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▎ ARA-290 Ọdịdị
Isi mmalite: PubChem |
Usoro: XEQLERALNSS Ụdị mkpụrụ ndụ: C 51H 84N 16O21 Arọ molekụla: 1257.3g/mol Nọmba CAS: 1208243-50-8 PubChem CID: 91810664 Ihe atụ: Cibinetide |
▎ ARA-290 Nnyocha
Kedu ihe ndabere nyocha nke ARA-290?
Mmepe nke ARA-290 sitere na inyocha ike ọgwụgwọ nke erythropoietin (EPO). Ndị ọkà mmụta sayensị chọpụtara na ọ bụghị nanị na EPO na-akwalite erythropoiesis kamakwa ọ nwere ọrụ nchebe anụ ahụ dị ka mgbochi mkpali na mgbochi apoptosis. Otú ọ dị, mkpali hematopoietic nke EPO nwere ike ime ka viscosity ọbara dịkwuo elu na ihe ize ndụ ndị ọzọ, na-egbochi iji ya na-agwọ ọrịa ndị na-abụghị ndị na-adịghị anaemia. Iji jide mmetụta nchebe anụ ahụ nke EPO ma na-ezere mmetụta hematopoietic ya, ndị nchọpụta malitere ịmepụta peptides na-emepụta ihe, na-eduga na ịmepụta ARA-290.
Site na nyocha miri emi, uru pụrụ iche nke ARA-290 dị ka peptide na-abụghị hematopoietic ji nwayọọ nwayọọ mata. Ọ na-arụ ọrụ mgbochi mkpali na nrụzi anụ ahụ ụzọ mgbaàmà site na-ejikọta na innate ndozi receptor (IRR), na-egosipụta na-ekwe nkwa mmetụta n'ịgwọ ọrịa shuga mellitus, neuropathy, na akụrụ mmerụ. Nchọpụta ndị a tọrọ ntọala maka nyocha ọzọ na ngwa ụlọ ọgwụ nke ARA-290 ma kwalite mmepe nke usoro ọgwụgwọ ọhụrụ dabere na peptides sitere na EPO.
Kedu ihe bụ usoro nke ARA-290?
Mmetụta Mgbochi Ọrịa: ARA-290 na-egbochi nzuzo nke cytokines na-egbuke egbuke, si otú a na-ebelata nzaghachi mkpali, dị ka e gosipụtara na ọtụtụ ụdị ọrịa. Dịka ọmụmaatụ, na ụdị òké nke lupus erythematosus systemic (SLE), ọ na-ebelata mkpokọta serum nke cytokines na-egbuke egbuke IL-6, MCP-1, na TNF-α, na-eme ka mgbaàmà SLE dịkwuo mma {#Dahan, A,2016} (Dahan A, 2016). N'ụdị nephrotoxicity nke cisplatin na-ebute, ọ na-ebelata cytokines pro-inflammatory TNFa, IL6, na IL1β, na-ebelata mbufụt renal [2] (Ghassemi-Barghi N, 2023). Usoro mgbochi mkpali ya nwere ike ịgụnye ịchụdo onye na-anabata nrụzi ebumpụta ụwa (IRR), heterodimer nke onye na-anabata erythropoietin na β-common (CD131). Njide na IRR na-arụ ọrụ ụzọ mgbama mgbochi mkpali mgbada, si otú ahụ na-ebelata mbufụt [1].
Mmetụta Mgbochi Apoptotic: ARA-290 na-egbochi apoptosis cell ma na-akwalite ndụ sel anụ ahụ. N'ụdị oke oke ọrịa shuga, ọ na-egbochi apoptosis renal tubular epithelial cell apoptosis ma na-ebelata ngosipụta nke isi proteases na usoro apoptotic, si otú ahụ na-enwe mmetụta nchebe gbasara akụrụ. N'ụdị nephrotoxicity nke cisplatin na-ebute, ọ na-achịkwa okwu nke protein ndị metụtara apoptosis dị ka Bax na Bcl-2, na-egbochi ọrụ Caspase-3, na-ebelata apoptosis cell, ma na-ebelata mmebi mkpụrụ ndụ nke cisplatin kpatara [2].
