Lipatlisiso tse kholo mabapi le mekhoa ea lisele tsa senescence li lebisitse ho nts'etsopele ea FOXO4-DRI., motsoako oa senolytic o tsejoang hape e le IT-Inhibitor peptide. Peptide ena ea bioactive e bonts'a thepa e ts'episang ea ho thibela botsofali.
Liseleng tsa senescent, mohlala, FOXO4 e tlama ho p53, ho theha motsoako o tsejoang ka hore ke FOXO4-p53 aggregates. E rarahaneng ena e sebetsa e le inhibitor ea apoptosis qalo. Ka lebaka leo, tšebelisano ena e lelefatsa bophelo ba bofokoli ba cellular mme e lebisa ho bokelleng ha tsona ka nako.
Ka ho khetheha, FOXO4-DRI ha e tobane le FOXO1 ka ho toba, FOXO3, kapa liprotheine tsa p53. Ho e-na le hoo, e sebetsana ka ho khetheha le sebaka sa FOXO4 se tlamang ka har'a FOXO4-p53 complex.. Tšebelisano ena e khothalletsa ho arohana ha motsoako, e lokolloa p53, mme ka hona e kenya tshebetsong p53-induced apoptosis hape, kaofela ha a ntse a qenehela lisele tse tloaelehileng ho tloha litla-morao.
Litlaleho tse 'maloa li bonts'a ts'ebetso e matla ea FOXO4-DRI ho bolaee lisele tse hlabollang.. Ho feta moo, Liphuputso li bontša hore FOXO4-DRI e khutlisa ho fokotseha ha 'mele ho amanang le lilemo: e eketsa mamello ea 'mele le ts'ebetso ea motlakase, e tsosolosa mosebetsi oa renal le ho hōla ha moriri, 'me kahoo e liehisa ho bola ha lisele tse amanang le botsofali. Ka mohlala, mehlala ea litoeba tsa khale e bontša ka ho hlaka melemo ena. Ho phaella moo, FOXO4-DRI e fokotsa ho ruruha ho sa foleng le tšenyo ea lisele tse ka morao ho chemotherapy microenvironment, kahoo ho ntlafatsa boleng ba bophelo le ho khothalletsa bophelo bo botle ba nako e telele ho bakuli ba kankere.
Tatelano
H-D-Leu-D-Thr-D-Leu-D-Arg-D-Lys-D-Glu-D-Pro-D-Ala-D-Ser-D-Glu-D-Ile-D- Ala-D-Gln-D-Ser-D-Ile-D-Leu-D-Glu-D-Ala-D-Tyr-D-Ser-D-Gln-D-Asn-D-Gly- D-Trp-D-Ala-D-Asn-D-Arg-D-Arg-D-Ser-D-Gly-D-Gly-D-Lys-D-Arg-D-Pro-D-Pr o-D-Pro-D-Arg-D-Arg-D-Arg-D-Gln-D-Arg-D-Arg-D-Lys-D-Lys-D-Arg-D-Gly-OH
Nomoro ea CAS
2460055-10-9
Foromo ea limolek'hule
C228H388N86O64
Boima ba Molek'hule
5358.05
Patlisiso ea Melemo ea Foxo4-dri
1.Kgetho e khethehileng ea Senescent Cell Apoptosis
Mochine o ka sehloohong oa FOXO4-DRI o kenyelletsa ts'usumetso e khethehileng ea lefu la lisele tse hlophisitsoeng liseleng tsa senescent.. Mona, p53 e sebetsa e le ntho e fetolang liphatsa tsa lefutso tsa pro-apoptotic, ho baka apoptosis. Leha ho le joalo, tlasa maemo a tlwaelehileng a fisioloji, FOXO4-p53 complex e hatella tšebetso ena ea apoptotic.
Ka ho qothisana lehlokoa le p53, FOXO4-DRI e senya tšebelisano ea FOXO4-p53. Tšitiso ena e qala tsela ea intrinsic apoptosis ka ho khetheha liseleng tsa senescent.
