Na Cocer Peptides 
hashize iminsi 29
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Incamake
ARA-290 ni umurongo wa 11-amino acide umurongo utari hematopoietic polypeptide ukomoka kuri erythropoietin (EPO). Ikora ingaruka zitandukanye mubinyabuzima ihuza cyane na reseptor ivuka (IRR). Bitandukanye na EPO, ARA-290 igumana imirimo yo kurwanya inflammatory no kurinda tissue iranga EPO.
Igishushanyo 1 Ibinyabuzima bya reseptor yo gusana kuvuka birangwa no gutandukanya byigihe gito nu mwanya gutandukanya reseptor subunits zayo, zifatanya gukora reseptor yo gusana kavukire hamwe na ligand ya endogenous, hyposialated erythropoietin (HEPO).
Uburyo bwibikorwa
(1) Ingaruka zo Kurwanya inflammatory
Kubuza ingirabuzimafatizo gukora: Muburyo butandukanye bwo gutwika, ARA-290 yerekana ubushobozi bwo kubuza gukora selile. Kurugero, muburyo bwo kwiheba kwimbeba iterwa no guhangayika karande, ubuyobozi bwa buri munsi bwa ARA-290 bwahinduye ubwiyongere bwinshyi na / cyangwa umubare wa CD11b⁺Ly6Gʰⁱ neutrophile na CD11b⁺Ly6Cʰⁱ monocytes mumagufwa yamagufa na meninges biterwa no guhangayika karande, hamwe no guhindura ingaruka zisa na mikorobe zikora, hamwe no guhindura imitekerereze nkiyi ya flux.
Kugena ibibyimba bitera umuriro: ARA-290 igenga neza gusohora kwimpamvu. Muri sisitemu ya lupus erythematosus (SLE) yerekana imbeba, ARA-290 yagabanije serumu ya cytokine ikongora IL-6, MCP-1, na TNF-α, yahagaritse cyane serumu antinuclear autoantibodies (ANAs) hamwe na autoantibodies ya ADN irwanya kabiri, igabanya ubukana bwa IgG na C3. Muri moderi ya cisplatine iterwa na nephrotoxicity, mbere yo kuvura hamwe na ARA-290 yagabanije urugero rwa cytokine itera inflammatory nka TNF-α, IL-6, na IL-1β, bityo bikagabanya ibisubizo byumuriro mubice byimpyiko.
Kubuza inzira zerekana ibimenyetso: ARA-290 irashobora kugira ingaruka zayo zo kurwanya inflammatory muguhagarika inzira zimwe zerekana ibimenyetso. Iyo ihujwe na IRR, irashobora guhindura urukurikirane rwibintu bya molekuline yo hepfo ijyanye nibisubizo byokongoka, bityo bikabuza kwanduza no kongera ibimenyetso byerekana umuriro hanyuma bikagabanya ingaruka ziterwa no gutwika.
(2) Ingaruka zo gukingira indwara
Kugena imikorere ya macrophage: ARA-290 igira uruhare runini mugikorwa cya macrophage. Ubushakashatsi bwa vitro bwerekana ko bushobora kubuza gukora macrophage mugihe cyo guteza imbere imikorere ya fagocytike yerekeza kuri selile apoptotique. Muburyo bwimbeba ya SLE, ARA-290 igabanya umubare wutugingo ngengabuzima twa apoptotique mu mpyiko muguhindura imikorere ya macrophage, ishobora kuba imwe muburyo bwingenzi bushingiye ku kunoza ibimenyetso bya SLE.
Ingaruka ku buringanire bw'ingirabuzimafatizo: Mu ngero zimwe na zimwe z’indwara, ARA-290 irashobora kugira ingaruka ku mikorere y’umubiri ihindura uburinganire hagati y’uturemangingo dutandukanye tw’umubiri. Muburyo budashira buterwa no kwiheba kwimbeba, ARA-290 igenga umubare wabantu bafite ubudahangarwa bw'umubiri mu magufa na meninges bifasha kugarura ingirabuzimafatizo z'umubiri, bityo bikagabanya ingaruka ziterwa no gutwika imitsi no kunoza imyitwarire isa n'iyihebye.
