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.
Txheej txheem cej luam
Thymosin Alpha-1 (Tα1) yog peptide nrog lub zog tiv thaiv kab mob tseem ceeb. Nws yog thawj zaug cais tawm ntawm thymus cov ntaub so ntswg thiab muaj 28 amino acids, nrog N-terminal acetylation. Tα1 ua lub luag haujlwm tseem ceeb hauv kev tswj kev tiv thaiv kab mob thiab teb rau cov kab mob hauv lub cev. Raws li kev tiv thaiv kab mob, nws qhia tau hais tias muaj peev xwm zoo rau kev siv hauv kev kho mob thiab tiv thaiv ntau yam kab mob.
Daim duab 1 Thymosin alpha 1 muaj ntau yam kev ua haujlwm lom neeg. IL: Interleukin; IFN: Interferon; TLR: Tus xov tooj zoo li tus neeg txais xov tooj.
Nyob rau hauv cov xwm txheej ntawm lub cev, Tα1 koom nrog kev txhim kho ib txwm thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, ua rau muaj kev cuam tshuam loj rau kev sib txawv, kev loj hlob, thiab ua kom lub cev tiv thaiv kab mob. Nyob rau hauv cov kab mob pathological, xws li kab mob kis, qog nqaij hlav, thiab kev tiv thaiv kab mob tsis zoo, Tα1 tuaj yeem pab lub cev tiv thaiv kab mob los ntawm kev tswj lub cev tiv thaiv kab mob.
Hauv kev kis kab mob kis kab mob, Tα1 feem ntau yog siv los kho kab mob siab B (HBV) thiab kab mob siab C (HCV). Nws tuaj yeem tswj hwm kev tiv thaiv kab mob, pab lub cev tshem cov kab mob, thiab txhim kho cov neeg mob cov mob.
Immunomodulatory Mechanisms
(1) Kev sib cuam tshuam nrog Tus Xov Tooj Zoo li receptors (TLRs)
Ib txoj hauv kev tseem ceeb uas Tα1 ua rau nws lub cev tiv thaiv kab mob yog los ntawm kev cuam tshuam nrog Tus Xov Tooj Zoo li receptors (TLRs). TLRs yog ib chav kawm ntawm cov qauv kev lees paub receptors uas paub txog cov kab mob sib txuas nrog cov qauv molecular (PAMPs) thiab kev puas tsuaj cuam tshuam nrog cov qauv molecular (DAMPs), yog li ua kom lub cev tiv thaiv kab mob thiab pib lub cev tiv thaiv kab mob.
Tα1 tuaj yeem khi rau ntau TLRs, xws li TLR3, TLR4, thiab TLR9. Raws li kev khi rau cov receptors no, Tα1 qhib cov kev taw qhia qis qis, suav nrog cov kev tswj hwm kev tswj hwm interferon 3 (IRF3) thiab cov khoom siv hluav taws xob κB (NF-κB) cov kev taw qhia. Noj TLR3 ua piv txwv, tom qab Tα1 khi rau TLR3, nws txhawb cov phosphorylation ntawm IRF3, uas tom qab ntawd hloov mus rau lub cell nucleus, inducing kev qhia ntawm cov tshuaj tiv thaiv kab mob thiab kev tiv thaiv kab mob xws li hom I interferon (IFN-I). IFN-I muaj cov tshuaj tiv thaiv kab mob dav dav thiab kev tiv thaiv kab mob, ua kom lub cev tiv thaiv kab mob.
Rau TLR4, kev khi ntawm Tα1 zoo ib yam ua rau NF-κB teeb liab txoj hauv kev, txhawb kev qhia ntawm cytokines inflammatory xws li qog necrosis factor-α (TNF-α) thiab interleukin-6 (IL-6). Cov cytokines no ua lub luag haujlwm tseem ceeb hauv cov theem pib ntawm kev tiv thaiv kab mob, nrhiav cov kab mob tiv thaiv kab mob mus rau qhov chaw kis kab mob thiab txhim kho lub cev tiv thaiv kab mob.
Tsis tas li ntawd, TLR2 thiab TLR7 kuj tseem cuam tshuam nrog Tα1. Tα1 tuaj yeem qhib lub TLR2 / NF-κB, TLR2 / p38 mitogen-activated protein kinase (p38MAPK), lossis TLR7 / myeloid txawv qhov sib txawv 88 (MyD88) qhia txoj hauv kev, txhawb kev tsim tawm ntawm ntau yam cytokines xws li IL-1 thiab IL-12, muaj kev hloov pauv ntxiv hauv cov lus teb.
