Na Cocer Peptides 
1 mahina aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a maʻi paha. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
ʻIke kumu e pili ana iā KPV
ʻO KPV kahi tripeptide me nā waiwai anti-inflammatory koʻikoʻi, e hiki ai iā ia ke hana i kahi kuleana ma nā ʻano he nui.
Kiʻi 1 ʻO nā hopena lapaʻau o HA-KPV-NP e kūʻē iā UC ʻO ka lawelawe waha o HA-KPV-NP i hoʻokomo ʻia i loko o ka hydrogel (chitosan/alginate) hāʻawi i nā hopena therapeutic hui e kūʻē iā UC ma o ka hoʻolalelale ʻana i ka mucosa a me ka hoʻēmi ʻana i ka mumū.
Mechanism Anti-inflammatory o KPV
1. Hooponopono i na Alanui Hoailona Kelepona
Alanui Hōʻailona NF-κB: ʻO NF-κB kahi kumu transcription koʻikoʻi e pāʻani ana i kahi koʻikoʻi i nā pane inflammatory. Ke hōʻikeʻia nā pūnaewele i nā mea hoʻonāukiu, e unuhi ka NF-κB mai ka cytoplasm i ka nucleus, e hoʻomaka ana i ka unuhiʻana o nā genes cytokine pro-inflammatory. Hiki iā KPV ke kāohi i ka hoʻoulu ʻana o NF-κB. I loko o nā pūnaewele epithelial intestinal a me nā pūnaewele T kanaka, ua hoʻoulu ʻia nā cell me nā cytokines pro-inflammatory, a ua hoʻohui ʻia ʻo KPV i ka manawa like. Ke hoʻohana nei i nā ʻano e like me ka NF-κB luciferase gene reporter assays, protein immunoblotting, real-time reverse transcription polymerase chain reaction, a me ka enzyme-linked immunosorbent assay (ELISA), ua ʻike ʻia ʻo KPV ma nā nanomolar concentrations hiki ke kāohi i ka NF-κB activation, a laila e hōʻemi i ka huna o nā cytokines pro-inflammatory. He mea koʻikoʻi kēia ʻano hana i ka hoʻoponopono ʻana i ka mumū o ka ʻōpū, no ka mea, ʻo ka hoʻoulu nui ʻana o NF-κB i loko o nā cell epithelial intestinal a me nā cell immune kahi hiʻohiʻona nui o ka maʻi inflammatory bowel (IBD) a me nā maʻi ʻeha ʻē aʻe.
ʻO ke ala hōʻailona MAP kinase: ʻO ke ala hōʻailona mitogen-activated protein kinase (MAPK) kahi ala hoʻoponopono koʻikoʻi ʻē aʻe i nā pane inflammatory, me ka extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), a me p38 MAPK. Hoʻohana ʻia kēia mau kinases i ka wā e hōʻike ʻia ai nā cell i nā mea hoʻonāukiuki, e alakaʻi ana i ka phosphorylation o nā kumu transcription downstream a hoʻolaha i ka hōʻike ʻana o nā genes pili i ka mumū. Hiki iā KPV ke kaohi i ke ala hōʻailona inflammatory MAP kinase. Ke hōʻike ʻia nā cell i nā mea hoʻonāukiuki, hiki iā KPV ke kāohi i ka hoʻoulu ʻana o MAPK, e hōʻemi ana i kāna phosphorylation o nā kumu transcription downstream, a laila e hoʻemi i ka hana ʻana o nā cytokine pro-inflammatory. I loko o kahi moku'āina inflammatory, hoʻouluʻia ka p38 MAPK e alakaʻi i ka hoʻonuiʻana i ka hōʻike o nā cytokines pro-inflammatory e like me TNF-α a me IL-6, aʻo KPV hiki ke kāohi i ka hana p38 MAPK, e ho'ēmi i ka huna o kēia mau cytokines a ma laila e ho'ēmi ai i ka pane inflammatory.
