{"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\/da\/mtor-signaling-pathway\/","title":{"rendered":"Effekten af magnolol, der regulerer SIRT3\/AMPK\/mTOR-signalvejen, p\u00e5 Th17\/Treg-immunbalancen i ulcer\u00f8s colitis-mus"},"content":{"rendered":"<p>Effekten af magnolol, der regulerer SIRT3\/AMPK\/mTOR-signalvejen, p\u00e5 Th17\/Treg-immunbalancen i ulcer\u00f8s colitis-mus<br \/>\nColitis ulcerosa (UC) er en kronisk inflammatorisk tarmsygdom, der er forbundet med dysbiose i tarmens mikrobiota. Selvom medicinsk behandling (herunder 5-aminosalicylsyre, kortikosteroider, immunosuppressiva, biologiske l\u00e6gemidler og probiotika) p\u00e5 nuv\u00e6rende tidspunkt kan lindre symptomerne, er disse behandlinger begr\u00e6nset af h\u00f8je tilbagefaldsrater og uundg\u00e5elige bivirkninger (s\u00e5som kvalme, opkastning, knoglemarvssuppression, infektion og kr\u00e6ftrisiko). Derfor er der et presserende behov for at udvikle nye og effektive behandlinger for UC. Genetiske faktorer, tarmmilj\u00f8, immunrespons, celleapoptose og infektion er alle forbundet med UC. If\u00f8lge rapporter udviser UC-patienter nedsat tarmmikrobiota, hvilket f\u00f8rer til \u00f8get permeabilitet af tarmepitelcellebarrieren og udl\u00f8ser intestinale inflammatoriske reaktioner; og i udviklingen af UC \u00f8ges T-hj\u00e6lper 17-celler (Th17), der for\u00e5rsager inflammation, normalt, mens regulatoriske T-celler (Treg), der h\u00e6mmer inflammation, falder. Regulering af Th17\/Treg-balancen ved at modulere tarmens mikrobiota kan behandle UC. Derfor er regulering af Th17\/Treg-balancen blevet et vigtigt m\u00e5l for behandling af UC.<\/p>\n<p>Osmanthus-ekstrakt er et naturprodukt, der findes i mange forskellige planter som f.eks. krysantemum, peberfrugt og perilla. Det har antiinflammatoriske, antioxidante, antitumorale og antivirale virkninger. Flere og flere beviser tyder p\u00e5, at magnolol kan reducere udskillelsen af pro-inflammatoriske cytokiner som TNF - \u03b1 og IL-6 og derved h\u00e6mme inflammatoriske reaktioner. Det er blevet anvendt til behandling af inflammationsrelaterede sygdomme, herunder UC. If\u00f8lge rapporter har luteolin en regulerende effekt p\u00e5 tarmmikrobiotaen og kan have en effektiv indvirkning p\u00e5 behandlingen af UC ved at justere sammens\u00e6tningen og strukturen af tarmmikrobiotaen. Det er dog stadig uklart, om magnolol kan regulere Th17\/Treg-balancen i UC.<\/p>\n<p>Den dynamiske balance mellem Treg og Th17 reguleres af flere signalveje, blandt hvilke den AMP-aktiverede proteinkinase (AMPK)\/mammalske m\u00e5l for rapamycin (mTOR) signalvej er en af dens vigtige reguleringsveje. Forskning har vist, at ved at \u00f8ge fosforyleringsniveauet for AMPK og reducere fosforyleringsniveauet for mTOR, kan human Th17\/Treg-celledifferentiering reguleres, og denne effekt kan blokeres af AMPK-signalinhibitor Compound C; I dextransulfatnatrium (DSS) - induceret UC-rotte-model kan forbedret AMPK-phosphorylering reducere mTOR-ekspression og niveauer af forskellige inflammatoriske cytokiner, hvilket f\u00f8rer til reduceret Th17-celledifferentiering. Silent information regulator 3 (SIRT3) er et antiinflammatorisk og tumorundertrykkende gen, der interagerer med tarmmikrobiotaen under tumorigenese i tyktarmen. Det er blevet rapporteret, at mus med SIRT3-mangel er meget f\u00f8lsomme over for colitis og tumorudvikling. Tip: SIRT3 kan v\u00e6re forbundet med udviklingen af UC. I mellemtiden er SIRT3 ogs\u00e5 en opstr\u00f8ms regulator af AMPK\/mTOR-vejen, og dens overekspression kan opregulere AMPK-phosphorylering og nedregulere mTOR-phosphorylering, hvilket h\u00e6mmer inflammation. En nylig unders\u00f8gelse viste, at magnolol kan \u00f8ge SIRT3-ekspressionen og forhindre cerebral isk\u00e6mi-reperfusionsskade ved at regulere SIRT3\/AMPK\/mTOR-signalvejen. Derfor har denne unders\u00f8gelse til form\u00e5l at unders\u00f8ge, om den beskyttende virkning af magnolol p\u00e5 UC er relateret til Th17\/Treg-immunbalancen, og analysere dens mekanisme for at afklare den beskyttende virkning af magnolol p\u00e5 UC og give reference til behandling af UC og anvendelse af magnolol.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6569\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-239.png\" alt=\"\" width=\"661\" height=\"201\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6570\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-200.png\" alt=\"\" width=\"333\" height=\"273\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6571\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-187.png\" alt=\"\" width=\"659\" height=\"552\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6572\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-167.png\" alt=\"\" width=\"596\" height=\"860\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-167.png 596w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-167-499x720.png 499w\" sizes=\"(max-width: 596px) 100vw, 596px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6573\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-151.png\" alt=\"\" width=\"658\" height=\"246\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6574\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-137.png\" alt=\"\" width=\"659\" height=\"165\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6575\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-125.png\" alt=\"\" width=\"662\" height=\"253\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-6576\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-113.png\" alt=\"\" width=\"652\" height=\"328\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-113.png 652w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-113-650x328.png 650w\" sizes=\"(max-width: 652px) 100vw, 652px\" \/>I de senere \u00e5r er traditionel kinesisk medicin blevet brugt i vid udstr\u00e6kning til behandling af UC. Et stigende antal unders\u00f8gelser tyder p\u00e5, at traditionel kinesisk medicin spiller en vigtig rolle i reguleringen af tarmens mikrobiota under behandlingen af UC. Osmanthus fragrans er en af de mest grundigt unders\u00f8gte bioflavonoider. Flavonoider er naturlige forbindelser med lav toksicitet, og indtil videre er deres anvendelse ikke blevet registreret med alvorlige bivirkninger, hvilket g\u00f8r dem meget sikre. I dette studie blev effekten af magnolol p\u00e5 DSS-induceret UC unders\u00f8gt in vivo. Vores resultater viser, at magnolol har en betydelig effekt p\u00e5 UC, hvilket kan p\u00e5vises ved v\u00e6gttab, DAI-score, reduktion af mukosal nekrose og infiltration af inflammatoriske celler. Dette er i overensstemmelse med tidligere forskning og bekr\u00e6fter endnu en gang magnolols beskyttende effekt p\u00e5 UC.<br \/>\nTidligere unders\u00f8gelser har vist, at luteolin kan h\u00e6mme Th17-respons i T-cellemedierede autoimmune sygdomme; Og det kan ud\u00f8ve antiinflammatoriske virkninger ved at inducere CD4 + CD25- til at omdanne til Treg-celler. Der er ogs\u00e5 rapporter om, at luteolin kan h\u00e6mme produktionen af proinflammatoriske cytokiner s\u00e5som TNF - \u03b1, IL-1 \u03b2, IL-6 og IL-17 i UC-modelmus; Osmanthus-derivater kan ud\u00f8ve in vivo-beskyttende virkninger i DSS-inducerede UC-modeller ved at reducere niveauerne af Th1-, Th2- og Th17-celler. Vi unders\u00f8gte yderligere effekten af magnolol p\u00e5 Th17\/Treg-balancen, som er en af de vigtige mekanismer, der ligger til grund for udviklingen af UC. I denne unders\u00f8gelse fandt vi et signifikant fald i procentdelen af Treg-celler og en signifikant stigning i procentdelen af Th17-celler i miltlymfocytter fra UC-mus. Th17\/Treg-forholdet i UC-mus er i alvorlig ubalance. Milten er et vigtigt immunorgan, og DSS kan fremkalde immundysfunktion hos UC-mus, hvilket f\u00f8rer til kompenserende splenomegali; Og luteolin kan reducere miltindekset og lindre DSS-induceret colitis hos mus. Denne unders\u00f8gelse bekr\u00e6fter yderligere den betydelige Th17\/Treg-ubalance i miltlymfocytter fra UC-mus, hvilket er i overensstemmelse med menneskelig UC.<br \/>\nDifferentieringsprocessen for Th17-celler medieres af den transkriptionelle regulering af ROR \u03b3 t. Th17-celler producerer pro-inflammatoriske cytokiner, herunder IL-17, IL-21, IL-22, IL-23 og IL-25, som bidrager til udviklingen af UC. Differentieringen af Tregs reguleres af Foxp3, og modne Tregs udtrykker h\u00f8je niveauer af Foxp3. Derudover udskiller Tregs h\u00e6mmende cytokiner, herunder IL-10, IL-35 og TGF - \u03b2, som kan undertrykke adaptive og medf\u00f8dte immunresponser. Forskning har vist, at \u00f8gede Th17-celler producerer h\u00f8je niveauer af IL-17 og IL-23 og dermed fremmer inflammation. Differentieringen af Treg h\u00e6mmes imidlertid, hvilket f\u00f8rer til et fald i immunosuppressive cytokiner, herunder IL-10. Forbedring af Th17\/Treg-ubalancen kan hj\u00e6lpe med at genopbygge tarmens immunhom\u00f8ostase og reducere UC. Denne unders\u00f8gelse viste, at det antiinflammatoriske cytokin IL-10 blev \u00f8get, og at de proinflammatoriske cytokiner IL-6, IL-17 og IL-23 blev reduceret i luteolingruppen; Tip: Intervention af magnolol forbedrede Th17\/Treg-ubalancen i DSS-induceret UC-model, i overensstemmelse med tidligere unders\u00f8gelser; Derudover viste yderligere analyse, at magnolol signifikant nedregulerede ROR \u03b3 t og opregulerede Foxp3 i UC-mus. P\u00e5 grund af den positive sammenh\u00e6ng mellem ROR \u03b3 t og Th17-celledifferentiering og den positive sammenh\u00e6ng mellem Foxp3 og Treg-celledifferentiering viser vores forskningsresultater yderligere, at magnolol bidrager til balancen mellem Th17\/Treg-celledifferentiering.<br \/>\nTh17\/Treg-celledifferentiering reguleres af to vigtige n\u00e6ringssensorveje, AMPK og mTOR. SIRT3 er en effektiv deacetylase, som har vist sig at aktivere AMPK\/mTOR-vejen for at fremme autofagi, mens SIRT3-mangel kan h\u00e6mme AMPK\/mTOR-vejen. I denne unders\u00f8gelse observerede vi, at niveauerne af SIRT3-protein og p-AMPK\/AMPK-forholdet i tyktarmsv\u00e6vet hos UC-mus var betydeligt lavere end hos normale mus, mens p-mTOR\/mTOR-forholdet var betydeligt h\u00f8jere end hos normale mus, hvilket indikerer en mangel p\u00e5 SIRT3 hos UC-mus og h\u00e6mning af AMPK-aktivering. Osmanthus fragrans kan regulere AMPK-aktiviteten ved at modulere udtrykket af silencerende reguleringsproteiner. Liu et al.s unders\u00f8gelse viste, at magnolol kan \u00f8ge transduktionen af SIRT3, aktivere SIRT3\/AMPK\/mTOR-vejen og lindre cerebral isk\u00e6misk skade. Derfor spekulerer vi i, at magnolols effekt p\u00e5 Th17\/Treg-balancen i UC-mus kan v\u00e6re relateret til SIRT3\/AMPK\/mTOR-vejen. Western blot-resultaterne viste, at magnolol kan \u00f8ge niveauet af SIRT3-protein i tyktarmsv\u00e6vet hos UC-mus, forbedre fosforyleringsniveauet af AMPK og nedregulere fosforyleringsniveauet af mTOR, hvilket bekr\u00e6fter vores hypotese. 3-TYP er en selektiv h\u00e6mmer af SIRT3 og er blevet rapporteret til at h\u00e6mme SIRT3-ekspression. I denne unders\u00f8gelse kombinerede vi magnolol med 3-TYP for yderligere at afklare den beskyttende mekanisme for magnolol p\u00e5 UC-mus. Resultaterne viste, at 3-TYP kunne h\u00e6mme aktiveringen af AMPK betydeligt og sv\u00e6kke effekten af magnolol p\u00e5 differentieringsbalancen af Th17\/Treg-celler i UC-mus betydeligt. Tip: Osmanthus-ekstrakt kan fremme Th17\/Treg-balancen i UC-mus ved at aktivere SIRT3\/AMPK\/mTOR-vejen.<br \/>\nSammenfattende kan magnolol forbedre Th17\/Treg-ubalancen i DSS-inducerede UC-musemodeller, og dens virkningsmekanisme kan v\u00e6re relateret til aktiveringen af SIRT3\/AMPK\/mTOR-vejen. Denne unders\u00f8gelse unders\u00f8gte forel\u00f8bigt den beskyttende mekanisme af magnolol p\u00e5 UC-mus ud fra Th17\/Treg-balancen, hvilket indikerer, at magnolol kan v\u00e6re en effektiv kandidatingrediens til behandling af tarmbet\u00e6ndelse, hvilket giver en lovende behandlingsmetode for UC og giver retning for yderligere forskning i mekanismen for magnolol, der forbedrer UC. For eksempel regulerer SIRT3\/AMPK\/mTOR-stien autofagi, og hvorvidt magnolols rolle i UC er relateret til autofagi, vil blive udforsket yderligere i fremtidig forskning. Derudover er dyrefors\u00f8g et vigtigt led i pr\u00e6klinisk forskning, og i fremtidige studier vil der blive foretaget en grundig analyse af magnolols toksicitet og sikkerhed, hvilket vil danne grundlag for at fremme pr\u00e6klinisk forskning og opn\u00e5 klinisk overs\u00e6ttelse af l\u00e6gemidler.<\/p>","protected":false},"excerpt":{"rendered":"<p>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 [&hellip;]<\/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":"<!-- This site is optimized with the Yoast SEO plugin v23.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>The 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\/da\/mtor-signaling-pathway\/\" \/>\n<meta property=\"og:locale\" content=\"da_DK\" \/>\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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