{"id":7485,"date":"2024-08-06T20:06:46","date_gmt":"2024-08-06T20:06:46","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=7485"},"modified":"2024-08-06T20:06:46","modified_gmt":"2024-08-06T20:06:46","slug":"colon-tumors","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/da\/colon-tumors\/","title":{"rendered":"Jolkinolid B's mekanisme i behandlingen af tyktarmstumorer baseret p\u00e5 netv\u00e6rksfarmakologi og eksperimentel forskning"},"content":{"rendered":"

Jolkinolid B's mekanisme i behandlingen af tyktarmstumorer baseret p\u00e5 netv\u00e6rksfarmakologi og eksperimentel forskning
\nKolorektal cancer (CRC) er den tredje mest almindelige maligne tumor i verden, hvilket er en alvorlig trussel mod menneskers sundhed. I 2015 n\u00e5ede antallet af d\u00f8dsfald som f\u00f8lge af tyktarmskr\u00e6ft op p\u00e5 774.000. P\u00e5 grund af de enorme \u00e6ndringer i folks livsstil og koststruktur stiger forekomsten og d\u00f8deligheden af tyktarmskr\u00e6ft \u00e5r for \u00e5r. Styrkelse af forskningen i forebyggelse og behandling af tyktarmskr\u00e6ft er et af de vigtige omr\u00e5der inden for kr\u00e6ftbek\u00e6mpelse i Kina. Det bliver stadig vigtigere at s\u00f8ge efter ledende forbindelser fra naturlige ressourcer, der kan ramme tyktarmstumorer og fremme apoptose af tumorceller. Den traditionelle kinesiske medicin \"wolfberry\" har en lang brugshistorie og bruges ofte til behandling af tyktarmskr\u00e6ft i folkemedicin. Denne medicin er inkluderet i 2020-udgaven af den kinesiske farmakop\u00e9 og er den t\u00f8rrede rod af Euphorbia fis cheriana Steud og Euphorbia ebracteolata Hayata-planter i Euphorbiaceae-familien. Den blev f\u00f8rste gang optaget i \"Shennong Materia Medica\" og bruges hovedsageligt mod hoste, ophobninger, s\u00e5r, musenekrose og forgiftning. Folk i det nord\u00f8stlige Kina bruger dens afkog til at behandle tyktarmskr\u00e6ft. Forskning har vist, at den traditionelle kinesiske medicin \"wolfberry\" kan forl\u00e6nge overlevelsesraten for dyr med tyktarmskr\u00e6ft med 47%.<\/p>\n

De aktive sekund\u00e6re metabolitter i ulvegift er hovedsageligt terpenoider, som er rigelige i indhold. I den tidlige fase isolerede vores fors\u00f8gsgruppe strukturelt forskellige diterpener som ent abietan, rosan og diterpenoiddimerer fra de t\u00f8rrede r\u00f8dder af Euphorbia lanceolata, en l\u00e6geplantekilde til ulveb\u00e6r. Blandt dem kan ent abietan-diterpen Jolkinolite B (struktur vist i figur 1) effektivt h\u00e6mme spredningen af tyktarmstumorcelle SW480 (IC50=9,5 \u03bc mpl\/L), hvilket giver et materielt grundlag for behandling af CRC, men virkningsmekanismen er endnu ikke klar. P\u00e5 baggrund af tidligere forskning planl\u00e6gger vi at bruge netv\u00e6rksfarmakologiske metoder kombineret med in vitro-cellefors\u00f8g til at udforske virkningsmekanismen for det aktive stof Jolkinolid B i behandlingen af CRC, hvilket giver eksperimentel evidens for efterf\u00f8lgende l\u00e6gemiddeludvikling og kliniske anvendelser.<\/p>\n

