Los ntawm Cocer Peptides 
1 month ago
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Melanotan-II Txheej txheem cej luam
Melanotan-II (MT-II) yog ib qho hluavtaws α-melanocyte-stimulating hormone (α-MSH) analogues ntawm melanocortin agonists. MT-II tsis yog tsuas yog siv rau tanning lub hom phiaj; Hauv kev tshawb fawb txog kev kho mob, nws tab tom tshawb nrhiav rau cov ntawv thov hauv kev kho mob xws li erectile kawg.
Daim duab 1 Tus qauv ntawm Melanotan-II.
Melanotan-II Mechanism of Action
MT-II feem ntau siv nws cov teebmeem los ntawm kev cuam tshuam nrog melanocortin receptors (MCRs). melanocortin receptor tsev neeg suav nrog ntau yam subtypes xws li MC1R, MC2R, MC3R, MC4R, thiab MC5R. MT-II yog ib qho tsis xaiv melanocortin receptor agonist uas tuaj yeem khi rau thiab qhib ntau MCRs.
Nyob rau hauv daim tawv nqaij, MT-II khi rau MC1R nyob rau saum npoo ntawm melanocytes, activating adenylate cyclase, uas tsub kom cyclic AMP (cAMP), li no activating protein kinase A (PKA). PKA activates microphthalmia-associated transcription factor (MITF) los ntawm phosphorylation. MITF yog ib qho tseem ceeb ntawm kev hloov pauv hauv melanin synthesis, Nws txhawb nqa kev qhia ntawm cov noob xws li tyrosinase, tyrosinase-related protein-1 (TRP-1), thiab tyrosinase-related protein-2 (TRP-2), uas yog cov enzymes koom nrog hauv melanin synthesis, thaum kawg ua rau cov tawv nqaij pigmentation thiab tanning.
Hauv lub paj hlwb, MT-II kuj cuam tshuam qee cov kab mob neuroendocrine. Nws tuaj yeem txhawb nqa lub hauv paus oxytocin. Cov kev tshawb fawb tau pom tias kev txhaj tshuaj ntawm MT-II ua rau muaj qhov tshwm sim ntawm Fos hauv cov neurons loj ntawm suprachiasmatic nucleus (SON) thiab paraventricular nucleus (PVN) ntawm hypothalamus, cov lus teb uas tuaj yeem txo qis los ntawm kev txhaj tshuaj ua ntej intracerebroventricular ntawm melanocortin antagonist19.SHU-9. Cov ntaub ntawv pov thawj electrophysiological qhia tau hais tias kev txhaj tshuaj txhaj tshuaj ntawm MT-II nce qhov kev sib tw ntawm oxytocin neurons hauv SON tab sis tsis ua rau dendritic oxytocin tso tawm hauv SON. Vim tias cov kev tshawb fawb yav dhau los qhia tau hais tias kev siv ncaj qha ntawm melanocortin agonists inhibits supraoptic nucleus (SON) oxytocin neurons, cov teebmeem ntawm cov hlab ntsha MT-II tuaj yeem yog qhov tsawg kawg yog ib feem ntawm kev sib haum xeeb, uas muaj feem cuam tshuam los ntawm kev ua kom muaj kev nkag los ntawm lub hlwb caudal, qhov twg MT-II kuj nce Fos qhia.
Tsis tas li ntawd, MT-II muaj qee yam kev ua haujlwm ntawm lub zog metabolism thiab thermoregulation. Hauv kev sim nas, kev txhaj tshuaj intraperitoneal ntawm MT-II induces qhov tseem ceeb thiab ntuav hypometabolism / hypothermia. Qhov tshwm sim hypothermic no ploj mus hauv Cov Khoom Siv W-sh / W-sh nas tsis muaj cov hlwb mast, qhia tias cov hlwb mast yog qhov tseem ceeb rau MT-II-induced hypothermia. MT-II tuaj yeem txhawb nqa cov hlwb los ntawm ob qho tib si MRGPRB2-dependent thiab-independent mechanisms tso tawm histamine, uas ua rau hypothermia ntawm histamine H 1 receptors, raws li kev xaiv antagonist pyrilamine lossis ablation ntawm H 1 receptors ua rau txo qis cov nyhuv hypothermic.
Cov teebmeem ntawm Melanotan-II
Lub luag haujlwm hauv daim tawv nqaij Pigmentation
Ib qho ntawm cov teebmeem tseem ceeb tshaj plaws ntawm MT-II yog ua rau cov tawv nqaij pigmentation ntxiv, piv txwv li, ua tiav cov nyhuv tanning. Cov lus tawm tswv yim los ntawm cov neeg siv qhia tau hais tias yuav luag txhua tus neeg koom nrog uas sim tanning nrog MT-II pom cov tawv nqaij tsaus. Qhov no qhia tau hais tias MT-II muaj qee qhov kev ywj pheej hauv kev ua rau cov tawv nqaij pigmentation, tsis yog nyob ntawm ultraviolet hluav taws xob los pib lub tshuab melanogenesis.Hauv qee cov kev tshawb fawb, kev soj ntsuam los ntawm cov qauv tsiaj thiab hauv vitro cell thwmsim tau pom tias MT-II ncaj qha txhawb cov melanocytes, upregulating cov kev qhia ntawm enzymes kev tsim tawm ntawm daim tawv nqaij, muaj feem xyuam rau melanin. xim. Cov nyhuv no muaj lwm txoj hauv kev rau cov neeg nrhiav lub ntsej muag bronze thaum muaj kev txhawj xeeb txog UV-induced tawv nqaij puas.
Cov teebmeem ntawm Neurobehavior
Hais txog cov teebmeem neurobehavioral, MT-II nthuav tawm ntau yam kev ua. Hauv cov kev tshawb fawb siv zebrafish ua tus qauv, nws tau pom tias txawm tias cov khoom noj muaj roj tsawg (HF) ntev (tsuas yog kwv yees li 1% ntawm tus nees zebrafish lub neej, lossis peb lub lis piam) tuaj yeem ua rau muaj kev nco tsis zoo, nce kev ntxhov siab, thiab txo qis kev tshawb nrhiav hauv zebrafish. MT-II tuaj yeem thim rov qab cov kev txawv txav no tshwm sim los ntawm kev noj zaub mov muaj roj ntau, ua kom cov tsiaj txhu paub txog kev nco, kev ntxhov siab, thiab kev tshawb nrhiav tus cwj pwm mus rau qib zoo ib yam li cov pab pawg noj zaub mov.
Hauv kev tshawb fawb txog kev puas siab puas ntsws, siv tus qauv niam txiv lub cev tiv thaiv kab mob (MIA) nas los simulate autism, txiv neej MIA nas muaj cov yam ntxwv zoo li autism, xws li kev coj tus cwj pwm tsis zoo, txo kev sib txuas lus, thiab nce tus cwj pwm rov ua dua. Tom qab xya hnub ntawm kev kho mob MT-II, kev coj tus cwj pwm kev coj noj coj ua hauv txiv neej MIA nas tau txhim kho, thaum kev coj tus cwj pwm hauv C57 cov nas uas muaj keeb kwm yav dhau los pom tsis muaj kev hloov pauv tseem ceeb tom qab kho MT-II. Qhov no qhia tias MT-II muaj peev xwm kho tau cov teebmeem hauv kev txhim kho kev puas siab puas ntsws zoo li tus cwj pwm tsis zoo, muab cov lus qhia tshiab rau kev tshawb fawb txog kev kho mob autism.
Daim duab 2 Cov neeg laus txiv neej MIA nas tau pom qhov nce ntawm oxytocin receptor qhia nyob rau hauv lub anterior cingulate cortex.
Cov teebmeem ntawm lub zog metabolism thiab thermoregulation
MT-II kuj tseem muaj txiaj ntsig zoo rau lub zog metabolism thiab thermoregulation. Hauv kev sim nas, nas nrog pituitary adenylate cyclase-activating peptide deficiency (PACAP) tau muab MT-II los ntawm kev txhaj tshuaj peripheral txhua hnub rau peb lub lis piam sib law liag thaum lub caij txias hloov. Cov txiaj ntsig tau pom tias MT-II tuaj yeem ua rau qee qhov rov qab kho qhov tsis muaj peev xwm thermogenesis ntawm cov nas. Los ntawm kev ntsuas norepinephrine-induced metabolic tus nqi, nws tau pom tias lub peev xwm thermogenic ntawm nas kho nrog MT-II tau rov qab ib nrab. Tsis tas li ntawd, MT-II kev kho mob kho qhov tsis xws luag hauv kev siv lipid nyob rau hauv adrenergic stimulation, qhia tias MT-II tuaj yeem cuam tshuam cov thermogenesis hauv cov ntaub so ntswg adipose los ntawm kev tswj hwm kev ua siab zoo, yog li ua lub luag haujlwm hauv kev tswj hwm lub zog metabolic.
MT-II tuaj yeem ua rau mob ntshav qab zib hauv cov nas los ntawm kev ua kom cov kabmob mast thiab tso cov tshuaj histamine. Cov txheej txheem no qhia txog lub luag haujlwm ntawm MT-II hauv cov txheej txheem ntsuas kub.
Muaj peev xwm cuam tshuam rau lub cev xeeb tub
MT-II kuj muaj peev xwm cuam tshuam rau lub cev xeeb tub. Nws tau raug kawm rau kev kho mob ntawm erectile kawg, uas muaj feem xyuam rau nws cov teebmeem stimulatory ntawm lub cev xeeb tub.
Kev siv ntawm Melanotan-II
Kev siv hauv kev lag luam kev zoo nkauj
Hauv kev lag luam kev zoo nkauj, MT-II feem ntau yog siv los ua tus neeg sawv cev tanning. Nrog lub siab xav kom muaj kev noj qab haus huv, bronze complexion thiab kev txhawj xeeb txog cov tawv nqaij puas tsuaj los ntawm kev raug tshav ntuj (xws li sunburn thiab muaj kev pheej hmoo ntawm mob qog noj ntshav), MT-II tau txais kev saib xyuas raws li cov khoom thov kom ua tiav tanning yam tsis muaj kev cia siab rau hnub raug. Txawm li cas los xij, txij li nws tsis tau pom zoo los ntawm cov koom haum muaj cai xws li FDA thiab tsis muaj kev tshawb fawb txog kev nyab xeeb thiab kev ua tau zoo, nws daim ntawv thov hauv kev lag luam kev zoo nkauj tseem nyob hauv thaj chaw grey. Hauv qee lub tebchaws thiab cheeb tsam, kev muag khoom hauv online tsis raug cai ntawm MT-II rau cov hom phiaj tshuaj pleev ib ce qee zaus tshwm sim.
Cov ntawv thov hauv Kev Tshawb Fawb Kev Kho Mob
Hauv kev tshawb fawb txog kev kho mob, daim ntawv thov ntawm MT-II feem ntau tsom rau kev tshawb nrhiav nws cov peev txheej kho mob rau ntau yam kab mob. Nyob rau hauv cov ntsiab lus ntawm neurobehavioral ntshawv siab, MT-II tau ua kom pom kev ua tau zoo hauv kev txhim kho neurobehavioral abnormalities tshwm sim los ntawm kev noj zaub mov muaj roj ntau hauv zebrafish thiab autism-zoo li kev coj tus cwj pwm tsis zoo hauv cov txiv neej MIA nas, muab cov lus qhia tshiab rau kev kho mob ntsig txog paj hlwb.
Hauv kev tshawb fawb ntawm lub zog metabolism thiab cov kab mob thermoregulation, MT-II cov txiaj ntsig khaws cia ntawm thermogenesis hauv PACAP-tsis muaj nas qhia nws cov txiaj ntsig zoo hauv kev kho cov kab mob metabolic xws li rog rog. Kev tshawb nrhiav ntxiv rau hauv cov txheej txheem tswj hwm ntawm MT-II ntawm lub zog metabolism-txog kev taw qhia txoj hauv kev tuaj yeem ua rau kev txhim kho cov tshuaj kho tshiab rau cov kab mob metabolic. Kev tshawb fawb ntawm cov txheej txheem hauv qab MT-II-vim hypothermia tuaj yeem ua rau peb nkag siab tob txog cov txheej txheem ntawm lub cev ntawm thermoregulation, muab lub hauv paus theoretical rau kev kho mob ntawm cov kab mob cuam tshuam nrog thermoregulatory abnormalities.
Hauv kev ua haujlwm ntawm cov kab mob hauv kev ua me nyuam, kev tshawb fawb txog kev siv MT-II rau kev kho mob ntawm erectile kawg, txawm tias tseem nyob rau hauv nws cov theem ua ntej, muaj kev xaiv tshiab rau kev kho mob ntawm cov txiv neej kev sib deev dysfunction.
Xaus
Melanotan-II, raws li cov khoom siv hluavtaws α-melanocyte-stimulating hormone analog, muaj ntau yam kev ua haujlwm lom neeg uas cuam tshuam nrog cov tawv nqaij pigmentation, cov txheej txheem neurobehavioral, lub zog metabolism, thermoregulation, thiab kev ua me nyuam. Nyob rau hauv cov nqe lus ntawm daim tawv nqaij pigmentation, nws tuaj yeem ua rau cov tawv nqaij darkening, muab txoj hauv kev rau tanning. Hauv kev tshawb fawb txog kev kho mob, MT-II qhia txog kev siv dav dav. Kev tshawb fawb txog cov kab mob neurobehavioral, lub zog metabolism thiab cov kab mob thermoregulation, thiab cov kab mob hauv lub cev tsis zoo muab cov lus qhia tshiab rau kev kho mob ntawm cov mob no.
Qhov chaw
[1] McKenzie N, Gonzalez N, Huang C, et al. Daim ntawv tshaj tawm nthuav qhia PS09 Cov neeg siv kev paub ntawm Melanotan II txhaj rau tanning [J]. British Journal of Dermatology, 2024,191(Supplement_1):i179-i180.DOI:10.1093/bjd/ljae090.380.
[2] Wekwejt P, Wojda U, Kiryk A. Melanotan-II thim rov qab nco tsis taus vim yog kev noj haus HF luv luv [J]. Biomedicine & Pharmacotherapy, 2023,165:115129.DOI:10.1016/j.biopha.2023.115129.
[3] Tomassi S, Dimmito MP, Cai M, et al. CLIPSing Melanotan-II kom pom ntau yam kev xaiv xaiv hMCR Agonists[J]. Phau ntawv Journal of Medicinal Chemistry, 2022,65(5):4007-4017.DOI:10.1021/acs.jmedchem.1c01848.
[4] Gilhooley E, Daly S, McKenna D. Melanotan II Kev Paub Tus Neeg Siv: Kev Kawm Zoo ntawm Cov Rooj Sib Tham Hauv Online [J]. Dermatology, 2021,237(6):995-999.DOI:10.1159/000514492.
[5] Peters B, Hadimeri H, Wahlberg R, et al. Melanotan II: ib qho ua rau lub raum tsis ua haujlwm: tshuaj xyuas cov ntaub ntawv thiab cov ntaub ntawv qhia [J]. Cen Case Reports, 2020,9(2):159-161.DOI:10.1007/s13730-020-00447-z.
[6] Paiva L, Sabatier N, Leng G, et al. Qhov cuam tshuam ntawm Melanotan-II ntawm Brain Fos Immunoreactivity thiab Oxytocin Neuronal Activity thiab secretion hauv nas [J]. Phau ntawv Journal of Neuroendocrinology, 2017,29(2).DOI:10.1111/jne.12454.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
