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ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ di tin dɛn we dɛn dɔn lan
ARA-290 na 11-amino asid linya nכn-hεmatopoiεtik polipεptida we kכmכt frכm εrythropoietin (EPO). i de du difrεn bayolojikal ifekt dεm bay we i de spεshal biεn to di innate ripa rεsεpכta (IRR). difrεnt frכm EPO, ARA-290 de rεtεn di anti-inflammatory εn tisu-protektiv fכnshכn dεm we kכntribyut to EPO.
Figure 1 di bayoloji fכ di innate ripa rεsεpכta de kכl am di tεmporal εn spatial separeshכn fכ in rεsεpכta sεbyunit dεm, we de asosiet fכ fכm di innate ripa rεsεpכta εn in εndojεnik ligεnd, hayposialated εrythropoietin (hEPO).
Mekanism fɔ Akshɔn
(1) Ifɛkt dɛn we de mek pɔsin nɔ gɛt inflammatory
inhibishכn fכ inflammatory sεl aktibכshכn: insay difrεn inflammatory mכdel dεm, ARA-290 de sho di abiliti fכ inhibit inflammatory sεl aktibכshכn. fכ egzampl, insay wan maws dεpreshכn mכdel we krכnik strεs indyuz, di de administreshכn fכ ARA-290 rivεs di inkrεs pan di frεkwεns εn/כ nכmba fכ CD11b0Ly6Gʰ0 nyutrofil dεm εn CD11b0Ly6Cʰ0 monosayt dεm na di bon mכro εn mεninges we krכnik strεs kכz, we i de rivεrs bak di krכnik strεs-indyuz maykroglia aktibכshכn, we de impruv diprεsiv lεk bihayvya insay mays, wit ifekt dεm we sכm kayn we lεk di wan dεm we fluoxetine de gi.
rεgulεshכn fכ inflammatory fכktכ sekreshכn: ARA-290 de rigul di sekreshכn fכ inflammatory fכktכ dεm fayn fayn wan. insay wan sistεmik lupus εrythematosus (SLE) maws mכdel, ARA-290 ridyus di sεrum lεvεl fכ inflammatory cytokines IL-6, MCP-1, εn TNF-α, sכmtεm sכpres sεrum antinyukliar כtoantibodi dεm (ANAs) εn anti-dכbl-strand DNA כtoantibodi dεm, rεdכks IgG εn C3 dεposishכn, εn impruv di nεfrayt simptom dεm. insay wan cisplatin-indyus nεfrotoksisiti mכdel, prε-tritmεnt wit ARA-290 rεdכks di lεvεl dεm fכ pro-inflammatory saytokεn dεm lεk TNF-α, IL-6, εn IL-1β, we de mek di inflammatory rispכns dεm na di rεnal tisu dεm.
inhibishכn fכ inflammatory signal pathways: ARA-290 kin εksyεrt in anti-inflammatory ifekt dεm bay we i de inhibit sכm inflammatory-related signal pathways. we i biεn to IRR, i kin infכlכw wan siriכs dכwnstrכm mכlikul ivent dεm we de aכsכsiayt wit inflammatory rεspכns, we de blכk di transmishכn εn amplifyushכn fכ inflammatory signal dεm εn ultimately i de εliviet inflammatory riakshכn dεm.
(2) Imyunmodulatory ifekt dεm
rεgulεshכn fכ makrofag fכnshכn: ARA-290 de ple wan siknifikant rεgεdyushכn rol insay makrofag fכnshכn. in vitro εkspεriεns sho se i kin inhεbit di inflammatory aktibכshכn fכ makrofag dεm we i de promuot dεn fagosaytik fכnshכn tכwεd apoptotik sεl dεm. insay wan SLE maws mכdel, ARA-290 de ridyus di nכmba fכ di apoptotik sεl dεm na di kidni dεm bay we i de rεgεl di makrofag fכnshכn, we kin bi wan pan di kכl mεkanism dεm we de כndalayn in impruvmεnt fכ SLE simptom dεm.
inflכεns pan imyun sεl bεlε: insay sכm sik mכdel dεm, ARA-290 kin εksyεrt imyun rεgεdyushכn ifekt dεm bay we i de mכdulet di bεlε bitwin difrεn imyun sεl populeshכn dεm. insay wan krכnik strεs-indyus maws dεpreshכn mכdel, ARA-290 in rεguleshכn fכ spεsifi k imyun sεl populeshכn dεm na di bon mכro εn mεninges de εp fכ rεstכr imyun sεl bεlε, we de mek di impak we inflammatory rεspכns dεm gεt pan di nεv sεstem εn impruv diprεshכn lεk bihayvya.
Figure 2 aktibכshכn fכ innate ripa rεsεpכta dεm de ridyus mεkanikal allodynia afta spared nεv injuri (SNI) in rat.
(3) Di tin dɛn we de protɛkt di tisu
fכ protεkt sεl rεpa εn rigεnεreshכn: ARA-290 de sho di abiliti fכ protεkt sεl ripa εn rigεnεreshכn insay difrεn tisu injuri mכdel dεm. insay wan dayabεtik fut כlsa (DFU) rat mכdel, lokal aplikεshכn fכ ARA-290 de aksεlεrat di wund kכloshכn sכmtεm, i de inkrεs kolagen εn protin kכntεnt, εn i de mek di skin wund ripa. dis de apin bay we dεn de aktibכt di IRR, we in tכn de initiate wan siriכs intasεlulyar signal path dεm, we de protεkt sεl proliferashכn, maygrεshכn, εn difrεns, we de lid to tisu ripa.
fכ ridyus di כksidεtiv strεs dεm we de pwεl: כksidεtiv strεs de ple imכtant rol fכ divεlכpmεnt fכ plεnti sik dεm we de fכm inflameshn. ARA-290 kin ridyus di damej we di oksidativ strεs indyuz to di tisu sεl dεm. insay stכdi dεm pan atεrosklεrosis (AS), ARA-290 kin inhεbit di prodyushכn fכ riaktiv כksijεn spεs (ROS) bay makrofag dεm כnda inflammatory kכndishכn, rεdכks כksidεtiv strεs lεvεl dεm, εn dכn dכn di damej to εndoteyl sεl dεm we כksidεtivli modifyed lipoprotein dεm kכz, we de inhεbit di prכgreshכn fכ AS. insay wan cisplatin-indyus nεfrotoksisiti mכdel, ARA-290 de εliviet כksidεtiv strεs-indyus kidni dεmεj bay we i de inkrεs di antioksidant εnzym lεvεl dεm, inklud glutathione pεrכksidεz (GPx) εn supεrכksayd dismutase (SOD), εn ridyus di malondialdehyde (MDA) εn ROS lεvεl dεm.
Aplikeshɔn dɛn
(1) Nyurolɔjik Dizayd
Dipreshɔn Disɔda: Stɔdi dɛm pan kronik strɛs-indyuz dipreshɔn mɔdel sho se ARA-290 impɔtant dipreshɔn-layk bihayvya na mays, we sho se i kin yuz am fɔ trit dipreshɔn disɔda. Di pathogenesis fɔ diprɛshɔn gɛt fɔ du wit di inflammatory rispɔns dɛm, ɛn di ARA-290 in anti-inflammatory ɛn immunomodulatory ifekt dɛm kin gi nyu strateji fɔ dipreshɔn tritmɛnt, we kin mek i bi wan nyu antidipreshan drɔg.
Ischemic Stroke: insay wan midul sεribra atεri oklushכn (MCAO) maws mכdel, ARA-290 sho nyuroprotεktiv ifekt dεm we sכm kayn we lεk di wan dεm fכ εrythropoietin (EPO), we rili ridyus nyuronal apoptosis εn inflammatory cytokine lεvεl dεm na di bren tisu. di nyuroprotektiv ifekt dεm fכ ARA-290 de mεdiet tru di β-adrenergic rεsεpכta (βCR) εn dεn nכ de indyuz εrythropoiesis. Dis de gi nyu intavεnshכn tכgεt εn pכtεnshal tεrapi dεm fכ di tritmεnt fכ ischemic strok.
(2) Di sik dɛn we pɔsin kin gɛt we i de fɛt insɛf
Systemic lupus erythematosus (SLE): stכdi dεm we dεn du pan SLE maws mכdel dεm sho se ARA-290 de impruv SLE simptom dεm bכku bכku wan, i de inhibit di prodakshכn fכ כtoantibodi dεm, i de ridyus di kidni inflameshn εn damej, εn i nכ de mek hεmatopoiesis. Gi di limiteshɔn dɛn we de naw na SLE tritmɛnt, ARA-290 gɛt prɔmis as nyu kandidet drɔg fɔ SLE, we de gi pasɛnt dɛn mɔ ifɛktiv tritmɛnt opshɔn dɛn.
(3) Kɔmplikɛshɔn dɛn we gɛt fɔ du wit dayabitis
Dayabitik fut ɔlsa: Insay wan rat mɔdel fɔ dayabitik fut ɔlsa, lokal aplikeshɔn fɔ ARA-290 de ɛp fɔ mek wund wɛl, i de mek di glukɔs ɛn lipid mɛtabolism bɛtɛ, ɛn i de ridyus di inflammatory factor lɛvɛl. Dis sho se ARA-290 gɛt pɔtɛnɛshɛl aplikeshɔn fɔ trit di wund we gɛt fɔ du wit dayabitis, we de gi nyu insayt ɛn we fɔ manej di dayabitik fut ɔlsa.
(4) Kidni sik dɛn
Cisplatin-induced nephrotoxicity: Insay wan cisplatin-induced nephrotoxicity model, ARA-290 alɛviet cisplatin-induced kidni damej tru in anti-apoptotic, anti-inflammatory, ɛn antioxidant ifekt dɛm. Dis sho se ARA-290 kin bi nyu strateji fɔ protɛkt ɛn trit cisplatin-induced akyu kidni injuri, we de gi kidni protɛkshɔn to pasɛnt dɛn we de du cisplatin kemotɛrapi.
(5) Di sik dɛn we kin apin to di at ɛn di blɔd
atεrosklεrosis: כl tu in vitro εn in vivo εkspεriεns dεm sho se ARA-290 de inhεbit inflammatory rispכns dεm, riaktiv כksijεn spεshal prodakshכn, apoptosis, maygrεshכn, εn fכm sεl fכmeshכn insay maws makrofag dεm, εn bak di growth fכ plek εria insay maws aortas. dis sho se ARA-290 gεt pכtεnshal aplikεshכn valyu insay anti-atεrosklεrosis εn dεn kin divεlכp am to wan nyu dכg fכ di prεvεnshכn εn tritmεnt fכ kכdivaskyul sik dεm.
Dɔn
fכ sכmari, ARA-290, as pεptida wit yunik anti-inflammatory, immunomodulatory, εn tisu-protektiv ifekt dεm, gεt sכm tεrapi pכtεnshal fכ trit difrεn sik dεm we rilet to inflameshn.
Sos dɛn we dɛn pul
[1] Wang R, Yang Z, Huang Y, ɛn ɔda pipul dɛn. εrythropoietin‐dεrivεd pεptida ARA290 de mεdiet bren tisu protεkshכn tru di $eta$‐kכmכn rεsεpכta in mays wit sεribral ischemic strok[J]. Cns Nyurosayns & Tɛrapi, 2024,30. https://api.semanticscholar.org/CorpusID:268414491. Di wan dɛn we de stɔdi bɔt di Baybul
[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, ɛn ɔda pipul dɛn. Mεkanikal Aprכch fכ Protεktiv Efεkt fכ ARA290, wan Sεsifi k Ligand fכ di Erythropoietin/CD131 Hεterorεsεptor, εgεst Cisplatin-Induse Nεfrotoksisiti, di Invכlvmεnt fכ Apoptosis εn Inflamεshכn Pathways[J]. Inflameshn, 2023, 46 (1): 342-358.DOI: 10.1007/s10753-022-01737-7.
[3] Mashreghi M, Bayrami Z, Sichani N, ɛn ɔda pipul dɛn. wan in vivo invεstigeshכn pan di wund-hεlin aktvכti fכ Sεsifi k ligεnd fכ di innate ripa rεsεptכr, ARA290, we yuz wan dayabεtik animal mכdel[M]. 2023.10.21203/rs.3.rs-2520194/v1.
[4] Xu G, Zou T, Deng L, ɛn ɔda pipul dɛn. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorate Kronik Stres-Induse Dipreshɔn-Lɛk Bihayvya ɛn Inflameshɔn insay Mays[J]. Frɔntiers in Famakɔlɔji, 2022,13:896601.DOI:10.3389/fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, ɛn ɔda pipul dɛn. nכn-εritropoiεtik εrythropoietin-dεriv pεptida de protεkt mays frכm sεstεmik lupus εrythεmatosus[J]. J ɔ rnal ov S ɛ l i l ɔ r ɛn M ɔ l i k ɔ l M ɛ d ɛ sin, 2018,22(7):3330-3339.DOI: 10.1111/jcmm.13608.
[6] Dahan A, Brines M, Niesters M, ɛn ɔda pipul dɛn. tכgεt di innate ripa rεsεpכta fכ trit nyuropati[J]. Pen Ripɔt, 2016,1(1):e566.DOI:10.1097/PR9.0000000000000566.
[7] Zhang W, Yu G, Zhang M. ARA 290 de rilif pathophysiological pen bay we i de target TRPV1 chanɛl: Integreshɔn bitwin imyun sistɛm ɛn nosisepshɔn[J]. Pεptid, 2016,76:73-79.DOI:10.1016/j.pεptida.2016.01.003.
Prodak we de fɔ yuz fɔ risach nɔmɔ:
