u0131n\u0131r ve sunulur, b\u00f6ylece ba\u011f\u0131\u015f\u0131kl\u0131k tepkisi yeni, orijinal olarak yabanc\u0131 antijenden ba\u011f\u0131ms\u0131z epitoplara do\u011fru geni\u015fler. Bu s\u00fcre\u00e7, ba\u011f\u0131\u015f\u0131kl\u0131k sisteminde d\u00fczenleyici&nbsp;<strong>IL-10<\/strong>&nbsp;verst\u00e4rkt, was zu einer unkontrollierten Autoimmunit\u00e4t f\u00fchren kann.<\/li>\n\n\n\n<li><strong>Kal\u0131c\u0131 peptidoglikanlar otoreaktif T h\u00fccrelerini tetikler<\/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>Geleneksel terapi bi\u00e7imleri<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 class=\"wp-block-paragraph\">Non-steroid anti-inflamatuar ila\u00e7lar (NSAID'ler) inflamasyonu azaltan, a\u011fr\u0131y\u0131 dindiren ve ate\u015fi d\u00fc\u015f\u00fcren ila\u00e7lard\u0131r ancak kortikosteroidlerin aksine steroid de\u011fildirler.<br>Steroidlerin aksine, NSA\u0130\u0130'ler enfeksiyon oran\u0131n\u0131 art\u0131rmaz.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Prostaglandin ve tromboksan \u00fcreten COX (siklooksijenaz)-1 ve COX-2 enzimlerini se\u00e7ici olmayan bir \u015fekilde inhibe ederler.<br>COX-1 her zaman aktifken (inaktif veya inhibe edilmi\u015fse, \u00f6rne\u011fin mide \u00fclserlerine, b\u00f6brek sorunlar\u0131na ve kanama e\u011filimine neden olur), COX-2 iltihaplanma s\u0131ras\u0131nda yukar\u0131 do\u011fru d\u00fczenlenir.<br>COX-2'nin bloke edilmesi, inflamasyon ve a\u011fr\u0131n\u0131n azalt\u0131lmas\u0131, ate\u015fin d\u00fc\u015f\u00fcr\u00fclmesi gibi istenen etkilerle sonu\u00e7lan\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Se\u00e7ici olmayan NSA\u0130\u0130'ler her iki enzimi de e\u015fit derecede inhibe etti\u011finden, yukar\u0131da belirtilen istenmeyen (yan) etkilere de sahiptirler.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>NSA\u0130\u0130'lerin sadece semptomatik etkisi vard\u0131r<\/strong>. Patojen hala mevcut ve aktiftir, inflamatuar mediat\u00f6rler (pro-inflamatuar sitokinler) engellenmeden \u00fcretilmeye devam eder ve k\u0131k\u0131rdak erozyonu h\u0131z kesmeden devam eder.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Se\u00e7ici olmayan NSA\u0130\u0130'lerin en yayg\u0131n aktif bile\u015fenleri \u015funlard\u0131r<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Asetizalisilik asit<\/li>\n\n\n\n<li>Diklofenak<\/li>\n\n\n\n<li>\u0130buprofen<\/li>\n\n\n\n<li>\u0130ndometasin<\/li>\n\n\n\n<li>Ketoprofen<\/li>\n\n\n\n<li>Meloksikam<\/li>\n\n\n\n<li>Naproksen<\/li>\n\n\n\n<li>Piroksikam<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">(COX-2) inhibit\u00f6rlerinin en yayg\u0131n se\u00e7ici aktif maddeleri \u015funlard\u0131r<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Selekoksib<\/li>\n\n\n\n<li>Etorikoksib<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Rofecoxib (kalp krizi riskinin artmas\u0131 nedeniyle) ve valdecoxib piyasadan \u00e7ekilmi\u015ftir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">COX-2-se\u00e7ici NSA\u0130\u0130'ler koroner kalp hastal\u0131\u011f\u0131 (KKH) olan hastalara veya kalp krizinden sonra verilmemelidir, \u00e7\u00fcnk\u00fc bu hastal\u0131klar\u0131 desteklerler.<\/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 class=\"wp-block-paragraph\">DMARD kategorisi sadece semptomlar\u0131 hafifletmekle kalmay\u0131p (NSA\u0130\u0130'ler gibi) ayn\u0131 zamanda <strong>hastal\u0131\u011f\u0131n ilerlemesini aktif olarak yava\u015flat\u0131r veya durdurur<\/strong> ve uzun vadede ba\u011f\u0131\u015f\u0131kl\u0131k sistemi.<\/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>\u00d6rnek ARLA hastas\u0131 - NSA\u0130\u0130'ler ve DMARD'lar<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Hasta: ARLA'l\u0131 42 ya\u015f\u0131nda erkek (Lyme sonras\u0131 diz monartriti)<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Ba\u015flang\u0131\u00e7:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Naproksen 500 mg g\u00fcnde 2 kez<\/li>\n\n\n\n<li>G\u00fcnde bir kez 20 mg omeprazol (mide korumas\u0131)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A\u011fr\u0131 7\/10<br>Eklem ef\u00fczyonu 200 ml<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>2 hafta sonra<\/strong>:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\u011fr\u0131 4\/10 (daha iyi \u201eesenlik\u201c)<br>Eklem ef\u00fczyonu hala 180 ml <br>\u015ei\u015flik neredeyse hi\u00e7 d\u00fczelmedi<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>DMARD'a y\u00fckseltme:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>+ metotreksat 15 mg\/hafta<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">veya <\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>+ biyolojikler (TNFi veya JAKi)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>8-12 haftal\u0131k kombinasyon tedavisinden sonra:<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\u011fr\u0131 0-1\/10<br>Eklem ef\u00fczyonu &lt; 50 ml<br>Hareketlilik yeniden sa\u011fland\u0131<br>\u0130yile\u015fme sa\u011fland\u0131!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Biologika\"><\/span>Biyolojikler<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Biyolojik ila\u00e7lar, biyoteknolojik olarak \u00fcretilen, insan proteinleri, n\u00fckleik asitler veya antikorlar \u00f6rnek al\u0131narak modellenen daha b\u00fcy\u00fck molek\u00fcllerdir ve mide asidi taraf\u0131ndan erken par\u00e7alanmalar\u0131 nedeniyle tablet \u015feklinde uygulanamazlar, ancak deri alt\u0131na enjeksiyon veya inf\u00fczyon \u015feklinde uygulanabilirler. Sadece JAK inhibit\u00f6rleri a\u011f\u0131zdan al\u0131n\u0131r.<br>Sitokinler, resept\u00f6rler veya ba\u011f\u0131\u015f\u0131kl\u0131k h\u00fccreleri \u00fczerinde d\u00fczenleyici bir etkiye sahip olabilirler. \u0130ns\u00fclin de (1982'de ilk kez) bir biyolojiktir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">ARLA ba\u011flam\u0131nda, bunlar d\u00f6rt hiyerar\u015fiye ayr\u0131l\u0131r<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">1. se\u00e7im - <strong>TNF-\u03b1 inhibit\u00f6rleri (TNFi)<\/strong> - 4-8 hafta sonra 50-70% ile yan\u0131t<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Adalimumab<\/li>\n\n\n\n<li>\u0130nfliksimab<\/li>\n\n\n\n<li>Etanersept<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">2. se\u00e7enek - <strong>IL-6 inhibit\u00f6rleri (IL-6i)<\/strong> - 4-12 hafta sonra 50-60%'de yan\u0131t<\/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 class=\"wp-block-paragraph\">TNFi'ye yan\u0131t vermeyenlerde de etkilidir (hastalar\u0131n ~30-50%'si)<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">3. se\u00e7enek - <strong>JAK inhibit\u00f6rleri (JAKi) <\/strong>- 2-4 hafta sonra yan\u0131t al\u0131nd\u0131 - hala geli\u015ftirme a\u015famas\u0131nda<br>JAK1 (birincil, g\u00fc\u00e7l\u00fc), JAK2 (ikincil, zay\u0131f) ve TYK2'yi (ikincil, zay\u0131f) bloke ederler, bu nedenle STAT3 fosforile edilemez ve bu nedenle inaktif kal\u0131r ve IL-6'ya ba\u011fl\u0131 genler transkribe edilmez. \u00d6te yandan JAK3 engellenmez, bu da enfeksiyona kar\u015f\u0131 daha iyi bir savunma i\u00e7in olumludur (kaynak - maliyetli tam metin): <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/312615\/\" target=\"_blank\" rel=\"noreferrer noopener\">Kronik Lyme artriti. Romatoid artritten klinik ve imm\u00fcnogenetik farkl\u0131la\u015fma<\/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 class=\"wp-block-paragraph\">4. se\u00e7enek - <strong>B-h\u00fccresi t\u00fcketenler<\/strong> - 40-50%'de yan\u0131t - sadece TNFi + IL-6i + JAKi yan\u0131ts\u0131zlar\u0131 i\u00e7in<\/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>Huaier mantar\u0131 - bir alternatif mi?