A cikin yakin da aka kwashe tsawon karni ana yi tsakanin bil'adama da kansa, a ko da yaushe yanayi yana ba da alamu don magance matsalar ta hanyoyin da ba a zata ba. A cikin 'yan shekarun nan, da alama monosaccharide na yau da kullun - Mannose - ya zama abin da aka fi mayar da hankali kan binciken kimiyya a duniya saboda abubuwan da ke da ala?a da cutar kansa. Wannan hexose, wanda aka fi samunsa a cikin cranberries da 'ya'yan itatuwa citrus, ya tashi daga matsayin tallafi a fagen abinci mai gina jiki zuwa babban rawar da ake takawa a cikin binciken ?wayar cuta, yana bayyana sabon nau'in abubuwan sukari a cikin tsarin rayuwa. Wannan labarin zai yi nazari sosai kan yadda mannose ke sake fasalin yanayin maganin ciwon daji daga bangarori hudu: bincike na asali, tsarin aiki, sauyin asibiti da makomar masana'antu.

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Babi Na Farko: Karya Fahimci: Faruwar Cutar Kanjamau ta Kwayoyin Za?i

1.1 Matsakaicin Matsayi a cikin binciken Carbohydrate

A cikin tunanin al'ada, sukari (carbohydrates) an da?e ana ?aukarsa a matsayin "ku?in kuzari". Musamman ma glucose, a matsayin ginshi?i na numfashin salula, ha?in gwiwa tsakanin abubuwan da ba su da kyau na rayuwa da ci gaban ciwon daji ya kasance cikakke. Duk da haka, wani bincike na ci gaba da Cancer Research UK ya buga a cikin mujallar Nature a cikin 2018 ya sake rubuta wannan labari gaba ?aya - ?ungiyar bincike ta tabbatar a karon farko cewa mannose na iya za?ar hana yaduwar ?wayoyin cutar kansa ta hanyar tsoma baki tare da hanyar ciwon sukari na ?wayar cuta, tare da ?an tasiri akan kyallen takarda na yau da kullun. Wannan binciken ba wai kawai ya juyar da ra'ayin cewa "duk masu ciwon sukari suna inganta cutar kansa ba", har ma yana bu?e sabon fagen fama don maganin sa baki.

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1.2 Binciken Halittu na Mannose

A matsayin isomer na glucose, an rarraba mannose a cikin yanayin kyauta akan epidermis na 'ya'yan itatuwa kamar citrus da apples a cikin yanayi, ko kuma yana shiga cikin ginin membranes na halitta a cikin nau'i na glycoproteins. A cikin jikin mutum, mannose yana phosphorylated don samar da mannose-6-phosphate (M6P), wanda ya zama ma?alli mai mahimmanci don rarraba enzyme lysosomal. Tun da farko binciken asibiti ya bayyana tsarinsa na hana kamuwa da cutar yoyon fitsari: ta hanyar yin gasa ga masu kar?ar ?wayoyin cuta na ?wayoyin cuta, yana toshe musu mulkin mallaka akan urothelium. Wannan siffa ta haifar da nau'ikan kayan abinci iri-iri da suka ta'allaka kan mannose, amma gano yuwuwar rigakafin cutar kansa ya haifar da ha?akar ?imar aikin sa.

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Babi na Biyu: ?ididdigar Kimiyya: Laifin Sau Uku na Mannose Against Cancer

2.1 Hijacking Metabolic: Kashe "jarabar ciwon sukari" da ke samar da kwayoyin cutar kansa.

Sakamakon Warburg na ?wayoyin tumo (wanda har yanzu yana dogara ga glycolysis don makamashi ko da a cikin yanayi mai wadatar oxygen) yana ba da damar ?aukar glucose su zama har sau goma na sel na al'ada. Wata tawagar Burtaniya ta gano ta hanyar fasahar gano isotope cewa bayan mannose ya shiga cikin kwayoyin cutar kansa, hexokinase ne ke sarrafa shi ya zama M6P kuma yana taruwa da yawa a cikin sel. Wannan "pseudo-metabolite" ba wai kawai ya mamaye tashoshi na jigilar glucose ba (GLUT), amma kuma yana gasa don hana ayyukan phosphoglucose isomerase, wanda ya haifar da rashin ma?alli masu mahimmanci a cikin glycolysis da tricarboxylic acid sake zagayowar, a ?arshe yana haifar da rikicin makamashi a cikin ?wayoyin kansa (Figure 1).

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2.2 Epigenetics: Sake fasalin ?ananan ?wayoyin ?wayar cuta

Wani bincike da Jami'ar Fudan ta buga a cikin Cell Metabolism a cikin 2023 ya kara bayyana cewa mannose na iya juyar da rashin lafiyar epigenetic a cikin kwayoyin cutar kansa ta hanyar daidaita matakan histone acetylation. Gwaje-gwaje sun nuna cewa a cikin kwayoyin cutar kansar pancreatic da aka bi da su tare da mannose, an rage matakin acetylation na yankin mai ha?akawa na oncogene MYC, kuma an hana aikin rubutunsa sosai. Wannan sakamako na sake tsarawa na epigenetic yana raunana halayen ?arna da bushewar ?wayoyin ?wayar cuta, yana ba da cikakkiyar ka'idar don ha?akar ha?a??un magungunan epigenetic.

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2.3 Ha?in kai na rigakafi: Cire "Cloak Invisibility" na PD-L1

Ko da ?arin ?arna shine cewa ?ungiyar guda ta gano cewa mannose na iya kai hari ga hanyar tsirar ?wayar cuta. Ta hanyar bincike mai zurfi, masu bincike sun tabbatar da cewa mannose yana hana daidaitaccen nadawa da daidaitawar ?wayar jikin furotin PD-L1 ta hanyar tsoma baki tare da gyaran N-glycosylation. Sunan furotin PD-L1, wanda ya rasa "laima mai kariya" na sarkar sukari, ya fi dacewa da zama a ko'ina kuma a lalata shi, ta haka yana kawar da siginar hanawa akan ?wayoyin T. A cikin ?irar linzamin kwamfuta na melanoma, ha?in mannose da anti-PD-1 antibody ya karu da raguwar ?wayar ?wayar cuta zuwa 78%, wanda ya wuce na maganin guda ?aya (Hoto 2).

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Babi na uku: Daga dakin gwaje-gwaje zuwa Na asibiti: Hanyar Cigaban Magungunan Fassara

3.1 Manufofin bincike na gaskiya

A cikin gwaje-gwajen dabbobi da yawa, mannose ya nuna yuwuwar rigakafin cutar kansa. Wata tawagar Burtaniya ta shiga tsakani samfurin ciwon daji na pancreatic tare da ruwan sha mai kashi 20% na mannose kuma sun gano cewa girman ?wayar ?wayar cuta ya jinkirta da kusan kashi 40%, kuma babu wani babban hanta ko ?wayar koda. Har ma da ban sha'awa, lokacin da aka yi amfani da shi tare da gemcitabine, lokacin rayuwa na berayen ya tsawaita da sau 2.3, yana nuna ?imar ilimin chemotherapy. Gwaje-gwaje masu zaman kansu a Cibiyar Ciwon daji na MD Anderson a Amurka sun nuna cewa mannose yana da tasiri daidai da nau'in ciwon daji kamar ciwon nono mai sau uku da glioblastoma.

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3.2 Binciko A Tsanake Na Gwajin Dan Adam

Duk da cikakkun bayanai masu ban sha'awa, gwajin ?an adam yana fuskantar ?alubale na musamman. Gwajin asibiti na Phase I (NCT05220739) wanda aka fara a cikin 2022 shine farkon don kimanta amincin mannose na baka a cikin marasa lafiya da ciwace-ciwacen ciwace-ciwace. Bayanai na farko sun nuna cewa marasa lafiya a cikin rukunin kashi na 5g na yau da kullun suna da ha?uri mai kyau, kuma matakan DNA da ke yawo da ?ari (ctDNA) a wasu lokuta sun ragu sosai. Koyaya, lokacin da adadin ya haura zuwa 10g, kusan 15% na marasa lafiya sun sami zawo mai laushi, yana nuna bu?atar ha?aka tsarin maganin.

