Youdaoplaceholder0 1.1 lālā huna o ka ?ohana kō ?

Ma ke ?ano he kumu ikehu kumu o nā mea ola, ua lō?ihi ka pa?a ?ana o ka ?ōnaehana ho?oka?awale ?ana o nā carbohydrates i loko o nā puke: monosaccharides (e like me ka glucose a me ka fructose), oligosaccharides (e like me ka lactose), a me nā polysaccharides (e like me ka starch). Eia nō na?e, aia ka ?oko?a o ka mannose i kāna "?ike ?elua" - ?a?ole ia he mea komo wale i ka metabolism ikehu akā he "?ano ?ōlelo huna" no ka kama?ilio kelepona. Aia ?o Mannose i kahi moku?āina manuahi i ka papa pectin o nā hua citrus a me nā paia cell o nā algae hohonu. I loko o ke kino kanaka, lilo ia i kumu mole o nā ka?ina hana physiological ko?iko?i e like me ka ?ike ?ana i ka immune a me ka ho?opili ?ana o ke kelepona ma o ka N-link glycosylation modification o glycoproteins.

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Youdaoplaceholder0 1.2 Ho?ololi ?ike mai ke Ola Urinary i nā Paionia ma?i ma?i ?

I ka ho?omaka ?ana o nā makahiki 1980, ua ?ike ke kaiāulu lapa?au hiki i ka mannose ke pale i nā ma?i ma?i urinary ma o ka ho?okūkū ho?okūkū i nā adhesins o nā bacteria pathogenic. ?O kēia ?ano hana i ho?āla ai i ke kū?ai wela o nā huahana olakino cranberry extract. Akā ?a?ole hiki i ka makahiki 2018 kahi noi?i ?āina a Cancer Research UK (CRUK) i ka puke pai Nature i hāpai maoli i ka pale i kāna mau hana anti-cancer: Ma kahi ki?i ki?i o ka ma?i ma?i pancreatic, ho?ohui ?ia he 20% mannose i ka wai inu i ho?emi i ka ulu ulu ?ana o ka ma?i e 40%, a i ka hui pū ?ana me ka lā?au chemotherapy gemcitabine, ua ho?olō?ihi ?ia ka manawa ola o nā ?iole. Ua ho?ohuli kēia ?ike i ka mana?o ma?amau "?o nā kō a pau e hāpai i ka ma?i kanesa".

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Youdaoplaceholder0 Mokuna 2 Ho?ololi i ka Mechanism Anti-Cancer: ?Ekolu "loka kō" Wehe i ka laina ola o ka Tumor ?

?O Youdaoplaceholder0 2.1 Ho?opa?a ?ia ka Metabolic: ?O ka "Trojan horse" i ho?ololi ?ia me he glucose ?

?O ka "Warburg Effect" o nā pūnaewele tumo e hiki ai i ka lawe ?ana o ka glucose i ?umi mau manawa ma mua o nā cell ma?amau. Ua ?ike ka hui CRUK ma o carbon-13 isotope tracing technology e hiki i ka mannose ke ho?okomo i nā pūnaewele ma?i ma?i ma o ke ?ano like o ka mea lawe glucose (GLUT1/3) me kahi ?ano like me ka glucose. Eia nō na?e, ma hope o ke komo ?ana, ua ho?opa?a wikiwiki ?ia e ka hexokinase i ka mannose-6-phosphate (M6P). ?A?ole hiki i kēia metabolic intermediate ke komo i ke ala glycolytic akā e hō?ili?ili ?ia i loko o ke kelepona e hana i kahi "pale metabolic", e alaka?i ana i ke keakea ?ana o ka synthesis ATP a me ka ?ā?ī ?ana o nā ?ano oxygen reactive (ROS), i ka hopena e ho?oulu ai i ka apoptosis o nā pūna?i kanesa (Figure 1).

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Youdaoplaceholder0 2.2 Ho?oponopono epigenetic: Ke kākau hou ?ana i ka "code memory" o nā ma?i ma?i ma?i ?

Ma 2023, ua hō?ike hou ?ia kahi hui noi?i mai ke Kulanui ?o Fudan ma Cell Metabolism e hiki i ka mannose ke hana ma ke ?ano he "ho?oponopono epigenome". I ka pancreatic ductal adenocarcinoma (PDAC), ua ho?emi nui ka mālama mannose i ka pae acetylation o ka paena histone H3K27, ka hopena i ka pale ?ana i nā hana transcriptional o ka oncogenes MYC a me KRAS. ?Oi aku ka kupanaha, ho?omau kēia hopena reprogramming - ?oiai ke ho?opau ?ia ka lawelawe ?ana i ka lā?au lapa?au, mālama mau nā cell cancer i ka invasive ha?aha?a, e hā?awi ana i nā mana?o hou no ka mālama radical.

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Youdaoplaceholder0 2.3 Ho?oponopono hou ?ana i ka microenvironment immune: Wehe i ka "ho?ololi ?ana i ke kō" o PD-L1 ?

Ua ?ike ?ia ka hui like ma nā ha?awina hope e hiki ai i ka mannose ke haki i ke ?ano palekana palekana o nā ma?i ma?i ma o ke keakea ?ana i ka ho?ololi glycosylation o ka programmed death ligand 1 (PD-L1). Ua hō?ike ?ia ka nānā ?ana o ka nui spectrometry i ka mannose i kāohi i ka N-glycosylation o asparagine ma ke kūlana 192 o ka protein PD-L1, ka hopena i kona hiki ?ole ke pelu pololei a heleuma ma ka membrane cell. ?O PD-L1, ka mea i nalowale i ka pale o ka "pale kō", ua hō?ailona ?ia e ka E3 ubiquitin ligase FBXW41 a ho?oha?aha?a ?ia e ka proteasome. I nā ?iole melanoma, ?o ka hui pū ?ana o ka mannose a me ka anti-PD-1 antibodies i ho?onui i ka nui o ka regression tumor piha mai 28% a i 79% (Figure 2).

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Youdaoplaceholder0 Mokuna 3 Mai nā ?ano holoholona a i nā ho?ā?o ?ana o ke kanaka: The Thorny Road of Translational Medicine ?

Youdaoplaceholder0 3.1 Nā Kūlana a me nā palena o ka noi?i preclinical ?

Ma ke ?ano ma?i ma?i pancreatic o CRUK, ?oiai ?o ka monotherapy me ka mannose i ho?opane?e i ka pi?i ?ana o ka tumo, ?a?ole hiki ke ho?okō i ke kala piha. Eia nō na?e, i ka hui pū ?ana me ka regimen chemotherapy FOLFIRINOX, ua ho?olō?ihi ?ia ka manawa ola median o nā ?iole mai 42 lā a i 98 lā, a ?a?ohe pi?i o ka ?ona. Ua ho?opuka hou ?ia kēia hopena ma ke ?ano ho?ohālike o ka ma?i ma?i umauma triple-negative ma MD Anderson Cancer Center. Eia nō na?e, ?ike pū nā mea noi?i ma kahi o 15% o nā ma?i ?a?ole i pane i ka mannose. Ua hō?ike hou ?ia ka nānā ?ana ua hō?ike nui ?ia kēia mau keena kū?oko?a lā?au i ka mannose-phosphate isomerase (PMI), hiki ke ho?ololi i ka M6P i fructose-6-phosphate a ho?ohui hou i ke ala glycolytic.

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Youdaoplaceholder0 3.2 He wana?ao maka?ala o nā ho?okolohua kanaka ?

?O ka ho?okolohua lapa?au Phase I mua o ka mannose i ho?omaka i ka makahiki 2022 (NCT05220739) i loa?a he 32 mau mea ma?i me nā ma?i koko pa?a. Ma ka pū?ulu o ka ho?okele waha o kēlā me kēia lā o 5g mannose, ua emi iho ka pae o ka DNA tumor (ctDNA) o 8 mau mea ma?i ma mua o 50%, ma waena o ka nui o nā metastases ate i ho?okahi ma?i ma?i ma?i pancreatic i ho?emi ?ia e 31%. Eia nō na?e, i ka pi?i ?ana o ka ma?i i 10g, ua loa?a ka ma?i ma?i pae III i 3 mau ma?i, e mana?o ana e pono e ho?olālā ?ia ka ho?olālā ho?okele. I kēia manawa, ho?omākaukau ?ia ka intravenous mannose me ka ho?ohana ?ana i ka ?enehana encapsulation nano-liposome. Hō?ike ka ?ikepili preclinical i ka hiki i ka 78% ka maika?i o ka lawe ?ana i ka ma?i ma?i, a ua ho?emi nui ?ia ko lākou ?ona.

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Youdaoplaceholder0 Mokuna 4 Ho?ololi ?oihana a me ka ho?opa?apa?a: ?O nā pilikia maoli o ka ho?ololi ?ana ?

Youdaoplaceholder0 4.1 Ho?oholo ka biology Synthetic i ka Puzzle hana nui ?

?O ka mannose i unuhi maoli ?ia ke kumu kū?ai (e pili ana i ka kilokani)

1200

He pa?akikī ke ho?okō i nā koi anti-cancer dose (i kēlā me kēia lā)

?O ke ala e ho?onui ai i ka huahana i

Ua hā?ule ke kumukū?ai i 1200), he mea pa?akikī ke ho?okō i ka koi anti-cancer dose (10-20g i kēlā me kēia lā). Ua ho?onui ?o Synthetic biology giant GinkgoBioworks i ka hua i 30g/L a ua ho?emi i ke kumukū?ai i 50/kg ma ka ho?ololi ?ana i ke ala mannose-1 - guanosine phosphate transferase (MPG) o Escherichia coli. ?O nā ?enehana holomua hou a?e e like me ka CRISPR-Cas9-edited Saccharomyces cerevisiae engineered bacteria i hiki ke hana pa?a i ka mannose ma?ema?e ki?eki?e i ka wā fermentation mau.

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Youdaoplaceholder0 4.2 ?O ka pā?ani ma waena o Hype pā?oihana a me nā loina ?epekema ?

Me ka mana?o o ka "anti-cancer sugar" e lilo i mea kaulana, he mau haneli o nā huahana olakino mannose e ?ōlelo nei he "lā?au kōkua no nā ?ōpū" i puka mai ma ka paepae Amazon, me nā kumukū?ai kumukū?ai he ?umi mau manawa. I ka makahiki 2023, ua ho?opuka ka US FDA i nā leka ho?omaopopo i nā ?oihana 23, e hō?ike ana "?a?ole pono nā mea?ai mea?ai e koi i nā hopena therapeutic i nā ma?i." Ke hopohopo nei ka po?e ?epekema ?o ka lawe makapō ?ana i ka nui o ka mannose e ho?opilikia i ka flora intestinal - ua hō?ike ?ia nā ho?okolohua holoholona i ka lawe ?ana i ka wā lō?ihi e alaka?i i ka 80% emi i ka nui o Faecalibacterium prausnitzii a me ka pi?i ?ana o ka Fusobacterium nucleatum. ?O ka mea hope e pili kokoke ana i ka holomua o ka ma?i kanesa colorectal.

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Youdaoplaceholder0 Mokuna ?Elima Nā Mana?o e hiki mai ana: ?O ka moana nui o nā lā?au lapa?au Glyco ?

Youdaoplaceholder0 5.1 ?O ka Glycolic Revolution in Precision Medicine ?

Ke puka mai nei nā ho?olālā lapa?au pilikino e pili ana i ka heterogeneity metabolic tumor. Hiki i ke kumu ho?ohālike "Mannose Sensitivity Score" (MSS) i ho?omohala ?ia e ka Broad Institute ma ?Amelika Hui Pū ?Ia hiki ke wānana i ka pane ?ana o ka po?e ma?i i ka mannose ma ka ?ike ?ana i ka pae hō?ike o GLUT1, ka hana hexokinase a me ke kūlana mutation PMI i loko o nā ?i?o tumora. I ka ho?olālā ?ana o nā ho?okolohua lapa?au Phase II, e hā?awi ?ia nā mea ma?i ma?i ma?i pancreatic me ka helu MSS o ≥75% i mea nui no ka ho?opili ?ana e ho?omaika?i i ka helu pane ?ana.

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Youdaoplaceholder0 5.2 Ka hui ?ana o ke kōpa?a o nā lā?au ?enekinia ?

?A?ole ?olu?olu ka noi?i Frontier me ka ho?ohana ?ana o ka mannose maoli. Ua ho?olālā ka hui MIT i kahi conjugate "mannose-paclitaxel", e ho?ohana ana i ka ho?onui ki?eki?e o ka mannose e nā cell tumor e ho?okō ai i ka hā?awi ?ana i nā lā?au lapa?au chemotherapy. Ma nā hi?ohi?ona ma?i ma?i ma?i umauma, ?oi aku ka maika?i o kēia conjugate i ?ekolu manawa ma mua o ka paclitaxel ku?una, a ua ho?emi ?ia kona cardiotoxicity e 60%. ?O kekahi holomua mai ke Kulanui ?o Shanghai Jiao Tong: ma ka hui ?ana i ka mannose me ka photosensitizer Ce6, kahi "photodynamic therapy" i hiki ke ho?āla ?ia e nā kukui infrared kokoke i ho?omohala ?ia, e hō?ike ana i ka hiki ke ho?opau i ka ?ōpū hohonu.

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Youdaoplaceholder0 Ka hopena: ?O ka "mole mole" e kākau hou ana i nā lula anti-cancer ?

?O ka huaka?i anti-cancer o mannose he ?ālohilohi i ho?āla ?ia e ka hui ?ana o ka ?epekema kumu a me nā pono lapa?au. Mai ka hana metabolic a hiki i ka ho?oponopono immune, mai ka monotherapy a hiki i nā regimens hui pū ?ana, ke wāwahi nei kēia mole kōpa?a i ka laina pale pale me nā ho?olālā ho?ouka kaua nui. ?Oiai ke kū nei ke ala kū?ai aku i nā pilikia e like me ka ho?onui ?ana i ka dosis, nā ?ano hana kū?ē i ka lā?au lapa?au, a me nā kūlana ho?oponopono, ke mana?o nui nei ke kaiāulu ?epekema no ia - e like me kā ka Nobel laureate James Watson i ?ōlelo ai, "?O ke ?ano o ka ma?i kanesa ?o ka ma?i genomic, a ke a?o mai nei ka mannoglucose iā mākou e hiki ke ho?iho?i i ka ?ōnaehana metabolic. Ke alaka?i ?ia e nā huila ?elua o ka lā?au lapa?au pololei a me ka biology synthetic, hiki i kēia "ho?ololi ?olu?olu" ke ho?omaka i kahi au hou o ka mālama ?ana i ka ma?i kanesa.