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Cachexia chirwere chesystemic chinoratidzwa nekuderera kwehuremu, tsandanyama uye adipose tishu atrophy, uye systemic kuzvimba. Cachexia ndeimwe yematambudziko makuru uye zvikonzero zvekufa kwevarwere vegomarara. Pamusoro pegomarara, cachexia inogona kukonzerwa nezvirwere zvakasiyana-siyana zvisingaperi, zvisingaperi, zvinosanganisira kutadza kushanda kwemoyo, kusashanda zvakanaka kwetsvo, chirwere chisingaperi chemapapu, chirwere chetsinga, AIDS, uye rheumatoid arthritis. Zvinofungidzirwa kuti chiitiko checachexia muvarwere vegomarara chinogona kusvika 25% kusvika 70%, izvo zvinokanganisa zvakanyanya hupenyu hwevarwere (QOL) uye zvinowedzera huturu hune chekuita nekurapa.

Kupindira kunobudirira kwecachexia kwakakosha zvikuru pakuvandudza hupenyu uye kufungidzira kwevarwere vegomarara. Zvisinei, pasinei nekufambira mberi mukudzidza kwepathophysiological mechanisms ye cachexia, mishonga yakawanda yakagadzirwa zvichienderana nemaitiro anogoneka inongoshanda zvishoma kana kuti isingabatsiri. Parizvino hapana kurapwa kunoshanda kwakabvumidzwa neUS Food and Drug Administration (FDA).

Pane zvikonzero zvakawanda zvekukundikana kwemakiriniki ekuedzwa pa cachexia, uye chikonzero chikuru chinogona kunge chiri mukushayikwa kwekunyatsonzwisisa kwemaitiro uye maitiro echisikigo e cachexia. Munguva pfupi yapfuura, Muzvinafundo Xiao Ruiping uye muongorori Hu Xinli kubva kuCollege of Future Technology yePeking University vakabatana vakaburitsa chinyorwa mukati Nature Metabolism, ichiburitsa basa rakakosha reiyo lactic-GPR81 nzira mukuitika kwekenza cachexia, ichipa pfungwa nyowani yekurapa cachexia. Isu tinopfupikisa izvi nekugadzira mapepa kubva kuNat Metab, Sainzi, Nat Rev Clin Oncol nemamwe mapepanhau.

Kurasikirwa kwehuremu kunowanzokonzerwa nekuderedza kudya kwekudya uye / kana kuwedzera kushandiswa kwesimba. Zvidzidzo zvakapfuura zvakaratidza kuti shanduko idzi dzemuviri mune bundu-inosanganisirwa cachexia inofambiswa nemamwe ma cytokines akavanzika ne tumor microenvironment. Semuenzaniso, zvinhu zvakadai sekukura kwekusiyanisa chinhu 15 (GDF15), lipocalin-2 uye insulini-yakafanana neprotein 3 (INSL3) inogona kudzivisa kudya kwekudya nekusunga kune nzvimbo dzekutonga kwechido mukati mehutano hwehutano, zvichiita kuti anorexia kune varwere. IL-6, PTHrP, activin A uye zvimwe zvinhu zvinotyaira uremu uye atrophy yetishu nekuita iyo catabolic nzira uye kuwedzera simba rekushandisa. Parizvino, tsvakiridzo pamusoro pemagadzirirwo ecachexia yakanyanya kutarisisa kune aya akavanzwa mapuroteni, uye zvishoma zvidzidzo zvakabatanidza kusangana pakati pebundu metabolites uye cachexia. Muzvinafundo Xiao Ruiping uye muongorori Hu Xinli vatora nzira nyowani yekuburitsa nzira yakakosha yebundu-inoenderana cachexia kubva pakuona kwebundu metabolites.

Chekutanga, timu yaProfessor Xiao Ruiping yakaongorora zviuru zvemetabolites muropa rezvinodzora zvine hutano uye mhando yemakonzo ekenza yemapapu cachexia, uye yakawana kuti lactic acid ndiyo yaive yakanyanya kukwidziridzwa metabolite mumakonzo ane cachexia. Serum lactic acid level yakawedzera nekukura kwebundu, uye yakaratidza kuwirirana kwakasimba nekushanduka kwehuremu hwemakonzo anotakura bundu. Serum samples inounganidzwa kubva kuvarwere vekenza yemapapu inosimbisa kuti lactic acid inoitawo basa rakakosha mukufambira mberi kwekenza yemunhu cachexia.

Kuti uone kana yakakwira lactic acid inokonzeresa cachexia, timu yekutsvagisa yakaendesa lactic acid kuropa remakonzo ane hutano kuburikidza nepombi yeosmotic yakasimwa pasi peganda, ichisimudza serum lactic acid mazinga kusvika pamwero wemakonzo ane cachexia. Mushure memavhiki maviri, mbeva dzakagadzira yakajairika phenotype ye cachexia, senge kuonda, mafuta uye tsandanyama atrophy. Mhedzisiro iyi inoratidza kuti lactate-induced mafuta remodeling yakafanana neiyo inokonzerwa nekenza maseru. Lactate haingori hunhu hwemetabolite yekenza cachexia, asiwo murevereri akakosha wekenza-induced hypercatabolic phenotype.

Tevere, vakaona kuti kudzima kwelactate receptor GPR81 kwaibatsira mukuderedza bundu uye serum lactate-induced cachexia kuratidzwa pasina kukanganisa serum lactate mazinga. Nekuti GPR81 inoratidzirwa zvakanyanya muadipose tissue uye shanduko muadipose tissue pamberi peskeletal muscle panguva yekugadzirwa kwecachexia, iyo chaiyo knockout mhedzisiro yeGPR81 mumbeva adipose tishu yakafanana neye systemic knockout, kunatsiridza bundu-induced uremu uye mafuta uye skeletal tsandanyama kushandiswa. Izvi zvinoratidza kuti GPR81 mune adipose tishu inodiwa pakuvandudza kenza cachexia inotungamirwa nelactic acid.

Zvimwe zvidzidzo zvakasimbisa kuti mushure mekusunga kuGPR81, lactic acid molecules inotyaira mafuta Browning, lipolysis uye yakawedzera systemic kupisa kugadzirwa kuburikidza neGβγ-RhoA/ROCK1-p38 nzira yekuratidzira, pane yekirasi PKA nzira.

Pasinei nemigumisiro inovimbisa mupathogenesis yekenza-yakabatana cachexia, izvi zvakawanikwa hazvisati zvashandurwa kuva kurapa kunobudirira, saka parizvino hapana mitemo yekurapa yevarwere ava, asi dzimwe nzanga, dzakadai seESMO neEuropean Society of Clinical Nutrition uye Metabolism, dzakagadzira mazano ekliniki. Parizvino, nhungamiro dzepasirese dzinokurudzira zvakasimba kusimudzira metabolism uye kuderedza catabolism kuburikidza nenzira dzakadai sekudya, kurovedza muviri uye mishonga.