Youdaoplaceholder0 1.1 Tus tswv cuab zais ntawm tsev neeg qab zib

Raws li lub zog tseem ceeb ntawm cov kab mob muaj sia, kev faib tawm ntawm cov carbohydrates tau ntev tau ua tiav hauv cov ntawv nyeem: monosaccharides (xws li qabzib thiab fructose), oligosaccharides (xws li lactose), thiab polysaccharides (xws li cov hmoov txhuv nplej siab). Txawm li cas los xij, qhov tshwj xeeb ntawm mannose nyob hauv nws "dual tus kheej" - nws tsis yog tsuas yog koom nrog hauv lub zog metabolism, tab sis kuj yog "tus cim lo lus zais" rau kev sib txuas lus ntawm tes. Mannose yog dav nyob rau hauv ib tug dawb lub xeev nyob rau hauv lub pectin txheej ntawm citrus txiv hmab txiv ntoo thiab lub cell phab ntsa ntawm tob-sea algae. Hauv tib neeg lub cev, nws dhau los ua lub hauv paus molecular ntawm cov txheej txheem physiological tseem ceeb xws li kev paub txog kev tiv thaiv kab mob thiab cell adhesion los ntawm N-link glycosylation hloov kho ntawm glycoproteins.

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Youdaoplaceholder0 1.2 Cognitive Iteration los ntawm Urinary Health rau Cancer Pioneers

Thaum ntxov li xyoo 1980, cov neeg kho mob tau tshawb pom tias mannose tuaj yeem tiv thaiv cov kab mob urinary los ntawm kev sib tw inhibiting adhesins ntawm cov kab mob pathogenic. Cov txheej txheem no tau ua rau kub muag ntawm cranberry extract cov khoom noj qab haus huv. Tab sis nws tsis yog txog xyoo 2018 uas txoj kev tshawb fawb keeb kwm los ntawm Cancer Research UK (CRUK) hauv phau ntawv Journal Nature tau nqa daim ntaub thaiv ntawm nws cov kev tiv thaiv kab mob: Hauv tus nas qauv ntawm tus kab mob qog noj ntshav, ntxiv 20% mannose rau haus dej txo cov qog loj hlob los ntawm 40%, thiab thaum ua ke nrog cov tshuaj kho mob, cov tshuaj tiv thaiv kab mob m2. sij hawm. Qhov kev tshawb pom no tau thim rov qab qhov kev pom zoo uas "tag nrho cov suab thaj txhawb kev mob qog noj ntshav".

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Youdaoplaceholder0 Tshooj 2 Kev Txiav Txim Siab Kev Tiv Thaiv Kab Mob Cancer: Peb "qab zib xauv" Xauv cov qog lub neej

Youdaoplaceholder0 2.1 Metabolic Hijacking: Tus "Trojan nees" disguised li qabzib

Qhov "Warburg Effect" ntawm cov qog hlwb ua rau lawv cov piam thaj nce siab li kaum npaug ntawm cov cell qub. Pab pawg CRUK tshawb pom los ntawm carbon-13 isotope tracing thev naus laus zis uas mannose tuaj yeem nkag mus rau cov qog nqaij hlav cancer los ntawm tib hom glucose transporter (GLUT1/3) nrog cov qauv zoo ib yam li cov piam thaj. Txawm li cas los xij, tom qab nkag mus, nws tau nrawm phosphorylated los ntawm hexokinase rau mannose-6-phosphate (M6P). Qhov nruab nrab metabolic no tsis tuaj yeem nkag mus rau hauv glycolytic txoj hauv kev tab sis hloov mus rau hauv lub cell los tsim "metabolic barrier", ua rau muaj kev cuam tshuam ntawm ATP synthesis thiab tawg ntawm reactive oxygen hom (ROS), thaum kawg ua rau apoptosis ntawm cov qog nqaij hlav cancer (Daim duab 1).

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Youdaoplaceholder0 2.2 Epigenetic regulation: Rewriting the "nco code" of cancer cells

Xyoo 2023, pab pawg tshawb fawb los ntawm Fudan University hauv Cell Metabolism tau tshaj tawm tias mannose tuaj yeem ua "epigenome editor". Hauv cov qauv pancreatic ductal adenocarcinoma (PDAC), mannose kev kho mob txo qis qib acetylation ntawm histone H3K27 site, uas ua rau inhibition ntawm transcriptional kev ua ub no ntawm oncogenes MYC thiab KRAS. Tsis tas li ntawd xav tsis thoob, qhov pom tau hais tias qhov kev rov ua dua tshiab no tsis tu ncua - txawm tias kev tswj hwm tshuaj raug tso tseg, cov qog nqaij hlav cancer tseem muaj kev cuam tshuam tsawg, muab cov tswv yim tshiab rau kev kho mob radical.

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Youdaoplaceholder0 2.3 Immune microenvironment remodeling: Tearing off the "qab zib-coated disguise" ntawm PD-L1

Tib pab pawg pom hauv cov kev tshawb fawb tom ntej uas mannose tuaj yeem tawg lub cev tiv thaiv kab mob ntawm cov qog los ntawm kev cuam tshuam nrog kev hloov kho glycosylation ntawm programmed tuag ligand 1 (PD-L1). Kev tsom xam spectrometry tau qhia tias mannose inhibited N-glycosylation ntawm asparagine ntawm txoj hauj lwm 192 ntawm PD-L1 protein, uas ua rau nws tsis muaj peev xwm folds kom raug thiab thauj tog rau nkoj ntawm lub cell membrane. PD-L1, uas poob kev tiv thaiv ntawm "cov ntaub thaiv npog", yog sau los ntawm E3 ubiquitin ligase FBXW41 thiab degraded los ntawm cov proteasome. Hauv cov nas melanoma, kev sib xyaw ntawm mannose thiab anti-PD-1 cov tshuaj tiv thaiv tau nce qhov ua tiav cov qog regression ntawm 28% mus rau 79% (Daim duab 2).

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Youdaoplaceholder0 Tshooj 3 Los Ntawm Cov Qauv Tsiaj Rau Tib Neeg Kev Kho Mob: Thorny Road of Translational Medicine

Youdaoplaceholder0 3.1 Kev Tshaj Tawm thiab Kev Txwv ntawm Kev Tshawb Fawb Txog Kev Tshawb Fawb

Hauv cov qauv mob qog noj ntshav ntawm CRUK, txawm hais tias monotherapy nrog mannose ncua kev mob qog noj ntshav, nws ua tsis tau tiav kev tshem tawm. Txawm li cas los xij, thaum ua ke nrog FOLFIRINOX chemotherapy regimen, lub sijhawm nyob nruab nrab ntawm cov nas tau ncua ntev li ntawm 42 hnub mus rau 98 hnub, thiab tsis muaj tshuaj lom ntxiv. Cov txiaj ntsig no tau rov ua dua tshiab hauv peb tus qauv mob qog noj ntshav tsis zoo ntawm MD Anderson Cancer Center: Mannose tau nce cov qog nqaij hlav ntawm paclitaxel los ntawm 45% mus rau 72%. Txawm li cas los xij, cov kws tshawb fawb kuj pom tias kwv yees li 15% ntawm cov qog tsis teb rau mannose. Kev tshuaj xyuas ntxiv tau qhia tias cov tshuaj tiv thaiv kab mob no tau nthuav tawm mannose-phosphate isomerase (PMI), uas tuaj yeem hloov M6P rau hauv fructose-6-phosphate thiab rov txuas mus rau txoj kev glycolytic.

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Youdaoplaceholder0 3.2 Kev ceev faj kaj ntug ntawm tib neeg kev sim siab

Thawj Phase I kev soj ntsuam ntawm mannose pib hauv 2022 (NCT05220739) suav nrog 32 tus neeg mob uas muaj cov qog nqaij hlav siab heev. Hauv cov koob tshuaj txhua hnub ntawm kev tswj hwm qhov ncauj ntawm 5g mannose, circulating qog DNA (ctDNA) theem ntawm 8 tus neeg mob tau txo qis los ntawm ntau dua 50%, nrog rau qhov ntim ntawm daim siab metastases hauv ib tus neeg mob qog noj ntshav txo qis los ntawm 31%. Txawm li cas los xij, thaum koob tshuaj nce mus txog 10g, qib III raws plab tau tshwm sim hauv 3 tus neeg mob, qhia tias kev tswj hwm lub tswv yim yuav tsum tau ua kom zoo dua. Tam sim no, kev npaj cov tshuaj mannose uas siv nano-liposome encapsulation tshuab yog nyob rau hauv kev txhim kho. Cov ntaub ntawv kho mob ua ntej qhia tau tias lawv cov qog nqaij hlav ua haujlwm tau nce mus txog 78%, thiab lawv cov tshuaj lom tau txo qis.

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Youdaoplaceholder0 Tshooj 4 Muaj Kev Hloov Kho thiab Kev Tsis Txaus Siab: Qhov Kev Sib Tw Tiag Tiag ntawm Kev Hloov Kho Qab Zib

Youdaoplaceholder0 4.1 Synthetic biology daws cov kev tsim khoom loj

Naturally extracted mannose yog kim (txog ib kilogram)

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Nws yog qhov nyuaj kom ua tau raws li qhov yuav tsum tau txhaj tshuaj tiv thaiv kab mob qog noj ntshav (txhua hnub)

Txoj kev mus kom ze yog nce cov zis rau

Tus nqi tau nqis mus rau 1200), uas nyuaj ua kom tau raws li qhov yuav tsum tau txhaj tshuaj tiv thaiv kab mob (10-20g ib hnub). Synthetic biology giant GinkgoBioworks tau nce cov txiaj ntsig mus rau 30g / L thiab txo tus nqi rau 50 / kg los ntawm kev hloov kho mannose-1 - guanosine phosphate transferase (MPG) txoj hauv kev ntawm Escherichia coli. Ntau cov thev naus laus zis xws li CRISPR-Cas9-edited Saccharomyces cerevisiae engineered bacteria tau muaj peev xwm ruaj khov tsim cov txiv neej siab dawb huv thaum lub sij hawm fermentation tas li.