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <a href=\"https:\/\/aditum.org\/journals\/international-journal-of-medical-case-reports-and-medical-research\/archive\/967\" target=\"_blank\" rel=\"noreferrer noopener\">Tanaka \u00e7al\u0131\u015fmas\u0131<\/a> Huaier'in aktif bile\u015fenlerinin \u00f6ncelikle t\u00fcm k\u00f6kenlerden kanserle ilgili etkisine \u0131\u015f\u0131k tutmaktad\u0131r (beyin t\u00fcm\u00f6rleri hari\u00e7, \u00e7\u00fcnk\u00fc b\u00fcy\u00fck aktif bile\u015fen molek\u00fclleri kan-beyin bariyerini ge\u00e7ememektedir).<br>Ayr\u0131 bir <a href=\"https:\/\/csiag.eu\/tr\/kanser-tedavi%cc%87si%cc%87nde-huai%cc%87er-mantari\/\" target=\"_blank\" rel=\"noreferrer noopener\">Katk\u0131<\/a>, ayr\u0131ca <a href=\"https:\/\/csiag.eu\/tr\/kanser-tedavi%cc%87si%cc%87nde-huai%cc%87er-mantari\/#Dosierungsempfehlung\" target=\"_blank\" rel=\"noreferrer noopener\">Dozaj talimatlar\u0131<\/a> ve <a href=\"https:\/\/nutrimentas-shop.de\/products\/vitalpilz-huaier-trametes-robiniophila-fur-wissenschaftliche-zwecke\" target=\"_blank\" rel=\"noreferrer noopener\">Tedarik kayna\u011f\u0131<\/a> \u00c7al\u0131\u015fmada kullan\u0131lan gran\u00fcllerin 32 % polisakkarit ile.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>Dikkat<\/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 class=\"wp-block-paragraph\">\u00c7al\u0131\u015fmalar, Huaier mantar\u0131n\u0131n aktif bile\u015fenlerinin geni\u015f bir yelpazede tamamen d\u00fczenleyici ve programlay\u0131c\u0131 \u00f6zelliklere sahip oldu\u011funu g\u00f6stermi\u015ftir. Yanl\u0131\u015f y\u00f6nlendirilmi\u015f genleri orijinal i\u015flevlerine geri d\u00f6nd\u00fcrebilir ve hatta onlar\u0131 normal i\u015flevlerine do\u011fru yeniden programlayabilirler.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Genler a\u00e7\u0131labilir veya kapat\u0131labilir ve yukar\u0131 veya a\u015fa\u011f\u0131 d\u00fczenlenebilir. Normal aral\u0131kta olmayan t\u00fcm ko\u015fullar, sinyallere kar\u015f\u0131 buna ba\u011fl\u0131 olarak a\u015f\u0131r\u0131 veya engellenmi\u015f tepkilerle sonu\u00e7lan\u0131r. Huaier aktif bile\u015fenleri, bireysel olarak do\u011fru d\u00fczenleyici davran\u0131\u015f\u0131 se\u00e7ici olarak geri y\u00fckleyebilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">ARLA ile mekanistik paralellikler vard\u0131r, bu nedenle Huaier'in ARLA patogenezinde etkisini g\u00f6sterebilece\u011fi d\u00f6rt kritik molek\u00fcler m\u00fcdahale noktas\u0131 vard\u0131r:<\/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 yola\u011f\u0131 inhibisyonu (plazma membran sinyalizasyonu)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Enfeksiyon sonras\u0131 Lyme artritinde, borrelia'n\u0131n ba\u015far\u0131l\u0131 antibiyotik tedavisinden sonra, s\u00f6zde <em>kal\u0131c\u0131 peptidoglikanlar<\/em>, \u00f6l\u00fc borrelia'n\u0131n h\u00fccre duvar\u0131 bile\u015fenleri, sinovyal s\u0131v\u0131da ve eklem dokusunda. Bu peptidoglikanlar ba\u011f\u0131\u015f\u0131kl\u0131k sistemi taraf\u0131ndan s\u00fcrekli olarak tan\u0131n\u0131r, \u00f6zellikle de <em>Toll benzeri Resept\u00f6r 2<\/em> (TLR2), makrofajlar\u0131n, dendritik h\u00fccrelerin ve di\u011fer do\u011fu\u015ftan gelen ba\u011f\u0131\u015f\u0131kl\u0131k h\u00fccrelerinin y\u00fczeyinde bulunur.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">TLR2 kal\u0131c\u0131 peptidoglikanlar\u0131 tan\u0131d\u0131\u011f\u0131nda, klasik peptidoglikanlar\u0131n aktivasyonuna yol a\u00e7an bir sinyal kaskad\u0131 harekete ge\u00e7er <em>NF-\u03baB sinyal yolu<\/em> yol a\u00e7ar. Bu, a\u015fa\u011f\u0131daki gibi adapt\u00f6r proteinlerin i\u015fe al\u0131nmas\u0131yla ger\u00e7ekle\u015fir <em>TIRAP<\/em> ve <em>MyD88<\/em> aktive edilmi\u015f TLR2 resept\u00f6r\u00fcne.<br>Bu adapt\u00f6r proteinler daha sonra a\u015fa\u011f\u0131dakiler de dahil olmak \u00fczere bir kinaz kompleksini i\u015fe al\u0131r <em>IKK kompleksi<\/em> (\u03baB kinaz inhibit\u00f6r\u00fc), inhibit\u00f6r protein olan <em>I\u03baB\u03b1<\/em> fosforile edilmi\u015f ve b\u00f6ylece proteazomal bozunma i\u00e7in etiketlenmi\u015ftir. I\u03baB\u03b1'n\u0131n bozunmas\u0131 ile <em>Transkripsiyon fakt\u00f6r\u00fc dimeri p50\/p65<\/em> NF-\u03baB'den sal\u0131n\u0131r ve h\u00fccre \u00e7ekirde\u011fine translokasyon yapabilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">NF-\u03baB h\u00fccre \u00e7ekirde\u011finde bulunur bulunmaz, pro-inflamatuar sitokinlerin promot\u00f6r b\u00f6lgelerindeki \u03baB DNA ba\u011flanma b\u00f6lgelerine ba\u011flan\u0131r ve bunlar\u0131n kitlesel transkripsiyonunu ba\u015flat\u0131r. Bu da s\u00fcrekli ve kal\u0131c\u0131 olarak <em>TNF-\u03b1, IL-6, IL-1\u03b2, IL-8<\/em> ve di\u011fer kemokinler gibi <em>MCP-1<\/em> ve <em>KC<\/em>.<br>ARLA hastalar\u0131nda bu s\u00fcre\u00e7 kendi kendini s\u0131n\u0131rlamaz. Peptidoglikanlar mevcut kald\u0131\u011f\u0131 s\u00fcrece haftalar, aylar ve y\u0131llar boyunca devam eder. Temel sorun budur: sava\u015f\u0131lmas\u0131 gereken yeni bir enfeksiyon yoktur, ancak ba\u011f\u0131\u015f\u0131kl\u0131k sistemi iltihaplanma modunda tak\u0131l\u0131 kal\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Huaier bu s\u00fcreci nas\u0131l kesintiye u\u011fratabilir?<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier \u015fu a\u00e7\u0131dan zengindir <em>\u03b2-glukanlar<\/em> ve di\u011ferleri <em>Polisakkaritler<\/em>, TLR2 d\u0131\u015f\u0131nda bir resept\u00f6re ba\u011flanan, yani s\u00f6zde <em>Dectin-1 resept\u00f6r\u00fc<\/em> (Dectin-1 bir <em>C-tipi lektin resept\u00f6r\u00fc<\/em>, \u00f6ncelikle makrofajlar ve dendritik h\u00fccreler \u00fczerinde ifade edilir). Huaier'den elde edilen \u03b2-glukanlar Dectin-1'e ba\u011fland\u0131\u011f\u0131nda, NF-\u03baB'yi de aktive eder, ancak alternatif, daha az pro-inflamatuar bir sinyal yolu \u00fczerinden.<br>Klasik yerine <em>TIRAP\/MyD88 rotas\u0131<\/em> TLR2 sinyalle\u015fmesinde oldu\u011fu gibi, sinyalle\u015fme a\u015fa\u011f\u0131dakiler taraf\u0131ndan ger\u00e7ekle\u015ftirilir <em>Syk kinaz<\/em> ve <em>Kart9<\/em>, Bu da bir t\u00fcr \u201ed\u00fczenlenmi\u015f\u201c NF-\u03baB sinyaline yol a\u00e7ar.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Buna ek olarak Huaier, a\u015fa\u011f\u0131dakiler arac\u0131l\u0131\u011f\u0131yla \u00e7al\u0131\u015fmaktad\u0131r <em>miRNA arac\u0131l\u0131<\/em> NF-\u03baB bile\u015fenlerinin kendilerinin azalmas\u0131na yol a\u00e7an mekanizmalar. Huaier taraf\u0131ndan yukar\u0131 reg\u00fcle edilen spesifik mikroRNA'lar (\u00f6rne\u011fin <em>miRNA-223, miRNA-146a<\/em> ve di\u011ferleri), IKK alt birimlerinin ve RelA'n\u0131n (NF-\u03baB'nin p65 alt birimi) mRNA's\u0131n\u0131 do\u011frudan bozabilir. Bu, kal\u0131c\u0131 peptidoglikanlar hala mevcut olsa ve TLR2'yi uyarsa bile, h\u00fccrelerde aktive edilebilecek daha az genel NF-\u03baB kompleksi oldu\u011fu anlam\u0131na gelir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier'in bu ikili m\u00fcdahalesinin pratik sonucu, peptidoglikanlar taraf\u0131ndan s\u00fcrekli NF-\u03baB aktivasyonunun b\u00fcy\u00fck \u00f6l\u00e7\u00fcde azalt\u0131lmas\u0131d\u0131r. TNF-\u03b1 \u00fcretimi azal\u0131r, IL-6 \u00fcretimi azal\u0131r ve IL-1\u03b2 \u00fcretimi azal\u0131r. Klinik olarak bu durum, NF-\u03baB ile ind\u00fcklenen bir akut faz proteini olan C-reaktif proteinde (CRP) h\u0131zl\u0131 bir azalmaya yol a\u00e7ar.<br>Kemokin olarak g\u00f6rev yapan TNF-\u03b1 ve IL-6'n\u0131n azalmas\u0131yla, eklem ef\u00fczyonu da daha h\u0131zl\u0131 emilir \u00e7\u00fcnk\u00fc l\u00f6kositlerin ekleme al\u0131nmas\u0131 azal\u0131r. Hastalar, Huaier uygulamas\u0131n\u0131n ba\u015flamas\u0131ndan sonraki ilk 1-2 hafta i\u00e7inde \u015fi\u015flik ve a\u011fr\u0131da h\u0131zl\u0131 bir azalma oldu\u011funu bildirmektedir. Bu durum NF-\u03baB bask\u0131lanmas\u0131 ile tutarl\u0131d\u0131r.<\/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 yola\u011f\u0131 mod\u00fclasyonu (endosomal sinyalizasyon + IL-6 geri bildirimi)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">ARLA a\u015f\u0131r\u0131 \u00fcretimdir <em>Tip I interferonlar<\/em> (interferon-\u03b1 ve interferon-\u03b2) olarak bilinen \u201e<em>IFN amplifikasyon d\u00f6ng\u00fcs\u00fc<\/em>\u201c olarak etiketlenmi\u015ftir. Bu, az \u00f6nce NF-\u03baB ile tart\u0131\u015ft\u0131\u011f\u0131m\u0131z klasik TLR2 sinyali de\u011fildir. Bunun yerine, bu farkl\u0131 bir yolla ger\u00e7ekle\u015fir: kal\u0131c\u0131 borrelia <em>Makrofajlar<\/em> ve <em>dendritik h\u00fccreler<\/em> fagosite edilir. Fagozom i\u00e7ine al\u0131nd\u0131klar\u0131nda, endozomal Toll benzeri resept\u00f6rler taraf\u0131ndan tan\u0131n\u0131rlar, \u00f6zellikle <em>TLR7, TLR8<\/em> ve <em>TLR9<\/em>. Bu resept\u00f6rler v\u00fccudun i\u00e7 y\u00fczeyinde bulunur. <em>endozomal\/fagozomal vezik\u00fcller<\/em> ve Borrelia RNA ve DNA's\u0131n\u0131 tan\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">TLR7\/8\/9 bakteriyel n\u00fckleik asitler taraf\u0131ndan uyar\u0131ld\u0131\u011f\u0131nda, adapt\u00f6r proteini al\u0131rlar <em>MyD88<\/em> ve\/veya <em>TRIF<\/em> ve interferon d\u00fczenleyici fakt\u00f6rlerin aktivasyonuna yol a\u00e7ar, \u00f6zellikle <em>IRF3<\/em> ve <em>IRF7<\/em>. Bu IRF transkripsiyon fakt\u00f6rleri daha sonra \u00e7ekirde\u011fe girer ve tip I interferon genlerinin transkripsiyonunu ba\u015flat\u0131r: ba\u015flang\u0131\u00e7ta <em>\u0130nterferon-\u03b2<\/em> ve bunu ikincil bir dalga takip eder <em>\u0130nterferon-\u03b1<\/em>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">IFN-\u03b1 ve IFN-\u03b2 sinovyal s\u0131v\u0131ya ve kana sal\u0131nd\u0131ktan sonra, a\u015fa\u011f\u0131dakiler de dahil olmak \u00fczere neredeyse t\u00fcm h\u00fccrelerde bulunan interferon-\u03b1\/\u03b2 resept\u00f6r\u00fcne (IFNAR) ba\u011flan\u0131rlar <em>T h\u00fccreleri, makrofajlar<\/em> ve <em>sinovyal fibroblastlar<\/em>.<br>IFNAR ba\u011flanmas\u0131 iki kinaz\u0131 resept\u00f6re ba\u011flar: <em>JAK1<\/em> ve <em>TYK2<\/em>. Bu kinazlar daha sonra STAT proteinlerini fosforile eder <em>STAT1<\/em> ve <em>STAT2<\/em> (<strong>de\u011fil<\/strong> <em>STAT3<\/em> bu \u00f6zel yolakta). Fosforlanm\u0131\u015f STAT1\/STAT2 ile birlikte <em>IRF9<\/em> bir transkripsiyon fakt\u00f6r\u00fc kompleksi <em>ISGF3<\/em> ve h\u00fccre \u00e7ekirde\u011fine gider.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">H\u00fccre \u00e7ekirde\u011finde, ISGF3 a\u015fa\u011f\u0131dakilere ba\u011flan\u0131r <em>\u0130nterferonla Uyar\u0131lm\u0131\u015f Yan\u0131t Unsurlar\u0131<\/em> (ISRE'ler) promot\u00f6r b\u00f6lgelerinde <em>\u0130nterferon ile uyar\u0131lan genler<\/em> (ISG'ler). Bu ISG'ler a\u015fa\u011f\u0131dakiler gibi genleri i\u00e7erir <em>OAS<\/em> (2\u2032,5\u2032-oligoadenilat sentetaz), <em>MxA<\/em> (Miksovir\u00fcs Diren\u00e7 Proteini A), <em>PBR<\/em> (protein kinaz R) ve di\u011ferleri. Bu genler b\u00fcy\u00fck \u00f6l\u00e7\u00fcde yukar\u0131 do\u011fru d\u00fczenlenir ve h\u00fccrelerde bir \u201eanti-viral durum\u201c yarat\u0131r. Bu durum ger\u00e7ek viral enfeksiyonda normal ve adaptiftir, ancak ARLA'da aktif viral enfeksiyon olmad\u0131\u011f\u0131 i\u00e7in maladaptiftir. Bu bir t\u00fcr \u201eyanl\u0131\u015f alarm \u201cd\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Sorun bir geri besleme mekanizmas\u0131yla daha da k\u00f6t\u00fcle\u015fir: interferon \u00fcreten h\u00fccreler daha fazla interferon \u00fcretir, bu da di\u011fer h\u00fccrelerde daha g\u00fc\u00e7l\u00fc IFNAR sinyalini tetikler, bu da daha fazla ISG transkripsiyonuna yol a\u00e7ar ve bu da daha fazla IFN \u00fcretimi olas\u0131l\u0131\u011f\u0131n\u0131 art\u0131r\u0131r. Bu, \u201e<em>IFN amplifikasyon d\u00f6ng\u00fcs\u00fc<\/em>\u201e, enfeksiyon sonras\u0131 ARLA'n\u0131n karakteristi\u011fidir. Bu d\u00f6ng\u00fc kendi kendini devam ettirir: t\u00fcm canl\u0131 borrelia \u00f6ld\u00fcr\u00fcld\u00fckten sonra bile bu yol devam eder \u00e7\u00fcnk\u00fc \u00f6l\u00fc bakteriler ve n\u00fckleik asitleri hala fagosite edilmektedir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ayn\u0131 zamanda, bu tip I IFN durumu T h\u00fccrelerinin aktivasyonuna ve geni\u015flemesine de yol a\u00e7ar, \u00f6zellikle <em>Th1 h\u00fccreleri<\/em> ve daha sonra da <em>Th17 h\u00fccreleri<\/em>. Th17 h\u00fccreleri farkl\u0131 bir mekanizma ile aktive olurlar: bu h\u00fccrelerin <em>IL-6<\/em> ile birlikte <em>TGF-\u03b2<\/em>. IL-6 ayr\u0131ca NF-\u03baB taraf\u0131ndan ve ayn\u0131 zamanda interferonla uyar\u0131lan genler taraf\u0131ndan da \u00fcretilir. Dolay\u0131s\u0131yla IL-6'ya yol a\u00e7an birka\u00e7 yol vard\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">IL-6 \u00f6nemli miktarlarda bulunur bulunmaz ilgin\u00e7 bir \u015fey olur: IL-6 kendi resept\u00f6r\u00fcne ba\u011flan\u0131r (<em>IL-6R<\/em>) ad\u0131 verilen bir yard\u0131mc\u0131 resept\u00f6r ile birlikte <em>gp130<\/em> T h\u00fccrelerinin, sinovyal fibroblastlar\u0131n ve di\u011fer h\u00fccrelerin y\u00fczeyinde. Bu ba\u011flanma JAK1 ve JAK2'yi resept\u00f6re ba\u011flar. JAK1 ve JAK2 daha sonra STAT proteini STAT3'\u00fc fosforile eder. Bu fosforilasyon ile STAT3 aktive olur ve h\u00fccre \u00e7ekirde\u011fine girer, burada DNA ba\u011flanma b\u00f6lgelerine ba\u011flan\u0131r ve IL-17 ve transkripsiyon fakt\u00f6r\u00fc ROR\u03b3t'nin transkripsiyonunu ba\u015flat\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu da daha fazla IL-17 \u00fcreten Th17 h\u00fccrelerinin muazzam bir \u015fekilde geni\u015flemesine yol a\u00e7ar. IL-17 y\u00fcksek oranda pro-enflamatuard\u0131r ve sinovyal fibroblastlar (FLS - fibroblast benzeri sinoviyositler) \u00fczerinde etki ederek daha da fazla IL-6 \u00fcretir. Bu ikinci bir geri bildirim sistemi olu\u015fturur: IL-6 \u2192 Th17 geni\u015flemesi \u2192 IL-17 \u00fcretimi \u2192 FLS'den daha fazla IL-6 \u2192 daha da fazla Th17 \u2192 daha da fazla IL-17. IFN amplifikasyon d\u00f6ng\u00fcs\u00fcnde oldu\u011fu gibi, bu kendi kendini s\u00fcrd\u00fcr\u00fcr ve ARLA'ya kronik, kontrol edilmesi zor karakterini verir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Huaier bu s\u00fcreci nas\u0131l kesintiye u\u011fratabilir?<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier, JAK1 veya JAK2'yi do\u011frudan bloke etmekten daha temel bir d\u00fczeyde bu JAK\/STAT yola\u011f\u0131na m\u00fcdahale eder (\u00e7\u00fcnk\u00fc <em>JAK inhibit\u00f6rleri<\/em> gibi <em>Upadacitinib<\/em> yap). <strong>Bunun yerine, Huaier miRNA arac\u0131l\u0131 transkripsiyonel d\u00fczenleme yoluyla hareket eder<\/strong>. Huaier polisakkaritleri taraf\u0131ndan yukar\u0131 reg\u00fcle edilen spesifik mikroRNA'lar JAK proteinlerinin mRNA's\u0131n\u0131 yok eder veya bozar.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu, zarif bir d\u00fczenleyici mekanizma arac\u0131l\u0131\u011f\u0131yla ger\u00e7ekle\u015fir: Huaier polisakkaritleri Dectin-1'e ba\u011fland\u0131\u011f\u0131nda ve h\u00fccreyi sinyallerle uyard\u0131\u011f\u0131nda, yaln\u0131zca tek bir sinyal yolu aktive olmakla kalmaz, ayn\u0131 zamanda miRNA i\u015fleme enzimleri de h\u0131zlan\u0131r. Bunlar, \u00e7e\u015fitli kanonik ve kanonik olmayan miRNA'lar\u0131n biyogenezine yol a\u00e7ar. Bu miRNA'lardan baz\u0131lar\u0131, \u00f6rne\u011fin <strong>miR-223, miR-146a<\/strong> ve <strong>miR-34a<\/strong>, 3\u2032 \u00e7evrilmemi\u015f b\u00f6lgede ba\u011flanma b\u00f6lgelerine sahiptir (<strong>3\u2032-UTR<\/strong>) dan <em>JAK1, JAK2<\/em> ve <em>STAT3 mRNA<\/em>.<br>Bu miRNA'lar bu dizilerle hibridize olduklar\u0131nda, mRNA'y\u0131 RNA interferans bozunmas\u0131 i\u00e7in i\u015faretlerler. <strong>RISC kompleksi<\/strong> (RNA-\u0130nd\u00fcklenmi\u015f Susturma Kompleksi). Sonu\u00e7, mRNA'n\u0131n bozulmas\u0131 ve bu proteinlerin art\u0131k verimli bir \u015fekilde \u00fcretilmemesidir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier'e maruz kald\u0131ktan sonra birka\u00e7 g\u00fcn ila bir hafta i\u00e7inde, h\u00fccreler basit\u00e7e <strong>daha az JAK1-, JAK2-<\/strong> ve <strong>STAT3 proteini<\/strong>. Bu, basit\u00e7e kinaz aktivitesini bloke etmekten daha temeldir. Bu, resept\u00f6r aktive oldu\u011funda ve JAK'\u0131 fosforile etmeye \u00e7al\u0131\u015ft\u0131\u011f\u0131nda bile fosforile edilecek daha az JAK molek\u00fcl\u00fc oldu\u011fu anlam\u0131na gelir. Bu da <strong>JAK'a ba\u011fl\u0131 sitokin sinyaline yan\u0131t<\/strong> bu nedenle <strong>b\u00fcy\u00fck \u00f6l\u00e7\u00fcde azald\u0131<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">JAK ifadesindeki bu azalma tip I IFN amplifikasyon d\u00f6ng\u00fcs\u00fcn\u00fc kesintiye u\u011frat\u0131r. TLR7\/8\/9 interferon \u00fcretimini denemeye devam etse bile, IFN-\u03b1\/\u03b2 \u00fcreten h\u00fccreler daha az JAK1\/TYK2'ye sahiptir, bu nedenle STAT1\/STAT2 daha az verimli bir \u015fekilde fosforile edilebilir. Bu da daha az ISGF3 aktivasyonuna, daha az ISG transkripsiyonuna ve dolay\u0131s\u0131yla <strong>daha az \u201eanti-viral durum\u201c<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ayn\u0131 zamanda, JAK1 ve JAK2'nin azalmas\u0131 IL-6 geri bildirim d\u00f6ng\u00fcs\u00fcn\u00fc de kesintiye u\u011frat\u0131r. IL-6 mevcut olsa ve T h\u00fccreleri \u00fczerindeki IL-6R'ye ba\u011flansa bile, fosforile edilecek daha az JAK1 ve JAK2 vard\u0131r, bu nedenle STAT3 daha az fosforile olur. Daha az aktif STAT3 ile daha az ROR\u03b3t ve IL-17 \u00fcretilir ve bu nedenle Th17 h\u00fccreleri agresif bir \u015fekilde geni\u015flemez. Bu, daha az IL-17 \u00fcretimi, IL-6 \u00fcretmek i\u00e7in FLS'nin daha az uyar\u0131lmas\u0131 anlam\u0131na gelir - ve d\u00f6ng\u00fc bozulur.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Laboratuvar terimleriyle, bunu bir <strong>IFN-\u03b3 seviyelerinde azalma<\/strong> (tip I IFN ile de yukar\u0131 reg\u00fcle edilen Th1 aktivitesi i\u00e7in belirte\u00e7), <strong>IL-6 seviyelerinde azalma <\/strong>(IL-6 geri bildirim sistemi i\u00e7in i\u015faretleyici) ve <strong>IL-17 seviyelerinde azalma<\/strong> (Th17 i\u00e7in i\u015faretleyici). Bu, NF-\u03baB bask\u0131lanmas\u0131ndan (g\u00fcnler i\u00e7inde ger\u00e7ekle\u015fir) daha yava\u015f ger\u00e7ekle\u015fir - miRNA tabanl\u0131 etkilerin tam olarak ger\u00e7ekle\u015fmesi yakla\u015f\u0131k 2-4 hafta s\u00fcrer, ancak bir kez ger\u00e7ekle\u015fti\u011finde daha kal\u0131c\u0131d\u0131r.<\/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>Kar\u015f\u0131la\u015ft\u0131rma: JAK1i (upadacitinib gibi) vs Huaier:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A <strong>JAK1 inhibit\u00f6r\u00fc<\/strong> gibi <em>Upadacitinib<\/em> (ticari ad\u0131 Rinvoq) Huaier'den tamamen farkl\u0131 bir mekanizma ile \u00e7al\u0131\u015f\u0131r, ancak her ikisi de sonu\u00e7ta JAK\/STAT sinyal yollar\u0131n\u0131 mod\u00fcle eder. Upadacitinib, do\u011frudan ila\u00e7 olarak kullan\u0131labilen k\u00fc\u00e7\u00fck bir molek\u00fcld\u00fcr. <em>ATP ba\u011flama cebi<\/em> ve <em>JAK1 kinaz<\/em> ve onlar\u0131 fiziksel olarak bloke eder. Bu bir t\u00fcr \u201emekanik engelleyicidir\u201c.<br>JAK1 bloke edildi\u011finde, resept\u00f6r JAK'\u0131 aktive etmek i\u00e7in ne kadar u\u011fra\u015f\u0131rsa u\u011fra\u015fs\u0131n, STAT proteinleri \u00fczerindeki tirozin amino asidini art\u0131k fosforile edemez. Etki h\u0131zl\u0131d\u0131r: upadacitinib kan dola\u015f\u0131m\u0131na emilip h\u00fccrelere ula\u015ft\u0131\u011f\u0131nda JAK1 inhibe edilir. Bu nedenle JAK inhibit\u00f6rleri h\u0131zl\u0131 bir ba\u015flang\u0131ca sahiptir, tipik olarak 2-4 haftada g\u00f6zle g\u00f6r\u00fcl\u00fcr klinik iyile\u015fmeler g\u00f6r\u00fcl\u00fcr.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ancak bu do\u011frudan blokaj\u0131n dezavantajlar\u0131 da vard\u0131r. JAK1 inhibit\u00f6rleri sadece JAK1\u201ei de\u011fil, se\u00e7iciliklerine ba\u011fl\u0131 olarak di\u011fer JAK kinazlar\u0131 da de\u011fi\u015fen derecelerde inhibe eder. \u201cJAK1-se\u00e7ici\" inhibit\u00f6rler bile JAK2 ve TYK2'yi belirli bir dereceye kadar zay\u0131f bir \u015fekilde inhibe eder. Bu \u015fu sonu\u00e7lara yol a\u00e7ar <strong>Yan etkiler<\/strong>, i\u00e7in \u00f6zellikle artan risk <strong>Herpes zoster<\/strong> (zona) \u00e7\u00fcnk\u00fc JAK3 blokaj\u0131 T-h\u00fccresi proliferasyonunu bozar ve b\u00f6ylece gizli vir\u00fcslerin kontrol\u00fcn\u00fc <em>Varisella zoster<\/em> zay\u0131flar. Genel olarak, JAK2'nin blokaj\u0131 <strong>Tromboembolizm aktivasyonu<\/strong> inhibisyon yerine (\u00f6zellikle JAK2'yi daha g\u00fc\u00e7l\u00fc bir \u015fekilde bloke eden baricitinib).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Huaier<\/strong> tamamen farkl\u0131 bir seviyede \u00e7al\u0131\u015f\u0131r. JAK proteinini do\u011frudan bloke etmez. Bunun yerine <strong>azalt\u0131lm\u0131\u015f<\/strong> o <strong>JAK proteini miktar\u0131<\/strong>, h\u00fccrenin hi\u00e7 \u00fcretmedi\u011fi. Bu, JAK mRNA's\u0131n\u0131n miRNA arac\u0131l\u0131 bozunmas\u0131 yoluyla ger\u00e7ekle\u015fir. Avantaj\u0131, bu mekanizman\u0131n daha incelikli ve muhtemelen daha fizyolojik olmas\u0131d\u0131r. H\u00fccreler, proteini zorla bloke eden bir ila\u00e7 yerine ne kadar JAK \u00fcrettiklerini basit\u00e7e a\u015fa\u011f\u0131 do\u011fru d\u00fczenlerler. Dezavantaj\u0131 ise bu s\u00fcrecin daha yava\u015f olmas\u0131d\u0131r. MiRNA'lar\u0131n yeterli miktarda d\u00fczenlenmesi birka\u00e7 g\u00fcn ila bir hafta s\u00fcrer ve ard\u0131ndan JAK protein seviyelerinin belirgin \u015fekilde d\u00fc\u015fmesi i\u00e7in yeterli JAK mRNA's\u0131n\u0131n bozulmas\u0131 birka\u00e7 g\u00fcn daha al\u0131r. Huaier'in JAK\/STAT'a ba\u011fl\u0131 s\u00fcre\u00e7ler \u00fczerinde fark edilebilir etkilere kadar muhtemelen 4-8 hafta gibi daha yava\u015f bir ba\u015flang\u0131ca sahip olmas\u0131n\u0131n nedeni budur.