Nnyocha siri ike n'ime usoro senescence cell ebutela mmepe nke FOXO4-DRI., Ngwakọta senolytic nke a makwaara dị ka peptide IT-Inhibitor. Nke a peptide bioactive na-egosi ihe ndị na-egbochi ịka nká.
N'ime sel anụ ahụ, dị ka ọmụmaatụ, FOXO4 jikọtara ya p53, na-akpụ mgbagwoju anya dị ka FOXO4-p53 aggregates. Nke a mgbagwoju-eme ihe dị ka inhibitor nke apoptosis mmalite. N'ihi ya, mmekọrịta a na-agbatị ogologo ndụ nke cellular senescence ma na-eduga n'ịchịkọta ha ka oge na-aga.
Karịsịa, FOXO4-DRI anaghị elekwasị anya FOXO1 ozugbo, FOXO3, ma ọ bụ protein p53. Kama, ọ na-emekọrịta ihe kpọmkwem na saịtị njikọ FOXO4 n'ime mgbagwoju FOXO4-p53.. Mmekọrịta a na-akwalite mgbasa nke mgbagwoju anya, ewepụtara p53, ma si otú a na-emegharị apoptosis nke p53 kpatara, niile mgbe ị na-echekwa sel nkịtị site na mmetụta-akụkụ.
Ọtụtụ akụkọ na-egosi ịdị irè nke FOXO4-DRI n'ime nhọrọ igbu mkpụrụ ndụ sesescent.. Ọzọkwa, Ọmụmụ ihe na-egosi na FOXO4-DRI na-agbanwe ọdịda physiological metụtara afọ: ọ na-abawanye ntachi obi anụ ahụ na arụmọrụ moto, na-eweghachi ọrụ gbasara akụrụ na uto ntutu, ma si otú a na-ebelata ire anụ ahụ ndị metụtara afọ. Ọmụmaatụ, ụdị òké merela agadi na-egosi n'ụzọ doro anya uru ndị a. Na mgbakwunye, FOXO4-DRI na-ebelata mbufụt na-adịghị ala ala na mmebi anụ ahụ na microenvironment post-chemotherapy, si otú ahụ na-emeziwanye ndụ ndụ na ịkwalite ahụike ogologo oge na ndị ọrịa cancer.
Usoro
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
Nọmba CAS
2460055-10-9
Usoro ihe omimi
C228H388N86O64
Ibu molekụla
5358.05
Nyocha nke uru Foxo4-dri
1.Nhọrọ ntinye nke Senescent Cell Apoptosis
Usoro bụ isi nke FOXO4-DRI gụnyere mkpali kpọmkwem nke ọnwụ cell emebere n'ime sel sesescent.. Ebe a, p53 na-arụ ọrụ dị ka ihe na-eme mgbanwe maka mkpụrụ ndụ ihe nketa pro-apoptotic, na-akpata apoptosis. Agbanyeghị, n'okpuru ọnọdụ physiological nkịtị, mgbagwoju FOXO4-p53 na-emebi ọrụ apoptotic a.
Site n'ịsọ mpi maka njikọ p53, FOXO4-DRI na-akpaghasị mmekọrịta FOXO4-p53. Ọgba aghara a na-ebute ụzọ apoptosis dị n'ime kpọmkwem n'ime mkpụrụ ndụ senescent.
Na oke oke, ọgwụgwọ a na-eji FOXO4-DRI mee ka ntutu na-eto eto ka ọ dị ka ụmụ oke ndị agadi ma kwalite arụmọrụ moto nke ọma..
2.Ogo nke ndụ maka ndị ọrịa kansa
Ndị na-eme nchọpụta na-enyocha FOXO4-DRI dị ka ọgwụ nwere ike ime ka ndụ dịkwuo mma maka ndị ọrịa cancer mgbe e mesịrị. chemotherapy. Ebe ọtụtụ ọgwụ anticancer na-emetụta mkpụrụ ndụ tumo, ha na-ebutekwa mmerụ ahụ na-abụghị nke akọwapụtara na mkpụrụ ndụ nkịtị, na-abawanye ibu nke senescence nke ọgwụgwọ na-akpata(TIS).
Nnyocha dị ukwuu na-akwado na FOXO4-DRI nwere ike iwepụ ma mkpụrụ ndụ senescent nke na-ahụghị onwe ya na ọgwụgwọ., na-eme ka chemotherapy dị elu ọrịa adịghị ike. Dị ka ọmụmaatụ, Nnyocha e mere na Cell gosipụtara mgbake na nlanarị n'ime ụmụ oke ndị a na-agwọ chemotherapy. Nchọpụta ndị a gosipụtara ike ọgwụgwọ adjuvant siri ike nke FOXO4-DRI na oncology..
3.Ọrịa imeju na-emewanyewanye nke ọma
N'ime NASH(Steatohepatitis na-adịghị egbu egbu) ndị ọrịa, mkpụrụ ndụ senescent na-agbakọba na imeju ma na-ezobe pro-inflammatory na pro-fibrotic ụmụ irighiri ihe site na phenotype nzuzo nke senescence jikọtara ya (SASP), na-anya ọrịa ọganihu. Nnyocha na-eji ụdị NASH òké chọpụtara na FOXO4-DRI kpochapụrụ sel ndị a na-ahụ maka imeju, na-egbochi mmepụta SASP na isi mmalite ya.
4.Ọgwụgwọ ụmụ oke na Bleomycin kpatara Fibrosis nke akpa ume
FOXO4-DRI na-akpalite p53 nhọpụta nuklia na nkewa nke mgbagwoju FOXO4-p53. N'ụdị òké na-ebute bleomycin, ọgwụgwọ na FOXO4-DRI belatara ọkwa nke Collagen, ụdị I, alfa 1 (Kọl1a1) na α-SMA na anụ ahụ ngụgụ. Mbelata a na-egosi mbelata mmepụta nke matrix extracellular na mgbochi nke myofibroblast ịgbalite.
Ọ bụ ezie na ọmụmụ ihe ahụ akọwapụtaghị ụzọ ziri ezi nke mmekọrịta FOXO4-DRI na p53., ọ gosipụtara n'ụzọ doro anya mgbochi dị irè nke fibrosis, na-akọwapụta atụmatụ ọgwụgwọ nwere ike maka idiopathic pulmonary fibrosis (IPF).
5.Ihe metụtara afọ na-ebelata Hypogonadism (Enweghi ike nke testosterone)
hypogonadism mmalite mmalite nke nwoke bụ arụrụ ọrụ ịka nká na-emebi mkpụrụ ndụ Leydig merela agadi. Ikpochapụ sel ndị a na-ahụ anya nwere ike ime ka ọrụ anụ ahụ dịghachi ọhụrụ. Nnyocha na-egosi na FOXO4-DRI na-eme kpọmkwem na testicular mmadụ Mkpụrụ ndụ Leydig. Ịkwanye ya na ụmụ oke merela agadi mere ka microenvironment nke testicular dịkwuo mma, na-egbochi ụkọ testosterone metụtara afọ. A 2021 ọmụmụ gosiri mmụba dị ukwuu na ọkwa testosterone serum n'ime ụmụ oke ndị meworo agadi.
Usoro a na-atụ aro gụnyere mkpochapụ kpọmkwem nke p53 nuklia localization na dissociation nke FOXO4-p53 mgbagwoju., na-ebute apoptosis senescent-cell. Nsonaazụ ndị a na-atụ aro ụzọ ọgwụgwọ nwere ike isi gwọọ mbelata testosterone metụtara afọ.
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