Youdaoplaceholder0 1.1 Setho se ipatileng sa lelapa la tsoekere

E le matla a mantlha a lintho tse phelang, tsamaiso ea likarolo tsa lik'habohaedreite haesale e tiile libukeng tsa thuto: monosaccharides (joalo ka tsoekere le fructose), oligosaccharides (joalo ka lactose), le polysaccharides (joalo ka starch). Leha ho le joalo, ho khetheha ha mannose ho it?etlehile ka "boitsebahatso ba bobeli" - ha se feela karolo ea metabolism ea matla empa hape ke "password character" bakeng sa puisano ea lisele. Mannose e teng hohle sebakeng se lokolohileng karolong ea pectin ea litholoana tsa citrus le maboteng a lisele tsa algae e tebileng ea leoatle. 'Meleng oa motho, e fetoha motheo oa limolek'hule oa lits'ebetso tsa bohlokoa tsa' mele tse kang ho lemoha 'mele oa ho it?ireletsa mafung le ho khomarela lisele ka ho fetola N-link glycosylation ea glycoprotein.

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Youdaoplaceholder0 1.2 T?ebeliso ea kelello ho tloha ho Bophelo bo Botle ba Moroto ho ea ho Bo-pula-maliboho ba Mofets'e

Khale koana lilemong tsa bo-1980, sechaba sa bongaka se ile sa fumana hore mannose e ka thibela t?oaetso ea moroto ka ho thibela ka tlholisano likhomaretsi tsa baktheria ea pathogenic. Mokhoa ona o hlahisitse thekiso e chesang ea lihlahisoa tsa bophelo bo botle ba cranberry. Empa e bile ka 2018 moo phuputso ea bohlokoa e entsoeng ke Cancer Research UK (CRUK) koranteng ea Nature e hlile e phahamisitse lesira boitekong ba eona ba ho loants'a mofets'e: Moetsong oa toeba oa mofets'e oa pancreatic, ho eketsa mannose ea 20% metsing a nooang ho fokotsitse sekhahla sa kholo ea hlahala ka 40%, mme ha e kopantsoe le chemotherapy drug gemcitabine, nako ea ho phela e ile ea eketsoa makhetlo a 3 ka mi2. T?ibollo ena e felisitse maikutlo a tloaelehileng a hore "tsoekere eohle e khothalletsa kankere".

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Youdaoplaceholder0 Khaolo ea 2 Ho Khetholla Mokhoa oa ho Thibela Mofets'e: "Linotlolo tse tharo tsa tsoekere" Notlolla tsela ea bophelo ea Tumor

Youdaoplaceholder0 2.1 Hijacking ea Metabolic: "Trojan pere" e ikhakantseng joalo ka tsoekere

"Warburg Effect" ea lisele tsa tumor e etsa hore boemo ba bona ba tsoekere bo be makhetlo a leshome ho feta lisele tse tloaelehileng. Sehlopha sa CRUK se sibolotse ka theknoloji ea ho latella isotope ea carbon-13 hore mannose e ka kenella liseleng tsa mofet?e ka mofuta o t?oanang oa sepalangoang sa tsoekere (GLUT1/3) se nang le sebopeho se ts'oanang le sa tsoekere. Leha ho le joalo, ka mor'a ho kena, ka potlako phosphorylated ke hexokinase ho mannose-6-phosphate (M6P). Setsi sena sa metabolic ha se khone ho kena tseleng ea glycolytic empa ho e-na le hoo se bokellana ka har'a sele ho theha "thibelo ea metabolic", e lebisang t?itisong ea ATP synthesis le ho phatloha ha mefuta ea oksijene e sebetsang (ROS), e qetellang e baka apoptosis ea lisele tsa mofet?e (Set?oant?o sa 1).

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Youdaoplaceholder0 2.2 Taolo ea Epigenetic: Ho ngola hape "khoutu ea memori" ea lisele tsa mofet?e

Ka 2023, sehlopha sa lipatlisiso se tsoang Univesithing ea Fudan ho Cell Metabolism se ile sa boela sa senola hore mannose e ka sebetsa e le "epigenome editor". Moetsong oa pancreatic ductal adenocarcinoma (PDAC), kalafo ea mannose e ile ea fokotsa haholo boemo ba acetylation ea sebaka sa histone H3K27, e leng se ileng sa fella ka ho thibela mesebetsi ea mongolo oa oncogenes MYC le KRAS. Ho makatsang le ho feta, phello ena e bonahalang ea ho hlophisa bocha e ntse e tsoela pele - leha tsamaiso ea lithethefatsi e emisoa, lisele tsa mofet?e li ntse li lula li le tlase, li fana ka mehopolo e mecha bakeng sa kalafo e matla.

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Youdaoplaceholder0 2.3 Ho lokisoa bocha ha tikoloho ea 'mele ea ho it?ireletsa mafung: Ho qhaqha "seaparo se koahetsoeng ka tsoekere" sa PD-L1

Sehlopha se t?oanang se fumanoeng liphuputsong tse latelang tsa hore mannose e ka senya mokhoa oa ho baleha ha 'mele oa ho it?ireletsa mafung ka ho kena-kenana le phetoho ea glycosylation ea programmed death ligand 1 (PD-L1). Tlhahlobo ea "mass spectrometry" e senotse hore mannose e thibela N-glycosylation ea asparagine sebakeng sa 192 sa protheine ea PD-L1, e leng se etsang hore e se ke ea khona ho phutha ka nepo le ho khomarela lera la sele. PD-L1, e lahleheloang ke t?ireletso ea "thebe ea tsoekere", e ngotsoe ke E3 ubiquitin ligase FBXW41 le ho senyeha ke proteasome. Ho litoeba tsa melanoma, motsoako oa mannose le li-anti-PD-1 li ekelitse tekanyo e feletseng ea ho fokotseha ha hlahala ho tloha ho 28% ho ea ho 79% (Set?oant?o sa 2).

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Youdaoplaceholder0 Khaolo ea 3 Ho Tloha Mehlala ea Liphoofolo ho ea Litekong tsa Batho: The Thorny Road of Translational Medicine

Youdaoplaceholder0 3.1 Katleho le Mefokolo ea lipatlisiso tsa Preclinical

Moetsong oa mofet?e oa pancreatic oa CRUK, leha monotherapy e nang le mannose e liehile ho tsoela pele ha hlahala, e ile ea hloleha ho fihlela t?oarelo e felletseng. Leha ho le joalo, ha e kopantsoe le FOLFIRINOX chemotherapy regimen, nako ea ho phela ha litoeba e ile ea lelefatsoa ho tloha matsatsing a 42 ho ea ho matsatsi a 98, 'me ha hoa ka ha e-ba le keketseho ea chefo. Sephetho sena se ile sa hlahisoa hape ka mohlala oa mofet?e oa matsoele oa makhetlo a mararo ho MD Anderson Cancer Center: Mannose e ekelitse sekhahla sa khatello ea tumor ea paclitaxel ho tloha 45% ho isa ho 72%. Leha ho le joalo, bafuputsi ba fumane hape hore hoo e ka bang 15% ea lihlahala ha lia ka tsa arabela mannose. Liphuputso tse ling li senotse hore lisele tsena tse hanyetsanang le lithethefatsi li hlahisa haholo mannose-phosphate isomerase (PMI), e ka fetolang M6P ho fructose-6-phosphate le ho ikopanya hape le tsela ea glycolytic.

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Youdaoplaceholder0 3.2 Meso e hlokolosi ea liteko tsa batho

Teko ea pele ea bongaka ea Mokhahlelo oa I ea mannose e qalileng ka 2022 (NCT05220739) e kenyelelitse bakuli ba 32 ba nang le lihlahala tse tiileng tse tsoetseng pele. Sehlopheng sa tekanyetso ea letsatsi le letsatsi ea tsamaiso ea molomo ea 5g mannose, maemo a potolohang a hlahala a DNA (ctDNA) a bakuli ba 8 a fokotsehile ka ho feta 50%, moo palo ea metastases ea sebete ho mokuli a le mong oa mofet?e oa pancreatic e fokotsehileng ka 31%. Leha ho le joalo, ha tekanyo e nyolohela ho 10g, let?ollo la sehlopha sa III le ile la hlaha ho bakuli ba 3, ho fana ka maikutlo a hore leano la tsamaiso le hloka ho ntlafatsoa. Hona joale, litokisetso tsa "intravenous mannose" tse sebelisang theknoloji ea nano-liposome encapsulation li ntse li tsoela pele. Lintlha tsa preclinical li bonts'a hore ts'ebetso ea bona ea phano e lebisitsoeng ho tumor e fihla ho 78%, mme chefo ea bona e fokotsehile haholo.

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Youdaoplaceholder0 Khaolo ea 4 Phetoho ea Liindasteri le Khohlano: Mathata a Sebele a Phetohelo e Monate

Youdaoplaceholder0 4.1 Synthetic biology e Rarolla Papali ea tlhahiso ea Boima

Mannose e nkiloeng ka tlhaho e bitsa chelete e ngata (hoo e ka bang k'hilograma)

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Ho thata ho fihlela litlhoko tsa tekanyetso ea anti-cancer (letsatsi le letsatsi)

Mokhoa ke ho eketsa tlhahiso ho

Litsenyehelo li theohetse ho 1200), e leng ho leng thata ho finyella tlhokahalo ea tekanyo e khahlanong le mofet?e (10-20g ka letsatsi). Synthetic biology giant GinkgoBioworks e ekelitse chai ho 30g/L mme e theotse lit?enyehelo ho 50/kg ka ho fetola tsela ea mannose-1 - guanosine phosphate transferase (MPG) ea Escherichia coli. Litheknoloji tse tsoetseng pele joalo ka libaktheria tse entsoeng ka Saccharomyces cerevisiae tse hlophisitsoeng ke CRISPR-Cas9 li khonne ho hlahisa mannose e hloekileng haholo nakong ea ho belisoa ho tsoelang pele.

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Youdaoplaceholder0 4.2 Papali e lipakeng tsa Hype ea khoebo le melao ea boit?oaro ea mahlale

Ka mohopolo oa "tsoekere e khahlanong le mofets'e" e ntseng e tsebahala, lihlahisoa tse makholo tsa bophelo bo botle ba mannose tse ipolelang hore ke "phekolo e thusang bakeng sa lihlahala" li hlahile sethaleng sa Amazon, ka litefiso tsa theko e phahameng ho feta makhetlo a leshome. Ka 2023, US FDA e ile ea fana ka mangolo a lemosang ho likhoebo tse 23, e hatisa hore "litlatsetso tsa lijo ha lia lokela ho ipolela hore li na le litlamorao tsa kalafo ho mafu." Bo-rasaense ba t?oenyehile hore ho nka litekanyetso tse phahameng tsa mannose ka bofofu ho ka senya limela tsa mala - liteko tsa liphoofolo li bont?itse hore ho ja nako e telele ho lebisa phokotsong ea bongata ba Faecalibacterium prausnitzii le keketseho e imenneng hahlano ea Fusobacterium nucleatum. Ea ho qetela e amana haufi-ufi le tsoelo-pele ea kankere ea mala.

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Youdaoplaceholder0 Khaolo ea Bohlano Litebello tsa Kamoso: Leoatle le leholo la Lithethefatsi tse thehiloeng ho Glyco

Youdaoplaceholder0 5.1 Phetoho ea Glycolic ho Precision Medicine

Maano a kalafo a motho ka mong a ipapisitseng le tumor metabolic heterogeneity ea hlaha. Moetso oa "Mannose Sensitivity Score" (MSS) o ntlafalitsoeng ke Setsi sa Broad United States o ka bolela esale pele monyetla oa karabelo ea bakuli ho mannose ka ho bona boemo ba polelo ea GLUT1, ts'ebetso ea hexokinase le boemo ba phetoho ea PMI liseleng tsa hlahala. Moqaping oa liteko tsa bongaka tsa Phase II, bakuli ba mofet?e oa pancreatic ba nang le lintlha tsa MSS tsa ≥75% ba tla fuoa pele bakeng sa ho kenyelletsoa ho ntlafatsa sekhahla sa karabo ea kalafo.

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Youdaoplaceholder0 5.2 Ho kopanngoa ha moeli oa litlhare tsa boenjiniere ba tsoekere

Patlisiso ea Frontier ha e sa khotsofatsoa ke ts'ebeliso e le 'ngoe ea mannose ea tlhaho. Sehlopha sa MIT se thehile "mannose-paclitaxel" conjugate, e nkang monyetla oa ho ts'oaroa ha mannose ke lisele tsa tumor ho fihlela phepelo e lebisitsoeng ea litlhare tsa chemotherapy. Mehlaleng ea mofet?e oa matsoele, katleho ea ho bolaea tumor ea conjugate ena e ne e le makhetlo a mararo ho feta ea paclitaxel ea setso, mme lefu la pelo la eona le fokotsehile ka 60%. Katleho e 'ngoe e tsoa Univesithing ea Shanghai Jiao Tong: ka ho kopanya mannose le photosensitizer Ce6, "phekolo e thehiloeng ho tsoekere e thehiloeng ho tsoekere" e ka hlahisoang ke leseli le haufi le infrared e se e ntlafalitsoe, e bonts'a monyetla oa ho nt?a hlahala e tebileng.

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Youdaoplaceholder0 Qetello: "Molek'hule e monate" e ngolang hape melao e khahlanong le mofet?e.

Leeto le khahlanong le mofet?e la mannose ke tlhase e khanyang e hlahisitsoeng ke ho thulana ha mahlale a mantlha le litlhoko tsa bongaka. Ho tloha ts'ebetsong ea metabolic ho ea taolong ea 'mele ea ho it?ireletsa mafung, ho tloha ho monotherapy ho ea ho li-regimens tse kopaneng, molek'hule ena ea tsoekere e theola mohala oa ts'ireletso ea tumor ka maano a tlhaselo ea mefuta e mengata. Le hoja tsela ea khoebo e ntse e tobana le mathata a kang ho ntlafatsa lethal dose, mekhoa ea ho hanyetsa lithethefatsi, le litloaelo tsa taolo, sechaba sa saense se na le t?epo e kholo bakeng sa eona - joalo ka ha mohapi oa Nobel James Watson a boletse, "Mohloli oa mofet?e ke lefu la genomic, 'me mannoglucose e re ruta hore ho kenella ka metabolic ho ka khutlisa taolo." E tsamaisoa ke mabili a mabeli a bongaka bo nepahetseng le baeloji ea maiketsetso, "phetoho ena e monate" e ka tlisa nako e ncha ea kalafo ea mofet?e.