Cov ntsiab lus tseem ceeb ntawmIGF 1 LR3 Sprayyog IGF-1 LR3 (Long R3 Insulin zoo li Growth Factor-1), ib qho genetic engineered insulin-zoo li kev loj hlob factor-1 (IGF-1) analogue. Nws tuaj yeem thim rov qab cov leeg nqaij los ntawm inhibiting protein ntau thiab txhawb cov leeg nqaij synthesis, tab sis tam sim no txwv rau kev tshawb fawb preclinical. Cov kev sim tsiaj tau pom tias IGF-1 LR3 tuaj yeem txhim kho cov leeg nqaij fiber ntau, tab sis tib neeg kev sim tsis tau ua. Cov nyhuv neurotrophic ntawm IGF-1 LR3 tuaj yeem txhawb nqa axonal regeneration thiab neuronal ciaj sia taus, tab sis nws muaj peev xwm nkag mus rau cov ntshav-hlwb barrier xav tau kev siv tau ntxiv. Nws accelerates qhov txhab kho los ntawm stimulating fibroblast proliferation, tab sis yuav tsum tau ceev faj tiv thaiv kev pheej hmoo ntawm hypoglycemia.
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IGF 1 LR3 COA
Raw khoom thiab genetic engineering hloov kho
cov khoom siv thev naus laus zis
Gene qhov chaw thiab xaiv tus tswv tsev
IGF 1 LR3 Sprayyog tsim los ntawm genetic recombination technology, thiab nws cov gene sequence yog hloov kho raws li tib neeg insulin-zoo li kev loj hlob zoo-1 (IGF-1). Tus tswv tsev rau kev qhia feem ntau yog xaiv los ntawm Escherichia coli (xws li COH strains) lossis mammalian hlwb (xws li CHO hlwb), uas cov kab ke E. coli tau siv dav vim nws qhov ua tau zoo thiab tus nqi qis hauv high-density fermentation.
Kev hloov pauv ntawm Amino acid ib ntus
R3 kev hloov pauv: Qhov thib peb amino acid ntawm ntuj IGF-1 yog glutamic acid (Glu), uas yog hloov los ntawm arginine (Arg) los ntawm IGF-1 LR3, ua tus cim "R3". Qhov kev hloov pauv no txo qis nws txoj kev sib raug zoo rau insulin-zoo li kev loj hlob zoo li kev khi cov proteins (IGFBPs), nce nws cov concentration dawb los ntawm ntau dua 1000 zaug, thiab txhim kho nws txoj haujlwm lom neeg los ntawm 2-3 zaug.
N-terminal extension: Ntxiv 13 amino acid residues ntawm qhov kawg ntawm B saw los tsim cov qauv saw ntawm 83 amino acids (qee cov ntaub ntawv hais txog 93 amino acids, uas tej zaum yuav yog vim qhov sib txawv ntawm cov txheej txheem purification los yog kev tshawb nrhiav), ntxiv dag zog rau nws txoj haujlwm.
Fermentation thiab purification txheej txheem
txheej txheem fermentation
High density fermentation: Escherichia coli qhia yog tshwm sim los ntawm cua sov ntawm 42 degree, thiab lub tank fermentation tuaj yeem ncav cuag 50L. Lub hom phiaj protein suav rau 30% -40% ntawm tag nrho cov kab mob protein.
Kev ua kom zoo ntawm kab lis kev cai nruab nrab: Tswj cov khoom sib txuam ntawm cov khoom noj metabolic (xws li acetic acid) thiab txhim kho cov khoom purity los ntawm kev pub mis batch cog qoob loo.
Kev ua kom huv huv
Rough thiab ntshiab theem:
Ion pauv chromatography: siv cov protein sib txawv sib cais kom purity ntau dua 90%.
Hydrophobic kev sib cuam tshuam chromatography: ntxiv tshem tawm impurities, ua tiav purity ntau dua 95%.