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bir di\u011fer \u00f6nemli fark ise tersine \u00e7evrilebilirliktir. Bir hasta upadacitinib almay\u0131 b\u0131rakt\u0131\u011f\u0131nda, upadacitinibin yar\u0131 \u00f6mr\u00fc k\u0131sa oldu\u011fu i\u00e7in JAK blokaj\u0131 24-48 saat i\u00e7inde sona erer. JAK1 tekrar aktif hale gelir ve STAT'\u0131 fosforile edebilir. Bu, bir hasta enfeksiyonlardan muzdaripse ve ilaca ara vermesi gerekiyorsa yararl\u0131d\u0131r, ancak ayn\u0131 zamanda s\u00fcrekli bir g\u00fcnl\u00fck al\u0131m\u0131n gerekli oldu\u011fu anlam\u0131na gelir. Huaier daha uzun s\u00fcreli bir etkiye sahip olabilir \u00e7\u00fcnk\u00fc miRNA tabanl\u0131 d\u00fczenleme daha uzun s\u00fcrer. MiRNA'lar\u0131n kendileri k\u00fc\u00e7\u00fck molek\u00fcllerden daha uzun yar\u0131 \u00f6mre sahiptir ve Huaier maruziyeti durdu\u011funda JAK proteininin iyile\u015fmesi daha uzun s\u00fcrer.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Daha da ince bir fark \u00f6zg\u00fcll\u00fckte yatmaktad\u0131r. Upadacitinib JAK1-se\u00e7icidir, yani JAK1'i g\u00fc\u00e7l\u00fc bir \u015fekilde bloke eder, JAK2'yi zay\u0131f bir \u015fekilde bloke eder ve JAK3'\u00fc \u00e7ok az bloke eder. Bu asl\u0131nda JAK1 se\u00e7icili\u011finin amac\u0131d\u0131r, yani T-h\u00fccresi i\u015flevlerini daha iyi korumak i\u00e7in JAK3'\u00fc bloke etmekten ka\u00e7\u0131nmakt\u0131r.<br>Huaier, hangi miRNA'lar\u0131n yukar\u0131 reg\u00fcle edildi\u011fine ba\u011fl\u0131 olarak muhtemelen JAK1, JAK2 ve muhtemelen TYK2'yi az ya da \u00e7ok orant\u0131l\u0131 olarak azalt\u0131r. Bu, Huaier'in bir etkiye sahip oldu\u011fu anlam\u0131na gelebilir. <strong>daha geni\u015f JAK bask\u0131lamas\u0131<\/strong> Bu da tip I IFN sinyali (TYK2'ye ihtiya\u00e7 duyar) gibi \u015feyler i\u00e7in iyi olabilir, ancak potansiyel olarak daha fazla JAK2 etkisine yol a\u00e7ar (teorik olarak tromboembolizm riski).<\/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 aktivasyonu (mitokondriyal restorasyon + Treg deste\u011fi)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">ARLA ile ilgili \u00fc\u00e7\u00fcnc\u00fc b\u00fcy\u00fck sorun sadece pro-inflamatuar sitokinlerin s\u00fcrekli \u00fcretimi de\u011fil, ayn\u0131 zamanda normalde bu inflamasyonu s\u0131n\u0131rlayacak sistemlerin bozulmas\u0131d\u0131r. Enflamasyonu kontrol eden en \u00f6nemli sistem, d\u00fczenleyici T h\u00fccreleri pop\u00fclasyonudur (<em>Tregler<\/em>), \u00f6zellikle <em>CD4+CD25+Foxp3+ <\/em>Tregler.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Sa\u011fl\u0131kl\u0131 insanlarda Treg'ler ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin ayr\u0131lmaz bir par\u00e7as\u0131d\u0131r ve a\u015fa\u011f\u0131dakiler gibi anti-enflamatuar sitokinlerin \u00fcretimi yoluyla hareket ederler <em>IL-10<\/em> ve <em>TGF-\u03b2<\/em>, pro-enflamatuar T h\u00fccrelerini ind\u00fcklemek i\u00e7in do\u011frudan h\u00fccreden h\u00fccreye temas\u0131n yan\u0131 s\u0131ra (<em>Efekt\u00f6r T h\u00fccreleri<\/em>) bast\u0131r\u0131lacak.<br>Tregler metabolik olarak \u00e7ok aktiftir ve oksidatif fosforilasyona dayan\u0131rlar. <em>Mitokondri<\/em> Bu, i\u015fleyen mitokondriye ve s\u00fcrekli bir besin kayna\u011f\u0131na ihtiya\u00e7 duyduklar\u0131 anlam\u0131na gelir. <em>ATP<\/em>. Ayr\u0131ca protein sentezleme yetene\u011fine de ihtiya\u00e7 duyarlar, \u00f6zellikle de <em>Transkripsiyon D\u00fczenleyici <\/em>Foxp3 proteini ve bask\u0131lay\u0131c\u0131 sitokinler IL-10 ve TGF-\u03b2.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">ARLA hastalar\u0131nda birka\u00e7 \u015fey yanl\u0131\u015f gitmi\u015ftir. \u0130lk olarak, s\u00fcrekli TLR2 ve TLR7\/8 stim\u00fclasyonu nedeniyle <strong>Mitokondri kronik olarak stres alt\u0131nda<\/strong>. S\u00fcrekli \u00fcretim <em>ROS<\/em> (reaktif oksijen t\u00fcrleri) i\u00e7 mitokondriyal membran\u0131 okside eder ve elektron ta\u015f\u0131ma zincirindeki komplekslere zarar verir. Mitokondriyal DNA oksitlenerek transkripsiyonun bozulmas\u0131na yol a\u00e7abilir. Mitokondri, kronik enflamatuar bir durumda t\u00fcm h\u00fccreleri beslemek i\u00e7in yeterli ATP \u00fcretemez.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130kinci olarak <strong>kronik <em>ER stres durumu<\/em><\/strong> (\u00e7\u00fcnk\u00fc enflamatuar h\u00fccreler s\u00fcrekli olarak b\u00fcy\u00fck miktarlarda sitokin \u00fcretir ve <em>Protein katlama kapasitesi<\/em> .. <em>endoplazmik retikulum<\/em> bunalm\u0131\u015fsa) <em>Protein sentez kapasitesi<\/em> h\u00fccrelerin say\u0131s\u0131 k\u00fcresel olarak azal\u0131r.<br>Ribozomlar protein \u00fcretiminin arac\u0131d\u0131r ve ER stres alt\u0131ndayken ribozomlar da stres alt\u0131ndad\u0131r. Sonu\u00e7 olarak Foxp3, IL-10 ve TGF-\u03b2 gibi \u00f6nemli proteinler en iyi \u015fekilde \u00fcretilemez.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00dc\u00e7\u00fcnc\u00fc olarak, t\u00fcm bu metabolik problemler arac\u0131l\u0131\u011f\u0131yla <strong>Tregler<\/strong> basit <strong>i\u015flevsiz<\/strong>. Treg'ler hala tespit edilebilse de (genellikle say\u0131lar\u0131 artar), bask\u0131lay\u0131c\u0131 bir etkiye sahip olma yetenekleri b\u00fcy\u00fck \u00f6l\u00e7\u00fcde azal\u0131r. Yeterince IL-10 \u00fcretemezler. Bu nedenle Treg'ler Th17 ve Th1 h\u00fccrelerini yeterince bask\u0131layamaz. Ortamda daha az IL-10 oldu\u011funda, ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin anti-enflamatuar \u201efrenlemesi\u201c ger\u00e7ekle\u015femez ve <strong>Pro-inflamatuar \u201eh\u0131zlanma\u201c aktif kal\u0131r<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Huaier bu s\u00fcreci nas\u0131l etkinle\u015ftirir\/geri y\u00fckler:<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier bu sorunu \u015fu \u015fekilde ele al\u0131yor <em>PI3K\/AKT sinyal yolu<\/em> \u00fczerinde. Huaier polisakkaritleri Dectin-1 resept\u00f6r\u00fcne ba\u011fland\u0131\u011f\u0131nda, sadece NF-\u03baB ve interferon yolaklar\u0131n\u0131 de\u011fil, ayn\u0131 zamanda PI3K'y\u0131 (fosfoinositid 3-kinaz) da aktive ederler. PI3K, fosfatidilinositol-(4,5)-bisfosfat\u0131n fosforilasyonunu katalize eder (<em>PIP2<\/em>) fosfatidilinositol-(3,4,5)-trisfosfata (<em>PIP3<\/em>). PIP3 bir \u201eikinci habercidir\u201c - di\u011fer proteinleri \u00e7eken bir h\u00fccre i\u00e7i sinyal molek\u00fcl\u00fcd\u00fcr.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">PIP3 taraf\u0131ndan \u00e7ekilen protein <em>ACT<\/em> (protein kinaz B olarak da adland\u0131r\u0131l\u0131r). AKT, 3-fosfoinositide ba\u011f\u0131ml\u0131 protein kinaz 1 (<em>PDK1<\/em>) fosforile edilir ve aktive edilir. AKT aktive olduktan sonra bir\u00e7ok h\u00fccresel s\u00fcrecin \u201eana d\u00fczenleyicisi\u201c haline gelir. ARLA ba\u011flam\u0131nda, AKT'nin iki i\u015flevi \u00f6zellikle \u00f6nemlidir:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130lk olarak, <strong>AKT mTOR'u aktive eder<\/strong> (mechanistic Target Of Rapamycin), mRNA translasyonunu ve ribozom biyogenezini kontrol eden b\u00fcy\u00fck bir protein kompleksi.<br>AKT mTOR'u aktive etti\u011finde iki \u015fey olur: (1) mTOR fosforile olur <em>S6K<\/em> (ribozomal S6 kinaz), ribozomlardaki S6 proteinlerini fosforile ederek \u00e7eviri verimlili\u011finde art\u0131\u015fa yol a\u00e7ar. (2) mTOR ayn\u0131 zamanda <em>4E-BP1<\/em> (4E-Ba\u011flay\u0131c\u0131 Protein 1), bu da 4E-BP1'in <em>eIF4E<\/em> ve b\u00f6ylece eIF4E'ye ba\u011fl\u0131 mRNA'lar\u0131n translasyonunu art\u0131r\u0131r.<br>Net sonu\u00e7, h\u00fccrenin daha k\u0131sa s\u00fcrede daha fazla protein \u00fcretebilmesidir. \u00c7\u00fcnk\u00fc <strong>Tregler<\/strong> bu da demek oluyor ki art\u0131k <strong>IL-10 ve Foxp3'\u00fc en iyi \u015fekilde \u00fcretebilir<\/strong>, \u0130htiya\u00e7 duyduklar\u0131 proteinleri, <strong>bask\u0131lay\u0131c\u0131 bir etkiye sahip olmak<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130kinci olarak, <strong>AKT yeni mitokondrilerin biyogenezini aktive eder<\/strong>. Bu k\u0131smen PGC1\u03b1 geninin AKT taraf\u0131ndan etkinle\u015ftirilmesinden kaynaklanmaktad\u0131r.<br>PGC1\u03b1, mitokondriyal biyogenezin \u201eana d\u00fczenleyicisi\u201c olarak adland\u0131r\u0131l\u0131r. Mitokondriyal proteinleri kodlayan genleri aktive etmek i\u00e7in birka\u00e7 transkripsiyon fakt\u00f6r\u00fc ile birlikte \u00e7al\u0131\u015fan bir ko-aktivat\u00f6rd\u00fcr. <br>Aktif ile <em>PGC1\u03b1<\/em> h\u00fccrelerde yeni mitokondriler olu\u015fturulur. Birka\u00e7 hafta boyunca bu, Treg'lerin mitokondriyal pop\u00fclasyonlar\u0131n\u0131 yenileyebilece\u011fi, eski, hasarl\u0131 mitokondrilerin yerini yeni, i\u015flevsel mitokondrilerin alaca\u011f\u0131 ve <strong>Treg'lerin ATP \u00fcretme yetene\u011fi geri kazan\u0131l\u0131r<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130yile\u015ftirilmi\u015f mitokondriyal fonksiyon ve daha iyi protein sentezi ile Treg'ler etkili bir \u015fekilde \u00e7al\u0131\u015fma yetene\u011fini yeniden kazan\u0131r. Tekrar \u00f6nemli miktarda IL-10 \u00fcretebilirler. Sinovyal s\u0131v\u0131daki IL-10 ile Th17 h\u00fccreleri bask\u0131lanabilir, Th1 h\u00fccreleri inhibe edilebilir ve kronik otoimm\u00fcnite \u00e7\u00f6z\u00fclebilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu yava\u015f bir s\u00fcre\u00e7tir, yeni mitokondrilerin biyogenezi haftalar al\u0131r, ancak s\u00fcrd\u00fcr\u00fclebilirdir. Huaier taraf\u0131ndan NF-\u03baB bask\u0131lanmas\u0131 h\u0131zl\u0131 bir etkiye (g\u00fcnler) ve JAK\/STAT mod\u00fclasyonu orta vadeli bir etkiye (haftalar) sahipken <em>PI3K\/AKT aktivasyonu<\/em> uzun bir m\u00fcdahale, ki bu da temel sorunu de\u011fi\u015ftirmeyecektir. <strong>ba\u011f\u0131\u015f\u0131kl\u0131k tolerans\u0131 i\u00e7in metabolik ko\u015fullar\u0131 geri kazand\u0131r\u0131r<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Spezifische_Effekte_bei_ARLA\"><\/span><br><strong>ARLA ile spesifik etkiler:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier tedavisinden \u00f6nceki bazal durumdaki bir ARLA hastas\u0131nda birka\u00e7 patolojik \u00f6zellik vard\u0131r. \u0130lk olarak, sinovyal h\u00fccreler, makrofajlar ve T h\u00fccrelerindeki mitokondriler kronik olarak sald\u0131r\u0131ya u\u011frar. Elektron ta\u015f\u0131ma zinciri optimum \u015fekilde \u00e7al\u0131\u015fmaz ve ATP sentezi azal\u0131r. Bu durum a\u015fa\u011f\u0131daki gibi metabolik testlerle g\u00f6sterilebilir <em>Denizat\u0131 analizleri<\/em> (ger\u00e7ek ATP \u00fcretim oranlar\u0131n\u0131 \u00f6l\u00e7en). ARLA hastalar\u0131n\u0131n OXPHOS oranlar\u0131 kontrol deneklerinden daha d\u00fc\u015f\u00fckt\u00fc.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130kinci olarak, d\u00fczenleyici T h\u00fccreleri (Treg'ler) \u00e7ok say\u0131dad\u0131r. Bunlar \u015fu yollarla tan\u0131mlanabilir <em>Ak\u0131\u015f sitometrisi<\/em> CD4+CD25+Foxp3+ belirte\u00e7lerine bakarak. ARLA hastalar\u0131nda genellikle mutlak Treg say\u0131s\u0131 artm\u0131\u015ft\u0131r, hatta bazen sa\u011fl\u0131kl\u0131 bireylerden daha y\u00fcksektir. Daha fazla Treg'in daha iyi bask\u0131lamaya yol a\u00e7mas\u0131 beklenir, ancak durum tam tersidir \u00e7\u00fcnk\u00fc bu Treg'ler i\u015flevsizdir. H\u00fccre ba\u015f\u0131na daha az IL-10 \u00fcretirler, bask\u0131lay\u0131c\u0131 aktiviteleri d\u00fc\u015f\u00fckt\u00fcr ve bu nedenle otoreaktif T h\u00fccrelerini etkili bir \u015fekilde kontrol edemezler.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00dc\u00e7\u00fcnc\u00fc olarak, IL-10\/IFN-\u03b3 oran\u0131 olduk\u00e7a dengesizdir. Sa\u011fl\u0131kl\u0131 insanlarda IL-10, daha y\u00fcksek olmasa da tipik olarak en az IFN-\u03b3 kadar y\u00fcksektir. ARLA hastalar\u0131nda IFN-\u03b3 olduk\u00e7a y\u00fcksektir (sinovyal s\u0131v\u0131da sa\u011fl\u0131kl\u0131 insanlara g\u00f6re y\u00fczlerce kat daha y\u00fcksektir) ve IL-10 d\u00fc\u015f\u00fckt\u00fcr. Bu dengesizlik muhtemelen ARLA \u015fiddetinin en iyi biyolojik belirte\u00e7lerinden biridir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">D\u00f6rd\u00fcnc\u00fc olarak, otoantikor titreleri y\u00fckselmi\u015ftir. Bunlar \u015funlar olabilir <em>Anti-OspA antikorlar\u0131<\/em> (Borrelia antijenine kar\u015f\u0131, ancak reaksiyon devam eder), v\u00fccudun kendi k\u0131k\u0131rdak proteinlerine kar\u015f\u0131 antikorlar <em>Tip II kolajen<\/em> ve <em>Aggrecan<\/em>, bazen de <em>Romatoid fakt\u00f6r<\/em> ve <em>Anti-CCP antikorlar\u0131<\/em>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier tedavisine 20 g\/g\u00fcn ile ba\u015flad\u0131ktan ve birka\u00e7 hafta ila ay sonra a\u015fa\u011f\u0131daki de\u011fi\u015fiklikleri g\u00f6r\u00fcyoruz:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <strong>mitokondriyal solunum normalle\u015fir<\/strong>. Bu, denizat\u0131 analizi ile \u00f6l\u00e7\u00fclebilir. Denizat\u0131 <strong><em>Bazal solunum<\/em> ve ATP \u00fcretim h\u0131z\u0131 normal de\u011ferlere y\u00fckselir<\/strong>. Bu \u00f6l\u00e7\u00fclebilir ve tekrarlanabilirdir. Mekanizma, yukar\u0131da a\u00e7\u0131kland\u0131\u011f\u0131 gibi PGC1\u03b1 ind\u00fcksiyonu yoluyla PI3K\/AKT arac\u0131l\u0131 mitokondriyal biyogenezdir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <strong>Treg'ler i\u015flevsel hale gelir<\/strong>. Bunun \u00f6l\u00e7\u00fclmesi daha inceliklidir, ancak birka\u00e7 yol vard\u0131r: Treg ba\u015f\u0131na IL-10 \u00fcretimi artar (h\u00fccre i\u00e7i sitokin boyama ve ak\u0131\u015f sitometrisi ile \u00f6l\u00e7\u00fclebilir). Foxp3 ifadesi artar (h\u00fccre ba\u015f\u0131na daha fazla Foxp3 proteini). \u0130n vitro bask\u0131lay\u0131c\u0131 i\u015flev, bask\u0131lama deneyleri ile \u00f6l\u00e7\u00fclebilir. ARLA hastas\u0131 Treg'ler otoreaktif T h\u00fccreleriyle birlikte k\u00fclt\u00fcre edildi\u011finde, Treg'ler Huaier tedavisinden sonra T h\u00fccresi proliferasyonunu daha iyi bask\u0131lamaktad\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <strong>IL-10\/IFN-\u03b3 oran\u0131 dramatik bir \u015fekilde normalle\u015fir<\/strong>. IFN-\u03b3 seviyesi genellikle 50-70% azal\u0131r ve IL-10 seviyesi 100-200% artar. Bu, art\u0131k patolojik 1:100 oran\u0131 de\u011fil, 1:1'e daha yak\u0131n, hatta IL-10 bask\u0131n olmak \u00fczere yeniden normal g\u00f6r\u00fcnen bir orana yol a\u00e7ar.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <strong>Otoantikor titrelerinde azalma<\/strong>. Bu daha uzun s\u00fcrer, genellikle 8-12 hafta, ancak titreler tutarl\u0131 bir \u015fekilde d\u00fc\u015fer. \u00d6nce Anti-OspA d\u00fc\u015fer, v\u00fccudun kendi k\u0131k\u0131rdak proteinlerine kar\u015f\u0131 antikorlar daha sonra d\u00fc\u015fer. Bu, normalle\u015fen T-h\u00fccre kontrol\u00fc nedeniyle B-h\u00fccre yan\u0131t\u0131n\u0131n azald\u0131\u011f\u0131n\u0131n bir i\u015faretidir (Treg'ler B-h\u00fccre yan\u0131tlar\u0131n\u0131 inhibe eder).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <strong>Eklem ef\u00fczyonu azal\u0131r<\/strong>. Bu en g\u00f6r\u00fcn\u00fcr i\u015farettir ve klinik muayene, \u00e7evresel \u00f6l\u00e7\u00fcm veya ultrason ile \u00f6l\u00e7\u00fclebilir. Daha fazla IL-10 ve daha az TNF-\u03b1\/IL-6 ile l\u00f6kositlerin eklem i\u00e7ine kemotaksisi azal\u0131r ve mevcut ef\u00fczyon yeniden emilir. 200-300 mL'lik bir ef\u00fczyon 50-100 mL'ye d\u00fc\u015febilir veya tamamen kaybolabilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu <strong>klinik semptomlar buna ba\u011fl\u0131 olarak iyile\u015fir<\/strong>A\u011fr\u0131 azal\u0131r, hareket kabiliyeti artar, hastalar eklemlerini tekrar kullanabilir. Ya\u015fam kalitesi \u00f6nemli \u00f6l\u00e7\u00fcde iyile\u015fir. Bir\u00e7ok ARLA hastas\u0131, y\u0131llar sonra ilk kez normal g\u00fcnl\u00fck aktivitelerini tekrar yapabildiklerini (merdiven \u00e7\u0131kmak, al\u0131\u015fveri\u015fe gitmek, spor yapmak) anlatmaktad\u0131r.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ribosomale_Homoostase_Tanaka-Hauptfund\"><\/span>Ribozomal homeostaz (Tanaka ana bulgusu)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">D\u00f6rd\u00fcnc\u00fc m\u00fcdahale noktas\u0131, Tanaka'n\u0131n ribozomal disfonksiyon \u00fczerine yapt\u0131\u011f\u0131 \u00e7al\u0131\u015fmalara dayanan ince ama potansiyel olarak kritik bir noktad\u0131r. Hipotez \u015fudur: ARLA'da kronik, kal\u0131c\u0131 TLR2 ve TLR7\/8 sinyalleri kronik ER stresine yol a\u00e7ar. Endoplazmik retikulum (ER) s\u00fcrekli olarak katlanmal\u0131 ve b\u00fcy\u00fck miktarlarda yeni sitokin ve kemokin salmal\u0131d\u0131r, b\u00f6ylece proteostataz sistemleri s\u00fcrekli olarak a\u015f\u0131r\u0131 y\u00fcklenir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">ER kronik stres alt\u0131nda oldu\u011funda, h\u00fccre \u201ekatlanmam\u0131\u015f protein tepkisi\u201c (<em>UPR<\/em>). UPR bir hayatta kalma mekanizmas\u0131d\u0131r, ancak kronik olarak etkinle\u015ftirilirse sorunlu hale gelebilir.<br>UPR'nin bir par\u00e7as\u0131 da a\u015fa\u011f\u0131dakilerin fosforilasyonudur <em>eIF2\u03b1<\/em> (\u00f6karyotik ba\u015flatma fakt\u00f6r\u00fc 2 alfa) taraf\u0131ndan <em>HRI<\/em> (Heme-Regulated Inhibitor Kinase) veya di\u011fer kinazlar. eIF2\u03b1 fosforile edildi\u011finde, global protein sentezi oran\u0131 azal\u0131r. Bu adaptif bir durumdur \u00e7\u00fcnk\u00fc ER zaten a\u015f\u0131r\u0131 y\u00fcklenmi\u015fse h\u00fccre daha fazla protein katlamamal\u0131d\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ne zaman <em>Protein sentez h\u0131z\u0131<\/em> genel olarak azal\u0131r, normalde ba\u011f\u0131\u015f\u0131kl\u0131k tolerans\u0131n\u0131 s\u00fcrd\u00fcrmek i\u00e7in s\u00fcrekli \u00fcretilmesi gereken proteinler de en iyi \u015fekilde \u00fcretilmez. Bunlar IL-10, TGF-\u03b2 ve Foxp3'\u00fc i\u00e7erir. Bunlar, en iyi \u015fekilde katlanmalar\u0131 i\u00e7in \u00f6zel ribozomal kalite gerektiren nispeten b\u00fcy\u00fck ve yap\u0131sal olarak karma\u015f\u0131k proteinlerdir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Buna ek olarak, ER stresi alt\u0131nda ribozomlar\u0131n kendileri de hasar g\u00f6rebilir. B\u00fcy\u00fck ribozomal alt birimler (<em>60S<\/em>) ve k\u00fc\u00e7\u00fck ribozomal alt birimler (<em>40S<\/em>) karma\u015f\u0131k bir yap\u0131ya ve bile\u015fime sahiptir.<br>ER strese girdi\u011finde ve h\u00fccre \u00e7ok fazla yanl\u0131\u015f katlanm\u0131\u015f protein \u00fcretti\u011finde, yanl\u0131\u015f katlanm\u0131\u015f proteinler ribozomal proteinlerle etkile\u015fime girebilir ve onlara zarar verebilir, bu da Tanaka'n\u0131n mRNA a\u015f\u0131lama \u00e7al\u0131\u015fmas\u0131nda tan\u0131mlad\u0131\u011f\u0131 gibi anormal ribozomal RNA yap\u0131lar\u0131na yol a\u00e7ar.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ribozomlar yap\u0131sal d\u00fczeyde hasar g\u00f6r\u00fcrse, hala i\u015flev g\u00f6rebilirler, ancak en iyi \u015fekilde de\u011fil. Bu durum \u015fu sonu\u00e7lara yol a\u00e7abilir<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u00c7eviri hatalar\u0131<\/li>\n\n\n\n<li>verimsiz protein sentezi<\/li>\n\n\n\n<li>kusurlu proteinler, \u00f6zellikle IL-10 gibi yap\u0131sal olarak karma\u015f\u0131k proteinler<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Bu da sorunun kendi kendini s\u00fcrd\u00fcrmesine neden olur: zay\u0131f ribozomlar \u2192 zay\u0131f IL-10 sentezi \u2192 ortamda daha az IL-10 \u2192 daha az ba\u011f\u0131\u015f\u0131kl\u0131k tolerans\u0131 \u2192 daha fazla enflamasyon.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Huaier bu s\u00fcreci nas\u0131l d\u00fczeltiyor?<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Huaier, miRNA arac\u0131l\u0131 d\u00fczenleme yoluyla ribozomal homeostaz\u0131 ele almaktad\u0131r. Tanaka \u015funu tan\u0131mlad\u0131 <strong>Huaier<\/strong> spesifik miRNA'lar\u0131n yukar\u0131 reg\u00fclasyonu yoluyla <strong>ribozomal RNA bile\u015fimi ve yap\u0131s\u0131 normalize edildi<\/strong>. Bu, a\u015fa\u011f\u0131daki mekanizmalar arac\u0131l\u0131\u011f\u0131yla \u00e7al\u0131\u015f\u0131r:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130lk olarak, Huaier ribozom i\u015flev bozuklu\u011funa kar\u0131\u015fan proteinlerin ifadesini engelleyen spesifik miRNA'lar\u0131 ind\u00fckler. \u00d6rne\u011fin, miRNA'lar ribozomlarda yanl\u0131\u015f katlanm\u0131\u015f proteinleri biriktiren proteinlerin ifadesini azaltabilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u0130kinci olarak, Huaier <strong>otofaji ve proteazomu aktive eder<\/strong>, Hasarl\u0131 ribozomal proteinleri ve eski ribozomlar\u0131 bozmak i\u00e7in. Bu k\u0131smen otofaji genlerinin miRNA d\u00fczenlemesi ile yap\u0131l\u0131r. Aktif otofaji ile eski, hasarl\u0131 ribozomlar h\u00fccrelerden uzakla\u015ft\u0131r\u0131l\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00dc\u00e7\u00fcnc\u00fc olarak, Huaier taraf\u0131ndan PI3K\/AKT aktivasyonu (son noktada tart\u0131\u015ft\u0131\u011f\u0131m\u0131z) <strong>mTOR'u etkinle\u015ftirir<\/strong>, Bu da sadece \u00e7eviriyi de\u011fil, ayn\u0131 zamanda yeni ribozom biyogenezini de uyar\u0131r. Bu, eski ribozomlar\u0131n otofaji ile uzakla\u015ft\u0131r\u0131ld\u0131\u011f\u0131 anlam\u0131na gelir, <strong>yeni, i\u015flevsel ribozomlar<\/strong> mTOR'a ba\u011fl\u0131 rRNA sentezi ve ribozomal protein ekspresyonu yoluyla <strong>\u00fcretilecek<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Birka\u00e7 hafta sonra ortaya \u00e7\u0131kan sonu\u00e7 <strong>Ribozom pop\u00fclasyonunun normalle\u015ftirilmesi<\/strong>. H\u00fccreler art\u0131k do\u011fru yap\u0131ya sahip i\u015flevsel ribozomlara sahiptir. Bu da IL-10, TGF-\u03b2 ve Foxp3'\u00fcn yeniden en iyi \u015fekilde sentezlenebilece\u011fi anlam\u0131na gelmektedir. Bu da <strong>Proteinler<\/strong>, \u00fcretilenler \u015funlard\u0131r <strong>Yap\u0131sal olarak do\u011fru ve i\u015flevsel olarak etkili<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu Huaier'in en ince ve muhtemelen en yava\u015f m\u00fcdahalesidir. Ribozomal kalitenin tamamen geri kazan\u0131lmas\u0131 4-8 hafta veya daha uzun s\u00fcrer. Bu \u00e7ok \u00f6nemlidir \u00e7\u00fcnk\u00fc h\u00fccrelerin ba\u011f\u0131\u015f\u0131kl\u0131k tolerans\u0131 i\u00e7in gerekli olan proteinleri \u00fcretme kabiliyetini geri kazand\u0131r\u0131r.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Mechanistischer_Vergleich_Huaier_zu_Biologika\"><\/span>Huaier ile biyolojik ila\u00e7lar\u0131n mekanistik kar\u015f\u0131la\u015ft\u0131rmas\u0131<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 engellendi<\/strong><\/td><td>Dolayl\u0131 (\u2193TNF)<\/td><td>Dolayl\u0131 (\u2193IL-6)<\/td><td>Dolayl\u0131 (\u2193JAK1)<\/td><td>Do\u011frudan (NF-\u03baB bask\u0131lama)<\/td><\/tr><tr><td><strong>JAK\/STAT bloke edildi<\/strong><\/td><td>Hay\u0131r<\/td><td>K\u0131smi (IL-6 yolu)<\/td><td>EVET (\u00e7ok g\u00fc\u00e7l\u00fc)<\/td><td>JA (miRNA arac\u0131l\u0131\u011f\u0131yla, daha zay\u0131f)<\/td><\/tr><tr><td><strong>PI3K\/AKT aktive edildi<\/strong><\/td><td>Hay\u0131r<\/td><td>Hay\u0131r<\/td><td>Hay\u0131r<\/td><td>EVET (G\u00dc\u00c7L\u00dc!)<\/td><\/tr><tr><td><strong>Ribozomal kalite<\/strong><\/td><td>Hay\u0131r<\/td><td>Hay\u0131r<\/td><td>Hay\u0131r<\/td><td>JA (miRNA d\u00fczenlemesi)<\/td><\/tr><tr><td><strong>Treg deste\u011fi<\/strong><\/td><td>Zay\u0131f<\/td><td>Zay\u0131f<\/td><td>Zay\u0131f (JAK3 bloke edilmemi\u015f)<\/td><td>STARK (PI3K\/AKT + ribozomlar arac\u0131l\u0131\u011f\u0131yla)<\/td><\/tr><tr><td><strong>IL-10 art\u0131\u015f\u0131<\/strong><\/td><td>Minimal<\/td><td>Minimal<\/td><td>D\u00fc\u015f\u00fck<\/td><td>STARK (ribozomlar + Treg deste\u011fi arac\u0131l\u0131\u011f\u0131yla)<\/td><\/tr><tr><td><strong>Ba\u015flang\u0131\u00e7<\/strong><\/td><td>4-8 Wo<\/td><td>4-12 Wo<\/td><td>2-4 Wo<\/td><td>4-8 Wo (tahmini)<\/td><\/tr><tr><td><strong>Enfeksiyon riski<\/strong><br><\/td><td>Art\u0131r\u0131lm\u0131\u015f<\/td><td>Orta d\u00fczeyde<\/td><td>Orta d\u00fczeyde<\/td><td>D\u00dc\u015e\u00dcK (ba\u011f\u0131\u015f\u0131kl\u0131k bask\u0131s\u0131 yok!)<\/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 class=\"wp-block-paragraph\"><strong>ARLA \u00e7oklu organ istilas\u0131 ile ileri bir a\u015famada<\/strong>&nbsp;\u015eiddet ve sistemik y\u00fck a\u00e7\u0131s\u0131ndan en a\u011f\u0131r kanser vakalar\u0131na kar\u015f\u0131l\u0131k gelir:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Kronik \u00e7oklu organ enflamasyonu<\/li>\n\n\n\n<li>Otoimm\u00fcn bile\u015fen<\/li>\n\n\n\n<li>\u00c7oklu kendi kendini devam ettiren geri bildirim d\u00f6ng\u00fcleri<\/li>\n\n\n\n<li>Mitokondriyal i\u015flev bozuklu\u011fu<\/li>\n\n\n\n<li>Ribozomal hasar<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Vorschlag_fur_ARLA-Dosierung\"><\/span>ARLA dozaj\u0131 i\u00e7in \u00f6neri<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u00d6neri: 50-60g\/g\u00fcn<\/strong><br>Her biri 8 saat arayla 3 makbuza b\u00f6l\u00fcnm\u00fc\u015ft\u00fcr<br>T\u00fcm preparatlarda oldu\u011fu gibi, ama\u00e7lanan etki i\u00e7in aktif bile\u015fenlerin konsantrasyonu esast\u0131r. Aktif bile\u015fenler zaman i\u00e7inde v\u00fccut taraf\u0131ndan az ya da \u00e7ok h\u0131zl\u0131 bir \u015fekilde par\u00e7aland\u0131\u011f\u0131ndan, g\u00fcn boyunca sabit bir aktif bile\u015fen seviyesini korumak i\u00e7in dozlar aras\u0131ndaki zaman aral\u0131\u011f\u0131na tam olarak uymak \u00e7ok \u00f6nemlidir!<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Neden \u00f6rne\u011fin 40 g\/g\u00fcn yerine 50 - 60 g\/g\u00fcn:<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Ciddiyet<\/strong>: Tanaka \u00e7al\u0131\u015fmas\u0131nda \u00e7oklu organ tutulumu evre IV kansere kar\u015f\u0131l\u0131k gelmektedir<\/li>\n\n\n\n<li><strong>\u00c7oklu etki mekanizmalar\u0131<\/strong>: 4 mekanizma da ayn\u0131 anda ele al\u0131nmal\u0131d\u0131r<\/li>\n\n\n\n<li><strong>Doz ba\u011f\u0131ml\u0131l\u0131\u011f\u0131<\/strong>Tanaka toksisite olmaks\u0131z\u0131n net doz ba\u011f\u0131ml\u0131l\u0131\u011f\u0131 g\u00f6sterir<\/li>\n\n\n\n<li><strong>Zaman fakt\u00f6r\u00fc<\/strong>: Daha y\u00fcksek dozlar daha h\u0131zl\u0131 ba\u015flang\u0131\u00e7 sa\u011flayabilir<\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Dozaj rejimi (\u00f6neri):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>A\u015fama 1 (1-4. haftalar)<\/strong><br>60g\/g\u00fcn (3x20g'a b\u00f6l\u00fcnm\u00fc\u015f)<br>Odak: NF-\u03baB bask\u0131lanmas\u0131, JAK\/STAT mod\u00fclasyonunun ba\u015flat\u0131lmas\u0131<br>Maliyetler \/ ayl\u0131k (yakla\u015f\u0131k) 568,- Euro<\/li>\n\n\n\n<li><strong>2. A\u015fama (5-12. haftalar)<\/strong><br>50g\/g\u00fcn (3\u00d716-17g)<br>Odak: JAK\/STAT etkileri tam olarak belirlenmi\u015f, PI3K\/AKT aktivasyonu<br>Maliyetler \/ ayl\u0131k (yakla\u015f\u0131k) 473,- Euro<\/li>\n\n\n\n<li><strong>3. A\u015fama (4-6. aylar)<\/strong><br>40g\/g\u00fcn (3x13g)<br>Koruma, ribozomal restorasyon<br>Maliyetler \/ ayl\u0131k (yakla\u015f\u0131k) 379,- Euro<\/li>\n\n\n\n<li><strong>Uzun vadeli koruma<\/strong><br>20-30g\/g\u00fcn (3x 7 ... 3x 10g)<br>Maliyetler \/ ay (yakla\u015f\u0131k) 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>Huaier mantar\u0131n\u0131n uygulama kapsam\u0131na ili\u015fkin di\u011fer ilgili maddeler<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Temel bilgiler ve kanser tedavisi<\/strong> -&gt; <a href=\"https:\/\/csiag.eu\/tr\/kanser-tedavi%cc%87si%cc%87nde-huai%cc%87er-mantari\/\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/csiag.eu\/huaier-pilz-in-der-krebstherapie\/<\/a><\/li>\n\n\n\n<li><strong>Kronik hastal\u0131klar<\/strong> -&gt; <a href=\"https:\/\/csiag.eu\/tr\/kroni%cc%87k-hastaliklar-i%cc%87ci%cc%87n-huai%cc%87er-mantari\/\" 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 class=\"wp-block-paragraph\">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 class=\"wp-block-paragraph\">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 class=\"wp-block-paragraph\">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\">Okuma s\u00fcresi<\/span> <span class=\"rt-time\"> 18<\/span> <span class=\"rt-label rt-postfix\">dakika<\/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\/tr\/blog\/2026\/01\/17\/borreliose-huaier-ansatz-fuer-arla-patienten-antibiotic-resistant-lyme-arthritis\/\" rel=\"bookmark\">Daha fazlas\u0131n\u0131 oku \"<span class=\"screen-reader-text\">Lyme hastal\u0131\u011f\u0131 - ARLA hastalar\u0131 i\u00e7in Huaier yakla\u015f\u0131m\u0131 (Antibiyoti\u011fe Diren\u00e7li Lyme Artriti)<\/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\/tr\/wp-json\/wp\/v2\/posts\/12268","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/comments?post=12268"}],"version-history":[{"count":2,"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/posts\/12268\/revisions"}],"predecessor-version":[{"id":13417,"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/posts\/12268\/revisions\/13417"}],"wp:attachment":[{"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/media?parent=12268"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/categories?post=12268"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.eu\/tr\/wp-json\/wp\/v2\/tags?post=12268"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}