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I-Cachexia sisifo se-systemic esibonakaliswa ukunciphisa umzimba, i-muscle kunye ne-adipose tissue atrophy, kunye nokuvuvukala kwenkqubo. I-Cachexia yenye yeengxaki eziphambili kunye nezizathu zokufa kwizigulane ezinomhlaza. Ukongeza kumhlaza, i-cachexia inokubangelwa zizifo ezininzi ezingapheliyo, ezingezizo ezinobungozi, ezibandakanya ukungaphumeleli kwentliziyo, ukungaphumeleli kwezintso, isifo semiphunga esingapheliyo, izifo zemithambo-luvo, uGawulayo kunye nesifo samathambo. Kuqikelelwa ukuba iziganeko ze-cachexia kwizigulane ezinomhlaza zingafikelela kwi-25% ukuya kwi-70%, echaphazela kakhulu umgangatho wobomi bezigulane (QOL) kwaye ikhulise ubutyhefu obunxulumene nonyango.

Ungenelelo olusebenzayo lwe-cachexia lubaluleke kakhulu ekuphuculeni umgangatho wobomi kunye ne-prognosis yabaguli abanomhlaza. Nangona kunjalo, ngaphandle kwenkqubela phambili kuphononongo lweendlela ze-pathophysiological ye-cachexia, uninzi lwamachiza aphuhlisiwe ngokusekelwe kwiindlela ezinokwenzeka zisebenza ngokuyinxenye okanye zingasebenzi. Okwangoku alukho unyango olusebenzayo oluvunywe yi-US Food and Drug Administration (FDA).

Kukho izizathu ezininzi zokungaphumeleli kwezilingo zeklinikhi kwi-cachexia, kwaye isizathu esisisiseko sinokulala ekunqongophelweni kokuqonda kakuhle indlela kunye nekhosi yendalo ye-cachexia. Kutshanje, uNjingalwazi uXiao Ruiping kunye nomphandi u-Hu Xinli ovela kwiKholeji yeTekhnoloji yeFuture yeYunivesithi yasePeking ngokudibeneyo bapapashe inqaku kwiNature Metabolism, ebonisa indima ebalulekileyo yendlela ye-lactic-GPR81 ekuveleni kwe-cachexia yomhlaza, enika ingcamango entsha yonyango lwe-cachexia. Sishwankathela oku ngokwenza amaphepha avela kwi-Nat Metab, iSayensi, i-Nat Rev Clin Oncol kunye nezinye iijenali.

Ukwehla kobunzima kudla ngokubangelwa kukuncitshiswa kokutya kunye/okanye ukunyuka kwenkcitho yamandla. Uphononongo lwangaphambili lucebise ukuba olu tshintsho lwe-physiological kwi-cachexia ehambelana ne-tumor iqhutywa ziicytokines ezithile ezikhutshelwe yi-tumor microenvironment. Ngokomzekelo, izinto ezifana nokuhlukana kokukhula kwe-15 (GDF15), i-lipocalin-2 kunye ne-insulin-efana neprotheyini ye-3 (INSL3) inokuthintela ukutya ngokuzibophelela kwiindawo zokulawula ukutya kwi-system ye-nervous central, ekhokelela kwi-anorexia kwizigulane. I-IL-6, i-PTHrP, i-activ A kunye nezinye izinto ziqhuba ukulahleka kwesisindo kunye ne-tissue atrophy ngokuvula indlela ye-catabolic kunye nokwandisa inkcitho yamandla. Okwangoku, uphando malunga nendlela ye-cachexia igxile kakhulu kwezi proteni zifihliweyo, kwaye izifundo ezimbalwa zibandakanya ubudlelwane phakathi kwe-tumor metabolites kunye ne-cachexia. Unjingalwazi uXiao Ruiping kunye nomphandi u-Hu Xinli bathathe indlela entsha yokubonisa indlela ebalulekileyo ye-cachexia enxulumene ne-tumor ngokwembono ye-tumor metabolites.

