Kwidabi lenkulungwane elide phakathi koluntu kunye nomhlaza, indalo ibisoloko ibonelela ngemikhondo yokusombulula ingxaki ngeendlela ebezingalindelekanga. Kwiminyaka yakutshanje, i-monosaccharide ebonakala iqhelekile - iMannose - iye yaba lugxininiso lwehlabathi lophando lwezenzululwazi ngenxa yeempawu zayo ezichasene nomhlaza. Le hexose, efumaneka ngokubanzi kwi-cranberries kunye neziqhamo ze-citrus, iphakame kwindima exhasayo kwintsimi yesondlo ukuya kwindima ekhokelayo kuphando lwe-tumor metabolism, ityhila i-brand-new dimension ye-sugar substances kulawulo lobomi. Eli nqaku liza kuhlalutya nzulu indlela i-mannose elungisa ngayo imeko yonyango lomhlaza ukusuka kwimiba emine: uphando olusisiseko, indlela yokwenza, inguqu yeklinikhi kunye nethemba loshishino.

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Isahluko sokuQala: Ukuguqula iNgcaciso: Ukuvuswa kwe-Anti-Cancer yeeMolekuli eziSwiti

1.1 I-Paradigm Shift kuphando lweCarbohydrate

Ngokweengcamango zemveli, iswekile (iicarbohydrates) kudala zithathwa njenge "mali yamandla". Ngokukodwa i-glucose, njenge-substrate engundoqo yokuphefumla kweselula, unxulumano phakathi kokungahambi kakuhle kwe-metabolic kunye nophuhliso lomhlaza lubonakaliswe ngokupheleleyo. Nangona kunjalo, uphando olwenziwayo olupapashwe nguCancer Research UK kwijenali yeNdalo ngo-2018 yabhala ngokutsha le ngxelo - iqela lophando liqinisekisile okokuqala ukuba i-mannose inokuthintela ngokukhetha ukwanda kweeseli zomhlaza ngokuphazamisana ne-tumor's metabolism pathway, kunye nefuthe elincinci kwizicubu eziqhelekileyo. Oku kufunyanisiweyo akupheleli nje ekubhukuqeni inkolelo yokuba "zonke iiswekile zikhuthaza umhlaza", kodwa zikwavula ibala elitsha ledabi lonyango longenelelo lwe-metabolic.

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1.2 Ukulandelelwa kwebhayoloji yeMannose

Njenge-isomer ye-glucose, i-mannose ihanjiswa kwindawo ekhululekile kwi-epidermis yeziqhamo ezifana ne-citrus kunye ne-apula kwindalo, okanye ithatha inxaxheba ekwakhiweni kweembrane ze-biological ngendlela ye-glycoproteins. Emzimbeni womntu, i-mannose iphosphorylated ukwenza i-mannose-6-phosphate (M6P), ethi ibe yimolekyuli engundoqo yokubonisa i-lysosomal enzyme. Izifundo zeklinikhi zangaphambili zibonakalise indlela yayo yokuthintela usulelo lwe-urinary tract: ngokuzibophelela ngokhuphiswano kwi-adhesion receptors yeebhaktheriya ze-pathogenic, ibhloka ikholoni yabo kwi-urothelium. Olu phawu luye lwavelisa iintlobo ezahlukeneyo zezongezo zokutya ezigxile kwi-mannose, kodwa ukufunyanwa kwamandla ayo okulwa nomhlaza kuye kwakhokelela ekunyuseni okubonakalayo kwixabiso layo lokusebenza.

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Isahluko seSibini: Ukuchazwa kweNzululwazi: Ukuhlaselwa kathathu kweMannose ngokuchasene noMhlaza

2.1 Ukuqweqwediswa kweMetabolic: Ukuphelisa "umlutha weswekile" kwikhonkco lokubonelela ngeeseli zomhlaza.

Isiphumo se-Warburg yeeseli zethumba (esaxhomekeke kwi-glycolysis yamandla nakwimekobume etyebileyo yeoksijini) yenza ukuba ukuthathwa kweglucose ibe kuphindwe kalishumi kwiiseli eziqhelekileyo. Iqela laseBhritane lafumanisa ngetekhnoloji yokulandelela isotopu ukuba emva kokuba i-mannose ingene kwiiseli zomhlaza, yenziwa yi-hexokinase ukuze yenze i-M6P kwaye iqokelele ngobuninzi ngaphakathi kweeseli. Le "pseudo-metabolite" ayihlali nje kuphela kwiitshaneli ze-glucose transporter (GLUT), kodwa ikhuphisana nokuthintela umsebenzi we-phosphoglucose isomerase, okubangela ukungabikho kwezinto eziphambili kwi-glycolysis kunye nomjikelo we-tricarboxylic acid, ekugqibeleni kubangele ingxaki yamandla kwiiseli zomhlaza (Umfanekiso 1).

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2.2 I-Epigenetics: Ukuhlaziya i-tumor microenvironment

Uphononongo olupapashwe yiYunivesithi yaseFudan kwi-Cell Metabolism ngo-2023 lubonise ngakumbi ukuba i-mannose inokubuyisela ukuguqulwa kwe-epigenetic kwiiseli zomhlaza ngokulawula amanqanaba e-histone acetylation. Iimvavanyo zibonise ukuba kwiiseli zomhlaza we-pancreatic ziphathwe nge-mannose, i-acetylation degree ye-promoter yengingqi ye-oncogene MYC iyancitshiswa, kwaye umsebenzi wayo wokubhaliweyo unqatshelwe kakhulu. Le epigenetic reprogramming isiphumo buthathaka iimpawu invasive kunye owomileyo iiseli ithumba, ukubonelela fulcrum ithiyori kuphuhliso amachiza epigenetic ezidityanisiweyo.

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2.3 I-Immune Synergy: Ukususa i-"Invisibility Cloak" yePD-L1

Okona kubhukuqisayo kukuba iqela elifanayo lifumanise ukuba i-mannose inokujolisa indlela yokuphunyuka kwethumba. Ngohlalutyo lwe-mass spectrometry, abaphandi baqinisekisile ukuba i-mannose ithintela ukugoqa okuchanekileyo kunye ne-membrane yendawo yeprotheni ye-PD-L1 ngokuphazamisa ukuguqulwa kwayo kwe-N-glycosylation. Iprotheni ye-PD-L1, elahlekelwa "i-umbrella yokukhusela" yekhonkco leswekile, inokwenzeka ukuba ibe yindawo yonke kwaye ihlaziywe, ngaloo ndlela iphelisa isignali yokuthintela kwiiseli ze-T. Kwimodeli yegundane ye-melanoma, indibaniselwano ye-mannose kunye ne-anti-PD-1 ye-antibody inyuse izinga lokubuyisela ithumba ukuya kwi-78%, ligqithise kakhulu kunyango olulodwa (Umfanekiso 2).

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Isahluko sesithathu: Ukusuka kwiLebhu ukuya kwiKlinikhi: Indlela yokuPhumelela kweMithi yokuGuqulela

3.1 Amanqaku aphambili ophando lwezonyango

Kwiimvavanyo ezininzi zezilwanyana, i-mannose ibonise amandla okulwa nomhlaza obanzi. Iqela laseBrithani lingenelele imodeli yeempuku zomhlaza we-pancreatic kunye ne-20% yamanzi okusela i-mannose kwaye yafumanisa ukuba ukukhula kwe-tumor volume kulibaziseka ukuya kuma-40%, kwaye kwakungekho yingozi ebalulekileyo yesibindi okanye izintso. Okona kuvuyisa ngakumbi, xa isetyenziswa ngokudibeneyo ne-gemcitabine, ixesha lokusinda kweempuku landiswa ngamaxesha e-2.3, libonisa ixabiso layo le-chemotherapy-sensitizing. Iimvavanyo zokuqinisekisa ezizimeleyo kwi-MD Anderson Cancer Centre e-United States zibonise ukuba i-mannose isebenza ngokulinganayo ngokuchasene neentlobo zomhlaza we-refractory ezifana nomhlaza webele we-triple-negative kunye ne-glioblastoma.

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3.2 Ukuphononongwa ngobunono kovavanyo lwabantu

Ngaphandle kwedatha enomtsalane yangaphambili, ulingo lwabantu lujongene nemingeni ekhethekileyo. Ulingo lwezonyango lweSigaba I (NCT05220739) olwaqalwa ngo-2022 lwaba lolokuqala ukuvavanya ukhuseleko lwemannose yomlomo kwizigulana ezinamathumba aqinileyo aqinileyo. Idatha yokuqala ibonisa ukuba izigulane kwiqela le-5g yemihla ngemihla zinokunyamezela okulungileyo, kwaye i-tumor ejikelezayo ye-DNA (ctDNA) amanqanaba kwezinye iimeko ziye zehla kakhulu. Nangona kunjalo, xa ithamo linyuke laya kutsho kwi-10g, malunga ne-15% yezigulane ziye zafumana urhudo olungephi, nto leyo ecebisa imfuneko yokwandisa irejimeni yokudosa.

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3.3 Imiqobo yobuGcisa kushishino

Nangona imannose ekhutshwe ngokwendalo ikhuselekile, ifuna idosi ephezulu kakhulu ukufikelela kugxininiso oluchasene nomhlaza (elilingana nokutya iikhilogram ezi-5 zamaqunube mihla le), nto leyo eqhubele phambili ukuveliswa kweteknoloji kwibhayoloji yokwenziwa. Okwangoku, i-Escherichia coli eyenziwe ngokwemfuza inokwandisa imveliso yemannose ngamaxesha angama-20, ngoxa i-immobilised enzyme catalysis inciphisa iindleko zemveliso ibe ngaphantsi kwee-$50 ngekhilogram. Ukongezelela, iteknoloji ye-nano-liposome encapsulation inokunyusa ukusebenza kakuhle kwe-tumor ekujoliswe kuyo kwi-80%, icacisa indlela yokuguqulwa kweklinikhi.

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ISahluko sesine Ingxabano kunye nokuCacisa: Iingcamango ezibandayo kwiCarnival yeSayensi

4.1 "Ikrele elintlangothi-mbini" Isiphumo songenelelo lweMetabolic

Kuyafaneleka ukuba uqaphele ukuba i-mannose ayikho i-panacea. Ezinye iiseli zomhlaza ezithwele i-mutation ye-mannose phosphate isomerase (PMI) inokuguqula i-mannose-6-phosphate ibe yi-fructose-6-phosphate, endaweni yoko iphucula i-glycolytic flux. Le nto "yokusinda kwemetabolism" yafunyanwa malunga ne-7% yeesampulu zomhlaza we-colorectal, iphakamisa imfuneko yokuphuhlisa iziphawuli zovavanyo lomntu ngamnye.

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4.2 Ngokwendalo ≠ Ekhuselekileyo: UbuGcisa boLawulo lweDosaji

Nangona i-mannose ivunyiwe ukuba isetyenziswe ekutyeni njengento ye-GRAS (Ibonwa Jikelele njengeKhuselekileyo), ubutyhefu bayo bexesha elide kwiidosi ezichasene nomhlaza kusafuneka ukuba zithathwe ngokungqongqo. Uvavanyo lwezilwanyana lufumanise ukuba ukuthathwa kwedosi ephezulu ngokuqhubekayo kunokukhokelela ekuphazamisekeni kwamathumbu emathunjini, kunye nobuninzi beebhaktheriya ezithile ezithatha amathuba (ezifana ne-Klebsiella) zinyuka ngokuphindwe kalishumi. Oku kufuna ukuba uphando lwexesha elizayo kufuneka lulinganise ukusebenza konyango kunye ne-microecological homeostasis.

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4.3 Umdlalo phakathi kweNgcaciso yoRhwebo kunye neNgqiqo yobuNzululwazi

Ngombono othi "iswekile echasene nomhlaza" iyathandwa, abanye abarhwebi baye bayibaxa imiphumo yonyango yeemveliso zempilo ye-mannose. I-FDA yaseUnited States ikhuphe iileta ezilumkisa amashishini amathathu ngokukhuthazwa kwawo ngokungekho mthethweni, igxininisa ukuba "izongezo zokutya azikwazi ukuthatha indawo yonyango lweziyobisi." Izazinzulu zihlaba ikhwelo lokuba kusekwe uluhlu olumhlophe lweshishini ukulawula ukuleyibhile kunye nokuthengiswa kweemveliso ezinemannose.

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Isiphelo: Umfanekiso wexesha elizayo wenguqu emnandi

Uhambo lokulwa nomhlaza lwe-mannose alukho nje ukudibana okugqibeleleyo kwezipho zendalo kunye nobulumko bomntu, kodwa kunye nemodeli yokuqaliswa kwezinto ezintsha. Ukusuka kwi-metabolic reprogramming ukuya kuhlengahlengiso lwe-immune microenvironment, ukusuka kwiityhubhu zovavanyo lwaselabhoratri ukuya kwiifektri zamayeza, le "revolution imnandi" iphinda ibhale incwadi yomthetho yonyango lomhlaza. Nangona kusekho imingeni emininzi ezayo, kunokubonwa kwangaphambili ukuba isizukulwana esilandelayo samachiza asekelwe kwi-glyco-based based mannose sinokungenisa ixesha elitsha lokuchasana nomhlaza. Kanye njengokuba iNdalo yathi: “Xa inzululwazi idanisa nendalo, intsimbi yomhla wentshabalalo sele ikhala.”

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