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AOD 9604 ka wale fila: Oksidan ni farikolojɔli dɛmɛ

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Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *in glass*, o kɔrɔ ye gilasi minɛnw na) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.


Fasa ni a ni farikoloɲɛnajɛ gɛlɛyaw kɛra diɲɛ foroba kɛnɛyako ye, o de y’a to fɛɛrɛ minnu tɛ mɔgɔ tɔɔrɔ ani minnu bɛ se ka kɛ, olu ɲinini nafa ka bon kosɛbɛ. Hali ni hadamaden ka bonya hormone (hGH) b’a jira ko a bɛ se ka fasa furakɛ, lakana haminankow bɛ dan sigi a tali kuntaalajan na. AOD9604, n’o ye pepitiri yɔrɔ ye min bɛ bɔ hGH ka C-terminal yɔrɔ la (Tyr-hGH177-191), a jirala ko hGH ka tulumafɛnw dɔgɔyali baara bɛ a la, k’a sɔrɔ a nɔ jugu ma kɛ a la. Kɔsa in na, kalan minnu kɛra, olu ye dɔ fara a ka baarakɛcogo kan, ni farikolo tangalanw ni farikoloɲɛnajɛ dɛmɛni nɔw bɔra kɛnɛ kan i n’a fɔ ɲininikɛyɔrɔ jɔnjɔnw.

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Jaa 1 Fasa caya Ameriki balikuw la (san 20–74).




1. AOD9604 ka farikolo tangalanw


Jɛɲɔgɔnya min bɛ oksidan degun ni bana cɛ

Oksidan degun bɛ tali kɛ cogoya la, farikolo bɛ oksizɛni suguya caman (ROS) ni azote suguya minnu bɛ se ka kɛ (RNS) hakɛ caya kojugu, o bɛ na ni oksidan tiɲɛni ye min ka ca ni farikolo seko ye ka o suguya ninnu saniya. O balanbaliya min bɛ oksidan ni farikolo tangalanw cɛ, o bɛ na ni farikolo yɔrɔw tiɲɛni ye. Bana caman, i n’a fɔ dusukunnabana, farikoloɲɛnajɛ, farikolojidɛsɛbanaw, ani sugunɛbilenni min tɛ dɔlɔ ye (NAFLD), olu ni oksidan degun bɛ tali kɛ ɲɔgɔn na kosɛbɛ. Nin bana ninnu na, ROS hakɛ caman bɛ selilu kɔnɔ, olu bɛ bin biyomolekuli kan i n’a fɔ tulumafɛnw, farikolojɔlifɛnw ani ADN, o bɛ na ni selilɛriw ka baarakɛbaliya ni saya ye.


AOD9604 Antioxydant ka baarakɛcogo

AOD9604 b’a nɔw jira ni farikolo kɔnɔ farikolo tangalan anzimu (enzyme antioxydant) labɛnni ye. Superoxide dismutase (SOD), glutathione peroxidase (GPx), ani catalase (CAT) ye farikolo tangalan nafamaw ye minnu bɛ se ka ROS sɛgɛsɛgɛ ani ka selilu kɔnɔ redox balansi mara. AOD9604 bɛ se ka nin farikolo tangalan ninnu jiracogo walima u baaracogo kɔrɔta, o la, a bɛ se ka farikolo tangalanw lafasali seko bonya. Faan wɛrɛ fɛ, AOD9604 bɛ se ka a sen don a yɛrɛ la ka ɲɛsin radikaliw bɔli ma. Jɛkulu dɔw bɛ a ka molekiyɔmu jɔcogo la, se bɛ se ka kɛ u la ka ROS ni RNS minɛ, o la, u bɛ dɔ bɔ u ka tiɲɛni na seliluw la.


Sɛgɛsɛgɛli dɔ la, min kɛra ni sosow ka misali ye, min kɛra sugunɛbilenni na min tɛ dɔlɔ ye, furakɛli ni AOD9604 ye, o kɛra sababu ye ka dɔ bɔ kosɛbɛ malondialdehyde (MDA) hakɛ la sugunɛbilenni na. MDA ye lipidi perokisidi sɔrɔfɛn ye, wa a hakɛ dɔgɔyali b’a jira ko oksidan degun bɛ dɔgɔya. SOD ni GPx ka baara cayara sugunɛ na, o b’a jira ko AOD9604 bɛ se ka oksidan degun tiɲɛni nɔgɔya ni oksidan kɛlɛli anzimuw ka baara caya ye. O b’a jira ko AOD9604 bɛ nɔ ɲuman bila sugunɛ ka oksidan degun cogoya ɲɛ, o bɛ daliluw di a kɛcogo kan banaw furakɛli la minnu bɛ tali kɛ ɲɔgɔn na.




2. AOD9604 ka farikoloɲɛnajɛ dɛmɛni nɔw


A bɛ nɔ minnu bila sukarodunbana na

AOD9604 bɛ sariyasunba nɔba jira tulumafɛnw falenni na. Sogo fasalenw ka misali la, AOD9604 pikiri kuntaalajan kɛli kɔnɔbara la, o kɛra sababu ye ka farikolo girinya ni farikolo tulu dɔgɔya. O nɔ bɛ se ka kɛ ni β-adrénergique sira ye, kɛrɛnkɛrɛnnenya la β(3)-adrenergic receptor (β(3)-AR), o ye lipolytic receptor fɔlɔ ye adipocytes kɔnɔ. AOD9604 tali tile 14 kɔfɛ sogo fasalenw na, β(3)-AR ARN jiracogo hakɛ cayara, o ye β(3)-AR ARN hakɛ dantigɛlen segin sogo fasalenw na ka se hakɛ ma min bɛ se ka suma ni sogo fasalenw ta ye, o bɛ kɛ sababu ye ka tulumafɛnw bɔli sabati ani ka tulumafɛnw sɛgɛsɛgɛli sabati. β(3)-AR knockout sogow la, AOD9604 tali kuntaalajan ma se ka girinya caman yeli ni farikolojidɛsɛ sabatili nɔ kelenw lase i n’a fɔ kungosogo suguya kɔlɔsili sogow la, o b’a jira ko β(3)-AR jɔyɔrɔ ka bon kosɛbɛ AOD9604 ka tulumafɛnw sɛnɛcogo ɲɛnabɔli la. Kɔrɔbɔli gɛlɛnw na, AOD9604 ye fanga musaka ni tulumafɛnw oksidan caya hali bi β(3)-AR jamu knockout sogow la, o b’a jira ko AOD9604 bɛ se ka nɔ bila fana tulumafɛnw falenni na sira wɛrɛw fɛ.

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Jaa 2 Kɔgɔjida la, AOD9604, walima hadamaden ka bonya hormone (hGH) hakɛ kelen don o don kɔnɔbara la (ip) bɛ nɔ min bila farikolo girinya caman yeli la sogo cɛmanw na minnu farikolo tɛ C57BL/6J (A) walima minnu fasalen don (ob/ob) (B) tile 14 kɔnɔ.


A bɛ nɔ minnu bila witaminiw sɛnɛcogo la

Glucides metabolisme siratigɛ la, AOD9604 ni hGH tɛ kelen ye kosɛbɛ. Kɛnɛyaso sɛgɛsɛgɛliw y’a jira ko AOD9604 tɛ nɔ bila IGF-1 hakɛ la joli la, o bɛ hakilina in sinsin ko a tɛ baara kɛ IGF-1 fɛ. Da kɔnɔ sukaro muɲuni sɛgɛsɛgɛli jaabiw y’a jira ko, a tɛ i n’a fɔ hGH, AOD9604 tɛ nɔ jugu bila witaminiw sɛnɛcogo la. O kɔrɔ ye ko AOD9604 bɛ se ka tulumafɛnw sɛnɛcogo ɲɛnabɔ k’a sɔrɔ a ma witaminiw sɛnɛcogo ɲuman bali, o bɛ nafa kɛrɛnkɛrɛnnen di farikoloɲɛnajɛ cogoya ɲɛnabɔli la.


A bɛ nɔ bila sugunɛbilenni na

Sɛgɛsɛgɛli minnu kɛra sosow kan minnu ka sugunɛbilenni tɛ dɔlɔ ye, AOD9604 tɛ nɔ bila tulumafɛnw falenni dɔrɔn na, nka a bɛ sugunɛ farikoloɲɛnajɛ cogoya bɛɛ lajɛlen fana labɛn. Ka fara oksidan degun dɔgɔyali kan, AOD9604 bɛ se ka sugunɛbilenni ɲɛ ka kɛɲɛ ni jamu jirali ye min bɛ tali kɛ tulumafɛnw dilanni na, u tacogo la ani u falenni na sugunɛ na. A bɛ se ka nɔ bila anzimu jɔnjɔnw jirali la i n’a fɔ asidi fatɔ sintasi (FAS) ani asetili-CoA karɔkisilazi (ACC), ka asidi tuluma sɔrɔli dɔgɔya sugunɛ na, ka asidi tuluma β-oxydation sabati, wa o bɛ sugunɛ tuluma dalajɛli nɔgɔya.




3. AOD9604 ka wale fila kɛcogo minnu bɛ se ka kɛ


A kɛcogo Fasa ni farikoloɲɛnajɛ banaw la minnu bɛ tali kɛ a la

Ni an y’a jateminɛ ko AOD9604 ka farikolo tangalan ni farikoloɲɛnajɛ dɛmɛni nafa bɛ se ka kɛ a la, a bɛ se ka kɛ fasa furakɛli la ani farikoloɲɛnajɛ bana minnu bɛ tali kɛ a la i n’a fɔ farikoloɲɛnajɛ suguya 2 ani sugunɛbilenni min tɛ dɔlɔ ye. Banabagatɔ fasalenw na, AOD9604 bɛ se ka tulumafɛnw falenfalenni sabati, ka farikolo tulu dɔgɔya, ka inisɔndiya kɛcogo ɲɛ, o la, a bɛ dɛmɛ don joli sukaro hakɛ kunbɛnni na. Banabagatɔ minnu ka sugunɛbilenni tɛ dɔlɔ ye, a bɛ se ka sugunɛbilenni degun tiɲɛni nɔgɔya ani ka sugunɛbilenniw sɛnɛcogo ɲɛnabɔ, o bɛ se ka kɛ fɛɛrɛ kura ye walasa ka sugunɛ baara ɲɛ ani ka bana taabolo sumaya.


A kɛcogo Spor balocogo la

Spor balo siratigɛ la, AOD9604 ka farikolo tangalan ni farikoloɲɛnajɛ dɛmɛni fana bɛ mɔgɔ ɲɛnajɛ. Degeliw senfɛ minnu fanga ka bon, farikoloɲɛnajɛla bɛ ROS hakɛ caman bɔ, o bɛ na ni oksidan degun tiɲɛni ye, ka sɔrɔ fanga fɛnɲɛnamafagalan ɲinini bɛ bonya. AOD9604 bɛ se ka dɛmɛ don ka ROS jɛya, ka farikolo sɛgɛn ni tiɲɛni dɔgɔya, ka sɔrɔ ka tulumafɛnw oksidan sabati fanga kama, o la, a bɛ farikoloɲɛnajɛ muɲuli ni kɛnɛya seko bonya. Hali ni AOD9604 bɛ farikolo tangalan ni farikoloɲɛnajɛ dɛmɛcogo ɲuman jira, a lakanani nafa ka bon kosɛbɛ. Kalan caman ye AOD9604 lakanani jateminɛ. Kɔrɔbɔli wɔɔrɔ kɔnɔ minnu kɛra ni mɔgɔw ye, minnu kɛra ni mɔgɔ fila ye, minnu kɛra ni furakisɛw ye, AOD9604 ma nɔ bila IGF-1 hakɛ la joli la, a ma nɔ jugu bila witaminiw sɛnɛcogo la, ani AOD9604 kɛlɛli farikolojidɛsɛbanakisɛ si ma sɔrɔ. A tali dabila taamasiɲɛ si ma fɔ walima kɔlɔlɔ juguman minnu bɛ tali kɛ AOD9604 tali la. Toxicologie basigilen sɛgɛsɛgɛliw la, minnu kɛra sosow ni cynomolgus sonsanninw kan, AOD9604 tali da la waati jan kɔnɔ, o fana y’a jira ko a lakanani bɛɛ lajɛlen don, ni jamu toxicité taamasiɲɛ si tɛ a la.


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Jaa 3 AOD9604 tiɲɛni in vitro la sosow ka joli la so funteni na. Miniti 56 kɔfɛ, pepitiri bɛ bɔ pewu. A tilancɛ-ɲɛnamaya bɛ Taa miniti 4 ɲɔgɔn na. AOD9604 amino-terminal truncated fragments (-xaa) yecogo jiralen don.




4. Kuncɛli


AOD9604, i n’a fɔ pepitiri yɔrɔ min ka baara fila ɲɔgɔn tɛ, o bɛ dɛmɛ don farikolo tangalanw ni farikoloɲɛnajɛ dɛmɛni na. A ka farikolo tangalan baara bɛ dɛmɛ ka farikolo yɔrɔw tiɲɛni nɔgɔya min bɛ sɔrɔ oksidan degun fɛ, ka sɔrɔ a ka farikoloɲɛnajɛ dɛmɛni baara bɛ tulumafɛnw, witaminiw ani sugunɛ farikoloɲɛnajɛw ɲɛnabɔ cogo ɲuman na. O b’a to a nafa ka bon fasa ni farikoloɲɛnajɛ banaw furakɛli la minnu bɛ tali kɛ o la, ka fara farikoloɲɛnajɛ balocogo kan.




Sosow (Sɔrɔyɔrɔw).


[1] Dehbashi M, Fathie M, Hosseini SRA, ani a ɲɔgɔnnaw. اثر هشت هفته تمرین استقامتی و تزریق قطعه پولیتیک هورمون رشد (AOD9604) بر آنزیمهای کبد و CK18 موشهای سوری القاء شده به کبد چرب غیرالکلی ناشی از رژیم غذایی پر چرب، 2021 sàn[C]. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew


[2] EMIM, Kenley D L. AOD9604 lakanani ni sukarodunbana, balodɛsɛ fura kura min bɛ farikoloɲɛnajɛ kɛnɛya sabati[J]. Ɲɛgɛnɛsiraw ani sukarodunbana, 2014,4:64-77. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew


[3] Stier H, Vos E, Kenley D L. Hexadecapeptide AOD9604 lakanani ni a muɲuni hadamadenw na[J]. Ɲɛgɛnɛsiraw ani sukarodunbana, 2013,3:7-15. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew

[4] Melnikova I, Wages D. Fasa kɛlɛli furakɛli[J]. Sigida lajɛw fura sɔrɔli, 2006,5(5):369-370.DOI:10.1038/nrd2037.


[5] Heffernan M, Summers RJ, Thorburn A, ani a ɲɔgɔnnaw. Adamaden ka GH n’a ka tulumafɛnw (AOD9604) nɔ minnu bɛ tulumafɛnw sɛnɛcogo la furakɛli kuntaalajan kɔfɛ sogo fasalenw ni beta(3)-AR knock-out sogow la[J]. Endocrinologie, 2001,142(12):5182-5189.DOI:10.1210/endo.142.12.8522. Ɲɛgɛnɛsiraw ani mɔgɔ dogoyɔrɔw.


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