Na Cocer Peptides 
1 mahina aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a i ʻole maʻi. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
Nānā nui
ʻO Thymosin Alpha-1 (Tα1) he peptide me nā hana hoʻoponopono koʻikoʻi. Ua hoʻokaʻawale mua ʻia mai ka ʻiʻo thymus a loaʻa iā 28 amino acids, me ka N-terminal acetylation. He kuleana koʻikoʻi ko Tα1 i ka mālama ʻana i ka pale pale a me ka pane ʻana i nā kūlana maʻi i loko o ke kino. Ma ke ʻano he mea hoʻoikaika kino, hōʻike ia i ka mana nui no ka hoʻohana ʻana i ka mālama ʻana a me ka pale ʻana i nā maʻi like ʻole.
Kiʻi 1 ʻO Thymosin alpha 1 ka laulā o nā hana olaola. IL: Interleukin; IFN: Interferon; TLR: ʻO nā mea loaʻa like ʻole.
Ma lalo o nā kūlana physiological, komo ʻo Tα1 i ka hoʻomohala maʻamau a me ka mālama ʻana i ka hana o ka ʻōnaehana pale, e hana ana i ka mana koʻikoʻi i ka ʻokoʻa, maturation, a me ka hoʻoulu ʻana o nā cell immune. Ma lalo o nā kūlana pathological, e like me nā maʻi viral, tumorigenesis, a me nā hemahema immune, hiki iā Tα1 ke kōkua i ke kino e hakakā i nā maʻi ma o ka hoʻoponopono ʻana i nā pane kūlohelohe.
Ma ke kahua o nā maʻi lele, hoʻohana mau ʻia ʻo Tα1 no ka mālama ʻana i nā maʻi maʻi hepa B (HBV) a me nā maʻi hepa C (HCV). Hiki iā ia ke hoʻoponopono i ka hana immune, kōkua i ke kino i ka hoʻomaʻemaʻe ʻana i nā maʻi maʻi, a hoʻomaikaʻi i nā kūlana o nā maʻi.
Nā Mechanisms Immunomodulatory
(1) Ka launa pū ʻana me nā mea loaʻa e like me Toll (TLRs)
ʻO kahi ala koʻikoʻi e hoʻokō ai ʻo Tα1 i kāna mau hopena hoʻoponopono kūlohelohe ma o ka launa pū ʻana me Toll-like receptors (TLRs). ʻO nā TLR kahi papa o nā mea hoʻokae ʻike kumu e ʻike ai i nā kumu molekala pili pathogen (PAMPs) a me nā ʻano molekala pili i ka pōʻino (DAMP), a laila e hoʻāla ai i nā cell immune a hoʻomaka i nā pane kūlohelohe.
Hiki iā Tα1 ke hoʻopaʻa i nā TLR he nui, e like me TLR3, TLR4, a me TLR9. Ma ka hoʻopaʻa ʻana i kēia mau mea loaʻa, hoʻāla ʻo Tα1 i nā ala hōʻailona o lalo, me ka interferon regulatory factor 3 (IRF3) a me ka nuclear factor κB (NF-κB) nā ala hōʻailona. ʻO ka lawe ʻana iā TLR3 ma ke ʻano he laʻana, ma hope o ka hoʻopaʻa ʻana o Tα1 iā TLR3, hoʻolaha ia i ka phosphorylation o IRF3, a laila unuhi ʻia i ka nucleus cell, e hoʻoulu ai i ka hōʻike ʻana o nā genes antiviral a me ka immune-regulatory genes e like me ke ʻano I interferon (IFN-I). Loaʻa i ka IFN-I nā hana antiviral a me ka immune-regulatory, e hoʻonui i ke kū'ē o ke kino i nā maʻi maʻi.
No TLR4, ho'āla like ka paʻa ʻana o Tα1 i ke ala hōʻailona NF-κB, e hoʻonui i ka hōʻike o nā cytokine inflammatory e like me ka tumor necrosis factor-α (TNF-α) a me interleukin-6 (IL-6). He kuleana koʻikoʻi kēia mau cytokines i ka hoʻomaka ʻana o ka pane ʻana o ka pale ʻana, ke kiʻi ʻana i nā cell immune i ke kahua o ka maʻi a me ka hoʻonui ʻana i ka hiki ke pale aku i ke kino.
Eia hou, pili pū ʻia ʻo TLR2 a me TLR7 me Tα1. Hiki iā Tα1 ke hoʻoikaika i nā ala hōʻailona TLR2/NF-κB, TLR2/p38 mitogen-activated protein kinase (p38MAPK), a i ʻole TLR7/myeloid differentiation factor 88 (MyD88), e hoʻoikaika ana i ka hana ʻana o nā cytokines like ʻole e like me IL-1 a me IL-12, no laila e hoʻomaikaʻi hou ai i ka immune innate.
(2) Nā hopena hoʻoponopono i nā cell immune
nā pūʻali T
Hoʻopili ʻo Tα1 i ka hoʻomohala ʻana, ka ʻokoʻa, a me ka hoʻōla ʻana o nā pūnae T. I loko o ka thymus, Tα1 e hoʻonui i ka hoʻopiha a me ka oʻo ʻana o nā thymocytes. Ua hōʻike ʻia nā haʻawina ma hope o ka pale ʻana i ka hana antibody T cell-mediated antibody i nā ʻiole me ka hoʻohana ʻana i ka 5-fluorouracil (5-FU), hiki i ka Tα1 i hoʻohuihui kemika ke hoʻihoʻi i kēia mana hana antibody, a hōʻike i ka hana ma kahi haʻahaʻa o 30 μg/kg.
Ua hōʻike ʻia ka loiloi cytometry kahe e hoʻolalelale kēia ʻano o Tα1 i ka hoʻopiha hou ʻana a me ka oʻo ʻana o nā thymocytes; akā naʻe, ʻaʻole ia e pili i ka hōʻike ʻana o Smoothened (Smo), kahi mea hoʻoponopono ʻino ʻole o ke ala hōʻailona Hedgehog (Hh) ma CD4⁻CD8⁻ thymocytes. Hōʻike kēia i hiki iā Tα1 ke hoʻoikaika i ka hoʻomaʻamaʻa ʻana o ka cell T ma o nā ala hōʻailona kikoʻī e kāʻalo a kūʻokoʻa paha i nā ala Smo-regulated.
Ma nā ʻōlelo o nā pūnaewele T makua, hiki iā Tα1 ke hoʻoponopono i ke koena o nā subset cell T. I loko o ka microenvironment tumor, hiki iā Tα1 ke hoʻololi i ka lakio o CD8⁺ T cell a me regulatory T cell (Tregs) ma o ka hoʻoponopono ʻana i ka ʻokoʻa dendritic cell (DC) a me nā kiʻi hōʻike chemokine, ma laila e hoʻonui ai i ka pane ʻana o ke kino antitumor.
Kiʻi 2 Thymosin α1 (Tα1) pale i ka epithelial pōʻino ma DSS me anti-CTLA-4-induced colitis.
nā pūnaewele B
ʻOiai ʻaʻole liʻiliʻi nā haʻawina pololei e pili ana i nā hopena o Tα1 ma nā pūnaewele B, ʻike ʻia ka noiʻi ʻana e hiki ke hoʻololi pono ʻole i ka hana cell B ma o ka hoʻoponopono ʻana i nā cell T. No ka mea, he koʻikoʻi ko nā cell T i ka hoʻoulu ʻana o ka cell B, ka hoʻololi ʻana o ka papa antibody, a me ka maturation affinity, hiki i ka hoʻoponopono ʻana o Tα1 i ka hana cell T hiki ke hoʻohuli pololei i ka hana antibody cell B, a laila e hoʻonui ai i ka pane kūlohelohe humoral o ke kino.
Macrophages
He hopena koʻikoʻi ko Tα1 i ka hana macrophage. Ke hoʻohana nei i ka MTT assay, ua ʻike ʻia ua hōʻike ʻo Tα1 i nā hopena cytotoxic ma RAW 264.7 macrophages, me ka hapalua-maximal inhibitory concentration (IC50) o 368.105 μg/ml. Ke piʻi aʻe ka manaʻo o Tα1, piʻi ka hopena cytotoxic ma nā cell RAW 264.7, e alakaʻi ana i ka emi ʻana o ka nui o nā cell.
Hōʻike pū ʻo Tα1 i nā hopena anti-inflammatory, i loiloi ʻia e ka nānā ʻana i ka hana nitric oxide (NO) i loko o nā cell RAW 264.7. Ua hōʻike nā hualoaʻa i loko o ka pae hoʻonaʻauao o 7.813-31.25 μg / ml, NO ka hana i loko o ka hui Tα1-treated i ho'ēmiʻia ma keʻano o ka hopena i hoʻohālikelikeʻia me ka pūʻulu mana, e hōʻike ana e hiki i ka Tα1 ke hoʻohana i kona mau hopena anti-inflammatory ma ke kāohiʻana i ka hana NO i nā macrophages, a laila e hoʻoponopono i nā pane immune.
Nā pūnana pepehi maoli (NK cell)
Hoʻoikaika ka Tα1 i ka hoʻonui a me ka hoʻoulu ʻana o ka cell NK, e hoʻonui ana i kā lākou hana cytotoxic. He mea koʻikoʻi nā pūnaewele NK o ka ʻōnaehana pale kino maoli, hiki ke pepehi i nā maʻi maʻi a me nā pūnana tumora. Hoʻonui ʻo Tα1 i ko lākou hiki ke hoʻomaopopo a pepehi i nā cell target ma ka hoʻonui ʻana i ka hōʻike ʻana o nā mea loaʻa hoʻāla ma ka ʻili o nā pūnaewele NK, a laila e pāʻani ana i kahi kuleana koʻikoʻi i ka maʻi antiviral a me ka pale antitumor.
(3) Hoʻoponopono i ka pūnaewele cytokine
Hoʻohana ʻo Tα1 i kāna mau hana immunoregulatory ma o ka hoʻoponopono ʻana i ka pūnaewele cytokine. ʻO Cytokines kahi papa o nā protein molecular liʻiliʻi i huna ʻia e nā cell immune a me kekahi mau cell non-immune, e hoʻouna i ka ʻike ma waena o nā cell a hoʻoponopono i ka hana o nā cell immune a me ka ikaika a me ke ʻano o nā pane kūlohelohe.
Hiki iā Tα1 ke hoʻoikaika i ka hana ʻana o nā cytokines like ʻole, e like me interleukin-2 (IL-2), interleukin-3 (IL-3), a me interferon-γ (IFN-γ). ʻO IL-2 he mea nui ka ulu ʻana o ka cell T e hoʻoikaika ana i ka hoʻonui a me ka hoʻoulu ʻana o ka cell T, hoʻonui i ka hana o nā pūnaewele NK a me nā cytotoxic T lymphocytes (CTLs), ma laila e hoʻomaikaʻi ai i ka hiki ke pale i ke kino. Hoʻolaha ʻo IL-3 i ka hoʻonui a me ka hoʻokaʻawale ʻana o nā ʻano ʻāpana hematopoietic stem cell a me nā cell progenitor, e kōkua ana i ka mālama ʻana i ka haku mele a me ka hana o ka ʻōnaehana pale. Loaʻa i ka IFN-γ nā hana he nui, me ka antiviral, antitumor, a me nā hopena regulatory immune, hoʻonui i nā mana phagocytic a me cytotoxic o macrophages, e hoʻoikaika ana i ka ʻokoʻa o nā cell Th1, a me ka hoʻoponopono ʻana i ka pane ʻana o ka immune i kahi alakaʻi immune cellular.
Eia hou, hiki iā Tα1 ke hoʻoponopono i ke kaulike ma waena o nā cytokine pro-inflammatory a me anti-inflammatory. I ka wā o nā pane inflammatory, hiki iā Tα1 ke hoʻopau i ka overproduction o nā cytokine pro-inflammatory e like me TNF-α a me IL-1, ʻoiai e hāpai ana i ka hana ʻana o nā cytokine anti-inflammatory e like me interleukin-10 (IL-10), a laila e hōʻemi i ka pōʻino i hana ʻia e nā pane inflammatory i ke kino a mālama i ka pale pale pale.
Nā hopena hoʻoikaika kino
(1) ʻO ka maʻi antiviral
Hepatitis B a me ka Hepatitis C
He kuleana koʻikoʻi ko Tα1 i ka mālama ʻana i ka maʻi hepa B a me ka maʻi hepa C. No ka maʻi maʻi hepa B (HBV) mau loa, hiki iā Tα1 ke hoʻoponopono i ka hana pale o ke kino a hoʻonui i kona hiki ke hoʻomaʻemaʻe i ka HBV. Hoʻoulu ʻo Tα1 i nā cell immune e like me nā cell T a me NK cell, e hiki ai iā lākou ke ʻike maikaʻi a hoʻopau i nā pūnaewele ate i hoʻopili ʻia e ka HBV. Hiki iā Tα1 ke hoʻoponopono i ka pūnaewele cytokine, e hoʻoikaika ana i ka hanaʻana o nā cytokines antiviral e like me IFN-γ a ke kāohi nei i ka HBV replication.
I ka mālama ʻana i ka maʻi hepatitis C (HCV), hōʻike pū ʻo Tα1 i nā hopena maikaʻi. Hiki iā ia ke hoʻoikaika i ka pane ʻana o ke kino, kōkua i ka hoʻomaʻemaʻe ʻana i ka HCV, a hōʻike i nā hopena synergistic ke hoʻohana pū ʻia me nā lāʻau antiviral ʻē aʻe, a laila e hoʻomaikaʻi ai i nā helu kūleʻa o ka mālama ʻana.
ʻO nā maʻi viral ʻē aʻe
Ma waho aʻe o HBV a me HCV, hiki i ka Tα1 ke pāʻani i nā maʻi maʻi ʻē aʻe. Hiki ke kōkua ʻo Tα1 i ka hoʻomaikaʻi ʻana i ka wānana o nā maʻi maʻi nui me COVID-19. Ma ka hoʻoponopono ʻana i nā pōʻino i hana ʻia e ka lymphocyte immune overactivation a me ka pale ʻana i ka hoʻoulu ʻana o T-cell nui, hiki iā Tα1 ke hoʻēmi i nā hōʻailona maʻi a hoʻomaikaʻi i nā helu ola.
(2) Hoʻoponopono i ka Immune a me Anti-Inflammation
Hoʻoponopono ʻana i ke koena pale
He kuleana koʻikoʻi ko Tα1 i ka mālama ʻana i ka pale pale pale i ke kino. Ma nā moku'āina palekana, hiki iā Tα1 ke hoʻoikaika i ka hoʻonui a me ka hoʻokaʻawaleʻana o nā pūnaewele immune, e hoʻihoʻi i ka hana palekana o ke kino. No ka laʻana, i kekahi mau maʻi ʻole o ka immune congenital a i ʻole nā moku'āina i hoʻopaʻa ʻia i ka immune ma muli o ka chemotherapy a i ʻole radiation therapy, hiki iā Tα1 ke kōkua i ke kino e hoʻokumu hou i ka pale pale ma o ka hoʻoponopono ʻana i ka hoʻomohala ʻana a me ka hana o nā cell immune.
I loko o nā maʻi autoimmune, hiki i ka Tα1 ke hoʻopaʻa i nā pane kūlohelohe nui a hōʻemi i ka pōʻino autoimmune ma o ka hoʻoponopono ʻana i ka hana o nā cell immune a me ka pūnaewele cytokine.
Nā hopena anti-inflammatory
Loaʻa iā Tα1 nā hopena anti-inflammatory. I ka wā o nā pane inflammatory, hiki iā Tα1 ke hoʻoponopono i ka hōʻike ʻana o nā cytokines pili i ka mumū a keʻakeʻa i nā hopena inflammatory nui. E like me ka mea i ʻōlelo ʻia ma mua, hiki i ka Tα1 ke kāohi i ka hana NO i loko o nā macrophages, e hoʻemi i ka hōʻike ʻana o nā cytokine pro-inflammatory e like me TNF-α a me IL-1, a i ka manawa like e hoʻoikaika i ka hana o nā cytokine anti-inflammatory e like me IL-10.
Kiʻi 3 Hoʻokuʻu ʻia ka Nitric oxide ma hope o ka mālama ʻana me LPS a me nā ʻano ʻokoʻa like ʻole o Tα-1 ma nā pūnaewele RAW 264.7.
I loko o kahi hoʻohālike eha ʻeha, hoʻopau ʻo Tα1 i ka allodynia mechanical a me ka hyperalgesia i hoʻokomo ʻia e ka hoʻokō ʻana o Freund's adjuvant (CFA), a hoʻemi i ka upregulation o nā mediators inflammatory e like me IFN-γ, TNF-α, a me ka brain-derived neurotrophic factor (BDNF) i hoʻokomo ʻia e CFA. Eia hou, hiki iā Tα1 ke hoʻoponopono i ke ala hōʻailona Wnt3a/β-catenin i loko o ke kuamoʻo, i hoʻāla ʻia i ka wā o ke kaʻina hana ʻeha, a hiki iā Tα1 ke hoʻohuli i kona kūlana i hoʻāla ʻia, a laila e hoʻēmi ana i ka ʻeha ʻeha.
Nā noi lāʻau lapaʻau
(1) Lapaʻau ʻana i ka Hepatitis Viral
I loko o ka lāʻau lapaʻau o ka maʻi hepatitis viral, ua hoʻohana nui ʻia ʻo Tα1. No nā poʻe maʻi me ka maʻi hepatitis B mau, ua hōʻike ʻia nā haʻawina he nui i hui pū ʻia ʻo Tα1 me ka nucleoside (acid) analogues a i ʻole interferon therapy e hoʻokō i nā helu kiʻekiʻe o HBV DNA seroconversion, HBeAg seroconversion, a me ALT normalization i hoʻohālikelike ʻia me ka monotherapy. I kekahi mau hoʻokolohua lapaʻau, ʻo ka hui pū ʻana o Tα1 a me ka entecavir no ka mālama ʻana i nā maʻi hepa B maʻi i hopena i ka nui o ka HBV DNA seroconversion ma hope o 48 mau pule o ka mālama ʻana i hoʻohālikelike ʻia me ka hui i mālama ʻia me ka entecavir wale nō, a ua hoʻomaikaʻi pū ka nui o ka HBeAg seroconversion.
I ka mālama ʻana i ka maʻi hepa C, hiki i ka Tα1 i hui pū ʻia me nā lāʻau antiviral direct-acting (DAAs) hiki ke hoʻoikaika i ka pono antiviral, ʻoi aku hoʻi no kekahi mau maʻi maʻi hepatitis C kūʻokoʻa, hiki ke hoʻomaikaʻi i nā helu kūleʻa o ka mālama ʻana.
(2) Hoʻomaʻamaʻa i nā maʻi immunodeficiency
No kekahi mau maʻi immunodeficiency mua, e like me ka congenital thymic hypoplasia, hiki ke hoʻohana ʻia ʻo Tα1 ma ke ʻano o ka lāʻau lapaʻau ʻē aʻe. ʻOiai ʻaʻole hiki i ka Tα1 ke hoʻōla loa i kēia mau maʻi, hiki iā ia ke hoʻoponopono i ka hana immune, hoʻonui i ka pale ʻana o nā maʻi, hoʻemi i ka pinepine a me ka paʻakikī o nā maʻi, a hoʻomaikaʻi i ka maikaʻi o ke ola o nā maʻi.
I loko o ka loaʻa ʻana o nā maʻi kīnā ʻole, e like me HIV/AIDS, ʻo Tα1 i hui pū ʻia me ka antiretroviral therapy (ART) hiki ke hoʻoikaika i ka hoʻoponopono hou ʻana, hoʻonui i ka helu CD4⁺ T cell, hoʻomaikaʻi i ka hana immune, a hoʻemi i ka nui o nā maʻi opportunistic.
(3) Nā noi ʻē aʻe
Lapaau Adjuvant no na ma'i lele
I ka mālama ʻana i nā maʻi koʻikoʻi e like me ka sepsis, hiki ke hoʻohana ʻia ʻo Tα1 ma ke ʻano he adjuvant therapy. Loaʻa pinepine ka poʻe maʻi Sepsis i ka pale kino. Hoʻoponopono ʻo Tα1 i ka hana cell immune a me nā pūnaewele cytokine, e kōkua ana i ka hoʻihoʻi ʻana i ka pale pale pale, e hōʻemi i nā pane ʻeha, a hoʻomaikaʻi i ka nui o ke ola maʻi.
I ka mālama ʻana i nā maʻi maʻi maʻi maʻi e like me ka maʻi maʻi, ʻo Tα1 i hui pū ʻia me nā lāʻau antituberculosis hiki ke hoʻonui i ka hiki ke hoʻomaʻemaʻe i ke kino i ka Mycobacterium tuberculosis a hoʻomaikaʻi i ka maikaʻi o ka mālama ʻana.
ʻO nā maʻi pili i ka mumū
I ka mālama ʻana i nā maʻi e pili ana i ka ʻāʻī e like me ka rheumatoid arthritis a me ka maʻi ʻōpū ʻeha, hiki i nā hopena anti-inflammatory a me immune-modulating o Tα1 ke loaʻa i ka waiwai noi. ʻOiai ua kaupalena ʻia ka hoʻohana ʻana i ka lāʻau lapaʻau i kēia manawa, ua hōʻike ʻia kekahi mau noiʻi kumu a me nā hoʻokolohua lapaʻau liʻiliʻi e hōʻemi paha ʻo Tα1 i nā pane inflammatory a hoʻomaikaʻi i nā kūlana maʻi ma o ka hoʻoponopono ʻana i nā cell immune a me nā cytokines.
Ka hopena
ʻO Thymosin α1 (Tα1), ma ke ʻano he peptide me nā waiwai hoʻoikaika kino, ua hōʻike i nā hopena nui a hohonu i ke kahua o ka hoʻoponopono pale. Mai kāna hana o ka hana, hui pū ʻo Tα1 me nā mea loaʻa like Toll e hoʻāla i nā ala hōʻailona he nui i lalo, a laila hoʻoponopono i ka hana o nā cell immune a me nā pūnaewele cytokine, a loaʻa i ka mana pololei o ka pane ʻana o ke kino.
Ma keʻano o nā hopena e hoʻonui ai i ka immune, he kuleana koʻikoʻi ka Tα1 i ka maʻi antiviral, ka hana antitumor, ka hoʻoponopono palekana palekana, a me nā hopena anti-inflammatory. Ma ke kahua antiviral, hōʻike ʻo Tα1 i nā manaʻo noiʻi ākea, inā paha no nā maʻi maʻamau e like me ka maʻi hepa B a me C, a i ʻole no nā maʻi maʻi e kū mai ana e like me COVID-19. ʻO ke kuleana o Tα1 i nā maʻi kīnā ʻole a me nā maʻi e pili ana i ka mumū e hōʻike ana e hiki ke kōkua i ka hoʻihoʻi ʻana i ka pale pale a hoʻemi i ka pōʻino inflammatory. Ma ke ʻano holoʻokoʻa, he kuleana koʻikoʻi ko Tα1 ma ke ʻano he mea hoʻoikaika kino.
Nā kumu
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