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.
Kunnafoni jɔnjɔnw KPV kan
KPV ye tripeptide ye min ka banakisɛfagalanw nafa ka bon, o b’a to a jɔyɔrɔ ka bon baara caman na.
Jaa 1 HA-KPV-NPw ka furakɛli nɔ minnu bɛ UC la HA-KPV-NPw tali da la minnu sirilen don hidrojɛli la (kitosan/alginate) o bɛ furakɛli nɔ faralenw di UC ma ni a bɛ ɲɛgɛnɛsira kɛnɛyali teliya ani ka funu nɔgɔya.
KPV ka funu kɛlɛli fɛɛrɛ
1. Selilu taamasiɲɛw siraw labɛnni
NF-κB taamasiɲɛw sira : NF-κB ye sɛbɛnnikɛlan jɔnjɔn ye min jɔyɔrɔ ka bon funu jaabiw la. Ni farikolokisɛw bilala funufɛnw na, NF-κB bɛ bɔ sitoplasma la ka taa nukili la, o bɛ funu dɛmɛbagaw ka sitokini jamu sɛbɛnni daminɛ. KPV bɛ se ka NF-κB baarakɛli bali. Adamadenw ka banakɔtaa ɲɛgɛnɛsiralabanaw ni hadamadenw ka T selilɛriw la, seliluw lawulila ni sitokiniw ye minnu bɛ banakisɛw dɛmɛ, ka KPV fara a kan waati kelen na. Ni aw kɛra ni fɛɛrɛw ye i n’a fɔ NF-κB luciferase gene reporter assays, protein immunoblotting, real-time reverse transcription polymerase chain reaction, ani enzyme-linked immunosorbent assay (ELISA), a jirala ko KPV ni nanomolari hakɛ bɛ se ka NF-κB baarakɛli bali, o la, a bɛ dɔ bɔ sitokiniw bɔli la minnu bɛ banakisɛw dɛmɛ. Nin fɛɛrɛ in nafa ka bon kosɛbɛ banakɔtaa funu ɲɛnabɔli la, barisa NF-κB baarakɛli kojugu banakɔtaa ɲɛgɛnɛsiralabanaw ni farikolo tangalanw na, o ye banakɔtaa funubana (IBD) ni banakɔtaa funu cogoya wɛrɛw taamasiɲɛba ye.
MAP kinase taamasiɲɛ sira : Mitogène-activé proteine kinase (MAPK) taamasiɲɛ sira ye ɲɛnabɔli sira nafama wɛrɛ ye funu jaabiw la, i n’a fɔ extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), ani p38 MAPK. O kinase ninnu bɛ baara kɛ ni seliluw bilala funufɛnw na, o bɛ na ni duguma sɛbɛnnikɛlanw fosforilasi ye ani ka funu ni ɲɔgɔn cɛ jamu jirali sabati. KPV bɛ se ka MAP kinase funu taamasiɲɛw sira fana bali. Ni farikolokisɛw bilala funufɛnw na, KPV bɛ se ka MAPK baarakɛcogo bali, ka dɔ bɔ a ka fosforilasi la duguma sɛbɛnnikɛlanw na, o la, a bɛ dɔ bɔ funu dɛmɛbagaw ka sitokiniw bɔli la. Funu cogoya la, p38 MAPK baarakɛli bɛ na ni funu dɛmɛnan sitokiniw jirali caya ye i n’a fɔ TNF-α ani IL-6, ka sɔrɔ KPV bɛ se ka p38 MAPK baara bali, ka dɔ bɔ o sitokiniw bɔli la ani o la ka funu jaabi nɔgɔya.
2. Kɔnɔnatumuw tabaga ka nɔ minnu bɛ sɔrɔ
PepT1 tabaga : PepT1 ye di/tripeptide tabaga ye min bɛ sɔrɔ banakɔtaa fitini na nka a bɛ bila kɔnɔbara la IBD waati. KPV ka funu kɛlɛli nɔ dɔw bɛ sɔrɔ PepT1 fɛ. Taamacogo kɔlɔsiliw la, KPV nɛnɛma kɛra hPepT1 balilan ye min bɛ se ka ɲɔgɔn sɔrɔ i n’a fɔ fɛn min bɛ taamasiyɛn kɛ ni radiyowaati ye, walima [⊃3;H]KPV kɛra ka KPV minɛcogo taamasiɲɛw dɔn. KPV bɛ don farikolo tangalanw ni banakɔtaa ɲɛgɛnɛsiraw la hPepT1 fɛ. O b’a jira ko PepT1, n’o ye fɛnw tabaga ye, o bɛ KPV doncogo nɔgɔya farikolokisɛw kɔnɔ walasa k’a ka banakisɛfagalanw kɛ. Ni PepT1 baara balila, KPV doncogo hakɛ bɛ dɔgɔya farikolokisɛw la, wa a ka banakisɛfagalanw fanga bɛ dɔgɔya o cogo kelen na. Kɔnɔnatumuw ka misaliw la minnu bɛ PepT1 jiracogo knockdown, hali ni a kɛra ni a hakɛ kelen ye, KPV bɛ dɔ bɔ kosɛbɛ balili nɔ na NF-κB baarakɛli la ani ka dɔ bɔ banakisɛfagalanw bɔli la ni i ye a suma ni seliluw ye minnu ka PepT1 jiracogo bɛ cogo la, o bɛ PepT1 jɔyɔrɔba sinsin ka t’a fɛ KPV ka banakisɛfagalanw kɛcogo la.