Okokuqala, iqela likaNjingalwazi uXiao Ruiping livavanye amawaka eemetabolites egazini lolawulo olusempilweni kunye nemodeli yeempuku zecachexia yomhlaza wemiphunga, kwaye yafumanisa ukuba i-lactic acid yayiyeyona metabolite iphakame kakhulu kwiimpuku ezinecachexia. Inqanaba le-serum lactic acid liye landa ngokukhula kwethumba, kwaye libonise ulungelelwaniso oluqinileyo kunye nokutshintsha kobunzima beempuku ezithwele ithumba. Iisampulu zeSerum eziqokelelwe kwizigulana ezinomhlaza wemiphunga ziqinisekisa ukuba iasidi ye-lactic ikwadlala indima ephambili ekuqhubeleni phambili kwe-cachexia yomhlaza womntu.

Ukufumanisa ukuba amanqanaba aphezulu e-lactic acid abangela i-cachexia, iqela lophando lihambisa i-lactic acid egazini leempuku ezinempilo ngokusebenzisa ipompo ye-osmotic efakwe phantsi kwesikhumba, iphakamisa ngokufanelekileyo amanqanaba e-serum lactic acid kwinqanaba leegundane ezine-cachexia. Emva kweeveki ezi-2, iigundane zavelisa i-phenotype ye-cachexia eqhelekileyo, njengokunciphisa umzimba, i-fat and muscle tissue atrophy. Ezi ziphumo zibonisa ukuba ukulungiswa kwe-lactate-induced fat remodeling kuyafana noko kubangelwa ngamaseli omhlaza. I-Lactate ayilona nje uphawu lwe-metabolite ye-cachexia yomhlaza, kodwa kunye nomlamli ophambili we-hypercatabolic phenotype ebangelwa ngumhlaza.

Emva koko, bafumanisa ukuba ukucinywa kwe-lactate receptor GPR81 kwakusebenzayo ekunciphiseni ithumba kunye neserum lactate-induced cachexia manifestations ngaphandle kokuchaphazela amanqanaba e-serum lactate. Ngenxa yokuba i-GPR81 ibonakaliswe kakhulu kwizicubu ze-adipose kunye notshintsho kwizicubu ze-adipose ngaphambili kunesihlunu samathambo ngexesha lophuhliso lwe-cachexia, isiphumo sokunkqonkqoza se-GPR81 kwithishu ye-adipose yegundwane iyafana naleyo ye-systemic knockout, ukuphucula ukwehla kobunzima obubangelwa lithumba kunye namafutha kunye nokusetyenziswa kwemisipha. Oku kuphakamisa ukuba i-GPR81 kwi-adipose tissue iyafuneka kuphuhliso lwe-cachexia yomhlaza eqhutywa yi-lactic acid.

Uphando olongezelelweyo luqinisekisile ukuba emva kokubophezela kwi-GPR81, i-molecule ye-lactic acid iqhuba i-Browning enamafutha, i-lipolysis kunye nokwandisa ukuveliswa kobushushu benkqubo ngokusebenzisa i-Gβγ-RhoA/ROCK1-p38 indlela yokubonisa, kunokuba i-classical PKA indlela.

Nangona iziphumo ezithembisayo kwi-pathogenesis ye-cachexia enxulumene nomhlaza, ezi ziphumo azikaguqulelwa kunyango olusebenzayo, ngoko ke akukho migangatho yonyango yezi zigulana, kodwa ezinye iintlanga, ezifana ne-ESMO kunye ne-European Society of Clinical Nutrition and Metabolism, ziye zaphuhlisa izikhokelo zeklinikhi. Okwangoku, izikhokelo zamazwe ngamazwe zincoma ngamandla ukukhuthaza imetabolism kunye nokunciphisa i-catabolism ngeendlela ezifana nesondlo, umthambo kunye namayeza.