Na Cocer Peptides bin rayt am 
1 mɔnt dɔn pas
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Fɔ ol, as natin we nɔ go ɛva apin na di tin dɛn we gɛt layf, dɔn bi wan men tin we sayɛnsman dɛn dɔn du fɔ lɔng tɛm. as di כganism dεm de ol, sכmtεm di sεl dεm de go insay wan stet we de sכmtεm sכmtεm sכmtεm, εn we dεn sεl dεm ya de kכmכt kin ambɔg di nכmal fכnshכn fכ di tisu dεm εn כgan dεm, we kin mek dεn gεt difrεn sik dεm we de kכmכt frכm di ej. FOX04 – DRI na bεnεfit fכ klia senesεnt sεl dεm.
Ovaviu fɔ FOX04 - DRI
FOX04 - DRI na sεntetik pεptida, wit di ful nem fכk hεd bכks O transkripshכn fכktכ 4 - D - Rεtro - Invεso. di diskovri we i dכn kכmכt frכm dip risεch pan di rεgεdyushכn mεkanism dεm fכ di senesεnt sεl dεm. di tεm we di sεl dεm de sεns, mכltipכl mכlikul mεkanism dεm de involv, εn di FOX04 transkripshכn fכktכ de ple wan kכl rol insay dis prכsεs. FOX04 de sho spεsifi k εksprεshכn patεn dεm εn fכnshכnal chenj dεm na di senesεnt sεl dεm. bay we dεn elucidate in mεkanism fכ akshכn, sayɛnsman dεm disayn εn sεntez FOX04-DRI fכ spεshal tכkכt senesεnt sεl dεm, we dεn aim fכ adrεs εj-rεlatεd ishu dεm.
Figure 1 Skematik ilustrashכn fכ di εliminεshכn fכ sigrεt smok-indyus senesεnt lכng fכblast dεm we de yuz FOXO4 siRNA-lod DNA nanopartikl dεm.
mεkanism fכ FOX04-DRI in klia senesεnt sεl dεm
intafεreshכn wit FOX04-p53 intarakshכn: insay senesεnt sεl dεm, FOX04 de intarakt wit di p53 protin. di p53 protin de ple sεntri rol insay sεlyul strεs rispכns, sεl saykl rεguleshכn, εn apoptosis. כnda nכmal kכndishכn dεm, p53 de protεkt apoptosis insay dεmεj כ senesεnt sεl dεm bay we i de aktibכt di εksprεshכn fכ wan siriכs apoptosis-rεlatεd jin dεm, we de mek i de mεnten di hεlth fכ di sεl populeshכn. insay senesεnt sεl dεm, FOX04 de biεn p53, we de inhεbit in transpכt to di sεl nyuklios, we de mek p53 nכ de du in pro-apoptotic fכnshכn, we de rizulta in di sכvayv εn akyumyuleshכn fכ senesεnt sεl dεm. FOX04-DRI kin spεshal intafεr wit dis intarakshכn bitwin FOX04 εn p53, blכk dεn binding, alaw p53 fכ ri-enta di sεl nyuklios, aktibכt di apoptosis signal path, εn indyuz apoptosis insay senesεnt sεl dεm, we de achy di kliarεns fכ senesεnt sεl dεm.
rεgulεshכn fכ di intasεlulyar signal path dεm: apat frכm we i de intafεr di FOX04-p53 intarakshכn, FOX04-DRI kin infכlכw bak di fεt fכ di senesεnt sεl dεm bay we i de rεgεl כda intasεlulyar signal path dεm. di PI3K/AKT signal path de ple wan ki rεgεdyushכn rol insay difrεn aspek dεm fכ di sεl gro, proliferashכn, sכvayv, εn mεtabolism. stכdi dεn sho se di aktvכti fכ di PI3K/AKT signal path kin chenj bכku tεm insay senesεnt sεl dεm, we de afekt dεn nכmal fכnshכn dεm. FOX04-DRI kin rεgεl di aktvכti fכ di PI3K/AKT signal path, altεr di bεlε fכ signal transdyushכn insay senesεnt sεl dεm, we de mek wan nכ fayn intasεlulyar envayroment fכ dεn sכvayv εn indyuz apoptosis. rεguleshכn fכ dis signal path kin infכlכw bak di sεlyul mεtabolik stet dεm, fכ drεb senesεnt sεl dεm fכ tכwεd apoptosis.
infכmeshכn pan di Senesεns-Asכsiet Sekretri Fεnotayp (SASP): di sεnsεnt sεl dεm de sekret wan siriכs saytokכn, kεmokin, εn proteas, we de fכm di senesεns-asכsiet sekretri fεnotayp (SASP). SASP nכ de nכmכ nεgεtivli afekt di nכmal sεl dεm we de rawnd, i de disrupt dεn nכmal fכnshכn, bכt i de trigεr krεse inflammatory rispכns dεm, we de aksεleret di ol prכsεs fכ di tisu dεm εn כgan dεm mכr. FOX04-DRI kin mitigate di advεs ifekt dεm we di senesεnt sεl dεm de gi pan di maykro envayroment we de rawnd bay we i de inhεbit di εksprεshכn εn sekreshכn fכ SASP-rεlatεd fכktכ dεm na di senesεnt sεl dεm. insay di stכdi, dεn fכnshכn se afta dεn trit sεnesεnt sεl dεm wit FOX04-DRI, di εksprεshכn lεvεl dεm fכ SASP-rεlatεd fכktכ dεm lεk IL-1α, IL-1β, tכmכr nεkrכsis fכktכ α (TNFα), εn MMP2 insay senesεnt sεl dεm bin rεdכks bכku bכku wan. dis sho se FOX04-DRI kin ebul fכ rεgεl di SASP fכ di senesεnt sεl dεm fayn fayn wan, impruv di sεlyul maykro envayroment, εn indayktli promuot di kliarεns fכ di senesεnt sεl dεm εn di rεkכvri fכ di tisu maykro envayroment.
Di Rol we FOX04-DRI de ple pan difrεn tisu dεm εn sik dεm
di rol we di rεprכdaktiv sistεm de ple: di man let-onset haypogonadism na sik we de kכmכt frכm di ej we in kכr mεkanism na di disfכnkshכn fכ di ol tεstikul intastitial sεl dεm. FOX04 de spεshal εksprεs insay hכman tεstikul intastitial sεl dεm, εn insay di ol pipul dεm, di nyuklia translכkeshכn fכ FOX04 de sho se i de ridyus tεstostεron sεntesis. we dεn yuz haydrojεn pεrכksayd-indyuz εj TM3 tεstikul intastitial sεl dεm as in vitro mכdel, dεn obsεv se FOX04 kin mεnten di viabiliti fכ ol tεstikul intastitial sεl dεm εn inhεbit dεn apoptosis. FOX04-DRI sεlektivli indyuz p53 nyuklia εkspכt εn apoptosis fכ ol tεstikul intastitial sεl dεm bay we i de disrupt di FOX04-p53 intarakshכn. insay wan nεchכral εj maws mכdel, administreshכn fכ FOX04-DRI impruv di tεstikul maykro envayroment εn alivεt εj-rεlatεd tεstostεron sekreshכn dεfisiεns. So, FOX04-DRI kin bεnεfit fכ di tritmεnt fכ man let-onset haypogonadism.
Figure 2 Eksprεshכn fכ FOXO4 insay hכman tεst dεm we dεn dεtekt bay immunofluorescent staining.
Rol in di respiratory sistεm
Pulmonary fibrosis: Pulmonary fibrosis (PF) na wan sik we de go bifo pan intastitial lכng. di insidεns εn prεvalεns we i de inkrεs wit di ej, εn dεn kכnsidr di sεl dεm senesεns as wan pan di kכl drεvin fכs fכ in pathogenesis. In wan bleomycin (BLM)-induced PF mouse model, FOX04-DRI demonstret ifekt dem we fiba di wan dem we di apruv drog pirfenidone get. i de ridyus di nכmba fכ di senesεnt sεl dεm, dכwnrεgul di εksprεshכn fכ di senesεns-asכsiet sekret fεnotayp (SASP), εn i de εliviet di BLM-indyus mכfכlכjik chenj dεm εn kolagen dεposishכn insay lכng tisu. apat frכm dat, FOX04-DRI de inkrεs di prכpכshכn fכ tayp 2 alvεolar εpitεlial sεl dεm (AEC2) εn fכblas dεm we i de ridyus di nכmba fכ mayofibroblast dεm. in vitro εkspεriεns sho se we dεn kכmpεr wit maws εn hυman lכng fכblas sεl layn dεm, FOX04-DRI bin mכr inklin fכ kil transfכm gכt fכktכ-β (TGF-β)-indyus mayofibroblast dεm, εn bay we i inhεbit mayofibroblast dεm, i lid to di dכwnrεgulεshכn fכ εkstrasεlyul matris (ECM) rεsεptכr intarakshכn path dεm na BLM-indyus PF.
Chronic obstructive pulmonary disease (COPD): di pathogenesis εn di prכgreshכn fכ COPD de kכlכsכl wit di sεlyul senesεns. insay di sigrεt smok-indyuz senesεnt pulmonary fibroblast dεm, FOX04 εksprεshכn de εlevεt. Fכ knockdown FOX04 in senescent fibroblasts, sεlf-assembling DNA nanotubes (siFOXO4-NT) we lod wit singl-strand FOX04 siRNA bin disayn εn sεntez. stכdi dεn sho se siFOXO4-NT kin enta hכman lכng fכblas (HFL-1 sεl dεm) insay wan kכnsantreshכn- εn tεm-dipεndεnt we, we de ridyus FOX04 lεvεl in vitro. siFOXO4-NT selektivli eliminet ej HFL-1 sel dεm bay we i de ridyus di εlevεt BCLXL εksprεshכn εn BCL2/BAX rεshכ in sigrεt smok εkstrakt (CSE)-indyus εj HFL-1 sεl dεm.
di rol we di kכtilaj de ple: כ tכlכg kכndrכsayt implantεshכn (ACI) na wan mεtכd fכ trit di joyn kכtilaj dεm we dεn dכn pwεl εn fכ mek dεn nכ gεt כstio-arayt afta di traumatik. di tεm we di in vitro εkspεns fכ di kכndrכsayt dεm, we na wan nεsεsary stεp insay ACI, dεn de jεnarεt senesεnt sεl dεm, we de nεgεtivli impכkt di kwaliti εn kwantiti fכ di nyu kכtilaj we dεn fכm. di risach pipul dεm bin hypothεsis se FOX04-DRI tritmεnt kin pul di senesεnt sεl dεm frכm di εkspεnd kכndrכsayt dεm, we de εnhans dεn pכtεnshal fכ jεnarεt hכy kwaliti kכtilaj. fכ simul di in vitro εkspεns prכsεs insay ACI, dεn bin εkspεnd di kכndrכsayt dεm we dεn aylכt frכm hεlty dכna dεm to populeshכn dכblεn lεvεl (PDL) 9, we rεprεsεnt di kכndrכsayt dεm we rεdi fכ implant, we di sεl dεm na PDL3 bin de sεv as minimal εkspεnsכn kכntrכl. di rizulεt sho se FOX04-DRI tritmεnt rεmov ova haf pan di sεl dεm na PDL9 bכt i nכ gεt nכ sכmtin ifekt pan di nכmba כf PDL3 kכndrכsayt dεm. di senesεns lεvεl fכ PDL9 kכndrכsayt dεm we dεn trit wit FOX04-DRI bin sכmtεm rεdכks. Bays pan standad maykro-klɔsta kɔlchɔ rizɔlt, FOX04-DRI prɛtritmɛnt nɔ bin ɛnhans di kɔndrɔjɛnik pɔtɛnɛshɔn fɔ PDL9 kɔndrosayt dɛn, bɔt di kɔndrɔyd tisu we kɔmɔt frɔm FOX04-DRI-prɛtrit PDL9 sɛl dɛn sho lɔwa ɛksprɛshɔn fɔ ol-asɔsiet sɛkret faktɔ dɛn. FOX04-DRI ifektivli rimobul senesεnt sεl dεm frכm PDL9 kכndrכsayt dεm.
di rol we di rεdyushכn-induse pulmonary fibrosis (RIPF): RIPF na kכmכn εn siriכs kכmplikεshכn we de fכlכ tכraks tכmכro rεdyutεrapi. C57BL/6 mays dɛn bin randomly divayd insay iradyeshɔn ɛn iradyeshɔn + FOX04-DRI grup dɛn, wit di rayt ɛmitɔraks fɔ ɛni grup we gɛt 17 Gy X-ray iradyeshɔn. FOX04-DRI grup ɛn irradiation + FOX04-DRI grup mays dɛn bin administret FOX04-DRI via intraperitoneal injɛkshɔn na wik 16 ɛn 20 post-iradiation. di risalts sho se FOX04-DRI ridyus kolagen diposishכn in lכng tisu fכ RIPF mays, dεkrεs εksprεshכn fכ col1α1 εn α-SMA, εn ridyus di nכmba fכ β-galactosidase (β-gal) positifu sεl dεm (wan mak fכ senesεnt sεl dεm) insay lכng tisu. FOX04-DRI bin ebul fכ inhεbit di εksprεshכn fכ P21 εn P16^(Ink4a) jin dεm εn protin dεm na di lכng tisu fכ RIPF mays, εn bak di εksprεshכn fכ SASP jin dεm IL-1α, IL-1β, tכmכro nεkrכsis fכktכ α (TNFα), εn MMP2. FOX04-DRI de ridyus di riaktiv כksijεn spεs (ROS) lεvεl dεm bak na di lכng tisu fכ RIPF mays dεm εn i de promuot di aktibכshכn fכ p-AKT εn p-PI3K protin dεm. dis sho se FOX04-DRI de ridyus oksidativ strεs εn inhεbit sεlyul sεnesεns bay we i de aktibכt di PI3K/AKT signal path, we de rivεs RIPF.
Figure 3 FOXO4-DRI de aliviet myofibroblast difrεns in BLM-indyus PF mays.
Dɔn
fכ sכmari, FOX04-DRI, as rivכlyushכn drog we ebul fכ spεshal εliminet senesεnt sεl dεm, de ple imכtant rol fכ trit sik dεm we de kכmכt frכm di ej εn intavεnshכn fכ ol.
Sos dɛn we dɛn pul
[1] Han Y, Wu Y, H ɛ B, ɛn ɔda pipul dɛn. DNA nanopartikl dεm we de tכk bכt FOXO4 de sεlektivli εliminet di sigrεt smok-indyuz senesεnt lכng fכblas dεm[J]. Nanoskayl Advans, 2023, 5 (21): 5965-5973.DOI: 10.1039/d3na00547j.
[2] Han X, Yuan T, Zhang J, ɛn ɔda pipul dɛn. FOXO4 pεptida de tכgεt myofibroblast de ameliorate bleomycin-induced pulmonary fibrosis in mays tru ECM-rεsεptor intarakshכn path[J]. J ɔ rnal ov S ɛ lular ɛn Mɔlikul Mɛdisin, 2022,26(11):3269-3280.DOI: 10.1111/jcmm.17333.
[3] Huang Y, H ɛ Y, Makarcyzk M. J., ɛn ɔda pipul dɛn. Sεnolaytik Pεptid FOXO4-DRI Sεlektivli Rimov Sεnesεnt Sεl Dεm Fכ in vitro εkspεnd Hכman Kכndrכsayt dεm[J]. Frɔntiers in Bayoɛnjɛnɛri ɛn Bayoteknɔlɔji, 2021,9:677576.DOI:10.3389/fbioe.2021.677576.
[4] Zhang C, Xie Y, Chen H, ɛn ɔda pipul dɛn. FOXO4-DRI de alivεt εj-rεlatεd tεstostεron sekreshכn insufisεns bay we i de tכk bכt senesεnt Leydig sεl dεm insay ol mays[J]. Aging (Albany Ny), 2020,12 (2): 1272-1284.DOI: 10.18632/ɛj.102682. Di wan dɛn we de ol.
[5] Baar M P. DNA Dεmεj Indyuz Sεl Fεt dεm di tεm we i de ol, 2019[C]. 196682180. Di wan dɛn we de stɔdi bɔt di Baybul
Prodak we de fɔ yuz fɔ risach nɔmɔ:
