Youdaoplaceholder0 1.1 Xubinta qarsoon ee qoyska sonkorta

Sida walaxda tamarta xudunta u ah noolaha noolaha, nidaamka kala soocida karbohaydraytyada ayaa muddo dheer lagu xoojiyay buugaagta waxbarashada: monosaccharides (sida glucose iyo fructose), oligosaccharides (sida lactose), iyo polysaccharides (sida istaarijka). Si kastaba ha ahaatee, gaar ahaaneed ee mannose waxay ku jirtaa "aqoonsiga laba-geesoodka ah" - ma aha oo kaliya ka qaybqaatayaasha dheef-shiid kiimikaadka tamarta laakiin sidoo kale "dabeecadda sirta ah" ee isgaarsiinta unugyada. Mannose wuxuu si weyn ugu jiraa xaalad xor ah lakabka pectin ee miraha liinta iyo darbiyada unugga ee algae-badeedka. Jirka bini'aadamka, waxay noqotaa saldhigga molecular ee hababka nafsiga ah ee muhiimka ah sida aqoonsiga difaaca iyo adhesion unug iyada oo loo marayo N-link glycosylation modification of glycoproteins.

?

Youdaoplaceholder0 1.2 Soo Celinta Garashada ee Caafimadka Kaadida ilaa Hormoodka Kansarka

Horaantii 1980-meeyadii, bulshada caafimaadku waxay ogaatay in maansada ay ka hortagi karto caabuqyada kaadi mareenka iyagoo si tartan ah u xakameynaya adhesins-ka bakteeriyada pathogenic. Habkani waxa uu keenay iibka kulul ee alaabta caafimaadka ee laga soo saaro karamberriga. Laakiin ma ahayn ilaa 2018 in daraasad taariikhi ah oo ay samaysay Cancer Research UK (CRUK) ee joornaalka Nature ayaa si dhab ah kor ugu qaaday xijaabka dadaalkeeda ka hortagga kansarka: Qaabka jiirka ee kansarka ganaca, ku darista 20% mannose biyaha la cabbo waxay hoos u dhigtay heerka koritaanka burada 40%, iyo marka lagu daro daawada chemotherapy gemcitabine, badbaadada 2 ayaa la kordhiyay. Daah-furkani waxa uu meesha ka saaray aragtidii caadiga ahayd ee ahayd in "dhammaan sonkortu ay kor u qaadaan kansarka".

?

Goobta-haystaha0 Cutubka 2aad Go'aaminta Habka Ka-hortagga Kansarka: Saddex "quful sonkor ah" Fur khadka nolosha ee Tumor

Youdaoplaceholder0 2.1 Afduubka dheef-shiid kiimikaadka: "Faraska Trojan" oo loo ekeysiiyay gulukoos

"Saamaynta Warburg" ee unugyada burooyinka waxay awood u siinaysaa qaadashada gulukooska inay toban jeer ka badan tahay unugyada caadiga ah. Kooxda CRUK waxay ku ogaadeen tignoolajiyada raadraaca kaarboon-13 isotope isotope in mannose uu ku dhex milmi karo unugyada kansarka iyada oo loo marayo nooca gulukoosta qaada (GLUT1/3) oo leh qaab la mid ah kan gulukooska. Si kastaba ha ahaatee, ka dib marka la galo, waxaa si degdeg ah fosfooraska by hexokinase si mannose-6-phosphate (M6P). Dhexdhexaadiyaha dheef-shiid kiimikaadkani ma geli karo dariiqa glycolytic, laakiin taa beddelkeeda wuxuu ku ururaa gudaha unugga si uu u sameeyo "caqabadda dheef-shiid kiimikaadka", taasoo horseedaysa xannibaadda isku-dhafka ATP iyo dillaaca noocyada ogsijiinta falcelinta (ROS), ugu dambeyntii kicinta apoptosis ee unugyada kansarka (Jaantus 1).

?

Youdaoplaceholder0 2.2 Xeerka Epigenetic: Dib u qorida "koodhka xusuusta" ee unugyada kansarka

2023, koox cilmi baaris ah oo ka socota Jaamacadda Fudan ee dheef-shiid kiimikaadka unugyada ayaa sii daaha ka qaaday in mannose uu u dhaqmi karo sidii "tafatiraha epigenome". Qaabka adenocarcinoma ductal pancreatic (PDAC), daaweynta mannose waxay si weyn hoos ugu dhigtay heerka acetylation ee goobta histone H3K27, taasoo keentay in la joojiyo dhaqdhaqaaqyada qoraalka ee MYC iyo KRAS ee oncogenes. Xitaa si ka sii yaab badan, saameyntan dib-u-habeyn ee muuqata waa mid joogto ah - xitaa marka maamulka daroogada la joojiyo, unugyada kansarku waxay weli sii wadaan qulqulitaan hoose, iyagoo siinaya fikrado cusub oo daaweyn xagjir ah.

?

Youdaoplaceholder0 2.3 Dib-u-habaynta difaaca jirka ee microevironment: Jeexitaanka " qarinta sonkorta-dahaarka leh" ee PD-L1 ?

Koox isku mid ah ayaa laga helay daraasadihii xigay in mannose uu jebin karo habka difaaca difaaca ee burooyinka iyaga oo farageliya isbeddelka glycosylation ee barnaamijka dhimashada ligand 1 (PD-L1). Falanqaynta spectrometry mass ayaa shaaca ka qaaday in mannose uu xannibay N-glycosylation of asparagine booska 192 ee borotiinka PD-L1, taasoo keentay in uu awoodi waayo inuu si sax ah u laalaabsado oo uu ku xidho xuubka unugyada. PD-L1, kaas oo luminaya ilaalinta "gashaanka sonkorta", waxaa lagu calaamadeeyay E3 ubiquitin ligase FBXW41 oo ay hoos u dhigtay proteasome. Jiirarka melanoma, isku-darka mannose iyo ka-hortagga-PD-1-ka-hortagga unugyada waxay kordhiyeen heerka dib-u-celinta buro oo dhammaystiran min 28% ilaa 79% (Jaantuska 2).

?

Youdaoplaceholder0 Cutubka 3 Laga Soo Bilaabo Qaababka Xayawaanka ilaa Tijaabada Caafimaadka Aadanaha: Waddada Qodaxsan ee Daawada Turjumaada

Youdaoplaceholder0 3.1 Horumarrada iyo Xaddidaadda cilmi-baarista hore

Qaabka kansarka ganaca ee CRUK, in kasta oo monotherapy leh mannose ay daahisay horumarka burada, waxay ku guul darreysatay inay gaarto cafis dhammaystiran. Si kastaba ha ahaatee, marka lagu daro nidaamka FOLFIRINOX kiimoterabiga, wakhtiga badbaadada dhexdhexaadka ah ee jiirarka ayaa laga dheeraaday 42 maalmood ilaa 98 maalmood, mana jirin korodhka sunta. Natiijadan waxa lagu soo saaray qaabka kansarka naasaha ee saddex-geesoodka ah ee MD Anderson Cancer Center: Mannose wuxuu kordhiyey heerka xakamaynta buro ee paclitaxel min 45% ilaa 72%. Si kastaba ha ahaatee, cilmi-baarayaashu waxay sidoo kale ogaadeen in qiyaastii 15% burooyinka aysan ka jawaabin mannose. Falanqaynta dheeraadka ah ayaa shaaca ka qaaday in unugyadan daawada u adkaysta ay si aad ah u muujiyeen mannose-phosphate isomerase (PMI), taas oo u beddeli karta M6P fructose-6-fosfate waxayna dib ugu xiri kartaa dariiqa glycolytic.

?

Youdaoplaceholder0 3.2 Waa waabeer oo taxaddar leh oo tijaabooyinka aadanaha

Tijaabada caafimaad ee Wajiga koowaad ee mannose ee la bilaabay 2022 (NCT05220739) waxaa ku jiray 32 bukaan oo qaba burooyin adag oo horumarsan. Kooxda qiyaasta maalinlaha ah ee maamulka afka ee 5g mannose, heerarka wareegga DNA-da ee buro (ctDNA) ee 8 bukaan ayaa hoos u dhacay in ka badan 50%, taas oo mugga beerka beerka ee hal bukaan kansarka ganaca uu hoos u dhacay 31%. Si kastaba ha noqotee, markii qiyaasta kor u kacday 10g, heerka shubanka III ayaa ku dhacay 3 bukaan, taasoo soo jeedinaysa in istaraatiijiyadda maamulka loo baahan yahay in la hagaajiyo. Waqtigan xaadirka ah, diyaargarowga mannose-ka ee xididada iyadoo la adeegsanayo tignoolajiyada encapsulation nano-liposome ayaa socda. Xogta saxda ah waxay muujineysaa in waxtarkooda dhalmada ee buro-bartilmaameedka ah ay gaareyso 78%, iyo suntooda si weyn loo dhimay.

?

Qofkastaoplaceholder0 Cutubka 4 Isbeddelka Warshadaha iyo Muran: Caqabadaha Dhabta ah ee Kacaanka Macaan

Youdaoplaceholder0 4.1 bayoloji synthetic ayaa xalliya halxiraalaha wax soo saarka tirada badan

Mannose si dabiici ah loo soo saaray waa qaali (qiyaastii kiilogaraam)

1200

Way adag tahay in la buuxiyo shuruudaha qiyaasta ka hortagga kansarka (maalin kasta)

Habka waa in la kordhiyo wax soo saarka ilaa

Qiimaha ayaa hoos ugu dhacay ilaa 1200), taas oo ay adag tahay in la buuxiyo shuruudaha qiyaasta ka hortagga kansarka (10-20g maalintii). GinkgoBioworks ayaa kordhisay wax-soo-saarka ilaa 30g/L waxayna hoos u dhigtay 50/kg iyadoo wax ka baddalaysa dariiqa mannose-1-guanosine phosphate transferase (MPG) ee Escherichia coli. Tignoolajiyada horumarsan sida CRISPR-Cas9-edited Saccharomyces cerevisiae bakteeriyada ayaa awooday in ay si degan u soo saarto mannose saafi ah oo sarreeya inta lagu jiro halsano joogto ah.