Pure theem:
Molecular exclusion chromatography (SEC-HPLC): cais cov hom phiaj proteins los ntawm dimers los yog oligomers nrog ib tug purity ntawm ntau dua los yog sib npaug rau 95% (kuaj los ntawm SDS-PAGE).
Ultrafiltration concentration: Concentrate cov protein siv tangential flow filtration technology, thaum hloov qhov tsis nrog PBS (pH 7.4) system.
Terminal filtration: Siv 0.22 μ m lim membrane rau kom tsis muaj menyuam kom tsis muaj menyuam.
kev tswj kom zoo
Kev ua pov thawj ntawm kev ua: Cov kev ua lom lom tau raug ntsuas los ntawm kev kuaj ntshav dawb tsis pub dhau ntawm MCF-7 tib neeg cov qog nqaij hlav cancer mis, thiab ED50 tus nqi tsawg dua lossis sib npaug li 1.5 ng / mL.
Kev kuaj purity: SDS-PAGE thiab SEC-HPLC ua ke tshawb pom, purity Ntau dua lossis sib npaug li 95%.
Kev tswj hwm impurity: cov ntsiab lus endotoxin Tsawg dua lossis sib npaug rau 10 EU / mg, cov khoom noj muaj protein tsawg dua lossis sib npaug li 0.005%, exogenous DNA residue Tsawg dua lossis sib npaug li 10 ng / mg.
Kev npaj thiab kev ruaj ntseg
Freeze drying protectant formula
Siv 8% trehalose los yog 5% mannitol li khov- cov tshuaj tiv thaiv kom qhuav, ua ke nrog 0.01% Tween 80 (solubilizer), kua protein hloov mus ua hmoov dawb los ntawm khov- tshuab ziab khaub ncaws, nrog cov dej noo tsawg dua 3%.
Kev ruaj ntseg lav
Lub sij hawm ntev cia
Cov hmoov qhuav qhuav tuaj yeem khaws cia rau 36 lub hlis ntawm -20℃rau -80 degree, thiab tom qab rov kho dua, nws tuaj yeem muab tso rau hauv cov xwm txheej tsis muaj menyuam ntawm -20℃txog -80℃rau 6 lub hlis, thiab ntawm 2℃txog 8℃rau 7-10 hnub.
Kev thauj mus los: Cov pob khoom xiav xiav tau tso rau hauv tub yees rau kev thauj mus los, kom ntseeg tau tias qhov kub thiab txias ntawm 2-8℃thiab tsis txhob rov khov thiab thawing.
Cov khoom siv ntau lawm thiab GMP ua raws
Cov Khoom Siv Core
Fermentation system: 50L siab tsis siv neeg fermentation tank (nrog pH, yaj oxygen, ntsuas kub hauv online).
Purification system: AKTA Avant protein purifier (txhawb automated chromatographic sib cais).
Cov cuab yeej npaj: Mini Spray Dryer B-290 (tswj tshuab ziab khaub ncaws) lossis lub tshuab ziab khaub ncaws (rau cov hmoov npaj).
Cov cuab yeej tshuaj ntsuam xyuas: HPLC-MS (kev lees paub qhov hnyav molecular), lub teeb pom kev zoo dynamic (particle loj faib khoom), enzyme-txuas kev tshuaj ntsuam xyuas immunosorbent (ELISA).
Ua raws li GMP
Qhov chaw tsim khoom ua raws li "Kev Tswj Xyuas Zoo rau Kev Siv Tshuaj (Tshuaj Kho Dua Tshiab hauv 2010)" thiab tswj nruj me ntsis cov ntsuas xws li cov kab mob endotoxins thiab cov khoom noj muaj protein ntau.
Muab cov ntaub ntawv ua tiav zoo, suav nrog COA (Certificate of Quality), MSDS (Safety Data Sheet), thiab cov ntaub ntawv tswj hwm.
IGF 1 LR3 Spray distorts cov metabolic phenotype thiab kev ua haujlwm sib txawv ntawm glial hlwb
IGF 1 LR3 Sprayyog ib qho kev npaj uas muaj IGF-1 LR3 tivthaiv, uas yog ib qho kev hloov kho ntev ntev - ua haujlwm insulin- zoo li kev loj hlob. Nws muaj kev ua haujlwm siab dua li ntuj IGF-1, ib nrab ntawm lub neej ntev hauv lub cev, thiab kev loj hlob zoo txhawb kev cuam tshuam, uas tuaj yeem txhawb kev faib, tsiv teb tsaws, thiab kev sib txawv ntawm cov hlwb feem ntau. Hauv kev lag luam tshuaj, IGF-1 LR3 tau txais kev saib xyuas thoob plaws vim nws cov yam ntxwv lom neeg tshwj xeeb thiab tau kawm los tshawb txog cov peev txheej kho mob ntawm ntau yam kab mob.
Glial hlwb yog ib qho tseem ceeb ntawm lub hauv nruab nrab lub paj hlwb, nrog rau microglia, astrocytes, thiab lwm yam. Lawv ua lub luag haujlwm tseem ceeb hauv kev tswj hwm lub cev ua haujlwm ntawm lub paj hlwb, txhawb kev muaj sia nyob ntawm neuronal, thiab koom nrog hauv kev tiv thaiv kab mob. Cov metabolic phenotype thiab kev ua haujlwm ntawm cov hlwb glial muaj feem cuam tshuam nrog kev noj qab haus huv ntawm lub paj hlwb, thiab txhua yam uas cuam tshuam rau lawv cov metabolism thiab kev ua haujlwm yuav cuam tshuam rau lub paj hlwb.
Metabolic phenotype thiab kev ua haujlwm ntawm glial hlwb
Hom thiab kev faib tawm ntawm glial hlwb
Cov hlwb glial nyob rau hauv nruab nrab paj hlwb feem ntau suav nrog microglia thiab astrocytes. Microglia yog cov tshuaj tiv thaiv kab mob hauv nruab nrab ntawm lub paj hlwb, nthuav dav thoob plaws hauv lub hlwb thiab qaum qaum. Lawv ua raws li "tus neeg saib xyuas" ntawm lub paj hlwb, saib xyuas kev hloov pauv hauv ib puag ncig ib puag ncig thiab ua lub luag haujlwm tseem ceeb hauv kev tswj hwm lub cev tiv thaiv kab mob hauv lub paj hlwb.Astrocytes yog hom ntau tshaj plaws ntawm glial hlwb nyob rau hauv lub hauv paus paj hlwb, muaj ntau yam ntaub ntawv thiab kev ua haujlwm. Astrocytes tsim kev sib raug zoo nrog cov neurons, cov hlab ntsha, thiab lwm yam los ntawm lawv cov txheej txheem, koom nrog hauv kev tsim cov ntshav - hlwb teeb meem, muab kev noj haus rau cov neurons, tswj cov uptake thiab metabolism ntawm neurotransmitters, thiab muaj kev cuam tshuam tseem ceeb ntawm kev ua haujlwm ntawm cov neurons thiab kev sib kis ntawm neural signals.
Metabolic phenotype ntawm ib txwm glial hlwb
Raws li ib txwm muaj lub cev muaj zog, glial hlwb muaj cov tshuaj metabolic phenotypes. Microglia ua haujlwm tiv thaiv kab mob hauv lub xeev so, thiab lawv cov kev ua haujlwm hauv metabolic kuj tsawg, feem ntau yog nyob ntawm oxidative phosphorylation txoj hauv kev kom tau txais lub zog. Thaum txhawb los ntawm cov kab mob ntxeem tau, cov ntaub so ntswg puas, thiab lwm yam, microglia tau qhib, thiab lawv cov phenotype metabolic tau hloov pauv, hloov mus rau hom metabolic tswj los ntawm glycolysis, sai sai ua lub zog thiab bioactive molecules los daws cov teeb meem sab nraud. Nyob rau hauv ib qho xwm txheej, kev ua haujlwm metabolic ntawm astrocytes yog hloov mus rau cov metabolic. Lawv muab kev txhawb zog rau lawv tus kheej thiab neurons los ntawm aerobic oxidation los ntawm kev noj cov piam thaj. Nyob rau tib lub sijhawm, astrocytes kuj koom nrog lub voj voog glutamate glutamine, hloov glutamate tso tawm los ntawm cov neurons rau hauv glutamine thiab thauj nws rov qab mus rau cov neurons los ua ke glutamate dua. Cov txheej txheem no yog ib qho tseem ceeb rau kev tswj cov neurotransmitter tshuav nyiaj li cas thiab ib txwm ua haujlwm neuronal.
Kev ua haujlwm ntawm glial hlwb
Glial hlwb muaj ntau yam haujlwm tseem ceeb hauv lub hauv nruab nrab paj hlwb. Raws li lub cev tiv thaiv kab mob, microglia tuaj yeem paub thiab tshem tawm cov kab mob, cov hlwb puas, thiab cov protein sib txawv txawv txav, thiab koom nrog kev tswj hwm ntawm cov lus teb neuroinflammatory. Thaum lub sij hawm neural txoj kev loj hlob, microglia kuj koom nrog hauv synaptic pruning, pab txhim kho cov kev sib txuas ntawm neural circuits.
Lub luag haujlwm ntawm astrocytes yog dav dua. Lawv tsis tsuas yog muab kev noj haus thiab kev txhawb nqa rau cov neurons, tab sis kuj koom nrog hauv kev tswj hwm kev tso tawm thiab kev txhawb nqa ntawm cov neurotransmitters, tswj hwm neurotransmitter homeostasis. Tsis tas li ntawd, astrocytes tswj cov ntshav hauv hlwb thiab koom nrog kev tswj hwm cov ntshav - lub hlwb thaiv los ntawm kev cuam tshuam nrog cov hlab ntsha, tiv thaiv cov hlab ntsha los ntawm cov khoom tsis zoo hauv qhov chaw.
Cov nyhuv ntawm IGF-1 LR3 Txau ntawm qhov cuam tshuam metabolic phenotype ntawm glial hlwb
Kev hloov pauv hauv cov txheej txheem metabolic
IGF-1 LR3 nyob rau hauv IGF-1 LR3 Txau tuaj yeem ua rau cov kev taw qhia qis qis los ntawm kev khi rau IGF-1 receptors nyob rau saum npoo ntawm glial hlwb, yog li cuam tshuam rau txoj hauv kev metabolic ntawm glial hlwb. Nyob rau hauv cov nqe lus ntawm lub zog metabolism, ua kom lub IGF-1 signaling txoj kev yuav txhawb txoj kev hloov ntawm glial hlwb los ntawm oxidative phosphorylation mus rau glycolysis. Raws li ib txwm muaj, oxidative phosphorylation yog txoj hauv kev tseem ceeb rau cov hlwb los tsim lub zog, nrog kev ua haujlwm siab tab sis kuj qeeb qeeb; Txawm hais tias glycolysis ua kom muaj zog tsawg, nws tuaj yeem muab lub zog sai sai hauv lub sijhawm luv luv.
Thaum IGF-1 LR3 ua rau cov hlwb glial, nws tuaj yeem txhim kho qhov kev qhia ntawm glycolytic enzymes thiab txhim kho glycolytic kev ua si los ntawm kev ua kom muaj kev taw qhia xws li PI3K / Akt thiab Ras / MAPK. Kev hloov pauv ntawm txoj hauv kev metabolic no tuaj yeem ua rau "kev cuam tshuam" hauv lub zog ntawm cov hlwb glial, uas ua rau muaj kev cuam tshuam tsis zoo ntawm cov metabolism hauv lub zog thaum ntsib kev sib txawv ntawm lub cev lossis lub xeev pathological.
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