Cocer Peptides fɛ 
a bɛ kalo 1 bɔ
BƐƐRƐ KUNNAFONIW NI FƐRƐW KUNNAFONIW BƐƐ MIN BƐ NI WEBSITE KAN NA, U BƐ KUNNAFONIW FƆLƆ DƆRƆN NI KALANSENW YE.
Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *glasi kɔnɔ*, o kɔrɔ ye gilasi kɔnɔ) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki ka dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.
Kɔrɔya, n’o ye fɛn ye min tɛ se ka bali fɛnɲɛnamaw la, o kɛra dɔnniya ɲininiw jɔyɔrɔba ye kabini tuma jan. Ni fɛnɲɛnamaw bɛ kɔrɔbaya, farikolokisɛw bɛ don dɔɔni dɔɔni kɔrɔya cogo la, wa o kɔrɔyabanakisɛw dalajɛli bɛ se ka nɔ jugu bila farikolo yɔrɔw ni farikolo yɔrɔw baaracogo ɲuman na, o bɛ na ni bana suguya caman ye minnu bɛ sɔrɔ kɔrɔya fɛ. FOX04 – DRI nafa ka bon farikolo kɔrɔlenw bɔli la.
FOX04 - DRI ka ɲɛfɔli kunbaba
FOX04 - DRI ye pepitiri sintetiki ye, a tɔgɔ dafalen foroko kunkolo kɛsu O transcription factor 4 - D - Retro - Inverso. A sɔrɔli bɛ Bɔ ɲininibaw la minnu Kɛra kɔrɔya-banakisɛw ka ɲɛnabɔli fɛɛrɛw kan. Kɔnɔnatumuw ka kɔrɔya waati, molekiyɔmu fɛɛrɛ caman bɛ sen na, wa FOX04 sɛbɛnnikɛlan jɔyɔrɔ ka bon o baara in na. FOX04 bɛ a jiracogo kɛrɛnkɛrɛnnenw jira ani baarakɛcogo caman yeli selilu kɔrɔlenw na. Dɔnniyakɛlaw y’a ka baarakɛcogo ɲɛfɔ, u ye FOX04-DRI labɛn ani k’a labɛn walasa ka se ka kɔrɔya selilɛriw laɲini kɛrɛnkɛrɛnnenya la, k’a laɲini ka koɲɛw ɲɛnabɔ minnu bɛ tali kɛ kɔrɔya la.
Jaa 1 Sigarɛti sisi bɛ fogonfogon fibroblaste kɔrɔlenw bɔli jiracogo jira ni FOXO4 siRNA-loaded ADN nanoparticules ye.
FOX04-DRI ka fɛɛrɛ min bɛ kɛ ka selilu kɔrɔlenw saniya
FOX04-p53 ka ɲɔgɔn sɔrɔli bali : Kɔrɔya selilɛriw la, FOX04 bɛ ɲɔgɔn sɔrɔ ni p53 furakisɛ ye. p53 furakisɛ jɔyɔrɔ ka bon selilɛriw ka degun jaabiw la, selilɛriw ka taamacogo ɲɛnabɔli la, ani apoptose la. Ni a bɛ cogo la, p53 bɛ apoptose (banakisɛfagalan) sabati farikolokisɛ tiɲɛnenw walima farikolokisɛ kɔrɔlenw na, a kɛtɔ ka apoptose ni ɲɔgɔn cɛ jamu caman jirali baara, o la, a bɛ selilu jamanadenw ka kɛnɛya sabati. Kɔnɔnatumu kɔrɔlenw na, FOX04 bɛ siri p53 la, k’a tacogo bali ka taa selilu nucléaire la, o bɛ p53 bali k’a ka pro-apoptotic baara kɛ, o bɛ na ni selilu kɔrɔlenw ka ɲɛnamaya ni u dalajɛli ye. FOX04-DRI bɛ se ka kɛrɛnkɛrɛnnenya la ka nin jɛɲɔgɔnya in bali FOX04 ni p53 cɛ, k’u sirili bali, ka p53 bila ka segin ka don selilɛri kɔnɔ, ka apoptose taamasiɲɛ sira baara, ka apoptose bila selilu kɔrɔlenw na, o la, a bɛ se ka selilu kɔrɔlenw bɔli ma.
Selilu kɔnɔ taamasiɲɛw siraw labɛnni : Ka fara FOX04-p53 ka jɛɲɔgɔnya bali kan, FOX04-DRI bɛ se ka nɔ bila fana selilu kɔrɔlenw ka siniɲɛsigi la ni a bɛ selilu kɔnɔ taamasiɲɛ sira wɛrɛw labɛn. PI3K/AKT taamasiɲɛw sira jɔyɔrɔ ka bon kosɛbɛ labɛnni na farikolokisɛw falenni, u caya, u ka ɲɛnamaya ani u ka farikoloɲɛnajɛ fan caman na. Kɔlɔsiliw y’a jira ko PI3K/AKT taamasiɲɛw sira baara bɛ Changé tuma caman na farikolokisɛ kɔrɔlenw na, o bɛ nɔ bila u ka baarakɛcogo la. FOX04-DRI bɛ se ka PI3K/AKT taamasiɲɛw sira baara ɲɛnabɔ, ka taamasiɲɛw cili balansi caman sɛmɛntiya mɔgɔkɔrɔbaw kɔnɔ, o la, a bɛ se ka kɛ sababu ye ka selilu kɔnɔ sigida jugu dɔ dilan u ka ɲɛnamaya kama ani ka apoptose bila mɔgɔ la. O taamasiɲɛw sira labɛnni fana bɛ se ka nɔ bila selilɛriw ka farikoloɲɛnajɛ cogoyaw la, ka farikolokisɛ kɔrɔlenw bila ka taa apoptose (banakisɛfagalan) la ka taa a fɛ.
Kɔrɔya-sɔrɔ-sɔrɔ-fɛnotipi (SASP) nɔfɛta : Kɔrɔya-banakisɛw bɛ sitokiniw, kemokiniw ani poroteyizi caman bɔ ɲɔgɔn na, ka kɛ sababu ye ka kɔrɔya-sɔgɔsɔgɔninjɛ fɛnɲɛnamafagalan (SASP) kɛ. SASP tɛ nɔ jugu bila dɔrɔn farikolokisɛw lamini na minnu bɛ kɛnɛya la, ka u ka baara kɛcogo ɲumanw tiɲɛ, nka a bɛ funu jaabi basigilenw fana lawuli, ka farikolo yɔrɔw ni farikolo yɔrɔw kɔrɔya teliya ka taa a fɛ. FOX04-DRI bɛ se ka kɔrɔyabanakisɛw nɔ juguw nɔgɔya lamini sigida misɛnninw na, a kɛtɔ ka SASP ni ɲɔgɔn cɛ fɛnw jirali ni u bɔli bali kɔrɔyabanakisɛw la. Nin ɲinini in kɔnɔ, a jirala ko mɔgɔkɔrɔbaw furakɛli kɔfɛ ni FOX04-DRI ye, SASP ni fɛn minnu bɛ tali kɛ ɲɔgɔn na i n’a fɔ IL-1α, IL-1β, tumor necrosis factor α (TNFα), ani MMP2, olu jirali hakɛ dɔgɔyara kosɛbɛ selilu kɔrɔlenw na. O b’a jira ko FOX04-DRI bɛ se ka selilu kɔrɔlenw ka SASP labɛn ka ɲɛ, ka selilɛriw ka sigida mikoro ɲɛ, ani ka selilu kɔrɔlenw bɔli sabati ani ka farikolo yɔrɔ fitininw seginni sabati cogo la min tɛ siratigɛ la.
FOX04-DRI jɔyɔrɔ farikolo yɔrɔw ni bana suguya wɛrɛw la
Jɔrɔ min bɛ bangekɔlɔsi fɛɛrɛw la : Cɛw ka sɔgɔsɔgɔninjɛ min bɛ daminɛ kɔfɛ, o ye bana ye min bɛ sɔrɔ u si hakɛ fɛ, a kɛcogo jɔnjɔn ye cɛya ni musoya cɛmancɛla selilɛri kɔrɔlenw ka baarakɛbaliya ye. FOX04 bɛ jira kɛrɛnkɛrɛnnenya la hadamadenw ka cɛya cɛmancɛ la, wa mɔgɔkɔrɔbaw la, FOX04 nukilila jiginni bɛ tali kɛ tetarasikilini sɔrɔli dɔgɔyali la. Ni baara kɛra ni TM3 cɛya cɛmancɛ selilu kɔrɔlenw ye minnu bɛ sɔrɔ perokisidi idɔrɔji fɛ, i n’a fɔ misali in vitro, a kɔlɔsira ko FOX04 bɛ se ka cɛya cɛmancɛ selilu kɔrɔlenw ka ɲɛnamaya sabati ani k’u ka apoptose bali. FOX04-DRI bɛ p53 nukilila bɔli ni apoptose (banakisɛfagalan) bila sen kan, o bɛ kɛ sababu ye ka cɛya ni musoya cɛmancɛla selilu kɔrɔlenw ka apoptose (banakisɛfagalanw) bila sen kan, a kɛtɔ ka FOX04-p53 ka jɛɲɔgɔnya tiɲɛ. Sogo kɔrɔbayalen cogoya la, FOX04-DRI tali ye cɛya lamini fitinin ɲɛ ani ka tetarasikilini bɔli dɛsɛ nɔgɔya min bɛ sɔrɔ kɔrɔya fɛ. O la, FOX04-DRI bɛ se ka nafa sɔrɔ cɛw ka jolidɛsɛ furakɛli la min bɛ daminɛ kɔfɛ.
Jaa 2 FOXO4 jirali hadamadenw ka cɛya la min sɔrɔla ni immunofluorescent staining ye.
Jɔrɔ min bɛ ninakilidege la
Fogonfogonlabana : Fogonfogonlabana (PF) ye fogonfogonlabana ye min bɛ taa ɲɛ. A sɔrɔli ni a caya bɛ bonya ni mɔgɔ si hakɛ ye, wa selilɛriw ka kɔrɔya bɛ jate a banakisɛ sɔrɔli sababuba dɔ ye. Bleomycine (BLM)-induite PF sosɛti modɛli dɔ la, FOX04-DRI ye nɔ jira min ni fura dabɔlen pirfenidone ta bɔlen don. A bɛ dɔ bɔ kɔrɔyabanakisɛw hakɛ la, ka kɔrɔya-associé secretory phenotype (SASP) jiracogo dɔgɔya, ani ka BLM ka fɛnɲɛnɛmafagalanw ni kolajɛ bilali nɔgɔya fogonfogon la. Ka fara o kan, FOX04-DRI bɛ dɔ fara sɔgɔsɔgɔninjɛ suguya 2 (AEC2) ni fiɲɛbanakisɛw hakɛ kan ka sɔrɔ ka dɔ bɔ mikorofibɔrɔsi hakɛ la. Kɔrɔbɔli minnu kɛra in vitro la, olu y’a jira ko ni i ye u suma ni sosow ni hadamadenw ka fogonfogon fibroblaste selilɛriw ye, FOX04-DRI tun ka teli ka transforming growth factor-β (TGF-β)-induite myofibroblasts faga, wa ni a ye myofibroblasts bali, o kɛra sababu ye ka extracellular matrix (ECM) receptor interaction siraw jigin BLM-induite PF kɔnɔ.
