Cilmi-baaristii ugu dambeysay ee Sayniska: Kaabista shahwada waxay kor u qaadi kartaa habka difaaca jirka ee ka hortagga burooyinka
Nidaamka difaaca jirku hoos buu u dhacaa da'da, dadka da'da ah ayaa aad ugu nugul infekshannada iyo kansarka, iyo PD-1 ka hortagga, daaweynta caadiga ah, ayaa inta badan waxtar u leh dadka da'da ah marka loo eego dadka da'da yar. Daraasaduhu waxay muujiyeen in ay jiraan spermidine bayooloji ah oo ku jira jidhka bini'aadamka kaas oo yaraada da'da, iyo kabidda shahwada waxay wanaajin kartaa ama dib u dhigi kartaa qaar ka mid ah cudurrada da'da la xiriira, oo ay ku jiraan cudurrada nidaamka difaaca. Si kastaba ha ahaatee, xidhiidhka ka dhexeeya yaraanta shahwada ee la socota gabowga iyo ka-hortagga ka-hortagga unugga T-ga ma cadda.
Dhawaan, cilmi-baarayaal ka socda Jaamacadda Kyoto ee Japan ayaa daabacay warqad cilmi-baaris ah oo cinwaankeedu yahay "Spermidine waxay kicisaa borotiinka trifunctional mitochondrial waxayna wanaajisaa difaaca antitumor ee jiirarka" ee Sayniska. Daraasadani waxay daaha ka qaadaysaa in spermidine ay si toos ah u xidho oo ay u kiciso borotiinka trifunctional mitochondrial MTP, waxay kicisaa oksaydhka aashitada dufanka leh, ugu dambeyntiina waxay keentaa kor u qaadista dheef-shiid kiimikaadka mitochondrial ee unugyada CD8+ T waxayna kor u qaadaysaa difaaca ka hortagga burooyinka. Natiijooyinku waxay muujiyeen in daawaynta la isku daray ee shahwada iyo anti-PD-1 antibody ay kor u qaaday kororka, wax soo saarka cytokine iyo soosaarka mitochondrial ATP ee unugyada CD8+ T, iyo shahwada spermidine waxay si wax ku ool ah u wanaajisay shaqada mitochondrial waxayna si weyn u kordhisay dheef-shiid kiimikaadka dufanka dufanka leh ee mitochondrial 1 saac gudahood.
Si loo sahamiyo in shahwadu ay si toos ah u hawlgeliso oxidase dufanka leh (FAO) ee mitochondria, kooxda cilmi-baadhista ayaa lagu go'aamiyay falanqaynta biochemical ee in shahwadadu ay ku xidho borotiinka trifunctional mitochondrial (MTP), enzyme dhexe ee fatty acid β-oxidation. MTP waxay ka kooban tahay α iyo β subunits, labaduba waxay xidhaan shahwada. Tijaabooyinka la isticmaalayo MTP-yada la farsameeyey oo laga nadiifiyey E. coli waxay muujiyeen in shahwadu ay ku xidho MTP-yada xidhiidh adag [isku xidhidhaanshaha joogtada ah, Kd) = 0.1 μM] waxayna kor u qaadaysaa dhaqdhaqaaqooda oksaydhka dufanka enzymatic. Hoosudhaca gaarka ah ee qaybta MTPα ee unugyada T waxay tirtirtay saamaynta awoodda spermidine ee PD-1-suppressive immunotherapy, taasoo soo jeedinaysa in MTP looga baahan yahay firfircoonida unugyada shahwada-ku-tiirsan.
Gebogebadii, spermidine waxay kor u qaadaysaa oksaydhka aashitada dufanka leh iyadoo si toos ah u xidhaysa oo u hawlgelinaysa MTP. Kaabista spermidine waxay kor u qaadi kartaa dhaqdhaqaaqa oksaydhka dufanka leh, hagaajinta dhaqdhaqaaqa mitochondrial iyo shaqada cytotoxic ee unugyada CD8+ T. Kooxda cilmi-baaristu waxay leeyihiin faham cusub oo ku saabsan sifooyinka spermidine, taas oo laga yaabo inay gacan ka geysato horumarinta xeeladaha looga hortagayo oo loo wanaajiyo natiijada cudurrada difaaca ee da'da iyo la dagaallanka jawaab-celin la'aanta daaweynta PD-1 ee ka hortagga kansarka, iyada oo aan loo eegin xajmiga da'da.
Waqtiga boostada: Febraayo-27-2023