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Youdaoplaceholder0 4.2 Qhov Kev Ua Si ntawm kev lag luam Hype thiab kev coj ncaj ncees

Nrog lub tswv yim ntawm "anti-cancer qab zib" tau nrov, pua pua ntawm cov khoom noj qab haus huv mannose thov kom ua "kev pab kho mob qog noj ntshav" tau tshwm sim ntawm Amazon platform, nrog cov nqi them nqi siab txog kaum npaug. Xyoo 2023, US FDA tau tshaj tawm tsab ntawv ceeb toom rau 23 lub tuam txhab, hais tias "cov tshuaj noj yuav tsum tsis txhob lees tias muaj kev cuam tshuam rau cov kab mob." Cov kws tshawb fawb tau txhawj xeeb tias qhov muag tsis pom kev noj cov tshuaj mannose ntau tuaj yeem cuam tshuam cov kab mob hauv plab - kev sim tsiaj tau pom tias kev noj haus mus ntev ua rau 80% txo qis hauv kev nplua nuj ntawm Faecalibacterium prausnitzii thiab nce tsib npaug ntawm Fusobacterium nucleatum. Cov tom kawg yog ze ze rau kev mob qog noj ntshav hauv plab.

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Youdaoplaceholder0 Tshooj Tsib Tsib Lub Zeem Muag Yav Tom Ntej: Dej hiav txwv loj ntawm Glyco-based Tshuaj

Youdaoplaceholder0 5.1 Lub Glycolic Revolution hauv Precision Tshuaj

Cov tswv yim kho tus kheej raws li qog nqaij hlav metabolic heterogeneity tau tshwm sim. Tus qauv "Mannose Sensitivity Score" (MSS) tus qauv tsim los ntawm Broad Institute hauv Tebchaws Meskas tuaj yeem kwv yees cov lus teb tshwm sim ntawm cov neeg mob rau mannose los ntawm kev txheeb xyuas cov theem ntawm GLUT1, hexokinase kev ua thiab PMI kev hloov pauv hauv cov ntaub so ntswg. Hauv kev tsim ntawm Phase II kev sim tshuaj, cov neeg mob qog noj ntshav pancreatic nrog MSS tus qhab nia ntawm ≥75% yuav muab qhov tseem ceeb rau kev suav nrog txhawm rau txhim kho cov lus teb kho mob.

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Youdaoplaceholder0 5.2 Hla-border fusion ntawm qab zib Engineering tshuaj

Kev tshawb fawb Frontier tsis txaus siab rau ib daim ntawv thov ntawm ntuj mannose. Pab pawg MIT tau tsim ib qho "mannose-paclitaxel" conjugate, uas yuav siv sij hawm kom zoo dua ntawm kev nce siab ntawm mannose los ntawm cov qog hlwb kom ua tiav cov hom phiaj xa cov tshuaj kho mob. Hauv cov qauv mob qog noj ntshav, cov qog-tua ua tau zoo ntawm qhov kev sib txuas no yog peb zaug ntawm cov tshuaj paclitaxel, thiab nws cov cardiotoxicity raug txo los ntawm 60%. Lwm qhov kev ua tiav los ntawm Shanghai Jiao Tong University: los ntawm kev sib txuas mannose nrog cov duab sensitizer Ce6, "qab zib-raws li kev kho mob photodynamic" uas tuaj yeem ua haujlwm los ntawm lub teeb ze-infrared tau tsim, ua kom pom muaj peev xwm hauv cov qog nqaij hlav sib sib zog nqus.

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Youdaoplaceholder0 Xaus: Cov "qab zib molecule" rov sau dua cov cai tiv thaiv kabmob

Txoj kev tiv thaiv kab mob qog noj ntshav ntawm mannose yog qhov ci ntsa iab uas tshwm sim los ntawm kev sib tsoo ntawm cov kev tshawb fawb yooj yim thiab cov kev xav tau kho mob. Los ntawm kev cuam tshuam metabolic mus rau kev tiv thaiv kab mob, los ntawm kev kho mob monotherapy mus rau kev sib xyaw ua ke, cov piam thaj molecule no tau rhuav tshem cov qog tiv thaiv kab mob nrog ntau qhov kev tawm tsam. Txawm hais tias txoj kev lag luam tseem tab tom ntsib teeb meem xws li kev siv tshuaj kom zoo, tshuaj tiv thaiv kab mob, thiab cov cai tswj hwm, cov zej zog kev tshawb fawb tau muaj kev cia siab rau nws - raws li Nobel laureate James Watson tau hais tias, "Lub ntsiab lus ntawm kev mob qog noj ntshav yog kab mob genomic, thiab mannoglucose qhia peb tias kev cuam tshuam ntawm metabolic tuaj yeem rov qab txiav txim dua." Tsav los ntawm ob lub log ntawm cov tshuaj precision thiab hluavtaws biology, qhov "qab zib kiv puag ncig" tuaj yeem ua rau lub sijhawm tshiab ntawm kev kho mob qog noj ntshav.