FOX04 DRI 10 mg

▎ FOXO4-DRI Structure

Source: PubChem

Sequence: LTLRKEPASEIAQSILEAYSQNGWANRRSGKRPPPRRRQRRKKRG Molecular Formula: C 228H 388N 86O64 Molecular Luj: 5358g / mol PubChem CID: 168431240 Cov ntsiab lus: EX-A7431

▎ FOXO4-DRI Kev Tshawb Fawb

Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm FOXO4-DRI?

In-depth Research ntawm Cellular Senescence: 

Nrog rau kev kawm txuas ntxiv mus rau qhov tob ntawm cov txheej txheem ntawm cellular senescence, nws tau pom tias cellular senescence plays lub luag haujlwm tseem ceeb hauv ntau cov txheej txheem physiological nrog rau qhov tshwm sim thiab kev loj hlob ntawm cov kab mob. Senescent hlwb yuav sib sau thiab zais ntau yam cytokines thiab inflammatory mediators, cuam tshuam rau kev ua haujlwm ntawm cov hlwb nyob ib puag ncig, thiab yog li ua rau poob ntawm cov ntaub so ntswg thiab lub cev ua haujlwm. Yog li ntawd, nrhiav txoj hauv kev los cuam tshuam cov txheej txheem ntawm cellular senescence tau dhau los ua qhov kev tshawb fawb hotspot.

Kev tshawb pom ntawm FOXO4 Protein: 

FOXO4 yog ib tug tswv cuab ntawm lub forkhead box protein O tsev neeg (FOXO) thiab ua lub luag haujlwm tseem ceeb hauv ntau yam txheej txheem lom neeg xws li kev loj hlob ntawm tes, sib txawv, apoptosis, thiab kev ntxhov siab. Cov kev tshawb fawb tau pom tias FOXO4 muaj feem cuam tshuam nrog cellular senescence, thiab nws tuaj yeem cuam tshuam cov txheej txheem senescence ntawm cov hlwb los ntawm kev tswj cov kev qhia ntawm ntau cov noob. Piv txwv li, FOXO4 tuaj yeem qhib qhov kev nthuav qhia ntawm qee cov noob caj noob ces antioxidant thiab DNA kho cov noob, txhim kho lub cell tiv thaiv oxidative kev nyuaj siab thiab DNA puas, yog li ncua cellular senescence.

Kev tshuaj ntsuam ntawm Me Me Molecule Compounds: 

Raws li kev nkag siab txog kev ua haujlwm ntawm FOXO4 protein, cov kws tshawb fawb tau pib tshuaj xyuas cov tshuaj me me uas tuaj yeem tswj hwm cov haujlwm ntawm FOXO4. Lawv vam tias yuav nrhiav tau cov khoom me me uas tuaj yeem ua kom cov FOXO4 protein, yog li siv nws cov nyhuv tiv thaiv kev laus thiab kho cov kab mob. Tom qab ib tug loj tus naj npawb ntawm kev sim tshuaj ntsuam xyuas thiab optimizations, lub me me molecule compound FOXO4-DRI thaum kawg tau pom. Nws tuaj yeem khi tshwj xeeb rau FOXO4 protein, qhib nws txoj hauv kev taw qhia nqes hav, thiab ua lub luag haujlwm hauv kev tswj hwm cellular senescence thiab lwm yam physiological functions.

Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm FOXO4-DRI?

1. Anti-aging

FOXO4-DRI tuaj yeem qhib FOXO4 protein, thiab tom qab ntawd tswj cov cell metabolism, kev loj hlob, thiab cov txheej txheem apoptosis. FOXO4 protein ua lub luag haujlwm tseem ceeb hauv cov hlwb. Nws tuaj yeem txhim kho lub cell tiv thaiv kev ntxhov siab los ntawm kev tswj cov kev qhia ntawm cov noob caj ces, thiab txo cov cellular senescence thiab kev puas tsuaj. Piv txwv li, FOXO4 tuaj yeem txhawb kev nthuav tawm ntawm cov enzymes antioxidant thiab txo cov qib ntawm intracellular reactive oxygen hom, yog li alleviating kev puas tsuaj ntawm oxidative kev nyuaj siab rau hlwb ^{[1, 2]} . Tsis tas li ntawd, FOXO4 tseem tuaj yeem tswj cov kev qhia ntawm cov noob muaj feem xyuam rau lub voj voog ntawm tes, inhibit cell proliferation ntau dhau, thiab tswj cov metabolism thiab ua haujlwm ntawm cov hlwb.

2. Mechanism of Action in Txiv neej Late-Onset Hypogonadism

Kev sib tham nrog FOXO4 thiab p53: 

Txiv neej lig-pib hypogonadism yog ib yam kab mob uas muaj hnub nyoog, thiab nws cov txheej txheem tseem ceeb yog qhov ua tsis tau zoo ntawm cov hlwb Leydig hauv cov qog ntshav. Nws tau raug pom tias lub thawv forkhead O (FOXO) kev hloov pauv ntawm FOXO4 yog tshwj xeeb hauv tib neeg Leydig hlwb, thiab nws txoj kev hloov mus rau cov nucleus hauv cov neeg laus muaj feem cuam tshuam txog kev txo qis hauv testosterone synthesis. Raws li ib qho tshwj xeeb FOXO4 blocker, FOXO4-DRI xaiv induces p53 nuclear cais tawm thiab apoptosis hauv senescent Leydig hlwb los ntawm kev cuam tshuam kev cuam tshuam ntawm FOXO4 thiab p53 ^[1].

Txhim kho Testicular Microenvironment: 

Hauv cov nas uas muaj hnub nyoog ib txwm muaj, FOXO4-DRI tuaj yeem txhim kho cov kab mob qog noj ntshav thiab txo cov hnub nyoog ntsig txog testosterone tsis txaus. Qhov no qhia tau hais tias FOXO4-DRI tuaj yeem rov ua haujlwm li qub ntawm cov qog nqaij hlav los ntawm kev tswj cov kev taw qhia txog txoj kev loj hlob ntawm Leydig hlwb, yog li nce qib testosterone secretion ^[1].

3. Mechanism of Action hauv Pulmonary Fibrosis

Txo Senescent Cells thiab Downregulating SASP Qhia: 

Pulmonary fibrosis yog ib hom kab mob ntsws interstitial uas muaj kev kho mob tsawg. Cellular senescence yog suav hais tias yog ib qho ntawm cov kab mob pathogenic ntawm pulmonary fibrosis, thiab kev tshem tawm ntawm cov hlwb senescent tuaj yeem txhim kho lub ntsws ua haujlwm. Nyob rau hauv tus qauv nas ntawm pulmonary fibrosis tshwm sim los ntawm bleomycin, FOXO4-DRI, zoo ib yam li cov tshuaj pom zoo pirfenidone, tuaj yeem txo qis hlwb, txo qis kev qhia ntawm senescence-associated secretory phenotype (SASP), thiab alleviate the morphological change and collagen deposition induced by bleomy ^[2].

Influencing qhov ratio ntawm Cell Hom: 

FOXO4-DRI tuaj yeem nce qhov kev faib ua feem ntawm hom 2 alveolar epithelial hlwb (AEC2) thiab fibroblasts thiab txo qhov kev faib ua feem ntawm myofibroblasts hauv tus qauv nas ntawm pulmonary fibrosis induced los ntawm bleomycin. Hauv kev sim hauv vitro, piv nrog cov nas thiab tib neeg lub ntsws fibroblast cell kab, FOXO4-DRI muaj kev nyiam ntau dua los tua myofibroblasts induced los ntawm transforming loj hlob factor-β (TGF-β) ^[2].

Regulating Extracellular Matrix Receptor Interaction Pathway: 

Cov nyhuv inhibitory ntawm FOXO4-DRI ntawm myofibroblasts ua rau txo qis ntawm extracellular matrix (ECM) receptor kev cuam tshuam txoj hauv kev hauv bleomycin-induced pulmonary fibrosis. Qhov no qhia tau hais tias FOXO4-DRI tuaj yeem txhim kho cov txheej txheem pathological ntawm pulmonary fibrosis los ntawm kev tswj cov tiam thiab cov metabolism hauv ECM ^[2].

FOXO4-DRI ameliorates bleomycin (BLM)-induced pulmonary fibrosis (PF). (A) Schematic daim duab qhia qhov kev sim tsim. (B) Cov neeg sawv cev scanned dluab ntawm haematoxylin-eosin (HE) staining thiab Masson trichrome-staining ntawm lub ntsws cov ntaub so ntswg.

Source: PubMed ^[2]

Dab tsi yog cov ntawv thov ntawm FOXO4-DRI?

1. Anti-aging

FOXO4-DRI muaj peev xwm muaj txiaj ntsig hauv kev txhim kho hnub nyoog cuam tshuam txog kev ua haujlwm poob qis. Nrog rau kev loj hlob ntawm lub hnub nyoog, ntau yam hauv nruab nrog cev thiab lub cev ntawm lub cev yuav muaj kev sib txawv ntawm kev laus thiab kev ua haujlwm tsis zoo, xws li kev txo qis hauv kev tiv thaiv kab mob, kev ua haujlwm tsis muaj zog ntawm cov hlab plawv, thiab kev poob ntawm cov paj hlwb. Los ntawm kev ua kom FOXO4 protein, FOXO4-DRI tuaj yeem ncua cov txheej txheem ntawm cellular senescence, txhim kho cell vitality thiab muaj nuj nqi, thiab yog li pab txhim kho tag nrho cov kev noj qab haus huv ntawm lub cev. Piv txwv li, hauv cov qauv nas laus, kev kho mob nrog FOXO4-DRI tuaj yeem txhim kho kev tawm dag zog thiab kev txawj ntse ntawm cov nas thiab txo qhov tshwm sim ntawm cov kab mob uas muaj hnub nyoog ^{[1, 2]}.

2. Kev Kho Cov Kab Mob Neurodegenerative

Kev sib raug zoo nrog Neuron Aging thiab Death: 

Cov kab mob neurodegenerative xws li Alzheimer's kab mob thiab Parkinson's kab mob yog ze ze rau kev laus thiab kev tuag ntawm neurons. Hauv cov kab mob no, cov neurons yuav raug puas tsuaj los ntawm ntau yam xws li oxidative kev nyuaj siab, inflammatory teb, thiab protein aggregation, ua rau kom tsis tu ncua ntawm neuronal muaj nuj nqi thiab thaum kawg ua rau kev txawj ntse thiab lub cev muaj zog tsis ua hauj lwm. Los ntawm kev ua kom lub FOXO4 signaling txoj kev, FOXO4-DRI tuaj yeem txhawb txoj kev ciaj sia thiab kho cov neurons thiab txhim kho lawv cov kev tiv thaiv rau oxidative kev nyuaj siab thiab apoptotic signals.

FOXO4 protein tuaj yeem tswj cov kev qhia ntawm ntau cov noob hauv cov neurons, suav nrog antioxidant enzymes, anti-apoptotic proteins, paj hlwb loj hlob, thiab lwm yam. Piv txwv li, hauv tus qauv nas ntawm Alzheimer's tus kab mob, kev kho mob nrog FOXO4-DRI tuaj yeem txo qhov tso tawm ntawm amyloid proteins, txhim kho neuronal muaj nuj nqi, thiab txo qis kev loj hlob ntawm tus kab mob. Hauv tus qauv Parkinson tus kab mob, FOXO4-DRI kuj tseem tuaj yeem tiv thaiv dopaminergic neurons thiab txhim kho kev tawm dag zog ntawm nas ^{[3, 4]} . Yog li ntawd, FOXO4-DRI yuav tsum tau siv rau hauv kev kho mob ntawm cov kab mob neurodegenerative kom qeeb ntawm kev loj hlob ntawm tus kab mob thiab txhim kho kev txawj ntse thiab lub cev muaj zog ntawm cov neeg mob.

3. Kev tiv thaiv thiab kev kho mob ntawm cov kab mob plawv

Tiv thaiv Cardiomyocytes: 

Hauv cov hlab plawv, FOXO4-DRI tuaj yeem tiv thaiv cardiomyocytes los ntawm oxidative kev nyuaj siab thiab kev puas tsuaj apoptotic. Cardiomyocytes yog lub luag haujlwm tseem ceeb ntawm lub plawv, thiab lawv qhov kev puas tsuaj thiab kev tuag yog ib qho tseem ceeb ntawm cov kab mob plawv. FOXO4-DRI tuaj yeem qhib cov FOXO4 protein, txhawb kev qhia ntawm cov enzymes antioxidant, txo cov qib ntawm intracellular reactive oxygen hom nyob rau hauv cardiomyocytes, thiab alleviate kev puas tsuaj ntawm oxidative kev nyuaj siab rau cardiomyocytes. Nyob rau tib lub sijhawm, FOXO4-DRI kuj tseem tuaj yeem txhawb nqa kev qhia ntawm cov tshuaj tiv thaiv apoptotic, inhibit qhov kev ua haujlwm ntawm apoptotic signaling pathway, thiab tiv thaiv cardiomyocytes los ntawm apoptosis ^[4].

Txhawb txoj haujlwm ntawm Vascular Endothelial Cells: 

FOXO4-DRI kuj tseem tuaj yeem txhawb nqa kev ua haujlwm ntawm cov hlab ntsha endothelial thiab tswj kev ruaj khov thiab elasticity ntawm cov hlab ntsha. Vascular endothelial hlwb yog ib qho tseem ceeb ntawm cov hlab ntsha phab ntsa, thiab lawv cov kev ua haujlwm txawv txav yuav ua rau muaj cov kab mob plawv xws li nce vascular permeability, thrombosis, thiab atherosclerosis. FOXO4-DRI tuaj yeem qhib cov FOXO4 protein, tswj cov kev qhia ntawm ntau cov noob hauv vascular endothelial hlwb, txhawb kev loj hlob, kev tsiv teb tsaws, thiab kho cov vascular endothelial hlwb, thiab tswj kev ua haujlwm ntawm cov hlab ntsha. Piv txwv li, FOXO4-DRI tuaj yeem txhim kho qhov kev qhia ntawm vascular endothelial kev loj hlob zoo (VEGF), txhawb kev loj hlob ntawm vascular endothelial hlwb thiab angiogenesis; Nws tseem tuaj yeem txhim kho qhov kev qhia ntawm endothelial nitric oxide synthase (eNOS), txhawb kev tsim cov nitric oxide, dilate cov hlab ntsha, thiab txo cov ntshav siab ^[4].

Tiv thaiv thiab kho cov kab mob plawv: 

Hauv cov ntsiab lus, FOXO4-DRI pab tiv thaiv thiab kho cov kab mob plawv xws li myocardial infarction, plawv tsis ua hauj lwm, thiab atherosclerosis. Hauv cov qauv tsiaj ntawm myocardial infarction, kev kho mob nrog FOXO4-DRI tuaj yeem txo qhov kev tuag ntawm cardiomyocytes, txhawb kev kho cov ntaub so ntswg myocardial, thiab txhim kho lub plawv ua haujlwm. Hauv cov qauv plawv tsis ua haujlwm, FOXO4-DRI tuaj yeem cuam tshuam cov apoptosis ntawm cardiomyocytes, txhim kho myocardial contractility, thiab txhim kho lub zog ntawm lub plawv. Hauv cov qauv atherosclerosis, FOXO4-DRI tuaj yeem txo qhov kev puas tsuaj ntawm vascular endothelial hlwb, inhibit qhov inflammatory teb, thiab txo qhov kev pheej hmoo ntawm atherosclerosis ^[4].

Hauv kev xaus, los ntawm nws cov txheej txheem ntawm kev ua, suav nrog inducing lub apoptosis ntawm senescent hlwb, txhim kho cov ntaub so ntswg microenvironment, thiab ncua cov txheej txheem kev laus, FOXO4-DRI qhia tau hais tias muaj peev xwm siv tus nqi hauv kev tiv thaiv kev laus, kev kho mob ntawm cov qog nqaij hlav, cov kab mob pulmonary fibrosis, cov kab mob neurodegenerative, thiab kev tiv thaiv kab mob.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Han X yog tus kws tshawb fawb koom nrog ntau lub koom haum sib txawv, suav nrog Jiangxi Academy of Sciences, Fudan University, Hunan University, Zhengzhou University, University of Geosciences, Sichuan University, National University of Singapore, Ministry of Natural Resources of the People's Republic of, Suav Academy ntawm Kev Kho Mob Sciences - Peking Union Medical College, Peking Union Medical College, Jiang Xiilin, S. Tianjin University, thiab Northeast Normal University - . Cov kev koom tes no qhia txog nws cov keeb kwm kev kawm dav dav thiab ntau haiv neeg.

Nws txoj kev tshawb fawb nyiam nthuav dav thoob plaws ntau yam kev kawm tseem ceeb. Nws nquag koom nrog kev tshawb fawb hauv thaj chaw ntawm Chemistry, Environmental Sciences & Ecology, Kev Tshawb Fawb & Kev sim tshuaj, Oncology, thiab Biochemistry & Molecular Biology. Nws txoj haujlwm qhia txog kev paub dav dav thiab muaj txiaj ntsig zoo rau thaj chaw no. Han X tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [2].

▎ Cov Lus Qhia Tseem Ceeb

[1] Zhang C, Xie Y, Chen H, et al. FOXO4-DRI alleviates lub hnub nyoog hais txog testosterone secretion insufficiency los ntawm lub hom phiaj senescent Leydig hlwb nyob rau hauv cov laus nas [J]. Aging (Albany Ny), 2020,12(2):1272-1284.DOI:10.18632/aging.102682.

[2] Han X, Yuan T, Zhang J, et al. FOXO4 peptide tsom rau myofibroblast ameliorates bleomycin-induced pulmonary fibrosis hauv nas los ntawm ECM-receptor kev sib cuam tshuam [J]. Phau ntawv Journal of Cellular and Molecular Medicine, 2022,26(11):3269-3280.DOI:10.1111/jcm.17333.

[3] Theoharides TC, Tsilioni I. Tetramethoxyluteolin for the Treatment of Neurodegenerative Diseases[J]. Cov ncauj lus tam sim no hauv Tshuaj Kho Mob, 2018,18(21):1872-1882.DOI:10.2174/ 15680266176 66 18111915424 7.

[4] Aslam DI, Jiyanboyevich Y, Ergashboevna A. Kev Tiv Thaiv & Kev Kho Mob Ntawm Cov Kab Mob plawv[J]. The American Journal of Medical Sciences and Pharmaceutical Research, 2021,03:180-188.DOI:10.37547/TAJMSPR/Volume03Issue06-28.

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.