Youdaoplaceholder0 1.1 Ilungu elifihlakeleyo losapho lweswekile

Njengeyona nto ingundoqo yamandla ezinto eziphilayo, inkqubo yokuhlelwa kwe-carbohydrates sele iqiniswe kwiincwadi zokufunda: i-monosaccharides (efana ne-glucose kunye ne-fructose), i-oligosaccharides (efana ne-lactose), kunye ne-polysaccharides (efana nesitashi). Nangona kunjalo, ubungcali be-mannose bulele "kwi-identity" yayo - ayithathi nxaxheba kuphela kwi-metabolism yamandla kodwa "ngumlinganiswa wephasiwedi" wonxibelelwano lweseli. I-Mannose ikhona ngokubanzi kwindawo ekhululekileyo kwi-pectin layer yeziqhamo ze-citrus kunye neendonga zeeseli ze-algae enzulu yolwandle. Emzimbeni womntu, iba sisiseko se-molecular yeenkqubo eziphambili ze-physiological ezifana nokuqatshelwa kwe-immune kunye ne-cell adhesion ngokusebenzisa i-N-link glycosylation modification ye-glycoproteins.

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Youdaoplaceholder0 1.2 I-Cognitive Iteration ukusuka kwiMpilo yoMchamo ukuya kumaVulindlela oMhlaza

Kwangoko ngeminyaka yoo-1980, abezonyango bafumanisa ukuba imannose inokuthintela usulelo lwendlela yomchamo ngokuthintela ukuncamathela kwebhaktiriya ye-pathogenic. Lo matshini ubangele ukuthengiswa okushushu kweemveliso zezempilo zecranberry extract. Kodwa akuzange kube ngo-2018 apho uphononongo olubalulekileyo olwenziwe nguCancer Research UK (CRUK) kwijenali yeNdalo ngokwenene yasiphakamisa isigqubuthelo kwiinzame zayo zokulwa nomhlaza: Kwimodeli yempuku yomhlaza wepancreatic, ukongeza i-20% yemannose kumanzi okusela yanciphisa izinga lokukhula kwethumba nge-40%, kwaye xa kudityaniswa ne-chemotherapy drug gemcitabine, ixesha lokusinda landiswa ngamaxesha ama-3 we-mi2. Oku kufunyaniswayo kuye kwabhukuqa imbono eqhelekileyo yokuba "zonke iiswekile zikhuthaza umhlaza".

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I-Youdaoplaceholder0 Isahluko sesi-2 Ukuchaza iNdlela yokuNqanda uMhlaza: "Izitshixo zeswekile" eziThathu Ukuvula indlela yokuphila ye-Tumor

Youdaoplaceholder0 2.1 Ukuqweqwediswa kweMetabolic: "Ihashe leTrojan" liguqulwe njengeglucose

"I-Warburg Effect" yeeseli zethumba yenza ukuba i-glucose ifumaneke ibe phindwe kashumi kwiiseli eziqhelekileyo. Iqela le-CRUK lifumene nge-carbon-13 isotope yokulandelela iteknoloji yokuba i-mannose ingangena kwiiseli zomhlaza ngokusebenzisa uhlobo olufanayo lwe-glucose transporter (GLUT1/3) enesakhiwo esifana neso seswekile. Nangona kunjalo, emva kokungena, i-phosphorylated ngokukhawuleza yi-hexokinase kwi-mannose-6-phosphate (M6P). Le metabolism intermediate ayikwazi ukungena kwindlela ye-glycolytic kodwa endaweni yoko iqokelela ngaphakathi kwiseli ukwenza "umqobo we-metabolic", ekhokelela ekuthinteleni kwe-ATP synthesis kunye nokuqhuma kweentlobo ze-oksijini esebenzayo (ROS), ekugqibeleni ibangele i-apoptosis yeeseli zomhlaza (Umfanekiso 1).

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I-Youdaoplaceholder0 2.2 Ummiselo we-Epigenetic: Ukubhala kwakhona "ikhowudi yememori" yeeseli zomhlaza

Ngo-2023, iqela lophando elivela kwiYunivesithi yaseFudan kwi-Cell Metabolism libonise ngakumbi ukuba i-mannose inokusebenza "njengomhleli we-epigenome". Kwimodeli ye-pancreatic ductal adenocarcinoma (PDAC), unyango lwe-mannose luye lwanciphisa kakhulu inqanaba le-acetylation yesiza se-histone H3K27, okubangelwa ukuvinjelwa kwemisebenzi yokubhaliweyo kwe-oncogenes MYC kunye ne-KRAS. Okona kumangalisa ngakumbi, le mpembelelo ibonakalayo yohlengahlengiso iyaqhubekeka - nokuba ulawulo lwechiza luyekile, iiseli zomhlaza zigcina ukuhlasela okuphantsi, zibonelela ngeembono ezintsha kunyango oluqatha.

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I-Youdaoplaceholder0 2.3 Uhlengahlengiso lwe-immune microenvironment: Ukukrazula "i-disguise eqatywe iswekile" yePD-L1

Iqela elifanayo elifunyenwe kwizifundo ezilandelayo ukuba i-mannose inokukrazula indlela yokuphunyuka kwe-immune yamathumba ngokuphazamisa ukuguqulwa kwe-glycosylation ye-programmed death ligand 1 (PD-L1). Uhlalutyo lwe-mass spectrometry lubonise ukuba i-mannose inqanda i-N-glycosylation ye-asparagine kwindawo ye-192 yeprotheni ye-PD-L1, okubangelwa ukungakwazi kwayo ukugoqa ngokuchanekileyo kunye ne-anchor kwi-membrane yeseli. I-PD-L1, elahlekelwa ukukhuselwa "kwesikhuselo seshukela", ibhalwe yi-E3 ubiquitin ligase FBXW41 kwaye ithotywe yiproteasome. Kwiigundane ze-melanoma, ukudibanisa kwe-mannose kunye ne-anti-PD-1 antibodies yandisa i-tumor regression rate epheleleyo ukusuka kwi-28% ukuya kwi-79% (Umfanekiso 2).

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Youdaoplaceholder0 Isahluko sesi-3 Ukusuka kwiMifuziselo yeZilwanyana ukuya kulingo lwezonyango zoLuntu: Indlela enameva yoGuqulelo lweyeza

I-Youdaoplaceholder0 3.1 Impumelelo kunye neMida yoPhando lwePreclinical

Kwimodeli yomhlaza we-pancreatic ye-CRUK, nangona i-monotherapy ene-mannose ilibazise ukuqhubela phambili kwethumba, ayiphumelelanga ukuphumeza uxolelo olupheleleyo. Nangona kunjalo, xa idityaniswe ne-FOLFIRINOX chemotherapy regimen, ixesha eliphakathi lokusinda kweempuku landiswa ukusuka kwiintsuku ze-42 ukuya kwiintsuku ze-98, kwaye kwakungekho ukwanda kwetyhefu. Esi siphumo saphinda saveliswa kwimodeli yomhlaza webele kathathu-negative kwi-MD Anderson Cancer Centre: I-Mannose yandisa izinga lokunciphisa ithumba le-paclitaxel ukusuka kwi-45% ukuya kwi-72%. Nangona kunjalo, abaphandi bafumanisa ukuba malunga ne-15% yamathumba awazange aphendule kwi-mannose. Uhlalutyo olongezelelweyo lubonise ukuba ezi seli ezichasene neziyobisi zibonakaliswe kakhulu i-mannose-phosphate isomerase (PMI), enokuguqula i-M6P ibe yi-fructose-6-phosphate kwaye iphinde idibanise kwindlela ye-glycolytic.

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Youdaoplaceholder0 3.2 Isifingo esilumkileyo sezilingo zabantu

Isigaba sokuqala solingo lwezonyango lwe-mannose olwaqalwa ngo-2022 (NCT05220739) lubandakanya izigulane ezingama-32 ezinamathumba aqinileyo aphezulu. Kwiqela le-dose yolawulo lomlomo lwemihla ngemihla ye-5g mannose, i-tumor ejikelezayo ye-DNA (ctDNA) amanqanaba ezigulane ezi-8 zehla ngaphezu kwe-50%, apho umthamo we-metastases yesibindi kwesinye isigulana somhlaza we-pancreatic wehla ngama-31%. Nangona kunjalo, xa umthamo wenyuka ukuya kwi-10g, isifo sohudo se-grade III senzeke kwizigulane ze-3, ebonisa ukuba isicwangciso solawulo kufuneka siphuculwe. Okwangoku, amalungiselelo e-mannose emithanjeni esebenzisa iteknoloji ye-nano-liposome encapsulation iphantsi kophuhliso. Idatha ye-preclinical ibonisa ukuba ukuhanjiswa kwe-tumor ekujoliswe kuyo kufikelela kwi-78%, kwaye ubutyhefu babo buyancipha kakhulu.

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Youdaoplaceholder0 Isahluko sesi-4 soGuquko lwezoShishino kunye neempikiswano: Imingeni yokwenyani yeRevolution eSweet

Youdaoplaceholder0 4.1 Ibhayoloji yoSynthetic Sombulula iPuzzle yemveliso yeMisa

Imannose ekhutshwe ngokwendalo iyabiza (malunga nekhilogram nganye)

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Kunzima ukuhlangabezana neemfuno zedosi yokulwa nomhlaza (imihla ngemihla)

Indlela kukwandisa imveliso ukuya

Iindleko ziye zehla ukuya kwi-1200), okunzima ukuhlangabezana nemfuneko yedosi yokulwa nomhlaza (10-20g ngosuku). I-Synthetic biology giant GinkgoBioworks inyuse isivuno ukuya kwi-30g/L kwaye yanciphisa iindleko ukuya kwi-50/kg ngokuguqula indlela ye-mannose-1 - guanosine phosphate transferase (MPG) ye-Escherichia coli. Itekhnoloji ephucuke ngakumbi efana ne-CRISPR-Cas9-ehleliweyo ye-Saccharomyces cerevisiae ibhaktiriya yobunjineli ikwazile ukuvelisa ngokuzinzileyo i-mannose ecocekileyo kakhulu ngexesha lokuvutshelwa okuqhubekayo.

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Youdaoplaceholder0 4.2 Umdlalo phakathi kweHype yeshishini kunye neenqobo zokuziphatha zenzululwazi

Ngombono othi "iswekile echasene nomhlaza" iyathandwa, amakhulu eemveliso zezempilo ze-mannose ezibanga "unyango oluncedisayo lwamathumba" ziye zavela kwiqonga le-Amazon, kunye neentlawulo zexabiso eliphezulu ukuya kumaxesha alishumi. Ngo-2023, i-US FDA yakhupha iileta ezilumkisayo kumashishini angama-23, igxininisa ukuba "izongezo zokutya kufuneka zingabi neziphumo zonyango kwizifo." Izazinzulu zixhalabile ukuba ngokumfameka ukuthatha iidosi eziphezulu zemannose kunokuphazamisa intyantyambo yamathumbu - imifuniselo yezilwanyana ibonise ukuba ukuthatha ixesha elide kukhokelela ekunciphiseni ngama-80% kubuninzi beFaecalibacterium prausnitzii kunye nokunyuka ngokuphindwe kahlanu kwi-Fusobacterium nucleatum. Le yokugqibela inxulumene ngokusondeleyo nokuqhubela phambili komhlaza we-colorectal.

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I-Youdaoplaceholder0 iSahluko seSihlanu samaThemba ekamva: ULwandlekazi olukhulu lweGlyco-based Drugs

Youdaoplaceholder0 5.1 IGlycolic Revolution kwiPrecision Medicine

Izicwangciso zonyango zomntu ngamnye ezisekelwe kwi-tumor metabolic heterogeneity ziyavela. Imodeli ye-"Mannose Sensitivity Score" (MSS) ephuhliswe yi-Broad Institute e-United States inokuqikelela ukusabela okunokwenzeka kwezigulana kwi-mannose ngokubona inqanaba lokuthetha le-GLUT1, umsebenzi we-hexokinase kunye nemo yokuguqula i-PMI kwizihlunu zethumba. Kuyilo lweemvavanyo zekliniki zeSigaba sesi-II, izigulane zomhlaza we-pancreatic ezinenqaku le-MSS ye-≥75% ziya kunikwa kuqala ukubandakanywa ukuphucula izinga lokuphendula unyango.

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Youdaoplaceholder0 5.2 Udibaniso olunqamlezileyo lweswekile yobunjineli bamachiza

Uphando lwe-Frontier alusanelisekanga kusetyenziso olunye lwemannose yendalo. Iqela le-MIT lenze i-conjugate ye-"mannose-paclitaxel", ethatha ithuba lokunyuswa okuphezulu kwe-mannose ngeeseli ze-tumor ukuphumeza ukuhanjiswa okujoliswe kuko kwamachiza e-chemotherapy. Kwiimodeli zomhlaza wamabele, ukusebenza kakuhle kokubulawa kwethumba kule conjugate kwakuphindwe kathathu kune-paclitaxel yendabuko, kwaye i-cardiotoxicity yayo yancitshiswa ngama-60%. Olunye ugqatso luvela kwiYunivesithi yaseShanghai Jiao Tong: ngokudibanisa imannose kunye ne-photosensitizer Ce6, "unyango olusekwe kwiswekile olusekwe kwifotodynamic" olunokuthi luvulwe sisibane esikufuphi ne-infrared sele luphuhlisiwe, lubonisa ukuba kunokwenzeka ukukhupha ithumba elinzulu.

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Youdaoplaceholder0 Isiphelo: "Imolekyuli eswiti" iphinda ibhale imithetho echasene nomhlaza.

Uhambo lokulwa nomhlaza lwemannose luyintlantsi eqaqambileyo ebangelwe kukungqubana kwesiseko senzululwazi kunye neemfuno zeklinikhi. Ukusuka kungenelelo lwe-metabolic ukuya kulawulo lwe-immune, ukusuka kwi-monotherapy ukuya kwiirejimeni ezidityanisiweyo, le molekyuli yeswekile iqhekeza umgca wokukhusela ithumba kunye nezicwangciso zokuhlaselwa kwe-multi-dimensional. Nangona indlela yokuthengisa isajongene nemingeni efana nokulungiswa kwedosi, iindlela zokuxhathisa iziyobisi, kunye nemimiselo yokulawula, uluntu lwezenzululwazi lunethemba elikhulu kuyo - njengoko u-Nobel laureate uJames Watson ebeka, "Undoqo womhlaza yi-genomic disorder, kwaye i-mannoglucose isifundisa ukuba ungenelelo lwe-metabolic lunokubuyisela ucwangco." Iqhutywa ngamavili amabini eyeza elichanekileyo kunye nebhayoloji yokwenziwa, le "revolution imnandi" inokuzisa ixesha elitsha lonyango lomhlaza.