3. Sitokiniw minnu bɛ funu bila mɔgɔ la, olu labɛnni
Sitokiniw balili : KPV bɛ se ka sitokini caman sɔrɔli ni u bɔli bali kosɛbɛ. TNF-α ye sitokini jɔnjɔn ye funu jaabiw la, a bɛ se ka farikolo tangalanw baara, ka funu dɛmɛbaga sitokini wɛrɛw dilan, ani ka farikolo yɔrɔw tiɲɛ. Funu kɛcogo suguya caman na, TNF-α jiracogo hakɛ dɔgɔyara kosɛbɛ KPV furakɛli kɔfɛ. Misali la, sosow ka kɔnɔboli misali dɔ la, min bɛ sɔrɔ sulfate de sodium fɛ, furakɛli ni KPV ye, o kɛra sababu ye ka TNF-α ka ARNm jirali dɔgɔya kosɛbɛ kolotuguda la, i n’a fɔ a sɔrɔla cogo min na RT-PCR waati yɛrɛ la, ani ka TNF-α farikolojɔlifɛnw hakɛ dɔgɔya kosɛbɛ joli la, i n’a fɔ a sɔrɔla cogo min na ELISA fɛ. IL-1β, IL-6 ani sitokini wɛrɛw fana balila KPV fɛ. IL-1β bɛ se ka funu ka cascade reaction (furu kasɛti) waleya, ka funu cɛmancɛlafɛn wɛrɛw bɔli sabati. KPV bɛ se ka dɔ bɔ a jirali ni a bɔli la funu yɔrɔw la, o bɛ funu jaabi fanga nɔgɔya.
Sitokiniw minnu bɛ banakisɛw kɛlɛ : Ka fara sitokiniw balili kan minnu bɛ banakisɛw kɛlɛ, KPV bɛ se ka banakisɛfagalanw jirali fana sabati. Interleukin-10 (IL-10) ye sitokini nafama ye min bɛ se ka farikolo tangalanw ka baara bali ani ka dɔ bɔ banakisɛfagalanw dilanni na.
4. Banakisɛfagalanw ka ɲɛnabɔli
T-cell baara ɲɛnabɔli : T-cell jɔyɔrɔ ka bon farikolo tangacogo ni funu labɛnni na. Funu cogoyaw la, T-cell bɛ baara kɛ ani ka funu dɛmɛni sitokiniw bɔ. Kɔlɔsiliw y’a jira ko KPV bɛ se ka T-cell baara ɲɛnabɔ. Kɔrɔbɔliw la ni hadamaden ka T-cell line Jurkat ye, ni Jurkat seliluw lawulila ni sitokiniw ye minnu bɛ banakisɛfagalanw kɛ, KPV farali ye T-cell baarakɛcogo bali ani ka dɔ bɔ sitokiniw bɔli la minnu bɛ funu dɛmɛ i n’a fɔ IFN-γ. O bɛ se ka kɛ ni NF-κB ni MAPK taamasiɲɛw siraw balili ye T selilɛriw kɔnɔ. Ka fara o kan, baganw ka misali dɔw la, i n’a fɔ CD45RB(hi) kolotuguda funu misali, KPV furakɛli bɛ se ka T-cell doncogo ni baara kɛcogo ɲɛnabɔ banakɔtaa kɔnɔ, ka T-cell kulu fitininw dɔgɔya minnu bɛ sɔrɔ funu fɛ i n’a fɔ Th1 ni Th17 selilɛriw, ani ka dɔ fara T-cell ɲɛnabɔbagaw hakɛ kan, o bɛ banakɔtaa funu nɔgɔya.
Makɔrɔfaga baarakɛcogo caman sɛgɛsɛgɛli : Makrofagaw ye farikolo tangalan nafamaw ye funu jaabi la, wa u bɛ se ka tila ka kɛ M1 makɔrɔfagaw ye minnu bɛ baara kɛ klasiki la ani M2 makɔrɔfaga minnu bɛ baara kɛ cogo wɛrɛ la ka kɛɲɛ n’u ka baarakɛcogo ye. M1 makɔrɔfagaw bɛ sitokiniw caman bɔ minnu bɛ banakisɛfagalanw bɔ, ka sɔrɔ M2 makɔrɔfagaw bɛ banakisɛfagalanw ni farikolo yɔrɔw dilan baara kɛ. KPV bɛ se ka makɔrɔfaga polarize (polarize) labɛn. Kɔrɔbɔli minnu kɛra in vitro la, olu y’a jira ko ni makɔrɔfagaw lawulila ni lipopolisakaridi (LPS) ye walasa u ka polarize ka taa M1 suguya la, KPV tali ɲɔgɔn fɛ, o bɛ makɔrɔfaga polarize bali ka taa M1 suguya la, o bɛ dɔ bɔ M1 makɔrɔfaga taamasiɲɛw jirali la, ka sɔrɔ ka u polarize yiriwa ka taa M2 suguya la, ka dɔ fara M2 makɔrɔfaga taamasiɲɛw jirali kan (i n’a fɔ arginase-1 Arg-1) ye. In vivo funu misaliw la, i n’a fɔ DSS-induite colitis sosow la, furakɛli ni KPV ye, o kɛra sababu ye ka makɔrɔfaga caman sɔrɔ kolotuguda la ka polarize ka taa M2 suguya fan fɛ, o la, funu jaabiw bɛ nɔgɔya ani ka farikolo yɔrɔw dilancogo sabati.
5. Lakanali nɔ minnu bɛ banakɔtaa ɲɛgɛnɛsiraw la
Epiteliyali barika baara sabatili : Farikolo barika min bɛ dilan banakɔtaa ɲɛgɛnɛsiraw fɛ, o bɛ kɛ farikolo tangalan fɔlɔ ye banakisɛw ni fɛn juguw binkanni ma. Funu cogoyaw la, banakɔtaa ɲɛgɛnɛsiralabanaw ka baara dɔgɔyali bɛ na ni banakisɛw jiginni ye ani kɔnɔbara basigilenw bɔli ye, o bɛ funu jaabiw juguya ka taa a fɛ. KPV bɛ se ka banakɔtaa ɲɛgɛnɛsiralabanaw ka barika baara bonya. In vitro selilɛriw ka sɛgɛsɛgɛliw, banakɔtaa ɲɛgɛnɛsiraw furakɛra ni sitokiniw ye minnu bɛ funu dɛmɛ walasa ka funu sigida ladege, o kɛra sababu ye ka fɛnɲɛnamafagalanw jirali dɔgɔya (i n’a fɔ ZO-1 ani occludin) ani ka barika baara tiɲɛ. Nka, KPV farali bɛ ɲɔgɔndan poroteyini sirilenw jirali sabati, ka seliluw ni ɲɔgɔn cɛ jɛɲɔgɔnyaw sabati, ani ka banakɔtaa ɲɛgɛnɛsiralabanaw ka barika baara segin. DSS-induite colitis sogow la minnu furakɛra ni KPV ye, immunohistochimie ni Western blot analyse y’a jira ko tight junction proteines jirali cayara kolotuguda la ani ka banakɔtaa doncogo dɔgɔya, o b’a jira ko KPV bɛ banakɔtaa epiteliyali barika lakana in vivo, ka dɔ bɔ fɛn juguw binkanni na, ani ka funu jaabiw nɔgɔya.
