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.
Tsufa, a matsayin wani tsari na halitta wanda ba makawa a cikin halittu masu rai, ya daɗe yana zama tushen binciken kimiyya. Yayin da kwayoyin halitta suka tsufa, sel sannu a hankali suna shiga yanayin da ba a iya gani ba, kuma tarin wadannan kwayoyin halitta na iya haifar da mummunan aiki na kyallen takarda da gabobin jiki, wanda ke haifar da cututtuka daban-daban da suka shafi shekaru. FOX04 - DRI yana da amfani don share sel masu hankali.
Bayanin FOX04-DRI
FOX04 - DRI shine peptide na roba, tare da cikakken sunan cokali mai yatsa O factor factor 4 - D - Retro - Inverso. Ganowarsa ya samo asali ne daga zurfafa bincike a cikin tsarin sarrafa kwayoyin halitta. A lokacin tsinkayar salon salula, nau'ikan kwayoyin halitta da yawa suna da hannu, kuma ma'aunin rubutun FOX04 yana taka muhimmiyar rawa a cikin wannan tsari. FOX04 yana nuna ƙayyadaddun tsarin magana da canje-canjen aiki a cikin ƙwayoyin ji. Ta hanyar bayyana tsarin aikin sa, masana kimiyya sun tsara da kuma haɗa FOX04-DRI don yin niyya ta musamman ga ƙwayoyin sel, da nufin magance matsalolin da suka shafi shekaru.
Hoto 1 Misalin tsari na kawar da hayakin sigari da ke haifar da fibroblasts na huhu ta hanyar amfani da FOXO4 siRNA-loaded DNA nanoparticles.
Hanyar FOX04-DRI a cikin share sel masu hankali
Tsangwama tare da hulɗar FOX04-p53: A cikin sel masu hankali, FOX04 yana hulɗa tare da furotin p53. Sunan furotin na p53 yana taka muhimmiyar rawa a cikin amsawar danniya ta salula, tsarin sake zagayowar tantanin halitta, da apoptosis. A karkashin yanayi na al'ada, p53 yana inganta apoptosis a cikin lalacewa ko kwayoyin halitta ta hanyar kunna maganganun jerin kwayoyin da ke da alaka da apoptosis, don haka kiyaye lafiyar yawan kwayar halitta. A cikin sel masu hankali, FOX04 yana ɗaure zuwa p53, yana hana jigilar sa zuwa tsakiya tantanin halitta, yana hana p53 yin aikin sa na pro-apoptotic, yana haifar da rayuwa da tarawar sel. FOX04-DRI na iya tsoma baki musamman tare da wannan hulɗar tsakanin FOX04 da p53, tare da toshe ɗaurin su, ƙyale p53 don sake shiga cikin kwayar halitta, kunna hanyar siginar apoptosis, da kuma haifar da apoptosis a cikin sel masu hankali, don haka samun izinin sel masu hankali.
Ka'idar hanyoyin siginar intracellular: Bugu da ƙari ga tsoma baki tare da hulɗar FOX04-p53, FOX04-DRI na iya rinjayar makomar sel ta hanyar daidaita sauran hanyoyin siginar ciki. Hanya ta sigina ta PI3K/AKT tana taka muhimmiyar rawa ta tsari a fannoni daban-daban na haɓakar tantanin halitta, yaɗuwa, rayuwa, da haɓaka. Nazarin ya nuna cewa ayyukan hanyar siginar PI3K/AKT galibi ana canza su a cikin sel masu hankali, suna shafar ayyukansu na yau da kullun. FOX04-DRI na iya tsara ayyukan hanyar siginar PI3K/AKT, canza ma'auni na siginar siginar a cikin sel masu hankali, don haka ƙirƙirar yanayi mara kyau na intracellular don rayuwarsu da haifar da apoptosis. Tsarin wannan hanyar siginar na iya yin tasiri ga jihohin rayuwa ta salula, da kara tuki sel masu hankali zuwa apoptosis.
Tasiri a kan Senescence-Associated Secretory Phenotype (SASP): Kwayoyin halitta suna ɓoye jerin cytokines, chemokines, da proteases, suna samar da nau'in ɓoyayyiyar ɓoyayyiyar ɓarna (SASP). SASP ba wai kawai yana rinjayar sel na al'ada da ke kewaye da su ba, yana rushe ayyukan su na yau da kullum, amma kuma yana haifar da amsawar kumburi na kullum, yana kara hanzarta tsarin tsufa na kyallen takarda da gabobin. FOX04-DRI na iya rage mummunan tasirin kwayoyin halitta a kan microenvironment da ke kewaye da su ta hanyar hana magana da ɓoye abubuwan da ke da alaka da SASP a cikin kwayoyin halitta. A cikin binciken, an gano cewa bayan da aka kula da kwayoyin halitta tare da FOX04-DRI, matakan maganganu na abubuwan da suka shafi SASP irin su IL-1a, IL-1β, tumor necrosis factor α (TNFα), da MMP2 a cikin kwayoyin halitta sun ragu sosai. Wannan yana nuna cewa FOX04-DRI na iya daidaita tsarin SASP na sel masu hankali yadda ya kamata, inganta microenvironment na salula, kuma a kaikaice inganta kawar da sel masu hankali da kuma dawo da microenvironment na nama.
Matsayin FOX04-DRI a cikin Nama da Cututtuka daban-daban
Matsayin da ke cikin Tsarin Haihuwa: Namiji hypogonadism marigayi-farawa cuta ce mai alaƙa da shekaru wacce tushen tsarin ta tabarbare ne na tsofaffin ƙwayoyin interstitial na testicular. FOX04 an bayyana shi musamman a cikin sel interstitial na ɗan adam, kuma a cikin tsofaffi, canjin nukiliya na FOX04 yana da alaƙa da rage ƙwayar testosterone. Yin amfani da hydrogen peroxide wanda ya haifar da tsofaffi na TM3 testicular interstitial sel a matsayin samfurin in vitro, an lura cewa FOX04 na iya kula da iyawar tsofaffin sel masu tsaka-tsakin jini kuma ya hana apoptosis. FOX04-DRI yana zaɓar p53 fitarwa na nukiliya da apoptosis na tsofaffin ƙwayoyin interstitial na testicular ta hanyar rushe hulɗar FOX04-p53. A cikin samfurin linzamin kwamfuta na halitta, gudanarwa na FOX04-DRI ya inganta microenvironment na testicular da kuma rage ƙarancin ɓoyewar testosterone mai alaka da shekaru. Sabili da haka, FOX04-DRI na iya zama da amfani don maganin hypogonadism na farko na namiji.
Hoto 2 Bayanin FOXO4 a cikin gwaje-gwajen ɗan adam da aka gano ta hanyar lalatawar immunofluorescent.
Matsayi a cikin tsarin numfashi
Fibrosis na huhu: Fibrosis na huhu (PF) cuta ce ta huhu mai ci gaba. Abubuwan da ke faruwa da yaɗuwar sa suna ƙaruwa da shekaru, kuma ana ɗaukar jin daɗin wayar salula ɗaya daga cikin mahimman abubuwan motsa jiki a cikin cututtukan ta. A cikin bleomycin (BLM) -induced PF linzamin kwamfuta model, FOX04-DRI ya nuna sakamako kama da na pirfenidone miyagun ƙwayoyi da aka yarda. Yana rage yawan adadin sel masu hankali, yana raguwa da bayyanar da yanayin da ake dangantawa da yanayin sirri (SASP), kuma yana rage BLM-induced morphological canje-canje da ƙaddamar da collagen a cikin nama na huhu. Bugu da ƙari, FOX04-DRI yana ƙara yawan nau'in nau'in 2 alveolar epithelial cell (AEC2) da fibroblasts yayin da rage yawan myofibroblasts. Gwaje-gwajen in vitro sun nuna cewa idan aka kwatanta da linzamin kwamfuta da huhu na huhu fibroblast cell Lines, FOX04-DRI ya fi karkata zuwa kashe canza girma factor-β (TGF-β) myofibroblasts, da kuma hana myofibroblasts, shi ya haifar da downregulation na extracellular matrix (ECM) mai karɓa hanyoyin sadarwa BLM.PF.
Cutar cututtuka na huhu na yau da kullum (COPD): Hanyoyin cututtuka da ci gaba na COPD suna da alaƙa da haɗin gwiwar salula. A cikin hayakin sigari da ke haifar da fibroblasts na huhu na huhu, FOX04 an ɗaukaka magana. Don ƙwanƙwasa FOX04 a cikin fibroblasts na hankali, DNA nanotubes masu haɗa kai (siFOXO4-NT) waɗanda aka ɗora tare da FOX04 siRNA guda ɗaya an ƙirƙira su kuma haɗa su. Nazarin ya nuna cewa siFOXO4-NT na iya shiga cikin fibroblasts na huhu na mutum (HFL-1 Kwayoyin) a cikin maida hankali da kuma dogara da lokaci, don haka rage matakan FOX04 a cikin vitro. siFOXO4-NT yana zaɓi yana kawar da ƙwayoyin HFL-1 da suka tsufa ta hanyar rage girman girman BCLXL magana da BCL2 / BAX rabo a cikin cirewar hayaki na sigari (CSE) wanda ya haifar da tsofaffin ƙwayoyin HFL-1.
Matsayi a cikin ƙwayar guringuntsi: Autologous chondrocyte implantation (ACI) hanya ce don magance lalacewar guringuntsi na haɗin gwiwa da kuma hana ciwon osteoarthritis na baya-bayan nan. A lokacin haɓakar in vitro na chondrocytes, matakin da ya dace a cikin ACI, ana haifar da sel masu hankali, waɗanda ke yin mummunan tasiri ga inganci da adadin sabbin ƙwayoyin guringuntsi. Masu bincike sun yi hasashen cewa maganin FOX04-DRI zai iya cire sel masu hankali daga faɗaɗa chondrocytes, don haka haɓaka damar su don samar da ingantacciyar guringuntsi. Don yin kwatankwacin tsarin fadada in vitro a cikin ACI, chondrocytes keɓe daga masu ba da gudummawa lafiya an faɗaɗa su zuwa matakin ninka yawan jama'a (PDL) 9, wakiltar chondrocytes a shirye don dasawa, yayin da sel a PDL3 suka yi aiki azaman ƙaramin haɓakawa. Sakamakon ya nuna cewa maganin FOX04-DRI ya cire fiye da rabin sel a PDL9 amma ba shi da wani tasiri mai mahimmanci akan adadin PDL3 chondrocytes. Matsayin jin daɗi na PDL9 chondrocytes da aka bi da su tare da FOX04-DRI ya ragu sosai. Dangane da daidaitattun sakamakon al'adun micro-cluster, pretreatment na FOX04-DRI bai haɓaka yuwuwar chondrogenic na PDL9 chondrocytes ba, amma ƙwayar chondroid da aka samu daga FOX04-DRI-pretreated PDL9 Kwayoyin sun nuna ƙananan maganganun abubuwan sirri masu alaƙa da tsufa. FOX04-DRI yadda ya kamata ya cire sel masu hankali daga PDL9 chondrocytes.
Matsayi a cikin fibrosis na huhu da ke haifar da radiation (RIPF): RIPF cuta ce ta gama gari kuma mai tsanani bayan maganin ƙwayar ƙwayar cuta ta thoracic. C57BL / 6 berayen sun kasu kashi bazuwar zuwa iska da iska mai iska + FOX04-DRI kungiyoyin, tare da dama hemithorax na kowane rukuni yana karɓar 17 Gy X-ray irradiation. Ƙungiyar FOX04-DRI da irradiation + FOX04-DRI ƙungiyar beraye an gudanar da su FOX04-DRI ta hanyar allurar intraperitoneal a makonni 16 da 20 bayan iska. Sakamako ya nuna cewa FOX04-DRI ya rage adadin collagen a cikin huhu na huhu na RIPF mice, rage yawan maganganun col1α1 da α-SMA, kuma ya rage adadin β-galactosidase (β-gal) sel masu kyau (alamar alama ta sel) a cikin ƙwayar huhu. FOX04-DRI ya iya hana bayyanar P21 da P16 ^ (Ink4a) kwayoyin halitta da sunadarai a cikin huhu nama na RIPF mice, da kuma bayanin SASP genes IL-1a, IL-1β, tumor necrosis factor α (TNFα), da MMP2. FOX04-DRI kuma yana rage matakan iskar oxygen mai amsawa (ROS) a cikin ƙwayar huhu na berayen RIPF kuma yana haɓaka kunna p-AKT da p-PI3K sunadaran. Wannan yana nuna cewa FOX04-DRI yana rage danniya na oxidative kuma yana hana jin daɗin salula ta hanyar kunna hanyar siginar PI3K/AKT, ta haka yana juyawa RIPF.
Hoto 3 FOXO4-DRI yana rage bambancin myofibroblast a cikin BLM-induced PF mice.
Kammalawa
A taƙaice, FOX04-DRI, a matsayin magani na juyin juya hali mai iya kawar da kwayoyin halitta na musamman, yana taka muhimmiyar rawa wajen magance cututtuka masu alaka da tsufa.
Sources
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[2] Han X, Yuan T, Zhang J, et al. FOXO4 peptide yana hari myofibroblast yana haɓaka fibrosis na huhu mai haifar da bleomycin a cikin mice ta hanyar hulɗar ECM-receptor [J]. Journal of Cellular and Molecular Medicine, 2022,26 (11): 3269-3280.DOI: 10.1111 / jcmm.17333.
[3] Huang Y, He Y, Makarcyzk MJ, et al. Senolytic Peptide FOXO4-DRI Zaɓaɓɓen Yana Cire Sel ɗin Senescent Daga In vitro Fadada Chondrocytes na Dan Adam [J]. Iyaka a Bioengineering da Biotechnology, 2021,9:677576.DOI:10.3389/fbiee.2021.677576.
[4] Zhang C, Xie Y, Chen H, et al. FOXO4-DRI yana rage rashin wadatar siginar testosterone da ke da alaƙa ta hanyar yin niyya ga ƙwayoyin Leydig a cikin tsofaffin mice [J]. Tsufa (Albany Ny), 2020,12(2):1272-1284.DOI:10.18632/tsufa.102682.
[5] Baar MP https://api.semanticscholar.org/CorpusID:196682180
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