I-Youdaoplaceholder0 1.1 Ilungu elifihliwe lomndeni kashukela

Njengengxenye yamandla eyinhloko yezinto eziphilayo, uhlelo lokuhlukanisa ama-carbohydrate sekuyisikhathi eside luqiniswa ezincwadini zokufunda: ama-monosaccharides (njenge-glucose ne-fructose), ama-oligosaccharides (afana ne-lactose), nama-polysaccharides (njengesitashi). Kodwa-ke, ukubaluleka kwe-mannose kulele "kubunikazi bayo obukabili" - akuyena nje umhlanganyeli kumetabolism yamandla kodwa futhi "uhlamvu lwephasiwedi" lokuxhumana kwamaselula. I-Mannose ikhona kakhulu endaweni ekhululekile ongqimbeni lwe-pectin lwezithelo ezisawolintshi kanye nezindonga zamaseli we-deep-sea algae. Emzimbeni womuntu, iba yisisekelo samangqamuzana sezinqubo ezibalulekile zomzimba ezifana nokuqashelwa kwamasosha omzimba kanye nokunamathela kwamaseli ngokuguqulwa kwe-N-link glycosylation yama-glycoprotein.

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I-Youdaoplaceholder0 1.2 I-Cognitive Iteration kusukela ku-Urinary Health kuya kuma-Cancer Pioneers

Kudala ngeminyaka yawo-1980, umphakathi wezokwelapha wathola ukuthi i-mannose ingavimbela izifo zomgudu womchamo ngokuvimbela ngokuncintisana ukunamathela kwamabhaktheriya e-pathogenic. Le nqubo idale ukuthengiswa okushisayo kwemikhiqizo yezempilo ye-cranberry. Kepha kuze kube ngu-2018 lapho ucwaningo oluyingqopha-mlando olwenziwe yiCancer Research UK (CRUK) ephephabhukwini i-Nature lwaphakamisa ngempela iveli emizamweni yalo yokulwa nomdlavuza: Kumodeli yegundane lomdlavuza we-pancreatic, ukwengeza i-20% mannose emanzini okuphuza kwehlise izinga lokukhula kwesimila ngo-40%, kwathi lapho kuhlanganiswa nomuthi we-chemotherapy, i-gemcitabine, isikhathi sokusinda sandiswa izikhathi ezi-3 nge-mi2. Lokhu kutholakala kuye kwawuchitha umbono ovamile wokuthi "wonke ushukela ukhuthaza umdlavuza".

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I-Youdaoplaceholder0 Isahluko 2 Sichaza Indlela Yokulwa Nomdlavuza: "Izikhiya zikashukela" ezintathu Zivula ulayini wezempilo we-Tumor

I-Youdaoplaceholder0 2.1 Ukudunwa Kwe-Metabolic: I-"Trojan horse" iguqulwe njenge-glucose

"I-Warburg Effect" yamaseli e-tumor yenza ukuthi ukumuncwa kwawo kwe-glucose kuphindwe kashumi kunamaseli avamile. Ithimba le-CRUK lithole ngobuchwepheshe bokulandelela i-carbon-13 isotope ukuthi i-mannose ingangena kumaseli omdlavuza ngokusebenzisa uhlobo olufanayo lwe-glucose transporter (GLUT1/3) enesakhiwo esifana nesikashukela. Kodwa-ke, ngemva kokungena, i-phosphorylated ngokushesha yi-hexokinase ku-mannose-6-phosphate (M6P). Lokhu okuphakathi kwe-metabolic akukwazi ukungena endleleni ye-glycolytic kodwa esikhundleni salokho kunqwabelana ngaphakathi kweseli ukuze kwakheke "umgoqo we-metabolic", okuholela ekuvinjweni kwe-ATP synthesis kanye nokuqhuma kwezinhlobo ze-oxygen esebenzayo (ROS), ekugcineni kubangele i-apoptosis yamangqamuzana omdlavuza (Figure 1).

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I-Youdaoplaceholder0 2.2 Umthetho we-Epigenetic: Ukubhala kabusha "ikhodi yememori" yamaseli omdlavuza

Ngo-2023, ithimba labacwaningi abavela eFudan University in Cell Metabolism laphinde laveza ukuthi i-mannose ingasebenza "njengomhleli we-epigenome". Kumodeli ye-pancreatic ductal adenocarcinoma (PDAC), ukwelashwa kwe-mannose kwehlise kakhulu izinga le-acetylation lesayithi le-histone H3K27, okuholele ekuvinjweni kwemisebenzi yokubhala ye-oncogenes MYC ne-KRAS. Okumangalisa nakakhulu, lo mphumela wokuhlela kabusha obonakalayo uyaphikelela - ngisho nalapho ukuphathwa kwezidakamizwa kuyekwa, amangqamuzana omdlavuza asalokhu ehlasela kancane, enikeza imibono emisha yokwelashwa okuqinile.