2. Nā hopena i hoʻopili ʻia e ka transporter cell
Mea lawe PepT1: ʻO PepT1 kahi mea lawe di/tripeptide i hōʻike pinepine ʻia i loko o ka ʻōpū liʻiliʻi akā hoʻokomo ʻia i loko o ke kolonā i ka wā o IBD. Hoʻopili ʻia nā hopena anti-inflammatory o KPV e PepT1. Ma nā hoʻokolohua uptake, ua hoʻohana ʻia ʻo KPV anuanu ma ke ʻano he mea hoʻokūkū hoʻokūkū no ka hPepT1 ma ke ʻano he substrate lepili radioactive, a i ʻole [⊃3;H]KPV i hoʻohana ʻia no ka hoʻoholo ʻana i nā ʻano kinetic o ka lawe ʻana o KPV. KPV komo i loko o ka immune cell a me ka intestinal epithelial cell ma o hPepT1. Hōʻike kēia i ka PepT1, ma ke ʻano he transporter, hoʻomaʻamaʻa i ke komo ʻana o KPV i loko o nā cell e hoʻokō i kāna mau hopena anti-inflammatory. Ke kāohi ʻia ka hana PepT1, e emi ana ka nui o ke komo ʻana o KPV i nā pūnaewele, a ua nāwaliwali nā hopena anti-inflammatory. I loko o nā hiʻohiʻona pūnaewele me ka hoʻokuʻu ʻana o ka ʻōlelo PepT1, ʻoiai ke lawelawe ʻia ma ka ʻike like, hōʻike ʻo KPV i ka hōʻemi nui ʻana i nā hopena inhibitory i ka hoʻoulu ʻana o NF-κB a hoʻemi i ka huna ʻana o nā cytokine pro-inflammatory i hoʻohālikelike ʻia me nā cell me ka ʻōlelo PepT1 maʻamau, e hōʻoia hou ana i ka hana mediating koʻikoʻi o PepT1 i ka mīkini anti-inflammatory o KPV.
3. Hoʻoponopono i nā cytokine inflammatory
Ka pale ʻana i nā cytokine pro-inflammatory: Hiki i ka KPV ke kāohi nui i ka hana a me ka hoʻokuʻu ʻana o nā cytokine pro-inflammatory. ʻO TNF-α kahi cytokine kī i loko o nā pane inflammatory, hiki ke hoʻoulu i nā cell immune, hoʻoulu i ka hana ʻana o nā cytokine pro-inflammatory ʻē aʻe, a me ka hōʻino ʻana i ke kino. Ma nā ʻano hoʻohālike inflammatory like ʻole, ua hoʻemi nui ʻia nā pae hōʻike o TNF-α ma hope o ka mālama ʻana iā KPV. No ka laʻana, ma ka sodium sulfate-induced mouse colitis model, lapaʻau ʻia me KPV ka hopena i ka hōʻemi nui ʻana o ka hōʻike mRNA o TNF-α i loko o ka ʻiʻo colon, e like me ka ʻike ʻia e ka RT-PCR manawa maoli, a me ka emi nui o ka ʻike protein o TNF-α i ka serum, e like me ka ʻike ʻia e ELISA. ʻO IL-1β, IL-6, a me nā cytokine pro-inflammatory ʻē aʻe i kāohi ʻia e KPV. Hiki i ka IL-1β ke hoʻoulu i kahi hopena cascade inflammatory, e hoʻolaha ana i ka hoʻokuʻu ʻana i nā mea hoʻolaha ʻē aʻe. Hiki i ka KPV ke ho'ēmi i kona hōʻike a me ka hunaʻana i nāʻiʻo inflammatory, a laila e hoʻohaʻahaʻa i ka ikaika o ka pane inflammatory.
Hoʻolaha i nā cytokine anti-inflammatory: Ma waho aʻe o ka pale ʻana i nā cytokine pro-inflammatory, hiki nō hoʻi iā KPV ke hoʻoikaika i ka hōʻike o nā cytokine anti-inflammatory. ʻO Interleukin-10 (IL-10) kahi cytokine anti-inflammatory koʻikoʻi e hiki ke kāohi i ka hoʻoulu ʻana o nā cell immune a hoʻemi i ka hana ʻana o nā cytokine pro-inflammatory.