Fogonfogonlabana basigilen (COPD): Ɲɛgɛnɛsiraw sɔrɔcogo ni a taabolo bɛ tali kɛ farikolokisɛw ka kɔrɔya la kosɛbɛ. Sigarɛti sisi bɛ fogonfogon fibroblaste kɔrɔlenw na, FOX04 jirali bɛ caya. Walasa ka FOX04 gosi fibroblaste kɔrɔlenw kɔnɔ, ADN nanotubes (siFOXO4-NT) minnu bɛ u yɛrɛ lajɛ, minnu falen bɛ FOX04 siRNA kelen na, olu dabɔra ka u labɛn. Kɔlɔsiliw y’a jira ko siFOXO4-NT bɛ se ka don hadamadenw ka fogonfogon la (HFL-1 selilɛriw) cogo la min bɛ bɔ a hakɛ ni waati la, o bɛ FOX04 hakɛ dɔgɔya in vitro. siFOXO4-NT bɛ HFL-1 selilɛri kɔrɔlenw bɔ yen ka sugandi, a kɛtɔ ka BCLXL jiracogo kɔrɔlen ni BCL2/BAX hakɛ dɔgɔya sigarɛti sisi bɔlen (CSE) fɛ HFL-1 selilɛri kɔrɔlenw na.
Jɔrɔ min bɛ kolotugudaw la : Kɔnɔnatumuw doncogo yɛrɛma (ACI) ye fɛɛrɛ ye min bɛ kɛ ka kolotugudaw tiɲɛni furakɛ ani ka kolotugudaw bali min bɛ sɔrɔ bɔnɛ kɔfɛ. Kɔnɔnatumuw falenni senfɛ in vitro, o ye fɛɛrɛ wajibiyalen ye ACI kɔnɔ, farikolokisɛ kɔrɔlenw bɛ sɔrɔ, o bɛ nɔ jugu bila kolotugudaw kura dilancogo ɲuman n’a hakɛ la. Ɲininikɛlaw y’a jira ko FOX04-DRI furakɛli bɛ se ka kɔrɔyabanakisɛw bɔ ɲɛgɛnɛsiraw la minnu bonyalen don, o bɛ dɔ fara u ka seko kan ka kolotugudaw labɔ minnu ka ɲi kosɛbɛ. Walasa ka in vitro farali taabolo ladege ACI kɔnɔ, kondrositɛri minnu bɔra dɛmɛbaga kɛnɛmanw na, olu bonyalen don ka se jamanadenw hakɛ fila hakɛ (PDL) 9 ma, o bɛ kɔndɔrositɛriw jira minnu labɛnnen don ka don u kɔnɔ, k’a sɔrɔ selilu minnu bɛ PDL3 la, olu kɛra farali kɔlɔsili fitinin ye. Jateminɛw y’a jira ko FOX04-DRI furakɛli ye farikolokisɛ tilancɛ ni kɔ bɔ PDL9 la nka a ma nɔba bila PDL3 kɔnɔbara hakɛ la. PDL9 kondrositɛri minnu furakɛra ni FOX04-DRI ye, olu kɔrɔbayali hakɛ dɔgɔyara kosɛbɛ. Ka da micro-cluster culture results standards kan, FOX04-DRI furakɛli ɲɛfɛ, o ma dɔ fara PDL9 kondrositɛriw ka kondrojeni seko kan, nka kɔndɔrozi farikolo minnu bɔra PDL9 selilɛriw la minnu furakɛra ka kɔn FOX04-DRI ɲɛ, olu ye kɔrɔya ni gundolafɛnw jiracogo dɔgɔya jira. FOX04-DRI ye selilu kɔrɔlenw bɔ PDL9 kɔnɔbara la ka ɲɛ.
Jɔrɔ min bɛ fogonfogonlabana la (RIPF): RIPF ye gɛlɛya ye min ka teli ka sɔrɔ ani min ka jugu kosɛbɛ barajuru tumu furakɛli kɔfɛ. C57BL/6 sogow tilalen don k’u kɛ fiɲɛbɔ ni fiɲɛbɔ + FOX04-DRI kuluw ye k’u kɛ, ni kulu kelen-kelen bɛɛ ka kininbolo hemithorax ye 17 Gy X-ray radiation sɔrɔ. FOX04-DRI kulu ni fiɲɛ bilali + FOX04-DRI kulu sogow ye FOX04-DRI pikiri kɛ kɔnɔbara la dɔgɔkun 16 ni 20 fiɲɛ bilali kɔfɛ. Jateminɛw y’a jira ko FOX04-DRI ye dɔ bɔ kolajɛ bilali la RIPF sogow fogonfogon la, ka dɔ bɔ col1α1 ni α-SMA jirali la, ka dɔ bɔ β-galactosidase (β-gal) selilu ɲumanw hakɛ la (o ye selilu kɔrɔlenw taamasiɲɛ ye) fogonfogon la. FOX04-DRI sera ka P21 ni P16^(Ink4a) jamu ni farikolojɔlifɛnw jirali bali RIPF sogow fogonfogon la, ka fara SASP jamu IL-1α, IL-1β, tumor necrosis factor α (TNFα), ani MMP2 jirali kan. FOX04-DRI fana bɛ dɔ bɔ oksizɛni suguya (ROS) hakɛ la RIPF sogow fogonfogon la ani ka p-AKT ni p-PI3K furakisɛw baara sabati. O b’a jira ko FOX04-DRI bɛ dɔ bɔ oksidan degun na ani ka selilɛriw ka kɔrɔya bali ni PI3K/AKT taamasiɲɛw sira baara ye, o la, a bɛ RIPF kɔsegin.
Jaa 3 FOXO4-DRI bɛ mikorofibroblaste danfara nɔgɔya BLM-induite PF sogow la.
Kuncɛli
Kuma surun na, FOX04-DRI, n’o ye fura ye min bɛ fɛn caman sɛmɛntiya, n’a bɛ se ka mɔgɔkɔrɔbaw bɔ kɛrɛnkɛrɛnnenya la, o jɔyɔrɔ ka bon banaw furakɛli la minnu bɛ sɔrɔ kɔrɔya fɛ ani kɔrɔya fɛɛrɛw la.
Sosow (Sɔrɔyɔrɔw).
[1] Han Y, Wu Y, He B, ani a ɲɔgɔnnaw. ADN nanoparticules minnu bɛ FOXO4 laɲini, olu bɛ fogonfogon fibroblaste kɔrɔlenw ban minnu bɛ sɔrɔ sigarɛti sisi fɛ[J]. Nanoscale ɲɛtaa, 2023,5(21):5965-5973.DOI:10.1039/d3na00547j.
[2] Han X, Yuan T, Zhang J, ani mɔgɔ wɛrɛw. FOXO4 pepitiri min bɛ miyɔfibroblaste laɲini, o bɛ fogonfogon la fibrose min bɛ sɔrɔ bleomycine fɛ, o ɲɛnabɔ sosow la ECM-recepteur interaction sira fɛ[J]. Selulɛri ni molekiyɔmu furakɛli gafe, 2022,26(11):3269-3280.DOI:10.1111/jcmm.17333.
[3] Huang Y, He Y, Makarcyzk M. J., ani mɔgɔ wɛrɛw. Peptide senolytique FOXO4-DRI bɛ selilu kɔrɔlenw bɔ a sugandilen na ka bɔ hadamadenw ka kondrositɛriw la minnu bonyalen don in vitro[J]. Dancɛw Bioengineering ni Biotechnologie la, 2021,9:677576.DOI:10.3389/fbioe.2021.677576.
[4] Zhang C, Xie Y, Chen H, ani mɔgɔ wɛrɛw. FOXO4-DRI bɛ tetarasikilini bɔli dɛsɛ nɔgɔya min bɛ sɔrɔ kɔrɔya fɛ, a kɛtɔ ka Leydig selilɛri kɔrɔlenw laɲini soso kɔrɔbaw la[J]. Kɔrɔya (Albany Ny), 2020,12(2):1272-1284.DOI:10.18632/kɔrɔya.102682.
[5] Baar M P. ADN tiɲɛni min bɛ sɔrɔ selilɛriw ka siniɲɛsigi la kɔrɔya waati, 2019[C]. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew
Fɛn min bɛ sɔrɔ ɲininiw dɔrɔn kama:
