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1 kits (10 Vials)
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▎ ARA-290 Tsarin
Source: PubChem |
Jeri: XEQLERALNSS Tsarin kwayoyin halitta: C 51H 84N 16O21 Nauyin Kwayoyin Halitta: 1257.3g/mol Lambar CAS: 1208243-50-8 Saukewa: 91810664 Synonyms: Cibinetide |
▎ ARA-290 Bincike
Menene asalin bincike na ARA-290?
Haɓakawa na ARA-290 ya samo asali ne daga bincika yiwuwar warkewar erythropoietin (EPO). Masana kimiyya sun gano cewa EPO ba wai kawai yana inganta erythropoiesis ba amma har ma yana da ayyuka masu kariya na nama irin su anti-inflammatory da anti-apoptosis. Duk da haka, EPO's hematopoietic stimulating na iya ƙara dankon jini da sauran haɗari, yana iyakance amfani da shi wajen magance cututtuka marasa jini. Don riƙe tasirin kariya na nama na EPO yayin guje wa illolin sa na hematopoietic, masu bincike sun fara tsara peptides na asali, wanda ke haifar da ƙirƙirar ARA-290.
Tare da bincike mai zurfi, an gane fa'idodi na musamman na ARA-290 azaman peptide ba hematopoietic a hankali. Yana kunna hanyoyin siginar siginar rigakafin kumburi da nama ta hanyar ɗaure zuwa mai karɓar gyare-gyare na asali (IRR), yana nuna sakamako mai ban sha'awa a cikin magance rikice-rikicen ciwon sukari, neuropathy, da raunin koda. Wadannan binciken sun kafa harsashi don ƙarin bincike da aikace-aikacen asibiti na ARA-290 kuma sun inganta ci gaba da sababbin hanyoyin kwantar da hankali bisa ga peptides na EPO.
Menene tsarin aikin ARA-290?
Anti-Inflammatory Effect: ARA-290 inhibits the secretion of inflammatory cytokines, thereby reducing inflammatory responses, as demonstrated in multiple disease models. Alal misali, a cikin samfurin linzamin kwamfuta na tsarin lupus erythematosus (SLE), yana rage yawan ƙwayar jini na cytokines mai kumburi IL-6, MCP-1, da TNF-α, inganta alamun SLE{#Dahan, A,2016} (Dahan A, 2016). A cikin tsarin nephrotoxicity na cisplatin-induced, yana rage pro-inflammatory cytokines TNFa, IL6, da IL1β, rage kumburi na koda [2] (Ghassemi-Barghi N, 2023). Tsarinsa na rigakafin kumburi na iya haɗawa da niyya mai karɓar mai karɓar gyara na asali (IRR), heterodimer na mai karɓar erythropoietin da mai karɓar β-na kowa (CD131). Daure zuwa IRR yana kunna hanyoyin siginar sigina na ƙasa, ta haka yana rage kumburi [1].
Tasirin Anti-Apoptotic: ARA-290 yana hana apoptosis na sel kuma yana haɓaka rayuwar ƙwayoyin nama. A cikin ƙirar bera mai ciwon sukari, yana hana apoptosis na tubular tubular epithelial cell apoptosis kuma yana rage furcin maɓalli na proteases a cikin tsarin apoptotic, don haka yana yin tasirin kariya na koda. A cikin nau'ikan nephrotoxicity da ke haifar da cisplatin, yana daidaita maganganun sunadarai masu alaƙa da apoptosis kamar Bax da Bcl-2, yana hana ayyukan Caspase-3, yana rage apoptosis na sel, kuma yana rage lalacewar ƙwayoyin koda na cisplatin [2].
Sakamakon Anti-Oxidative: ARA-290 yana hana lalacewar danniya na oxidative kuma yana rage samar da abubuwa masu cutarwa kamar nau'in oxygen mai amsawa (ROS). A cikin ƙirar koda na bera mai ciwon sukari, yana hana maganganun ƙwayoyin ƙwayoyin cuta na koda, yana rage matakan ROS na renal, kuma yana rage malondialdehyde (MDA) magana, yana sauƙaƙa lalacewar damuwa na oxidative. A cikin nazarin atherosclerosis, gwaje-gwajen in vitro sun nuna cewa ARA-290 yana hana samar da ROS a cikin macrophages a ƙarƙashin yanayin kumburi, yana rage lalacewar danniya na oxidative.
Ka'idar Ayyukan Kwayoyin cuta: ARA-290 yana daidaita aikin ƙwayoyin rigakafi kamar macrophages. A cikin vitro, yana hana kumburin kunnawa na macrophages yayin da suke haɓaka aikin su na phagocytic zuwa sel apoptotic, yana taimakawa kula da tsarin garkuwar jiki homeostasis da share ƙwayoyin apoptotic don guje wa kumburi da ke haifar da tarawar su (Dahan A, 2016). A cikin bincike na atherosclerosis, ARA-290 yana hana ƙaura na macrophage da haɓakar ƙwayoyin kumfa, rage raguwar lipid a cikin intima na jijiyoyin jini da rage ci gaban atherosclerosis.
Neuroprotective Mechanism: A cikin samfurin linzamin kwamfuta na ischemia cerebral, ARA-290 yana haifar da tasirin neuroprotective ta hanyar mai karɓar β-na kowa (βCR). Yana da mahimmanci rage ƙananan apoptosis na neuronal da matakan cytokine mai kumburi a cikin ƙwayar kwakwalwa, inganta aikin ƙwayar cuta. Allurar da siRNA da aka yi niyya na βCR yana hana tasirin ARA-290 na neuroprotective, yana nuna cewa βCR yana taka muhimmiyar rawa a tsarin sa [3].
Kayan aikin analgesic: ARA-290 na iya haifar da tasirin analgesic ta hanyar kai tsaye kai tsaye ga nociceptors na gefe. Nazarin ya nuna shi musamman yana hana ayyukan tashar TRPV1 kuma yana rage tasirin allodynia na injiniya na capsaicin, yana ba da shawarar ARA-290 na iya zama sabon antagonist na tashar TRPV1, yana ba da sabbin fahimta don jin zafi [4].
Menene aikace-aikacen ARA-290?
Maganin Neuropathies
Raɗaɗin Raɗaɗi da Inganta Alamar Alamar: ARA-290 yadda ya kamata ya kawar da ciwon neuropathic, musamman a cikin cututtuka tare da neuropathy irin su ciwon sukari da sarcoidosis. A cikin gwaje-gwaje na asibiti don marasa lafiya na sarcoidosis, ARA-290 ya inganta haɓakar cututtukan neuropathy da cututtukan cututtuka na autonomic, inganta yanayin rayuwa, da rage yawan ciwo, tare da irin wannan tasiri a cikin marasa lafiya na ciwon sukari. Tsarinsa ya haɗa da ɗaure ga mai karɓar gyare-gyare na asali (IRR), kunna anti-mai kumburi da hanyoyin gyaran nama, daidaita kumburin neurogenic, da rage jin zafi [1, 4]..
Ƙaddamar da Jijiya Fiber Regeneration: ARA-290 yana inganta farfadowa na fiber jijiya. In sarcoidosis patients, 28 consecutive days of ARA-290 treatment induced corneal small nerve fiber regeneration, demonstrating repair capacity for specific nerve fibers and potential to improve neurological function, although it had no effect on epidermal nerve fibers [1].
Rage Nephrotoxicity
Rage Cytotoxicity da Genotoxicity: A cikin nau'ikan nephrotoxicity na cisplatin-induced, ARA-290 yana rage girman cytotoxicity da genotoxicity da ke haifar da cisplatin, kamar raguwar sigogin lalacewar DNA a cikin ƙididdigar comet da mitar micronucleus, kare ƙwayoyin ƙwayoyin cuta na salula da rage lalacewar ƙwayoyin koda [1].
Regulation of Oxidative Stress and Inflammation: ARA-290 improves cisplatin-induced oxidative stress by reducing malondialdehyde (MDA) and ROS levels and enhancing antioxidant enzyme activity. Hakanan yana rage kumburin koda ta hanyar rage cytokines pro-mai kumburi (misali, TNF-α, IL-6, IL-1β), yana ba da kariya daga raunin da ya haifar da cisplatin [1] .
Hanawa na Apoptosis: ARA-290 yana hana cisplatin-induced apoptosis ta hanyar daidaita kwayoyin halitta da sunadaran da ke da alaka da apoptosis (misali, ragewar Caspase-3 da Bax, ƙara bayyanar Bcl-2), ci gaba da rayuwa na ƙwayar koda da kuma riƙe da yiwuwar kula da marasa lafiya na koda [1].
Inganta Alamomin Bacin rai
Rage Halayen Damuwa-Kamar Halayyar: A cikin nau'ikan linzamin kwamfuta na matsanancin danniya mara tsinkaya da damuwa na yau da kullun na zamantakewar al'umma, gwamnatin ARA-290 ta yau da kullun ta inganta halayen ɓacin rai, kwatankwacin fluoxetine na yau da kullun na antidepressant. ARA-290 yana haifar da tasirin antidepressant ba tare da tasiri sosai akan haemoglobin na gefe ko jajayen ƙwayoyin jini ba [5].
Tsarin Tsarin Kwayoyin Kwayoyin cuta da Kumburi: ARA-290 yana juyar da haɓakar damuwa na yau da kullun a cikin mita da adadin CD11b⁺Ly6Ghi neutrophils da CD11b⁺Ly6Chi monocytes a cikin kasusuwan kasusuwa da meninges, kazalika da kunna microglial, yana kawar da alamun damuwa da kuma samar da sabbin hanyoyin magance kumburi ..
Kariya Daga Lalacewar Koda Mai Ciwon Suga
Hana Renal Tubular Epithelial Apoptosis: ARA-290 yana hana renal tubular epithelial cell apoptosis, rage shirye-shiryen mutuwar kwayar halitta da kare ƙwayoyin koda.
Haɓaka Alamar Ayyukan Renal: ARA-290 yana rage yawan fitowar albumin na fitsari a cikin berayen masu ciwon sukari, yana rage lalacewar cututtukan koda, inganta aikin koda, kuma yana jinkirta ci gaban nephropathy na ciwon sukari.
Maganin Lupus Erythematosus (SLE)
Hana Haɓakawa na Autoantibody Production da Immune Complex Deposition: ARA-290 yana hana maganin antinuclear antibody (ANA) da anti-biyu-stranded DNA antibody matakan a jawo SLE mice, rage IgG da C3 jigo a cikin kodan, rage alamun nephritis, da kuma inganta ci gaban cuta [6].
Hoto 1 ARA290 magani ya hana amsawar kumburi a cikin mice SLE da ke haifar da pristane. (A) An gano matakan IL-6, IL-10, MCP-1, IFN-γ, TNF-α, IL-12p70 da TGF-β a cikin maganin da aka kwatanta a cikin Hoto 1 (n = 6). (B) Macrophage mai kumburi F4/80 infiltration ya kasance mai mahimmanci ta hanyar sa baki ta ARA 290 idan aka kwatanta da kulawar PBS. (C) The spleen and lymph node weights were measured following ARA290 treating in SLE mice (n = 6). Sandunan sikelin suna wakiltar 30 μm.
Source:PubMed [6]
Rage matakan Cytokine mai kumburi: ARA-290 yana rage yawan ƙwayar ƙwayar cuta na cytokines mai kumburi IL-6, MCP-1, da TNF-α a cikin mice SLE, rage kumburi da rage alamun cututtuka [6].
Ragewar Apoptosis: ARA-290 yana rage adadin ƙwayoyin apoptotic a cikin kodan, yana kare ƙwayoyin renal, kuma yana hana kunna kumburin macrophages yayin haɓaka phagocytosis na ƙwayoyin apoptotic a cikin vitro, yana daidaita tsarin rigakafi da riƙe yuwuwar maganin SLE [6].
Rage Gubar Magungunan Chemotherapeutic
Rage lalacewar DNA: A cikin doxorubicin (DOX) -induced cytotoxicity model, ARA-290 da muhimmanci rage DOX-induced DNA lalacewa, kamar rage wutsiya DNA adadin a comet assays da micronucleus mita, kare salon salula kwayoyin halitta da kuma rage chemotherapeutic lalacewa ga al'ada Kwayoyin [7].
Rage damuwa na Oxidative da Kumburi: ARA-290 yana rage lalacewar DOX da ke haifar da lalacewar aikin enzyme antioxidant, yana rage kumburi da apoptosis, da kuma kare kariya daga DOX-induced oxidative danniya da cell lalacewa, mai yiwuwa ciki har da zuciya Kwayoyin, don rage m effects a chemotherapy marasa lafiya [7].
Rigakafi da Maganin cutar Alzheimer
Jinkirin Ci gaba da Ci gaban Ilimin Halittu da Ingantacciyar fahimta: Gudanarwar farko na ARA-290 a cikin matasa APP/PS1 mice (samfurin farko na Alzheimer) yana rage jinkirin β-amyloid (Aβ) ci gaba da cututtukan cututtukan cuta kuma yana haɓaka aikin fahimi, yana nuna mahimmancin sa don shiga tsakani [8].
Tsarin Ayyukan Monocyte: ARA-290 na musamman yana ƙarfafa tsararrun Ly6C⁻ masu sintiri na monocyte subsets, yana ƙara yawan matakan kewayawa, yana inganta cirewar Aβ daga tasoshin jini na kwakwalwa, yana rage nauyin Aβ na kwakwalwa, kuma yana jinkirta ci gaba da cututtuka. Koyaya, ba shi da tasiri a cikin ƙirar zamani (tsohuwar APP/PS1 mice), yana nuna mahimmancin sa baki da wuri [8].
Inganta Maganin Rauni Mai Ciwon Suga
Ƙunƙarar Rauni: A cikin streptozotocin-induced diabetic incisional rat model, aikace-aikacen ARA-290 na gida yana haɓaka ƙullewar rauni, yana rage lokacin sake dawowa, kuma yana inganta ingantaccen warkar da rauni [9] .
Tsarin Alamar Gyaran Nama: ARA-290 yana haɓaka collagen da abun ciki na furotin a cikin kyallen gyare-gyare, yana daidaita insulin na jini, glucose na jini, matakan lipid, matsayin antioxidant, da matakan cytokine mai kumburi, ƙirƙirar microenvironment mai dacewa don warkar da rauni da samar da sabbin dabarun magance cututtukan ƙafa masu ciwon sukari [9].
Maganin Ciwo
Hana Ayyukan Tashoshin TRPV1: ARA-290 yana kawar da allodynia na inji ta capsaicin ta hanyar hana mai karɓar mai karɓa mai aiki mai yiwuwa na vanilloid subtype 1 (TRPV1) tashar tashar, kai tsaye da ke kaiwa ga nociceptors na gefe da kuma samar da sababbin hanyoyin warkewa da hanyoyin magance jin zafi [4].
Kammalawa
ARA-290 shine polypeptide wanda aka samu EPO tare da anti-mai kumburi, anti-apoptotic, da tasirin oxidative. Zai iya magance ciwo a cikin ciwon sukari da sarcoidosis, inganta farfadowa na fiber jijiya, magance nephrotoxicity, SLE, damuwa, da kuma rage zafi ta hanyar ƙin TRPV1. Tare da yuwuwar farkon shiga tsakani na Alzheimer da sauran fagage, yana riƙe da fa'idodin aikace-aikacen asibiti.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Al-Onaizi, Mohammed masani ne mai zurfin gogewa a fannin nazarin halittu. Yana da alaƙa ta kut-da-kut da mashahuran ilimi da cibiyoyin bincike, waɗanda suka haɗa da Cibiyar Ciwon sukari ta Dasman (DDI), Jami'ar Kuwait, Jami'ar Laval, Jami'ar Yamma (Jami'ar Western Ontario), da Jami'ar Ibrananci ta Urushalima. Abubuwan bincikensa suna da fa'ida, suna rufe ilimin Neurosciences & Neurology, Biochemistry & Molecular Biology, Immunology, Psychiatry, da sauran batutuwa a cikin Kimiyyar Rayuwa & Biomedicine. Waɗannan lamuran suna da mahimmanci don samun zurfin fahimtar hanyoyin ilimin halittar ɗan adam, hanyoyin cututtuka, da haɓaka sabbin jiyya. Al-Onaizi, binciken Mohammed ya sami sakamako mai mahimmanci a cikin ilimin kimiyya na asali kuma ya ba da goyon baya mai mahimmanci na ka'idar da jagoranci mai amfani ga likitancin likita da bincike na kwayoyin halitta.
