Youdaoplaceholder0 1.1 Wobisika wabanja la shuga

Monga maziko a mphamvu zamoyo zamoyo, dongosolo lamagulu lazakudya lakhala lolimba m'mabuku: monosaccharides (monga shuga ndi fructose), oligosaccharides (monga lactose), ndi polysaccharides (monga wowuma). Komabe, makamaka cha mannose chagona ake "awiri identity" - si otenga nawo mbali mu kagayidwe mphamvu komanso "achinsinsi khalidwe" kwa selo kulankhulana. Mannose amapezeka kwambiri mu free state mu pectin wosanjikiza wa zipatso za citrus ndi makoma a cell of deep-sea algae. M'thupi la munthu, limakhala maziko a mamolekyu azinthu zazikulu zakuthupi monga kuzindikira kwa chitetezo chamthupi komanso kumamatira kwa ma cell kudzera pakusintha kwa N-link glycosylation kwa glycoproteins.

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Youdaoplaceholder0 1.2 Cognitive Iteration from Urinary Health to Cancer Pioneers

Kumayambiriro kwa zaka za m'ma 1980, azachipatala adapeza kuti mannose amatha kupewa matenda a mkodzo poletsa mopikisana zomatira za mabakiteriya oyambitsa matenda. Njirayi yapangitsa kuti pakhale kugulitsa kotentha kwa cranberry extract zathanzi. Koma sizinali mpaka chaka cha 2018 pomwe kafukufuku wodziwika bwino wa Cancer Research UK (CRUK) mu nyuzipepala ya Nature adakwezadi chophimba pa zoyesayesa zake zolimbana ndi khansa: Mu mtundu wa mbewa wa khansa ya kapamba, kuwonjezera 20% mannose kumadzi akumwa kunachepetsa kukula kwa chotupa ndi 40%, komanso kuphatikizidwa ndi mankhwala a chemotherapy gemcitabine, kupulumuka kunatalikitsidwa nthawi zitatu za mi2. Kupeza uku kwasintha malingaliro odziwika kuti "shuga onse amalimbikitsa khansa".

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Youdaoplaceholder0 Mutu 2 Kufotokozera Njira Yolimbana ndi Khansa: "Maloko atatu a shuga" Tsegulani njira yamoyo ya Chotupa

Youdaoplaceholder0 2.1 Kubera kwa Metabolic: "Trojan horse" yobisika ngati shuga

"Warburg Effect" ya maselo otupa amathandizira kuti glucose awonjezeke kuchulukitsa kakhumi kuposa ma cell abwinobwino. Gulu la CRUK lidazindikira kudzera muukadaulo wa carbon-13 isotope tracing kuti mannose amatha kulowa m'maselo a khansa kudzera mumtundu womwewo wa glucose transporter (GLUT1/3) wokhala ndi mawonekedwe ofanana ndi a shuga. Komabe, ikalowa, imalowa mwachangu phosphorylated ndi hexokinase kupita ku mannose-6-phosphate (M6P). Kagayidwe kachakudya kameneka sikangathe kulowa mumsewu wa glycolytic koma m'malo mwake amadziunjikira mkati mwa selo kuti apange "chotchinga kagayidwe kachakudya", zomwe zimapangitsa kutsekeka kwa kaphatikizidwe ka ATP komanso kuphulika kwa mitundu yogwira ntchito ya okosijeni (ROS), kenako ndikuyambitsa apoptosis ya maselo a khansa (Chithunzi 1).

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Youdaoplaceholder0 2.2 Epigenetic regulation: Kulembanso "memory code" ya maselo a khansa

Mu 2023, gulu lofufuza kuchokera ku Fudan University ku Cell Metabolism linanenanso kuti mannose amatha kukhala "epigenome editor". Muchitsanzo cha pancreatic ductal adenocarcinoma (PDAC), chithandizo cha mannose chinachepetsa kwambiri mulingo wa acetylation wa malo a histone H3K27, zomwe zidapangitsa kuti ntchito zolembera za oncogenes MYC ndi KRAS zilephereke. Chodabwitsa kwambiri, kukonzanso kowoneka bwino kumeneku kumakhala kosalekeza - ngakhale kuyimitsidwa kwamankhwala kumasiya, maselo a khansa amakhalabe osawukira, ndikupereka malingaliro atsopano ochizira mwamphamvu.

