Cocer Peptides ye ŋlɔe 
ŋkeke 29 enye sia
NYATAKAKAWO KPLE NUSIWO WOTSƆ ƑE NYATAKAKA SIWO KAtã WOÐO LE NYATAKAKADZRAÐOƑE SIA ME LA KPLE NYATAKAKAWO kaka KPLEE NUFIAFIA ƑE TAÐOÐOWO KO.
Wotrɔ asi le atike siwo wona le nyatakakadzraɖoƒe sia ŋu na numekuku le vitro ɖeɖeko. Wowɔa numekuku le vitro (Latingbe me: *le ahuhɔ̃e me*, si gɔmee nye le ahuhɔ̃e me) le amegbetɔ ƒe ŋutilã godo. Atike siawo menye atikewo o, United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda asi ɖe wo dzi o, eye mele be woazã wo atsɔ axe mɔ ɖe atikewɔwɔ, dɔléle, alo dɔléle aɖeke nu, adae, alo adae o. Se de se vevie be woatsɔ atike siawo ade amegbetɔ alo lãwo ƒe ŋutilã me le mɔ ɖesiaɖe nu.
Kpɔɖeŋu bliboa
ARA-290 nye amino acid 11 ƒe linear non-hematopoietic polypeptide si wokpɔ tso erythropoietin (EPO) me. Ewɔa nugbagbeviwo ƒe ŋusẽkpɔɖeamedzi vovovowo to alesi wòbla ɖe dzɔdzɔmenuwo ɖɔɖɔɖoxɔla (IRR) ŋu koŋ me. To vovo na EPO la, ARA-290 léa dɔlékuiwutike kple lãmenugbagbeviwo takpɔkpɔ ƒe dɔwɔwɔ siwo ɖe dzesi le EPO ŋu la me ɖe asi.
Nɔnɔmetata 1 Dzɔdzɔme ɖɔɖɔɖoxɔla ƒe nugbagbeŋutinunya ƒe dzesi enye eƒe xɔla ƒe akpa suewo ƒe mama le ɣeyiɣi kple teƒe, siwo do ƒome tsɔ wɔa dzɔdzɔme ɖɔɖɔɖoxɔla kple eƒe lãmenugbagbeviwo ƒe ligand, hyposialated erythropoietin (hEPO).
Dɔwɔwɔ ƒe Mɔnu
(1) Ŋusẽkpɔɖeamedzi si Tsi Tre Ðe Dzoxɔxɔ Ŋu
Mɔxexe ɖe dɔdzẽ ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ nu: Le dɔdzẽ ƒe kpɔɖeŋu vovovowo me la, ARA-290 ɖe ŋutete si le esi be wòaxe mɔ ɖe dɔdzẽ ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ nu fiana. Le kpɔɖeŋu me dɔwɔwɔ, si wɔnɛ be nuwɔna si le abe blanuiléle ene nyona ɖe edzi le sisiblisiwo me, eye eƒe ŋusẽkpɔɖeamedziwo sɔ kple fluoxetine tɔ.
Dɔdzẽ ƒe nusiwo dona le lãme na ame ƒe ɖoɖowɔwɔ: ARA-290 kpɔa dɔdzẽ ƒe nusiwo dona le lãme na ame dzi nyuie. Le systemic lupus erythematosus (SLE) mouse model me la, ARA-290 ɖe inflammatory cytokines IL-6, MCP-1, kple TNF-α ƒe agbɔsɔsɔ dzi kpɔtɔ le ʋumenugbagbeviɣi me, te serum antinuclear autoantibodies (ANAs) kple anti-double-stranded DNA autoantibodies ɖe to ŋutɔ, eɖe IgG kple C3 ƒe tsɔtsɔ dzi kpɔtɔ, eye wòna nephritis ƒe dzesiwo nyo ɖe edzi. Le ayiku me aɖi si cisplatin hena vɛ ƒe kpɔɖeŋu me la, ARA-290 zazã do ŋgɔ na dɔdzẽ ƒe cytokines abe TNF-α, IL-6, kple IL-1β ene ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ, si wɔe be dɔdzẽ ƒe ŋuɖoɖowo dzi ɖe kpɔtɔ le ayiku ƒe lãmenugbagbeviwo me.
Mɔxexe ɖe dɔdzẽ ƒe dzesimɔwo nu: ARA-290 ate ŋu awɔ eƒe dɔlékuiwutikewo ŋudɔ to mɔxexe ɖe dzesimɔ aɖewo siwo do ƒome kple dɔdzẽ nu me. Ne ebla ɖe IRR ŋu la, ate ŋu akpɔ ŋusẽ ɖe molecule ƒe nudzɔdzɔ siwo kplɔ wo nɔewo ɖo siwo do ƒome kple dɔdzẽ ƒe ŋuɖoɖowo dzi, si ana wòaxe mɔ ɖe dɔdzẽ ƒe dzesiwo ƒe kaka kple woƒe dzidziɖedzi nu eye mlɔeba wòaɖe dɔdzẽ ƒe dɔwɔwɔ dzi akpɔtɔ.
(2) Dɔlélenutsiŋutete ƒe tɔtrɔ ƒe ŋusẽkpɔɖeamedzi
Macrophage ƒe dɔwɔwɔ dzi kpɔkpɔ: ARA-290 wɔa akpa vevi aɖe le ɖoɖowɔwɔ me le macrophage ƒe dɔwɔwɔ me. Dodokpɔ siwo wowɔ le vitro ɖee fia be ate ŋu axe mɔ ɖe macrophages ƒe dɔdzẽ ƒe dɔwɔwɔ nu esime wòle woƒe phagocytic dɔwɔwɔ dom ɖe ŋgɔ ɖe apoptotic cells ŋu. Le SLE sisiblisi ƒe kpɔɖeŋu me la, ARA-290 ɖea apoptotic cells ƒe xexlẽme dzi kpɔtɔna le ayiku me to macrophage ƒe dɔwɔwɔ dzi kpɔkpɔ me, si ate ŋu anye mɔnu vevi siwo gbɔ wòtona be SLE ƒe dzesiwo nanyo ɖe edzi la dometɔ ɖeka.
Ŋusẽkpɔɖeamedzi ɖe dɔlélenutsiŋutete ƒe lãmenugbagbeviwo ƒe dadasɔ dzi: Le dɔléle ƒe kpɔɖeŋu aɖewo me la, ARA-290 ate ŋu awɔ dɔlélenutsiŋutete ƒe ɖoɖowɔwɔ ƒe ŋusẽkpɔɖeamedzi to asitɔtrɔ le dɔlélenutsiŋutete ƒe lãmenugbagbevi vovovowo ƒe dadasɔ ŋu me. Le sisiblisi ƒe blanuiléle si nuteɖeamedzi atraɖii hena vɛ ƒe kpɔɖeŋu me la, ARA-290 ƒe dɔlélenutsiŋutete ƒe lãmenugbagbevi tɔxɛ siwo le ƒumeŋuɖui kple ƒumeŋuɖui me ƒe ɖoɖowɔwɔ kpena ɖe dɔlélenutsiŋutete ƒe lãmenugbagbeviwo ƒe dadasɔ ŋu, si wɔnɛ be dɔdzẽ ƒe ŋuɖoɖowo ƒe ŋusẽkpɔɖeamedzi ɖe lãmekawo dzi dzi ɖena kpɔtɔna eye wònaa nuwɔna si le abe blanuiléle ene nyona ɖe edzi.
Nɔnɔmetata 2 Dzɔdzɔmenuwo ɖɔɖɔɖoxɔlawo ƒe dɔwɔwɔ ɖea mɔ̃ɖaŋununya ƒe allodynia dzi kpɔtɔna le lãmekawo ƒe abi si womeɖe o (SNI) megbe le sisiblisiwo me.
(3) Lãmetsiŋusẽ ƒe ametakpɔkpɔ ƒe ŋusẽkpɔɖeamedzi
Lãmenugbagbeviwo ɖɔɖɔɖo kple wo gbugbɔgadzɔ dodo ɖe ŋgɔ: ARA-290 ɖe ŋutete si le esi be wòado lãmenugbagbeviwo ɖɔɖɔɖo kple gbugbɔgadzɔ ɖe ŋgɔ le lãmenugbagbeviwo ƒe abixɔxɔ ƒe kpɔɖeŋu vovovowo me fia. Le suklidɔléla ƒe afɔdzideƒe (DFU) ƒe sisiblisi ƒe kpɔɖeŋu me la, ARA-290 zazã le teƒea naa abi ƒe tutu kabakaba ŋutɔ, enaa collagen kple protein ƒe agbɔsɔsɔ dzina ɖe edzi, eye wòdoa ŋutigbalẽ ƒe abi ɖɔɖɔɖo ɖe ŋgɔ. Esia dzɔna to IRR ƒe dɔwɔwɔ me, si hã dzea lãmenugbagbeviwo me dzesimɔ siwo kplɔ wo nɔewo ɖo gɔme, si doa lãmenugbagbeviwo ƒe dzidziɖedzi, ʋuʋu, kple vovototodedeameme ɖe ŋgɔ, si wɔnɛ be lãmenugbagbeviwo dzrana ɖo mlɔeba.
Oxidative stress ƒe nugbegblẽ dzi ɖeɖe kpɔtɔ: Oxidative stress wɔa akpa vevi aɖe le dɔléle geɖe siwo do ƒome kple dɔdzẽ ƒe dzɔdzɔ me. ARA-290 ate ŋu aɖe nusiwo oxidative stress hena vɛ na lãmenugbagbeviwo ƒe lãmenugbagbeviwo dzi akpɔtɔ. Le numekuku siwo wowɔ tso ʋukawo ƒe ʋuʋu (AS) ŋu me la, ARA-290 ate ŋu axe mɔ na macrophages ƒe oxygen ƒomevi siwo wɔa dɔ (ROS) wɔwɔ le dɔdzẽ ƒe nɔnɔmewo me, aɖe oxidative stress ƒe agbɔsɔsɔ dzi akpɔtɔ, eye wòaɖe nusiwo gblẽ le endothelial cells ŋu si lipoproteins siwo woɖɔli oxidatively hena vɛ dzi akpɔtɔ, si ana AS ƒe ŋgɔyiyi natsi. Le ayiku ƒe aɖi si cisplatin hena vɛ ƒe kpɔɖeŋu me la, ARA-290 ɖea ayiku ƒe gbegblẽ si oxidative stress hena vɛ dzi kpɔtɔna to antioxidant enzyme ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ me, siwo dometɔ aɖewoe nye glutathione peroxidase (GPx) kple superoxide dismutase (SOD), kple malondialdehyde (MDA) kple ROS ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ me.
Dɔbiagbalẽviwo
(1) Ahɔhɔ̃mekawo ƒe Dɔlélewo
Blanuiléledɔ: Numekuku siwo wowɔ le blanuiléle si nuteɖeamedzi atraɖii hena vɛ ƒe kpɔɖeŋuwo me ɖee fia be ARA-290 na nuwɔna si le abe blanuiléle ene nyo ɖe edzi le sisiblisiwo me, si ɖee fia be woate ŋu azãe le blanuiléledɔ dada me. Blanuiléle ƒe dɔléle dzɔdzɔ do ƒome kplikplikpli kple dɔdzẽ ƒe ŋuɖoɖowo, eye ARA-290 ƒe dɔlékuiwutikewo kple dɔlélenutsiŋutete ƒe dɔwɔwɔ ate ŋu ana mɔnu yeyewo nasu ame si woatsɔ ada blanuiléle, si ate ŋu ava zu blanuilélenutsitike yeye aɖe.
Ischemic Stroke: Le middle cerebral artery occlusion (MCAO) mouse model me la, ARA-290 ɖe ahɔhɔ̃mekawo takpɔkpɔ ƒe ŋusẽkpɔɖeamedzi siwo sɔ kple erythropoietin (EPO) tɔ fia, si ɖe ahɔhɔ̃mekawo ƒe apoptosis kple inflammatory cytokine ƒe agbɔsɔsɔ dzi kpɔtɔ ŋutɔ le ahɔhɔ̃mekawo me. ARA-290 ƒe ahɔhɔ̃mekawo takpɔkpɔ ƒe ŋusẽkpɔɖeamedziwo toa β-adrenergic receptor (βCR) dzi eye womehea ʋumenugbagbeviɣidɔ vɛ o. Esia naa nudede nyawo me ƒe taɖodzinu yeyewo kple atike siwo woate ŋu azã atsɔ ada ʋusɔgbɔdɔ si me ʋu sina tona.
(2) Dɔléle Siwo Dɔlélenutsiŋutete Le
Systemic lupus erythematosus (SLE): Numekuku siwo wowɔ le SLE sisiblisi ƒe kpɔɖeŋuwo ŋu ɖee fia be ARA-290 nana SLE ƒe dzesiwo nyona ɖe edzi ŋutɔ, xea mɔ na autoantibodies ƒe wɔwɔ, eɖea ayiku ƒe dɔdzẽ kple nugbegblẽ dzi kpɔtɔna, eye meʋãa ʋu ƒe wɔwɔme o. Ne míebu seɖoƒe siwo li fifia le SLE dada me ŋu la, ŋugbedodo le ARA-290 ŋu be enye atike yeye si woate ŋu azã na SLE, si ana atikewɔmɔnu siwo awɔ dɔ nyuie wu dɔnɔwo.
(3) Kuxi siwo do ƒome kple suklidɔ
Suklidɔ ƒe afɔ ƒe abi: Le suklidɔ ƒe afɔ ƒe abi ƒe kpɔɖeŋu si wowɔ le sisiblisi me la, ARA-290 zazã le teƒea doa abi ƒe dɔyɔyɔ ɖe ŋgɔ nyuie, enaa sukli kple ami ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu nyona ɖe edzi, eye wòɖea dɔdzẽ ƒe agbɔsɔsɔ dzi kpɔtɔna. Esia fia be woate ŋu azã ARA-290 le abi siwo do ƒome kple suklidɔ ƒe dɔyɔyɔ me, eye wòna gɔmesese yeyewo kple mɔnu siwo dzi woato akpɔ suklidɔ ƒe afɔdzideƒewo gbɔ.
(4) Ayikudɔlélewo
Aɖi si cisplatin hena vɛ: Le ayiku ƒe aɖi si cisplatin hena vɛ ƒe kpɔɖeŋu me la, ARA-290 ɖe ayiku ƒe gbegblẽ si cisplatin hena vɛ dzi kpɔtɔ to eƒe ŋusẽ si tsia tre ɖe ayiku ŋu, esi tsia dzodzodzoe, kple esi tsia dzoxɔxɔ nu me. Esia fia be ARA-290 ate ŋu anye mɔnu yeye aɖe si woatsɔ axe mɔ ɖe ayiku ƒe abi sesẽ si cisplatin hena vɛ nu ahadae, si ana ayiku takpɔkpɔ dɔnɔ siwo le cisplatin ƒe atikewɔmɔnu zãm.
(5) Dzitodzito me dɔlélewo
Ʋukawo ƒe ʋuʋu: Dodokpɔ siwo wowɔ le vitro kple vivo siaa ɖee fia be ARA-290 xea mɔ nyuie na dɔdzẽ ƒe ŋuɖoɖowo, oxygen ƒomevi siwo wɔa dɔ, apoptosis, ʋuʋu, kple foam cell ƒe wɔwɔ le mouse macrophages me, kpakple plaque area ƒe tsitsi le mouse aortas me. Esia fia be asixɔxɔ si woate ŋu azã le ARA-290 ŋu le ʋukawo ƒe ʋuʋu nu eye woate ŋu atrɔ asi le eŋu wòazu atike yeye aɖe si woatsɔ axe mɔ ɖe dzitodzito me dɔlélewo nu ahada wo.
Nyanuwuwuw
Kpuie ko la, ARA-290, abe peptide si si dɔlékuiwutike, dɔlélenutsiŋutete ƒe tɔtrɔ, kple lãmenugbagbeviwo takpɔkpɔ ƒe ŋusẽkpɔɖeamedzi tɔxɛwo le ene la, ƒe atikewɔwɔ ƒe ŋutete aɖewo le dɔléle vovovo siwo do ƒome kple dɔdzẽ dada me.
Dzɔtsoƒewo
[1] Wang R, Yang Z, Huang Y, kple ame bubuwo. Erythropoietin‐derived peptide ARA290 nye domenɔla na ahɔhɔ̃mekawo takpɔkpɔ to $eta$‐common receptor dzi le mice siwo ŋu cerebral ischemic stroke le me[J]. Cns Ahɔhɔ̃ŋutinunya & Atikewɔwɔ, 2024,30. https://api.semanticscholar.org/CorpusID: 268414491. Eƒe lãmesẽnyawo gbɔ kpɔkpɔ
[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, kple ame bubuwo. Mɔ̃ɖaŋununya ƒe Mɔnu na Ametakpɔkpɔ ƒe Ŋusẽkpɔɖeamedzi si ARA290, si nye Ligand Tɔxɛ aɖe na Erythropoietin/CD131 Heteroreceptor, ɖe Cisplatin-Induced Nephrotoxicity, Apoptosis kple Dzoxɔxɔ Mɔwo ƒe Gomekpɔkpɔ Ŋu[J]. Dzoxɔxɔ, 2023, 46 (1): 342-358.DOI: 10.1007 / s10753-022-01737-7.
[3] Mashreghi M, Bayrami Z, Sichani N, kple ame bubuwo. Numekuku aɖe si wowɔ le agbe me le abidada ƒe dɔwɔwɔ si le Specific ligand na innate repair receptor, ARA290, ŋu to suklidɔlélawo ƒe lã ƒe kpɔɖeŋu zazã me[M]. 2023.10.21203/rs.3.rs-2520194/v1.
[4] Xu G, Zou T, Deng L, kple ame bubuwo. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ðea Nuwɔna Siwo Le Abe Blanuiléle Si Le Nuteɖeamedzi Atraɖii Gbɔ Kple Dɔdzẽ Si Le Mice Me Dzi Ðena Ðe Edzi[J]. Liƒowo le Atikeŋutinunya me, 2022,13:896601.DOI:10.3389/fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, kple ame bubuwo. Peptide si woɖe tso erythropoietin me si mewɔa ʋumenugbagbeviɣidɔ o kpɔa sisiblisiwo ta tso systemic lupus erythematosus me[J]. Lãmenugbagbeviwo kple Molekyulãwo ƒe Atikewɔwɔ ƒe Agbalẽ, 2018,22 (7): 3330-3339.DOI: 10.1111 / jcmm.13608.
[6] Dahan A, Brines M, Niesters M, kple ame bubuwo. Taɖodzinu na dzɔdzɔmenuwo ɖɔɖɔɖodɔlékui be woatsɔ ada ahɔhɔ̃mekawo ƒe dɔléle[J]. Vevesese Ŋuti Nyatakakawo, 2016, 1 (1): e566.DOI: 10.1097 / PR9.0000000000000566.
[7] Zhang W, Yu G, Zhang M. ARA 290 ɖea dɔlélenutsiŋutete ƒe vevesese dzi kpɔtɔna to taɖodzinu TRPV1 mɔ̃ dzi: Dɔlélenutsiŋutete kple nociception dome ɖekawɔwɔ[J]. Peptides, 2016, 76: 73-79.DOI: 10.1016 / j. peptides.2016.01.003.
Adzɔnu si li na numekuku zazã ɖeɖeko:
