I ke kaua lō?ihi ma waena o ke kanaka a me ka ma?i kanesa, ua hā?awi mau ke ?ano i nā hō?ailona e ho?oponopono ai i ka pilikia ma nā ala i mana?o ?ole ?ia. I nā makahiki i hala iho nei, ua lilo kahi monosaccharide ma?amau - Mannose - i mea nui o ka noi?i ?epekema ma muli o kāna mau waiwai anti-cancer. ?O kēia hexose, ka mea i ?ike nui ?ia i loko o nā cranberries a me nā hua citrus, ua pi?i a?e mai kahi kuleana kāko?o i ke kula o ka mea?ai i ka hana alaka?i i ka noi?i ?ana i ka metabolism tumor, e hō?ike ana i kahi ?ano hou o nā mea kō i ka ho?oponopono ?ana i ke ola. E nānā hohonu kēia ?atikala pehea e ho?ololi hou ai ka mannose i ka ?āina lapa?au ma?i ma?i mai ?ehā mau ?ao?ao: ka noi?i kumu, ka hana o ka hana, ka ho?ololi ?ana i ka lā?au lapa?au a me nā kūlana ?oihana.

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Mokuna One: Subverting Cognition: The Anti-Cancer Alaala o Sweet Molecules

1.1 Paradigm Shift in Carbohydrate noi?i

I nā mana?o ku?una, ua mana?o ?ia ke kō (carbohydrates) he "kālā ikehu". ?Oi aku ka glucose, ?o ia ke kumu kumu o ka hanu cellular, ua hō?ike piha ?ia ka hui ?ana ma waena o kāna mau mea ?ino a me ka ulu ?ana o ka ma?i kanesa. Eia nō na?e, kahi ha?awina holomua i pa?i ?ia e Cancer Research UK ma ka puke mo?olelo Nature ma 2018 ua kākau hou i kēia mo?olelo - ua hō?oia ka hui noi?i no ka manawa mua e hiki i ka mannose ke koho koho i ka ho?onui ?ana o nā ma?i ma?i ma?i ma o ka ho?opili ?ana i ke ala o ke kōpa?a o ke kō, me ka li?ili?i o ka hopena i nā kiko ma?amau. ?A?ole i ho?ohuli wale kēia ?ike i ka stereotype "ho?oikaika nā sugars āpau i ka ma?i kanesa", akā wehe pū kekahi i kahi kahua kaua hou no ka metabolic intervention therapy.

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1.2 Hiki i ke Koola o Mannose

Ma ke ?ano he isomer o ka glucose, ua māhele ?ia ka mannose i kahi moku?āina manuahi ma ka epidermis o nā hua e like me ka citrus a me nā ?āpala i ke ?ano, a i ?ole ke komo ?ana i ke kūkulu ?ana i nā membrane biological i ke ?ano o glycoproteins. I loko o ke kino o ke kanaka, ua phosphorylated ka mannose e hana i ka mannose-6-phosphate (M6P), i lilo i molekele hō?ailona nui no ka ho?oka?awale ?ana i ka enzyme lysosomal. Ua hō?ike ?ia nā ha?awina ma mua i kāna hana i ka pale ?ana i nā ma?i urinary tract: ma ka ho?okūkū pa?a ?ana i nā mea ho?opa?a adhesion o nā bacteria pathogenic, ua poloka ia i ko lākou noho ?ana ma ka urothelium. ?O kēia hi?ohi?ona ka mea i ho?āla ai i nā ?ano mea?ai mea?ai e pili ana i ka mannose, akā ?o ka loa?a ?ana o kona hiki ke pale i ka ma?i ma?i i alaka?i i ka pi?i nui o kāna waiwai hana.

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Mokuna ?Elua: Ho?oka?awale ?epekema: ?O ka hana ?ekolu o ka Mannose Against Cancer

2.1 Ho?opa?a ?ana i ka metabolic: ?oki ?ana i ke kaulahao ho?olako "sugar addiction" o nā ma?i ma?i ma?i

?O ka hopena Warburg o nā pu?upu?u pu?upu?u (e hilina?i mau nei i ka glycolysis no ka ikehu a i loko o kahi kaiapuni waiwai nui o ka oxygen) hiki i kā lākou lawe ?ana i ka glucose a hiki i ka ?umi mau manawa ma mua o nā cell ma?amau. Ua ?ike ?ia kahi hui Pelekania ma o ka ?enehana isotope tracing ma hope o ke komo ?ana o ka mannose i nā pūnaewele ma?i ma?i, ua ho?opa?a ?ia e ka hexokinase e hana i ka M6P a hō?ili?ili i nā mea nui i loko o nā cell. ?A?ole ?o kēia "pseudo-metabolite" e noho wale i nā kahawai o ka transporter glucose (GLUT), akā ho?okūkū pū nō ho?i e kāohi i ka hana o ka phosphoglucose isomerase, ka hopena i ka nele o nā kī waena i ka glycolysis a me ka tricarboxylic acid cycle, i ka hopena e ho?oulu ai i kahi pilikia ikehu i loko o nā ma?i kanesa (Figure 1).

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2.2 Epigenetics: Ho?oponopono hou i ka microenvironment tumor

?O kahi noi?i i pa?i ?ia e Fudan University in Cell Metabolism i 2023 i hō?ike hou ?ia e hiki i ka mannose ke ho?ohuli i ka epigenetic aberrations i nā ma?i kanesa ma o ka ho?oponopono ?ana i nā pae acetylation histone. Ua hō?ike ?ia nā ho?okolohua i loko o nā pūnaewele ma?i ma?i pancreatic i mālama ?ia me ka mannose, ua ho?emi ?ia ke degere acetylation o ka wahi ho?olaha o ka oncogene MYC, a ua kāohi nui ?ia kāna hana transcriptional. Ho?onāwaliwali kēia hopena reprogramming epigenetic i nā hi?ohi?ona invasive a malo?o o nā cell tumo, e hā?awi ana i kahi fulcrum theoretical no ka ho?omohala ?ana i nā lā?au epigenetic hui.

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2.3 Immune Synergy: Wehe i ka "Invisibility Cloak" o PD-L1

?Oi aku ka ho?ohaunaele i ?ike ?ia e ka hui like hiki i ka mannose ke kuhikuhi i ka mīkini pale pale pale. Ma o ka nānā ?ana o ka spectrometry, ua hō?oia nā mea noi?i e pale ana ka mannose i ka ho?opili pololei ?ana a me ka localization membrane o ka protein PD-L1 ma o ka ho?opili ?ana i kāna ho?ololi N-glycosylation. ?O ka protein PD-L1, ka mea i nalowale i ka "umbrella pale" o ke kaulahao kō, ?oi aku ka maika?i o ka ubiquitinated a ho?oha?aha?a ?ia, ma laila e ho?opau ai i ka hō?ailona pale ma nā pūnaewele T. Ma ke ?ano ?iole melanoma, ?o ka hui pū ?ana o ka mannose a me ka anti-PD-1 antibody i ho?onui i ka nui o ka regression tumor i 78%, ?oi aku ma mua o ka lā?au ho?okahi (Figure 2).

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Mokuna ?Ekolu: Mai ka Laboratory a Clinical: The Breakthrough Path of Translational Medicine

3.1 Milestones o ka noi?i preclinical

Ma nā ho?okolohua holoholona he nui, ua hō?ike ?o mannose i ka hiki ke kū i ka ma?i kanesa ākea. Ua komo kekahi hui Pelekania i nā ?iole ho?ohālike o ka ma?i ma?i pancreatic me ka wai inu mannose he 20% a ?ike ?ia ua ho?opane?e ?ia ka pi?i ?ana o ka nui o ka ma?i ma?i a hiki i 40%, a ?a?ohe mea nui o ka ate a i ?ole ka ?ona. ?Oi aku ka hau?oli, ke ho?ohana pū ?ia me ka gemcitabine, ua ho?olō?ihi ?ia ke ola o nā ?iole e 2.3 mau manawa, e hō?ike ana i kāna waiwai ho?onaninani chemotherapy. Ua hō?ike ?ia nā ho?okolohua hō?oia kū?oko?a ma MD Anderson Cancer Center ma ?Amelika Hui Pū ?Ia i ka maika?i o ka mannose i nā ?ano ma?i ma?i refractory e like me ka ma?i ma?i umauma triple-negative a me glioblastoma.

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3.2 E ?imi akahele i nā ho?okolohua kanaka

?Oiai ?o ka ?ike preclinical maika?i loa, ke kū nei nā ho?okolohua kanaka i nā pilikia kū?oko?a. ?O ka Phase I clinical trial (NCT05220739) i ho?omaka i ka makahiki 2022 ?o ia ka mea mua e loiloi i ka palekana o ka mannose waha i nā ma?i me nā ma?i ma?i pa?a. Hō?ike ka ?ikepili mua i nā po?e ma?i i ka hui 5g i kēlā me kēia lā i ka ho?omanawanui maika?i, a ua emi nui ka pae o ka DNA tumor (ctDNA) i kekahi mau hihia. Eia nō na?e, i ka pi?i ?ana o ka nui i ka 10g, ma kahi o 15% o nā mea ma?i i loa?a i ka ma?i ma?i ma?i, e hō?ike ana i ka pono e ho?omaika?i i ke ?ano o ka dosing regimen.

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3.3 ?O nā pale ?enehana i ka ?oihana

?Oiai he palekana ka mannose i unuhi maoli ?ia, pono ia i ka nui ki?eki?e loa e hiki ai i kahi ?ano anti-cancer (e like me ka ?ai ?ana i 5 kilokani cranberries i kēlā me kēia lā), ka mea i ho?oikaika i nā ?enehana hou i ka biology synthetic. I kēia manawa, hiki i ka Escherichia coli ke ho?onui i ka hana mannose i nā manawa he 20, ?oiai ?o ka immobilized enzyme catalysis e ho?emi ana i nā kumukū?ai hana ma lalo o $50 no ka kilo. Eia kekahi, hiki i ka ?enehana encapsulation nano-liposome ke ho?onui i ka maika?i o ka lawe ?ana i ka ma?i ma?i i ka 80%, e ho?oma?ema?e i ke ala no ka ho?ololi ?ana.

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Mokuna ?Ehā Ho?opa?apa?a a me ka No?ono?o: Nā Mana?o Anuu i ka Carnival of Science

4.1 ?O ka "pahi pahi lua" ka hopena o ka hana Metabolic

He mea pono e ho?omaopopo ?a?ole he panacea ka mannose. Hiki ke ho?ololi i ka mannose-6-phosphate i loko o ka fructose-6-phosphate i kekahi mau ma?i ma?i e lawe ana i ka mutation o ka mannose phosphate isomerase (PMI), kahi e ho?onui ai i ka glycolytic flux. Ua ?ike ?ia kēia ?ano "metabolic escape" ma kahi o 7% o nā la?ana ma?i ma?i colorectal, e hō?ike ana i ka pono e ho?omohala i nā hō?ailona hō?ailona ho?okahi.

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4.2 Kūlohelohe ≠ Palekana: ?O ke ?ano o ka ho?omalu ?ana

?Oiai ua ?ae ?ia ka mannose no ka ho?ohana ?ana i ka mea?ai ma ke ?ano he mea GRAS (Generally Recognized as Safe), ?o kona ?ona lō?ihi ma nā ?ano anti-cancer pono e mālama pono ?ia. Ua ?ike ?ia nā ho?okolohua holoholona e hiki ke alaka?i i nā ma?i pua o ka ?ōpū, me ka pi?i ?ana o kekahi mau hua bacteria pathogenic (e like me Klebsiella) he ?umi. Pono kēia i ka noi?i e hiki mai ana e kaulike i ka pono therapeutic a me ka homeostasis microecological.

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4.3 Ka pā?ani ma waena o Commercial Hype a me Scientific Rationality

Me ka mana?o o "anti-cancer sugar" e lilo i mea kaulana, ua ho?onui kekahi mau mea kālepa i nā hopena therapeutic o nā huahana olakino mannose. Ua ho?opuka ka FDA o ?Amelika i nā leka ho?olaha i ?ekolu mau ?oihana no kā lākou ho?olaha ?ana i ke kānāwai, e hō?ike ana "?a?ole hiki i nā mea?ai mea?ai ke ho?ololi i ka lā?au lapa?au." Ke kāhea nei nā kānaka ?epekema i ka ho?okumu ?ana i kahi papa inoa ke?oke?o ?oihana e ho?oponopono i ka lepili a me ke kū?ai aku ?ana i nā huahana mannose.

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Ka hopena: ?O ke ki?i o ka wā e hiki mai ana o ke kipi

?O ka huaka?i anti-cancer o ka mannose ?a?ole ia he hālāwai kūpono loa o nā makana o ke ?ano a me ka na?auao kanaka, akā he kumu ho?ohālike o ka hana hou interdisciplinary. Mai ka metabolic reprogramming a hiki i ka ho?oponopono hou ?ana o ka microenvironment immune, mai nā paipu hō?ike ho?okolohua a i nā hale hana lā?au lapa?au, ke kākau hou nei kēia "sweet revolution" i ka rulebook o ka mālama ?ana i ka ma?i kanesa. ?Oiai he nui nā pilikia e hiki mai ana, hiki ke ?ike mua ?ia e hiki i ka hanauna hou o nā lā?au lapa?au glyco-based e pili ana i ka mannose ke ho?omaka i kahi au hou o ka anti-cancer pololei. E like me kā Nature i ?ōlelo ai: "I ka wā e hula ai ka ?epekema me ke ?ano, ua kani mua ka bele o ka lā make."

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