?

Youdaoplaceholder0 4.2 Ciyaarta u dhaxaysa Hype-ganacsiga iyo anshaxa sayniska

Iyadoo fikradda ah "sonkorta ka hortagga kansarka" ay noqoto mid caan ah, boqollaal alaabooyin caafimaad oo mannose ah oo sheeganaya inay yihiin "daawaynta kaaliyaha ee burooyinka" ayaa ka soo muuqday goobta Amazon, oo leh qiimo sare oo sarreeya ilaa toban jeer. Sannadka 2023, FDA-da Mareykanka ayaa waraaqo digniin ah u dirtay 23 shirkadood, iyadoo ku nuuxnuuxsatay in "kaabista cuntada ay tahay inaysan sheegan inay saameyn daweyn ku yeelanayso cudurrada." Saynis yahanadu waxa ay ka walaacsan yihiin in si indho la’aan ah loo qaato qiyaaso badan oo mannose ah in ay khalkhal galiso flora mindhicirka - tijaabooyinka xayawaanku waxa ay muujiyeen in qaadashada muddada dheer ay keenayso in 80% ay hoos u dhacdo tirada badan ee Faecalibacterium prausnitzii iyo korodhka shan laab ee Fusobacterium nucleatum. Tan dambe waxay si dhow ula xiriirtaa horumarka kansarka mindhicirka.

?

Youdaoplaceholder0 Cutubka Shanaad Rajada Mustaqbalka: Badweynta wayn ee Dawooyinka Glyco-salaysan

Youdaoplaceholder0 5.1 Kacaanka Glycolic ee Daawada Saxda ah

Xeeladaha daawaynta ee shakhsi ahaaneed ee ku salaysan kala duwanaanshaha dheef-shiid kiimikaadka buro ayaa soo baxaya. Qaabka "Mannose Sensitivity Score" (MSS) ee uu soo saaray Machadka Broad ee Maraykanka ayaa saadaalin kara suurtagalnimada jawaabta bukaannada ee mannose iyadoo la ogaanayo heerka muujinta GLUT1, dhaqdhaqaaqa hexokinase iyo heerka isbeddelka PMI ee unugyada burooyinka. Naqshadeynta tijaabooyinka bukaan-socodka ee Wajiga II, bukaannada kansarka ganaca ee leh dhibcaha MSS ee ≥75% ayaa la siin doonaa mudnaanta ka mid noqoshada si loo hagaajiyo heerka jawaabta daaweynta.

?

Youdaoplaceholder0 5.2 Isku-dubarid ka-tallaalidda sokorta daawooyinka injineernimada

Cilmi-baaristii hore kuma qanacsana hal mar oo la isticmaalo mannose dabiiciga ah. Kooxda MIT waxay nashqadeeyeen "mannose-paclitaxel" conjugate, kaas oo ka faa'iideysanaya qaadashada sare ee mannose ee unugyada burooyinka si loo gaaro gaarsiinta bartilmaameedka ah ee daawooyinka kemotherabi. Noocyada kansarka naasaha, waxtarka buro-dilka isku-xidhkaani wuxuu ahaa saddex jeer ka paclitaxel-dhaqameedka, iyo wadne-xannuunkeeda waxaa la dhimay 60%. Horumar kale ayaa ka yimid Jaamacadda Shanghai Jiao Tong: iyada oo la isku daray mannose iyo photosensitizer Ce6, "daaweyn photodynamic ku salaysan oo sonkor ah" oo lagu hawlgelin karo iftiinka infrared-ka dhow ayaa la sameeyay, taas oo muujinaysa suurtagalnimada burooyinka qoto dheer.

?

Youdaoplaceholder0 Gabagabo: "molecule-ka macaan" oo dib u qoraya xeerarka ka hortagga kansarka

Safarka ka hortagga kansarka ee mannose waa dhimbiil ifaya oo ka dhashay isku dhaca sayniska aasaasiga ah iyo baahiyaha caafimaad. Laga soo bilaabo faragelinta dheef-shiid kiimikaadka ilaa xakamaynta difaaca, laga bilaabo monotherapy ilaa hababka isku dhafan, molecule sonkortu waxay jebinaysaa khadka difaaca burada oo leh xeelado weerar oo dhinacyo badan leh. Inkasta oo dariiqa ganacsigu uu wali wajahayo caqabado ay ka mid yihiin hagaajinta qiyaasta, hababka iska caabbinta daroogada, iyo xeerarka sharciyeynta, bulshada sayniska ayaa rajo weyn ka qabta - sida ku guulaysta abaalmarinta Nobel James Watson, "Nuxurka kansarku waa cilladda genomic, iyo mannoglucose wuxuu ina barayaa in faragelinta dheef-shiid kiimikaadka ay soo celin karto nidaamka." Iyaga oo ay wadaan labada taayir ee daawada saxda ah iyo bayoolaji synthetic, "kacaanka macaan" waxa laga yaabaa inuu keeno xilli cusub oo daaweynta kansarka.