4. Hoʻoponopono i nā pūnaewele immune
Hoʻoponopono i ka hana o ka cell T: He kuleana koʻikoʻi nā cell T i nā pane kūlohelohe a me ka hoʻoponopono ʻana. Ma lalo o nā kūlana inflammatory, ho'ālaʻia nā pūnaewele T a hūnā i nā cytokine pro-inflammatory. Ua hōʻike nā haʻawina hiki iā KPV ke hoʻoponopono i ka hana cell T. I nā hoʻokolohua me ke kanaka T cell line Jurkat, i ka wā i hoʻouluʻia ai nā pūnaewele Jurkat me nā cytokines pro-inflammatory,ʻo ka hoʻohuiʻana o KPV i kāohi i ka hoʻouluʻana o T cell a ho'ēmi i ka huna o nā cytokines pro-inflammatory e like me IFN-γ. Hiki ke hoʻokō ʻia kēia ma ke kāohi ʻana i nā ala hōʻailona NF-κB a me MAPK i loko o nā pūnae T. Eia kekahi, i kekahi mau holoholona holoholona, e like me ka CD45RB(hi) colonic inflammation model, KPV treatment can regulate T cell infiltration and function in the contine, hoemi i ka ma'i-pili T cell subsets e like me Th1 a me Th17 cell, a hoonui i ka hapa o na keena T regulatory, pela e hooluolu ai i ka ma'i o ka opu.
Ka hoʻololi ʻana o ka hana macrophage: ʻO nā macrophages he mau cell immune koʻikoʻi i ka pane inflammatory a hiki ke hoʻokaʻawale ʻia i loko o nā macrophages M1 i hoʻoikaika ʻia a me nā macrophages M2 i hoʻololi ʻia e pili ana i ko lākou kūlana hoʻāla. Hoʻopili nā M1 macrophages i ka nui o nā cytokines pro-inflammatory, ʻoiai ʻo M2 macrophages i loaʻa nā hana anti-inflammatory a me nā hana hoʻoponopono kiko. Hiki iā KPV ke hoʻoponopono i ka polarization macrophage. Ua hōʻike ʻia nā hoʻokolohua in vitro i ka wā i hoʻoulu ʻia ai nā macrophages me ka lipopolysaccharide (LPS) e polarize i ke ʻano M1, ʻo ka hui pū ʻana o KPV i kāohi i ka macrophage polarization i ke ʻano M1, hoʻemi i ka hōʻike ʻana o nā māka macrophage M1, ʻoiai e hoʻolaha ana i kā lākou polarization i ke ʻano M2, e hoʻonui ana i ka hōʻike o M2s-Argina-argina1. I loko o nā vivo inflammatory models, e like me DSS-induced colitis i nā ʻiole, mālama ʻia me KPV ka hopena o nā macrophages i loko o ka ʻiʻo colon e polarizing i ke ʻano M2, a laila e hoʻēmi ana i nā pane ʻeha a me ka hoʻoikaika ʻana i ka hoʻoponopono kino.
5. Nā hopena pale ma nā pūnaewele epithelial intestinal
Hoʻonui i ka hana pale epithelial: ʻO ka pale kino i hoʻokumu ʻia e nā cell epithelial intestinal ma ke ʻano he laina mua o ka pale ʻana i ka pathogen a me ke komo ʻana o nā mea ʻino. I loko o nā moku'āina inflammatory, ka hana ʻino ʻana o ka ʻōpū epithelial barrier e alakaʻi i ka translocation bacteria a me ka leakage endotoxin, e hoʻonui hou i nā pane inflammatory. Hiki i ka KPV ke hoʻonui i ka hana pale o nā pūnaewele epithelial intestinal. ʻO nā hoʻokolohua in vitro cell, kahi i mālama ʻia ai nā laina cell epithelial intestinal me nā cytokine pro-inflammatory e hoʻohālikelike i kahi ʻona ʻona, ua hopena i ka hōʻemi ʻana o nā protein junction paʻa (e like me ZO-1 a me ka occludin) a me ka hana pale. Eia nō naʻe, ʻo ka hoʻohui ʻana o KPV e hoʻomau i ka hōʻike ʻana i nā protein junction paʻa, hoʻonui i nā pilina intercellular, a hoʻihoʻi i ka hana pale o nā ʻāpana epithelial intestinal. I loko o ka DSS-induced colitis mice i mālama ʻia me KPV, immunohistochemistry a me Western blot analysis i hōʻike i ka hoʻonui ʻana i ka hōʻike ʻana o nā protein junction paʻa i loko o ka ʻiʻo colon a me ka hoʻohaʻahaʻa ʻana o ka ʻōpū, e hōʻike ana i ka mālama ʻana o KPV i ka pale epithelial intestinal in vivo, hoʻemi i ka hoʻouka ʻana o nā mea ʻino, a hoʻēmi i nā pane inflammatory.
Ke hoʻoikaika nei i ka hoʻonui a me ka hoʻoponopono hou ʻana o ka epithelial cell: Hiki i ka mumū ke hana i ka pōʻino a me ka make o nā cell epithelial intestinal, e hōʻino ana i ka hana maʻamau o ka ʻōpū. Loaʻa iā KPV ka hiki ke hoʻoikaika i ka hoʻonui a me ka hoʻoponopono ʻana i nā ʻāpana epithelial intestinal. Ua hōʻike ʻia nā hoʻokolohua moʻomeheu in vitro cell i ka mālama ʻana i nā cell epithelial intestinal i pōʻino me ka KPV i hoʻonui i ka hoʻonui ʻana o ke kelepona, e like me ka ʻike ʻia e ka Cell Counting Kit (CCK-8). Hoʻohui hou, hōʻike ʻia ka loiloi immunofluorescence i ka hoʻonui ʻana o ka proliferating cell nuclear antigen (PCNA), e hōʻike ana aia nā cell i kahi kūlana proliferative ikaika. I loko o ka TNBS-induced ulcerative colitis rat model, ma hope o ka mālama ʻana me KPV/SH-PGA hydrogel, ua hōʻike ʻia nā hiʻohiʻona o ka mōʻaukala ua hoʻoponopono ʻia ka pōʻino o nā pūnana epithelial colonic, a ua hoʻi mālie nā hale crypt i ka maʻamau. Pili paha kēia i ka hoʻolaha ʻana o KPV i ka hoʻonui ʻana a me ka hoʻoponopono hou ʻana o nā cell epithelial, e kōkua ana i ka hoʻohaʻahaʻa ʻana i ka mumū a me ka hoʻolaʻa ʻana i ka ʻiʻo o ka ʻōpū.
Hōʻike 2 KPV he therapeutic i ka DSS colitis.
6. Nā hopena antioxidant
Hoʻoponopono i nā hōʻailona pili i ke koʻikoʻi oxidative: Hoʻopili pinepine ʻia ka inflammatory me nā hopena koʻikoʻi oxidative, me ka hoʻonui ʻana i ka hana o nā ʻano oxygen reactive (ROS) a me nā ʻano nitrogen reactive (RNS), e alakaʻi ana i ka pōʻino oxidative i nā cell a me nā kiko. Hōʻike ʻo KPV i nā hopena antioxidant a hiki ke hoʻoponopono i nā hōʻailona pili i ke kaumaha oxidative. I kekahi mau hi'ohi'ona ho'onapo'o, e like me ke kŘkohu 'iole granuloma i ho'okomo 'ia i ka pulupulu a me ke kükohu 'iole dorsal air sac synovitis i ho'okomo 'ia i ka pulupulu, ka pae ki'eki'e o malondialdehyde (MDA) a me ka hana ho'emi superoxide dismutase (SOD) i 'ike 'ia i loko o ka 'i'o inflammatory. Ma hope o ka mālama ʻana iā KPV, ua emi nui nā pae MDA, a ua hoʻonui ʻia ka hana SOD. ʻO MDA kahi huahana o ka lipid peroxidation, a ʻo kona mau pae i hōʻemi ʻia e hōʻike ana i ka emi ʻana o ka lipid peroxidation pōʻino i nā cell; ʻO ka SOD kahi enzyme antioxidant koʻikoʻi, a ʻo kāna hana hoʻonui e hōʻike ana i ka hiki ke hoʻonui i ka hiki ke scavenge i nā radical manuahi. Hiki i ka KPV ke ho'ēmi i ka pōʻino oxidative i loko o nā ʻiʻo inflammatory ma o ka hoʻoponopono ʻana i nā pae koʻikoʻi oxidative, a laila e hoʻokō ai i nā hopena anti-inflammatory.
7. Nā Mekini Hiki ʻē aʻe
Ka pilina me ka melanocortin receptor: ʻO KPV kahi tripeptide i loaʻa mai ka α-MSH. ʻOiai ua kūʻokoʻa ʻia kona mau hopena anti-inflammatory i ka hōʻailona MC1R, pili paha lākou me MC1R i kekahi mau ʻano. I nā holoholona e hōʻike ana i ka MC1Re/e, ʻo ka mālama ʻana i ka KPV ma hope o ka colitis i hoʻokomo ʻia e DSS ua hoʻokō mau i nā hopena anti-inflammatory koʻikoʻi, e hoʻopakele ana i nā holoholona āpau i ka hui lapaʻau mai ka make i ka wā DSS-induced colitis, e hōʻike ana he kūʻokoʻa nā hopena anti-inflammatory o KPV i ka hōʻailona MC1R. I nā holoholona me ka hōʻike MC1R maʻamau, hiki i ka KPV ke hoʻonui i nā hopena anti-inflammatory ma o ka launa pū ʻana me MC1R a i ʻole ka hoʻoponopono ʻana i kona mau ala hōʻailona lalo.
Nā hopena anti-inflammatory o KPV
1. Hana i nā ʻano hoʻohālike o ka ʻōpū
DSS-induced colitis model: I ka DSS-induced mouse colitis model, ua hōʻike ʻo KPV i nā hopena anti-inflammatory koʻikoʻi. Ma ke ʻano o ka hoʻololi ʻana o ke kaumaha, ua hoʻihoʻi hou nā ʻiole i mālama ʻia me KPV i ko lākou kaumaha ma mua a i ka nui o ka hoʻohālikelike ʻia me nā ʻiole i mālama ʻole ʻia. Ua hōʻike ʻia nā hiʻohiʻona mōʻaukala i ka hōʻemi nui ʻana o ka infiltration inflammatory i loko o ka ʻiʻo colon o nā ʻiole i mālama ʻia e KPV, i hōʻoia hou ʻia e ka emi nui o ka hana myeloperoxidase (MPO). ʻO MPO kahi enzyme i loaʻa i nā neutrophils, a ʻo kāna pae hana e hōʻike i ka nui o ka infiltration cell inflammatory i loko o nā ʻiʻo. ʻO ka hōʻemi ʻana i ka hana MPO ma hope o ka mālama ʻana i ka KPV e hōʻike ana i ka emi ʻana o ka neutrophil infiltration i loko o ka ʻiʻo colon a hoʻopau i nā pane ʻeha. Ma ka ʻike ʻana i ka hōʻike mRNA o nā cytokine pro-inflammatory i loko o ka ʻiʻo colonic, e like me TNF-α a me IL-1β, ua ʻike ʻia ua hoʻemi nui ka mālama KPV i nā pae hōʻike o kēia mau cytokine pro-inflammatory. Ua hōʻoluʻolu ʻo KPV i nā hōʻailona colitis i hoʻokomo ʻia e DSS mai nā ʻano he nui, me ka hōʻemi ʻana i ka infiltration cell inflammatory, ka hoʻohaʻahaʻa ʻana i ka hōʻike kumu inflammatory, a me ka hoʻoikaika ʻana i ke kaumaha.