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I-Youdaoplaceholder0 2.3 Ukulungiswa kabusha kwe-immune microenvironment: Ukudabula "i-disguise egcotshwe ushukela" ye-PD-L1

Ithimba elifanayo elitholwe ezifundweni ezalandela zokuthi i-mannose ingaqhekeza indlela yokuphunyuka kwamasosha omzimba yamathumba ngokuphazamisa ukuguqulwa kwe-glycosylation kwe-programmed death ligand 1 (PD-L1). Ukuhlaziywa kwe-mass spectrometry kwembula ukuthi i-mannose ivimbele i-N-glycosylation ye-asparagine endaweni engu-192 yeprotheni ye-PD-L1, okuholela ekungakwazini kwayo ukugoqa ngendlela efanele kanye nokubambelela kulwelwesi lweseli. I-PD-L1, elahlekelwa ukuvikeleka "kwesihlangu sikashukela", ibhalwe yi-E3 ubiquitin ligase FBXW41 futhi yehliswe yi-proteasome. Emagundaneni e-melanoma, inhlanganisela ye-mannose kanye ne-anti-PD-1 amasosha omzimba inyuse izinga eliphelele lokuhlehla kwesimila lisuka ku-28% laya ku-79% (Umfanekiso 2).

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I-Youdaoplaceholder0 Isahluko 3 Kusukela Kumamodeli Ezilwane Kuya Ezivivinyweni Zomtholampilo Zabantu: Umgwaqo Omuva Wemithi Yokuhumusha

I-Youdaoplaceholder0 3.1 Impumelelo Nemikhawulo Yocwaningo Lwangaphambi Komtholampilo

Kumodeli yomdlavuza we-pancreatic we-CRUK, nakuba i-monotherapy ene-mannose ilibazise ukukhula kwesimila, yehlulekile ukufeza ukuxolelwa okuphelele. Kodwa-ke, lapho kuhlanganiswa ne-FOLFIRINOX chemotherapy regimen, isikhathi esimaphakathi sokusinda samagundane sandiswa kusukela ezinsukwini ezingu-42 kuya ezinsukwini ezingu-98, futhi kwakungekho ukwanda kobuthi. Lo mphumela uphinde wakhiqizwa kumodeli yomdlavuza webele ophindwe kathathu e-MD Anderson Cancer Center: I-Mannose inyuse izinga lokucindezelwa kwesimila se-paclitaxel lisuka ku-45% laya ku-72%. Kodwa-ke, abacwaningi baphinde bathola ukuthi cishe amaphesenti angu-15 amathumba awazange aphendule ku-mannose. Ukuhlaziywa okwengeziwe kwembula ukuthi lawa maseli amelana nezidakamizwa aveze kakhulu i-mannose-phosphate isomerase (PMI), engaguqula i-M6P ibe i-fructose-6-phosphate futhi iphinde ixhume endleleni ye-glycolytic.

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I-Youdaoplaceholder0 3.2 Ukusa kokuqapha kwezilingo zabantu

Isivivinyo sokuqala somtholampilo seSigaba I se-mannose esaqalwa ngo-2022 (NCT05220739) sasihlanganisa iziguli ezingama-32 ezinamathumba aqinile athuthukile. Eqenjini lethamo lokuphathwa ngomlomo kwansuku zonke kwe-5g mannose, amazinga e-DNA yesimila (ctDNA) ejikelezayo ezigulini eziyi-8 ehle ngamaphesenti angaphezu kwama-50, phakathi kwawo umthamo wama-metastases esibindi esigulini esisodwa somdlavuza we-pancreatic wehle ngo-31%. Kodwa-ke, lapho umthamo ukhuphukela ku-10g, isifo sohudo sebanga lesi-III senzeke ezigulini ezi-3, okuphakamisa ukuthi isu lokuphatha lidinga ukuthuthukiswa. Njengamanje, amalungiselelo e-mannose emithanjeni esebenzisa ubuchwepheshe be-nano-liposome encapsulation asathuthukiswa. Idatha ye-preclinical ibonisa ukuthi ukusebenza kahle kokulethwa kwe-tumor okuhlosiwe kufinyelela ku-78%, futhi ubuthi babo buyancipha kakhulu.

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Youdaoplaceholder0 Isahluko 4 Uguquko Lwezimboni Nezingxabano: Izinselelo Zangempela Zenguquko Emnandi

I-Youdaoplaceholder0 4.1 I-Synthetic Biology Ixazulula Indida Yokukhiqiza Okuningi

I-mannose ekhishwe ngokwemvelo iyabiza (cishe ikhilogremu ngayinye)

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Kunzima ukuhlangabezana nezidingo zomthamo wokulwa nomdlavuza (nsuku zonke)

Indlela yokwenza iwukukhuphula okuphumayo ku

Izindleko zehle zafika ku-1200), okunzima ukuhlangabezana nemfuneko yomthamo wokulwa nomdlavuza (10-20g ngosuku). I-Synthetic biology giant GinkgoBioworks yenyuse isivuno saba ngu-30g/L futhi yehlisa izindleko zaba ku-50/kg ngokushintsha indlela ye-mannose-1 - guanosine phosphate transferase (MPG) ye-Escherichia coli. Ubuchwepheshe obuthuthuke kakhulu obufana nebhaktheriya eyakhelwe i-CRISPR-Cas9 i-Saccharomyces cerevisiae ikwazile ukukhiqiza ngokuzinza i-mannose ehlanzekile kakhulu ngesikhathi sokuvutshelwa okuqhubekayo.

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Youdaoplaceholder0 4.2 Umdlalo phakathi kweHype yebhizinisi kanye nezimiso zokuziphatha zesayensi

Ngomqondo wokuthi "ushukela olwa nomdlavuza" usudumile, amakhulu emikhiqizo yezempilo ye-mannose ethi "ukwelashwa okuyisizayo kwamathumba" kuvele endaweni yesikhulumi se-Amazon, ngamaphrimiyamu entengo ephakeme izikhathi eziyishumi. Ngo-2023, i-US FDA yakhipha izincwadi eziyisixwayiso kumabhizinisi angama-23, igcizelela ukuthi "izithako zokudla akumele zithi zinemiphumela yokwelapha ezifweni." Ososayensi bakhathazekile ngokuthi ukuthatha ngobumpumputhe imithamo ephezulu ye-mannose kungase kuphazamise ukumila kwamathumbu - ukuhlolwa kwezilwane kubonise ukuthi ukuthatha isikhathi eside kuholela ekwehleni ngo-80% kobuningi be-Faecalibacterium prausnitzii kanye nokwanda okuphindwe kahlanu kwe-Fusobacterium nucleatum. Lesi sakamuva sihlobene kakhulu nokuqhubeka komdlavuza we-colorectal.

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I-Youdaoplaceholder0 Isahluko Sesihlanu Sokubikezela Ikusasa: Ulwandle Olubanzi Lwezidakamizwa Ezisekelwe ku-Glyco

Youdaoplaceholder0 5.1 I-Glycolic Revolution in Precision Medicine

Amasu okwelapha angawodwana asekelwe ku-tumor metabolic heterogeneity ayavela. Imodeli ye-"Mannose Sensitivity Score" (MSS) eyakhiwe yi-Broad Institute e-United States ingabikezela amathuba okusabela eziguli ku-mannose ngokuthola izinga lenkulumo ye-GLUT1, umsebenzi we-hexokinase kanye nesimo sokuguqulwa kwe-PMI ezicutshini zesimila. Eklanyweni yokuhlolwa komtholampilo kweSigaba II, iziguli ezinomdlavuza we-pancreatic ezinesikolo se-MSS esingu-≥75% zizobekwa kuqala ukuze zifakwe ukuze kuthuthukiswe izinga lokusabela kokwelashwa.

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I-Youdaoplaceholder0 5.2 Ukuhlanganiswa okunqamula umngcele kwezidakamizwa zobunjiniyela zikashukela

Ucwaningo lwe-Frontier alusanelisekile ngokusetshenziswa okukodwa kwe-mannose yemvelo. Ithimba le-MIT liklame i-conjugate ye-"mannose-paclitaxel", esebenzisa ithuba lokutholwa okuphezulu kwe-mannose ngamaseli wesimila ukufeza ukulethwa okuhlosiwe kwezidakamizwa ze-chemotherapy. Kumamodeli omdlavuza webele, ukusebenza kahle kokubulawa kwesimila kwale conjugate kwakuphindwe kathathu kune-paclitaxel yendabuko, kanti ubuthi bayo benhliziyo bunciphe ngo-60%. Okunye ukuphumelela kuvela e-Shanghai Jiao Tong University: ngokuhlanganisa i-mannose ne-photosensitizer i-Ce6, "ukwelashwa kwe-photodynamic okusekelwe kushukela" okungase kwenziwe kusebenze ukukhanya okuseduze kwe-infrared sekusunguliwe, okubonisa amandla okukhipha isimila esijulile.

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I-Youdaoplaceholder0 Isiphetho: "I-molecule emnandi" ebhala kabusha imithetho yokulwa nomdlavuza

Uhambo lokulwa nomdlavuza lwe-mannose luyinhlansi ekhazimulayo ebangelwa ukungqubuzana kwesayensi eyisisekelo nezidingo zomtholampilo. Ukusuka ekungeneleleni kwe-metabolic kuya ekulawuleni amasosha omzimba, kusukela ku-monotherapy kuye ezinhlanganisweni zemithi, le molekyuli kashukela yephula umugqa wokuvikela isimila ngamasu okuhlasela ahlukahlukene. Nakuba indlela yokuthengisa isabhekene nezinselelo ezifana nokwenza kahle umthamo, izindlela zokumelana nezidakamizwa, kanye nezinkambiso zokulawula, umphakathi wesayensi unethemba elikhulu ngakho - njengoba uJames Watson owazuza umklomelo kaNobel ekubeka, "Ingqikithi yomdlavuza i-genomic disorder, futhi i-mannoglucose isifundisa ukuthi ukungenelela kwe-metabolic kungase kubuyisele ukuhleleka." Iqhutshwa amasondo amabili omuthi onembile kanye nebhayoloji yokwenziwa, le "nguquko emnandi" ingase ingenise inkathi entsha yokwelashwa komdlavuza.