Mmetụta mgbochi Oxidative: ARA-290 na-egbochi mmebi nrụgide oxidative ma belata mmepụta nke ihe ndị na-emerụ ahụ dị ka ụdị oxygen na-emeghachi omume (ROS). N'ụdị akụrụ oke na-arịa ọrịa shuga, ọ na-egbochi okwu mkpụrụ ndụ gbasara akụrụ, na-ebelata ọkwa ROS renal, ma na-ebelata okwu malondialdehyde (MDA), na-ebelata mmebi akụrụ na-akpata nrụgide oxidative. N'ime nchọpụta nke atherosclerosis, nnwale in vitro na-egosi na ARA-290 na-egbochi mmepụta ROS na macrophages n'okpuru ọnọdụ mkpali, na-ebelata nrụgide oxidative mmebi nke mkpụrụ ndụ.
Iwu nke Ọrụ Cell Immune: ARA-290 na-achịkwa ọrụ nke sel ndị na-adịghị ike dịka macrophages. Na vitro, ọ na-egbochi mkpali mkpali nke macrophages mgbe ha na-akwalite ọrụ phagocytic ha na mkpụrụ ndụ apoptotic, na-enyere aka ịnọgide na-enwe usoro mgbochi homeostasis na sel apoptotic doro anya iji zere mbufụt kpatara mkpokọta ha (Dahan A, 2016). N'ime nyocha nke atherosclerosis, ARA-290 na-egbochi ịkwaga macrophage na nhazi cell foam, na-ebelata ntinye lipid na intima vaskụla ma na-ebelata ọganihu atherosclerosis.
Mechanism Neuroprotective: N'ụdị òké nke ischemia cerebral, ARA-290 na-arụ ọrụ neuroprotective site na β-common receptor (βCR). Ọ na-ebelata nke ukwuu apoptosis neuronal na ọkwa cytokine na-egbu egbu na anụ ahụ ụbụrụ, na-eme ka ọrụ akwara dị mma. Ntunye nke βCR-ezubere iche siRNA na-egbochi mmetụta neuroprotective ARA-290 nke ukwuu, na-egosi na βCR na-arụ ọrụ dị mkpa na usoro ya [3].
Usoro analgesic: ARA-290 nwere ike ịkpata mmetụta analgesic site n'ịtụkwasị ndị nociceptors elu ozugbo. Nnyocha na-egosi na ọ na-egbochi ọrụ ọwa TRPV1 kpọmkwem ma na-ebelata capsaicin-induced mechanical allodynia, na-atụ aro ARA-290 nwere ike ịbụ onye na-emegide ọwa TRPV1 ọhụrụ, na-enye nghọta ọhụrụ maka ọgwụgwọ mgbu [4].
Kedu ihe bụ ngwa ARA-290?
Ọgwụgwọ Neuropathies
Mgbu mgbu na Mmelite Mgbaàmà: ARA-290 na-ebelata ihe mgbu neuropathic nke ọma, karịsịa na ọrịa ndị nwere neuropathy dị ka ọrịa shuga na sarcoidosis. N'ime ule ụlọ ọgwụ maka ndị ọrịa sarcoidosis, ARA-290 kwalitere neuropathy na autonomic nerve mgbaàmà, ndụ ndụ na-eme ka ọ dịkwuo mma, ma belata ọnụ ọgụgụ mgbu, na-enwe mmetụta yiri nke ahụ na ndị ọrịa neuropathy na-arịa ọrịa shuga. Usoro ya gụnyere ijikọ na onye na-anabata ihe nrụzi (IRR), na-arụ ọrụ mgbochi mkpali na ụzọ nrụzi anụ ahụ, na-achịkwa mbufụt neurogenic, na ibelata mgbu [1, 4]..
Nkwalite nke Nerve Fiber Regeneration: ARA-290 na-akwalite mmeghari akwara akwara. N'ime ndị ọrịa sarcoidosis, ụbọchị 28 na-esochi nke ọgwụgwọ ARA-290 kpatara corneal obere akwara akwara, na-egosipụta ikike nrụzi maka ụfọdụ akwara akwara na ikike iji melite ọrụ akwara ozi, n'agbanyeghị na ọ nweghị mmetụta na eriri akwara epidermal [1].
Mbelata nke Nephrotoxicity
Mbelata Cytotoxicity na Genotoxicity: N'ime ụdị nephrotoxicity nke cisplatin kpatara, ARA-290 na-ebelata cytotoxicity nke cisplatin na genotoxicity nke ukwuu, dị ka ibelata mmebi mmebi DNA na nyocha comet na micronucleus ugboro, na-echebe mkpụrụ ndụ mkpụrụ ndụ ihe nketa na ibelata mmebi akụrụ ..
Iwu nke Nchegbu Oxidative na mbufụt: ARA-290 na-eme ka nrụgide oxidative na-akpata cisplatin site na ibelata malondialdehyde (MDA) na ọkwa ROS na ịkwalite ọrụ enzyme antioxidant. Ọ na-ebelata mbufụt gbasara akụrụ site na ibelata cytokines pro-inflammatory (dịka ọmụmaatụ, TNF-a, IL-6, IL-1β), na-echebe megide mmerụ ahụ na-ebute cisplatin [1] .
Mgbochi nke Apoptosis: ARA-290 na-egbochi apoptosis nke cisplatin kpatara site n'ịchịkwa mkpụrụ ndụ ihe nketa na protein ndị metụtara apoptosis (dịka ọmụmaatụ, ibelata Caspase-3 na okwu Bax, na-abawanye okwu Bcl-2), na-edobe ndụ mkpụrụ ndụ gbasara akụrụ na ijide ikike ịgwọ ndị ọrịa akụrụ dị ukwuu [1].
Mmelite nke mgbaàmà ịda mbà n'obi
Mbelata nke ịda mbà n'obi-dị ka omume: N'ime ụdị òké nke nrụgide dị nro na-adịghị ala ala na-adịghị ala ala na-adịghị ala ala, nchịkwa ARA-290 kwa ụbọchị na-eme ka omume ịda mbà n'obi dịkwuo mma, tụnyere fluoxetine antidepressant nkịtị. ARA-290 gosipụtara mmetụta antidepressant na-enweghị mmetụta dị ukwuu na hemoglobin mpụta ma ọ bụ ọbara ọbara uhie [5].
Iwu nke mkpụrụ ndụ na-egbu egbu na mbufụt: ARA-290 na-agbanwe mmụba na-adịghị ala ala nke na-akpata nrụgide na ugboro na ọnụọgụ CD11b⁺Ly6Ghi neutrophils na CD11b⁺Ly6Chi monocytes na ụmị ọkpụkpụ na meninges, yana ịgbalite microglial, na-ebelata mgbaàmà ịda mbà n'obi na-enye mmetụta nke ịda mbà n'obi na ụzọ ọgwụgwọ ọhụrụ ..
Nchedo megide mmebi akụrụ ọrịa shuga
Mgbochi nke Renal Tubular Epithelial Apoptosis: ARA-290 na-egbochi renal tubular epithelial cell apoptosis, na-ebelata ọnwụ cell emebere na ichebe mkpụrụ ndụ gbasara akụrụ.
Mmelite nke ihe nrịbama gbasara ọrụ gbasara akụrụ: ARA-290 na-ebelata ọnụego mmịpụta nke albumin na mmamịrị na oke ndị ọrịa mamịrị, na-ebelata mmebi akwara gbasara akụrụ, na-eme ka ọrụ akụrụ dịkwuo mma, na-egbu oge na-aga n'ihu nephropathy na-arịa ọrịa shuga.
Ọgwụgwọ nke Lupus Erythematosus (SLE)
Mgbochi nke Mmepụta Autoantibody na Immune Complex Deposition: ARA-290 na-egbochi nke ọma serum antinuclear antibody (ANA) na mgbochi mgbochi DNA nke nwere mgbochi abụọ na-ebute ụmụ oke SLE, na-ebelata ntinye IgG na C3 na akụrụ, na-ebelata mgbaàmà nephritis, ma na-eme ka ọrịa na-aga n'ihu [6].
Nyocha 1 ARA290 ọgwụgwọ kwụsịrị nzaghachi mkpali na ụmụ oke SLE nke pristane kpatara. (A) Achọpụtara ọkwa nke IL-6, IL-10, MCP-1, IFN-γ, TNF-α, IL-12p70 na TGF-β na serum na-esote ọgwụgwọ akọwara na Figure 1 (n = 6). (B) Mmụba macrophage F4/80 na-afụ ụfụ bụ nke ARA 290 na-etinye aka na-ebelata nke ukwuu ma e jiri ya tụnyere njikwa PBS. (C) A tụrụ splin na ọnụ ọnụ ọnụ lymph na-esote ọgwụgwọ ARA290 na ụmụ oke SLE (n = 6). Ogwe ọnụ ọgụgụ na-anọchite anya 30 μm.
Isi mmalite: PubMed [6]
Mbelata nke ọkwa Cytokine na-egbuke egbuke: ARA-290 na-ebelata mkpokọta serum nke cytokines na-egbuke egbuke IL-6, MCP-1, na TNF-α na ụmụ oke SLE, na-ebelata mbufụt na ibelata mgbaàmà ọrịa [6]..
Mbelata Apoptosis: ARA-290 na-ebelata ọnụ ọgụgụ nke mkpụrụ ndụ apoptotic na akụrụ, na-echebe mkpụrụ ndụ akụrụ, ma na-egbochi mkpali nke macrophages mgbe ha na-akwalite phagocytosis nke mkpụrụ ndụ apoptotic in vitro, na-achịkwa usoro ahụ ji alụso ọrịa ọgụ na ijide ikike maka ọgwụgwọ SLE [6].
Mbelata nke nsi ọgwụ Chemotherapeutic
Mbelata mmebi DNA: Na ụdị cytotoxicity nke doxorubicin (DOX), ARA-290 na-ebelata mmebi DNA nke DOX na-akpata, dị ka ibelata pasent DNA ọdụ na nyocha comet na micronucleus ugboro, na-echebe mkpụrụ ndụ ihe nketa cell na ibelata mmebi chemotherapeutic na sel nkịtị [7].
Mbelata nke nrụgide Oxidative na mbufụt: ARA-290 na-ebelata mmebi nke DOX na-akpata ọrịa enzyme antioxidant, na-ebelata mbufụt na apoptosis, ma na-echebe megide nrụgide oxidative nke DOX na mmebi cell, nke nwere ike ịgụnye mkpụrụ ndụ obi obi, iji belata mmetụta ọjọọ na ndị ọrịa chemotherapy [7].
Mgbochi na ọgwụgwọ ọrịa Alzheimer
Ọganihu Pathological Slowed na Mmalite Nghọta: Nlekọta mmalite nke ARA-290 na ụmụ oke APP / PS1 na-eto eto (ụdị Alzheimer mbụ) na-ebelata β-amyloid (Aβ) ọganihu pathological ma na-eme ka ọrụ ọgụgụ isi dịkwuo mma, na-egosipụta mkpa ọ dị maka ntinye aka n'oge [8].
Iwu nke Ọrụ Monocyte: ARA-290 kpọmkwem na-akpali ọgbọ nke Ly6C⁻ patrolling monocyte subsets, na-abawanye ọkwa ha na-ekesa, na-akwalite nkwụsị Aβ site na arịa ọbara ụbụrụ, na-ebelata ụbụrụ Aβ ụbụrụ, na-egbu oge ọganihu ọrịa. Agbanyeghị, ọ naghị arụ ọrụ nke ọma na ụdị oge ikpeazụ (ndị agadi APP/PS1 merela agadi), na-egosi mkpa ọ dị itinye aka n'oge [8].
Nkwalite ọgwụgwọ ọnya ọrịa shuga
Mmechi ọnya dị ngwa ngwa: N'ụdị oke ọnya ọrịa shuga na-akpata ọrịa shuga streptozotocin, ngwa ARA-290 mpaghara na-eme ka mmechi ọnya dịkwuo ngwa ngwa, na-ebelata oge iweghachite, ma na-emeziwanye ọgwụgwọ ọnya [9] .
Iwu nke ihe nrịbama ndozi anụ ahụ: ARA-290 na-abawanye collagen na protein ọdịnaya n'ime anụ ahụ nrụzi, na-achịkwa insulin serum, glucose ọbara, ọkwa lipid, ọkwa antioxidant, na ọkwa cytokine pro-inflammatory, na-ekepụta microenvironment na-enyere aka ịgwọ ọnya na inye usoro ọhụrụ maka ịgwọ ọnya ụkwụ nke ọrịa shuga [9].
Mgbu mgbu
Mgbochi nke Ọrụ Channel Channel TRPV1: ARA-290 na-eme ka allodynia na-akpata capsaicin site na igbochi ọrụ nke vanilloid subtype 1 (TRPV1), na-elekwasị anya n'akụkụ nociceptors na-enye ọgwụgwọ ọhụrụ na ụzọ maka ọgwụgwọ mgbu [4].
Mmechi
ARA-290 bụ polypeptide sitere na EPO nwere mgbochi mkpali, mgbochi apoptotic, na mgbochi oxidative. Ọ nwere ike ịgwọ ihe mgbu na ọrịa shuga na sarcoidosis, na-akwalite mmepụta akwara akwara, ọgụ nephrotoxicity, SLE, ịda mbà n'obi, na ibelata ihe mgbu site na imegide TRPV1. N'ịbụ onye nwere ike ịmalite enyemaka Alzheimer na mpaghara ndị ọzọ, ọ na-enwe atụmanya ngwa ụlọ ọgwụ sara mbara.
Banyere Onye dere ya
Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.
Onye ode akwụkwọ akụkọ sayensị
Al-Onaizi, Mohammed bụ ọkammụta nwere nka miri emi na ngalaba nke biomedicine. O nwere njikọ chiri anya na ọtụtụ ụlọ akwụkwọ agụmakwụkwọ na nyocha, gụnyere Dasman Diabetes Institute (DDI), Mahadum Kuwait, Mahadum Laval, Mahadum Western (Mahadum Western Ontario), na Mahadum Hibru nke Jerusalem. Ihe gbasara nyocha ya sara mbara, na-ekpuchi Neurosciences & Neurology, Biochemistry & Molecular Biology, Immunology, Psychiatry, na isiokwu ndị ọzọ na Life Sciences & Biomedicine. Ọzụzụ ndị a dị oke mkpa maka inweta nghọta miri emi nke usoro physiological mmadụ, usoro ọrịa, na mmepe nke ọgwụgwọ ọhụrụ. Al-Onaizi, nyocha Mohammed enwetala nsonaazụ dị ịrịba ama na sayensị ndị bụ isi ma nyekwa nkwado usoro ihe ọmụma dị mkpa na nduzi bara uru maka ọgwụ ahụike na nchọpụta biomedical .. Al-Onaizi, Mohammed ka edepụtara na ntinye aka [8].
