ARA-290 16mg we yu de yuz

▎ ARA-290 Struktrɔ

Sos: PubChem

Sikyɔn: XEQLERALNSS Mɔlikul Fɔmula: C 51H 84N 16O21 Molikul Weyt: 1257.3g/mol CAS Nɔmba:1208243-50-8 PubChem CID: 91810664. Di wan dɛn we de wok Sinonim dɛn: Cibinetide

▎ ARA-290 Risach

Wetin na di risach bakgrɔn fɔ ARA-290?  

di divεlכpmεnt fכ ARA-290 kכmכt frכm fכ εksplכr di tεrapi pכtεnshal fכ εrythropoietin (EPO). sayɛnsman dεm fכnshכn se EPO nכ de כnli protεkt εrythropoiesis bכt i gεt tisu-protektiv fכnshכn dεm lεk anti-inflammation εn anti-apoptosis. Bɔt di ɛmatopoiɛtik stimulashɔn we EPO gɛt kin mek di blɔd viskɔsiti ɛn ɔda risk dɛn go ɔp, we kin mek dɛn nɔ yuz am fɔ trit sik dɛn we nɔ gɛt anemia. fכ kip EPO in tisu-protεktiv ifekt dεm we i de avכyd in hεmatopoietic sayd ifekt dεm, risechכr dεm bigin fכ disayn dεrivεtiv pεptida dεm, we mek dεn mek ARA-290.  

wit dip risach, dεn bin rεkכgnεz di yכnik advantej dεm fכ ARA-290 as nכn-hεmatopoiεtik pεptida sכmtεm. i de aktibכt di anti-inflammatory εn tisu ripa signal path dεm bay we i de biεn di innate ripa rεsεpכta (IRR), we de sho prכmis ifekt dεm fכ trit dayabεtik komplikεshכn dεm, nyuropathies, εn rεnal injuri dεm. dis fכndεshכn dεm lay di fawndeshכn fכ fכda risεch εn klinik aplikεshכn fכ ARA-290 εn prכmot di divεlכpmεnt כf nכvel tεrapi stratεji dεm we bεys pan EPO-dεriv pεpti dεm.  

Wetin na di we aw ARA-290 de wok?  

Anti-Inflammatory Effect: ARA-290 de inhibit di sekreshכn fכ inflammatory cytokines, we de ridyus inflammatory rispכns, lεk aw dεn sho insay mכltipכl sik mכdel dεm. fכ egzampl, insay wan maws mכdel fכ sistεmik lupus εrythematosus (SLE), i de ridyus di sεrum kכnsantreshכn fכ inflammatory cytokines IL-6, MCP-1, εn TNF-α, we de impruv SLE simptom dεm{#Dahan, A,2016} (Dahan A, 2016). insay wan cisplatin-indyus nεfrotoksisiti mכdel, i de dכn di pro-inflammatory saytokεn dεm TNFα, IL6, εn IL1β, we de εliviet rεnal inflameshn ^[2] (Ghassemi-Barghi N, 2023). in anti-inflammatory mεkanism kin involv fכ tכk bכt di innate ripa rεsεpכta (IRR), we na hεterodaymεr fכ di εrythropoietin rεsεpכta εn β-kכmכn (CD131) rεsεpכta. di binding to IRR de aktibכt di dכwnstrim anti-inflammatory signal path dεm, we de dכn rεgεl di inflameshn ^{[1] .}.

Anti-Apoptotic Effect: ARA-290 de inhεbit sεl apoptosis εn i de protεkt di tisu sεl sכvayvεns. insay wan dayabεtik rat mכdel, i de sכpres di rεnal tכbul εpitεlial sεl apoptosis εn i de ridyus di εksprεshכn fכ di ki proteas dεm na di apoptotik prכsεs, we de mek i de εksyεrt rεnal protεktiv ifekt dεm. insay cisplatin-indyus nεfrotoksisiti mכdel dεm, i de rεgεl di εksprεshכn fכ apoptosis-rilayt protin dεm lεk Bax εn Bcl-2, i de inhεbit Caspase-3 aktiviti, i de ridyus sεl apoptosis, εn i de mitigate di cisplatin-indyus rεnal sεl dεmεj ^[2]..  

Anti-Oxidative Effect: ARA-290 de inhibit oksidativ strεs damej εn de ridyus di prodakshכn fכ bad bad tin dεm lεk riaktiv כksijεn spεs (ROS). insay wan dayabεtik rat kidni mכdel, i de sכpres di rεnal jin εksprεshכn, i de ridyus di rεnal ROS lεvεl dεm, εn i de dכn di malondialdehyde (MDA) εksprεshכn, we de εliviet כksidεtiv strεs-indyus rεnal dεmεj. insay atεrosklεrosis stכdi dεm, in vitro εkspεriεns dεn sho se ARA-290 de inhεbit ROS prodakshכn insay makrofag dεm כnda inflammatory kכndishכn, we de ridyus כksidεtiv strεs dεmεj to sεl dεm.  

rεgulεshכn fכ di imyun sεl fכnshכn: ARA-290 de rεgεl di fכnshכn fכ imyun sεl dεm lεk makrofag dεm. in vitro, i de inhεbit inflammatory aktibכshכn fכ makrofag dεm we i de promuot dεn fagosaytik fכnshכn tכwכd apoptotik sεl dεm, i de εp fכ mεnten imyun sistεm homכstasis εn klia apoptotik sεl dεm fכ avכyd inflameshn we kכz bay dεn akyumyuleshכn (Dahan A, 2016). insay atεrosklεrosis risεch, ARA-290 de inhεbit makrofag maygrεshכn εn fכm sεl fכmeshכn, we de ridyus lipid dεposishכn na di vaskulכr intima εn slo atεrosklεrosis prכgreshכn.

Nyuroprotεktiv mεkanism: insay wan maws mכdel fכ sεribra ischemia, ARA-290 de εksyεrt nyuroprotεktiv ifekt dεm tru di β-kכmכn rεsεpכta (βCR). i de ridyus di nyuronal apoptosis εn inflammatory cytokine lεvεl dεm na di bren tisu bכku bכku wan, we de impruv nyurolכjik fכnshכn. injεkshכn fכ βCR-tכgεt siRNA de sכmtεm inhεbit ARA-290 in nyuroprotεktiv ifekt dεm, we de sho se βCR de ple wan kכl rol insay in mεkanism ^[3]..  

Analjεsik mεkanism: ARA-290 kin εksyεrt analjεsik ifekt dεm bay we i de tכk bכt di pεrifεral nosisεpכr dεm dεn wan dεm. stכdi dεm sho se i spεshal inhεbit TRPV1 chεnal aktvכti εn i de εliviet kapsaysin-indyus mεkanikal allodynia, we sho se ARA-290 kin sav as nכvel TRPV1 chεnal antagonist, we de gi nyu insayt fכ pen tritmεnt ^[4]..  

Wetin na di aplikeshɔn dɛn fɔ ARA-290?

Tritmɛnt fɔ Nyuropathies

Pen Rilif ɛn Simptom Improvement: ARA-290 de rili rilivu nyuropatik pen, mɔ pan sik dɛn we gɛt nyuropathy lɛk dayabitis ɛn sarkoidosis. Insay klinik trayal fɔ sarkoidosis pasɛnt dɛn, ARA-290 bin impɔtant fɔ impɔtant nyuropati ɛn ɔtonomik nɛv simptom dɛm, ɛp fɔ mek di kwaliti fɔ layf bɛtɛ, ɛn i bin ridyus di pen skɔ dɛm, wit di sem kayn ifɛkt pan di wan dɛm we gɛt dayabitis nyuropathy. di mεkanism we i de du involv fכ biεn di innate ripa rεsεpכta (IRR), fכ aktibכt di anti-inflammatory εn tisu ripa path dεm, fכ rεgεl nyurojεnik inflameshn, εn fכ sכm pen ^{[1, 4].}.

 

Promoshכn fכ Nεv Fayba Rijεnεreshכn: ARA-290 de promoshכn fכ nεv fayba rigεnεreshכn. pan sarcoidosis pasεnshכn dεm, 28 kכnsekyutiv dez ARA-290 tritmεnt indyuz kכnia sכm sכm nεv fayb rigεnεreshכn, we sho ripεr kεpasiti fכ spεsifi k nεv fayb dεm εn pכtεnshal fכ impruv nyurolכjik fכnshכn, pan כl we i nכ bin gεt nכ ifekt pan epidamal nεv fayb dεm ^[1]..  

Ridyushɔn pan Nɛfrotoksisiti  

di dεkrεshכn Saytotoksisiti εn Jεnotoksisiti: Insay cisplatin-indyus nεfrotoksisiti mכdel dεm, ARA-290 de ridyus cisplatin-indyus saytotoksisiti εn jεnotoksisiti bכku bכku wan, lεk di dεkrεshכn DNA dεmεj paramita dεm insay kכmεt asεy εn maykronyuklios frεkwεns, fכ protεkt sεlyul jεnεtik mεtirial εn mitigate rεnal sεl dεmεj ^{[1] .}.

 

rεgulεshכn fכ כksidεtiv strεs εn inflameshn: ARA-290 de impruv di cisplatin-indyus כksidεtiv strεs bay we i de ridyus di malondialdehyde (MDA) εn ROS lεvεl dεm εn εnhans di antioksidant εnzym aktiviti. i de εliviet di rεnal inflameshn bak bay we i de dכn di pro-inflammatory saytokεn dεm (εgz., TNF-α, IL-6, IL-1β), we de protεkt εgεst cisplatin-induse rεnal injuri ^[1]. .  

inhibishכn fכ Apoptosis: ARA-290 de inhεbit cisplatin-indyus apoptosis bay we i de rεgεl di apoptosis-rεlatεd jin dεm εn protin dεm (εgz., i de dכn di Caspase-3 εn Bax εksprεshכn, i de inkrεs Bcl-2 εksprεshכn), i de mεnten di rεnal sεl sכvayvεns εn i de hכl pכtεnshal fכ trit akyu kidni injuri pasεnshכn dεm ^[1].  

Improvement of Dipreshɔn Simptom dɛm  

Alivieshɔn fɔ Dipreshɔn-Lɛk Bihayvya: Insay maws mɔdel dɛm fɔ krɛse unprediktibɛl mild strɛs ɛn krɛse soshal dɛf strɛs, ɛvride ARA-290 administreshɔn impruv dipreshɔn-layk bihayvya, kɔmparabl to di kɔmɔn antidipreshɔn fluoxetine. ARA-290 bin εksεrt antidipreshכn ifekt dεm we nכ bin rili afekt di pεrifεral hεmoglobin כ rεd blכd sεl dεm ^[5]..  

rεgulεshכn fכ di imyun sεl dεm εn inflameshn: ARA-290 de rivεs di krכnik strεs-indyuz inkrεs pan di frεkwεns εn nכmba fכ CD11b0Ly6Ghi nyutrofil dεm εn CD11b+Ly6Chi monosayt dεm na bon mכro εn mεninges, εn bak maykroglial aktibכshכn, we de εliviet diprεsiv simptom dεm tru anti-inflammatory ifekt dεm εn gi nyu tritmεnt di rod dɛm fɔ pwɛl hat ^{[5] .}.  

Protɛkshɔn Agens Dayabitik Kidni Damej  

inhibishכn fכ di rεnal tubular εpitεlial apoptosis: ARA-290 de inhεbit di rεnal tubular εpitεlial sεl apoptosis, we de ridyus programmεd sεl dεd εn protεkt rεnal sεl dεm.  

Improvement of Renal Function Markers: ARA-290 de dכn di urinary albumin excretion rate in diabetic rat, i de mek di rεnal patכlayz damej, impruv di rεnal fכnshכn, εn i de delay di dayabitis nεfropathy prכgreshכn.  

Tritmɛnt fɔ Sistɛmik Lupus Ɛritɛmatosɔs (SLE) .  

inhibishכn fכ כtoantibodi prodakshכn εn imyun kכmpleks dεposishכn: ARA-290 de inhεbit sכmtεm inhεbit di sεrum antinyukliar antibodi (ANA) εn anti-dכbl-strand DNA antibodi lεvεl dεm na indyuz SLE mays, i de ridyus IgG εn C3 dεposishכn na di kidni dεm, i de εliviet di nεfrayt simptom dεm, εn i de impruv di sik prכgreshכn ^[6]..  

Figure 1 ARA290 tritmεnt sכpres inflammatory rεspכns in pristane‐indyus SLE mays. (A) Di lεvεl dεm fכ IL‐6, IL‐10, MCP‐1, IFN‐γ, TNF‐α, IL‐12p70 εn TGF‐β insay di sεrum we de fala di tritmεnt we dεn dεskrεb na Fig 1 bin dεtekt (n = 6). (B) Di inflammatory makrofag F4/80 infiltreshכn bin sכmtεm sכpres bay ARA 290 intavεnshכn kכmpεr to PBS kכntrכl. (C) Di splin ɛn limf node wet dɛn bin mɛzhɔ fɔ fala ARA290 we dɛn trit insay SLE mays (n = 6). Skel bar dɛn de riprizent 30 μm.

Sos:PubMed ^{[6] we dɛn pul am.}

rεdukshכn fכ di Inflammatory Cytokine Levels: ARA-290 de dכn di sεrum kכnsantreshכn fכ inflammatory cytokine IL-6, MCP-1, εn TNF-α insay SLE mays, i de ridyus inflameshכn εn i de εliviet di sik simptom dεm ^[6]..  

di apoptosis we dεn dכn dכn: ARA-290 de ridyus di nכmba fכ di apoptotik sεl dεm na di kidni dεm, i de protεkt di rεnal sεl dεm, εn i de inhεbit inflammatory aktibכshכn fכ makrofag dεm we i de promuot dεn fagosaytosis fכ di apoptotik sεl dεm in vitro, i de rεgεl di imyun sistεm εn i de hכld pכtεnshal fכ SLE tritmεnt ^[6]..  

Mitigashɔn fɔ Kimotɛrapi Drug Tɔksisiti  

rεdukshכn fכ DNA Dεmεj: insay dכksorubisin (DOX)-indyus saytotoksisiti mכdel dεm, ARA-290 de ridyus DOX-indyus DNA dεmεj bכku bכku wan, lεk fכ dכn di tel DNA pasεnshכn insay kכmεt asεy εn maykronyuklios frεkwεns, fכ protεkt sεlyul jεnεtik mεtirial εn ridyus kεmothεrapi dεmεj to nכmal sεl dεm ^[7]..  

εliviεshכn כf כksidεtiv strεs εn inflameshכn: ARA-290 de mitigate DOX-indyuz impεryans כf antioksidant εnzym aktiviti, rεdכks inflameshכn εn apoptosis, εn protεkt εgεst DOX-indyus כksidεtiv strεs εn sεl dεmεj, we kin inklud kadyak sεl dεm, fכ εliviet di bad ifekt dεm pan kεmothεrapi pasεnshכn dεm ^[7].  

Prɛvenshɔn ɛn Tritmɛnt fɔ Alzaima Sik  

Slowed Pathological Progression and Improved Cognition: di εli administreshכn fכ ARA-290 in yכng APP/PS1 mays dεm (εli Alzheimer mכdel) de slo β-amyloid (Aβ) patכlayz prכgrεshכn εn impruv kכgnitiv fכnshכn, we de hεlayt in siginifikכns fכ εli intavεnshכn ^[8]..

rεgulεshכn fכ Monocyte Fכnshכn: ARA-290 spεshal wan de stimul di jεnereshכn fכ Ly6C− we de patrul monosayt sכbsεt dεm, i de inkrεs dεn sirkulεt lεvεl dεm, i de protεkt Aβ kliarεns frכm sεribra blכd vεsul dεm, i de ridyus di bren Aβ bכdi, εn i de dilay di sik prכgreshכn. כltu, i nכ de wok bכku pan let-stej mכdel dεm (εj APP/PS1 mays), we de כndaskכr di imכpכtants fכ εli intavεnshכn ^[8]..  

Promoshɔn fɔ Dayabitik Wund Hiling

Aksεlεrayt Wכnd Kloz: Insay strεptozotocin-indyus dayabεtik insishכnal wund rat mכdel dεm, lokal ARA-290 aplikεshכn de sכmtεm aksεlεrayt wund kכloshכn, sכt rεpithelialization tεm, εn impruv wund hεlin efyushכn ^[9]. .  

rεgulεshכn fכ di Tisu Ripa Makεr dεm: ARA-290 de inkrεs kolagen εn protin kכntεnt insay ripa tisu dεm, de rεgεl di sεrum insulin, bכdi glukכs, lipid lεvεl, antioksidant stetכs, εn pro-inflammatory cytokine lεvεl, we de mek wan maykro envayroment we fayn fכ wund hεl εn gi nyu stratεji fכ trit dayabεtik fut כlsa ^{[9] .}.  

Fɔ mek pɔsin nɔ fil pen  

inhibishכn fכ TRPV1 Chanεl Aktiviti: ARA-290 de rilif kapsaysin-indyus mεkanikal allodynia bay we i de inhεbit transiεnt rεsεptכr pכtεnshal vεniloyd sכbtayp 1 (TRPV1) chanεl aktvכti, dεn de tכk bכt di pεrifεral nosisεptor dεm dεn wan εn de gi nyu tεrapi tכgεt εn aprכch fכ pen tritmεnt ^[4]..  

Dɔn  

ARA-290 na EPO-dεrivεd polypεptida wit anti-inflammatory, anti-apoptotic, εn anti-oxidative ifekt dεm. I kin trit pen we yu gɛt dayabitis ɛn sarkoidosis, i kin mek di nerve fayba kam bak, i kin fɛt di nephrotoxicity, SLE, dipreshɔn, ɛn i kin mek di pen nɔ bɔku bay we i de agens TRPV1. Wit potenshal in eli Alzaima intavɛnshɔn ɛn ɔda fild dɛm, i de ol brayt klinik aplikeshɔn prɔspɛkt dɛm.

Bɔt di pɔsin we rayt di buk

Di tin dɛm we wi dɔn tɔk bɔt ɔp na ɔl di risach, ɛdit ɛn kɔmpilayt na Cocer Peptides.

Sayɛns Jɔnal Author

Al-Onaizi, Mohammed na masta sabi bukman we gɛt dip ɛkspɛriɛns pan di fild fɔ bayɔmedisin. I gɛt tayt padi biznɛs wit sɔm big big akademik ɛn risach institiushɔn dɛn, lɛk Dasman Dayabitis Instityut (DDI), Kuwait Yunivasiti, Laval Yunivasiti, Wɛstɛn Yunivasiti (Yunivasiti ɔf Wɛstɛn Ɔntɛrio), ɛn Ibru Yunivasiti na Jerusɛlɛm. In risach intɛres na brayt, i kɔba Nyurosayns & Nyurolɔji, Bayokɛmistri & Mɔlikul Bayoloji, Imyunɔlɔji, Saykayatri, ɛn ɔda tɔpik dɛn na Layf Sayns & Bayomɛdisin. Dɛn disiplin ya impɔtant fɔ gɛt dip ɔndastandin bɔt aw mɔtalman bɔdi de wok, aw di sik kin du, ɛn aw fɔ mek nyu tritmɛnt dɛn. Al-Onaizi, Mohammed in risach dɔn ajɔst impɔtant rizɔlt insay besik sayɛns ɛn i dɔn gi impɔtant tiori sɔpɔt ɛn prɛktikal gayd fɔ klinik mɛdisin ɛn bayɔmɛdikal risach.. Al-Onaizi, Mohammed de list insay di rɛfrɛns fɔ saytayshɔn [8].

▎ Saytayshɔn dɛn we gɛt fɔ du wit dis

[1] Dahan A, Brines M, Niɛsters 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.

[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] 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.

[4] Zhang W, Yu G, Zhang M. ARA 290 de rilif pathophysiological pen bay we i de tכgεt TRPV1 chεnal: Integrεshכn bitwin imyun sistεm εn nosisepshכn[J]. Pεptid, 2016,76:73-79.DOI:10.1016/j.pεptida.2016.01.003.

[5] 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]. Frontiers in Famakɔlɔji, 2022,13:896601.

DOI: 10.3389/fphar.2022.896601. Di wan dɛn we de wok fɔ di kɔmni.

[6] 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.

[7] Shokrzadeh M, Etebari M, Ghassemi-Barghi N. Wan εnjinia nכn-εritropoiεtik εrythropoietin-dεriv pεptida, ARA290, de atεnuet dכksorubisin indyuz jεnotoksisiti εn כksidεtiv strεs[J]. Toksikɔlɔji in Vitro, 2020,66:104864.

DOI: 10.1016/j.tiv.2020.104864. Di wan dɛn we de wok fɔ di kɔmni.

[8] Al-Onaizi M. A., T ɛ riault P, L ɛ k ɔ d ɛ r S, ɛn ɔda pipul dɛn. εli monosayt mכduleshכn bay di nכn-εritropoiεtik pεptida ARA 290 de dεsεlεrayt AD-lεk patכlayz prכgrεshכn[J]. Bren Biheviɔr ɛn Imyuniti, 2022,99:363-382.

DOI: 10.1016/j.bbi.2021.07.016. Di wan dɛn we de stɔdi bɔt di Baybul.

[9] 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.DOI:10.21203/rs.3.rs-2520194/v1.

ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL DI INFƆMƐSHƆN DISƐMƐNƐSHƆN 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.