{"id":3717,"date":"2024-08-03T07:33:30","date_gmt":"2024-08-03T07:33:30","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=3717"},"modified":"2024-08-03T07:33:30","modified_gmt":"2024-08-03T07:33:30","slug":"glycolysis-cml","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/da\/glycolysis-cml\/","title":{"rendered":"Unders\u00f8gelse af glykolysens involvering i reguleringen af ceramids h\u00e6mning af proliferation af kroniske myeloide leuk\u00e6miceller"},"content":{"rendered":"<p>Unders\u00f8gelse af glykolysens involvering i reguleringen af ceramids h\u00e6mning af proliferation af kroniske myeloide leuk\u00e6miceller<br \/>\nKronisk myelogen leuk\u00e6mi (CML) er en klonal proliferativ leuk\u00e6mi i knoglemarvsceller, der tegner sig for ca. 15% af leuk\u00e6mitilf\u00e6ldene hos voksne. Dens \u00e5rlige forekomst er 2\/100000, h\u00f8j hos mennesker i alderen 50 ~ 55 \u00e5r. Kronisk myeloid leuk\u00e6mi er en tumor, der er forbundet med dannelsen af BCR-ABL1-fusionsprotein gennem Philadelphia-kromosomtranslokation. P\u00e5 nuv\u00e6rende tidspunkt anvendes tyrosinkinaseinhibitor (TKI) m\u00e5lrettede l\u00e6gemidler hovedsageligt til behandling, hvilket kan forbedre prognosen for CML-patienter betydeligt. Der er dog stadig et tilbagevendende problem med TKI-resistens for\u00e5rsaget af ustabilitet i tyrosinkinase-genet i BCR-ABL1-onkogenet. Traditionel kinesisk medicin har en terapeutisk effekt p\u00e5 CML, f.eks. ved at \u00f8ge effekten af kemoterapi og forbedre kroppens immunforsvar. Opdagelse af ledende anti-CML-forbindelser i traditionel kinesisk medicin og analyse af deres virkningsmekanismer kan give nye ideer og et eksperimentelt grundlag for behandling af CML.<\/p>\n<p>Rocaglamid (RocA), der stammer fra grene og blade af den traditionelle kinesiske medicinplante Spartina alterniflora, er et naturligt produkt, der indeholder et cyclopentan-benzofuran-skelet. Det har funktioner som forebyggelse og behandling af luftvejssygdomme som hoste og astma, inflammatoriske hudsygdomme, antiinflammatoriske virkninger, reduktion af l\u00e6gemiddelskader, neurobeskyttelse og antitumoreffekter. Tidligere unders\u00f8gelser har vist, at ceramid h\u00e6mmer v\u00e6ksten og spredningen af tumorceller ved nanomol\u00e6re koncentrationer. Dets antitumormekanisme involverer hovedsageligt h\u00e6mning af translationsinitieringsfaktorerne eIF4E og eIF4A i tumorceller, blokering af cellecyklussen ved at aktivere ATM\/ATR-Chk1\/CHK2-kontrolpunktsvejen og aktivering af tumorceller uden at p\u00e5virke MAPK p38- og JNK-vejene i normale celler. Nylige unders\u00f8gelser har vist, at sulfonamid kan forbedre kemoterapiens effektivitet og \u00f8ge leuk\u00e6micellernes f\u00f8lsomhed. Flere unders\u00f8gelser har vist, at sulfonamid har et stort potentiale som en kandidat til sm\u00e5 molekyler til udvikling af antitumorl\u00e6gemidler.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3718\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-2.png\" alt=\"\" width=\"1040\" height=\"402\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-2.png 1040w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-2-768x297.png 768w\" sizes=\"(max-width: 1040px) 100vw, 1040px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3719\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-1.png\" alt=\"\" width=\"1024\" height=\"336\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-1.png 1024w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-1-768x252.png 768w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3720\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-1.png\" alt=\"\" width=\"1002\" height=\"462\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-1.png 1002w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-1-768x354.png 768w\" sizes=\"(max-width: 1002px) 100vw, 1002px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3721\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-2.png\" alt=\"\" width=\"1058\" height=\"444\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-2.png 1058w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-2-768x322.png 768w\" sizes=\"(max-width: 1058px) 100vw, 1058px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3722\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-2.png\" alt=\"\" width=\"554\" height=\"474\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3723\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-2.png\" alt=\"\" width=\"982\" height=\"338\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-2.png 982w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-2-768x264.png 768w\" sizes=\"(max-width: 982px) 100vw, 982px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3724\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1.png\" alt=\"\" width=\"1036\" height=\"746\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1.png 1036w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1-768x553.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1-1000x720.png 1000w\" sizes=\"(max-width: 1036px) 100vw, 1036px\" \/>Nogle tumorceller gennemg\u00e5r metaboliske \u00e6ndringer for at opfylde deres energi- og biosyntetiske behov for overlevelse og hurtig spredning, og de \u00f8gede niveauer af aerob glykolyse (dvs. Wolberg-effekten) er en af de metaboliske mark\u00f8rer for tumorceller. Aerob glykolyse er blevet et vigtigt m\u00e5l for selektiv indgriben i leuk\u00e6mi. Det er ikke klart, om sulfonamid h\u00e6mmer CML-proliferation ved at regulere CML-glykolysen. Denne artikel bruger CML-cellelinjen K562 som en cellemodel til at unders\u00f8ge virkningerne af ceramid p\u00e5 CML-celleproliferation og glykolyse og udforske den aerobe glykolyses regulerende rolle i ceramids h\u00e6mning af CML-celleproliferation.<br \/>\nMelitamid er et aktivt stof, der udvindes af risorkid\u00e9en, og som har antitumoreffekter. Denne artikel unders\u00f8ger, om sulfonamid h\u00e6mmer spredningen af K562-celler gennem aerob glykolyse. Resultaterne af MTT-analysen viste, at v\u00e6ksten og spredningen af K562-celler blev signifikant h\u00e6mmet af melitamid p\u00e5 en tids- og koncentrationsafh\u00e6ngig m\u00e5de, og dets IC50 for h\u00e6mning af spredningen af K562-celler n\u00e5ede det nanomol\u00e6re niveau. Brugen af flowcytometri-teknologi har vist, at azepam h\u00e6mmer spredningen og inducerer apoptose af K562-celler ved at blokere G2\/M-fasen i cellecyklussen.<br \/>\nTumorceller udviser stadig h\u00f8je niveauer af glukoseoptagelse, glykolyse og laktatniveauer under aerobe forhold, kendt som Warburg-effekten. Transkriptionsfaktoren c-Myc er i vid udstr\u00e6kning involveret i reguleringen af cellul\u00e6re funktioner som celleproliferation, celleoverlevelse, v\u00e6vsmodellering og angiogenese og igangs\u00e6tter ogs\u00e5 metabolisk omprogrammering af tumorceller. c-Myc opregulerer glukosetransport\u00f8rer og n\u00e6sten alle glykolytiske enzymer og fremmer derved tumorcellernes glukosemetabolisme. 