By Cocer Peptides 
1 ọnwa gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
Thymosin Alpha-1 (Tα1) bụ peptide nwere nnukwu ọrụ nchịkwa nchịkwa. E bu ụzọ kewapụ ya na anụ ahụ thymus ma mejupụtara amino acid 28, yana N-terminal acetylation. Tα1 na-arụ ọrụ dị mkpa n'ịkwado nguzozi nke mgbochi yana ịzaghachi ọnọdụ ọrịa na ahụ. Dị ka onye na-ebuwanye ihe na-alụso ọrịa ọgụ, ọ na-egosi ike dị ukwuu maka ngwa na ọgwụgwọ na mgbochi nke ọrịa dị iche iche.
Onyonyo 1 Thymosin alpha 1 nwere ọtụtụ ihe omume ndu. IL: Interleukin; IFN: interferon; TLR: ndị na-anabata ego dị ka ego.
N'okpuru ọnọdụ physiological, Tα1 na-ekere òkè na mmepe nkịtị na ịrụ ọrụ nke usoro ahụ ji alụso ọrịa ọgụ, na-enwe mmetụta dị ukwuu na ọdịiche dị iche iche, maturation, na ịgbalite sel ndị na-alụso ọrịa ọgụ. N'okpuru ọnọdụ ọrịa, dị ka nje virus, tumorigenesis, na adịghị ike, Tα1 nwere ike inyere ahụ aka ịlụso ọrịa ọgụ site n'ịhazi nzaghachi mgbochi.
N'ihe banyere ọrịa nje na-efe efe, Tα1 na-ejikarị agwọ ọrịa ịba ọcha n'anya B (HBV) na nje ịba ọcha n'anya C (HCV). Ọ nwere ike ịhazi ọrụ mgbochi ọrịa, nyere ahụ aka ikpochapụ nje virus, ma melite ọnọdụ ndị ọrịa.
Usoro immunomodulatory
(1) Mmekọrịta ya na ndị na-anabata ihe dị ka Toll (TLRs)
Otu ụzọ dị mkpa site na nke Tα1 na-egosipụta mmetụta nchịkwa nchịkwa ya bụ site na iso ndị na-anabata ihe dị ka Toll (TLRs). TLR bụ klaasị nke nnabata nnabata nke na-amata ụkpụrụ molekụla metụtara pathogen-PaMPs na ụkpụrụ molekụla metụtara mebie (DAMPs), si otú ahụ na-eme ka mkpụrụ ndụ na-alụso ọrịa ọgụ na-amalite nzaghachi mgbochi.
Tα1 nwere ike jikọta na ọtụtụ TLR, dị ka TLR3, TLR4, na TLR9. N'elu njikọ ndị a na-anabata ya, Tα1 na-eme ka ụzọ akara ngosi nke ala, gụnyere interferon regulatory factor 3 (IRF3) na nuklia κB (NF-κB) ụzọ akara ụzọ. Na-ewere TLR3 dị ka ihe atụ, mgbe Tα1 jikọtara na TLR3, ọ na-akwalite phosphorylation nke IRF3, nke na-atụgharị gaa na cell cell, na-eme ka nkwupụta nke nje na-ahụ maka nje virus na-achịkwa dị ka ụdị I interferon (IFN-I). IFN-I nwere ọrụ mgbochi mgbochi yana mgbochi mgbochi, na-eme ka ahụ nwee ike iguzogide ọrịa nje.
Maka TLR4, njikọ nke Tα1 n'otu aka ahụ na-eme ka ụzọ akara NF-κB, na-eme ka nkwupụta nke cytokines na-egbuke egbuke dị ka tumor necrosis factor-α (TNF-α) na interleukin-6 (IL-6). Cytokines ndị a na-arụ ọrụ dị mkpa na mmalite nke nzaghachi mgbochi ahụ, na-ewebata mkpụrụ ndụ na-alụso ọrịa ọgụ na saịtị nke ọrịa na ịkwalite ikike nchebe nke ahụ.
Na mgbakwunye, TLR2 na TLR7 jikọtara ya na Tα1. Tα1 nwere ike rụọ ọrụ TLR2 / NF-κB, TLR2 / p38 mitogen-activated protein kinase (p38MAPK), ma ọ bụ TLR7 / myeloid differentiation factor 88 (MyD88) ụzọ akara ụzọ, na-akwalite mmepụta nke cytokines dị iche iche dị ka IL-1 na IL-12 na-emeziwanye mmeghachi omume na-adịghị mma.
(2) Mmetụta nchịkwa na sel ndị na-alụso ọrịa ọgụ
sel T
Tα1 na-emetụta mmepe, ọdịiche, na ịgbalite mkpụrụ ndụ T. Na thymus, Tα1 na-eme ka mmụba na maturation nke thymocytes. Nnyocha egosiwo na mgbe igbochi T cell mediated antibody mmepụta na ụmụ oke na-eji 5-fluorouracil (5-FU), kemịkalụ synthesized Tα1 nwere ike iweghachi ikike mmepụta ihe mgbochi a, ma gosipụta ọrụ ọbụna na obere dose nke 30 μg / kg.
Ntụle cytometry na-agba ọsọ gosiri na nke a nke Tα1 na-eme ka mmụba na maturation nke thymocytes; Otú ọ dị, ọ dịghị emetụta okwu nke Smoothened (Smo), isi ihe na-adịghị mma na-achịkwa ụzọ akara Hedgehog (Hh) na CD4⁻ CD8⁻ thymocytes. Nke a na-egosi na Tα1 nwere ike ịkwalite T cell maturation site na ụzọ mgbaama akọwapụtara nke na-agafe ma ọ bụ na-adabereghị na ụzọ Smo na-achịkwa.
N'ihe gbasara mkpụrụ ndụ T tozuru oke, Tα1 nwere ike ịhazi nguzozi nke mkpụrụ ndụ T cell. N'ime microenvironment tumor, Tα1 nwere ike gbanwee nha nke sel CD8⁺ T na sel T na-achịkwa (Tregs) site n'ịchịkwa ọdịiche nke cell dendritic (DC) na profaịlụ okwu chemokine, si otú ahụ na-eme ka mmeghachi omume mgbochi nke anụ ahụ dịkwuo elu.
Ọgụgụ 2 Thymosin α1 (Tα1) na-egbochi mmebi epithelial na DSS gbakwunyere mgbochi CTLA-4-induced colitis.
sel B
Ọ bụ ezie na ọmụmụ ihe kpọmkwem banyere mmetụta Tα1 na sel B dị ụkọ, nchọpụta dị adị na-egosi na ọ nwere ike imetụta ọrụ cell B n'ụzọ na-apụtaghị ìhè site n'ịchịkwa mkpụrụ ndụ T. Ebe ọ bụ na mkpụrụ ndụ T na-arụ ọrụ enyemaka dị mkpa n'ịgbalite cell B, mgbanwe klaasị mgbochi, na ntozu oke, ụkpụrụ Tα1 nke ọrụ T cell nwere ike imetụta mmepụta mkpụrụ ndụ B cell n'ụzọ na-apụtaghị ìhè, si otú ahụ na-eme ka mmeghachi omume mgbochi anụ ahụ dịkwuo mma.
Macrophages
Tα1 nwekwara mmetụta nchịkwa dị mkpa na ọrụ macrophage. N'iji nyocha nke MTT, a chọpụtara na Tα1 na-egosipụta mmetụta cytotoxic na RAW 264.7 macrophages, na ọkara nke ihe mgbochi mgbochi (IC50) nke 368.105 μg / ml. Ka ntinye uche Tα1 na-abawanye, mmetụta cytotoxic na mkpụrụ ndụ RAW 264.7 na-abawanye, na-eduga n'ibelata njupụta cell.
Tα1 na-egosipụtakwa mmetụta mgbochi mkpali, nke a na-enyocha site na nyochaa mmepụta nitric oxide (NO) na sel RAW 264.7. Nsonaazụ gosiri na n'ime ntinye uche nke 7.813-31.25 μg / ml, NO mmepụta na Tα1-agwọ ọrịa na-ebelata n'ụzọ na-adabere na dose ma e jiri ya tụnyere otu njikwa, na-egosi na Tα1 nwere ike ịmepụta mmetụta mgbochi mkpali ya site na igbochi NO mmepụta na macrophages, si otú ahụ na-achịkwa nzaghachi mgbochi.
Mkpụrụ ndụ egbu egbu (sel NK)
Tα1 na-akwalite mmụba cell NK na ịgbalite, na-akwalite ọrụ cytotoxic ha. Mkpụrụ ndụ NK bụ akụkụ dị mkpa nke usoro ahụ ji alụso ọrịa ọgụ, nke nwere ike igbu mkpụrụ ndụ nje butere na mkpụrụ ndụ tumor na-abụghị kpọmkwem. Tα1 na-akwalite ikike ha ịmata na igbu sel ndị e lekwasịrị anya site n'ịkwalite okwu nke ndị na-anabata ọrụ n'elu sel NK, si otú a na-ekere òkè dị mkpa na ọrịa nje na mgbochi antitumor.
(3) Iwu nke netwọk cytokine
Tα1 na-arụ ọrụ immunoregulatory ya site na ịhazi netwọk cytokine. Cytokines bụ otu klas nke obere protein molekụla zoro ezo site na mkpụrụ ndụ na-alụso ọrịa ọgụ na ụfọdụ sel ndị na-adịghị egbochi ọrịa, nke na-ebufe ozi n'etiti sel ma na-achịkwa ọrụ nke mkpụrụ ndụ na-alụso ọrịa ọgụ yana ike na ụdị nzaghachi mgbochi.
Tα1 nwere ike ịkwalite mmepụta nke cytokines dị iche iche, dị ka interleukin-2 (IL-2), interleukin-3 (IL-3), na interferon-γ (IFN-γ). IL-2 bụ ihe dị mkpa na-eto eto T cell nke na-akwalite mmụba T cell na ịgbalite, na-eme ka ọrụ nke mkpụrụ ndụ NK na cytotoxic T lymphocytes (CTLs), si otú a na-eme ka ikike nchebe nke anụ ahụ dịkwuo mma. IL-3 na-akwalite mmụba na ọdịiche dị iche iche nke mkpụrụ ndụ hematopoietic dị iche iche na sel progenitor, na-enyere aka ịnọgide na-arụ ọrụ cellular na ọrụ nke usoro ahụ ji alụso ọrịa ọgụ. IFN-γ nwere ọtụtụ ọrụ, gụnyere antiviral, antitumor, na usoro nchịkwa nchịkwa, na-eme ka ikike phagocytic na cytotoxic nke macrophages dịkwuo elu, na-akwalite ọdịiche nke mkpụrụ ndụ Th1, na ịhazi nzaghachi mgbochi na ntụziaka mgbochi cellular.
Na mgbakwunye, Tα1 nwere ike ịhazi nguzozi n'etiti cytokines pro-inflammatory na mgbochi mkpali. N'oge nzaghachi mkpali, Tα1 nwere ike ịkwụsị mmepụta nke cytokines pro-inflammatory dị ka TNF-α na IL-1, ebe ọ na-akwalite mmepụta nke cytokines mgbochi mkpali dị ka interleukin-10 (IL-10), si otú ahụ belata mmebi nke nzaghachi mkpali na-eme na ahụ na ịnọgide na-enwe nguzozi nke mgbochi.
Mmetụta na-eme ka mgbochi ọrịa
(1) Ọrịa na-efe efe
Ịba ọcha n'anya B na ịba ọcha n'anya C
Tα1 na-ekere òkè dị ukwuu n'ịgwọ ọrịa ịba ọcha n'anya B na ịba ọcha n'anya C. Maka ọrịa ịba ọcha n'anya B (HBV) na-adịghị ala ala, Tα1 nwere ike ịhazi ọrụ nchebe ahụ ma kwalite ikike ya ikpochapụ HBV. Tα1 na-arụ ọrụ sel ndị na-alụso ọrịa ọgụ dị ka mkpụrụ ndụ T na sel NK, na-enyere ha aka ịmata ma kpochapụ mkpụrụ ndụ imeju HBV. Tα1 nwere ike ịhazi netwọk cytokine, na-akwalite mmepụta nke cytokines antiviral dị ka IFN-γ na igbochi HBV mmegharị.
Na ọgwụgwọ ọrịa ịba ọcha n'anya C (HCV), Tα1 na-egosipụtakwa mmetụta dị mma. Ọ nwere ike ịkwalite nzaghachi mgbochi ahụ nke anụ ahụ, inye aka na ikpochapụ HCV, ma gosipụta mmetụta synergistic mgbe ejiri ya na ọgwụ nje ndị ọzọ, si otú ahụ na-eme ka ọ̀tụ̀tụ̀ ịga nke ọma ọgwụgwọ.
Ọrịa nje ndị ọzọ
Na mgbakwunye na HBV na HCV, Tα1 nwekwara ike rụọ ọrụ na ọrịa ndị ọzọ na-efe efe. Tα1 nwere ike inye aka melite prognosis nke ndị ọrịa nwere nnukwu ọrịa nwere COVID-19. Site n'ịrụzi mmebi nke ihe mgbochi lymphocyte na-akpata na igbochi oke ọrụ T-cell, Tα1 nwere ike ibelata mgbaàmà onye ọrịa ma melite ọnụego ndụ.
(2) Usoro mgbochi ọrịa na mgbochi mbufụt
Na-achịkwa Balance Immune
Tα1 na-arụ ọrụ dị mkpa n'ịkwado nguzozi nke mgbochi na ahụ. Na steeti ndị na-adịghị ahụkebe, Tα1 nwere ike ịkwalite mmụba na ọdịiche nke mkpụrụ ndụ mgbochi, na-eweghachi ọrụ mgbochi ahụ. Dịka ọmụmaatụ, n'ụfọdụ ọrịa na-adịghị ahụkebe ọrịa na-alụso ọrịa ọgụ ma ọ bụ steeti ndị na-egbochi mgbochi ọrịa nke chemotherapy ma ọ bụ ọgwụgwọ radieshon kpatara, Tα1 nwere ike inyere ahụ aka ịmaliteghachi nguzozi nke mgbochi site na ịhazi mmepe na ọrụ nke mkpụrụ ndụ na-alụso ọrịa ọgụ.
N'ime ọrịa autoimmune, Tα1 nwere ike igbochi nzaghachi mgbochi oke ma belata mmebi nke autoimmune site na ịhazi ọrụ nke mkpụrụ ndụ na-alụso ọrịa ọgụ na netwọk cytokine.
Mmetụta mgbochi mkpali
Tα1 nwere mmetụta mgbochi mkpali. N'oge nzaghachi mkpali, Tα1 nwere ike ịhazi okwu nke cytokines metụtara mbufụt ma gbochie mmeghachi omume mkpali dị ukwuu. Dị ka e kwuru na mbụ, Tα1 nwere ike igbochi NO mmepụta na macrophages, belata okwu nke pro-inflammatory cytokines dị ka TNF-a na IL-1, na n'out oge na-akwalite mmepụta nke anti-inflammatory cytokines dị ka IL-10.
Ọgụgụ 3 Nitric oxide tọhapụrụ mgbe ọgwụgwọ ya na LPS na ntinye dị iche iche nke Tα-1 na sel RAW 264.7.
N'ụdị ihe mgbu na-egbuke egbuke, Tα1 na-eme ka allodynia na-arụ ọrụ na-arụ ọrụ na hyperalgesia na-akpata site na Freund's adjuvant (CFA) zuru ezu, ma na-ebelata nhazi nke ndị mgbasa ozi na-egbuke egbuke dị ka IFN-γ, TNF-α, na ụbụrụ neurotrophic factor (BDNF) nke CFA kpatara. Tụkwasị na nke ahụ, Tα1 nwere ike ịhazi ụzọ akara Wnt3a / β-catenin na ọkpụkpụ azụ, nke a na-arụ ọrụ n'oge usoro ihe mgbu na-egbuke egbuke, na Tα1 nwere ike gbanwee ọnọdụ ya na-arụ ọrụ, si otú ahụ na-ebelata mgbu mgbu.
Ngwa ụlọ ọgwụ
(1) Ọgwụgwọ ịba ọcha n'anya
N'ịgwọ ọrịa ịba ọcha n'anya nke nje, Tα1 etinyere ya n'ọtụtụ ebe. Maka ndị ọrịa nwere ịba ọcha n'anya B na-adịghị ala ala, ọtụtụ nchọpụta ụlọ ọgwụ egosila na Tα1 jikọtara ya na nucleoside (acid) analogues ma ọ bụ ọgwụgwọ interferon na-enweta ọnụ ọgụgụ dị elu nke HBV DNA seroconversion, HBeAg seroconversion, na ALT normalization tụnyere monotherapy. N'ime ụfọdụ ule ụlọ ọgwụ, nchikota nke Tα1 na entecavir maka ọgwụgwọ ndị ọrịa ịba ọcha n'anya B na-eme ka ọnụọgụ HBV DNA seroconversion dị elu karịa mgbe izu 48 gasịrị ma e jiri ya tụnyere otu a na-emeso ya na entecavir naanị, na ọnụego nke HBeAg seroconversion dịkwa mma.
N'ọgwụgwọ ịba ọcha n'anya C, Tα1 jikọtara ya na ndị na-eme ihe na-eme ihe na-eme ihe ozugbo (DAAs) nwere ike ịkwalite nrụpụta antiviral, karịsịa maka ụfọdụ ndị ọrịa ịba ọcha n'anya C na-eguzogide ọgwụgwọ, nwere ike imeziwanye ọganihu ọgwụgwọ.
(2) Ọgwụgwọ nke ọrịa mgbochi ọrịa
Maka ụfọdụ ọrịa ọrịa na-adịghị ahụkebe nke mbụ, dị ka congenital thymic hypoplasia, Tα1 nwere ike iji dịka akụkụ nke ọgwụgwọ ọzọ. Ọ bụ ezie na Tα1 enweghị ike ịgwọ ọrịa ndị a kpam kpam, ọ nwere ike ịhazi ọrụ mgbochi ọrịa, welie ihe mgbochi ndị ọrịa, belata ugboro na ogo ọrịa, ma melite ogo ndụ ndị ọrịa.
N'ime ọrịa ụkọ ihe mgbochi enwetara, dị ka HIV / AIDS, Tα1 jikọtara ya na ọgwụgwọ antiretroviral (ART) nwere ike ime ka usoro ahụ ji alụso ọrịa ọgụ dịkwuo elu, mụbaa ọnụ ọgụgụ sel CD4⁺ T, melite ọrụ ahụ ji alụso ọrịa ọgụ, ma belata ohere nke ọrịa na-efe efe.
(3) Ngwa ndị ọzọ
Usoro ọgwụgwọ Adjuvant maka ọrịa na-efe efe
Na ọgwụgwọ nke ọrịa siri ike dị ka sepsis, Tα1 nwere ike iji dị ka ọgwụgwọ adjuvant. Ndị na-arịa ọrịa Sepsis na-enwekarị ọrụ mgbochi ọrịa. Tα1 na-achịkwa ọrụ cell na-alụso ọrịa ọgụ na netwọk cytokine, na-enyere aka iweghachi nguzozi mgbochi, belata nzaghachi mkpali, ma melite ọnụego ndụ onye ọrịa.
N'ịgwọ ọrịa na-efe efe na-adịghị ala ala dịka ụkwara nta, Tα1 jikọtara ya na ọgwụ mgbochi ụkwara nta nwere ike ịkwalite ikike nkwụsị nke anụ ahụ megide ụkwara nta Mycobacterium ma melite nrụpụta ọgwụgwọ.
Ọrịa ndị metụtara mbufụt
Na ọgwụgwọ nke ọrịa ndị metụtara mkpali dị ka rheumatoid ogbu na nkwonkwo na ọrịa obi na-egbuke egbuke, Tα1 na-eme ka ọ bụrụ ihe na-eme ka ọ bụrụ ihe na-eme ka ọ bụrụ ihe na-eme ka ọ bụrụ ihe na-eme ka ọ dị mma. Ọ bụ ezie na ngwa ụlọ ọgwụ dị ugbu a dị oke, ụfọdụ nchọpụta bụ isi na obere nyocha ụlọ ọgwụ egosila na Tα1 nwere ike belata nzaghachi mkpali ma melite ọnọdụ onye ọrịa site na ịhazi sel ndị na-alụso ọrịa ọgụ na cytokines.
Mmechi
Thymosin α1 (Tα1), dị ka peptide nwere ihe ndị na-eme ka ndị mmadụ na-alụso ọrịa ọgụ, egosila mmetụta dị ukwuu na nke dị ukwuu n'ọhịa nke nchịkwa nchịkwa. Site na usoro ọrụ ya, Tα1 na ndị na-anabata Toll na-emekọrịta ihe iji mee ka ụzọ mgbaàmà dị iche iche dị n'okpuru, si otú ahụ na-achịkwa ọrụ nke mkpụrụ ndụ na-alụso ọrịa ọgụ na netwọk cytokine, na ịnweta njikwa ziri ezi nke nzaghachi mgbochi ahụ.
N'ihe gbasara mmetụta na-eme ka ahụ ike na-alụso ọrịa ọgụ, Tα1 na-ekere òkè dị ịrịba ama na ọrịa nje virus, ọrụ antitumor, nhazi nguzozi ihe mgbochi, na mmetụta mgbochi mkpali. Na mpaghara mgbochi, Tα1 na-egosi atụmanya ngwa sara mbara, ma ọ bụ maka ọrịa nje na-efe efe dị ka ịba ọcha n'anya B na C, ma ọ bụ maka ọrịa nje na-apụta dị ka COVID-19. Ọrụ nke Tα1 na ọrịa na-adịghị alụso ọrịa ọgụ na ọrịa ndị metụtara mbufụt na-egosi na ọ nwere ike inye aka weghachite nguzozi nke mgbochi ma belata mmebi mkpali. N'ozuzu, Tα1 na-arụ ọrụ dị mkpa dị ka onye na-ebuli ọrịa ahụ.
Isi mmalite
[1] Tao N, Xu X, Ying Y, et al. Thymosin α1 na Ọrụ Ya na Ọrịa Na-efe efe Na-efe efe: The Mechanism and Clinical Application[J]. Molecules, 2023,28 (8).DOI:10.3390/molecules28083539.
[2] Bala I, Gupta N, Prabhakar P K. Mmetụta nke Thymosin Alpha-1 na Macrophages: Ọmụmụ Cytological na Anti-Inflammatory [J]. Akwụkwọ akụkọ nke Advanced Zoology, 2023. https://api.semanticscholar.org/CorpusID:264985939
[3] Binder U, Skerra A. PASylated Thymosin α1: Peptide Immunostimulatory na-eme ogologo oge maka ngwa na Oncology na Virology[J]. Akwụkwọ akụkọ International nke Science Molecular, 2020,22(1).DOI:10.3390/ijms22010124.
[4] Renga G, Bellet MM, Pariano M, et al. Thymosin α1 na-echebe site na CTLA-4 intestinal immunopathology[J]. Ndụ Science Alliance, 2020,3 (10).DOI:10.26508/lsa.202000662.
[5] Dominari A, Hathaway ID, Pandav K, et al. Thymosin alpha 1: Nlebanya zuru oke nke akwụkwọ[J]. Ụwa J Virol, 2020,9 (5):67-78.DOI:10.5501/wjv.v9.i5.67.
[6] Li CL, Zhang T, Saibara T, et al. Thymosin alpha1 na-eme ka mweghachi nke nzaghachi mgbochi mgbochi mmadụ nke T cell na-eme ka ọ dị n'ime ndị agha na-egbochi ọrịa [J]. Immunopharmacology mba ụwa, 2002,2 (1): 39-46.DOI: 10.1016 / s1567-5769 (01) 00136-9.
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