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Youdaoplaceholder0 2.3 Kukonzanso kwachilengedwe kwa chitetezo chamthupi: Kuchotsa "zobisika zopaka shuga" za PD-L1

Gulu lomwelo lomwe lidapezeka m'maphunziro otsatirawa kuti mannose amatha kusokoneza njira yopulumukira ya zotupa posokoneza kusintha kwa glycosylation kwa programmed death ligand 1 (PD-L1). Kusanthula kwa misa spectrometry kunawonetsa kuti mannose amalepheretsa N-glycosylation ya asparagine pamalo 192 a protein ya PD-L1, zomwe zimapangitsa kuti zisathe kupindika bwino ndikukhazikika pa nembanemba ya cell. PD-L1, yomwe imataya chitetezo cha "chishango cha shuga", imalembedwa ndi E3 ubiquitin ligase FBXW41 ndikunyozedwa ndi proteasome. Mu mbewa za melanoma, kuphatikiza kwa mannose ndi anti-PD-1 ma antibodies kumawonjezera kuchuluka kwa chotupa kuchokera ku 28% mpaka 79% (Chithunzi 2).

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Youdaoplaceholder0 Mutu 3 Kuchokera pa Zitsanzo Zanyama kupita ku Mayesero Achipatala a Anthu: The Thorny Road of Translational Medicine

Youdaoplaceholder0 3.1 Zotsogola ndi Zochepera pa kafukufuku wa Preclinical

Mu pancreatic khansa chitsanzo CRUK, ngakhale monotherapy ndi mannose kuchedwa chotupa, izo zinalephera kukwaniritsa chikhululukiro chathunthu. Komabe, ataphatikizidwa ndi FOLFIRINOX chemotherapy regimen, nthawi yapakati yopulumuka ya mbewa inatalikitsidwa kuchokera masiku 42 mpaka masiku 98, ndipo panalibe kuwonjezeka kwa poizoni. Zotsatirazi zidapangidwanso mu mtundu wa khansa ya m'mawere yopanda katatu ku MD Anderson Cancer Center: Mannose adachulukitsa kuchuluka kwa chotupa cha paclitaxel kuchoka pa 45% mpaka 72%. Komabe, ofufuza adapezanso kuti pafupifupi 15% ya zotupazo sizinayankhe mannose. Kusanthula kwina kunawonetsa kuti maselo osamva mankhwalawa amafotokoza kwambiri mannose-phosphate isomerase (PMI), omwe amatha kusintha M6P kukhala fructose-6-phosphate ndikulumikizananso ndi njira ya glycolytic.

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Youdaoplaceholder0 3.2 M'bandakucha wochenjera wa mayesero aumunthu

Kuyesa kwachipatala kwa Phase I kwa mannose komwe kunayambika mu 2022 (NCT05220739) kunaphatikizapo odwala 32 omwe anali ndi zotupa zolimba kwambiri. Mu gulu la mlingo wa tsiku ndi tsiku pakamwa makonzedwe a 5g mannose, kuzungulira chotupa DNA (ctDNA) milingo 8 odwala 8 anatsika ndi oposa 50%, mwa amene buku la chiwindi metastases mu mmodzi pancreatic khansa wodwala anatsika ndi 31%. Komabe, pamene mlingo ukukwera kufika ku 10g, kutsekula m'mimba kwa kalasi ya III kunachitika mwa odwala atatu, kutanthauza kuti njira yoyendetsera ntchito iyenera kukonzedwa. Pakalipano, kukonzekera kwa mtsempha wa mannose pogwiritsa ntchito teknoloji ya nano-liposome encapsulation ikuchitika. Deta ya preclinical ikuwonetsa kuti mphamvu yawo yoperekera chotupa imafika 78%, ndipo kawopsedwe wawo amachepa kwambiri.

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Youdaoplaceholder0 Mutu 4 Kusintha Kwamafakitale ndi Zotsutsana: Zovuta Zenizeni za Sweet Revolution

Youdaoplaceholder0 4.1 Synthetic Biology Imathetsa Puzzle yopanga Misa

Mannose otengedwa mwachilengedwe ndi okwera mtengo (pafupifupi kilogalamu imodzi)

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Ndizovuta kukwaniritsa zofunikira za mlingo wotsutsa khansa (tsiku ndi tsiku)

Njira ina ndikuwonjezera zotuluka ku

Mtengo watsikira ku 1200), zomwe zimakhala zovuta kukwaniritsa mlingo wotsutsa khansa (10-20g patsiku). Synthetic biology GinkgoBioworks yachulukitsa zokolola mpaka 30g/L ndikuchepetsa mtengo mpaka 50/kg posintha njira ya mannose-1 - guanosine phosphate transferase (MPG) ya Escherichia coli. Ukadaulo wapamwamba kwambiri monga mabakiteriya opangidwa ndi CRISPR-Cas9 opangidwa ndi Saccharomyces cerevisiae atha kutulutsa mannose oyera kwambiri panthawi yonseyi.

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Youdaoplaceholder0 4.2 Masewera apakati pa Hype yamabizinesi ndi machitidwe asayansi

Ndi lingaliro la "shuga wotsutsa khansa" kukhala wotchuka, mazana a mankhwala a mannose omwe amati ndi "mankhwala othandizira zotupa" atulukira pa nsanja ya Amazon, ndi malipiro amtengo wapatali mpaka kakhumi. Mu 2023, US FDA idapereka makalata ochenjeza kwa mabizinesi 23, kutsindika kuti "zakudya zopatsa thanzi siziyenera kunena kuti zili ndi chithandizo chamatenda." Asayansi akuda nkhawa kuti kumwa mowa wambiri wa mannose mosasamala kungasokoneze zomera za m'mimba - kuyesa kwa nyama kwasonyeza kuti kudya kwa nthawi yaitali kumabweretsa kuchepa kwa 80% ya Faecalibacterium prausnitzii ndi kuwonjezeka kasanu kwa Fusobacterium nucleatum. Chotsatiracho chikugwirizana kwambiri ndi kukula kwa khansa ya m'mimba.

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Youdaoplaceholder0 Mutu 5 Zoyembekeza Zam'tsogolo: Nyanja Yaikulu ya Mankhwala Ochokera ku Glyco

Youdaoplaceholder0 5.1 Kusintha kwa Glycolic mu Precision Medicine

Njira zochizira payekhapayekha zotengera chotupa cha metabolic heterogeneity zikutuluka. Mtundu wa "Mannose Sensitivity Score" (MSS) wopangidwa ndi Broad Institute ku United States ukhoza kulosera za kuthekera kwa odwala ku mannose pozindikira kuchuluka kwa mawu a GLUT1, zochitika za hexokinase ndi kusintha kwa PMI m'matumbo a chotupa. Popanga mayeso azachipatala a Phase II, odwala khansa ya pancreatic omwe ali ndi MSS ≥75% adzapatsidwa mwayi wophatikizidwa kuti athandizire kuyankha kwamankhwala.

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Youdaoplaceholder0 5.2 Kuphatikizika kwa malire a shuga Engineering mankhwala

Kafukufuku wa Frontier sakukhutiranso ndi kugwiritsa ntchito mannose achilengedwe kamodzi kokha. Gulu la MIT lapanga cholumikizira cha "mannose-paclitaxel", chomwe chimatenga mwayi pakutengedwa kwa mannose ndi ma cell chotupa kuti akwaniritse chithandizo chamankhwala a chemotherapy. M'mitundu ya khansa ya m'mawere, mphamvu yopha chotupa cha conjugate iyi inali katatu kuposa paclitaxel yachikhalidwe, ndipo mtima wake wamtima udachepetsedwa ndi 60%. Kupambana kwina kumachokera ku Shanghai Jiao Tong University: pophatikiza mannose ndi photosensitizer Ce6, "shuga-based photodynamic therapy" yomwe imatha kuyatsidwa ndi kuwala kwapafupi ndi infrared yapangidwa, kuwonetsa kuthekera kochotsa chotupa chakuya.

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Youdaoplaceholder0 Mapeto: "Molekyu yokoma" yolembanso malamulo odana ndi khansa.

Ulendo wotsutsana ndi khansa wa mannose ndiwowoneka bwino kwambiri woyambitsidwa ndi kugundana kwa sayansi ndi zofunikira zachipatala. Kuchokera pakuchitapo kanthu kwa kagayidwe kachakudya mpaka pakuwongolera chitetezo chamthupi, kuchokera ku monotherapy kupita kumagulu ophatikizika, molekyulu ya shuga iyi ikuphwanya mzere woteteza chotupa ndi njira zowukira zamitundu yambiri. Ngakhale njira yamalonda ikukumanabe ndi zovuta monga kukhathamiritsa kwa mlingo, njira zotsutsana ndi mankhwala, ndi ndondomeko zoyendetsera, gulu la asayansi liri ndi chiyembekezo chachikulu - monga momwe James Watson wopambana mphoto ya Nobel ananenera, "Chofunika kwambiri cha khansa ndi matenda a genomic, ndipo mannoglucose amatiphunzitsa kuti kulowererapo kwa metabolic kungabwezeretse dongosolo." Motsogozedwa ndi mawilo apawiri amankhwala olondola komanso biology yopangira, "kusintha kokoma" kumeneku kungayambitse nyengo yatsopano yochiza khansa.