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TB 500 Fragment (17–23) yog dab tsi?

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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.




Taw qhia


TB 500 (Thymosin Beta-4 Fragment 17–23) yog ib qho bioactive fragment ze ze nrog ntau yam txheej txheem tseem ceeb hauv tib neeg lub cev, tshwj xeeb hauv kev kho cov ntaub so ntswg thiab cell migration.


1-TB500 fragment

Daim duab 1 Cov qauv tshuaj TB 500 Fragment (17–23).




Cov ntaub ntawv tseem ceeb txog TB 500 Fragment (17–23)


TB 500 Fragment (17–23) yog N-terminal acetylated 17–23 fragment ntawm tib neeg thymosin beta-4 (Thymosin Beta-4). N-terminal acetylation plays lub luag haujlwm tseem ceeb hauv kev tswj cov protein-protein kev sib cuam tshuam thiab intracellular localization. Lub xub ntiag ntawm acetyl pawg tuaj yeem hloov pauv qhov kev faib tawm ntawm cov nqi molecular thiab spatial conformation, yog li cuam tshuam nws lub peev xwm los khi nrog lwm cov biomolecules. Nyob rau hauv tib neeg lub cev, thymosin β4 yog ib tug dav peptide faib, thiab TB 500 Fragment (17-23), raws li nws tshwj xeeb fragment, yuav ua tau los ntawm endogenous proteolytic txheej txheem.




Mechanism of Action of TB 500 Fragment (17–23)


(1) Cell Migration thiab Chemotaxis

Cov teebmeem ntawm Endothelial Cells: TB 500 Fragment (17–23) txhawb nqa kev txav chaw endothelial cell, txheej txheem tseem ceeb rau angiogenesis. Thaum kho qhov txhab lossis kho cov ntaub so ntswg, cov hlwb endothelial yuav tsum tsiv mus rau qhov chaw puas los tsim cov hlab ntsha tshiab, muab cov pa oxygen thiab cov as-ham rau cov ntaub so ntswg. TB 500 Fragment (17–23) tuaj yeem txhim kho endothelial cell migration los ntawm kev ua kom muaj ntau txoj hauv kev hauv lub cev, xws li PI3K-Akt signaling pathway, uas tswj cov kev hloov pauv ntawm cov cellular cytoskeleton. Kev ua kom lub PI3K-Akt signaling txoj kev txhawb nqa lub polymerization thiab depolymerization ntawm actin, ua kom cov hlwb txuas ntxiv pseudopodia thiab mus rau pem hauv ntej.


Cov nyhuv chemotactic ntawm lub cev tiv thaiv kab mob: Cov kab no kuj nthuav tawm cov teebmeem chemotactic ntawm lub cev tiv thaiv kab mob, nyiam cov macrophages, neutrophils, thiab lwm yam kab mob hauv lub cev mus rau qhov chaw mob lossis raug mob. Macrophages ua lub luag haujlwm tseem ceeb hauv kev kho cov ntaub so ntswg, vim lawv tuaj yeem tshem tawm cov ntaub so ntswg puas thiab cov kab mob thaum zais ntau yam kev loj hlob thiab cytokines los txhawb cov ntaub so ntswg kho thiab rov tsim dua tshiab. TB 500 Fragment (17–23) khi rau cov receptors tshwj xeeb nyob rau saum npoo ntawm lub cev tiv thaiv kab mob, ua kom muaj kev cuam tshuam hauv lub cev kom coj cov kab mob tiv thaiv kab mob mus rau qhov chaw raug mob.


(2) Cov ntaub so ntswg kho thiab rov tsim dua tshiab

Txhawb nqa fibroblast proliferation thiab collagen synthesis: Fibroblasts yog thawj cell hom nyob rau hauv cov ntaub so ntswg connective thiab yog lub luag hauj lwm rau synthesizing thiab secreting extracellular matrix Cheebtsam xws li collagen thaum lub qhov txhab kho. TB 500 Fragment (17–23) tuaj yeem txhawb kev loj hlob ntawm fibroblast, nce cov xov tooj ntawm tes thiab yog li ua kom cov collagen synthesis. Cov fragment no tuaj yeem txhim kho cov kev qhia ntawm cov noob ntsig txog collagen synthesis, xws li COL1A1 thiab COL3A1, thaum txhawb kev hloov pauv tom qab kev hloov pauv ntawm collagen hauv fibroblasts, yog li txhim kho collagen zoo thiab ruaj khov. Cov teebmeem no ua rau muaj kev tsim cov kab mob extracellular matrix, txhawb kev kho qhov txhab thiab kho cov ntaub so ntswg.


Kho cov leeg nqaij: Hauv kev kho cov leeg nqaij, TB 500 Fragment (17–23) kuj ua lub luag haujlwm tseem ceeb. Nws txhawb kev ua kom muaj zog thiab kev loj hlob ntawm cov hlwb satellite, uas yog cov qia hlwb myogenic hauv cov leeg pob txha nrog lub peev xwm rov ua dua tshiab thiab sib txawv rau cov leeg nqaij. TB 500 Fragment (17–23) tswj lub MyoD-Myogenin signaling txoj hauv kev nyob rau hauv satellite cell, txhawb lawv kev sib txawv rau hauv myotubes, uas tom qab ntawd fuse los tsim cov leeg nqaij tshiab, yog li ua tiav cov leeg nqaij kho thiab rov tsim dua tshiab. Qhov tawg no kuj tuaj yeem txo cov lus teb inflammatory tom qab cov leeg raug mob, txo qis kev puas tsuaj ntxiv rau cov leeg nqaij los ntawm o.


(3) Anti-inflammatory teebmeem

Inhibition of inflammatory factor expression: TB 500 Fragment (17–23) tuaj yeem inhibit qhov kev qhia ntawm ntau yam inflammatory yam, nrog rau cov qog necrosis factor-α (TNF-α) thiab interleukin-1β (IL-1β). Cov kab mob inflammatory no ua lub luag haujlwm tseem ceeb hauv cov lus teb inflammatory, thiab lawv cov lus qhia ntau dhau tuaj yeem ua rau muaj qhov ua kom muaj zog thiab ua rau mob, ua rau cov ntaub so ntswg puas. TB 500 Fragment (17–23) tuaj yeem txo qhov kev sau thiab txhais lus ntawm cov kab mob inflammatory los ntawm inhibiting lub activation ntawm nuclear factor-κB (NF-κB) taw qhia txoj kev, li no alleviating inflammatory teb. NF-κB yog qhov tseem ceeb ntawm kev hloov pauv ntawm lub hauv paus ntawm cov teeb liab inflammatory transduction, thiab nws qhov kev ua kom muaj peev xwm txhawb nqa qhov kev qhia ntawm ntau yam kab mob ntsig txog cov noob.


Kev tswj cov kab mob ntawm lub cev tiv thaiv kab mob: Ntxiv nrog rau inhibiting kev qhia ntawm cov kab mob inflammatory, TB 500 Fragment (17-23) kuj tuaj yeem tswj cov kab mob inflammatory ntawm lub cev tiv thaiv kab mob. Nws tuaj yeem cuam tshuam cov polarization ntawm macrophages mus rau hom pro-inflammatory (M1 hom) thiab txhawb lawv cov polarization mus rau hom tshuaj tiv thaiv (M2 hom). M1-hom macrophages feem ntau secrete pro-inflammatory yam, koom nrog hauv kev pib thiab nthuav dav ntawm o; whereas M2-type macrophages secrete anti-inflammatory yam, txhawb kev kho cov ntaub so ntswg thiab kev tiv thaiv kab mob. TB 500 Fragment (17–23) tswj lub xeev polarization ntawm macrophages, coj cov inflammatory teb mus rau cov kev taw qhia zoo rau cov ntaub so ntswg kho.




Kev siv TB 500 Fragment (17–23) hauv Kev Kho Mob Field


(1) Kev Kho Mob

Cov kab mob ntawm daim tawv nqaij: Hauv kev kho mob ntawm daim tawv nqaij, TB 500 Fragment (17–23) qhia txog kev txhawb nqa tseem ceeb. Cov kev tshawb fawb ua ntej qhia tau hais tias kev siv tshuaj pleev xim rau cov tshuaj uas muaj TB 500 Fragment (17–23) ua kom lub qhov txhab kaw thiab txhim kho kev kho kom zoo. Qhov no feem ntau yog vim nws txoj kev tswj hwm ntau yam ntawm cov hlwb endothelial, fibroblasts, thiab lub cev tiv thaiv kab mob. Accelerated endothelial cell migration txhawb kev tsim cov hlab ntsha tshiab, muab cov khoom noj txaus rau lub qhov txhab; nce fibroblast proliferation thiab collagen synthesis ua rau muaj zog dua cov ntaub so ntswg ntawm lub qhov txhab; thiab chemotactic thiab anti-inflammatory teebmeem ntawm lub cev tiv thaiv kab mob mitigate inhibitory cuam tshuam ntawm inflammatory teb rau qhov txhab kho. Hauv kev kho mob ntawm qee qhov mob ntev, xws li mob ntshav qab zib ko taw, TB 500 Fragment (17–23) kuj qhia tau tias muaj peev xwm kho tau tus nqi. Cov neeg mob ntshav qab zib tau ntsib kev kho mob qeeb thiab muaj kev pheej hmoo kis kab mob ntau ntxiv vim cov ntshav qab zib nce siab. TB 500 Fragment (17–23) tuaj yeem txhim kho microenvironment hauv zos, txhawb kev tsiv teb tsaws ntawm tes thiab kev loj hlob, thiab txhim kho qhov zoo ntawm cov qhov txhab mob.


Cov ntaub so ntswg sab hauv: Rau cov ntaub so ntswg sab hauv, xws li cov kab mob hauv plab thiab lub siab puas tsuaj, TB 500 Fragment (17–23) kuj muaj peev xwm kho tau. Nyob rau hauv tus qauv plab hnyuv kab mob, kev tswj hwm ntawm TB 500 Fragment (17-23) txhawb kev loj hlob thiab kho cov kab mob mucosal ntawm qhov chaw rwj, txo qhov mob plab. Nws cov txheej txheem ntawm kev ua yog cuam tshuam nrog kev txhawb nqa ntawm tes tsiv teb tsaws, tswj cov lus teb inflammatory, thiab ua kom cov txheej txheem ntawm matrix ntxiv. Hauv cov qauv kev raug mob rau daim siab, TB 500 Fragment (17–23) tuaj yeem txhawb lub siab cell rov tsim dua tshiab, txo qis kev puas tsuaj rau daim siab, thiab txhim kho daim siab ua haujlwm.


(2) Kev kho cov kab mob musculoskeletal

Cov leeg nqaij thiab kev raug mob: Hauv cov tshuaj kis las, cov leeg nqaij thiab kev raug mob yog cov teeb meem tshwm sim. TB 500 Fragment (17–23), vim nws cov teebmeem ntawm cov leeg nqaij, tau tshwm sim los ua tus neeg sawv cev kho mob rau cov leeg nqaij. Kev tswj hwm ntawm TB 500 Fragment (17-23) tom qab cov leeg nqaij tuaj yeem ua kom cov leeg muaj zog thiab txo qhov tshwm sim ntawm cov leeg nqaij. Cov leeg nqaij fibrosis yog ib qho teeb meem tshwm sim tom qab cov leeg raug mob, ua rau cov leeg nqaij tawv, txo elasticity, thiab cov leeg tsis muaj zog. TB 500 Fragment (17–23) txhawb nqa kev ua kom muaj zog thiab nthuav dav ntawm satellite cell, inhibits inflammatory teb, thiab txo qhov tsim ntawm cov leeg nqaij fibrosis, yog li txhim kho kev kho mob ntawm cov leeg nqaij.


Osteoarthritis: Osteoarthritis yog ib hom kab mob sib koom ua ke uas ua rau pob txha mos, pob txha o, thiab pob txha loj hlob. TB 500 Fragment (17–23) kuj tau pom muaj peev xwm kho mob osteoarthritis. Nws tuaj yeem txhawb kev loj hlob thiab matrix synthesis ntawm chondrocytes, inhibit chondrocyte apoptosis, yog li ua kom cov pob txha mos degeneration. Cov tshuaj tiv thaiv kab mob ntawm TB 500 Fragment (17–23) tuaj yeem txo cov kab mob synovial, txo qhov mob pob qij txha, thiab txo qhov o. Cov kev tshawb fawb tsiaj tau pom tias kev txhaj tshuaj intra-articular ntawm TB 500 Fragment (17-23) tuaj yeem txhim kho kev sib koom ua haujlwm hauv cov tsiaj txhu osteoarthritis thiab txo cov pob txha mos.


(3) Kev kho mob plawv

Myocardial infarction: Myocardial infarction yog ib qho kab mob loj heev uas tshwm sim los ntawm myocardial ischemia thiab necrosis vim yog cov hlab ntsha txhaws. TB 500 Fragment (17–23) muaj peev xwm siv tau tus nqi hauv kev kho mob myocardial infarction. Tom qab myocardial infarction, cov ntaub so ntswg myocardial tau txais cov lus teb inflammatory thiab cell apoptosis, ua rau lub plawv tsis ua haujlwm. TB 500 Fragment (17–23) tuaj yeem txhim kho lub plawv ua haujlwm tom qab myocardial infarction los ntawm inhibiting inflammatory teb, txo myocardial cell apoptosis, thiab txhawb angiogenesis. Cov kev tshawb fawb pom tau hais tias hauv cov qauv tsiaj ntawm myocardial infarction, kev siv TB 500 Fragment (17-23) tuaj yeem txo qhov loj me me, txhim kho lub plawv ejection feem, thiab txhim kho plawv contraction thiab so ua haujlwm.


Kev kho cov kab mob vascular: Hauv cov mob vascular raug mob, xws li endothelial puas tsuaj tom qab vascular intervention, TB 500 Fragment (17–23) tuaj yeem txhawb nqa endothelial cell migration thiab proliferation, accelerate endothelial kho, thiab txo qhov kev pheej hmoo ntawm thrombus tsim. Tom qab kev raug mob vascular endothelial, nthuav tawm collagen hauv qab ntawm endothelium tuaj yeem ua rau platelet adhesion thiab aggregation, ua rau thrombus tsim. TB 500 Fragment (17–23) txhawb nqa endothelial cell kho, kho cov vascular endothelial kev ncaj ncees, yog li txo cov thrombus tsim thiab tiv thaiv kev ua haujlwm vascular.




Xaus


TB 500 Fragment (17–23), raws li cov peptide fragment nrog cov cim lom lom, ua kom pom kev ua tau zoo hauv kev kho cov ntaub so ntswg, cell migration, thiab lwm qhov chaw.




Qhov chaw


[1] Esposito S, Deventer K, Goeman J, et al. Synthesis thiab characterization ntawm N-terminal acetylated 17-23 fragment ntawm thymosin beta 4 qhia nyob rau hauv TB-500, ib yam khoom uas xav tias yuav muaj peev xwm doping [J]. Kev Ntsuas Tshuaj thiab Tshuaj Ntsuam Xyuas, 2012,4(9): 733-738.DOI: 10.1002/dta.1402.


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TB-500-fragment--10mg

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