Cocer Peptides ye 
ŋlɔe ɣleti 1 enye sia
NYATAKAKAWO KPLE NUSIWO WOTSƆ ƑE NYATAKAKA SIWO KAtã WOÐO LE NYATAKAKADZRAÐOƑE SIA ME LA KPLE NYATAKAKAWO kaka KPLEE NUFIAFIA ƑE TAÐOÐOWO KO.
Wotrɔ asi le atike siwo wona le nyatakakadzraɖoƒe sia ŋu na numekuku le vitro ɖeɖeko. Wowɔa numekuku le vitro (Latingbe me: *le ahuhɔ̃e me*, si gɔmee nye le ahuhɔ̃e me) le amegbetɔ ƒe ŋutilã godo. Atike siawo menye atikewo o, United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda asi ɖe wo dzi o, eye mele be woazã wo atsɔ axe mɔ ɖe atikewɔwɔ, dɔléle, alo dɔléle aɖeke nu, adae, alo adae o. Se de se vevie be woatsɔ atike siawo ade amegbetɔ alo lãwo ƒe ŋutilã me le mɔ ɖesiaɖe nu.
Tsitsi, abe dzɔdzɔmenu si womate ŋu aƒo asa na le nu gbagbewo me ene, nye nusi ŋu dzɔdzɔmeŋutinunya me numekukuwo ku ɖo vevie tso gbaɖegbe ke. Ne nugbagbewo le tsitsim la, lãmenugbagbeviwo gena ɖe tsitsi ƒe nɔnɔme me vivivi, eye lãmenugbagbevi siawo siwo le tsitsim ƒe ƒuƒoƒo ate ŋu akpɔ ŋusẽ gbegblẽ ɖe lãmekawo kple ŋutinuwo ƒe dɔwɔwɔ nyuie dzi, si ahe dɔléle vovovo siwo do ƒome kple tsitsi vɛ. FOX04 – DRI ɖea vi na lãmenugbagbevi siwo le tsitsim la ɖeɖeɖa.
FOX04 ƒe wɔwɔfia - DRI
FOX04 - DRI nye peptide si wowɔ, si ƒe ŋkɔ bliboa nye fork head box O transcription factor 4 - D - Retro - Inverso. Nusi ŋu woke ɖo la tso numekuku deto siwo wowɔ le lãmenugbagbevi siwo tsina ƒe ɖoɖowɔwɔ ƒe mɔnuwo ŋu me. Le lãmenugbagbeviwo ƒe tsitsi me la, molecule ƒe mɔnu vovovowo kpɔa gome le eme, eye FOX04 ƒe nuŋɔŋlɔ ƒe akpa wɔa akpa vevi aɖe le ɖoɖo sia me. FOX04 ɖea eɖeɖefia ƒe ɖoɖo tɔxɛwo kple dɔwɔwɔ ƒe tɔtrɔwo fiana le lãmenugbagbevi siwo le tsitsim me. Dzɔdzɔmeŋutinunyalawo to alesi wòwɔa dɔe me kɔ nyuie me la, wowɔ FOX04-DRI hewɔe be wòaɖo taɖodzinu na lãmenugbagbevi siwo le tsitsim koŋ, eye woƒe taɖodzinue nye be yewoakpɔ nya siwo ku ɖe tsitsi ŋu gbɔ.
Nɔnɔmetata 1 Sigaret ƒe dzudzɔ hena tsitsi ƒe lãkusi ƒe fibroblasts ɖeɖeɖa ƒe nɔnɔmetata si wowɔ ɖe ɖoɖo nu to FOXO4 siRNA-loaded DNA nanoparticles zazã me.
FOX04-DRI ƒe mɔnu le lãmenugbagbevi siwo le tsitsim la ɖeɖeɖa me
Nusiwo doa kplamatse FOX04-p53 ƒe kadodo: Le lãmenugbagbevi siwo tsi me la, FOX04 wɔa dɔ kple p53 protein. P53 protein wɔa akpa vevi aɖe le lãmenugbagbeviwo ƒe nuteɖeamedzi ƒe ŋuɖoɖo, lãmenugbagbeviwo ƒe tsatsam ƒe ɖoɖowɔwɔ, kple apoptosis me. Le nɔnɔme siwo sɔ me la, p53 doa apoptosis ɖe ŋgɔ le lãmenugbagbevi siwo gblẽ alo tsitsi me to domenyiŋusẽfianu siwo do ƒome kple apoptosis ƒe ɖeɖefia ɖe wo nɔewo yome ƒe dɔwɔwɔ me, si wɔnɛ be lãmenugbagbeviawo ƒe lãmesẽ nɔa anyi. Le lãmenugbagbevi siwo tsi me la, FOX04 blana ɖe p53 ŋu, si xea mɔ na eƒe tsɔtsɔ yi lãmenugbagbeviwo ƒe nucleus me, si xea mɔ na p53 be megawɔa eƒe pro-apoptotic dɔwɔwɔ o, si wɔnɛ be lãmenugbagbevi siwo tsi agbe eye woƒoa ƒu. FOX04-DRI ate ŋu ado kplamatse kadodo sia si le FOX04 kple p53 dome koŋ, axe mɔ na woƒe kadodo, si ana p53 nagage ɖe lãmenugbagbeviwo ƒe nucleus me, awɔ apoptosis ƒe dzesimɔa ŋudɔ, eye wòana apoptosis le lãmenugbagbevi siwo le tsitsim me, si ana woaɖe lãmenugbagbevi siwo le tsitsim la ɖa.
Lãmenugbagbeviwo me dzesimɔwo dzi kpɔkpɔ: Tsɔ kpe ɖe FOX04-p53 ƒe kadodo si doa kplamatse wo ŋu la, FOX04-DRI ate ŋu akpɔ ŋusẽ ɖe lãmenugbagbevi siwo tsi ƒe dzɔgbese hã dzi to lãmenugbagbeviwo me dzesimɔ bubuwo dzi kpɔkpɔ me. PI3K/AKT ƒe dzesimɔa wɔa akpa vevi aɖe le ɖoɖowɔwɔ me le lãmenugbagbeviwo ƒe tsitsi, woƒe dzidziɖedzi, agbetsitsi, kple woƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe akpa vovovowo me. Numekukuwo ɖee fia be zi geɖe la, PI3K/AKT ƒe dzesimɔ ƒe dɔwɔwɔ trɔna le lãmenugbagbevi siwo tsi me, si kpɔa ŋusẽ ɖe woƒe dɔwɔwɔ nyuie dzi. FOX04-DRI ate ŋu aɖɔ PI3K/AKT dzesimɔ ƒe dɔwɔwɔ ɖo, atrɔ dzesiwo ƒe tɔtrɔ ƒe dadasɔ le lãmenugbagbevi siwo le tsitsim me, si ana lãmenugbagbeviwo me nɔnɔme si menyo o nanɔ anyi na woƒe agbetsitsi eye wòahe apoptosis vɛ. Dzesimɔ sia dzi kpɔkpɔ ate ŋu akpɔ ŋusẽ ɖe lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe nɔnɔmewo hã dzi, si ana lãmenugbagbevi siwo le tsitsim la nagakplɔ wo ayi apoptosis gbɔ.
Ŋusẽkpɔɖeamedzi ɖe Senescence-Associated Secretory Phenotype (SASP) dzi: Lãmenugbagbevi siwo le tsitsim la ɖea cytokines, chemokines, kple proteases ɖe wo nɔewo yome, eye wowɔa senescence-associated secretory phenotype (SASP). Menye ɖeko SASP kpɔa ŋusẽ gbegblẽ ɖe lãmenugbagbevi siwo ƒo xlãe siwo sɔ dzi, si gblẽa nu le woƒe dɔwɔwɔ nyuie ŋu ko o, ke ehea dɔdzẽ ƒe ŋuɖoɖo siwo nɔa anyi didi hã vɛ, si wɔnɛ be lãmekawo kple ŋutinuwo ƒe tsitsi kabakaba ɖe edzi. FOX04-DRI ate ŋu aɖe lãmenugbagbevi siwo tsi tsitsi ƒe ŋusẽkpɔɖeamedzi gbegblẽ ɖe nuto sue siwo ƒo xlãe dzi akpɔtɔ to mɔxexe ɖe nusiwo do ƒome kple SASP ƒe ɖeɖefia kple wo ɖeɖe ɖe go le lãmenugbagbevi siwo tsi me. Le numekukua me la, wokpɔe be esi wotsɔ FOX04-DRI da dɔ na lãmenugbagbevi siwo tsi vɔ la, nusiwo do ƒome kple SASP abe IL-1α, IL-1β, tumor necrosis factor α (TNFα), kple MMP2 ƒe ɖeɖefia ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ ŋutɔ le lãmenugbagbevi siwo tsi me. Esia ɖee fia be FOX04-DRI ate ŋu aɖɔ lãmenugbagbevi siwo tsi ƒe SASP ɖo nyuie, ana lãmenugbagbeviwo ƒe nuto suewo nanyo ɖe edzi, eye wòado lãmenugbagbevi siwo tsi ƒe ɖeɖeɖa kple lãmenugbagbeviwo ƒe nuto suea ƒe hayahaya ɖe ŋgɔ le mɔ si mele tẽ o nu.
Akpa Si FOX04-DRI Wɔna Le Lãmetsi Vovovowo Kple Dɔlélewo Me
Akpa si Wòwɔna le Vidzidzi ƒe Dɔwɔɖoɖo Me: Ŋutsuwo ƒe ʋumenugbagbeviɣidɔ si dzea egɔme megbe nye dɔléle si do ƒome kple tsitsi si ƒe dɔwɔwɔ vevitɔe nye vidzidɔ dome lãmenugbagbevi tsitsiwo ƒe dɔmawɔmawɔ nyuie. FOX04 dzena le amegbetɔ ƒe vidzidɔ dome lãmenugbagbeviwo me koŋ, eye le ame tsitsiwo gome la, FOX04 ƒe nuklia ƒe ʋuʋu do ƒome kple testosterone ƒe wɔwɔme dzi ɖeɖe kpɔtɔ. Esi wozã TM3 vidzidɔ dome lãmenugbagbevi tsitsi siwo hydrogen peroxide hena vɛ abe kpɔɖeŋu le vitro ene la, wode dzesii be FOX04 ate ŋu alé vidzidɔ dome lãmenugbagbevi tsitsiwo ƒe agbenɔnɔ me ɖe asi eye wòaxe mɔ ɖe woƒe apoptosis nu. FOX04-DRI tiaa p53 nuklia ƒe dɔdɔ kple apoptosis na vidzidɔ dome lãmenugbagbevi tsitsiwo to tɔtɔ FOX04-p53 ƒe kadodo me. Le dzɔdzɔme tsitsi ƒe sisiblisi ƒe kpɔɖeŋu me la, FOX04-DRI dodo na vidzidɔa ƒe nɔnɔme suesuesuewo nyo ɖe edzi eye wòɖe testosterone ƒe ʋuʋu si do ƒome kple tsitsi dzi kpɔtɔ. Eyata FOX04-DRI ate ŋu aɖe vi na ŋutsuwo ƒe ʋumenugbagbeviɣidɔ si dzea egɔme megbe la dada.
Figure 2 FOXO4 ƒe ɖeɖefia le amegbetɔ ƒe vidzidɔ me si wokpɔ to immunofluorescent staining me.
Akpa si wòwɔna le gbɔgbɔtsixe ƒe dɔwɔwɔ me
Aklã me ʋu ƒe sisi: Aklã me ʋu ƒe sisi (PF) nye aklãdɔ si yia edzi le ʋukawo dome. Eƒe dzɔdzɔ kple eƒe bɔbɔ dzina ɖe edzi ne ame tsi, eye wobua lãmenugbagbeviwo ƒe tsitsi be enye nu vevi siwo ʋãa eƒe dɔlékuiwo dometɔ ɖeka. Le PF sisiblisi ƒe kpɔɖeŋu si wotsɔ bleomycin (BLM) wɔ me la, FOX04-DRI ɖe ŋusẽkpɔɖeamedzi siwo sɔ kple atike si dzi woda asi ɖo si nye pirfenidone tɔ fia. Eɖea lãmenugbagbevi siwo tsina ƒe xexlẽme dzi kpɔtɔna, eɖea lãmenugbagbevi siwo do ƒome kple adzame ƒe nɔnɔme (SASP) ƒe ɖeɖefia dzi kpɔtɔna, eye wòɖea nɔnɔme ƒe tɔtrɔ siwo BLM hena vɛ kple kolagen ƒe tsɔtsɔ ɖe lãkusi me dzi kpɔtɔna. Tsɔ kpe ɖe eŋu la, FOX04-DRI dzia lãmenugbagbevi ƒomevi 2 siwo nye alveolar epithelial cells (AEC2) kple fibroblasts ƒe agbɔsɔsɔ ɖe edzi esime wòɖea myofibroblasts ƒe xexlẽme dzi kpɔtɔna. Dodokpɔ siwo wowɔ le vitro ɖee fia be ne wotsɔ FOX04-DRI sɔ kple sisiblisi kple amegbetɔ ƒe lãkusi me fibroblast lãmenugbagbeviwo la, elɔ̃na wu be yeawu transforming growth factor-β (TGF-β)-induced myofibroblasts, eye to mɔxexe ɖe myofibroblasts nu me la, ena extracellular matrix (ECM) receptor interaction pathways ƒe ɖiɖi le PF si BLM hena vɛ me.
Aklãdɔléle si xea mɔ na dɔléle si nɔa anyi didi (COPD): COPD ƒe dɔléle dzɔdzɔ kple eƒe ŋgɔyiyi do ƒome kplikplikpli kple lãmenugbagbeviwo ƒe tsitsi. Le aklã me lãkusi siwo tsina si sigaret ƒe dzudzɔ hena vɛ me la, FOX04 ƒe ɖeɖefia dzina ɖe edzi. Be woate ŋu agbã FOX04 le fibroblast siwo le tsitsim me la, wowɔ DNA nanotubes (siFOXO4-NT) siwo ƒoa wo ɖokui nu ƒu siwo me FOX04 siRNA si ƒe ka ɖeka le la eye wowɔ wo. Numekukuwo ɖee fia be siFOXO4-NT ate ŋu age ɖe amegbetɔ ƒe lãkusi me lãkusiwo (HFL-1 lãmenugbagbeviwo) me le mɔ si nɔa te ɖe eƒe agbɔsɔsɔme kple ɣeyiɣi dzi nu, si wɔnɛ be FOX04 ƒe agbɔsɔsɔ dzi ɖena kpɔtɔna le vitro. siFOXO4-NT ɖea HFL-1 lãmenugbagbevi tsitsiwo ɖa le tiatia me to BCLXL ƒe ɖeɖefia si dzi ɖe edzi kple BCL2/BAX ƒe xexlẽme dzi ɖeɖe kpɔtɔ le HFL-1 lãmenugbagbevi tsitsi siwo sigaret dzudzɔ (CSE) hena vɛ me.
Akpa si ƒunukpeƒetetedɔ wɔna: Autologous chondrocyte implantation (ACI) nye mɔnu si dzi woato ada ƒunukpeƒetetedɔ ƒe gbegblẽ eye woaxe mɔ ɖe ƒunukpeƒetetedɔ si dzɔna le afɔku megbe nu. Le ƒunukpeƒetetedɔ ƒe kekeɖenudɔwɔwɔ le vitro, si nye afɔɖeɖe si hiã le ACI me la, wowɔa lãmenugbagbevi siwo tsi, si kpɔa ŋusẽ gbegblẽ ɖe ƒunukpeƒe yeye siwo wowɔ ƒe nyonyome kple agbɔsɔsɔ dzi. Numekulawo susui be FOX04-DRI zazã ate ŋu aɖe lãmenugbagbevi siwo tsi le ƒunukpeƒeŋusẽ siwo keke ta me, si ana woƒe ŋutete be woawɔ ƒunukpeƒeŋusẽ deŋgɔwo nadzi ɖe edzi. Be woawɔ kekeɖenudɔ si wowɔna le vitro le ACI me ƒe kpɔɖeŋu la, wokeke ƒunukpeƒeŋusẽ siwo woɖe ɖe vovo tso nunala siwo le lãmesẽ me gbɔ va ɖo amewo ƒe xexlẽme ƒe dzidziɖedzi zi gbɔ zi eve (PDL) 9, si tsi tre ɖi na ƒunukpeƒeŋusẽ siwo le klalo na wo dede, evɔ lãmenugbagbevi siwo le PDL3 ya nye kekeɖenudɔwɔwɔ dzi kpɔkpɔ suetɔ kekeake. Emetsonuwo ɖee fia be FOX04-DRI zazã ɖe lãmenugbagbevi siwo wu afã ɖa le PDL9 gake mekpɔ ŋusẽ gã aɖeke ɖe PDL3 chondrocytes ƒe xexlẽme dzi o. PDL9 chondrocytes siwo wotsɔ FOX04-DRI da dɔe ƒe tsitsi ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ ŋutɔ. Wonɔ te ɖe micro-cluster culture ƒe emetsonu siwo wozãna ɖaa dzi gblɔ be FOX04-DRI ƒe atikewɔwɔ do ŋgɔ medo PDL9 chondrocytes ƒe chondrogenic ŋutete ɖe ŋgɔ o, gake chondroid lãkusi siwo wokpɔ tso FOX04-DRI-pretreated PDL9 cells me ɖe tsitsi-si do ƒome kple secretory factors ƒe ɖeɖefia si bɔbɔ wu fia. FOX04-DRI ɖe lãmenugbagbevi siwo tsi nyuie ɖa le PDL9 chondrocytes me nyuie.
Akpa si wòwɔna le aklã me dɔdzẽ si keklẽŋusẽ hena vɛ (RIPF) me: RIPF nye kuxi si bɔ eye wòsẽna le akɔta ƒe dɔdzẽ ƒe keklẽŋusẽdɔdamɔnu megbe. Woma C57BL/6 mice ɖe keklẽŋusẽ kple keklẽŋusẽ + FOX04-DRI ƒuƒoƒowo me le vome, eye wotsɔ 17 Gy X-ray keklẽŋusẽ na ƒuƒoƒo ɖesiaɖe ƒe ɖusime hemithorax. Wodo FOX04-DRI ƒuƒoƒo kple keklẽŋusẽ + FOX04-DRI ƒuƒoƒo ƒe mice to atike si wodo ɖe dɔgboa me dzi le kwasiɖa 16 kple 20 me le keklẽŋusẽ dodo vɔ megbe. Emetsonuwo ɖee fia be FOX04-DRI ɖe collagen ƒe sisi le RIPF mice ƒe lãkusi me dzi kpɔtɔ, eɖe col1α1 kple α-SMA ƒe ɖeɖefia dzi kpɔtɔ, eye wòɖe β-galactosidase (β-gal) positive cells (si nye lãmenugbagbevi siwo tsi ƒe dzesi) ƒe xexlẽme dzi kpɔtɔ le lãkusi me. FOX04-DRI te ŋu xe mɔ ɖe P21 kple P16^(Ink4a) domenyiŋusẽfianuwo kple proteinwo ƒe ɖeɖefia le RIPF mice ƒe lãkusi me, kpakple SASP domenyiŋusẽfianu siwo nye IL-1α, IL-1β, tumor necrosis factor α (TNFα), kple MMP2 ƒe ɖeɖefia nu. FOX04-DRI ɖea oxygen ƒomevi siwo wɔa dɔ (ROS) ƒe agbɔsɔsɔ dzi kpɔtɔna le RIPF mice ƒe lãkusi me eye wòdoa p-AKT kple p-PI3K proteinwo ƒe dɔwɔwɔ ɖe ŋgɔ. Esia fia be FOX04-DRI ɖea oxidative stress dzi kpɔtɔna eye wòxea mɔ na lãmenugbagbeviwo ƒe tsitsi to PI3K/AKT dzesimɔa ƒe dɔwɔwɔ me, si wɔnɛ be RIPF trɔna.
Nutata 3 FOXO4-DRI ɖea myofibroblast ƒe vovototodedeameme dzi kpɔtɔna le PF mice siwo BLM hena vɛ me.
Nyanuwuwuw
Kpuie ko la, FOX04-DRI, abe atike si trɔa asi le nu ŋu si te ŋu ɖea lãmenugbagbevi siwo tsina ɖa koŋ ene, wɔa akpa vevi aɖe le tsitsi ƒe dɔlélewo dada kple tsitsi ƒe nudede eme me.
Dzɔtsoƒewo
[1] Han Y, Wu Y, He B, kple ame bubuwo. DNA nanoparticles siwo tɔa ŋku FOXO4 la ɖea lãkusi me fibroblast siwo tsi si sigaret ƒe dzudzɔ hena vɛ la ɖa tiaa[J]. Nanoscale Ŋgɔyiyi, 2023, 5 (21): 5965-5973.DOI: 10.1039 / d3na00547j.
[2] Han X, Yuan T, Zhang J, kple ame bubuwo. FOXO4 peptide si tɔa ŋku myofibroblast la naa aklã me fibrosis si bleomycin hena vɛ la nyona ɖe edzi le mice me to ECM-receptor interaction pathway dzi[J]. Lãmenugbagbeviwo kple Molekyulãwo ƒe Atikewɔwɔ ƒe Agbalẽ, 2022, 26 (11): 3269-3280.DOI: 10.1111 / jcmm.17333.
[3] Huang Y, He Y, Makarcyzk M. J., kple ame bubuwo. Senolytic Peptide FOXO4-DRI Tiatia Ðe Lãmenugbagbevi Siwo Tsitsi Tso Amegbetɔ Ƒe Ʋuka Siwo Keke Ðe Edzi le vitro[J]. Liƒowo le Nu gbagbewo ƒe mɔ̃ɖaŋununya kple nugbagbeŋutinunya me, 2021,9:677576.DOI:10.3389/fbioe.2021.677576.
[4] Zhang C, Xie Y, Chen H, kple ame bubuwo. FOXO4-DRI ɖea testosterone ƒe ʋuʋu ƒe anyimanɔmanɔ si do ƒome kple tsitsi dzi kpɔtɔna to Leydig lãmenugbagbevi siwo tsi le sisiblisi tsitsiwo me la taɖodzinu ɖoɖo me[J]. Tsitsi (Albany Ny), 2020, 12 (2): 1272-1284.DOI: 10.18632 / tsitsi.102682.
[5] Baar M P. DNA ƒe Gbegblẽ hena Lãmenugbagbeviwo ƒe Dzɔgbese le Tsitsiɣi, 2019[C]. 196682180. Ƒe 196682180
Adzɔnu si li na numekuku zazã ɖeɖeko:
