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I-Cachexia yisifo se-systemic esibonakala ngokuncipha kwesisindo, i-muscle ne-adipose tissue atrophy, nokuvuvukala kwesistimu. I-Cachexia ingenye yezinkinga ezinkulu nezimbangela zokufa kweziguli ezinomdlavuza. Ngaphezu komdlavuza, i-cachexia ingabangelwa izifo ezihlukahlukene ezingalapheki, ezingenabungozi, ezihlanganisa ukuhluleka kwenhliziyo, ukwehluleka kwezinso, isifo se-chronic obstructive pulmonary disease, izifo zemizwa, ingculazi, nesifo samathambo. Kulinganiselwa ukuthi izehlakalo ze-cachexia ezigulini ezinomdlavuza zingafinyelela ku-25% kuya ku-70%, okuthinta kakhulu izinga lempilo yeziguli (QOL) futhi kubhebhethekise ubuthi obuhlobene nokwelashwa.

Ukungenelela okuphumelelayo kwe-cachexia kubaluleke kakhulu ekuthuthukiseni izinga lempilo kanye nokubikezelwa kweziguli ezinomdlavuza. Kodwa-ke, naphezu kwenqubekelaphambili ethile ocwaningweni lwezinqubo ze-pathophysiological of cachexia, izidakamizwa eziningi ezakhiwe ngokusekelwe ezindleleni ezingase zibe khona zisebenza kancane noma azisebenzi. Okwamanje akukho ukwelashwa okusebenzayo okugunyazwe i-US Food and Drug Administration (FDA).

Kunezizathu eziningi zokungaphumeleli kwezivivinyo zemitholampilo ku-cachexia, futhi isizathu esiyisisekelo singase silele ekuntulekeni kokuqonda kahle umshini kanye nenkambo yemvelo ye-cachexia. Muva nje, uSolwazi uXiao Ruiping kanye nomcwaningi u-Hu Xinli wase-College of Future Technology yase-Peking University bashicilele ngokuhlanganyela i-athikili ku-Nature Metabolism, eveza indima ebalulekile yendlela ye-lactic-GPR81 ekuveleni kwe-cachexia yomdlavuza, ehlinzeka ngombono omusha wokwelashwa kwe-cachexia. Sifingqa lokhu ngokuhlanganisa amaphepha avela ku-Nat Metab, Science, Nat Rev Clin Oncol namanye amajenali.

Ukuncipha kwesisindo kuvame ukubangelwa ukuncishiswa kokudla kanye/noma ukwanda kwezindleko zamandla. Ucwaningo lwangaphambilini luphakamise ukuthi lezi zinguquko zomzimba ku-cachexia ehambisana nesimila ziqhutshwa ama-cytokines athile akhiqizwe yi-tumor microenvironment. Isibonelo, izici ezifana nokuhlukanisa ukukhula kwe-factor 15 (GDF15), i-lipocalin-2 kanye ne-insulin-like protein 3 (INSL3) ingavimbela ukuthathwa kokudla ngokubophezela kumasayithi okulawula ukudla ohlelweni lwezinzwa olumaphakathi, okuholela ku-anorexia ezigulini. I-IL-6, i-PTHrP, i-activin A nezinye izici ziqhuba ukuncipha kwesisindo kanye ne-tissue atrophy ngokuvula indlela ye-catabolic nokwandisa izindleko zamandla. Njengamanje, ucwaningo ngendlela ye-cachexia lugxile kakhulu kulawa maprotheni afihliwe, futhi izifundo ezimbalwa eziye zahilela ukuhlangana phakathi kwama-tumor metabolites kanye ne-cachexia. USolwazi Xiao Ruiping kanye nomcwaningi u-Hu Xinli bathathe indlela entsha yokuveza indlela ebalulekile ye-cachexia ehlobene nesimila ngokombono we-tumor metabolites.

Okokuqala, ithimba likaProfesa Xiao Ruiping lihlole izinkulungwane zama-metabolite egazini lezilawuli ezinempilo kanye nemodeli yamagundane e-cachexia yomdlavuza wamaphaphu, futhi lathola ukuthi i-lactic acid yayiyi-metabolite ephakeme kakhulu kumagundane ane-cachexia. Izinga le-serum lactic acid lenyuka ngokukhula kwesimila, futhi labonisa ukuhlobana okuqinile nokushintsha kwesisindo samagundane aphethe isimila. Amasampula e-serum aqoqwe ezigulini ezinomdlavuza wamaphaphu aqinisekisa ukuthi i-lactic acid nayo idlala indima ebalulekile ekuqhubekeleni phambili kwe-cachexia yomdlavuza womuntu.

Ukuze kutholwe ukuthi ingabe amazinga aphezulu e-lactic acid abangela i-cachexia, ithimba locwaningo laletha i-lactic acid egazini lamagundane anempilo ngepompo ye-osmotic efakwe ngaphansi kwesikhumba, ikhuphula ngokuzenzela amazinga e-serum lactic acid ezingeni lamagundane ane-cachexia. Ngemva kwamaviki angu-2, amagundane aqala i-phenotype evamile ye-cachexia, njengokuncipha kwesisindo, amafutha kanye nezicubu zemisipha. Le miphumela iphakamisa ukuthi ukuguqulwa kwamafutha e-lactate kufana nalokho okubangelwa amangqamuzana omdlavuza. I-Lactate ayiyona nje i-metabolite yesici se-cachexia yomdlavuza, kodwa futhi ingumlamuleli oyinhloko we-hypercatabolic phenotype ebangelwa umdlavuza.

Okulandelayo, bathole ukuthi ukususwa kwe-lactate receptor GPR81 kwasebenza ngempumelelo ekwehliseni isimila kanye ne-serum lactate-induced cachexia ukubonakaliswa ngaphandle kokuthinta amazinga e-serum lactate. Ngenxa yokuthi i-GPR81 ivezwa kakhulu kusicubu se-adipose kanye nezinguquko kusicubu se-adipose ngaphambi kwesikhathi kunesiphazamiso sohlaka phakathi nokukhula kwe-cachexia, umphumela othize wokugoqa we-GPR81 kuzicubu ze-adipose yegundane ufana nowe-systemic knockout, ukuthuthukisa ukuncipha kwesisindo okubangelwa isimila kanye nokusetshenziswa kwamafutha kanye nemisipha yamathambo. Lokhu kuphakamisa ukuthi i-GPR81 kuzicubu ze-adipose iyadingeka ukuze kuthuthukiswe i-cachexia yomdlavuza eqhutshwa yi-lactic acid.

Ucwaningo olwengeziwe luqinisekisile ukuthi ngemva kokubophezela ku-GPR81, ama-molecule e-lactic acid aqhuba amafutha e-Browning, i-lipolysis kanye nokwanda kokukhiqizwa kokushisa kwesistimu ngokusebenzisa indlela yokusayina ye-Gβγ-RhoA/ROCK1-p38, kunendlela ye-PKA yakudala.

Naphezu kwemiphumela ethembisayo ku-pathogenesis ye-cachexia ehlobene nomdlavuza, lokhu okutholakele akukakahunyushwa ekwelapheni okuphumelelayo, ngakho-ke okwamanje azikho izindinganiso zokwelapha zalezi ziguli, kodwa eminye imiphakathi, njenge-ESMO kanye ne-European Society of Clinical Nutrition and Metabolism, iye yathuthukisa iziqondiso zomtholampilo. Njengamanje, imihlahlandlela yamazwe ngamazwe incoma kakhulu ukukhuthaza i-metabolism kanye nokunciphisa i-catabolism ngokusebenzisa izindlela ezifana nokudla, ukuvivinya umzimba kanye nemithi.