Na Cocer Peptides bin rayt am 
1 mɔnt dɔn pas
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto famasitik, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ di tin dɛn we dɛn dɔn lan
thymosin Alpha-1 (Tα1) na pεptida we gεt sכm imyun rεgεdyushכn fכnshכn dεm. i fכs ayzכlεt frכm taymus tisu εn i kכnsis fכ 28 amino asid dεm, wit N-tεrminal asetyleshכn. Tα1 de ple imכtant rol fכ mεnten imyun bεlε εn fכ rεspכnd to di sik stet dεm na di bכdi. As imyun εnhansa, i de sho big pכtεnshal fכ aplikεshכn fכ trit εn prεvεnshכn fכ difrεn sik dεm.
fig 1 Taymosin alfa 1 gεt bכku bכku bayolojikal aktiviti dεm. IL: Intalyukin we de na di wɔl; IFN: Intɛrfɛrɔn; TLR: Risεptor dεm we lεk tol.
כnda fisiolכjik kכndishכn dεm, Tα1 de tek pat pan di nכmal divεlכpmεnt εn fכnshכnal mεntenans fכ di imyun sistεm, we de εksyεrt sכm infכmeshכn pan di difrεns, machכreshכn, εn aktibכshכn fכ di imyun sεl dεm. כnda patכlayz kכndishכn dεm, lεk vayral infεkshכn, tumorigenesis, εn imyun dεfisiεns, Tα1 kin εp di bכdi fכ fכm sik dεm bay we i de rεgεl di imyun rεspכns dεm.
Insay di fild fɔ vayral infɛkshɔn sik dɛm, dɛn kin yuz Tα1 fɔ trit epataytis B vayrɔs (HBV) ɛn epataytis C vayrɔs (HCV) infɛkshɔn. I kin rigul di imyun fכnshכn, εp di bכdi fכ klin di vayrus dεm, εn impruv di sikman dεm in kכndishכn.
Imyunmodulatori Mεkanism dεm
(1) Intarakshכn wit Toll-layk rεsεpכta dεm (TLR) .
wan imכtant path we Tα1 de du in imyun rεgεdyushכn ifekt dεm na bay we i de intarakt wit Toll-lεk rεsεpכta dεm (TLR dεm). TLR dεm na wan klas fכ patεn rεkכgnishכn rεsεpכta dεm we de rεkכgnεz di patכgen-asכsiet mכlikul patεn (PAMP) εn damej-asכsiet mכlikul patεn (DAMP), we de aktibכt imyun sεl dεm εn initiate imyun rεspכns.
Tα1 kin biεn to mכltipכl TLR dεm, lεk TLR3, TLR4, εn TLR9. we i de biεn dεn risεptor dεm ya, Tα1 de aktibכt dכwnstrim signal path dεm, inklud di intafεron rεgεlyutכri fכktכ 3 (IRF3) εn nyuklia fכktכ κB (NF-κB) signal path dεm. we wi tek TLR3 as egzampl, afta Tα1 tay to TLR3, i de promuot di fכsfכrayleshכn fכ IRF3, we de transloket to di sεl nyuklios, we de indyuz di εksprεshכn fכ antivayral εn imyun-rεgεlεtכri jin dεm lεk tayp I intafεron (IFN-I). IFN-I gεt brayt antivayral εn imyun-rεgεlεtכri fכnshכn dεm, we de εnhans di bכdi in rεsistεns to vayral infεkshכn dεm.
fכ TLR4, di binding fכ Tα1 sεm kayn we de aktibכt di NF-κB signal path, we de upregulate di εksprεshכn fכ inflammatory saytokεn dεm lεk tכmכro nεkrכsis fכktכ-α (TNF-α) εn intalyukin-6 (IL-6). dis saytokכn dεm de ple imכtant rol insay di fכs stej dεm fכ di imyun rεspכns, we de rikrut di imyun sεl dεm to di sayt we di infεkshכn de εn fכ mek di bכdi in imyun difεns kεpabiliti dεm go bכku.
apat frכm dat, TLR2 εn TLR7 de כlso כsכsiayt wit Tα1. Tα1 kin aktibכt di TLR2/NF-κB, TLR2/p38 maytojen-aktibכt protin kinaz (p38MAPK), כ TLR7/mayloid difrεns fכktכ 88 (MyD88) signal path dεm, we de protεkt di prodyushכn fכ difrεn saytokεn dεm lεk IL-1 εn IL-12, we de mek i de εnhans di innate εn adaptiv imyun rεspכns dεm mכr.
(2) Rigyuletɔri ifɛkt dɛn pan imyun sɛl dɛn
T sɛl dɛn
Tα1 de infכlכw di divεlכpmεnt, difrεns, εn aktibכshכn fכ T sεl dεm. insay di taymus, Tα1 de aksεlεrayt di riplinishmεnt εn machכrayshכn fכ di taymכsayt dεm. stכdi dεn sho se afta dεn inhεbit T sεl-mεdiet antibodi prodakshכn insay mays dεm we de yuz 5-fluorouracil (5-FU), kεmikכl sεntez Tα1 kin rεstכr dis antibodi prodakshכn kapasiti, εn i de sho aktvכti ivin pan lכw dכz 30 μg/kg.
fכlכ saytכmetri analisis sho se dis dכz fכ Tα1 de aksεlεrayt di riplinishmεnt εn mεchurεshכn fכ di taymכsayt dεm; כltu, i nכ de afekt di εksprεshכn fכ Smoothened (Smo), we na wan kכl nεgεtiv rεgεlεt fכ di Hedgehog (Hh) signal path insay CD4−CD8− taymosayt dεm. dis sho se Tα1 kin protεkt T sεl mεchurεshכn tru spεsifi k signal path dεm we de baypas כ indipεndεnt frכm Smo-rεgεlεt path dεm.
in tεm dεm fכ machכ T sεl dεm, Tα1 kin rεgεl di bεlε fכ di T sεl sכbsεt dεm. insay di tכmכro maykro envayroment, Tα1 kin altεr di rεshכn fכ CD8+ T sεl dεm εn rεgεdyushכn T sεl dεm (Tregs) bay we i de rεgεl di dεndritik sεl (DC) difrεns εn kεmokin εksprεshכn profayl dεm, we de mek di bכdi in antitכm imyun rεspכns bכku.
Figure 2 Thymosin α1 (Tα1) de prεvεnt di εpitεlial dεmεj in DSS plεs anti–CTLA-4–indyus kolεt.
B sɛl dɛn
pan tap we dayrekt stכdi dεm pan di ifekt dεm we Tα1 gεt pan B sεl dεm nכ rili sכm, risεch we de naw sho se i kin indaykt infכmeshכn B sεl fכnshכn bay we i de rεgεl T sεl dεm. sכm T sεl dεm de ple wan ki כksijεn rol fכ B sεl aktibכshכn, antibodi klas swich, εn afiniti mεchurεshכn, Tα1 in rεguleshכn fכ T sεl fכnshכn kin indaykt infכmeshכn B sεl antibodi prodakshכn, we de εnhans di bכdi in humoral imyun rεspכns.
Makrofag dɛn
Tα1 gεt imכtant rεgεdyushכn ifekt dεm bak pan makrofag fכnshכn. Yuz di MTT asεy, dεn fכnshכn se Tα1 de sho saytכtoksik ifekt pan RAW 264.7 makrofag dεm, wit haf-maksimal inhibitory kכnsantreshכn (IC50) we na 368.105 μg/ml. as Tα1 kכnsantreshכn de inkrεs, di saytכtoksik ifekt dεm pan RAW 264.7 sεl dεm de intensif, we de mek di sεl dεnsiti dכn.
Tα1 de sho bak anti-inflammatory ifekt dεm, we dεn bin ases bay we dεn analכz naytrik oksayd (NO) prodakshכn insay RAW 264.7 sεl dεm. di risalts sho se insay di konsantreshכn rεnj we na 7.813–31.25 μg/ml, NO prodakshכn in di Tα1-trit grup dכn dכn in wan dכz-dipεndεnt we kכmpεr to di kכntrol grup, we sho se Tα1 kin εksyεrt in anti-inflammatory ifekt dεm bay we i de inhεbit NO prodakshכn insay makrofag dεm, we de rεgεl imyun rεspכns dεm.
Natural kilεr sεl dεm (NK sεl dεm) .
Tα1 de promuot NK sel proliferashכn εn aktibכshכn, we de εnhans dεn saytכtoksik aktiviti. NK sεl dεm na imכtant kכmכpכnt fכ di innate imyun sistεm, we ebul fכ kil nכn spεshal wan fכ kil di vayrus infεkt sεl dεm εn di tכmכro sεl dεm. Tα1 de εnhans dεn abiliti fכ rεkכgnεz εn kil tכgεt sεl dεm bay we i de upregulate di εksprεshכn fכ aktibכshכn rεsεpכta dεm na di sεf fכ NK sεl dεm, we de ple wan imכtant rol insay antivayral infεkshכn εn antitכmכr imuniti.
(3) Rεgulεshכn כf di saytokεn nεtwכk
Tα1 de du in imyun rεgεlεtכri fכnshכn dεm bay we i de rεgεl di saytokεn nεtwכk. saytokכn dεm na wan klas fכ sכm sכm mכlikul protin dεm we di imyun sεl dεm εn sכm sεl dεm we nכ de fכ imyun, we de transmit infכmeshכn bitwin sεl dεm εn de rεgεl di wok we di imyun sεl dεm de du εn bak di intensiti εn di kayn imyun rεspכns dεm.
Tα1 kin mek di prodakshכn fכ difrεn saytokכn dεm, lεk intalyukin-2 (IL-2), intalyukin-3 (IL-3), εn intafεron-γ (IFN-γ). IL-2 na imכtant T sεl growth fכktכ we de protεkt di T sεl proliferashכn εn aktibכshכn, i de εnhans di aktiviti fכ NK sεl dεm εn saytכtoksik T limfosayt dεm (CTL), we de mek di bכdi in imyun difεns kεpabiliti dεm impruv. IL-3 de promuot di proliferashכn εn difrεns fכ difrεn hεmatopoiεtik stεm sεl dεm εn di progenitor sεl dεm, we de εp fכ mεnten di sεl kכmכshכn εn fכnshכn fכ di imyun sistεm. IFN-γ gεt mכltipכl fכnshכn dεm, we inklud antivayral, antitכmכr, εn imyun rεgεdyushכn ifekt dεm, fכ εnhans di fagosaytik εn saytכtoksik kεpabiliti fכ makrofag dεm, fכ protεkt di difrεns fכ Th1 sεl dεm, εn rεgεl di imyun rεspכns to wan sεlyul imyun dairekshכn.
apat frכm dat, Tα1 kin rεgεl di bεlε bitwin di pro-inflammatory εn anti-inflammatory cytokines. di tεm we di inflammatory rεspכns dεm de, Tα1 kin sכpres di כva prodyushכn fכ di pro-inflammatory cytokines lεk TNF-α εn IL-1, we i de promuot di prodyushכn fכ anti-inflammatory cytokines lεk interleukin-10 (IL-10), we de ridyus di damej we inflammatory rεspכns dεm de kכz to di bכdi εn mεnten imyun bεlε.
Di tin dɛn we kin mek di bɔdi gɛt mɔ imyun
(1) Antivayrɔs infɛkshɔn
Epataytis B ɛn Epataytis C
Tα1 de ple imכtant rol fכ trit epataytis B εn epataytis C. fכ krכnik epataytis B vayrus (HBV) infεkshכn, Tα1 kin rεgεl di bכdi in imyun fכnshכn εn εnhans in abiliti fכ klia HBV. Tα1 de aktibכt imyun sεl dεm lεk T sεl dεm εn NK sεl dεm, we de mek dεn ebul fכ no εn pul di liva sεl dεm we gεt HBV bεtε. Tα1 kin rεgεl di saytokεn nεtwכk, we de protεkt di prodyushכn fכ antivayral saytokεn dεm lεk IFN-γ εn inhεbit HBV rεplikshכn.
insay di tritmεnt fכ di epataytis C vayrus (HCV) infεkshכn, Tα1 de sho bak pכsitiv ifekt dεm. I kin ɛp di bɔdi in imyun rispɔns, ɛp fɔ klia HCV, ɛn sho sinajɛstik ifɛkt we dɛn yuz am togɛda wit ɔda antivayrɔs drɔgs, we kin mek di tritmɛnt sakses rɛt bɛtɛ.
Ɔda vayral infɛkshɔn dɛn
apat frכm HBV εn HCV, Tα1 kin ple rol bak pan כda vayral infεkshכn sik dεm. Tα1 kin ɛp fɔ impɔtant di prɔgnosis fɔ di wan dɛn we sik bad bad wan wit COVID-19. bay we dεn de ripεr di damej we di limfosayt imyun ova aktibכshכn kכz εn fכ mek di T-sεl aktibכshכn pasmak, Tα1 kin mek di sikman in simptom dεm εn impruv di rεt fכ liv.
(2) Imyun Rɛgyuleshɔn ɛn Anti-Inflameshɔn
Rigul di Imyun Balans
Tα1 de ple imכtant rol fכ mεnten imyun bεlε na di bכdi. insay stet dεm we nכ gεt imyun, Tα1 kin protεkt di proliferashכn εn difrεns fכ di imyun sεl dεm, we de mek di bכdi in imyun fכnshכn bak. fכ egzampl, insay sכm sik dεm we dεn bכn wit di imyun dεfichεns כ di imyun-sכprεs stet dεm we kכz fכ kεmothεrapi כ rεdyushכn tεrapi, Tα1 kin εp di bכdi fכ rεstablish imyun bεlε bak bay we i de rεgεl di divεlכpmεnt εn fכnshכn fכ di imyun sεl dεm.
insay כtoimyun sik dεm, Tα1 kin sכpres di εksyכs imyun rεspכns dεm εn ridyus di כtoimyun dεmεj bay we i de rεgεl di aktvכti fכ di imyun sεl dεm εn di saytokεn nεtwכk.
Ifɛkt dɛn we de mek pɔsin nɔ gɛt inflammatory
Tα1 posεs anti-inflammatory ifekt dεm. di tεm we di inflammatory rεspכns dεm de, Tα1 kin rεgεl di εksprεshכn fכ inflammatory-related cytokines εn inhεbit fכ inflammatory riakshכn dεm we pasmak. as wi bin dכn tכk, Tα1 kin inhεbit NO prodakshכn insay makrofag dεm, ridyus di εksprεshכn fכ pro-inflammatory saytokεn dεm lεk TNF-α εn IL-1, εn wan tεm i kin promuot di prodyushכn fכ anti-inflammatory saytokεn dεm lεk IL-10.
Figure 3 Nitric oxide rilis afta tritmεnt wit LPS εn difrεnt kכnsantreshכn fכ Tα-1 in RAW 264.7 sεl dεm.
insay wan inflammatory pen mכdel, Tα1 de εliviet mεkanikal allodynia εn haypa aljesia we komplit Freund in adjuvant (CFA) indyuz, εn de ridyus di upregulashכn fכ inflammatory mεdiate dεm lεk IFN-γ, TNF-α, εn bren-dεriv nyurotrofik fכktכ (BDNF) we CFA indyuz. apat frכm dat, Tα1 kin rεgεl di Wnt3a/β-catenin signal path na di spεnal kכd, we de aktibכt di tεm we di inflammatory pen prכsεs de, εn Tα1 kin rivεs in aktibכt stet, we de mek di inflammatory pen.
Klinik Aplikeshɔn dɛn
(1) Tritmɛnt fɔ Vayral Ɛpataytis
Insay di klinik tritmɛnt fɔ vayral ɛpatitis, dɛn dɔn yuz Tα1 bɔku bɔku wan. Fɔ di pasɛnt dɛn we gɛt kronik ɛpatitis B, bɔku klinik stɔdi dɛn dɔn sho se Tα1 we dɛn kam togɛda wit nyukliɔsayd (asid) analɔg ɔ intafɛrɔn tɛrapi de ajɔst ay rɛt fɔ HBV DNA sɛrokɔnvɔshɔn, HBeAg sɛrokɔnvɔshɔn, ɛn ALT nɔmalayzeshɔn kɔmpia to monotɛrapi. Insay sɔm klinik trayal dɛn, di kɔmbaynshɔn fɔ Tα1 ɛn entecavir fɔ di tritmɛnt fɔ kronik ɛpatitis B pasɛnt dɛn bin rilizɔt wan signifyant ay rit fɔ HBV DNA sɛrokɔnvɔshɔn afta 48 wiks tritmɛnt kɔmpia to di grup we dɛn trit wit entecavir nɔmɔ, ɛn di rit fɔ HBeAg sɛrokɔnvɔshɔn sɛf impɔtant.
Insay di tritmɛnt fɔ epataytis C, Tα1 we dɛn kam togɛda wit dairekt-aktin antivayral ɛjɛn (DAA) kin ɛp fɔ mek di antivayral ɛfifikɛshɔn bɛtɛ, mɔ fɔ sɔm epataytis C pasɛnt dɛn we nɔ de tek tritmɛnt, we kin mek di tritmɛnt sakses rɛt bɛtɛ.
(2) Tritmɛnt fɔ di Immunodeficiency Disorders
fכ sכm praymar imyun dεfisiεns sik dεm, lεk kכnεjital taymik haypoplasia, dεn kin yuz Tα1 as pat pan כda tεrapi. pan ɔl we Tα1 nɔ kin ebul fɔ mɛn dɛn sik ya kɔmplit wan, i kin rigul di imyun fכnshכn, εnhans di sikman in imyuniti, ridyus di frεkuεns εn di siriכs infεkshכn, εn impruv di sikman in kwaliti כf layf.
Insay sik dɛn we pɔsin kin gɛt we i nɔ gɛt bɛtɛ imyun, lɛk HIV/AIDS, Tα1 we dɛn jɔyn wit antiretroviral therapy (ART) kin mek di imyun rikonstitushɔn, mek di CD4+ T sɛl dɛn bɔku, i kin mek di imyun wok fayn, ɛn i kin mek di infɛkshɔn we kin apin we pɔsin kin gɛt chans, nɔ bɔku.
(3) Ɔda Aplikeshɔn dɛn
Adjuvant Tɛrapi fɔ Infɛkshɔn Sik dɛn
insay di tritmεnt fכ siriכs infεkshכn lεk sεpsis, dεn kin yuz Tα1 as adjuvant tεrapi. Bɔku tɛm, di wan dɛn we gɛt sɛpsis kin gɛt di imyun disfɔkshɔn. Tα1 de rεgεl di imyun sεl fכnshכn εn saytokεn nεtwכk dεm, we de εp fכ rεstכr imyun bεlε, ridyus inflammatory rεspכns dεm, εn impruv di pasεnt sכvayv rεt.
We dɛn de trit sik dɛn we nɔ de mɛn lɛk TB, Tα1 we dɛn jɔyn wit antituberculosis drɔgs kin ɛp di bɔdi in imyun kliarens kapasiti agens Mycobacterium tuberculosis ɛn i kin mek di tritmɛnt wok fayn.
Sik dɛn we gɛt fɔ du wit inflamɛns
insay di tritmεnt fכ inflammatory-rεlatεd sik dεm lεk rεumatoid atraytis εn inflammatory bowel disease, Tα1 in anti-inflammatory εn immune-modulating ifekt dεm kin gεt pכtεnshal aplikεshכn valyu. pan ɔl we klinik aplikeshɔn nɔ bɔku naw, sɔm bɛsik risach ɛn smɔl klinik trayal dɛn dɔn sho se Tα1 kin ridyus inflammatory rispɔns ɛn impruv di pɔsin in kɔndishɔn bay we i de rigul di imyun sɛl ɛn saytokɛn.
Dɔn
thymosin α1 (Tα1), as pεptida wit imyun-εnhans prכpati dεm, dεn dכn sho bכku εn dip ifekt dεm na di fil fכ imyun rεguleshכn. frכm in mεkanism fכ akshכn, Tα1 de intarakt wit Toll-lεk rεsεpכta dεm fכ aktibכt mכltipכl dכwnstrכm signal path dεm, we de rεgεl di fכnshכn fכ imyun sεl dεm εn saytokεn nεtwכk dεm, εn achy prεsis kכntrכl fכ di bכdi in imyun rεspכns.
we i kam pan di imyun-εnhans ifekt dεm, Tα1 de ple imכtant rol insay antivayral infεkshכn, antitכmכr aktiviti, imyun bεlε rεguleshכn, εn anti-inflammatory ifekt dεm. Insay di antivayral fil, Tα1 de sho brayt aplikeshɔn prɔspɛkt, ilɛksɛf na fɔ kɔmɔn vayral infɛkshɔn lɛk ɛpatitis B ɛn C, ɔ fɔ vayral infɛkshɔn dɛn we de kɔmɔt lɛk COVID-19. di rol we Tα1 de ple pan di sik dεm we de mek di imyun dεfεshכn εn sik dεm we de fכ inflameshn de sho se i kin εp fכ mek di imyun bεlε bak εn ridyus di inflammatory damej. כl, Tα1 de ple wan siknifikant rol as imyun εnhans.
Sos dɛn we dɛn pul
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