Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm mgf peptide hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo mgf peptide rau muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
MGF Peptide hmoov(Mechanical Growth Factor) yog ib qho kev xaiv sib txawv ntawm cov tshuaj insulin-zoo li kev loj hlob zoo-1 (IGF-1) noob. Raws li tus kheej- zais cia / paracrine signaling molecule uas tsim los ntawm lub cev tam sim ntawd los teb rau cov neeg kho tshuab stimulation los yog cov ntaub so ntswg puas, nws lub luag haujlwm tseem ceeb yog pib kho cov kev pabcuam hauv zos thiab rov tsim dua tshiab. Nws qhib cov kev taw qhia tshwj xeeb (xws li PI3K / Akt), tiv thaiv cell apoptosis, thiab recruits satellite cell thiab qia hlwb mus rau qhov chaw puas, txhawb lawv txoj kev loj hlob thiab sib txawv rau hauv cov hlwb ua haujlwm. Piv nrog rau kev ua haujlwm ntawm IGF-1, MGF muaj cov nyhuv luv dua thiab meej dua. Nws qhov tshwj xeeb C-terminal txuas ntxiv ib ntus yog tus yuam sij rau nws txoj haujlwm lom neeg tshwj xeeb. Tam sim no, nws cov txiaj ntsig tseem ceeb yog tsom rau hauv thaj chaw ntawm cov tshuaj kho dua tshiab, txhawm rau tshawb nrhiav nws lub peev xwm los kho myocardial, neural, thiab cov leeg pob txha raug mob. Txawm li cas los xij, vim nws lub neej luv luv thiab kev ruaj ntseg tsis zoo, nws daim ntawv thov kev kho mob tseem ntsib cov teeb meem tseem ceeb. Cov txheej txheem xa khoom siab tshaj plaws yuav tsum tau ua kom tau txais kev kho mob zoo.
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MGF hmoov COA
MGF (Mechano Growth Factor, mechanical growth factor) peptides yog splicing variants ntawm insulin-zoo li kev loj hlob zoo-1 (IGF-1). Lawv cov txheej txheem tsim khoom muaj xws li kev tsim cov noob caj noob ces, tshuaj synthesis thiab hloov kho cov txheej txheem, txhawm rau txhim kho lawv cov kev ua haujlwm lom neeg, kev ruaj ntseg thiab ib nrab-lub neej. Cov nram qab no piav qhia txog kev tsim khoom ntawmMGF peptideslos ntawm plaub qhov ntev: tsim qauv molecular, txheej txheem synthesis, kev hloov kho tshuab thiab kev tswj kom zoo.
Molecular Design thiab Genetic Engineering Foundation
Kev tsim tawm ntawm MGF peptides pib nrog nws cov qauv tsim qauv molecular. Raws li kev sib txawv ntawm IGF-1, MGF muaj ib ntu peptide tshwj xeeb ntawm 24-25 amino acids ntawm C-terminal (xws li C-terminal sequence ntawm tib neeg MGF yog "QRRRKGSTFEEHK"), uas yog tsim los ntawm kev xaiv qhov sib txuas ntawm receptors thiab xa IGF.
Gene cloning thiab qhia:
Los ntawm PCR amplification, tshwj xeeb exons ntawm tib neeg IGF-1 noob (xws li exon 4 thiab exon 6) tau txais thiab MGF coding sequence tau tsim.
Lub hom phiaj noob tau muab tso rau hauv qhov kev qhia vector (xws li pET series), thiab hloov mus rau hauv Escherichia coli los yog poov xab system rau induced qhia. Piv txwv li, ib qho kev tshawb fawb tau siv Pichia pastoris qhia qhov system thiab ua tiav kev qhia tawm ntawm MGF los ntawm methanol induction, nrog rau cov txiaj ntsig ntawm 50mg / L.
Protein purification:
Lub hom phiaj protein tau muab cais los ntawm kev sib koom ua ke chromatography (xws li Nws -tag-Ni kem) lossis ion exchange chromatography, ua ke nrog ultrafiltration concentration thiab khov- cov txheej txheem ziab kom tau siab - purity hmoov. Cov khoom lag luam muaj qhov purity ntawm 98.77%, qhov hnyav ntawm molecular ntawm 2868.19 Da, thiab ua tau raws li kev tshawb fawb- tus qauv qib.
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Chemical synthesis: Daim ntawv thov tseem ceeb ntawm cov khoom siv -theem peptide synthesis (SPPS)
Rau luv - sawMGF peptides(xws li C-terminal 24 peptide), chemical synthesis vim nws qhov yooj yim thiab raug tau dhau los ua txoj kev nyiam.
Khoom -theem peptide synthesis txheej txheem
Resin loading:Txhim kho thawj cov amino acid (xws li Fmoc-Tyr-Wang resin) mus rau cov cab cab.
Sequential coupling:Ntxiv kev tiv thaiv cov amino acids (Fmoc / Boc lub tswv yim) ib los ntawm ib tug siv condensing agents xws li DCC / HOBt los yog HATU, maj mam txuas cov peptide saw.
Txiav thiab deprotection:Siv TFA (trifluoroacetic acid) los txiav cov saw peptide thiab tshem tawm cov saw hlau tiv thaiv ib sab kom tau txais peptide crude.
Synthesis optimization
Amino acid hloov pauv:Txhawm rau txhim kho kev ruaj ntseg, qee cov txheej txheem tsim khoom hloov L-hom arginine nrog D- hom arginine (xws li "D-Arg-D-Arg" qauv), txo qhov rhiab heev rau enzymatic degradation.
Fragment condensation:Rau ntev -chain peptides, siv lub tswv yim ntawm segmental synthesis ua raws li cov kua-theem condensation los txhim kho synthesis efficiency. Piv txwv li, ib qho kev tshawb fawb tau faib MGF rau hauv N-terminal (1-}12) thiab C-terminal (13-24) ntu, thiab muab lawv sib cais ua ntej txuas lawv los ntawm thioether daim ntawv cog lus.
Cov tswv yim hloov kho: PEGylation thiab ntev - hloov kho
Ib nrab-Lub neej ntawm MGF peptide ntuj yog luv heev (tsuas yog 5-7 feeb), txwv tsis pub nws daim ntawv thov kho mob. Los ntawm kev hloov kho PEG, lub sijhawm ua haujlwm tuaj yeem txuas ntxiv.
PEG process:
Kev xaiv ntawm PEG activated: Xaiv cov kab los yog ceg PEG-NHS esters nrog lub luj molecular ntawm 2000-5000 Da thiab hnov mob nrog N-terminal amino pawg lossis lysine sab saw ntawm MGF peptide.
Site-Kev hloov kho tshwj xeeb: Qhia cysteine (Cys) rau hauv MGF ib ntus los ntawm kev tsim kho caj ces thiab siv malonylhydrazide-PEG rau kev sib txuas tshwj xeeb kom txo qis heterogeneity.
Ntev -ntev nyhuv:
Ib nrab-lub neej ntawm PEG{1}}MGF tuaj yeem txuas ntxiv mus rau 48-72 teev, txhim kho bioavailability. Tsiaj thwmsim qhia tau hais tias tom qab ib qho kev txhaj tshuaj ntawm PEG-MGF, qhov ua kom cov leeg nqaij satellite hlwb yog peb zaug siab dua li ntawm MGF tsis hloov, thiab lub sijhawm ua haujlwm yog tsib zaug ntev dua.
Kev Tswj Xyuas Zoo: Kev tswj xyuas nruj los ntawm cov khoom siv raw mus rau cov khoom tiav
Kev tsim khoom ntawmMGF peptide hmoovyuav tsum ua raws li GMP cov qauv los xyuas kom meej cov khoom muaj kev ruaj ntseg thiab sib xws.
Raw khoom tshuaj xyuas
Cov amino acid raw cov ntaub ntawv yuav tsum ua raws li USP / EP cov qauv, nrog ib tug purity ntawm ntau tshaj los yog sib npaug zos rau 99.5% thiab ib tug hnyav hlau ntsiab lus ntawm tsawg dua los yog sib npaug zos rau 10 ppm.
Resins thiab condensing agents yuav tsum muab COA (daim ntawv pov thawj kev soj ntsuam) los xyuas kom meej tias cov kuab tshuaj seem (xws li DMF) ua raws li ICH cov lus qhia.
Kev soj ntsuam cov txheej txheem
Kev sib txuas ua haujlwm ntawm txhua kauj ruam ntawm cov txheej txheem synthesis yuav tsum tau kuaj xyuas los ntawm ninhydrin kom ntseeg tau ntau dua lossis sib npaug rau 99.0%.
Tom qab cov peptide crude yog purified los ntawm HPLC, lub purity ntawm lub ntsiab ncov yuav tsum tau ntau tshaj los yog sib npaug rau 95% thiab ib qho impurity tsawg dua los yog sib npaug rau 0.5%.
Cov khoom tso tawm
Qhov hnyav molecular yuav tsum tau lees paub los ntawm MS (mass spectrometry), purity yuav tsum tau txiav txim siab los ntawm HPLC, thiab cov qauv thib ob yuav tsum tau txheeb xyuas los ntawm cov voj voog dichroism (CD).
Kev kuaj kab mob microbial (xws li endotoxin <0.1 EU/mg) thiab kev kuaj tsis muaj menyuam yog qhov yuav tsum tau ua.
Los ntawm cov khoom kho hauv zos mus rau cov neeg xa xov xwm
MGF (Mechano Growth Factor, mechanical growth factor) peptides yog splicing variants ntawm insulin-zoo li kev loj hlob zoo-1 (IGF-1). Lawv cov qauv molecular thiab cov yam ntxwv ua haujlwm ua rau lawv ua ob lub luag haujlwm hauv kev kho cov ntaub so ntswg hauv zos thiab cov teeb liab hloov pauv. Los ntawm kev ua kom cov leeg qia hlwb mus rau kev sib koom tes sib koom ua ke, cov teebmeem lom neeg ntawm MGF tau dhau los ua cov txheej txheem kev txawj ntse thiab tau dhau los ua qhov kev tshawb fawb hotspot nyob rau hauv thaj chaw ntawm cov tshuaj regenerative.
Molecular Basis: Splicing Variants thiab cov qauv tshwj xeeb
MGF yog tsim los ntawm kev xaiv splicing los ntawm IGF-1 noob. Piv rau cov laus IGF-1 (70 amino acids), nws muaj qhov txuas ntxiv C- thaj tsam thaj chaw uas muaj 40-amino-acid E domain, ua rau 110-amino-acid yooj yim polypeptide. Qhov sib txawv ntawm cov qauv no muab cov haujlwm tshwj xeeb rau MGF:
Receptor khi Specification:MGF pib teeb liab hloov pauv los ntawm kev khi rau IGF-1 receptor, tab sis nws tus E domain tuaj yeem ua rau nws tus kheej qhib cov leeg nqaij satellite yam tsis muaj kev vam khom rau tag nrho IGF-1 receptor txoj kev.
Enzymatic stability:Lub proline-arginine- thaj chaw nplua nuj nyob rau hauv E domain tuaj yeem tiv thaiv proteolysis, ua kom ntev ib nrab- lub neej ntawm MGF hauv cov ntaub so ntswg mus rau 2-4 teev (tsis hloov IGF-1 tsuas yog 5-10 feeb).
Gelation nyiam:Lub hydrophobic core ntawm E domain txhawb nqa MGF los tsim cov dimers lossis tetramers, txhim kho nws txoj kev sib raug zoo rau cov cell membrane thiab txhim kho bioavailability hauv zos.
Kev kho hauv zos: "cov neeg teb thawj zaug" rau cov leeg mob
Tom qab cov leeg raug mob, MGF dominates cov txheej txheem kho thaum ntxov los ntawm cov txheej txheem hauv qab no:
Satellite cell activation
Tsis pub dhau 30 feeb tom qab raug mob, theem qhia hauv zos ntawm MGF nce los ntawm 10-15 zaug, ua kom cov hlwb quiescent satellite los ntawm txoj kev MAPK/ERK thiab txhawb lawv nkag mus rau hauv lub voj voog loj hlob.
Tsiaj thwmsim qhia tau hais tias tus nqi ua kom cov satellite hlwb hauv MGF- cov nas tsis muaj peev xwm raug txo los ntawm 60%, thiab cov nqaij ntshiv yog ncua 3-5 hnub.
Protein synthesis kev cai
MGF upregulates cov kev ua ntawm ribosomal protein S6 kinase (S6K1) los ntawm txoj kev mTOR, nce tus nqi ntawm cov nqaijrog protein synthesis los ntawm 40-60%.
Thaum ua ke nrog IGF-1, MGF nyiam txhawb cov synthesis ntawm myosin hnyav saw (MHC), ua kom cov kev hloov pauv ntawm cov leeg nqaij fiber ntau.
Anti-inflammatory thiab antioxidant
MGF tuaj yeem cuam tshuam kev sib dhos ntawm NLRP3 inflammasome, txo qhov tso tawm ntawm IL-1 thiab TNF-, thiab txo cov lus teb rau ntawm qhov chaw raug mob.
Los ntawm kev ua kom txoj hauv kev Nrf2, nws txhim kho kev ua haujlwm ntawm superoxide dismutase (SOD), tshem tawm cov pa oxygen ntau dhau (ROS).
Cov neeg xa xov xwm hauv lub cev: Kev sib koom tes sib koom ua ke rau kev hla - kho lub cev
Cov kev tshawb fawb tsis ntev los no tau qhia tias MGF tuaj yeem ua tiav cov ntaub so ntswg kho nyob deb ntawm kev ncig lossis exosomes:
Kev tiv thaiv plawv
Hauv cov qauv myocardial infarction, kev txhaj tshuaj hauv zos ntawm MGF tuaj yeem txo qhov mob hauv cheeb tsam los ntawm 25%, thiab nws tseem tuaj yeem thauj mus los ntawm cov ntshav mus rau daim siab, ua kom lub zais zis ntawm IGF-1 hauv daim siab hlwb, tsim "mob siab" kho axis.
MGF tuaj yeem txhim kho cov calcium ion ua lub peev xwm ntawm cov hlwb myocardial thiab txo qhov kev pheej hmoo ntawm arrhythmia.
Neural regeneration
Lub hlwb ischemia qauv qhia tau hais tias MGF tuaj yeem nkag mus rau hauv cov ntshav - lub hlwb teeb meem, txhawb kev loj hlob ntawm cov kab mob neural qia hlwb hauv hippocampus, thiab ua kom muaj sia nyob ntawm cov neurons los ntawm 35%.
Cov txheej txheem cuam tshuam nrog kev cuam tshuam kev ua haujlwm ntawm GSK-3, ua kom ruaj khov ntawm -catenin protein, thiab ua kom Wnt/ -catenin signaling txoj hauv kev.
Kho daim tawv nqaij thiab pob txha mos
Nyob rau hauv tus qauv mob ntev, MGF accelerates epidermal regeneration los ntawm upregulating lub synthesis ntawm collagen XVIII thiab hyaluronic acid, txo caws pliav thickness los ntawm 40%.
Hauv cov qauv osteoarthritis, MGF tuaj yeem cuam tshuam qhov kev qhia ntawm MMP-13, txo qhov degradation ntawm pob txha mos matrix, thiab txhawb kev loj hlob ntawm chondrocytes.
Kev txhais lus kho mob: Kev sib tw los ntawm chav kuaj mus rau daim ntawv thov
Txawm hais tias MGF qhia tau tias muaj peev xwm zoo, nws daim ntawv thov kev kho mob tseem ntsib ntau yam teeb meem:
Optimization ntawm txoj kev tswj hwm
Ib nrab-Lub neej ntawm MGF ntuj yog luv luv (5-7 feeb), ntev li -kev npaj ua yeeb yam (xws li PEG-MGF) lossis nanocarrier systems yuav tsum tau tsim.
Kev txhaj tshuaj hauv zos tuaj yeem ua rau cov leeg nqaij fibrosis, yog li cov thev naus laus zis xa tawm (xws li cov tshuaj tiv thaiv kab mob -cov tshuaj sib txuas) yuav tsum tau tshawb nrhiav.
Kev noj tshuaj thiab kev nyab xeeb
Cov koob tshuaj ntau ntawm MGF tuaj yeem ua rau cov tshuaj insulin tsis kam, yog li yuav tsum tau tsim ib koob tshuaj -cov qauv kev sib raug zoo.
Ntev- siv sijhawm ntev tuaj yeem ua rau muaj cov tshuaj tiv thaiv kab mob, yog li kev hloov pauv tib neeg los txo cov tshuaj tiv thaiv kab mob yog qhov tsim nyog.
Indications xaiv
Cov pov thawj tam sim no txhawb kev siv MGF rau cov leeg nqaij atrophy thiab ua ib qho kev kho mob ntxiv rau myocardial infarction, tab sis ntau dua III-theem kev sim tshuaj yog xav tau rau kev kuaj xyuas.
Hauv thaj tsam ntawm kev tiv thaiv- kev laus, cov kev pheej hmoo ntawm MGF (xws li txhawb cov qog loj hlob) yuav tsum tau soj ntsuam nruj me ntsis.
Cov lus qhia yav tom ntej: Precise regulation from a systems biology perspective
Nrog rau kev txhim kho ntawm ib leeg -cell sequencing thiab spatial transcriptomics technologies, cov kev tswj xyuas network ntawm MGF yog maj mam deciphered:
Temporal dynamics
Qhov kev qhia ntawm MGF tom qab raug mob qhia tau hais tias ib tug bimodal qauv (lub zos ncov nyob rau hauv thaum ntxov lub sij hawm thiab kev tso tawm nyob rau hauv lub tom ntej theem), thiab yuav tsum tau tsim ib tug temporal dosing tswv yim.
Cell hom tshwj xeeb
Kev ua kom muaj txiaj ntsig ntawm MGF ntawm cov neeg nyob hauv xov tooj cua satellite (xws li Pax7+/Myf5+} hlwb) txawv heev, thiab cov kev cai tseem ceeb yuav tsum raug txheeb xyuas los ntawm kev tshuaj ntsuam CRISPR.
Metabolic reprogramming
MGF tuaj yeem ua rau cov leeg hlwb hloov ntawm glycolysis mus rau oxidative phosphorylation, txhim kho kev siv hluav taws xob. Cov txheej txheem no yuav muab lub hom phiaj tshiab rau kev kho cov kab mob metabolic.
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