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3.3 Hanyoyin fasaha ga masana'antu

Ko da yake mannose da aka fitar a zahiri ba shi da ha?ari, yana bu?atar ?ayyadaddun ?ayyadaddun ?ayyadaddun ?ayyadaddun ?wayar cuta don isa matakin rigakafin cutar kansa (daidai da cinye kilogiram 5 na cranberries kowace rana), wanda ya haifar da sabbin fasahohi a cikin ilimin halitta na roba. A halin yanzu, Escherichia coli da aka kirkira ta kwayoyin halitta na iya kara yawan mannose da sau 20, yayin da rashin motsin enzyme catalysis yana rage farashin samarwa zuwa kasa da $50 a kowace kilogiram. Bugu da kari, fasahar encapsulation nano-liposome na iya ha?aka ingantaccen isar da ?wayar cuta zuwa 80%, yana share hanya don canjin asibiti.

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Babi na Hudu Rigima da Tunani: Tunani Mai sanyi a Bikin Bikin Kimiyya

4.1 "Takobi mai kaifi biyu" Tasirin shiga tsakani na Metabolic

Ya kamata a lura da cewa mannose ba panacea ba ne. Wasu kwayoyin cutar kansa da ke ?auke da maye gurbin mannose phosphate isomerase (PMI) na iya canza mannose-6-phosphate zuwa fructose-6-phosphate, wanda a maimakon haka yana ha?aka glycolytic flux. An gano wannan al'amari na "kubuta na rayuwa" a cikin kusan kashi 7% na samfuran ciwon daji na launin fata, yana nuna bu?atar ha?aka alamomin tantance mutum ?aya.

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4.2 Halitta ≠ Amintaccen: Fasahar Kula da Sashi

Ko da yake an yarda da mannose don amfani da abinci a matsayin GRAS (Gaba?aya An gane shi azaman Safe) abu, da?a??en gubarsa a allurai na rigakafin ciwon daji har yanzu yana bu?atar ?auka da mahimmanci. Gwaje-gwajen dabbobi sun gano cewa ci gaba da cin abinci mai yawa na iya haifar da rikice-rikice na flora na hanji, tare da yalwar wasu ?wayoyin cuta masu ha?ari (irin su Klebsiella) suna ?aruwa sau goma. Wannan yana bu?atar bincike na gaba dole ne ya daidaita tasirin warkewa da microecological homeostasis.

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4.3 Wasan Tsakanin Kasuwancin Kasuwanci da Mahimmancin Kimiyya

Tare da ra'ayin "ciwon daji na ciwon daji" ya zama sananne, wasu 'yan kasuwa sun yi karin gishiri game da lafiyar lafiyar mannose. FDA ta Amurka ta ba da wasi?un garga?i ga kamfanoni uku don tallata su ba bisa ?a'ida ba, tana mai jaddada cewa "kayan abinci ba zai iya maye gurbin maganin miyagun ?wayoyi ba." Masana kimiyya sun yi kira da a kafa ?wararrun masana'antu don tsara lakabi da tallan samfuran da ke ?auke da mannose.

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Kammalawa: Hoton nan gaba na juyin juya hali mai dadi

Tafiyar cutar kansa ta mannose ba kawai cikakkiyar saduwa ce ta kyaututtukan yanayi da hikimar ?an adam ba, har ma abin koyi ne na sabbin fasahohi. Daga tsarin sake fasalin rayuwa zuwa sake fasalin microenvironment na rigakafi, daga bututun gwajin dakin gwaje-gwaje zuwa masana'antar magunguna, wannan "juyin juya hali mai dadi" yana sake rubuta littafin ka'idojin maganin ciwon daji. Ko da yake har yanzu akwai ?alubale da yawa a gaba, ana iya hasashen cewa ?arni na gaba na magungunan glyco da ke kan mannose na iya haifar da sabon zamani na ainihin maganin cutar kansa. Kamar yadda Nature yayi sharhi: "Lokacin da kimiyya ke rawa tare da yanayi, kararrawa ranar lahira na ciwon daji ya riga ya buga."

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