Bya Cocer Peptides 
ennaku 29 eziyise
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okulambika okutwaliza awamu
ARA-290 ye polypeptide ya amino asidi 11 eya linear non-hematopoietic polypeptide evudde mu erythropoietin (EPO). Kikola ebikolwa eby’enjawulo eby’ebiramu nga kisiba mu ngeri ey’enjawulo ku kirungo ekizaalibwamu eky’okuddaabiriza (IRR). Okwawukanako ne EPO, ARA-290 esigaza emirimu gy’okulwanyisa okuzimba n’okukuuma ebitundu by’omubiri egy’engeri ya EPO.
Ekifaananyi 1 Ebiramu by’ekirungo ekizaalibwamu eky’okuddaabiriza kimanyiddwa olw’okwawukana kw’ekiseera n’ekifo kw’ebitundu byakyo ebikwatagana, ebikwatagana okukola ekirungo ekizaala eky’okuddaabiriza n’ekirungo kyayo eky’omunda, hyposialated erythropoietin (hEPO).
Enkola y’Ekikolwa
(1) Ebikolwa Ebiziyiza okuzimba
Okuziyiza okukola kw’obutoffaali obuzimba: Mu bikolwa eby’enjawulo eby’okuzimba, ARA-290 eraga obusobozi bw’okuziyiza okukola kw’obutoffaali obuzimba. Okugeza, mu nkola y’okwennyamira kw’ebibe eyaleetebwa situleesi etawona, okugaba ARA-290 buli lunaku kwakyusa okweyongera mu mirundi n’/oba omuwendo gwa CD11b0Ly6Gʰ0 neutrophils ne CD11b0Ly6Cʰ0 monocytes mu busimu bw’amagumba n’obusimu obuleetebwa situleesi etawona, ate nga nakyo kyazzaawo microglia ezireetebwa situleesi ezitawona activation, bwe kityo ne kitereeza enneeyisa eringa ey’okwennyamira mu mbeba, n’ebikolwa ebifaanagana n’ebya fluoxetine.
Okulungamya okufulumya ensonga ezizimba: ARA-290 etereeza bulungi okufulumya ensonga ezizimba. Mu nkola y’ebibe eya systemic lupus erythematosus (SLE), ARA-290 yakendeeza ku miwendo gya serum egya inflammatory cytokines IL-6, MCP-1, ne TNF-α, yanyigiriza nnyo serum antinuclear autoantibodies (ANAs) ne anti-double-stranded DNA autoantibodies, yakendeeza ku IgG ne C3 deposition, n’okulongoosa obubonero bw’ekibumba. Mu nkola ya cisplatin-induced nephrotoxicity model, nga tebannaba kujjanjabwa na ARA-290 kyakendeeza ku miwendo gya pro-inflammatory cytokines nga TNF-α, IL-6, ne IL-1β, bwe kityo ne kikendeeza ku kuddamu kw’okuzimba mu bitundu by’ekibumba.
Okuziyiza amakubo g’obubonero obuzimba: ARA-290 eyinza okukozesa ebikolwa byayo eby’okulwanyisa okuzimba ng’eziyiza amakubo agamu agalaga obubonero obukwatagana n’okuzimba. Ku kusiba ku IRR, kiyinza okukosa omuddirirwa gw’ebintu ebibaawo mu molekyu wansi ebikwatagana n’okuddamu kw’okuzimba, bwe kityo ne kiziyiza okutambuza n’okugaziya obubonero bw’okuzimba era okukkakkana nga kikendeezezza ku nkola z’okuzimba.
(2) Ebikosa okukyusa obusimu obuziyiza endwadde
Okulungamya enkola ya macrophage: ARA-290 ekola kinene nnyo mu kulungamya mu nkola ya macrophage. Okugezesa mu vitro kulaga nti kisobola okuziyiza okukola kw’okuzimba kwa macrophages ate nga kitumbula omulimu gwazo ogw’okulya (phagocytic function) eri obutoffaali obufa. Mu nkola y’ebibe ebya SLE, ARA-290 ekendeeza ku muwendo gw’obutoffaali obufa mu nsigo ng’etereeza enkola ya macrophage, eyinza okuba emu ku nkola enkulu ezisibukako okulongoosa kwayo obubonero bwa SLE.
Enkola ku bbalansi y’obutoffaali bw’abaserikale b’omubiri: Mu bikolwa by’endwadde ebimu, ARA-290 eyinza okukola ebikolwa eby’okulungamya abaserikale b’omubiri ng’ekyusakyusa bbalansi wakati w’obutoffaali bw’abaserikale b’omubiri obw’enjawulo. Mu nkola y’okwennyamira kw’ebibe okuva ku situleesi etawona, okulungamya kwa ARA-290 ku bungi bw’obutoffaali obuziyiza endwadde obw’enjawulo mu busimu bw’amagumba n’obusimu obuyitibwa meninges kiyamba okuzzaawo bbalansi y’obutoffaali bw’abaserikale, bwe kityo ne kikendeeza ku buzibu bw’okuddamu kw’okuzimba ku nkola y’obusimu n’okulongoosa enneeyisa eringa ey’okwennyamira.
Ekifaananyi 2 Okukola kw’ebikwata ku kuddaabiriza obuzaale kukendeeza ku mechanical allodynia oluvannyuma lw’okulumwa obusimu obutawona (SNI) mu nvunza.
(3) Ebikozesebwa mu kukuuma ebitundu by’omubiri
Okutumbula okuddaabiriza n’okuzza obuggya obutoffaali: ARA-290 eraga obusobozi okutumbula okuddaabiriza n’okuzza obuggya obutoffaali mu bikolwa eby’enjawulo eby’obuvune bw’ebitundu. Mu nkola y’envunza ey’amabwa g’ebigere aga ssukaali (DFU), okukozesa ARA-290 mu kitundu kyanguya nnyo okuggalawo ebiwundu, kyongera ku kolagini ne puloteyina, era kitumbula okuddaabiriza ebiwundu by’olususu. Kino kituukibwako nga tukola IRR, nga kino nakyo kitandika omuddirirwa gw’amakubo g’obubonero mu butoffaali, okutumbula okukula kw’obutoffaali, okusenguka, n’okwawukana, okukkakkana nga kivaako okuddaabiriza ebitundu.
Okukendeeza ku kwonooneka kwa oxidative stress: Oxidative stress ekola kinene mu kukula kw’endwadde nnyingi ezikwatagana n’okuzimba. ARA-290 esobola okukendeeza ku kwonooneka kw’obutoffaali bw’ebitundu obuva ku situleesi ya oxidative. Mu kunoonyereza ku bulwadde bwa atherosclerosis (AS), ARA-290 esobola okuziyiza okukola ebika bya oxygen ebikola (ROS) ebikolebwa macrophages mu mbeera ezizimba, okukendeeza ku miwendo gya oxidative stress, n’okukendeeza ku kwonooneka kw’obutoffaali bw’omubiri obuva ku lipoproteins ezikyusiddwa mu oxidatively, bwe kityo n’eziyiza okukulaakulana kwa AS. Mu nkola ya cisplatin-induced nephrotoxicity model, ARA-290 ekendeeza ku kwonooneka kw’ekibumba okuva ku oxidative stress-induced kidney levels nga eyongera ku antioxidant enzyme levels, omuli glutathione peroxidase (GPx) ne superoxide dismutase (SOD), n’okukendeeza ku malondialdehyde (MDA) ne ROS levels.
Okusaba
(1) Obuzibu bw’obusimu
Obuzibu bw‟okwennyamira: Okunoonyereza mu bikolwa eby‟okwennyamira ebiva ku situleesi etaggwaawo kwalaga nti ARA-290 yalongoosa enneeyisa eringa ey‟okwennyamira mu mbeba, ekiraga nti eyinza okukozesebwa mu kujjanjaba obuzibu bw‟okwennyamira. Enkola y’obulwadde bw’okwennyamira ekwatagana nnyo n’okuddamu kw’okuzimba, era ebikolwa bya ARA-290 ebiziyiza okuzimba n’okukyusa obusimu biyinza okuwa obukodyo obupya obw’okujjanjaba okwennyamira, ekiyinza okukulaakulana ne kifuuka eddagala eppya eriweweeza ku kweraliikirira.
Ischemic Stroke: Mu nkola y’ebibe eya middle cerebral artery occlusion (MCAO), ARA-290 yalaga ebikolwa eby’okukuuma obusimu okufaananako n’ebya erythropoietin (EPO), okukendeeza ennyo ku neuronal apoptosis n’emiwendo gya inflammatory cytokine mu bitundu by’obwongo. Ebikolwa by’okukuuma obusimu ebya ARA-290 bitabaganyizibwa okuyita mu β-adrenergic receptor (βCR) era tebireeta erythropoiesis. Kino kiwa ebigendererwa ebipya eby‟okuyingira mu nsonga n‟eddagala eriyinza okujjanjaba okujjanjaba obulwadde bwa ischemic stroke.
(2) Endwadde z’abaserikale b’omubiri
Systemic lupus erythematosus (SLE): Okunoonyereza mu bikolwa by’ebibe ebya SLE kulaga nti ARA-290 etereeza nnyo obubonero bwa SLE, eziyiza okukola autoantibodies, ekendeeza ku kuzimba n’okwonooneka kw’ekibumba, era tesitula kukola musaayi. Okusinziira ku buzibu obuliwo kati mu bujjanjabi bwa SLE, ARA-290 erina ekisuubizo ng’eddagala eppya erigenda okukozesebwa mu SLE, nga liwa abalwadde obujjanjabi obusingako obulungi.
(3) Ebizibu ebiva ku ssukaali
Amabwa g’ebigere aga ssukaali: Mu nkola y’envunza ey’amabwa g’ebigere aga ssukaali, okukozesa ARA-290 mu kitundu kitumbula bulungi okuwona kw’ebiwundu, kitereeza enkyukakyuka ya glucose n’amasavu, era kikendeeza ku miwendo gy’ensonga ezizimba. Kino kiraga nti ARA-290 erina okukozesebwa mu kujjanjaba okuwona ebiwundu ebikwata ku ssukaali, ng’ewa amagezi amapya n’enkola ez’okuddukanya amabwa g’ebigere aga ssukaali.
(4) Endwadde z’ekibumba
Cisplatin-induced nephrotoxicity: Mu nkola ya cisplatin-induced nephrotoxicity model, ARA-290 yakendeeza ku cisplatin-induced nephrotoxicity okuyita mu anti-apoptotic, anti-inflammatory, ne antioxidant effects zaayo. Kino kiraga nti ARA-290 eyinza okukola ng’enkola empya ey’okuziyiza n’okujjanjaba obuvune obw’amaanyi obuva ku cisplatin, ng’ewa obukuumi bw’ekibumba eri abalwadde abaweebwa eddagala lya cisplatin.
(5) Endwadde z’emisuwa n’emisuwa
Atherosclerosis: Okugezesa kwombi mu vitro ne in vivo kulaga nti ARA-290 eziyiza bulungi okuddamu kw’okuzimba, okukola ebika bya oxygen ebikola, apoptosis, okusenguka, n’okutondebwa kw’obutoffaali obufuumuuka mu macrophages z’ebibe, awamu n’okukula kw’ekitundu kya plaque mu aortas z’ebibe. Kino kiraga nti ARA-290 erina omugaso oguyinza okukozesebwa mu kulwanyisa okuzimba emisuwa era eyinza okukolebwa n’efuuka eddagala eppya eriziyiza n’okujjanjaba endwadde z’emisuwa.
Mu bufunzi
Mu bufunze, ARA-290, nga peptide erimu ebikolwa eby’enjawulo ebiziyiza okuzimba, okukyusa obusimu obuziyiza endwadde, n’okukuuma ebitundu by’omubiri, erina obusobozi obumu obw’obujjanjabi mu kujjanjaba endwadde ez’enjawulo ezeekuusa ku kuzimba.
Ensonda
[1] Wang R, Yang Z, Huang Y, n’abalala. Erythropoietin‐derived peptide ARA290 etabaganya okukuuma ebitundu by’obwongo okuyita mu $eta$‐common receptor mu mbeba ezirina cerebral ischemic stroke[J]. Cns Sayansi w'obusimu & Obujjanjabi, 2024,30. https://api.semanticscholar.org/CorpusID:268414491. Enkola y’okukuuma obutonde bw’ensi
[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, n’abalala. Enkola ey’enkola ey’okukuuma ARA290, Ligand Entongole eri Erythropoietin/CD131 Heteroreceptor, ku Cisplatin-Induced Nephrotoxicity, okwenyigira mu Apoptosis n’amakubo g’okuzimba[J]. Okuzimba, 2023, 46 (1): 342-358.DOI: 10.1007 / s10753-022-01737-7.
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[4] Xu G, Zou T, Deng L, n’abalala. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Etereeza Enneeyisa y’Okwennyamira Okuva ku Situleesi Okutawona n’okuzimba mu mbeba[J]. Ensalo mu by’eddagala, 2022,13:896601.DOI:10.3389/fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, n’abalala. Peptide evudde mu erythropoietin etali ya erythropoietic ekuuma ebibe okuva ku systemic lupus erythematosus[J]. Journal of Eddagala ly'obutoffaali ne molekyu, 2018,22 (7): 3330-3339.DOI: 10.1111 / jcmm.13608.
[6] Dahan A, Brines M, Niesters M, n’abalala. Okutunuulira ekirungo ekizaalibwamu eky’okuddaabiriza okujjanjaba obulwadde bw’obusimu[J]. Lipoota z’obulumi, 2016,1 (1): e566.DOI:10.1097/PR9.000000000000566.
[7] Zhang W, Yu G, Zhang M. ARA 290 ewummuza obulumi obw’omubiri nga etunuulira omukutu gwa TRPV1: Okugatta wakati w’abaserikale b’omubiri n’okuwulira obulumi[J]. Peptides, 2016,76:73-79.DOI:10.1016/j.peptides.2016.01.003.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
