Youdaoplaceholder0 1.1 Boyayyen memba na dangin sukari

A matsayin tushen makamashin halittu masu rai, tsarin rarraba carbohydrates ya da?e yana ?arfafawa a cikin litattafan karatu: monosaccharides (kamar glucose da fructose), oligosaccharides (kamar lactose), da polysaccharides (kamar sitaci). Duk da haka, musamman na mannose ya ta'allaka ne a cikin "dual ainihi" - ba kawai mai shiga cikin makamashi metabolism ba amma kuma "kalmar kalmar sirri" don sadarwar salula. Mannose yana ko'ina a cikin 'yanci a cikin pectin Layer na 'ya'yan itatuwa citrus da bangon tantanin halitta na algae mai zurfi. A cikin jikin mutum, ya zama tushen kwayoyin halitta na mahimmin hanyoyin ilimin lissafin jiki kamar ganewar rigakafi da mannewar kwayar halitta ta hanyar N-link glycosylation gyare-gyare na glycoproteins.

?

Mai ri?e da wurin zama0 1.2 Ha?aka Fahimta daga Lafiyar Urinary zuwa Majagaba na Ciwon daji

Tun farkon shekarun 1980, ?ungiyar likitocin sun gano cewa mannose na iya hana kamuwa da cututtukan urinary ta hanyar gasa ta hana adhesins na ?wayoyin cuta. Wannan tsari ya haifar da zazzafan tallace-tallacen kayan kiwon lafiya na cranberry. Amma ba har sai 2018 cewa wani muhimmin binciken da Cancer Research UK (CRUK) ya yi a cikin mujallar Nature da gaske ya ?aga mayafin akan ?o?arin da yake yi na rigakafin cutar kansa: A cikin ?irar linzamin kwamfuta na ciwon daji na pancreatic, ?ara 20% mannose zuwa ruwan sha ya rage girman ha?akar ?ari da 40%, kuma lokacin da aka ha?a shi da maganin chemotherapy gemcitabine, an tsawaita lokacin rayuwa ta 2. Wannan binciken ya kawar da tunanin al'ada cewa "duk masu ciwon sukari suna inganta ciwon daji".

?

Mai ri?e da wurinku0 Babi na 2 ?irar ?arfafa ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararrun ?wararru guda uku

Youdaoplaceholder0 2.1 Hijacking Metabolic: "Dokin Trojan" ya zama kamar glucose

"Tasirin Warburg" na ?wayoyin ?ari yana ba da damar ?aukar glucose su zama sau goma na sel na yau da kullun. Tawagar CRUK ta gano ta hanyar fasahar gano isotope na carbon-13 cewa mannose na iya shiga cikin ?wayoyin kansa ta hanyar nau'in jigilar glucose guda ?aya (GLUT1/3) tare da tsari mai kama da na glucose. Duk da haka, bayan shigar, yana da sauri phosphorylated ta hexokinase zuwa mannose-6-phosphate (M6P). Wannan tsaka-tsaki na rayuwa ba zai iya shiga hanyar glycolytic ba amma a maimakon haka yana tarawa a cikin tantanin halitta don samar da "shamakin ?wayar cuta", wanda ke haifar da toshewar ha?in ATP da fashewar nau'in oxygen mai amsawa (ROS), a ?arshe yana haifar da apoptosis na kwayoyin ciwon daji (Figure 1).

?

Youdaoplaceholder0 2.2 Tsarin Epigenetic: Sake rubuta "lambar ?wa?walwar ajiya" na ?wayoyin kansa

A cikin 2023, ?ungiyar bincike daga Jami'ar Fudan a cikin Ciwon Halittu ta ?ara bayyana cewa mannose na iya aiki azaman "edita na epigenome". A cikin tsarin pancreatic ductal adenocarcinoma (PDAC), maganin mannose ya rage girman matakin acetylation na shafin histone H3K27, wanda ya haifar da hana ayyukan rubutun na oncogenes MYC da KRAS. Har ila yau, abin mamaki, wannan sakamako na sake tsarawa yana dawwama - ko da lokacin da aka dakatar da gudanar da magani, kwayoyin cutar kansa suna ci gaba da raguwa, suna samar da sababbin ra'ayoyin don maganin tsattsauran ra'ayi.

?

Youdaoplaceholder0 2.3 Gyaran microenvironment na rigakafi: Yage "mai rufin sukari" na PD-L1 ?

?ungiyar guda ?aya da aka samu a cikin binciken da suka biyo baya cewa mannose na iya fashe tsarin tserewa na rigakafi na ciwace-ciwace ta hanyar tsoma baki tare da gyare-gyaren glycosylation na shirin mutuwa ligand 1 (PD-L1). Mass spectrometry bincike ya nuna cewa mannose ya hana N-glycosylation na asparagine a matsayi na 192 na furotin PD-L1, wanda ya haifar da rashin iyawarta daidai da daidaitawa akan membrane cell. PD-L1, wanda ya rasa kariyar "garkuwar sukari", an lakafta shi ta E3 ubiquitin ligase FBXW41 kuma ya lalata ta hanyar proteasome. A cikin mice na melanoma, ha?uwa da mannose da anti-PD-1 antibodies ya karu da cikakkiyar ?wayar ?wayar cuta daga 28% zuwa 79% (Hoto 2).

?

Mai ri?e wurin zama0 Babi na 3 Daga Samfuran Dabbobi zuwa Gwajin Asibiti na ?an adam: Hanyar ?ayayuwa ta Magungunan Fassara ?

Youdaoplaceholder0 3.1 Nasarori da Iyakance na bincike na farko

A cikin tsarin ciwon daji na pancreatic na CRUK, kodayake monotherapy tare da mannose yana jinkirta ci gaban ?ari, ya kasa samun cikakkiyar gafara. Koyaya, lokacin da aka ha?a shi da tsarin ilimin chemotherapy na FOLFIRINOX, lokacin rayuwa na tsaka-tsaki na mice ya tsawaita daga kwanaki 42 zuwa kwanaki 98, kuma babu ?aruwa a cikin guba. An sake haifar da wannan sakamakon a cikin nau'in cutar kansar nono mai sau uku a Cibiyar Ciwon daji ta MD Anderson: Mannose ya karu da ?wayar ?wayar cuta ta paclitaxel daga 45% zuwa 72%. Duk da haka, masu bincike sun gano cewa kusan kashi 15% na ciwace-ciwacen daji ba su amsa ga mannose. ?arin bincike ya nuna cewa wa?annan kwayoyin da ke da maganin miyagun ?wayoyi sun bayyana manose-phosphate isomerase (PMI), wanda zai iya canza M6P zuwa fructose-6-phosphate kuma ya sake ha?awa zuwa hanyar glycolytic.

?

Youdaoplaceholder0 3.2 A taka tsantsan alfijir na mutane

Gwajin asibiti na Farko na farko na mannose wanda aka fara a cikin 2022 (NCT05220739) ya ha?a da marasa lafiya 32 masu ciwace-ciwacen ciwace-ciwace. A cikin rukunin kashi na yau da kullun na sarrafa baki na 5g mannose, matakan ?wayar cutar ?wayar cuta ta DNA (ctDNA) na marasa lafiya 8 sun ragu da fiye da 50%, wanda adadin hanta metastases a cikin mai ciwon daji na pancreatic ya ragu da kashi 31%. Koyaya, lokacin da adadin ya hau zuwa 10g, zawo na aji III ya faru a cikin marasa lafiya 3, yana nuna cewa dabarun gudanarwa yana bu?atar ha?akawa. A halin yanzu, shirye-shiryen mannose na cikin jijiya ta amfani da nano-liposome fasahar encapsulation na kan ci gaba. Bayanai na asali sun nuna cewa ingancin isar da ?wayar cuta da aka yi niyya ya kai kashi 78%, kuma an rage yawan gubarsu.

?

Mai ri?e wurin zama0 Babi na 4 Canjin Masana'antu da Rigima: Ha?i?anin Kalubalen Juyin Juyin Juya Halin Da?i

Youdaoplaceholder0 4.1 Ilimin Halittar Halittu Yana Warware ?wararrun Samar da Jama'a ?

Mannose da aka fitar ta halitta yana da tsada (kimanin kilogiram ?aya)

1200

Yana da wahala a cika bu?atun maganin ciwon daji (a kowace rana)

Hanyar ita ce ?ara yawan fitarwa zuwa

Farashin ya ragu zuwa 1200), wanda ke da wahala a cika bu?atun maganin cutar kansa (10-20g kowace rana). GinkgoBioworks, GinkgoBioworks, ya ha?aka yawan amfanin ?asa zuwa 30g/L kuma ya rage farashin zuwa 50/kg ta hanyar gyara hanyar mannose-1 - guanosine phosphate transferase (MPG) na Escherichia coli. ?arin fasahohin ci-gaba kamar CRISPR-Cas9-edited Saccharomyces cerevisiae injiniyoyin ?wayoyin cuta sun sami damar samar da tsaftataccen mannose yayin ci gaba da fermentation.

