Na Cocer Peptides 
29 lā aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a i ʻole maʻi. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
Nānā nui
ʻO ARA-290 he 11-amino acid linear non-hematopoietic polypeptide i loaʻa mai ka erythropoietin (EPO). Hoʻohana ia i nā hopena olaola like ʻole ma o ka hoʻopaʻa ʻana i ka innate repair receptor (IRR). ʻAʻole e like me EPO, mālama ʻo ARA-290 i nā hana anti-inflammatory a me nā hana pale kino o ka EPO.
Kiʻi 1 Hōʻike ʻia ka biology o ka mea hoʻoponopono hoʻoponopono kino e ka hoʻokaʻawale ʻana a me ka spatial o kona mau subunits loaʻa, i hui pū ʻia e hana i ka mea hoʻoponopono hou a me kona ligand endogenous, hyposialated erythropoietin (hEPO).
Mechanism of Action
(1) Nā hopena anti-inflammatory
Hoʻopaʻa i ka hoʻoulu ʻana o ka cell inflammatory: Ma nā ʻano hoʻohālike inflammatory, hōʻike ʻo ARA-290 i ka hiki ke kāohi i ka hoʻoulu ʻana o ka cell inflammatory. No ka laʻana, i loko o kahi hiʻohiʻona hoʻohaʻahaʻa ʻiole i hoʻoulu ʻia e ke koʻikoʻi mau loa, hoʻololi ka hoʻokele ʻana o ARA-290 i kēlā me kēia lā i ka piʻi ʻana o ke alapine a / a i ʻole ka helu o CD11b⁺Ly6Gʰⁱ neutrophils a me CD11b⁺Ly6Cⁱ monocytes i loko o ka iwi iwi a me nā meninges i hoʻokumu ʻia e ke koʻikoʻi maʻamau, ʻoiai e hoʻohuli ana i ka microglia-induce like i laila. ka hana ʻana i nā ʻiole, me nā hopena like me nā fluoxetine.
Hoʻoponopono i ka huna ʻana o ka mea inflammatory: ARA-290 hoʻoponopono pono i ka huna ʻana o nā mea inflammatory. I loko o ka systemic lupus erythematosus (SLE) kiʻiʻiole, ARA-290 hoemi serum pae o inflammatory cytokines IL-6, MCP-1, a me TNF-α, hoʻopau loa i ka serum antinuclear autoantibodies (ANAs) a me ka anti-double-stranded DNA autoantibodies, hoemi IgG a me C3 nephritis, a hoʻomaikaʻi i ka nephritis. I loko o ka cisplatin-induced nephrotoxicity model, pre-treatment with ARA-290 i hoʻemi ʻia nā pae o nā cytokine pro-inflammatory e like me TNF-α, IL-6, a me IL-1β, a laila e hoʻohaʻahaʻa i nā pane ʻeha i loko o ka ʻiʻo renal.
Kāohi i nā ala hōʻailona inflammatory: Hiki i ka ARA-290 ke hoʻohana i kāna mau hopena anti-inflammatory ma ke kāohi ʻana i kekahi mau ala hōʻailona pili i ka mumū. Ma ka hoʻopaʻa ʻana i ka IRR, hiki ke hoʻopili i kahi ʻano o nā hanana molecular downstream e pili ana i nā pane ʻeha, a laila ke kāohi ʻana i ka hoʻouna ʻana a me ka hoʻonui ʻana i nā hōʻailona inflammatory a hoʻopau i nā hopena inflammatory.
(2) Nā hopena immunomodulatory
Hoʻoponopono i ka hana macrophage: He kuleana koʻikoʻi ko ARA-290 i ka hana macrophage. Hōʻike nā hoʻokolohua in vitro hiki iā ia ke kāohi i ka hoʻoulu ʻana o nā macrophages i ka wā e hāpai ana i kā lākou hana phagocytic i nā cell apoptotic. I loko o kahi kiʻi ʻiole SLE, hoʻemi ʻo ARA-290 i ka helu o nā cell apoptotic i loko o nā puʻupaʻa ma o ka hoʻoponopono ʻana i ka hana macrophage, ʻo ia paha kekahi o nā hana koʻikoʻi i lalo o kona hoʻomaikaʻi ʻana i nā hōʻailona SLE.
Ka hopena i ke koena o ka cell immune: I kekahi mau ʻano maʻi, hiki i ka ARA-290 ke hoʻokō i nā hopena hoʻoponopono kūlohelohe ma o ka hoʻololi ʻana i ke kaulike ma waena o nā heluna cell immune. I loko o kahi hoʻohālike hoʻohaʻahaʻa ʻiole i hoʻoulu ʻia i ke kaumaha, ʻo ka hoʻoponopono ʻana o ARA-290 i nā heluna cell immune kikoʻī i loko o ka iwi iwi a me nā meninges e kōkua i ka hoʻihoʻi ʻana i ke koena cell immune, a laila e hoʻemi i ka hopena o nā pane ʻeha ma ka ʻōnaehana nerve a me ka hoʻomaikaʻi ʻana i ke ʻano depressive-like.
