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ụbọchị 29 gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
ARA-290 bụ 11-amino acid linear na-abụghị hematopoietic polypeptide sitere na erythropoietin (EPO). Ọ na-egosipụta mmetụta dị iche iche nke ndu site na ijikọ kpọmkwem na ihe nnabata nrụzi ebumpụta ụwa (IRR). N'adịghị ka EPO, ARA-290 na-ejigide mgbochi mkpali na ọrụ nchebe anụ ahụ nke EPO.
Ihe onyonyo 1 Ihe omuma ihe omumu nke ihe nleba anya n’adighi nma bu nkewa nke oge na nke oghere nke subunits nke nnata ya, nke na-emekorita iji mebe ihe nrụzi nke ebumpụta ụwa na ligand endogenous, hyposialated erythropoietin (hEPO).
Usoro nke Omume
(1) Mmetụta mgbochi mkpali
Mgbochi nke cell cell na-eme ihe: N'ụdị dị iche iche na-egbuke egbuke, ARA-290 na-egosipụta ikike igbochi mkpali cell. Dịka ọmụmaatụ, na ụdị ịda mbà n'obi nke oke nke nrụgide na-adịghị ala ala kpatara, nchịkwa kwa ụbọchị nke ARA-290 weghaara mmụba nke ugboro na / ma ọ bụ ọnụ ọgụgụ CD11b⁺Ly6Gʰⁱ neutrophils na CD11b⁺Ly6Cʰⁱ monocytes na ụmị ọkpụkpụ na meninges kpatara nrụgide na-adịghị ala ala, ma na-ebelata nrụgide microglial. omume ịda mbà n'obi dị ka ụmụ oke, nwere mmetụta yiri nke fluoxetine.
Iwu nke ihe nzuzo na-akpata mkpali: ARA-290 na-achịkwa nke ọma na nzuzo nke ihe ndị na-emepụta ihe. N'ime usoro lupus erythematosus (SLE), ARA-290 belatara ọkwa serum nke cytokines na-egbu egbu IL-6, MCP-1, na TNF-α, na-egbochi serum antinuclear autoantibodies (ANAs) na mgbochi abụọ-stranded DNA autoantibodies, belata IgG, na Cd. N'ụdị nephrotoxicity nke cisplatin na-ebute, tupu ọgwụgwọ ya na ARA-290 belatara ọkwa nke cytokines pro-inflammatory dị ka TNF-α, IL-6, na IL-1β, si otú ahụ na-ebelata nzaghachi mkpali na anụ ahụ akụrụ.
Mgbochi nke ụzọ mgbaàmà na-egbuke egbuke: ARA-290 nwere ike ịmepụta mmetụta ya na-eme ka ọ ghara ịmịnye ya site na igbochi ụfọdụ ụzọ mgbaàmà metụtara mbufụt. Mgbe ejikọtara ya na IRR, ọ nwere ike imetụta usoro ihe omume molekụla mgbada nke jikọtara ya na nzaghachi mkpali, si otú a na-egbochi nnyefe na mmụba nke mgbaàmà mkpali na n'ikpeazụ na-ebelata mmeghachi omume mkpali.
(2) Mmetụta immunomodulatory
Iwu nke ọrụ macrophage: ARA-290 na-arụ ọrụ nchịkwa dị mkpa na ọrụ macrophage. Nnwale in vitro na-egosi na ọ nwere ike igbochi mkpali mkpali nke macrophages mgbe ha na-akwalite ọrụ phagocytic ha na mkpụrụ ndụ apoptotic. Na ụdị òké SLE, ARA-290 na-ebelata ọnụ ọgụgụ nke mkpụrụ ndụ apoptotic na akụrụ site n'ịhazi ọrụ macrophage, nke nwere ike ịbụ otu n'ime usoro ndị bụ isi na-akpata mmelite nke mgbaàmà SLE.
Mmetụta na nguzozi cell na-alụso ọrịa ọgụ: N'ụdị ọrịa ụfọdụ, ARA-290 nwere ike ịkpata mmetụta nchịkwa nke mgbochi site n'ịgbanwe nguzozi n'etiti ọnụ ọgụgụ sel mgbochi dị iche iche. N'ime ụdị ịda mbà n'obi na-akpata nrụgide na-adịghị ala ala, ụkpụrụ ARA-290 nke ọnụ ọgụgụ ndị na-adịghị ahụkebe kpọmkwem n'ime ụmị ọkpụkpụ na meninges na-enyere aka weghachite nguzozi nke cell, si otú a na-ebelata mmetụta nke nzaghachi mkpali na usoro ụjọ ahụ na imeziwanye omume ịda mbà n'obi.
Ọnụọgụ 2 Ịkwalite ndị na-anabata nrụzi ebumpụta ụwa na-ebelata allodynia n'ibu mgbe ọ gbasịrị mmerụ ahụ (SNI) na oke.
(3) Mmetụta nchebe anụ ahụ
Na-akwalite nrụzi cell na mmeghari ohuru: ARA-290 na-egosiputa ikike ịkwalite nrụzi cell na imeghari n'ụdị mmerụ ahụ dị iche iche. N'ime ụdị oke oke ọnya ụkwụ na-arịa ọrịa shuga (DFU), ngwa mpaghara nke ARA-290 na-eme ka mmechi ọnya dịkwuo ngwa ngwa, na-abawanye ọdịnaya nke collagen na protein, ma na-akwalite mmezi ọnya akpụkpọ ahụ. A na-enweta nke a site n'ịgbalite IRR, nke n'aka nke ya na-ebute usoro nke ụzọ mgbaàmà intracellular, na-akwalite mmụba cell, ịkwaga, na ọdịiche, n'ikpeazụ na-eduga n'ịrụzi anụ ahụ.
Mbelata mmebi nrụgide oxidative: Nchegbu oxidative na-ekere òkè dị ukwuu na mmepe nke ọtụtụ ọrịa metụtara mbufụt. ARA-290 nwere ike ibelata nrụgide oxidative kpatara mmebi nke mkpụrụ ndụ anụ ahụ. N'ime ọmụmụ banyere atherosclerosis (AS), ARA-290 nwere ike igbochi mmepụta nke ụdị oxygen reactive (ROS) site na macrophages n'okpuru ọnọdụ mkpali, belata nrụgide oxidative, ma belata mmebi nke mkpụrụ ndụ endothelial kpatara site na oxidatively modified lipoproteins, si otú ahụ na-egbochi ọganihu nke AS. N'ime ụdị nephrotoxicity nke cisplatin, ARA-290 na-ebelata mmebi akụrụ na-akpata nrụgide oxidative site n'ịbawanye ọkwa enzyme antioxidant, gụnyere glutathione peroxidase (GPx) na superoxide dismutase (SOD), na ibelata malondialdehyde (MDA) na ọkwa ROS.
Ngwa
(1) Ọrịa Neurological
Nsogbu ịda mbà n'obi: Nnyocha na ụdị ịda mbà n'obi na-akpata nrụgide na-adịghị ala ala gosiri na ARA-290 kwalitere omume ịda mbà n'obi dị ka ụmụ oke, na-egosi ngwa ya nwere ike ịgwọ ọrịa ịda mbà n'obi. Usoro nke ịda mbà n'obi nwere njikọ chiri anya na nzaghachi mkpali, na ARA-290 nke mgbochi mkpali na immunomodulatory mmetụta nwere ike inye usoro ọhụrụ maka ọgwụgwọ ịda mbà n'obi, nwere ike ịmalite ghọọ ọgwụ antidepressant ọhụrụ.
Ischemic Stroke: N'ime etiti ụbụrụ ụbụrụ ụbụrụ nke etiti (MCAO), ARA-290 gosipụtara mmetụta neuroprotective dị ka nke erythropoietin (EPO), na-ebelata obere apoptosis neuronal na ọkwa cytokine na-egbuke egbuke na ụbụrụ ụbụrụ. A na-edozi mmetụta neuroprotective nke ARA-290 site na onye na-anabata β-adrenergic (βCR) ma ghara ịkpata erythropoiesis. Nke a na-enye ebumnuche enyemaka ọhụrụ na ọgwụ ndị nwere ike ịgwọ ọrịa maka ọgwụgwọ ọrịa strok ischemic.
(2) Ọrịa autoimmune
Systemic lupus erythematosus (SLE): Nnyocha e mere na ụdị òké SLE na-egosi na ARA-290 na-eme ka mgbaàmà SLE dịkwuo mma, na-egbochi mmepụta nke autoantibodies, na-ebelata mbufụt na mmebi akụrụ, na anaghị akpali hematopoiesis. N'iburu n'uche njedebe dị ugbu a na ọgwụgwọ SLE, ARA-290 na-ekwe nkwa dị ka ọgwụ ọhụrụ maka SLE, na-enye ndị ọrịa nhọrọ ọgwụgwọ dị irè karị.
(3) Nsogbu ndị metụtara ọrịa shuga
Ọnya ụkwụ na-arịa ọrịa shuga: N'ụdị oke nke ọnya ụkwụ na-arịa ọrịa shuga, ntinye mpaghara nke ARA-290 na-akwalite ọgwụgwọ ọnya nke ọma, na-emezi glucose na metabolism lipid, ma na-ebelata ọkwa ihe mkpali. Nke a na-egosi na ARA-290 nwere ike itinye ngwa na ọgwụgwọ ọrịa ọnya metụtara ọrịa shuga, na-enye nghọta ọhụrụ na ụzọ maka njikwa ọnya ụkwụ na-arịa ọrịa shuga.
(4) Ọrịa akụrụ
Nephrotoxicity nke Cisplatin kpatara: N'ụdị nephrotoxicity nke cisplatin kpatara, ARA-290 belatara mmebi akụrụ cisplatin kpatara site na mgbochi apoptotic, mgbochi mkpali, na mmetụta antioxidant. Nke a na-egosi na ARA-290 nwere ike ịbụ atụmatụ ọhụrụ maka igbochi na ịgwọ nnukwu mmerụ ahụ nke cisplatin na-ebute, na-enye nchebe akụrụ maka ndị ọrịa na-enweta cisplatin chemotherapy.
(5) Ọrịa obi
Atherosclerosis: Nnwale in vitro na in vivo na-egosi na ARA-290 na-egbochi nzaghachi mkpali nke ọma, mmepụta ụdị oxygen na-arụ ọrụ, apoptosis, Mbugharị, na nguzobe cell foam na macrophages òké, yana uto nke ebe plaque na òké aortas. Nke a na-egosi na ARA-290 nwere ike itinye uru na mgbochi atherosclerosis na enwere ike ịmepụta ya ka ọ bụrụ ọgwụ ọhụrụ maka mgbochi na ọgwụgwọ ọrịa obi.
Mmechi
Na nchịkọta, ARA-290, dị ka peptide nwere mgbochi mkpali pụrụ iche, immunomodulatory, na anụ ahụ-echebe, nwere ụfọdụ ikike ọgwụgwọ na ọgwụgwọ nke ọrịa dị iche iche metụtara mbufụt.
Isi mmalite
[1] Wang R, Yang Z, Huang Y, et al. Erythropoietin-enwetara peptide ARA290 na-ebute nchebe anụ ahụ ụbụrụ site na $ beta $ - ihe na-anabata ihe na ụmụ oke nwere ọrịa ụbụrụ ischemic ụbụrụ [J]. Cns Neuroscience & Ọgwụgwọ, 2024,30. https://api.semanticcholar.org/CorpusID:268414491
[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, et al. Usoro usoro maka Mmetụta Nchebe nke ARA290, Ligand akọwapụtara maka Erythropoietin / CD131 Heteroreceptor, megide Nephrotoxicity nke Cisplatin na-ebute, ntinye aka nke Apoptosis na ụzọ mbufụt [J]. Mbufụt, 2023,46 (1): 342-358.DOI: 10.1007 / s10753-022-01737-7.
[3] Masreghi M, Bayrami Z, Sichani N, et al. Nnyocha in vivo na ọrụ ọgwụgwọ ọnya nke Specific ligand maka onye na-anabata nrụzi ebumpụta ụwa, ARA290, na-eji ụdị anụmanụ na-arịa ọrịa shuga [M]. 2023.10.21203/rs.3.rs-2520194/v1.
[4] Xu G, Zou T, Deng L, et al. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Oge Nchegbu Na-akpata ịda mbà n'obi-dị ka omume na mbufụt na oke [J]. Ihu ihu na Pharmacology, 2022,13:896601.DOI:10.3389/fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, et al. Ihe na-abụghị erythropoietic erythropoietin sitere na peptide na-echebe ụmụ oke site na lupus erythematosus systemic [J]. Akwụkwọ akụkọ nke Cellular and Molecular Medicine, 2018,22 (7): 3330-3339.DOI: 10.1111 / jcmm.13608.
[6] Dahan A, Brines M, Niesters M, et al. Ezubere onye na-anabata ihe nrụzi ebumpụta ụwa iji gwọọ neuropathy[J]. Akụkọ mgbu, 2016,1 (1): e566.DOI: 10.1097/PR9.0000000000000566.
[7] Zhang W, Yu G, Zhang M. ARA 290 na-ebelata ihe mgbu pathophysiological site n'ịtụle ọwa TRPV1: Njikọ n'etiti usoro ahụ ji alụso ọrịa ọgụ na nociception [J]. Peptides, 2016,76:73-79.DOI:10.1016/j.peptides.2016.01.003.
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