?

Youdaoplaceholder0 4.2 Wasan tsakanin Hype kasuwanci da ka'idodin kimiyya

Tare da ra'ayin "ciwon daji na rigakafin ciwon daji" ya zama sananne, daruruwan kayayyakin kiwon lafiya na mannose da ke da'awar zama "maganin taimako ga ciwace-ciwacen daji" sun fito a dandalin Amazon, tare da farashin farashi har sau goma. A cikin 2023, FDA ta Amurka ta ba da wasi?un garga?i ga kamfanoni 23, tare da jaddada cewa "kayan kayan abinci ba dole ba ne su yi i?irarin samun tasirin warkewa akan cututtuka." Masana kimiyya sun damu da cewa shan mannose mai yawa a makance na iya rushe flora na hanji - gwaje-gwajen dabbobi sun nuna cewa cin abinci na dogon lokaci yana haifar da raguwar 80% na yawan Faecalibacterium prausnitzii da karuwa sau biyar a cikin Fusobacterium nucleatum. Na ?arshe yana da ala?a da kusanci da ci gaban ciwon daji na launin fata.

?

Youdaoplaceholder0 Babi na Biyar Halayen Gaba: Fa?in Teku na Magungunan Glyco

Youdaoplaceholder0 5.1 Juyin Glycolic a Madaidaicin Magunguna

Dabarun jiyya na ?ai?aikun ?ai?aikun dangane da nau'ikan nau'ikan ?wayar cuta suna tasowa. Samfurin "Mannose Sensitivity Score" (MSS) wanda Cibiyar Broad Institute ta Amurka ta kirkira zai iya yin hasashen yiwuwar amsawar marasa lafiya zuwa mannose ta hanyar gano matakin GLUT1, ayyukan hexokinase da matsayin maye gurbin PMI a cikin kyallen takarda. A cikin ?irar gwaje-gwajen asibiti na Phase II, masu ciwon daji na pancreatic tare da maki MSS na ≥75% za a ba su fifiko don ha?awa don ha?aka ?imar amsawar jiyya.

?

Youdaoplaceholder0 5.2 Ha?in kan iyaka na sukari Injiniyan magunguna

Binciken gaba baya gamsu da aikace-aikacen mannose na halitta guda ?aya. Tawagar MIT ta ?ir?ira wani “mannose-paclitaxel” conjugate, wanda ke cin gajiyar yawan yawan mannose ta ?wayoyin ?ari don cimma isar da niyya na magungunan chemotherapy. A cikin nau'ikan ciwon daji na nono, tasirin kashe ?ari na wannan ha?in gwiwa ya ninka na paclitaxel na gargajiya sau uku, kuma an rage yawan cututtukan zuciya da kashi 60%. Wani ci gaba ya zo daga Jami'ar Shanghai Jiao Tong: ta hanyar hada mannose tare da photosensitizer Ce6, "maganin ciwon sukari na photodynamic" wanda za'a iya kunna shi ta hanyar hasken infrared na kusa da shi, wanda ke nuna yiwuwar zubar da ciki mai zurfi.

?

Youdaoplaceholder0 Kammalawa: "Kwayoyin halitta mai dadi" suna sake rubuta ka'idojin rigakafin ciwon daji

Tafiyar cutar sankara na mannose wani haske ne mai haske wanda ya haifar da karo na asali na kimiyya da bukatun asibiti. Daga shiga tsakani na rayuwa zuwa tsarin rigakafi, daga monotherapy zuwa tsarin hadewa, wannan kwayar cutar sukari tana rushe layin kariya na tumo tare da dabarun kai hari da yawa. Kodayake hanyar kasuwancin har yanzu tana fuskantar ?alubale kamar ha?aka kashi, hanyoyin juriya na miyagun ?wayoyi, da ?a'idodi masu ?a'ida, al'ummomin kimiyya suna da kyakkyawan fata a gare shi - kamar yadda mai ba da lambar yabo ta Nobel James Watson ya ce, "Mahimmancin ciwon daji shine cuta ta kwayoyin halitta, kuma mannoglucose yana koya mana cewa shiga tsakani na rayuwa zai iya dawo da tsari." ?un?arar ?afafu biyu na ingantattun magunguna da ilimin halitta na roba, wannan "juyin juya hali mai da?i" na iya haifar da sabon zamanin maganin cutar kansa.