Los ntawm Cocer Peptides 
29 hnub dhau los
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam
ARA-290 yog 11-amino acid linear non-hematopoietic polypeptide muab los ntawm erythropoietin (EPO). Nws exerts ntau yam kab mob lom los ntawm tshwj xeeb khi rau lub innate kho receptor (IRR). Tsis zoo li EPO, ARA-290 khaws cov tshuaj tiv thaiv kab mob thiab cov ntaub so ntswg tiv thaiv cov yam ntxwv ntawm EPO.
Daim duab 1 Lub biology ntawm lub innate kho receptor yog tus cwj pwm los ntawm lub sij hawm thiab spatial sib cais ntawm nws receptor subunits, uas koom ua ke los tsim lub innate kho receptor thiab nws endogenous ligand, hyposialated erythropoietin (hEPO).
Mechanism ntawm Action
(1) Anti-inflammatory teebmeem
Inhibition of inflammatory cell activation: Nyob rau hauv ntau yam inflammatory qauv, ARA-290 qhia lub peev xwm los inhibit inflammatory cell ua. Piv txwv li, hauv cov qauv kev nyuaj siab nas vim yog kev ntxhov siab ntev, kev tswj hwm niaj hnub ntawm ARA-290 thim rov qab qhov nce ntawm ntau zaus thiab / lossis tus naj npawb ntawm CD11b⁺Ly6Gʰⁱ neutrophils thiab CD11b⁺Ly6Cʰⁱ monocytes hauv cov pob txha pob txha thiab meninges tshwm sim los ntawm chronic stresses. Kev ua kom muaj zog, yog li txhim kho kev nyuaj siab zoo li tus cwj pwm hauv nas, nrog cov teebmeem zoo ib yam li cov tshuaj fluoxetine.
Kev tswj hwm ntawm inflammatory factor secretion: ARA-290 zoo tswj qhov tso tawm ntawm cov kab mob inflammatory. Nyob rau hauv ib qho systemic lupus erythematosus (SLE) nas qauv, ARA-290 txo cov ntshav cytokines IL-6, MCP-1, thiab TNF-α, ua rau muaj kev cuam tshuam loj heev rau cov tshuaj tiv thaiv kab mob autoantibodies (ANAs) thiab tiv thaiv ob npaug-kab DNA autoantibodies, txo cov tsos mob thiab kev txhim kho IgGG. Hauv cov qauv cisplatin-induced nephrotoxicity, kev kho ua ntej nrog ARA-290 txo qis ntawm pro-inflammatory cytokines xws li TNF-α, IL-6, thiab IL-1β, yog li txo qis cov lus teb rau hauv cov ntaub so ntswg.
Inhibition of inflammatory signaling pathways: ARA-290 tuaj yeem siv nws cov tshuaj tiv thaiv kab mob los ntawm inhibiting qee yam kab mob ntsig txog kev taw qhia. Raws li kev khi rau IRR, nws tuaj yeem cuam tshuam rau cov xwm txheej hauv qab dej molecular cuam tshuam nrog cov lus teb inflammatory, yog li thaiv kev sib kis thiab nthuav dav ntawm cov teeb liab inflammatory thiab thaum kawg alleviating inflammatory reactions.
(2) Immunomodulatory teebmeem
Kev cai ntawm macrophage muaj nuj nqi: ARA-290 plays lub luag haujlwm tseem ceeb hauv kev ua haujlwm macrophage. Kev sim hauv vitro qhia tau hais tias nws tuaj yeem cuam tshuam qhov ua kom mob ntawm macrophages thaum txhawb nqa lawv txoj haujlwm phagocytic rau apoptotic hlwb. Nyob rau hauv tus qauv SLE nas, ARA-290 txo tus naj npawb ntawm apoptotic hlwb nyob rau hauv ob lub raum los ntawm kev tswj cov macrophage muaj nuj nqi, uas tej zaum yuav yog ib qho ntawm cov txheej txheem tseem ceeb hauv qab nws txoj kev txhim kho ntawm SLE cov tsos mob.
Kev cuam tshuam ntawm lub cev tiv thaiv kab mob sib npaug: Hauv qee tus qauv kab mob, ARA-290 tuaj yeem ua rau lub cev tiv thaiv kab mob los ntawm kev hloov pauv qhov sib npaug ntawm cov neeg tiv thaiv kab mob sib txawv. Nyob rau hauv tus qauv kev nyuaj siab nas uas muaj kev ntxhov siab ntev ntev, ARA-290 txoj cai tswj hwm ntawm cov kab mob tiv thaiv kab mob hauv cov pob txha thiab meninges pab kho lub cev tiv thaiv kab mob sib npaug, yog li txo qhov cuam tshuam ntawm cov lus teb rau ntawm lub paj hlwb thiab txhim kho kev nyuaj siab zoo li tus cwj pwm.
Daim duab 2 Kev ua kom lub cev kho cov receptors txo cov neeg kho tshuab allodynia tom qab kev raug mob paj hlwb (SNI) hauv cov nas.
(3) Cov ntaub so ntswg tiv thaiv
Txhawb kev kho cell thiab rov tsim dua tshiab: ARA-290 qhia txog kev muaj peev xwm los txhawb kev kho cell thiab rov tsim dua tshiab hauv ntau yam qauv kev raug mob. Hauv cov kab mob ntshav qab zib ko taw (DFU) cov qauv nas, daim ntawv thov hauv zos ntawm ARA-290 ua rau nrawm nrawm kaw qhov txhab, nce collagen thiab protein cov ntsiab lus, thiab txhawb kev kho mob ntawm daim tawv nqaij. Qhov no yog ua tiav los ntawm kev ua kom IRR, uas nyob rau hauv lem pib ib tug series ntawm intracellular signaling pathways, txhawb cell proliferation, migration, thiab sib txawv, thaum kawg ua rau cov ntaub so ntswg kho.
Txo oxidative kev nyuaj siab puas tsuaj: Oxidative stress plays lub luag hauj lwm tseem ceeb nyob rau hauv kev loj hlob ntawm ntau yam kab mob o. ARA-290 tuaj yeem txo oxidative kev ntxhov siab vim kev puas tsuaj rau cov ntaub so ntswg. Hauv kev tshawb fawb ntawm atherosclerosis (AS), ARA-290 tuaj yeem cuam tshuam kev tsim cov pa oxygen reactive (ROS) los ntawm macrophages nyob rau hauv cov mob inflammatory, txo oxidative kev nyuaj siab, thiab txo kev puas tsuaj rau endothelial hlwb los ntawm oxidatively hloov lipoproteins, yog li inhibiting kev loj hlob ntawm AS. Hauv cov qauv cisplatin-induced nephrotoxicity, ARA-290 alleviates oxidative stress-induced raum puas tsuaj los ntawm kev ua kom cov tshuaj tiv thaiv kab mob antioxidant, suav nrog glutathione peroxidase (GPx) thiab superoxide dismutase (SOD), thiab txo cov malondialdehyde (MDA) thiab ROS qib.
Daim ntawv thov
(1) Neurological Disorders
Kev nyuaj siab ntxhov plawv: Kev tshawb fawb hauv cov qauv kev nyuaj siab uas ua rau muaj kev nyuaj siab ntev tau pom tias ARA-290 txhim kho kev nyuaj siab zoo li cov nas, qhia txog nws cov peev txheej hauv kev kho cov kev nyuaj siab. Lub pathogenesis ntawm kev nyuaj siab yog ze ze rau cov lus teb inflammatory, thiab ARA-290's anti-inflammatory thiab immunomodulatory cov teebmeem yuav muab cov tswv yim tshiab rau kev kho kev nyuaj siab, muaj peev xwm tsim mus rau hauv cov tshuaj antidepressant tshiab.
Ischemic Stroke: Nyob rau hauv nruab nrab cerebral artery occlusion (MCAO) tus qauv nas, ARA-290 nthuav tawm cov teebmeem neuroprotective zoo ib yam li cov erythropoietin (EPO), txo qis neuronal apoptosis thiab inflammatory cytokine theem hauv hlwb. Cov teebmeem neuroprotective ntawm ARA-290 yog kho los ntawm β-adrenergic receptor (βCR) thiab tsis txhob ua rau erythropoiesis. Qhov no muab cov phiaj xwm kev cuam tshuam tshiab thiab cov tshuaj muaj peev xwm kho tau rau kev kho mob stroke ischemic.
(2) Cov kab mob autoimmune
Systemic lupus erythematosus (SLE): Kev tshawb fawb hauv SLE nas qauv qhia tau hais tias ARA-290 txhim kho SLE cov tsos mob, inhibits zus tau tej cov autoantibodies, txo lub raum mob thiab puas, thiab tsis txhawb hematopoiesis. Muab cov kev txwv tam sim no hauv kev kho SLE, ARA-290 tuav cov lus cog tseg raws li cov tshuaj tshiab rau SLE, muab cov neeg mob kev kho mob zoo dua.
(3) Cov teeb meem mob ntshav qab zib
Mob ntshav qab zib ko taw rwj: Hauv cov qauv nas ntawm cov kab mob ntshav qab zib ko taw, daim ntawv thov hauv zos ntawm ARA-290 txhawb kev kho qhov txhab zoo, txhim kho cov piam thaj thiab lipid metabolism, thiab txo cov qib inflammatory. Qhov no qhia tau hais tias ARA-290 muaj peev xwm siv tau rau kev kho mob ntshav qab zib mob qhov txhab kho, muab cov kev nkag siab tshiab thiab cov txheej txheem rau kev tswj cov kab mob ntshav qab zib ko taw.
(4) kab mob raum
Cisplatin-induced nephrotoxicity: Hauv cov qauv cisplatin-induced nephrotoxicity, ARA-290 alleviated cisplatin-induced lub raum puas los ntawm nws cov tshuaj tiv thaiv apoptotic, tiv thaiv kev mob, thiab antioxidant. Qhov no qhia tias ARA-290 tuaj yeem ua lub tswv yim tshiab rau kev tiv thaiv thiab kho cisplatin vim raug mob raum mob, muab kev tiv thaiv raum rau cov neeg mob uas tau txais kev kho mob cisplatin.
(5) Cov kab mob plawv
Atherosclerosis: Ob qho tib si hauv vitro thiab hauv vivo thwmsim qhia tias ARA-290 zoo inhibits inflammatory teb, reactive oxygen hom tsim, apoptosis, tsiv teb tsaws, thiab ua npuas ncauj cell tsim nyob rau hauv nas macrophages, nrog rau kev loj hlob ntawm cov quav hniav nyob rau hauv nas aortas. Qhov no qhia tau hais tias ARA-290 muaj peev xwm siv tau rau kev tiv thaiv atherosclerosis thiab tej zaum yuav raug tsim los ua cov tshuaj tshiab rau kev tiv thaiv thiab kho cov kab mob plawv.
Xaus
Hauv cov ntsiab lus, ARA-290, raws li peptide nrog cov tshuaj tiv thaiv tshwj xeeb, immunomodulatory, thiab cov ntaub so ntswg tiv thaiv, muaj qee yam kev kho mob hauv kev kho mob ntawm ntau yam kab mob ntsig txog mob.
Qhov chaw
[1] Wang R, Yang Z, Huang Y, et al. Erythropoietin-derived peptide ARA290 kho cov ntaub so ntswg hlwb tiv thaiv los ntawm $eta$-hom receptor nyob rau hauv nas nrog cerebral ischemic stroke[J]. Cns Neuroscience & Therapeutics, 2024, 30. https://api.semanticscholar.org/CorpusID: 268414491
[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, et al. Mechanistic Approach for Protective Effect of ARA290, Ib qho tshwj xeeb Ligand rau Erythropoietin / CD131 Heteroreceptor, tiv thaiv Cisplatin-Induced Nephrotoxicity, Kev Koom Tes ntawm Apoptosis thiab Inflammation Pathways [J]. Inflamation, 2023,46(1):342-358.DOI:10.1007/s10753-022-01737-7.
[3] Mashreghi M, Bayrami Z, Sichani N, et al. Ib qho kev tshawb nrhiav hauv vivo ntawm lub qhov txhab-kho kev ua haujlwm ntawm Specific ligand rau qhov kho qhov muag hauv lub cev, ARA290, siv tus qauv tsiaj mob ntshav qab zib [M]. 2023.10.21203/rs.3.rs-2520194/v1.
[4] Xu G, Zou T, Deng L, et al. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-zoo li tus cwj pwm thiab mob hauv nas[J]. Frontiers in Pharmacology, 2022,13:896601.DOI:10.3389/fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, et al. Non-erythropoietic erythropoietin-derived peptide tiv thaiv nas los ntawm kab mob lupus erythematosus [J]. Phau ntawv Journal of Cellular and Molecular Medicine, 2018,22(7):3330-3339.DOI:10.1111/jcmm.13608.
[6] Dahan A, Brines M, Niesters M, et al. Targeting lub innate kho receptor los kho neuropathy [J]. Pain Reports, 2016,1(1):e566.DOI:10.1097/PR9.0000000000000566.
[7] Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological mob los ntawm lub hom phiaj TRPV1 channel: Kev koom ua ke ntawm kev tiv thaiv kab mob thiab nociception [J]. Peptides, 2016,76:73-79.DOI:10.1016/j.peptides.2016.01.003.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
