By Cocer Peptides 
Watanni 1 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Dubawa
Thymosin Alpha-1 (Tα1) peptide ne tare da mahimman ayyukan sarrafa rigakafi. An fara keɓe shi daga ƙwayar thymus kuma ya ƙunshi amino acid 28, tare da N-terminal acetylation. Tα1 yana taka muhimmiyar rawa wajen kiyaye ma'auni na rigakafi da amsawa ga jihohin cututtuka a cikin jiki. A matsayin mai haɓaka rigakafi, yana nuna babban damar yin amfani da shi a cikin jiyya da rigakafin cututtuka daban-daban.
Hoto na 1 Thymosin alpha 1 yana da faffadan ayyukan nazarin halittu. IL: Interleukin; IFN: Interferon; TLR: Masu karɓar kuɗi kamar masu karɓa.
A karkashin yanayin ilimin lissafi, Tα1 yana shiga cikin ci gaba na al'ada da kuma kula da aikin tsarin rigakafi, yana yin tasiri mai mahimmanci akan bambance-bambance, balaga, da kunna ƙwayoyin rigakafi. A ƙarƙashin yanayin cututtukan cututtuka, irin su cututtukan hoto, ƙwayar cuta, da ƙarancin rigakafi, Tα1 na iya taimakawa jiki yaƙar cututtuka ta hanyar daidaita martanin rigakafi.
A fannin cututtuka masu yaduwa, ana amfani da Tα1 da yawa don magance cututtukan hanta (HBV) da cutar hanta ta C (HCV). Yana iya daidaita aikin rigakafi, taimakawa jiki wajen kawar da ƙwayoyin cuta, da inganta yanayin marasa lafiya.
Hanyoyin Immunomodulatory
(1) Yin hulɗa tare da masu karɓa masu kama da Toll (TLRs)
Hanya ɗaya mai mahimmanci ta hanyar da Tα1 ke aiwatar da tasirin tsarin rigakafi shine ta hanyar hulɗa tare da masu karɓa na Toll-like (TLRs). TLRs wani nau'i ne na masu karɓa na ƙirar ƙira waɗanda ke gane alamun ƙwayoyin ƙwayoyin cuta masu alaƙa (PAMPs) da kuma lalata-hadarin ƙwayoyin ƙwayoyin cuta (DAMPs), don haka kunna ƙwayoyin rigakafi da fara amsawar rigakafi.
Tα1 na iya ɗaure zuwa TLRs da yawa, kamar TLR3, TLR4, da TLR9. Bayan ɗaure wa waɗannan masu karɓa, Tα1 yana kunna hanyoyin sigina na ƙasa, ciki har da 3 (IRF3) na interferon da siginar siginar κB (NF-κB). Ɗaukar TLR3 a matsayin misali, bayan Tα1 ya ɗaure zuwa TLR3, yana inganta phosphorylation na IRF3, wanda ya juya zuwa kwayar halitta tantanin halitta, yana haifar da bayyanar cututtuka na antiviral da kuma tsarin rigakafi kamar nau'in I interferon (IFN-I). IFN-I yana da faffadan aikin rigakafi da rigakafin rigakafi, yana haɓaka juriyar jiki ga ƙwayoyin cuta.
Don TLR4, ɗaurin Tα1 yana kunna hanyar siginar NF-κB, yana daidaita maganganun cytokines mai kumburi kamar ƙwayar necrosis factor-α (TNF-α) da interleukin-6 (IL-6). Waɗannan cytokines suna taka muhimmiyar rawa a farkon matakan rigakafin rigakafi, ɗaukar ƙwayoyin rigakafi zuwa wurin kamuwa da cuta da haɓaka ƙarfin kariya na rigakafi na jiki.
Bugu da ƙari, TLR2 da TLR7 suma suna da alaƙa da Tα1. Tα1 na iya kunna TLR2 / NF-κB, TLR2 / p38 mitogen-activated protein kinase (p38MAPK), ko TLR7 / myeloid bambanci factor 88 (MyD88) hanyoyin siginar sigina, inganta samar da daban-daban cytokines kamar IL-1 da IL-12 amsawa a cikin haka.
(2) Tasirin tsari akan ƙwayoyin rigakafi
Kwayoyin T
Tα1 yana rinjayar ci gaba, bambance-bambance, da kunna ƙwayoyin T. A cikin thymus, Tα1 yana haɓaka haɓakawa da maturation na thymocytes. Studies have shown that after inhibiting T cell-mediated antibody production in mice using 5-fluorouracil (5-FU), chemically synthesized Tα1 can restore this antibody production capacity, and exhibits activity even at a low dose of 30 μg/kg.
Binciken cytometry na gudana ya nuna cewa wannan kashi na Tα1 yana haɓaka haɓakawa da maturation na thymocytes; duk da haka, ba ya shafar maganganun Smoothened (Smo), maɓalli mara kyau mai kula da hanyar siginar Hedgehog (Hh) a CD4⁻ CD8⁻ thymocytes. This suggests that Tα1 may promote T cell maturation through specific signaling pathways that bypass or are independent of Smo-regulated pathways.
Dangane da manyan ƙwayoyin T, Tα1 na iya daidaita ma'auni na sassan T cell. In the tumor microenvironment, Tα1 can alter the ratio of CD8⁺ T cells and regulatory T cells (Tregs) by regulating dendritic cell (DC) differentiation and chemokine expression profiles, thereby enhancing the body's antitumor immune response.
Hoto 2 Thymosin α1 (Tα1) yana hana lalacewar epithelial a cikin DSS tare da maganin CTLA-4-induced colitis.
Kwayoyin B
Kodayake nazarin kai tsaye kan tasirin Tα1 akan ƙwayoyin B ba su da ɗan ƙaranci, bincike na yanzu yana nuna yana iya yin tasiri a kaikaice aikin ƙwayoyin B ta hanyar daidaita ƙwayoyin T. Tun da ƙwayoyin T suna taka muhimmiyar rawa a cikin kunna tantanin halitta B, canjin ajin antibody, da maturation na dangantaka, ƙa'idodin Tα1 na aikin ƙwayoyin T na iya yin tasiri a kaikaice samar da ƙwayoyin ƙwayoyin cuta na B, ta haka yana haɓaka amsawar rigakafi ta jiki.
Macrophages
Tα1 kuma yana da mahimman tasirin tsari akan aikin macrophage. Yin amfani da gwajin MTT, an gano cewa Tα1 yana nuna tasirin cytotoxic a kan RAW 264.7 macrophages, tare da raguwa mai mahimmanci na hanawa (IC50) na 368.105 μg / ml. Yayin da ƙaddamarwar Tα1 ke ƙaruwa, tasirin cytotoxic akan sel RAW 264.7 yana ƙaruwa, yana haifar da raguwar yawan ƙwayar sel.
Tα1 kuma yana nuna tasirin anti-mai kumburi, wanda aka kimanta ta hanyar nazarin samar da nitric oxide (NO) a cikin ƙwayoyin RAW 264.7. Sakamakon ya nuna cewa a cikin kewayon ƙaddamarwa na 7.813-31.25 μg / ml, NO samarwa a cikin ƙungiyar Tα1 da aka yi amfani da su ya ragu a cikin hanyar da aka dogara da kashi idan aka kwatanta da ƙungiyar kulawa, yana nuna cewa Tα1 na iya yin amfani da magungunan ƙwayoyin cuta ta hanyar hana NO samarwa a cikin macrophages, don haka daidaita matakan rigakafi.
Kwayoyin kashe kwayoyin halitta (NK Cells)
Tα1 yana haɓaka haɓakar ƙwayoyin NK da kunnawa, haɓaka ayyukan cytotoxic su. Kwayoyin NK wani muhimmin sashi ne na tsarin garkuwar jiki, wanda ke da ikon kashe ƙwayoyin da ke kamuwa da ƙwayoyin cuta da ƙwayoyin ƙari. Tα1 yana haɓaka ikon su na gane da kashe ƙwayoyin da aka yi niyya ta hanyar haɓaka maganganun masu karɓar kunnawa akan saman sel NK, ta haka suna taka muhimmiyar rawa a cikin kamuwa da cuta ta ƙwayoyin cuta da rigakafin rigakafi.
(3) Tsarin hanyar sadarwar cytokine
Tα1 yana aiwatar da ayyukansa na rigakafi ta hanyar daidaita hanyar sadarwar cytokine. Cytokines wani nau'i ne na ƙananan sunadaran kwayoyin halitta da aka ɓoye ta ƙwayoyin rigakafi da wasu ƙwayoyin da ba su da rigakafi, waɗanda ke watsa bayanai tsakanin sel da daidaita aikin ƙwayoyin rigakafi da kuma tsanani da nau'in amsawar rigakafi.
Tα1 na iya haɓaka samar da cytokines daban-daban, irin su interleukin-2 (IL-2), interleukin-3 (IL-3), da interferon-γ (IFN-γ). IL-2 shine mahimmancin haɓakar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar kuma IL-2 IL-2 ta inganta aikin kwayoyin NK da cytotoxic T lymphocytes (CTLs), ta haka ne inganta tsarin rigakafi na jiki. IL-3 yana haɓaka haɓakawa da bambance-bambance daban-daban na ƙwayoyin hematopoietic da sel masu haɓaka, suna taimakawa wajen kula da tsarin salula da aikin tsarin rigakafi. IFN-γ yana da ayyuka da yawa, ciki har da antiviral, antitumor, da kuma tasiri na rigakafi na rigakafi, inganta ƙarfin phagocytic da cytotoxic na macrophages, inganta bambancin kwayoyin Th1, da kuma daidaita tsarin rigakafi zuwa tsarin rigakafi na salula.
Bugu da ƙari, Tα1 na iya daidaita ma'auni tsakanin pro-mai kumburi da cytokines anti-mai kumburi. A lokacin amsawar kumburi, Tα1 na iya hana haɓakar haɓakar cytokines masu kumburi irin su TNF-a da IL-1, yayin haɓaka samar da cytokines anti-mai kumburi kamar interleukin-10 (IL-10), ta haka rage lalacewar da ke haifar da martani mai kumburi ga jiki da kiyaye daidaiton rigakafi.
Tasirin haɓaka rigakafi
(1) Kamuwa da cuta
Hepatitis B da Hepatitis C
Tα1 yana taka muhimmiyar rawa wajen maganin ciwon hanta na B da hepatitis C. Don kamuwa da cutar hanta na ciwon hanta (HBV), Tα1 na iya daidaita aikin garkuwar jiki da haɓaka ikonsa na kawar da HBV. Tα1 yana kunna ƙwayoyin rigakafi kamar ƙwayoyin T da ƙwayoyin NK, yana ba su damar gane da kuma kawar da ƙwayoyin hanta masu cutar HBV. Tα1 na iya daidaita hanyar sadarwar cytokine, inganta samar da cytokines na antiviral kamar IFN-γ da hana HBV kwafi.
A cikin maganin cutar cutar hepatitis C (HCV), Tα1 yana nuna sakamako mai kyau. Yana iya haɓaka amsawar rigakafi ta jiki, taimako wajen kawar da HCV, da kuma nuna tasirin haɗin gwiwa yayin amfani da su tare da sauran magungunan rigakafi, don haka inganta ƙimar nasarar jiyya.
Sauran cututtukan cututtuka
Baya ga HBV da HCV, Tα1 na iya taka rawa a cikin wasu cututtuka masu saurin kamuwa da cuta. Tα1 na iya taimakawa haɓaka hasashen majinyata marasa lafiya tare da COVID-19. Ta hanyar gyare-gyaren lalacewa ta hanyar haɓakar rigakafi na lymphocyte da kuma hana yawan kunnawa T-cell, Tα1 na iya rage alamun marasa lafiya da inganta yawan rayuwa.
(2) Ka'idojin rigakafi da rigakafin kumburi
Daidaita Ma'auni na rigakafi
Tα1 yana taka muhimmiyar rawa wajen kiyaye ma'auni na rigakafi a cikin jiki. A cikin jihohi marasa ƙarfi, Tα1 na iya inganta haɓakawa da bambance-bambancen ƙwayoyin rigakafi, maido da aikin rigakafi na jiki. Alal misali, a wasu cututtuka na rashin ƙarfi na rigakafi na haihuwa ko jihohin da aka hana rigakafi da ke haifar da chemotherapy ko radiation far, Tα1 zai iya taimakawa jiki ya sake daidaita ma'auni ta hanyar daidaita ci gaba da aikin ƙwayoyin rigakafi.
A cikin cututtuka na autoimmune, Tα1 na iya dakatar da amsawar rigakafi da yawa da kuma rage lalacewar autoimmune ta hanyar daidaita ayyukan ƙwayoyin rigakafi da cibiyar sadarwar cytokine.
Abubuwan da ke hana kumburi
Tα1 yana da tasirin anti-mai kumburi. A lokacin amsawar kumburi, Tα1 na iya daidaita maganganun cytokines da ke da alaƙa da kumburi kuma ya hana haɓakar haɓakar ƙwayar cuta. Kamar yadda aka ambata a baya, Tα1 na iya hana NO samarwa a cikin macrophages, rage maganganun cytokines masu kumburi irin su TNF-a da IL-1, kuma a lokaci guda suna inganta samar da cytokines masu kumburi kamar IL-10.
Hoto 3 Nitric oxide saki bayan jiyya tare da LPS da kuma daban-daban na Tα-1 a cikin sel RAW 264.7.
A cikin samfurin ciwo mai kumburi, Tα1 yana kawar da allodynia na injiniya da hyperalgesia wanda ya haifar da cikakken Freund's adjuvant (CFA), kuma yana rage haɓakar masu shiga tsakani kamar IFN-γ, TNF-α, da ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwa (BDNF) da CFA ta haifar. Bugu da ƙari, Tα1 na iya daidaita hanyar siginar Wnt3a / β-catenin a cikin kashin baya, wanda aka kunna a lokacin tsarin ciwo mai zafi, kuma Tα1 na iya jujjuya yanayin da aka kunna, don haka yana rage zafi mai zafi.
Aikace-aikace na asibiti
(1) Maganin Hepatitis
A cikin maganin asibiti na cutar hanta, Tα1 an yi amfani da shi sosai. Ga marasa lafiya da ciwon hanta na B, yawancin nazarin asibiti sun nuna cewa Tα1 tare da nucleoside (acid) analogues ko interferon far sun sami mafi girma na HBV DNA seroconversion, HBeAg seroconversion, da kuma daidaitawar ALT idan aka kwatanta da monotherapy. A cikin wasu gwaje-gwaje na asibiti, haɗuwa da Tα1 da entecavir don kula da marasa lafiya na ciwon hanta na kullum ya haifar da karuwa mai yawa na HBV DNA seroconversion bayan makonni 48 na jiyya idan aka kwatanta da ƙungiyar da aka yi da entecavir kadai, kuma adadin HBeAg seroconversion kuma ya inganta.
A cikin maganin ciwon hanta na C, Tα1 hade tare da magungunan antiviral masu aiki kai tsaye (DAAs) na iya haɓaka tasirin antiviral, musamman ga wasu marasa lafiya na ciwon hanta na C, mai yuwuwa inganta ƙimar nasarar magani.
(2) Maganin Rashin Lafiya
Ga wasu cututtukan rashin ƙarfi na farko, irin su hypoplasia na thymic, ana iya amfani da Tα1 azaman wani ɓangare na madadin magani. Ko da yake Tα1 ba zai iya warkar da waɗannan cututtuka gaba ɗaya ba, yana iya daidaita aikin rigakafi, haɓaka rigakafi na marasa lafiya, rage mita da tsananin cututtuka, da inganta rayuwar marasa lafiya.
A cikin cututtukan da aka samu na rashin ƙarfi na rigakafi, irin su HIV/AIDS, Tα1 tare da maganin rigakafi (ART) na iya haɓaka tsarin rigakafi, ƙara yawan CD4⁺ T cell, inganta aikin rigakafi, da rage yawan kamuwa da cututtuka na dama.
(3) Sauran Applications
Magungunan Adjuvant don Cututtuka masu Yaduwa
A cikin maganin cututtuka masu tsanani irin su sepsis, Tα1 za a iya amfani da shi azaman maganin adjuvant. Marasa lafiya na Sepsis sau da yawa suna da tabarbarewar rigakafi. Tα1 yana daidaita ayyukan ƙwayoyin cuta na rigakafi da cibiyoyin sadarwar cytokine, yana taimakawa wajen dawo da ma'auni na rigakafi, rage martani mai kumburi, da inganta ƙimar rayuwa mai haƙuri.
A cikin maganin cututtukan cututtuka na yau da kullun irin su tarin fuka, Tα1 tare da magungunan rigakafin tarin fuka na iya haɓaka ƙarfin kariya daga cutar tarin fuka na Mycobacterium da inganta ingantaccen magani.
Cututtuka masu alaƙa da kumburi
A cikin maganin cututtuka da ke da alaka da cututtuka irin su cututtuka na rheumatoid da cututtuka na ƙwayar cuta, Tα1 ta anti-mai kumburi da kuma rigakafi-modulating effects iya samun m aikace-aikace darajar. Kodayake aikace-aikacen asibiti a halin yanzu yana iyakance, wasu bincike na asali da ƙananan gwaje-gwaje na asibiti sun nuna cewa Tα1 na iya rage amsawar kumburi da inganta yanayin haƙuri ta hanyar daidaita ƙwayoyin rigakafi da cytokines.
Kammalawa
Thymosin α1 (Tα1), a matsayin peptide tare da kayan haɓaka rigakafi, ya nuna tasiri mai yawa da tasiri a cikin tsarin tsarin rigakafi. Daga tsarin aikinta, Tα1 yana hulɗa tare da masu karɓa kamar Toll don kunna hanyoyin sigina da yawa na ƙasa, ta haka ne ke daidaita aikin ƙwayoyin rigakafi da cibiyoyin sadarwar cytokine, da samun daidaitaccen sarrafa martanin rigakafi na jiki.
Dangane da tasirin haɓakar rigakafi, Tα1 yana taka muhimmiyar rawa a cikin kamuwa da cuta ta ƙwayoyin cuta, aikin antitumor, ƙa'idodin daidaituwa na rigakafi, da tasirin kumburi. A cikin filin antiviral, Tα1 yana nuna fa'idodin aikace-aikacen aikace-aikacen, ko don cututtukan cututtukan ƙwayar cuta na yau da kullun kamar hepatitis B da C, ko don kamuwa da cututtukan hoto kamar COVID-19. Matsayin Tα1 a cikin cututtuka na rashin ƙarfi na rigakafi da cututtukan da ke da alaka da kumburi yana nuna cewa zai iya taimakawa wajen dawo da ma'auni na rigakafi da kuma rage lalacewar ƙwayar cuta. Gabaɗaya, Tα1 yana taka muhimmiyar rawa a matsayin mai haɓaka rigakafi.
Sources
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