Ho litoeba tse tsofetseng, Kalafo ka FOXO4-DRI e lebisitse ho holeng ha moriri ho bapisoang le litoeba tsa lilemo tse mahareng le ts'ebetso e matla ea makoloi..
2.Boleng ba Bophelo ho Bakuli ba Kankere
Bafuputsi ba ntse ba hlahloba FOXO4-DRI e le sethethefatsi se ka thusang ho ntlafatsa bophelo ba bakuli ba mofetše ka mor'a phekolo ea lik'hemik'hale. Le ha li-anticancer tse ngata li ama lisele tsa hlahala, li boetse li baka kotsi e sa tloaelehang liseleng tse tloaelehileng, ho eketsa moroalo oa ho hlaphoheloa ho bakoang ke phekolo(TIS).
Liphuputso tse pharaletseng li tiisa hore FOXO4-DRI e khona ho felisa lisele tsa senescent tse bakoang ke phekolo., chemotherapy e ntlafatsang bophelo bo botle frailty syndrome. Mohlala, boithuto ho Cell bo bonts'itse ho fola ho ntlafetseng le ho phela litoeba tse phekoloang ka chemotherapy. Liphuputso tsena li totobatsa bokhoni bo matla ba phekolo ea adjuvant ea FOXO4-DRI ho oncology..
3.Ho matlafatsa Pathology ea Mafu a Sebete
Ho NASH(Steatohepatitis e seng joala) bakuli, lisele tsa senescent e bokellana ka har'a sebete ebe e ntša limolek'hule tsa pro-inflammatory le pro-fibrotic ka phenotype ea sephiri e amanang le senescence (SASP), ho khanna tsoelo-pele ea mafu. Lithuto tse sebelisang panya ea NASH mohlala li fumane hore FOXO4-DRI e felisitse lisele tsena tsa hepatic senescent, ho hatella tlhahiso ea SASP mohloling oa eona.
4.Kalafo ea Litoeba ka Bleomycin-Induced Pulmonary Fibrosis
FOXO4-DRI e etsa hore ho khethoe hore ho be le khetho ea nyutlelie ea p53 le ho arohana ha FOXO4-p53 complex.. Mehlala ea litoeba tse hlahisoang ke bleomycin, kalafo ka FOXO4-DRI e fokotsehile maemo a Collagen, mofuta oa I, alpha 1 (Col1a1) le α-SMA liseleng tsa matšoafo. Phokotso ena e fana ka maikutlo a ho fokotseha ha tlhahiso ea matrix a extracellular le thibelo ea myofibroblast kenya tshebetsong.
Leha thuto e sa ka ea hlakisa ka botlalo tsela e nepahetseng ea tšebelisano ea FOXO4-DRI le p53., e ile ea bontša ka ho hlaka thibelo e sebetsang ea fibrosis, ho totobatsa leano le ka 'nang la phekoloa bakeng sa idiopathic pulmonary fibrosis (IPF).
5.Ho Fokotsa Lilemo Tse Amanang Hypogonadism (Khaello ea Testosterone)
Hypogonadism ea banna ba morao-rao ke ho se sebetse ho amanang le botsofali ho holofatsang lisele tsa Leydig tse tsofetseng.. Ho hleka lisele tsena tsa senescent ho ka tsosolosa tšebetso ea lisele. Liphuputso li bontša hore FOXO4-DRI e sebetsa ka ho khetheha ho testicular ea motho Lisele tsa Leydig. Ho e fana ka litoeba tse tsofetseng ho ntlafalitse tikoloho ea testicular, ho thibela khaello ea testosterone e amanang le lilemo. A 2021 boithuto bo tlalehile keketseho e kholo ea maemo a serum testosterone ho litoeba tse tsofetseng tse tšoaroang.
Mochine o reriloeng o kenyelletsa khatello e khethehileng ea sebaka sa nyutlelie sa p53 le ho arohana ha FOXO4-p53 complex., ho fella ka senescent-cell apoptosis. Liphetho tsena li fana ka maikutlo a mokhoa oa kalafo o ka bang teng oa ho phekola phokotso ea testosterone e amanang le lilemo.
COA
HPLC
MOF