(2) Kev tswj cov kev cuam tshuam ntawm lub cev tiv thaiv kab mob
T hlwb
Tα1 cuam tshuam rau txoj kev loj hlob, sib txawv, thiab ua kom lub hlwb T. Nyob rau hauv lub thymus, Tα1 accelerates lub replenishment thiab maturation ntawm thymocytes. Cov kev tshawb fawb tau pom tias tom qab inhibiting T cell-mediated antibody ntau lawm hauv cov nas uas siv 5-fluorouracil (5-FU), chemically synthesized Tα1 tuaj yeem rov qab tau cov tshuaj tiv thaiv kab mob no, thiab nthuav tawm kev ua haujlwm txawm tias tsawg ntawm 30 μg / kg.
Flow cytometry tsom xam pom tias qhov koob tshuaj Tα1 no ua kom lub zog ntxiv thiab kev loj hlob ntawm thymocytes; Txawm li cas los xij, nws tsis cuam tshuam rau qhov kev qhia ntawm Smoothened (Smo), qhov tseem ceeb tsis zoo regulator ntawm Hedgehog (Hh) taw qhia txoj hauv kev hauv CD4⁻CD8⁻ thymocytes. Qhov no qhia tias Tα1 tuaj yeem txhawb T cell maturation los ntawm cov kev taw qhia tshwj xeeb uas hla los yog tsis muaj kev ywj pheej ntawm Smo-tswj txoj hauv kev.
Nyob rau hauv cov nqe lus ntawm paub tab T hlwb, Tα1 tuaj yeem tswj qhov sib npaug ntawm T cell subsets. Nyob rau hauv cov qog microenvironment, Tα1 tuaj yeem hloov qhov piv ntawm CD8⁺ T hlwb thiab tswj T hlwb (Tregs) los ntawm kev tswj cov dendritic cell (DC) sib txawv thiab chemokine qhia profiles, yog li txhim kho lub cev lub cev tiv thaiv kab mob.
Daim duab 2 Thymosin α1 (Tα1) tiv thaiv kev puas tsuaj ntawm epithelial hauv DSS ntxiv rau kev tiv thaiv-CTLA-4-induced colitis.
B hlwb
Txawm hais tias cov kev tshawb fawb ncaj qha ntawm qhov cuam tshuam ntawm Tα1 ntawm B hlwb tsis tshua muaj, kev tshawb fawb uas twb muaj lawm qhia tias nws tuaj yeem cuam tshuam rau B cell ua haujlwm los ntawm kev tswj T hlwb. Txij li thaum T hlwb ua lub luag haujlwm tseem ceeb hauv B cell activation, antibody class switching, and affinity maturation, Tα1's regulation of T cell function can indirectly influence B cell antibody production, li no pab txhawb lub cev humoral tiv thaiv kab mob.
Macrophages
Tα1 kuj tseem muaj kev tswj hwm tseem ceeb ntawm kev ua haujlwm macrophage. Siv MTT kev soj ntsuam, nws tau pom tias Tα1 nthuav tawm cov teebmeem cytotoxic ntawm RAW 264.7 macrophages, nrog ib nrab-qhov siab tshaj plaws inhibitory concentration (IC50) ntawm 368.105 μg / ml. Raws li Tα1 concentration nce, cov teebmeem cytotoxic ntawm RAW 264.7 hlwb intensify, ua rau txo qis ntawm cell ceev.
Tα1 kuj muaj cov tshuaj tiv thaiv kab mob, uas tau soj ntsuam los ntawm kev tshuaj xyuas nitric oxide (NO) ntau lawm hauv RAW 264.7 hlwb. Cov txiaj ntsig tau pom tias nyob rau hauv qhov concentration ntau ntawm 7.813–31.25 μg / ml, TSIS MUAJ ntau lawm hauv Tα1-kho pab pawg tau txo qis hauv kev siv tshuaj raws li kev siv tshuaj piv rau pawg tswj hwm, qhia tias Tα1 tuaj yeem siv nws cov tshuaj tiv thaiv kab mob los ntawm inhibiting NO ntau lawm hauv macrophages, yog li tswj kev tiv thaiv kab mob.
Ntuj Killer Cell (NK Cell)
Tα1 txhawb nqa NK cell proliferation thiab ua kom muaj zog, txhim kho lawv cov kev ua cytotoxic. NK hlwb yog ib qho tseem ceeb ntawm lub cev tiv thaiv kab mob hauv lub cev, muaj peev xwm tua tsis tau cov kab mob kis kab mob thiab cov qog hlwb. Tα1 txhim kho lawv lub peev xwm los paub txog thiab tua cov phiaj hlwb los ntawm kev txhim kho kev qhia ntawm kev ua kom cov receptors nyob rau saum npoo ntawm NK hlwb, yog li ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob thiab kev tiv thaiv kab mob.
(3) Kev tswj hwm ntawm cytokine network
Tα1 exerts nws immunoregulatory functions los ntawm kev tswj lub cytokine network. Cytokines yog ib chav kawm ntawm cov proteins me me uas tso tawm los ntawm lub cev tiv thaiv kab mob thiab qee lub hlwb tsis muaj zog, uas xa cov ntaub ntawv ntawm cov hlwb thiab tswj kev ua haujlwm ntawm lub cev tiv thaiv kab mob nrog rau kev siv zog thiab hom kev tiv thaiv kab mob.
Tα1 tuaj yeem txhawb kev tsim ntau yam cytokines, xws li interleukin-2 (IL-2), interleukin-3 (IL-3), thiab interferon-γ (IFN-γ). IL-2 yog ib qho tseem ceeb ntawm T cell loj hlob uas txhawb nqa T cell proliferation thiab ua kom muaj zog, txhim khu kev ua haujlwm ntawm NK hlwb thiab cytotoxic T lymphocytes (CTLs), yog li txhim kho lub cev tiv thaiv kab mob. IL-3 txhawb nqa kev loj hlob thiab kev sib txawv ntawm ntau yam hematopoietic qia hlwb thiab cov hlwb progenitor, pab tswj cov cellular muaj pes tsawg leeg thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob. IFN-γ muaj ntau yam haujlwm, suav nrog tshuaj tua kab mob, tshuaj tiv thaiv kab mob, thiab kev tiv thaiv kab mob tiv thaiv kab mob, txhim kho lub peev xwm ntawm phagocytic thiab cytotoxic ntawm macrophages, txhawb kev sib txawv ntawm Th1 hlwb, thiab tswj lub cev tiv thaiv kab mob rau lub cev tiv thaiv kab mob.
Tsis tas li ntawd, Tα1 tuaj yeem tswj hwm qhov sib npaug ntawm pro-inflammatory thiab anti-inflammatory cytokines. Thaum lub sij hawm inflammatory teb, Tα1 tuaj yeem cuam tshuam qhov kev tsim tawm ntau dhau ntawm cov cytokines xws li TNF-α thiab IL-1, thaum txhawb kev tsim cov tshuaj tiv thaiv cytokines xws li interleukin-10 (IL-10), yog li txo qhov kev puas tsuaj los ntawm inflammatory teb rau lub cev thiab tswj kev tiv thaiv kab mob.
Kev tiv thaiv kab mob
(1) Antiviral kab mob
Kab mob siab B thiab kab mob siab C
Tα1 ua lub luag haujlwm tseem ceeb hauv kev kho kab mob siab B thiab kab mob siab C. Rau tus kab mob siab B (HBV), Tα1 tuaj yeem tswj hwm lub cev tiv thaiv kab mob thiab txhim kho nws lub peev xwm los tshem HBV. Tα1 ua kom lub cev tiv thaiv kab mob xws li T hlwb thiab NK hlwb, ua kom lawv paub zoo dua thiab tshem tawm HBV-mob siab hlwb. Tα1 tuaj yeem tswj hwm lub cytokine network, txhawb kev tsim cov tshuaj tiv thaiv kab mob cytokines xws li IFN-γ thiab inhibiting HBV replication.
Hauv kev kho tus kab mob siab C (HCV), Tα1 kuj pom muaj txiaj ntsig zoo. Nws tuaj yeem txhim kho lub cev tiv thaiv kab mob, pab tshem tawm HCV, thiab pom muaj kev sib koom ua ke thaum siv nrog lwm cov tshuaj tiv thaiv kab mob, yog li txhim kho kev kho mob zoo.
Lwm yam kab mob
Ntxiv nrog rau HBV thiab HCV, Tα1 kuj tseem tuaj yeem ua lub luag haujlwm hauv lwm cov kab mob sib kis. Tα1 tuaj yeem pab txhim kho qhov kev cia siab ntawm cov neeg mob hnyav nrog COVID-19. Los ntawm kev kho cov kev puas tsuaj los ntawm lymphocyte tiv thaiv overactivation thiab tiv thaiv T-cell ua kom ntau dhau, Tα1 tuaj yeem txo cov tsos mob ntawm tus neeg mob thiab txhim kho kev ciaj sia.
(2) Kev tiv thaiv kab mob thiab tiv thaiv kab mob
Regulating Immune Balance
Tα1 ua lub luag haujlwm tseem ceeb hauv kev tswj kev tiv thaiv kab mob hauv lub cev. Hauv cov xeev tsis muaj zog tiv thaiv kab mob, Tα1 tuaj yeem txhawb kev loj hlob thiab kev sib txawv ntawm lub cev tiv thaiv kab mob, rov ua kom lub cev tiv thaiv kab mob. Piv txwv li, nyob rau hauv qee yam kab mob hauv lub cev tsis muaj zog lossis lub cev tiv thaiv kab mob los ntawm kev siv tshuaj khomob lossis kev kho hluav taws xob, Tα1 tuaj yeem pab lub cev rov tsim cov tshuaj tiv thaiv kab mob los ntawm kev tswj kev txhim kho thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob.
Hauv cov kab mob autoimmune, Tα1 tuaj yeem tiv thaiv cov kab mob tiv thaiv kab mob ntau dhau thiab txo cov kab mob autoimmune los ntawm kev tswj hwm cov haujlwm ntawm lub cev tiv thaiv kab mob thiab cov cytokine network.
Anti-inflammatory teebmeem
Tα1 muaj cov tshuaj tiv thaiv kab mob. Thaum lub sij hawm inflammatory teb, Tα1 tuaj yeem tswj cov kev qhia ntawm cov kab mob ntsig txog cytokines thiab inhibit cov kev mob tshwm sim ntau dhau. Raws li tau hais ua ntej, Tα1 tuaj yeem cuam tshuam tsis muaj kev tsim tawm hauv macrophages, txo qhov kev qhia ntawm cov cytokines pro-inflammatory xws li TNF-α thiab IL-1, thiab ib txhij txhawb kev tsim cov tshuaj tiv thaiv cytokines xws li IL-10.
Daim duab 3 Nitric oxide tso tawm tom qab kho nrog LPS thiab qhov sib txawv ntawm Tα-1 hauv RAW 264.7 hlwb.
Nyob rau hauv tus qauv mob inflammatory, Tα1 alleviates mechanical allodynia thiab hyperalgesia induced los ntawm ua tiav Freund's adjuvant (CFA), thiab txo cov upregulation ntawm inflammatory mediators xws li IFN-γ, TNF-α, thiab hlwb-derived neurotrophic yam (BDNF) induced los ntawm CFA. Tsis tas li ntawd, Tα1 tuaj yeem tswj hwm Wnt3a / β-catenin teeb liab txoj hauv kev hauv tus txha caj qaum, uas tau qhib thaum lub sijhawm ua haujlwm mob, thiab Tα1 tuaj yeem thim rov qab nws lub xeev qhib, yog li txo qhov mob.
Kev siv tshuaj kho mob
(1) Kev Kho Kab Mob Siab Viral Hepatitis
Hauv kev kho mob ntawm tus kab mob siab viral, Tα1 tau siv dav. Rau cov neeg mob uas muaj kab mob siab B ntev, ntau qhov kev tshawb fawb soj ntsuam tau pom tias Tα1 ua ke nrog nucleoside (acid) analogues lossis interferon therapy ua tiav ntau dua ntawm HBV DNA seroconversion, HBeAg seroconversion, thiab ALT normalization piv rau monotherapy. Hauv qee qhov kev sim tshuaj, kev sib xyaw ua ke ntawm Tα1 thiab entecavir rau kev kho mob ntawm cov neeg mob kab mob siab B mob ntev ua rau muaj tus nqi ntau dua ntawm HBV DNA seroconversion tom qab 48 lub lis piam ntawm kev kho mob piv rau cov pab pawg kho nrog entecavir ib leeg, thiab tus nqi ntawm HBeAg seroconversion kuj tau txhim kho.
Hauv kev kho kab mob siab C, Tα1 ua ke nrog cov tshuaj tiv thaiv kab mob ncaj qha (DAAs) tuaj yeem txhim kho kev ua haujlwm tiv thaiv kab mob, tshwj xeeb tshaj yog rau qee cov neeg mob uas tiv thaiv kab mob siab C, muaj peev xwm txhim kho kev kho mob tau zoo.
(2) Kev Kho Mob ntawm Immunodeficiency Disorders
Rau qee yam kab mob hauv lub cev tsis muaj zog, xws li congenital thymic hypoplasia, Tα1 tuaj yeem siv los ua ib feem ntawm lwm txoj kev kho. Txawm hais tias Tα1 tsis tuaj yeem kho cov kab mob no kom tiav, nws tuaj yeem tswj hwm kev tiv thaiv kab mob, txhim kho cov neeg mob kev tiv thaiv kab mob, txo qhov zaus thiab mob hnyav, thiab txhim kho cov neeg mob lub neej zoo.
Hauv cov kab mob tiv thaiv kab mob tsis muaj zog, xws li HIV / AIDS, Tα1 ua ke nrog kev kho tshuaj tiv thaiv kab mob (ART) tuaj yeem txhim kho lub cev tiv thaiv kab mob, nce CD4⁺ T cell suav, txhim kho kev tiv thaiv kab mob, thiab txo qhov tshwm sim ntawm kev kis kab mob.
(3) Lwm yam kev siv
Adjuvant Therapy for Infectious Diseases
Hauv kev kho mob hnyav xws li sepsis, Tα1 tuaj yeem siv los ua kev kho mob ntxiv. Cov neeg mob Sepsis feem ntau muaj lub cev tsis muaj zog. Tα1 tswj hwm lub cev tiv thaiv kab mob ua haujlwm thiab cytokine tes hauj lwm, pab txhawb kev tiv thaiv kab mob, txo cov kab mob, thiab txhim kho cov neeg mob ciaj sia.
Hauv kev kho cov kab mob sib kis ntev xws li tuberculosis, Tα1 ua ke nrog cov tshuaj tua kab mob tuaj yeem txhim kho lub cev tiv thaiv kab mob tiv thaiv kab mob Mycobacterium tuberculosis thiab txhim kho kev kho mob.
Kab mob ntsig txog kab mob
Hauv kev kho mob ntawm cov kab mob inflammatory xws li mob caj dab rheumatoid thiab inflammatory plob tsis so tswj kab mob, Tα1's anti-inflammatory thiab immune-modulating teebmeem yuav muaj peev xwm siv tau. Txawm hais tias daim ntawv thov kev kho mob tam sim no raug txwv, qee qhov kev tshawb fawb yooj yim thiab kev sim tshuaj me me tau qhia tias Tα1 tuaj yeem txo cov kev mob tshwm sim thiab txhim kho cov neeg mob los ntawm kev tswj hwm lub cev tiv thaiv kab mob thiab cytokines.
Xaus
Thymosin α1 (Tα1), raws li peptide nrog lub zog tiv thaiv kab mob, tau ua rau muaj kev cuam tshuam loj thiab muaj txiaj ntsig hauv kev tiv thaiv kab mob. Los ntawm nws cov txheej txheem ntawm kev ua, Tα1 cuam tshuam nrog Tus Hu-zoo li receptors los qhib ntau txoj hauv kev taw qhia hauv qab, yog li tswj kev ua haujlwm ntawm lub cev tiv thaiv kab mob thiab cytokine tes hauj lwm, thiab ua tiav kev tswj hwm ntawm lub cev tiv thaiv kab mob.
Hais txog kev tiv thaiv kev tiv thaiv kab mob, Tα1 plays lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob, kev ua haujlwm tiv thaiv kab mob, kev tiv thaiv kev tiv thaiv kab mob, thiab kev tiv thaiv kab mob. Hauv thaj chaw tshuaj tiv thaiv kab mob, Tα1 qhia txog kev siv dav dav, txawm tias muaj kab mob sib kis xws li kab mob siab B thiab C, lossis rau cov kab mob tshwm sim zoo li COVID-19. Lub luag haujlwm ntawm Tα1 hauv cov kab mob tiv thaiv kab mob tsis muaj zog thiab cov kab mob sib kis tau qhia tias nws tuaj yeem pab txhawb kev tiv thaiv kab mob thiab txo qis kev puas tsuaj. Zuag qhia tag nrho, Tα1 plays lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob.
Qhov chaw
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Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
