{"id":6568,"date":"2024-08-06T12:34:37","date_gmt":"2024-08-06T12:34:37","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=6568"},"modified":"2024-08-06T12:34:37","modified_gmt":"2024-08-06T12:34:37","slug":"mtor-signaling-pathway","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/tr\/mtor-sinyal-yolagi\/","title":{"rendered":"\u00dclseratif kolit farelerinde SIRT3\/AMPK\/mTOR sinyal yola\u011f\u0131n\u0131 d\u00fczenleyen magnolol\u00fcn Th17\/Treg ba\u011f\u0131\u015f\u0131kl\u0131k dengesi \u00fczerindeki etkisi"},"content":{"rendered":"

\u00dclseratif kolit farelerinde SIRT3\/AMPK\/mTOR sinyal yola\u011f\u0131n\u0131 d\u00fczenleyen magnolol\u00fcn Th17\/Treg ba\u011f\u0131\u015f\u0131kl\u0131k dengesi \u00fczerindeki etkisi
\n\u00dclseratif kolit (\u00dcK), ba\u011f\u0131rsak mikrobiyotas\u0131n\u0131n disbiyozu ile ili\u015fkili kronik inflamatuar bir ba\u011f\u0131rsak hastal\u0131\u011f\u0131d\u0131r. G\u00fcn\u00fcm\u00fczde, ila\u00e7 tedavisi (5-aminosalisilik asit, kortikosteroidler, imm\u00fcnosupresanlar, biyolojikler ve probiyotikler dahil) semptomlar\u0131 hafifletebilse de, bu tedaviler y\u00fcksek n\u00fcks oranlar\u0131 ve ka\u00e7\u0131n\u0131lmaz yan etkiler (bulant\u0131, kusma, kemik ili\u011fi bask\u0131lanmas\u0131, enfeksiyon ve kanser riski gibi) ile s\u0131n\u0131rl\u0131d\u0131r. Bu nedenle, \u00dcK i\u00e7in yeni ve etkili tedavilerin geli\u015ftirilmesine acil ihtiya\u00e7 vard\u0131r. Genetik fakt\u00f6rler, ba\u011f\u0131rsak ortam\u0131, ba\u011f\u0131\u015f\u0131kl\u0131k yan\u0131t\u0131, h\u00fccre apoptozu ve enfeksiyon \u00dcK ile ili\u015fkilidir. Raporlara g\u00f6re, UC hastalar\u0131 ba\u011f\u0131rsak mikrobiyotas\u0131nda bozulma sergileyerek ba\u011f\u0131rsak epitel h\u00fccre bariyerinin ge\u00e7irgenli\u011finin artmas\u0131na ve ba\u011f\u0131rsak enflamatuar yan\u0131tlar\u0131n\u0131n tetiklenmesine yol a\u00e7maktad\u0131r; UC'nin ilerlemesinde ise genellikle enflamasyona neden olan T helper 17 h\u00fccreleri (Th17) artarken, enflamasyonu engelleyen d\u00fczenleyici T h\u00fccreleri (Treg) azalmaktad\u0131r. Ba\u011f\u0131rsak mikrobiyotas\u0131n\u0131 mod\u00fcle ederek Th17\/Treg dengesini d\u00fczenlemek UC'yi tedavi edebilir. Bu nedenle, Th17\/Treg dengesinin d\u00fczenlenmesi \u00dcK tedavisi i\u00e7in \u00f6nemli bir hedef haline gelmi\u015ftir.<\/p>\n