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\nNetv\u00e6rksfarmakologi kan i h\u00f8j grad afspejle de komplekse interaktioner mellem biomolekyler og kemiske komponenter. Ved at screene virkningsm\u00e5let gennem netv\u00e6rksfarmakologi kan det danne grundlag for en mere m\u00e5lrettet forskning i traditionel kinesisk medicin og klarl\u00e6gge de optimale forbindelser og deres virkningsmekanismer i traditionel kinesisk medicin. Den traditionelle kinesiske medicin ulveb\u00e6r er en plante af Euphorbiaceae-familien, der tilh\u00f8rer Euphorbiaceae-sl\u00e6gten. Den har den virkning, at den fordriver vand og slim, nedbryder ophobning og dr\u00e6ber insekter. Forskningsresultaterne viser, at diterpenoider er det aktive stof i den traditionelle kinesiske medicin wolfberry med forskellige biologiske aktiviteter s\u00e5som antitumor, antiinflammatorisk, antibakteriel og reversering af multiresistens. Den traditionelle kinesiske medicin wolfberry har en lang historie med brug og bruges ofte til behandling af tyktarmskr\u00e6ft i folkemedicin. Baseret p\u00e5 dette udf\u00f8res farmakologisk mekanismeforudsigelse. Baseret p\u00e5 den tidligere forskning i de kemiske komponenter i den traditionelle kinesiske medicin wolfberry blev den fremragende forbindelse Jolkinolide B i wolfberry screenet gennem in vitro cytotoksisk aktivitetsscreening og in vivo biologiske eksperimenter. Et Jolkinolide B-m\u00e5lnetv\u00e6rk blev konstrueret for at unders\u00f8ge forholdet mellem den fremragende forbindelse Jolkinolide B-m\u00e5l i wolfberry, og funktionel annotation af m\u00e5lene blev udf\u00f8rt p\u00e5 genniveau. Dette giver et forskningsgrundlag for Jolkinolid B's farmakologiske mekanismer med flere m\u00e5l og flere veje.<\/p>\n

Jolkinolid B-PPI-interaktionsnetv\u00e6rksanalysen viser, at de vigtigste m\u00e5l er STAT3, MAPK8 og JUN, som er blevet bekr\u00e6ftet af relevant litteraturforskning; Disse m\u00e5l transmitterer signaler fra receptorer p\u00e5 celleoverfladen til DNA i kernen og deltager i biologiske processer s\u00e5som celled\u00f8d og cellecyklus samt regulering af patologiske processer s\u00e5som bet\u00e6ndelse og stressrespons. MAPK1 og MAPK3 er medlemmer af MAPK. STAT3 er en transkriptionsfaktor, der kan aktiveres af MAPK og spiller en n\u00f8glerolle i mange cellul\u00e6re processer som cellev\u00e6kst og apoptose, og som deltager i forekomsten og udviklingen af tumorer. Derudover er STAT3 afg\u00f8rende for differentieringen af TH17-hj\u00e6lper-T-celler og er forbundet med autoimmune sygdomme, tilbagevendende infektioner og andre sygdomme.<\/p>\n

GO's annotationsresultater indikerer, at de fleste af Jolkinolite B's m\u00e5l er placeret i den cellul\u00e6re matrix og transkriptionskomplekser og er involveret i forskellige stressresponser og biologiske processer i celler. Dette resultat tyder p\u00e5, at Jolkinolite B kan v\u00e6re involveret i at regulere de fleste cellul\u00e6re livsaktiviteter. Resultaterne af KEGG-berigelsesanalysen indikerer, at de farmakologiske virkninger af Jolkinolite B involverer interaktionen mellem flere veje, herunder IL-17-signalvejen, PD-1\/PD-L1-signalvejen og HIF-1-signalvejen. De molekyl\u00e6re dockingresultater indikerer, at Jolkinolid B danner hydrogen- og hydrofobe interaktioner med kerneproteiner STAT3, MAPK8 og JUN med stabil struktur og potentiel forskningsv\u00e6rdi, hvilket demonstrerer Jolkinolid B's multim\u00e5l- og multivejskarakteristika ved behandling af CRC.<\/p>\n

De vigtigste virkningsmekanismer for antitumorl\u00e6gemidler er at inducere tumorcelleapoptose, h\u00e6mme cellecyklussen og undertrykke migration. De eksperimentelle resultater p\u00e5 celleniveau viste, at Jolkinolite B signifikant h\u00e6mmede spredningen af HCT116-celler, fremmede celleapoptose og h\u00e6mmede cellemigration. N\u00e5r Bax var st\u00e6rkt udtrykt i celler, var cellerne f\u00f8lsomme over for d\u00f8dssignaler og fremmede apoptose. N\u00e5r Bcl-2 var st\u00e6rkt udtrykt, kunne Bcl-2 danne heterodimerer med Bax og h\u00e6mme celleapoptose. S\u00e5 forholdet mellem Bax\/Bcl-2 i celler spiller en vigtig rolle i bestemmelsen af f\u00f8lsomheden af celleapoptose. Derfor viste Western blot-valideringseksperimenter p\u00e5 celleniveau, at Jolkinolite B signifikant opregulerede forholdet mellem Bax \/ Bcl-2, hvilket fremmer apoptose i HCT116-celler. Baseret p\u00e5 resultaterne af netv\u00e6rksfarmakologianalysen kan Jolkinolid B gribe ind i CRC gennem flere m\u00e5l og veje, og dets antitumoraktivitet kan v\u00e6re relateret til dets indvirkning p\u00e5 udtrykket af apoptotiske gener Bax og Bcl-2.<\/p>\n

Invasion og metastase af tumorer er en kompleks proces, der involverer intercellul\u00e6re interaktioner og nedbrydning af ekstracellul\u00e6r matrix. Nedbrydningen af ekstracellul\u00e6r matrix afh\u00e6nger af syntese og aktivering af enzymer, der nedbryder matrixkomponenter. Matrixmetalloproteinaser (MMP'er) er en klasse af zinkafh\u00e6ngige proteolytiske enzymer med strukturel homologi. Deres vigtigste fysiologiske funktion er at nedbryde ekstracellul\u00e6re matrixkomponenter som kollagen, gelatine, elastin, fibronectin og proteoglycaner. Forskning har vist, at matrixmetalloproteinase-3 (MMP-3) og matrixmetalloproteinase-12 (MMP-12) spiller en afg\u00f8rende rolle i nedbrydningen af ekstracellul\u00e6r matrix medieret af tumorceller og er t\u00e6t forbundet med den potentielle invasion, metastase og prognose for forskellige maligne tumorer hos mennesker. Derfor viste Western blot-valideringseksperimenter p\u00e5 celleniveau, at Jolkinolide B signifikant nedregulerer ekspressionen af MMP-2 og MMP-12 for at h\u00e6mme tumorinvasion og metastase. Baseret p\u00e5 resultaterne af netv\u00e6rksfarmakologianalyse kan Jolkinolid B gribe ind i CRC gennem flere m\u00e5l og veje, og dets h\u00e6mning af tumorinvasion og metastase kan v\u00e6re relateret til dets indvirkning p\u00e5 ekspressionen af MMP-2 og MMP-12.<\/p>\n

Sammenfattende anvendte denne unders\u00f8gelse aktivitetsscreening, bioinformatik og molekyl\u00e6re dockingteknikker til at analysere mekanismen for Jolkinolid B i forebyggelse og behandling af kolorektal cancer (CRC) baseret p\u00e5 netv\u00e6rkskorrelationen mellem den aktive ingrediens Jolkinolid B i traditionel kinesisk medicin wolfberry og relaterede m\u00e5lproteiner, signalveje og biologiske funktioner. Resultaterne viste, at denne forbindelse behandler CRC med flere m\u00e5l, veje og biologiske funktioner, hvilket giver retning for yderligere forskning i mekanismen for Jolkinolide B i forebyggelse og behandling af CRC. I lyset af dette vil dette projekt forts\u00e6tte med at udf\u00f8re mekanismeforskning ved at kombinere molekyl\u00e6rbiologiske og patofysiologiske metoder i fremtiden.<\/p>","protected":false},"excerpt":{"rendered":"

Mechanism of Jolkinolide B in the treatment of colon tumors based on network pharmacology and experimental research Colorectal cancer (CRC) is the third most common malignant tumor in the world, which is a serious threat to human health. In 2015, the number of deaths from colon cancer reached 774000. Because of the tremendous changes in […]<\/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":"\nMechanism of Jolkinolide B in the treatment of colon tumors based on network pharmacology and experimental research - 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\/colon-tumors\/\" \/>\n<meta property=\"og:locale\" content=\"da_DK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Mechanism of Jolkinolide B in the treatment of colon tumors based on network pharmacology and experimental research - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Mechanism of Jolkinolide B in the treatment of colon tumors based on network pharmacology and experimental research Colorectal cancer (CRC) is the third most common malignant tumor in the world, which is a serious threat to human health. 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