ʻO CD45RB(hi) ke kumu hoʻonaʻauao colonic: Ma ka CD45RB(hi) hoʻohālike ʻaʻa ʻana o ka colonic, hōʻike pū ʻo KPV i nā hopena anti-inflammatory maikaʻi. Hoʻokomo ʻia kēia ʻano hoʻohālike e ka hoʻoili ʻana i nā pūnae T e hōʻike nui ana i ka CD45RB i loko o nā ʻiole immunodeficient. Ma hope o ka mālama ʻana iā KPV, ua hōʻike ʻia nā ʻiole i nā hōʻailona inflammatory maikaʻi, ka hoʻihoʻi ʻana i ke kaumaha, a me ka nānā ʻana i ka mōʻaukala i hōʻike ʻia i ka emi ʻana o ka hoʻololi ʻana o ka ʻōpū. Ua hōʻike ka hui i mālama ʻia e KPV i ka emi ʻana o ka infiltration cell inflammatory a me ka hōʻemi ʻana i ka pōʻino o ka crypt i loko o nā ʻiʻo ʻōpū, e hōʻike ana ua hoʻopau maikaʻi ʻo KPV i ka CD45RB(hi) -induced intestinal mumū a hoʻihoʻi i ka hana a me ka hana maʻamau.
TNBS-induced ulcerative colitis model: I loko o ka TNBS-induced ulcerative colitis rat model, KPV kekahi i hōʻike i nā hopena therapeutic koʻikoʻi. Ma hope o ka lawelawe ʻana i ka hydrogel KPV/SH-PGA ma ka pololei i nā ʻiole, ua hoʻomaikaʻi maikaʻi nā hōʻailona colitis. Ua hoʻemi ʻia ke kiʻekiʻe o ka pohō kaumaha o nā ʻiole, a ua emi ka helu helu hana maʻi (DAI). Noʻonoʻo ka helu DAI i nā hōʻailona e like me ka hoʻololi ʻana i ke kaumaha o ke kino ʻiole, nā ʻano fecal, a me ka hematochesia. Hōʻike kona hōʻemi ʻana e hiki i ka KPV/SH-PGA hydrogel ke hoʻohaʻahaʻa pono i ka paʻakikī o ka TNBS-induced ulcerative colitis. Kāohi ʻo KPV/SH-PGA hydrogel i ka pōkole ʻana o ka colon i nā ʻiole, hoʻemi ʻia nā pae myeloperoxidase colonic, a hoʻihoʻi hou i ke ʻano morphological colonic, me ka pale epithelial, nā crypts, a me nā ʻāpana kīʻaha paʻa. ʻO ka'ōlelo o nā cytokines pro-inflammatory, TNF-α a me IL-6, i loko o kaʻiʻo colonic ua hoʻemi nuiʻia, e hōʻike hou ana i ka hopena anti-inflammatory o KPV i ka TNBS-induced ulcerative colitis model.
Ka hopena
ʻO KPV, ma ke ʻano he tripeptide me nā waiwai anti-inflammatory, e hōʻike ana i nā hopena hoʻohiki i ka pale ʻana a me ka mālama ʻana i ka ʻāʻī o ka ʻōpū a me nā maʻi ʻē aʻe e pili ana i ka mumū. ʻO kāna mau hana anti-inflammatory e pili ana i nā ʻano he nui, me ka hoʻoponopono ʻana i nā ala hōʻailona cellular, ke kaumaha antioxidant, a me ka modulation o apoptosis a me autophagy.
Nā kumu
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[5] Kannengiesser K, Maaser C, Heidemann J, et al. Loaʻa i ka melanocortin tripeptide KPV ka mana anti-inflammatory i nā hiʻohiʻona murine o ka maʻi ʻeha ʻeha [J]. Nā maʻi ʻeha o ka ʻōpū, 2008,14(3):324-331.DOI:10.1002/ibd.20334.
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