Osmanthus \u00f6z\u00fc, krizantem, biber ve perilla gibi \u00e7e\u015fitli bitkilerde yayg\u0131n olarak bulunan do\u011fal bir \u00fcr\u00fcnd\u00fcr. Anti-enflamatuar, antioksidan, anti-t\u00fcm\u00f6r ve antiviral etkilere sahiptir. Giderek daha fazla kan\u0131t, magnolol\u00fcn TNF - \u03b1 ve IL-6 gibi pro-inflamatuar sitokinlerin salg\u0131lanmas\u0131n\u0131 azaltabilece\u011fini ve b\u00f6ylece inflamatuar yan\u0131tlar\u0131 inhibe edebilece\u011fini g\u00f6stermektedir. UC dahil olmak \u00fczere inflamasyonla ilgili hastal\u0131klar\u0131n tedavisinde uygulanm\u0131\u015ft\u0131r. Raporlara g\u00f6re, luteolin ba\u011f\u0131rsak mikrobiyotas\u0131 \u00fczerinde d\u00fczenleyici bir etkiye sahiptir ve ba\u011f\u0131rsak mikrobiyotas\u0131n\u0131n bile\u015fimini ve yap\u0131s\u0131n\u0131 ayarlayarak \u00dcK tedavisinde etkili bir etkiye sahip olabilir. Bununla birlikte, magnolol\u00fcn UC'de Th17\/Treg dengesini d\u00fczenleyip d\u00fczenleyemeyece\u011fi hala belirsizdir.<\/p>\n

Treg ve Th17 aras\u0131ndaki dinamik denge, aralar\u0131nda AMP aktive protein kinaz (AMPK)\/mammalian target of rapamycin (mTOR) sinyal yolunun \u00f6nemli d\u00fczenleyici yollar\u0131ndan biri oldu\u011fu \u00e7oklu sinyal yollar\u0131yla d\u00fczenlenir. Ara\u015ft\u0131rmalar, AMPK'n\u0131n fosforilasyon seviyesini art\u0131rarak ve mTOR'un fosforilasyon seviyesini azaltarak, insan Th17\/Treg h\u00fccre farkl\u0131la\u015fmas\u0131n\u0131n d\u00fczenlenebilece\u011fini ve bu etkinin AMPK sinyal inhibit\u00f6r\u00fc Compound C taraf\u0131ndan engellenebilece\u011fini g\u00f6stermi\u015ftir; Dekstran s\u00fclfat sodyum (DSS) ile ind\u00fcklenen UC s\u0131\u00e7an modelinde, geli\u015fmi\u015f AMPK fosforilasyonu, mTOR ekspresyonunu ve \u00e7e\u015fitli inflamatuar sitokinlerin seviyelerini azaltarak Th17 h\u00fccre farkl\u0131la\u015fmas\u0131n\u0131n azalmas\u0131na yol a\u00e7abilir. Sessiz bilgi d\u00fczenleyicisi 3 (SIRT3), kolon t\u00fcm\u00f6rigenezi s\u0131ras\u0131nda ba\u011f\u0131rsak mikrobiyotas\u0131 ile etkile\u015fime giren bir anti-enflamatuar ve t\u00fcm\u00f6r bask\u0131lay\u0131c\u0131 gendir. SIRT3 eksikli\u011fi olan farelerin kolit ve t\u00fcm\u00f6r geli\u015fimine kar\u015f\u0131 olduk\u00e7a hassas oldu\u011fu bildirilmi\u015ftir. \u0130pucu: SIRT3, UC'nin ilerlemesi ile ili\u015fkili olabilir. Bu arada, SIRT3 ayn\u0131 zamanda AMPK\/mTOR yolunun yukar\u0131 y\u00f6nl\u00fc bir d\u00fczenleyicisidir ve a\u015f\u0131r\u0131 ekspresyonu AMPK fosforilasyonunu yukar\u0131 ve mTOR fosforilasyonunu a\u015fa\u011f\u0131 do\u011fru d\u00fczenleyerek inflamasyonu inhibe edebilir. Yak\u0131n zamanda yap\u0131lan bir \u00e7al\u0131\u015fmada magnolol\u00fcn SIRT3 ekspresyonunu art\u0131rabildi\u011fi ve SIRT3\/AMPK\/mTOR sinyal yolunu d\u00fczenleyerek serebral iskemi-reperf\u00fczyon hasar\u0131n\u0131 \u00f6nleyebildi\u011fi g\u00f6sterilmi\u015ftir. Bu nedenle, bu \u00e7al\u0131\u015fma magnolol\u00fcn UC \u00fczerindeki koruyucu etkisinin Th17\/Treg ba\u011f\u0131\u015f\u0131kl\u0131k dengesi ile ili\u015fkili olup olmad\u0131\u011f\u0131n\u0131 ara\u015ft\u0131rmay\u0131 ve magnolol\u00fcn UC \u00fczerindeki koruyucu etkisini a\u00e7\u0131kl\u0131\u011fa kavu\u015fturmak ve UC tedavisi ve magnolol uygulamas\u0131 i\u00e7in referans sa\u011flamak amac\u0131yla mekanizmas\u0131n\u0131 analiz etmeyi ama\u00e7lamaktad\u0131r.<\/p>\n

\"\"\"\"\"\"\"\"\"\"\"\"\"\"\"\"Son y\u0131llarda, geleneksel \u00c7in t\u0131bb\u0131 \u00dcK tedavisi i\u00e7in yayg\u0131n olarak kullan\u0131lmaktad\u0131r. Giderek artan say\u0131da \u00e7al\u0131\u015fma, geleneksel \u00c7in t\u0131bb\u0131n\u0131n \u00dcK tedavisi s\u0131ras\u0131nda ba\u011f\u0131rsak mikrobiyotas\u0131n\u0131n d\u00fczenlenmesinde \u00f6nemli bir rol oynad\u0131\u011f\u0131n\u0131 g\u00f6stermektedir. Osmanthus fragrans en kapsaml\u0131 \u015fekilde \u00e7al\u0131\u015f\u0131lm\u0131\u015f biyoflavonoidlerden biridir. Flavonoidler d\u00fc\u015f\u00fck toksisiteye sahip do\u011fal bile\u015fiklerdir ve \u015fimdiye kadar kullan\u0131mlar\u0131 ciddi yan etkilerle kaydedilmemi\u015ftir, bu da onlar\u0131 olduk\u00e7a g\u00fcvenli k\u0131lmaktad\u0131r. Bu \u00e7al\u0131\u015fmada, magnolol\u00fcn DSS ile ind\u00fcklenen UC \u00fczerindeki etkisi in vivo olarak ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Sonu\u00e7lar\u0131m\u0131z magnolol\u00fcn \u00dcK \u00fczerinde \u00f6nemli bir etkiye sahip oldu\u011funu g\u00f6stermektedir; bu etki kilo kayb\u0131, DAI skoru, mukozal nekrozun azalmas\u0131 ve inflamatuar h\u00fccrelerin infiltrasyonu ile g\u00f6sterilebilir. Bu, magnolol\u00fcn \u00dcK \u00fczerindeki koruyucu etkisini bir kez daha do\u011frulayan \u00f6nceki ara\u015ft\u0131rmalarla tutarl\u0131d\u0131r.
\n\u00d6nceki \u00e7al\u0131\u015fmalar, luteolinin T h\u00fccresi arac\u0131l\u0131 otoimm\u00fcn hastal\u0131klarda Th17 yan\u0131t\u0131n\u0131 inhibe edebilece\u011fini; ve CD4+CD25-'i Treg h\u00fccrelerine d\u00f6n\u00fc\u015fmeye te\u015fvik ederek anti-enflamatuar etkiler g\u00f6sterebilece\u011fini g\u00f6stermi\u015ftir. Ayr\u0131ca luteolinin UC model farelerde TNF - \u03b1, IL-1 \u03b2, IL-6 ve IL-17 gibi pro-inflamatuar sitokinlerin \u00fcretimini inhibe edebilece\u011fi; Osmanthus t\u00fcrevlerinin Th1, Th2 ve Th17 h\u00fccrelerinin seviyelerini azaltarak DSS ile ind\u00fcklenen UC modellerinde in vivo koruyucu etkiler g\u00f6sterebilece\u011fi bildirilmi\u015ftir. Ayr\u0131ca magnolol\u00fcn \u00dcK'nin ilerlemesinin alt\u0131nda yatan \u00f6nemli mekanizmalardan biri olan Th17\/Treg dengesi \u00fczerindeki etkisini ara\u015ft\u0131rd\u0131k. Bu \u00e7al\u0131\u015fmada, UC farelerinin dalak lenfositlerinde Treg h\u00fccrelerinin y\u00fczdesinde anlaml\u0131 bir azalma ve Th17 h\u00fccrelerinin y\u00fczdesinde anlaml\u0131 bir art\u0131\u015f bulduk. UC farelerinde Th17\/Treg oran\u0131 ciddi \u015fekilde dengesizdir. Dalak \u00f6nemli bir ba\u011f\u0131\u015f\u0131kl\u0131k organ\u0131d\u0131r ve DSS UC farelerinde ba\u011f\u0131\u015f\u0131kl\u0131k fonksiyon bozuklu\u011funa neden olarak telafi edici splenomegaliye yol a\u00e7abilir; luteolin dalak indeksini azaltabilir ve farelerde DSS kaynakl\u0131 koliti hafifletebilir. Bu \u00e7al\u0131\u015fma ayr\u0131ca UC farelerinin dalak lenfositlerindeki \u00f6nemli Th17\/Treg dengesizli\u011fini do\u011frulamaktad\u0131r ki bu da insan UC'si ile tutarl\u0131d\u0131r.
\nTh17 h\u00fccrelerinin farkl\u0131la\u015fma s\u00fcrecine ROR \u03b3 t'nin transkripsiyonel d\u00fczenlemesi arac\u0131l\u0131k eder. Th17 h\u00fccreleri, UC'nin ilerlemesine katk\u0131da bulunan IL-17, IL-21, IL-22, IL-23 ve IL-25 dahil olmak \u00fczere pro-enflamatuar sitokinler \u00fcretir. Treg'lerin farkl\u0131la\u015fmas\u0131 Foxp3 taraf\u0131ndan d\u00fczenlenir ve olgun Treg'ler y\u00fcksek d\u00fczeyde Foxp3 ifade eder. Ayr\u0131ca Treg'ler IL-10, IL-35 ve TGF - \u03b2 gibi inhibit\u00f6r sitokinler salg\u0131layarak adaptif ve do\u011fal imm\u00fcn yan\u0131tlar\u0131 bask\u0131layabilir. Ara\u015ft\u0131rmalar, artan Th17 h\u00fccrelerinin y\u00fcksek d\u00fczeyde IL-17 ve IL-23 \u00fcretti\u011fini ve b\u00f6ylece enflamasyonu te\u015fvik etti\u011fini g\u00f6stermi\u015ftir. Bununla birlikte, Treg'in farkl\u0131la\u015fmas\u0131 engellenerek IL-10 da dahil olmak \u00fczere imm\u00fcnosupresif sitokinlerde azalmaya yol a\u00e7ar. Th17\/Treg dengesizli\u011finin iyile\u015ftirilmesi, ba\u011f\u0131rsak ba\u011f\u0131\u015f\u0131kl\u0131k homeostaz\u0131n\u0131n yeniden olu\u015fturulmas\u0131na ve UC'nin azalt\u0131lmas\u0131na yard\u0131mc\u0131 olabilir. Bu \u00e7al\u0131\u015fma, luteolin grubunda anti-inflamatuar sitokin IL-10'un artt\u0131\u011f\u0131n\u0131 ve pro-inflamatuar sitokinler IL-6, IL-17 ve IL-23'\u00fcn azald\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015ftir; Tip: Magnolol m\u00fcdahalesi, \u00f6nceki \u00e7al\u0131\u015fmalarla tutarl\u0131 olarak, DSS ile ind\u00fcklenen UC modelinde Th17\/Treg dengesizli\u011fini iyile\u015ftirmi\u015ftir; Ayr\u0131ca, ileri analizler magnolol\u00fcn UC farelerinde ROR \u03b3 t'yi \u00f6nemli \u00f6l\u00e7\u00fcde a\u015fa\u011f\u0131 reg\u00fcle etti\u011fini ve Foxp3'\u00fc yukar\u0131 reg\u00fcle etti\u011fini g\u00f6stermi\u015ftir. ROR \u03b3 t ile Th17 h\u00fccre farkl\u0131la\u015fmas\u0131 aras\u0131ndaki pozitif korelasyon ve Foxp3 ile Treg h\u00fccre farkl\u0131la\u015fmas\u0131 aras\u0131ndaki pozitif korelasyon nedeniyle, ara\u015ft\u0131rma sonu\u00e7lar\u0131m\u0131z magnolol\u00fcn Th17\/Treg h\u00fccre farkl\u0131la\u015fmas\u0131 dengesine katk\u0131da bulundu\u011funu g\u00f6stermektedir.
\nTh17\/Treg h\u00fccre farkl\u0131la\u015fmas\u0131, AMPK ve mTOR olmak \u00fczere iki ana besin alg\u0131lama yolu taraf\u0131ndan d\u00fczenlenir. SIRT3, otofajiyi te\u015fvik etmek i\u00e7in AMPK\/mTOR yolunu aktive etti\u011fi g\u00f6sterilen etkili bir deasetilazd\u0131r, SIRT3 eksikli\u011fi ise AMPK\/mTOR yolunu inhibe edebilir. Bu \u00e7al\u0131\u015fmada, UC farelerinin kolon dokusundaki SIRT3 protein seviyelerinin ve p-AMPK\/AMPK oran\u0131n\u0131n normal farelerinkinden \u00f6nemli \u00f6l\u00e7\u00fcde d\u00fc\u015f\u00fck oldu\u011funu, p-mTOR\/mTOR oran\u0131n\u0131n ise normal farelerinkinden \u00f6nemli \u00f6l\u00e7\u00fcde y\u00fcksek oldu\u011funu g\u00f6zlemledik, bu da UC farelerinde SIRT3 eksikli\u011fine ve AMPK aktivasyonunun inhibisyonuna i\u015faret etmektedir. Osmanthus fragrans, susturucu d\u00fczenleyici proteinlerin ifadesini mod\u00fcle ederek AMPK aktivitesini d\u00fczenleyebilir. Liu ve arkada\u015flar\u0131n\u0131n \u00e7al\u0131\u015fmas\u0131 magnolol\u00fcn SIRT3 transd\u00fcksiyonunu art\u0131rabildi\u011fini, SIRT3\/AMPK\/mTOR yolunu aktive edebildi\u011fini ve serebral iskemik hasar\u0131 hafifletebildi\u011fini g\u00f6stermi\u015ftir. Bu nedenle, magnolol\u00fcn UC farelerinde Th17\/Treg dengesi \u00fczerindeki etkisinin SIRT3\/AMPK\/mTOR yola\u011f\u0131 ile ili\u015fkili olabilece\u011fini d\u00fc\u015f\u00fcn\u00fcyoruz. Western blot sonu\u00e7lar\u0131 magnolol\u00fcn UC farelerinin kolon dokusunda SIRT3 protein seviyesini art\u0131rabildi\u011fini, AMPK fosforilasyon seviyesini y\u00fckseltebildi\u011fini ve mTOR fosforilasyon seviyesini d\u00fc\u015f\u00fcrebildi\u011fini g\u00f6stermi\u015ftir ki bu da hipotezimizi do\u011frulamaktad\u0131r. 3-TYP, SIRT3'\u00fcn se\u00e7ici bir inhibit\u00f6r\u00fcd\u00fcr ve SIRT3 ekspresyonunu inhibe etti\u011fi bildirilmi\u015ftir. Bu \u00e7al\u0131\u015fmada, magnolol\u00fcn UC fareleri \u00fczerindeki koruyucu mekanizmas\u0131n\u0131 daha da netle\u015ftirmek i\u00e7in, magnolol m\u00fcdahalesini 3-TYP ile birle\u015ftirdik. Sonu\u00e7lar, 3-TYP'nin AMPK aktivasyonunu \u00f6nemli \u00f6l\u00e7\u00fcde inhibe edebilece\u011fini ve magnolol\u00fcn UC farelerinde Th17\/Treg h\u00fccrelerinin farkl\u0131la\u015fma dengesi \u00fczerindeki etkisini \u00f6nemli \u00f6l\u00e7\u00fcde zay\u0131flatabilece\u011fini g\u00f6sterdi. \u0130pucu: Osmanthus \u00f6z\u00fct\u00fc, SIRT3\/AMPK\/mTOR yolunu aktive ederek UC farelerinde Th17\/Treg dengesini destekleyebilir.
\n\u00d6zetle, magnolol DSS ile ind\u00fcklenen UC fare modellerinde Th17\/Treg dengesizli\u011fini iyile\u015ftirebilir ve etki mekanizmas\u0131 SIRT3\/AMPK\/mTOR yola\u011f\u0131n\u0131n aktivasyonu ile ili\u015fkili olabilir. Bu \u00e7al\u0131\u015fma, magnolol\u00fcn UC fareleri \u00fczerindeki koruyucu mekanizmas\u0131n\u0131 Th17\/Treg dengesi perspektifinden \u00f6n ara\u015ft\u0131rmaya tabi tutarak, magnolol\u00fcn ba\u011f\u0131rsak iltihab\u0131n\u0131 tedavi etmek i\u00e7in etkili bir aday bile\u015fen olabilece\u011fini, UC i\u00e7in umut verici bir tedavi y\u00f6ntemi sa\u011flayabilece\u011fini ve UC'yi iyile\u015ftiren magnolol mekanizmas\u0131 hakk\u0131nda daha fazla ara\u015ft\u0131rma i\u00e7in y\u00f6n sa\u011flayabilece\u011fini g\u00f6stermektedir. \u00d6rne\u011fin, SIRT3\/AMPK\/mTOR yolu otofajiyi d\u00fczenler ve magnolol\u00fcn UC'deki rol\u00fcn\u00fcn otofaji ile ili\u015fkili olup olmad\u0131\u011f\u0131 gelecekteki ara\u015ft\u0131rmalarda daha fazla ara\u015ft\u0131r\u0131lacakt\u0131r. Buna ek olarak, hayvan deneyleri preklinik ara\u015ft\u0131rmada \u00f6nemli bir ba\u011flant\u0131d\u0131r ve gelecekteki \u00e7al\u0131\u015fmalarda, magnolol\u00fcn toksisitesi ve g\u00fcvenli\u011finin derinlemesine analizi yap\u0131lacak, preklinik ara\u015ft\u0131rmay\u0131 te\u015fvik etmek ve ila\u00e7lar\u0131n klinik \u00e7evirisini sa\u011flamak i\u00e7in temel olu\u015fturacakt\u0131r.<\/p>","protected":false},"excerpt":{"rendered":"

The effect of magnolol regulating the SIRT3\/AMPK\/mTOR signaling pathway on the Th17\/Treg immune balance in ulcerative colitis mice Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with dysbiosis of the gut microbiota. At present, although drug therapy (including 5-aminosalicylic acid, corticosteroids, immunosuppressants, biologics, and probiotics) can alleviate symptoms, these treatments are limited by […]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"\nThe effect of magnolol regulating the SIRT3\/AMPK\/mTOR signaling pathway on the Th17\/Treg immune balance in ulcerative colitis mice - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/tr\/mtor-sinyal-yolagi\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The effect of magnolol regulating the SIRT3\/AMPK\/mTOR signaling pathway on the Th17\/Treg immune balance in ulcerative colitis mice - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"The effect of magnolol regulating the SIRT3\/AMPK\/mTOR signaling pathway on the Th17\/Treg immune balance in ulcerative colitis mice Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with dysbiosis of the gut microbiota. 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