Kiʻi 2 ʻO ka hoʻoulu ʻana o nā mea hoʻoponopono hou e hōʻemi i ka allodynia mechanical ma hope o ka hōʻeha ʻana i ke aʻalolo (SNI) i nā ʻiole.
(3) Nā hopena pale o ka ʻili
Hoʻoikaika i ka hoʻoponopono a me ka hana hou ʻana: ARA-290 hōʻike i ka hiki ke hoʻoikaika i ka hoʻoponopono ʻana a me ka hana hou ʻana i nā hiʻohiʻona hōʻeha kino. Ma ke ʻano ʻiole maʻi maʻi maʻi ʻeha (DFU), ʻo ka noi kūloko o ARA-290 e hoʻolalelale i ka pani ʻana i ka ʻeha, hoʻonui i ka collagen a me ka protein, a hoʻoikaika i ka hoʻoponopono ʻana i ka ʻeha. Loaʻa kēia ma ka hoʻoulu ʻana i ka IRR, ʻo ia ka mea e hoʻomaka ai i ke ʻano o nā ala hōʻailona intracellular, e hāpai ana i ka hoʻonui ʻana o ka cell, migration, a me ka hoʻokaʻawale ʻana, e alakaʻi ana i ka hoʻoponopono ʻana i nā kiko.
Hoʻemi i ka pōʻino koʻikoʻi oxidative: He hana koʻikoʻi ke koʻikoʻi oxidative i ka hoʻomohala ʻana i nā maʻi e pili ana i ka mumū. Hiki i ka ARA-290 ke hōʻemi i ka pōʻino i hoʻoulu ʻia i ke kaumaha oxidative. I nā haʻawina e pili ana i ka atherosclerosis (AS), hiki i ka ARA-290 ke kāohi i ka hana ʻana o nā ʻano oxygen reactive (ROS) e nā macrophages ma lalo o nā kūlana inflammatory, hoʻemi i nā pae koʻikoʻi oxidative, a hoʻemi i ka pōʻino i nā cell endothelial i hoʻokumu ʻia e nā lipoproteins oxidatively modified, no laila ke keʻakeʻa nei i ka holomua o AS. I loko o ka cisplatin-induced nephrotoxicity model, ARA-290 alleviates oxidative stress-induced kidney poino ma ka hoʻonui ʻana i nā pae antioxidant enzyme, me ka glutathione peroxidase (GPx) a me ka superoxide dismutase (SOD), a me ka hoʻemi ʻana i ka malondialdehyde (MDA) a me nā pae ROS.
Nā noi
(1) Nā maʻi neurological
Depressive Disorders: Ua hōʻike nā haʻawina i nā hiʻohiʻona hoʻohaʻahaʻa i hoʻoulu ʻia i ke kaumaha maʻamau ua hoʻomaikaʻi ʻo ARA-290 i ke ʻano depressive-like i nā ʻiole, e hōʻike ana i kona hiki ke hoʻohana i ka mālama ʻana i nā maʻi depressive. ʻO ka pathogenesis o ke kaumaha e pili kokoke ana i nā pane inflammatory, a hiki i nā hopena anti-inflammatory a me immunomodulatory o ARA-290 ke hāʻawi i nā hoʻolālā hou no ka mālama ʻana i ke kaumaha, hiki ke ulu i kahi lāʻau antidepressant hou.
Ischemic Stroke: I loko o ka waena cerebral artery occlusion (MCAO) kiʻi kiʻi, ARA-290 hōʻike i nā hopena neuroprotective e like me ka erythropoietin (EPO), e hōʻemi nui ana i ka neuronal apoptosis a me nā pae cytokine inflammatory i loko o ka lolo. Hoʻopiliʻia nā hopena neuroprotective o ARA-290 ma o ka β-adrenergic receptor (βCR) aʻaʻole e hoʻoulu i ka erythropoiesis. Hāʻawi kēia i nā pahuhopu hou a me nā lāʻau lapaʻau kūpono no ka mālama ʻana i ka maʻi ischemic.
(2) Nā maʻi autoimmune
Systemic lupus erythematosus (SLE): Hōʻike nā haʻawina i nā kiʻi ʻiole SLE e hoʻomaikaʻi maikaʻi ʻo ARA-290 i nā hōʻailona SLE, keʻakeʻa i ka hana ʻana o nā autoantibodies, hoʻemi i ka ʻāʻī a me ka pōʻino, ʻaʻole hoʻoulu i ka hematopoiesis. Hāʻawi ʻia i nā palena i kēia manawa i ka mālama ʻana i ka SLE, paʻa ʻo ARA-290 i ka ʻōlelo hoʻohiki ma ke ʻano he lāʻau moho hou no SLE, e hāʻawi ana i nā mea maʻi i nā koho lapaʻau ʻoi aku ka maikaʻi.
(3) Nā pilikia pili i ka maʻi diabetes
ʻO nā maʻi maʻi maʻi maʻi wāwae: Ma kahi ʻano ʻiole o ka maʻi ʻeha wāwae diabetic, ʻo ka hoʻohana ʻana i ka wahi o ARA-290 e hoʻoikaika pono i ka ho'ōla ʻana i ka ʻeha, hoʻomaikaʻi i ka glucose a me ka metabolism lipid, a hoʻemi i nā pae kumu inflammatory. Hōʻike kēia i ka ARA-290 i nā noi kūpono i ka mālama ʻana i ka hoʻōla ʻana i ka maʻi diabetes, e hāʻawi ana i nā ʻike hou a me nā ala no ka mālama ʻana i nā maʻi ʻeha wāwae diabetic.
(4) Nā maʻi ʻāʻī
ʻO ka nephrotoxicity i hoʻokomo ʻia e Cisplatin: I loko o kahi kumu hoʻohālike nephrotoxicity i hoʻokomo ʻia e cisplatin, ua hoʻopau ʻo ARA-290 i ka hōʻino ʻana i ka cisplatin-induced kidney ma o kāna mau anti-apoptotic, anti-inflammatory, a me nā hopena antioxidant. Hōʻike kēia e hiki ke lawelawe ʻo ARA-290 ma ke ʻano he hoʻolālā hou no ka pale ʻana a me ka mālama ʻana i ka cisplatin-induced acute kidney injury, e hāʻawi ana i ka pale kīkī no nā maʻi e loaʻa ana i ka chemotherapy cisplatin.
(5) Nā maʻi maʻi maʻi
Atherosclerosis: ʻO nā hoʻokolohua in vitro a me in vivo e hōʻike ana i ka ARA-290 e pale maikaʻi i nā pane inflammatory, reactive oxygen species production, apoptosis, migration, a me ka hoʻokumu ʻana o ka foam cell i loko o nā macrophages ʻiole, a me ka ulu ʻana o ka wahi plaque i nā aortas ʻiole. Hōʻike kēia ʻo ARA-290 ka waiwai noi no ka anti-atherosclerosis a hiki ke hoʻomohala ʻia i lāʻau lapaʻau hou no ka pale ʻana a me ka mālama ʻana i nā maʻi cardiovascular.
Ka hopena
I ka hōʻuluʻulu ʻana, ʻo ARA-290, ma ke ʻano he peptide me nā ʻano anti-inflammatory, immunomodulatory, a me nā hopena pale-kiʻi, loaʻa i kekahi mau mea lapaʻau i ka mālama ʻana i nā maʻi e pili ana i ka mumū.
Nā kumu
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[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, et al. Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways [J]. ʻAha, 2023,46(1):342-358.DOI:10.1007/s10753-022-01737-7.
[3] Mashreghi M, Bayrami Z, Sichani N, et al. ʻO kahi noiʻi in vivo e pili ana i ka hana hoʻōla ʻeha o ka ligand kikoʻī no ka mea hoʻoponopono hoʻoponopono innate, ARA290, me ka hoʻohana ʻana i kahi ʻano holoholona maʻi diabetic [M]. 2023.10.21203/rs.3.rs-2520194/v1.
[4] Xu G, Zou T, Deng L, et al. ʻO ka Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Hoʻomaikaʻi i ke ʻano hoʻohaʻahaʻa e like me ke kaumaha a me ka ʻaʻa i loko o nā ʻiole [J]. Frontiers in Pharmacology, 2022,13:896601.DOI:10.3389/fphar.2022.896601.
[5] Huang B, Jiang J, Luo B, et al. ʻO ka peptide i loaʻa ʻole erythropoietic erythropoietin e pale i nā ʻiole mai systemic lupus erythematosus [J]. Ka Nupepa o ka Cellular and Molecular Medicine, 2018,22(7):3330-3339.DOI:10.1111/jcmm.13608.
[6] Dahan A, Brines M, Niesters M, et al. Ke kuhikuhi nei i ka mea hoʻoponopono hou e mālama i ka neuropathy [J]. Hōʻike ʻeha, 2016,1(1):e566.DOI:10.1097/PR9.0000000000000566.
[7] Zhang W, Yu G, Zhang M. ARA 290 hoʻomaha i kaʻeha pathophysiological ma ka huliʻana i ke ala TRPV1: Hoʻohui i waena o ka pūnaewele immune a me ka nociception [J]. Peptides, 2016,76:73-79.DOI:10.1016/j.peptides.2016.01.003.
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