Igishushanyo cya 2 Gukora ibyakiriwe neza byo gusana bigabanya allodynia yumukanishi nyuma yo gukomeretsa imitsi (SNI) yimbeba.
(3) Ingaruka zo gukingira
Guteza imbere gusana no kuvugurura ingirabuzimafatizo: ARA-290 yerekana ubushobozi bwo guteza imbere gusana ingirabuzimafatizo no kuvugurura muburyo butandukanye bwo gukomeretsa ingirangingo. Mu bwoko bw'imbeba ya diyabete (DFU), imikoreshereze y’ibanze ya ARA-290 yihutisha cyane gufunga ibikomere, kongera collagen na proteyine, kandi bigatera gusana ibikomere byuruhu. Ibi bigerwaho mugukora IRR, nayo itangiza urukurikirane rwinzira zerekana ibimenyetso, zitera ikwirakwizwa ryimikorere, kwimuka, no gutandukana, amaherezo biganisha ku gusana ingirangingo.
Kugabanya kwangirika kwa okiside: Guhangayikishwa na Oxidative bigira uruhare runini mugukuza indwara nyinshi ziterwa no gutwika. ARA-290 irashobora kugabanya kwangirika kwa okiside iterwa na selile. Mu bushakashatsi bwakozwe kuri aterosklerose (AS), ARA-290 irashobora kubuza umusaruro w’ubwoko bwa ogisijeni ikora (ROS) na macrophage mu bihe by’umuriro, bikagabanya urugero rw’imisemburo ya okiside, kandi bikagabanya kwangirika kw ingirabuzimafatizo ziterwa na lipoproteine zahinduwe na okiside, bityo bikabuza iterambere rya AS. Muri moderi ya cisplatine iterwa na nephrotoxicity, ARA-290 igabanya impyiko ziterwa na okiside itera impyiko yongera urugero rwa enzyme ya antioxydeant, harimo glutathione peroxidase (GPx) hamwe na superoxide disutase (SOD), no kugabanya malondialdehyde (MDA) na ROS.
Porogaramu
(1) Indwara zifata ubwonko
Indwara yo Kwiheba: Ubushakashatsi bwakozwe muburyo bwo kwiheba buterwa no kwiheba bwerekanye ko ARA-290 yahinduye imyitwarire imeze nk'iyihebye mu mbeba, byerekana ko ishobora gukoreshwa mu kuvura indwara zihebye. Indwara yo kwiheba ifitanye isano rya bugufi n’ibisubizo by’umuriro, kandi ingaruka za ARA-290 zirwanya inflammatory na immunomodulatory zirashobora gutanga ingamba nshya zo kuvura indwara yo kwiheba, zishobora kuba imiti igabanya ubukana.
Ischemic Stroke: Mugihe cyimbeba yo hagati yubwonko bwo hagati yubwonko (MCAO), ARA-290 yerekanye ingaruka za neuroprotective zisa niza erythropoietin (EPO), bigabanya cyane apoptose ya neuronal na cytokine ikongora mubice byubwonko. Ingaruka za neuroprotective ya ARA-290 zahujwe binyuze muri β-adrenergic reseptor (βCR) kandi ntibitera erythropoiesis. Ibi bitanga intego nshya zo gutabara hamwe nubuvuzi bushobora kuvura indwara yubwonko.
(2) Indwara ziterwa na Autoimmune
Sisitemu ya lupus erythematosus (SLE): Ubushakashatsi bwakozwe muburyo bwimbeba ya SLE bwerekana ko ARA-290 itezimbere cyane ibimenyetso bya SLE, ikabuza gukora autoantibodies, kugabanya impyiko no kwangirika, kandi ntibitera hematopoiesis. Urebye aho bigarukira mu kuvura SLE, ARA-290 isezeranya nk'umuti mushya w’abakandida kuri SLE, utanga abarwayi uburyo bwiza bwo kuvura.
(3) Ingorane zijyanye na diyabete
Ibisebe by'ibirenge bya diyabete: Mu buryo bw'imbeba y'ibisebe by'ibirenge bya diyabete, gukoresha mu gace ka ARA-290 bitera neza gukira ibikomere, kunoza glucose na metabolisme ya lipide, kandi bigabanya urugero rw'ibibyimba. Ibi byerekana ko ARA-290 ifite uburyo bushoboka bwo kuvura ibikomere biterwa na diyabete, bitanga ubumenyi bushya hamwe nuburyo bwo gucunga ibisebe bya diyabete.
(4) Indwara zimpyiko
Cisplatine iterwa na neprotoxicity: Mu buryo bwa cisplatine iterwa na neprotoxicity, ARA-290 yagabanije kwangirika kw'impyiko iterwa na cisplatine iterwa na anti-apoptotique, anti-inflammatory, na antioxydeant. Ibi byerekana ko ARA-290 ishobora kuba ingamba nshya zo gukumira no kuvura ibikomere bikabije byatewe na cisplatine, bitanga uburwayi bwimpyiko kubarwayi ba chimiotherapie cisplatine.
(5) Indwara z'umutima
Atherosclerose: Haba muri vitro ndetse no mubushakashatsi bwa vivo byerekana ko ARA-290 ibuza neza ibisubizo byokongoka, kubyara amoko ya ogisijeni ikora, apoptose, kwimuka, hamwe no gukora ingirabuzimafatizo muri macrophage yimbeba, ndetse no gukura kwicyapa muri aortas yimbeba. Ibi byerekana ko ARA-290 ifite agaciro gakoreshwa mukurwanya anti-aterosklerose kandi ishobora guhindurwa imiti mishya yo gukumira no kuvura indwara zifata umutima.
Umwanzuro
Muri make, ARA-290, nka peptide ifite anti-inflammatory idasanzwe, immunomodulatory, hamwe ningaruka zo gukingira tissue, ifite ubushobozi bwo kuvura mugukiza indwara zitandukanye ziterwa no gutwika.
Inkomoko
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[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, n'abandi. Uburyo bukoreshwa muburyo bwo gukingira ingaruka za ARA290, Ligand yihariye ya Erythropoietin / CD131 Heteroreceptor, kurwanya Cisplatine iterwa na Nephrotoxicity, Uruhare rwa Apoptose ninzira Zitwika [J]. Gutwika, 2023.46 (1): 342-358.DOI: 10.1007 / s10753-022-01737-7.
[3] Mashreghi M, Bayrami Z, Sichani N, n'abandi. Iperereza ryakozwe na vivo kubikorwa byo gukiza ibikomere bya ligand yihariye ya reseptor yo gusana ivuka, ARA290, ukoresheje icyitegererezo cyinyamaswa ya diyabete [M]. 2023.10.21203 / rs.3.rs-2520194 / v1.
[4] Xu G, Zou T, Deng L, n'abandi. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ihindura Imyitwarire idakira Yatewe no kwiheba-Imyitwarire no gutwika imbeba [J]. Imipaka muri Farumasi, 2022,13: 896601.DOI: 10.3389 / fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, n'abandi. Non-erythropoietic erythropoietin ikomoka kuri peptide irinda imbeba sisitemu ya lupus erythematosus [J]. Ikinyamakuru cyubuvuzi bwa selile na molecular, 2018,22 (7): 3330-3339.DOI: 10.1111 / jcmm.13608.
[6] Dahan A, Brines M, Niesters M, n'abandi. Kwibanda ku kuvura kuvuka kuvuka kuvura indwara ya neuropathie [J]. Raporo yububabare, 2016,1 (1): e566.DOI: 10.1097 / PR9.0000000000000566.
[W] Peptide, 2016,76: 73-79.DOI: 10.1016 / j.peptides.2016.01.003.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