13C-m\u00e6rket glukose viste, at c-Myc fremmede glukoseforbruget i Burkitt-lymfom og c-Myc-drevet leverkr\u00e6ft. Forskning har vist, at c-Myc fremmer udskillelsen af laktat, som ikke kun er et metabolisk stof, der er involveret i glykolysen, men ogs\u00e5 er med til at fremme angiogenese, immunflugt, cellemigration, metabolisk eftersp\u00f8rgsel og andre kr\u00e6ftfremkaldende effekter. Vi fandt gennem glukosesultbehandling af K562-celler, at fjernelse af glukose reducerede laktatproduktionsniveauet og proteinekspressionsniveauet for c-Myc og ikke var befordrende for spredning af K562-celler. Dette bekr\u00e6fter, at v\u00e6ksten og spredningen af K562-celler afh\u00e6nger af tilf\u00f8rslen af glukose, hvilket afspejler sammenh\u00e6ngen mellem c-Myc-niveauer og glukoseniveauer i K562-celler. Under sultebetingelser blev det konstateret, at den relative h\u00e6mning af formamid p\u00e5 K562-celler efter fjernelse af glukose var lavere end for den gruppe, der blev tilsat glukose. Derfor spekuleres der i, at formamids h\u00e6mning af K562-cellers v\u00e6kst er delvist afh\u00e6ngig af glukose, hvilket betyder, at formamid ikke yderligere kan fremkalde v\u00e6ksth\u00e6mning i K562-celler uden glukoseforsyning. Melitamid reducerede ogs\u00e5 signifikant glukoseforbruget og laktatproduktionen i supernatanten fra K562-celler, hvilket indikerer, at melitamid h\u00e6mmede den aerobe glykolyse i K562-celler.<br \/>\nHexokinase 2 (HK2) er et specifikt n\u00f8gleenzym i tumorcellers glykolyse, som kan binde sig til den ydre mitokondriemembran for at opretholde h\u00f8jhastigheds aerob glykolyse af tumorceller og give energi til hurtig spredning af tumorceller. Forskerne bekr\u00e6ftede, at HK2 spiller en vigtig rolle i forekomsten og udviklingen af brystkr\u00e6ft, lungekr\u00e6ft og andre tumorer ved hj\u00e6lp af musemodeller; Hexokinase 1 (HK1) udtrykkes bredt i voksnes v\u00e6v og betragtes som en husholdningssubtype af hexokinase; Phosphofructokinase P (PFKP) spiller en afg\u00f8rende rolle i initiering og metastase af kr\u00e6ft. Nogle unders\u00f8gelser har vist, at PFKP har potentiale til at v\u00e6re en diagnostisk mark\u00f8r eller et l\u00e6gemiddelm\u00e5l for brystkr\u00e6ft og lungekr\u00e6ft; Pyruvatkinase 2 (PKM2) udtrykkes i alle celler med h\u00f8je nukleinsyresyntesehastigheder, s\u00e5som normale prolifererende celler, embryonale celler og is\u00e6r tumorceller; Laktatdehydrogenase A (LDHA) katalyserer den gensidige transformation af pyruvat og L-m\u00e6lkesyre. LDHA-niveauet i mange humane tumorceller er h\u00f8jere end i normale celler. H\u00e6mning af LDHA kan reducere spredningen af tumorceller som hoved- og halskr\u00e6ft, bugspytkirtelkr\u00e6ft, livmoderhalskr\u00e6ft og prostatakr\u00e6ft. Vi analyserede virkningerne af ceramid p\u00e5 proteinekspressionsniveauerne af HK2, HK1, PFKP, PKM2, LDHA og den onkogene transkriptionsfaktor c-Myc i K562-celler og fandt, at ceramid n\u00e6ppe regulerede proteinekspressionsniveauerne af HK1, PFKP, PKM2 og LDHA, men signifikant nedregulerede proteinekspressionsniveauerne af c-Myc og HK2. Vi spekulerer i, at melinamid ud\u00f8ver sin anti-K562-celleaktivitet ved at nedregulere c-Myc og HK2 og h\u00e6mme aerobe glykolyseveje. Det regulatoriske forhold mellem c-Myc og HK2 kr\u00e6ver yderligere udforskning.<\/p>\n<p>&nbsp;<\/p>","protected":false},"excerpt":{"rendered":"<p>Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide Chronic myelogenous leukemia (CML) is a clonal proliferative leukemia of bone marrow cells, accounting for about 15% of adult leukemia cases. Its annual incidence rate is 2\/100000, high in people aged 50~55 years. Chronic myeloid leukemia [&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>Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide - 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\/glycolysis-cml\/\" \/>\n<meta property=\"og:locale\" content=\"da_DK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide Chronic myelogenous leukemia (CML) is a clonal proliferative leukemia of bone marrow cells, accounting for about 15% of adult leukemia cases. 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