Ka ɲɛgɛnɛsiralabanaw caya ani ka u dilan: Funu bɛ se ka banakɔtaa ɲɛgɛnɛsiralabanaw tiɲɛ ani ka u faga, ka banakɔtaa baara kɛcogo ɲuman tiɲɛ. KPV bɛ se ka banakɔtaa ɲɛgɛnɛsiralabanaw caya ni u dilancogo sabati. Kɔnɔnatumuw ladonni sɛgɛsɛgɛliw y’a jira ko banakɔtaa ɲɛgɛnɛsira tiɲɛnenw furakɛli ni KPV ye, o bɛ dɔ fara selilu caya kan, i n’a fɔ a jirala cogo min na Cell Counting Kit (CCK-8) fɛ. Ka fara o kan, immunofluorescence sɛgɛsɛgɛli y’a jira ko dɔ farala proliferating cell nuclear antigen (PCNA) jirali kan, o b’a jira ko seliluw tun bɛ proliferative state active la. TNBS-induite colitis ulcerative rat model kɔnɔ, furakɛli kɔfɛ ni KPV/SH-PGA hydrogel ye, histologique kɔlɔsiliw y’a jira ko tiɲɛni min kɛra kolotuguda ɲɛgɛnɛsiraw la, o dilanna, ani kripti jɔcogo seginna dɔɔni dɔɔni u cogo kɔrɔ la. O bɛ se ka kɛ sababu ye ka KPV ka epiteliyali selilɛriw caya ni u dilancogo sabati, o bɛ dɛmɛ ka funu nɔgɔya ani ka banakɔtaa yɔrɔw kɛnɛyali sabati.
Jaa 2 KPV ye furakɛli ye DSS kɔnɔboli la.
6. Oksidan kɛlɛli nɔw
Oksidan degun taamasiɲɛw ɲɛnabɔli : A ka ca a la funu bɛ taa ni oksidan degun ye, ni oksizɛni suguya minnu bɛ se ka kɛ (ROS) ani azote suguya minnu bɛ se ka kɛ (RNS) bɔli ye, o bɛ na ni oksidan tiɲɛni ye farikolokisɛw ni farikolo yɔrɔw la. KPV bɛ farikolo tangacogo jira ani a bɛ se ka oksidan degun taamasiɲɛw labɛn. Funucogo misali dɔw la, i n’a fɔ soso granuloma modɛli min bɛ sɔrɔ cotton ball fɛ ani soso kɔkanna fiɲɛbɔlan modɛli, malondialdehyde (MDA) hakɛ cayalenba ani superoxide dismutase (SOD) baara dɔgɔyali sɔrɔla funu yɔrɔw la. KPV furakɛli kɔfɛ, MDA hakɛ dɔgɔyara kosɛbɛ, ani SOD baara cayara. MDA ye tulumafɛnw bɔli ye, wa a hakɛ dɔgɔyali b’a jira ko tulumafɛnw tiɲɛni dɔgɔyara farikolokisɛw la; SOD ye farikolo tangalan nafama ye, wa a ka baara cayalenba b’a jira ko seko bɛ bonya ka ɲɛsin fɛnɲɛnamafagalanw bɔli ma. KPV bɛ se ka oksidan tiɲɛni nɔgɔya funu yɔrɔw la, a kɛtɔ ka oksidan degun hakɛw labɛn, o la, a bɛ funu kɛlɛli nɔ bila.
7. Fɛɛrɛ wɛrɛ minnu bɛ se ka kɛ
Jɛɲɔgɔnya ni melanocortin minɛbaga ye : KPV ye tripeptide ye min bɛ sɔrɔ α-MSH fɛ. Hali n’a ka banakisɛfagalanw tɛ MC1R taamasiɲɛw la yɔrɔ dɔ la, u bɛ se ka kɛ ni MC1R ye ko dɔw la. Bagan minnu bɛ MC1Re/e jira, KPV furakɛli min kɛra DSS fɛ kɔnɔboli kɔfɛ, o tun bɛ funu kɛlɛli nɔba bila hali bi, ka furakɛli kulu kɔnɔ baganw bɛɛ kisi saya ma DSS fɛ kɔnɔboli waati, o b’a jira ko KPV ka funu kɛlɛli nɔw tɛ bɔ MC1R taamasiɲɛw la a dɔgɔyalenba la. Bagan minnu ka MC1R jiracogo bɛnnen don, KPV bɛ se ka banakisɛfagalanw fanga bonya ni a ni MC1R bɛ ɲɔgɔn sɔrɔ walima k’a jigincogo taamasiɲɛw labɛn.
KPV ka banakisɛfagalanw nɔ minnu bɛ sɔrɔ
1. Jɔrɔ min bɛ banakɔtaa funu misaliw la
DSS-induite colitis model : DSS-iduced mouse colitis model (DSS-induite mouse colitis model) kɔnɔ, KPV ye banakisɛfagalanw nɔba jira. Kisɛya caman cili siratigɛ la, soso minnu furakɛra ni KPV ye, olu girinya seginna ka kɔn o ɲɛ ani ka caya ni u ni soso furakɛbaliw ta kɛra ɲɔgɔn fɛ. Kɔlɔsili minnu kɛra farikolo yɔrɔw la, olu y’a jira ko funu doncogo dɔgɔyara kosɛbɛ sogo minnu furakɛra ni KPV ye, olu ka kolotugudaw la, o min sinsinnen don ka t’a fɛ ni miyɛlopɛrokisidazi (MPO) baara dɔgɔyaliba ye. MPO ye anzimu ye min bɛ sɔrɔ neutrophils (banakisɛfagalanw) la, wa a ka baara hakɛ bɛ funubanakisɛw doncogo hakɛ jira farikolo yɔrɔw la. MPO baara dɔgɔyali KPV furakɛli kɔfɛ, o b’a jira ko neutrophiles doncogo dɔgɔyara kɔnɔbara la ani ka funu jaabiw nɔgɔya. Ni an ye sitokiniw ka ARNm jirali dɔn kolotuguda la, i n’a fɔ TNF-α ani IL-1β, a jirala ko KPV furakɛli ye dɔ bɔ kosɛbɛ o sitokiniw jirali hakɛ la. KPV ye DSS ka kɔnɔboli taamasiɲɛw nɔgɔya ka bɔ fan caman na, i n’a fɔ ka funubanakisɛw doncogo dɔgɔya, ka funufɛnw jiracogo dɔgɔya, ani ka farikolo girinya seginni sabati.
CD45RB(hi) kolotuguda funu misali : CD45RB(hi) kolotuguda funu misali la, KPV fana ye funu kɛlɛli nɔ ɲumanw jira. Nin misali in kɛra sababu ye ka T-cell minnu bɛ CD45RB jira kosɛbɛ, olu cili ye sosow la minnu farikolo tangacogo ka dɔgɔ. KPV furakɛli kɔfɛ, sosow ye funu taamasiɲɛw ɲɛnabɔ, u girinya bɛ kɛnɛya dɔɔni dɔɔni, ani farikolo yɔrɔw sɛgɛsɛgɛli y’a jira ko banakɔtaa funu yeli dɔgɔyara. KPV furakɛra kulu min ye funubanakisɛw doncogo dɔgɔyali jira ani ka kripti jɔcogo tiɲɛni dɔgɔya banakɔtaa la, o b’a jira ko KPV bɛ banakɔtaa funu nɔgɔya kosɛbɛ CD45RB(hi) fɛ ani ka banakɔtaa yɔrɔw sigicogo ni u baaracogo ɲuman segin a cogo kɔrɔ la.
TNBS-induite ulcerative colitis model : TNBS-induite ulcerative colitis rat model la, KPV fana ye furakɛli nɔba jira. KPV/SH-PGA hidrojɛli dili kɔfɛ sosow la kɔnɔbara la, kɔnɔboli taamasiɲɛw ɲɛnabɔra kosɛbɛ. Sogow ka girinya dɔgɔyali hakɛ dɔgɔyara, wa bana baarakɛcogo hakɛ (DAI) hakɛ dɔgɔyara. DAI jate bɛ taamasiɲɛw jateminɛ ka ɲɛ i n’a fɔ sosow farikolo girinya yeli, nɔgɔ cogoya, ani joli-sira-funu. A dɔgɔyali b’a jira ko KPV/SH-PGA hidrojɛli bɛ se ka TNBS ka kɔnɔboli jugumanba nɔgɔya kosɛbɛ. KPV/SH-PGA hidrojɛli furakɛli fana bɛ kolotuguda surunyali bali sosow la, ka kolotuguda miyɛlopɛrokisidazi hakɛ dɔgɔya, ani ka kolotuguda cogoya segin a cogo kɔrɔ la, i n’a fɔ epiteliyali barikalan, kriptiw ani goblɛti selilɛriw minnu ma tiɲɛ. Sitokiniw minnu bɛ banakisɛw dɛmɛ, n’olu ye TNF-α ani IL-6 ye, olu jirali fana dɔgɔyara kosɛbɛ kolotuguda la, o ye KPV ka banakisɛfagalanw nɔ jira ka t’a fɛ TNBS-induite colitis modele la.
Kuncɛli
KPV, i n’a fɔ tripeptide min bɛ ni funu kɛlɛli ye, o bɛ nɔ ɲumanw jira banakɔtaa funu kunbɛnni ni u furakɛli la ani bana suguya wɛrɛw minnu bɛ sɔrɔ funu fɛ. A ka banakisɛfagalanw bɛ tali kɛ fɛn caman na, i n’a fɔ selilɛriw ka taamasiɲɛw siraw labɛnni, oksidan kɛlɛli degun, ani apoptose ni autophagie sɛgɛsɛgɛli.
Sosow (Sɔrɔyɔrɔw).
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Fɛn min bɛ sɔrɔ ɲininiw dɔrɔn kama:
