Pankhondo yazaka zana limodzi pakati pa anthu ndi khansa, chilengedwe chakhala chikupereka njira zothetsera vutoli m'njira zosayembekezereka. M'zaka zaposachedwa, monosaccharide yowoneka ngati wamba - Mannose - yakhala gawo lalikulu padziko lonse lapansi pakufufuza kwasayansi chifukwa champhamvu yake yolimbana ndi khansa. Hexose iyi, yomwe imapezeka kwambiri mu cranberries ndi zipatso za citrus, yakwera kuchokera pakuthandizira gawo lazakudya kupita ku gawo lotsogola pa kafukufuku wa chotupa cha metabolism, kuwulula gawo latsopano la zinthu za shuga pakuwongolera moyo. Nkhaniyi isanthula mozama momwe mannose amasinthira mawonekedwe a chithandizo cha khansa kuchokera kuzinthu zinayi: kafukufuku wofunikira, makina ochitirapo kanthu, kusintha kwachipatala komanso chiyembekezo chamakampani.

?

Mutu Woyamba: Kugwetsa Chidziwitso: Kudzutsidwa kwa Anti-Cancer kwa Mamolekyulu Otsekemera

1.1 Paradigm Shift mu kafukufuku wa Carbohydrate

M'malingaliro achikhalidwe, shuga (zakudya zama carbohydrate) akhala akuwoneka ngati "ndalama zamphamvu". Makamaka glucose, monga gawo lalikulu la kupuma kwa ma cell, mgwirizano pakati pa zovuta zake za metabolic ndi kukula kwa khansa zawonetsedwa bwino. Komabe, kafukufuku wopambana wofalitsidwa ndi Cancer Research UK mu nyuzipepala ya Nature mu 2018 adalembanso nkhaniyi - gulu lofufuza lidatsimikizira kwa nthawi yoyamba kuti mannose amatha kuletsa kuchulukitsitsa kwa maselo a khansa posokoneza njira ya kagayidwe ka shuga wa chotupacho, osakhudzidwa pang'ono ndi minofu yabwinobwino. Kupeza kumeneku sikumangosintha malingaliro akuti "shuga onse amalimbikitsa khansa", komanso kumatsegula njira yatsopano yomenyera chithandizo cha metabolic.

?

1.2 Biological Traceability of Mannose

Monga isoma ya shuga, mannose imagawidwa mwaulere pa epidermis ya zipatso monga zipatso za citrus ndi maapulo m'chilengedwe, kapena imagwira nawo ntchito yomanga nembanemba zachilengedwe mu mawonekedwe a glycoproteins. M'thupi la munthu, mannose imakhala ndi phosphorylated kupanga mannose-6-phosphate (M6P), yomwe imakhala molekyu yofunikira pakusankha ma lysosomal enzyme. Maphunziro achipatala akale awonetsa njira yake yopewera matenda a mkodzo: pomanga mopikisana ndi ma adhesion receptors a mabakiteriya a pathogenic, amalepheretsa kukhazikika kwawo pa urothelium. Khalidweli lapangitsa kuti pakhale zakudya zosiyanasiyana zowonjezera zakudya zomwe zimayang'ana pa mannose, koma kupezeka kwa mphamvu zake zotsutsana ndi khansa kwachititsa kuti pakhale kuwonjezeka kwakukulu kwa ntchito yake.

?

Mutu Wachiwiri: Decoding Sayansi: Kukhumudwitsa Katatu kwa Mannose Against Cancer

2.1 Kubera kwa Metabolic: Kudula "chizolo?ezi cha shuga" chamagulu a khansa

Mphamvu ya Warburg ya maselo otupa (omwe amadalirabe glycolysis kuti apeze mphamvu ngakhale m'malo okhala ndi okosijeni) amathandizira kuti glucose awonjezeke kuchulukitsa kuwirikiza kakhumi kuposa ma cell abwinobwino. Gulu laku Britain lidazindikira kudzera muukadaulo wotsata isotopu kuti mannose ikalowa m'maselo a khansa, imapangidwa ndi hexokinase kuti ipange M6P ndikudziunjikira zambiri m'maselo. "pseudo-metabolite" iyi sikuti imangotenga mayendedwe a glucose transporter (GLUT), komanso amapikisana kuti alepheretse ntchito ya phosphoglucose isomerase, zomwe zimapangitsa kusowa kwapakati pa glycolysis ndi tricarboxylic acid cycle, potsirizira pake kumayambitsa vuto lamphamvu m'maselo a khansa (Chithunzi 1).

?

2.2 Epigenetics: Kukonzanso mawonekedwe a chotupa

Kafukufuku wofalitsidwa ndi Fudan University ku Cell Metabolism mu 2023 adawonetsanso kuti mannose imatha kusintha kusintha kwa epigenetic m'maselo a khansa powongolera kuchuluka kwa histone acetylation. Kuyesera kwawonetsa kuti m'maselo a khansa ya pancreatic omwe amathandizidwa ndi mannose, digiri ya acetylation ya gawo lolimbikitsa la oncogene MYC imachepetsedwa, ndipo ntchito yake yolembera imaletsedwa kwambiri. Izi epigenetic reprogramming zotsatira kufooketsa zowononga ndi youma makhalidwe a chotupa maselo, kupereka ongoyerekeza fulcrum kwa chitukuko ophatikizana epigenetic mankhwala.

?

2.3 Immune Synergy: Kuchotsa "Chovala Chosawoneka" cha PD-L1

Chosokoneza kwambiri ndi chakuti gulu lomwelo linapeza kuti mannose amatha kuthamangitsa chotupa choteteza chitetezo cha mthupi. Kupyolera mu kusanthula kwa misa spectrometry, ofufuza adatsimikizira kuti mannose imalepheretsa kupindika koyenera ndi nembanemba ya mapuloteni a PD-L1 posokoneza kusintha kwake kwa N-glycosylation. Puloteni ya PD-L1, yomwe imataya "ambulera yoteteza" ya shuga, imakhala yodziwika bwino komanso yowonongeka, motero imachotsa chizindikiro choletsa pa maselo a T. Muchitsanzo cha mbewa ya melanoma, kuphatikiza kwa mannose ndi anti-PD-1 antibody kunachulukitsa kuchuluka kwa chotupa mpaka 78%, kupitilira pamankhwala amodzi (Chithunzi 2).

?

Mutu Wachitatu: Kuchokera ku Laboratory kupita ku Zachipatala: Njira Yopambana ya Mankhwala Omasulira

3.1 Zofunikira pakufufuza koyambirira

Poyesa nyama zambiri, mannose yawonetsa kuthekera kothana ndi khansa. Gulu la Britain linalowererapo mbewa za khansa ya pancreatic ndi madzi akumwa a mannose 20% ndipo adapeza kuti kukula kwa chotupacho kudachedwa ndi 40%, ndipo kunalibe chiwopsezo chachikulu cha chiwindi kapena impso. Chochititsa chidwi kwambiri ndi chakuti, ikagwiritsidwa ntchito limodzi ndi gemcitabine, nthawi yopulumuka ya mbewa inatalikitsidwa ndi nthawi za 2.3, kusonyeza kufunika kwake kwa chemotherapy. Kuyesa kodziyimira pawokha ku MD Anderson Cancer Center ku United States kwawonetsa kuti mannose amagwiranso ntchito motsutsana ndi mitundu ya khansa ya refractory monga khansa ya m'mawere ya katatu ndi glioblastoma.

?

3.2 Kufufuza Mosamala kwa zoyeserera za anthu

Ngakhale pali zambiri zochititsa chidwi za preclinical, mayesero aumunthu amakumana ndi zovuta zapadera. Chiyeso chachipatala cha Phase I (NCT05220739) chomwe chinayambika mu 2022 chinali choyamba kuwunika chitetezo cha mano okamwa odwala omwe ali ndi zotupa zolimba kwambiri. Deta yoyambirira ikuwonetsa kuti odwala omwe ali mu gulu la 5g tsiku lililonse amalekerera bwino, ndipo milingo yozungulira ya DNA (ctDNA) nthawi zina yatsika kwambiri. Komabe, mlingo utakwera kufika pa 10g, pafupifupi 15% ya odwalawo adatsekula m'mimba pang'ono, zomwe zikutanthauza kuti pakufunika kukhathamiritsa kuchuluka kwa mankhwalawa.

?

3.3 Zolepheretsa zaukadaulo ku chitukuko cha mafakitale

Ngakhale mannose otengedwa mwachilengedwe ndi otetezeka, pamafunika mlingo wokwera kwambiri kuti mufike polimbana ndi khansa (yofanana ndi kudya ma kilogalamu 5 a cranberries tsiku lililonse), zomwe zayendetsa luso laukadaulo mu biology yopanga. Pakali pano, Escherichia coli yopangidwa ndi majini ingawonjezere kupanga mannose ka 20, pamene immobilized enzyme catalysis imachepetsa ndalama zopangira ndalama zosakwana $50 pa kilogalamu. Kuphatikiza apo, ukadaulo wa nano-liposome encapsulation ukhoza kukulitsa luso loperekera chotupa ku 80%, ndikutsegula njira yosinthira kuchipatala.

?

Mutu Wachinayi Kukangana ndi Kusinkhasinkha: Malingaliro Ozizira mu Carnival of Science

4.1 "Lupanga lakuthwa konsekonse" Zotsatira za kulowererapo kwa Metabolic

Ndikoyenera kudziwa kuti mannose si mankhwala. Maselo ena a khansa omwe amanyamula masinthidwe a mannose phosphate isomerase (PMI) amatha kusintha mannose-6-phosphate kukhala fructose-6-phosphate, yomwe m'malo mwake imapangitsa glycolytic flux. "Kuthawa kwa metabolic" kumeneku kudapezeka pafupifupi 7% ya zitsanzo za khansa yapakhungu, zomwe zikuwonetsa kufunikira kopanga zolembera payekhapayekha.

?

4.2 Zachilengedwe ≠ Zotetezedwa: Luso la Kuwongolera Mlingo

Ngakhale mannose yavomerezedwa kuti igwiritsidwe ntchito pazakudya monga chinthu cha GRAS (Yomwe Imadziwika Kuti Ndi Yotetezeka), kuopsa kwake kwanthawi yayitali pamankhwala odana ndi khansa kumafunikabe kuganiziridwa mozama. Zoyeserera zanyama zapeza kuti kumwa mopitirira muyeso kungayambitse matenda a m'mimba, ndi kuchuluka kwa mabakiteriya ena otengera mwayi (monga Klebsiella) akuchulukirachulukira kakhumi. Izi zimafuna kuti kafukufuku wamtsogolo akuyenera kulinganiza mphamvu zochiritsira komanso microecological homeostasis.

?

4.3 Masewera apakati pa Commercial Hype ndi Scientific Rationality

Ndi lingaliro la "shuga wotsutsa khansa" kukhala wotchuka, amalonda ena amakokomeza zotsatira zochiritsira za mankhwala a mannose. A FDA a ku United States apereka makalata ochenjeza kwa mabizinesi atatu chifukwa cha kukwezedwa kwawo kosaloledwa, akugogomezera kuti "zakudya zopatsa thanzi sizingalowe m'malo mwa chithandizo chamankhwala." Asayansi akufuna kuti pakhazikitsidwe gulu lovomerezeka lamakampani kuti liziwongolera kalembedwe ndi kutsatsa kwazinthu zomwe zili ndi mannose.

?

Kutsiliza: Chithunzi chamtsogolo cha kusintha kokoma

Ulendo wotsutsana ndi khansa ya mannose sikuti ndi kukumana koyenera kwa mphatso za chilengedwe ndi nzeru zaumunthu, komanso chitsanzo cha kusinthika kwamitundu yosiyanasiyana. Kuchokera pakukonzanso kagayidwe kachakudya mpaka kukonzanso kwa chitetezo chamthupi, kuchokera ku machubu oyesa ma labotale kupita ku mafakitale opanga mankhwala, "kusintha kokoma" uku ndikulembanso buku lachidziwitso cha chithandizo cha khansa. Ngakhale kuti padakali zovuta zambiri zomwe zikubwera kutsogoloku, zikhoza kuwonekeratu kuti mbadwo wotsatira wa mankhwala opangidwa ndi glyco opangidwa ndi mannose ukhoza kuyambitsa nthawi yatsopano yotsutsana ndi khansa. Monga momwe Nature anachitira ndemanga: "Pamene sayansi imavina ndi chilengedwe, belu la tsiku lachiwonongeko la khansa linalira kale."

?