Na Cocer Peptides 
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INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Intangiriro
Hamwe niterambere ryiterambere ryubumenyi bwubuzima, ubushakashatsi muburyo bwo gusaza bwarushijeho kwiyongera, kandi kubona uburyo bwiza bwo kurwanya gusaza byabaye ingingo yingenzi mubumenyi bwa siyanse. Telomeres, nkibikoresho byo kurinda impera za chromosomes, bifitanye isano rya bugufi no gusaza kwa selile. Epitalon, peptide ngufi ya syntetique ifite ingaruka zo kurwanya gusaza, yashimishije abantu mumyaka yashize.
Kurambura Telomere Ibirimo
(1) Imiterere n'imikorere ya Telomeres
Telomeres ibitswe cyane nucleotide ikurikirana cyane kumpera ya chromosomes, igizwe na ADN yoroshye ya tandem isubiramo ikurikirana hamwe na poroteyine bifitanye isano. Telomeres igira uruhare runini mugukomeza ubusugire bwimiterere ya gene hamwe na chromosomal. Muri buri gice cyo kugabana, telomereri igabanuka buhoro buhoro kubera ubushobozi buke bwo kwigana ADN. Iyo telomereri igabanije kurwego runaka, selile zinjira muri senescence cyangwa apoptose, niyo mpamvu telomereri mu buryo bw'ikigereranyo bita 'isaha yubuzima. '
Igishushanyo 1 Epitalon yagabanije urwego rudasanzwe rwa ROS.
(2) Uburyo bwo Kurambura Telomere
Inzira ya Telomerase
Telomerase ni ribonucleoprotein igizwe nibikorwa bya reverse transcriptase. Irashobora gukoresha RNA yayo nkicyitegererezo cyo guhuza telomere isubiramo ikurikirana hanyuma ikayongerera kumpera ya chromosomes, bityo igakomeza uburebure bwa telomere. Mu ngirabuzimafatizo zisanzwe zabantu, ibikorwa bya telomerase biri hasi cyangwa bidahari, kandi telomereri igabanuka buhoro buhoro hamwe na buri gice kigabanijwe. Nyamara, muri selile nyinshi yibibyimba, telomerase yongeye gukora, ituma selile yibibyimba ikura igihe kitarambiranye kandi ikagera kubudapfa. Muri primaire primaire metulloblastoma, selile zimwe na zimwe zibyimba zigenzura kurambura telomere binyuze mumikorere ya telomerase. Hafi ya 10.7% ya metullatic medulloblastoma itera itumanaho rya telomerase ikoresheje ihinduka rya TERT promoter mutation hamwe na hypermethylation ya UTSS, bityo bikagera kuri telomere.
ALT inzira
Usibye inzira ya telomerase, hariho uburyo bwigenga bwa telomerase buzwi nkuburyo bwo guhinduranya inzira ya telomereri (ALT). Iyi nzira iterwa cyane cyane no kudakora kwa ATRX kandi igira uruhare runini muri selile zimwe na zimwe. Muri medulloblastoma y'abana bato, abagera kuri 32.1% by'imanza bagera kuri telomere bakoresheje uburyo bwa ALT, hamwe na 30% by'icyitegererezo cyerekana ko ATRX yasibye, bityo igakora inzira ya ALT.
(3) Epitalon hamwe na Mechanism yo Kurambura Telomere
Ingaruka ya Epitalon kuri Telomerase
Epitalon ni peptide ngufi ya peptide igizwe na acide enye za amine (alanine, aside glutamic, aside aspartic, na glycine), ishingiye kuri peptide karemano Epithalamion yakuwe muri glande. Ubushakashatsi bwerekana ko Epitalon ishobora guhindura uburebure bwa telomere mugukangura ibikorwa bya telomerase. Itsinda ry’abashakashatsi b’Uburusiya bavumbuye bwa mbere mu myaka ya za 1980 ko Epitalon ishobora gutera telomerase, enzyme ishinzwe kurinda no kwagura telomereri ku mpera za chromosomes. Nubwo kuri ubu nta bimenyetso simusiga byerekana ko Epitalon ishobora kwagura telomereri mu bantu, ubushakashatsi bumwe bwerekanye ko bushobora kongera ibikorwa bya telomerase. Kongera ibikorwa bya telomerase bivuze ko telomere isubiramo ikurikiranye irashobora guhuzwa kandi ikongerwaho kumpera ya chromosomes, birashoboka ko umuvuduko wo kugabanuka kwa telomere ndetse ukagera no kurambura telomere.
Igishushanyo 2 Epitalon yarinze imikorere ya mitochondriya mugihe cya oocyte nyuma ya ovulatory ishaje muri vitro.
Epitalon igenga inzira yerekana ibimenyetso
Inzira yerekana ibimenyetso byerekana urusobe rugoye ruhuza kugenzura imikorere ya selile nko gukura, gukwirakwira, no gusaza. Epitalon irashobora kugira uruhare rutaziguye kurambura telomere muguhuza inzira zerekana. Kurugero, irashobora guhindura inzira zijyanye no kugenzura ingirabuzimafatizo, kuzamura uburyo bwo kurinda telomereri mugihe cyo kugabana. Byongeye kandi, nka antioxydeant, Epitalon igabanya umusaruro wubwoko bwa ogisijeni ikora (ROS) mu ngirabuzimafatizo. Ikwirakwizwa rya ROS rishobora kwangiza ADN, bityo bikagira ingaruka kuri telomere. Mugabanye urwego ROS, Epitalon ifasha kugumana imiterere isanzwe nimikorere ya telomereri, bigatera ibihe byiza byo kurambura telomere.
(4) Ibimenyamenya Byerekana Uruhare rwa Epitalon mu Kurambura kwa Telomere
Mubushakashatsi bwa vitro selile
Mubushakashatsi bwumuco wa vitro selile, kongeramo Epitalon murwego rwumuco byatumye ibikorwa bya telomerase byiyongera mubikorwa bimwe na bimwe. Abashakashatsi bongeyeho Epitalon ku gipimo cya 0.1 mM mu muco w’akagari. Nyuma yigihe cyo guhinga, byagaragaye ko urwego rwerekana imiterere ya genes zijyanye na telomerase mu ngirabuzimafatizo zariyongereye, byerekana ko Epitalon ishobora guteza imbere synthesis cyangwa gukora telomerase. Byongeye kandi, ibipimo by'uburebure bwa telomere byerekanaga ko, ugereranije nitsinda rishinzwe kugenzura ridafite Epitalon, umuvuduko wa telomere mu itsinda ry’ubushakashatsi wagabanutse cyane, kandi mu tugari tumwe na tumwe, telomere ndende yagaragaye.
Ubushakashatsi ku nyamaswa
Mu bushakashatsi bw’inyamaswa, Epitalon yahawe inyamaswa zigeragezwa (nk'imbeba) hakoreshejwe inshinge cyangwa ubuyobozi bwo mu kanwa, hanyuma hasesengurwa ingirabuzimafatizo zabo. Ibisubizo byerekanaga ko ibikorwa bya telomerase mubice bimwe na bimwe (nk'umwijima n'impyiko) byongerewe imbaraga, kandi uburebure bwa telomere bwagumye buhagaze neza. Mu bushakashatsi bwakozwe ku ngirabuzimafatizo z'umwijima, byagaragaye ko imbeba zavuwe na Epitalon zagize ibikorwa bya telomerase mu ngirabuzimafatizo z'umwijima ugereranije n'itsinda ritavuwe, kandi nyuma yo gukurikirana mu gihe cy'amezi menshi, urugero rwa telomere rugabanuka mu ngirabuzimafatizo z'umwijima rwaragabanutse cyane ugereranije no mu itsinda ritavuwe. Ibi birerekana kandi ko Epitalon igira ingaruka nziza kurambura telomere mubikoko.
Kurwanya Gusaza-Ibirimo
(1) Uburyo bwo gusaza
Oxidative Stress no Gusaza
Uko imyaka igenda yiyongera, uburinganire bwa redox mu ngirabuzimafatizo burahungabana, biganisha ku kwegeranya amoko ya ogisijeni (ROS). ROS ifite imbaraga zikomeye za okiside, zishobora okiside biomolecules selile nka proteyine, lipide, na ADN, bikaviramo kwangirika kwimikorere nimikorere. Poroteyine za oxydeize zirashobora gutakaza ibikorwa bisanzwe byibinyabuzima, lipide ya okiside irashobora kwangiza ingirabuzimafatizo ya selile kandi itajegajega, kandi kwangirika kwa okiside ya ADN bishobora gutera ihinduka ryimiterere ya gene no kudakora neza kwa selile, ibyo byose byihutisha gusaza kwingirabuzimafatizo hamwe n’ibinyabuzima.
Gusaza kwa selile na Apoptose
Senescence ya selile na apoptose nibintu byingenzi mugusaza. Iyo selile zihuye nibintu bitandukanye bitesha umutwe (nka stress ya okiside, kwangirika kwa ADN, nibindi), byinjira muri senescent. Ibiranga selile ya senescent harimo gufata ingirabuzimafatizo, impinduka za metabolike, hamwe no gusohora cytokine yihariye. Hagati aho, apoptose ni gahunda yurupfu rwa selile igira uruhare runini mukubungabunga urugo rwa homeostasis. Ariko, uko imyaka igenda yiyongera, uburyo bwo kugenzura apoptose burashobora guhungabana, kandi apoptose ikabije cyangwa idahagije irashobora gutuma imikorere yimitsi igabanuka, amaherezo bikagaragara nkubusaza bwibinyabuzima.
Kugabanuka kwa Telomere no gusaza
Nkuko byavuzwe haruguru, kugabanya telomere nimwe mubimenyetso byingenzi byo gusaza. Nkuko selile zikomeza kugabana, telomereri igabanuka buhoro buhoro. Iyo telomereri igeze ku burebure bukomeye, selile zihagarika amacakubiri kandi zinjira muri leta ya senescent. Kugabanuka kwa telomere birashobora kandi gutuma ADN yangirika mu ngirabuzimafatizo, bikarushaho kwihuta gusaza kwa selile na apoptose, bityo bikagira ingaruka ku gusaza kw’ibinyabuzima muri rusange.
Igicapo 3 Ingaruka za Epitalon kuri apoptose hakiri kare muri oocytes ishaje nyuma yintanga.
(2) Uburyo bwo Kurwanya Gusaza bwa Epitalon
Igikorwa cya Antioxydeant
Epitalon ni antioxydants ifite imbaraga za antioxydeant igereranywa na melatonine. Irashobora gusiba ROS mu ngirabuzimafatizo, kugabanya kwangiza okiside kuri biomolecules yatewe na ROS. Mu bushakashatsi bwa vitro ukoresheje oocytes yimbeba, wongeyeho 0.1 mM Epitalon murwego rwumuco byatumye igabanuka rikabije ryurwego ROS rudasanzwe. Kugabanuka kwa ROS bifasha kugumana ubudahangarwa bwimikorere ya selile, imikorere ya proteine isanzwe, hamwe na ADN itajegajega, bityo bigatinda gusaza kwa selile. Byongeye kandi, Epitalon irashobora kongera ubushobozi bwa antioxydants ya selile igenga ibikorwa bya sisitemu yo mu bwoko bwa antioxydeant ya antioxydeant (nka superoxide dismutase na catalase), bityo bikagabanya kwangirika kwa okiside iterwa na selile.
Kugenga imikorere ya mitochondial
Mitochondriya ni imbaraga zingirabuzimafatizo, kandi imikorere yazo ifitanye isano rya bugufi no gusaza kwa selile. Hamwe n'imyaka, imikorere ya mitochondial igenda igabanuka buhoro buhoro, bigaragazwa no kugabanuka kwa mitochondrial membrane ubushobozi, kugabanuka kwa ATP, no kongera ROS. Epitalon irashobora kongera mitochondrial membrane ubushobozi hamwe na kopi ya ADN ya mitochondial, bityo igateza imbere imikorere ya mito-iyambere. Mu bushakashatsi bwa vitro yo gusaza ukoresheje oocytes yimbeba, oocytes ivurwa na Epitalon yerekanaga cyane ubushobozi bwa mitochondrial membrane kandi byongera umubare wa kopi ya ADN ya mitochondial nyuma yamasaha 12 na 24 yo gusaza ugereranije nitsinda ritavuwe. Ibi byerekana ko Epitalon ishobora gukomeza imikorere isanzwe ya mito-iyambere kandi ikagabanya gusaza kwa selile iterwa no gukora nabi mito-iyambere. Kunoza imikorere ya mitochondial kandi bifasha kugumana ingufu za selile selile metabolism, gutanga ingufu zihagije mubikorwa bisanzwe bya physiologique no gutinda gusaza kwa selile.
Kurinda apoptose
Apoptose selile igira uruhare runini mugusaza. Apoptose ya selile ikabije irashobora gutuma igabanuka ryimikorere yimikorere ningingo. Epitalon igenga inzira ya apoptose yo mu nda ifitanye isano n'inzira zerekana ibimenyetso kugirango igabanye indwara ya apoptose. Mu bushakashatsi bwa vitro yo gusaza ukoresheje oocytes yimbeba, nyuma yamasaha 24 yo gusaza kwa vitro, igipimo cya apoptose ya oocytes mumatsinda yavuwe na Epitalon yari hasi cyane ugereranije no mumatsinda atavuwe. Ibi birashobora guterwa nubushobozi bwa Epitalon bwo kubuza gukora ibimenyetso bya apoptose hakoreshejwe uburyo nko kugabanya urwego rwa ROS no kunoza imikorere ya mito-iyambere, bityo kugabanya apoptose no gufasha kugumana imikorere isanzwe ningingo, no gutinda gusaza kumubiri.
(3) Ibimenyetso Byubushakashatsi Bya Epitalon Ingaruka Zirwanya Gusaza
Ingaruka zo gukingira oocytes
Mu bushakashatsi bwakoze iperereza ku ngaruka Epitalon yagize ku bwiza bwa oocyte, byagaragaye ko Epitalon irinda neza oocytes ibyangiritse bijyanye no gusaza nyuma ya ovulation. Mugihe nyuma ya ovulation yiyongera, ubushobozi bwiterambere bwa oocytes buragabanuka buhoro buhoro. Iyo 0.1 mM Epitalon yongewe kumuco, umuco wa oocyte wasuzumwe nyuma yamasaha 6, 12, na 24 yumuco. Ibisubizo byerekanye ko kuvura Epitalon byagabanije cyane inshuro nyinshi inenge ya spindle no gukwirakwiza bidasanzwe kwa granical cortique, mugihe byongera ubushobozi bwa mitochondrial membrane na numero ya kopi ya ADN ya mitochondial, no kugabanya oocyte apoptose. Ibi byerekana ko Epitalon ishobora gutinza gahunda yo gusaza kwa vitro ya oocytes, igakomeza ubuziranenge bwayo ndetse niterambere ryayo, kandi igatanga ibimenyetso byo murwego rwa selile byerekana ingaruka za Epitalon zirwanya ubusaza.
Ingaruka zo gusaza muri rusange
Mu bushakashatsi bw’inyamaswa, nyuma yubuyobozi bwigihe kirekire bwa Epitalon hakoreshejwe kugaburira cyangwa gutera inshinge, iterambere ryagaragaye mubipimo byinshi bifitanye isano no gusaza mu mbeba. Ugereranije n'imbeba zo kugenzura zitavuwe, imbeba zivuwe na Epitalon zerekanaga ubucucike, ubwoya bwa shinier, kongera umuvuduko, hamwe no kwagura ubuzima. Isesengura ry’imiterere y’imbeba ryerekanye ko kwangirika kw ingirabuzimafatizo no gusaza mu ngingo zikomeye nk'umwijima n'impyiko z'imbeba zavuwe na Epitalon zari hasi cyane ugereranije n'iz'itsinda rishinzwe kugenzura. Ibi byerekana ko Epitalon itagaragaza gusa ingaruka zo kurwanya gusaza kurwego rwa selile ahubwo inadindiza gusaza kurwego rwibinyabuzima, kuzamura ubuzima bwinyamaswa nubuzima bwiza.
Gusaba Ibyiringiro bya Epitalon
Ibishoboka mubisabwa mubuvuzi
Umuti urwanya gusaza
Ukurikije ubushakashatsi bwa Epitalon mubushakashatsi bwa telomere no kurwanya gusaza, bushobora kuba nk'igitabo gishya cyo kurwanya gusaza. Hamwe nihuta ryogusaza kwabaturage, icyifuzo cyo kuvura anti-gusaza kiriyongera. Epitalon itinda gusaza kwa selile ikoresheje uburyo bwinshi, itanga ubumenyi bushya bwo guteza imbere imiti yibasira indwara ziterwa n'imyaka nk'indwara z'umutima n'imitsi n'indwara zifata ubwonko. Ku ndwara zifata ubwonko, Epitalon irashobora kurinda neuron kwangirika kwa okiside kandi ikagumana uburebure bwa telomere, bityo bikadindiza gusaza no gupfa kwa neuronal, kunoza ibimenyetso byindwara, no kuzamura imibereho y’abarwayi.
Gutezimbere ubuzima bw'imyororokere
Mu rwego rwubuvuzi bwimyororokere, Epitalon igira ingaruka zimwe na zimwe zo kurinda oocytes. Mugihe abagore basaza, ubwiza bwa oocyte buragabanuka, byongera ibyago byo kutabyara no gukura kw'inda bidasanzwe. Epitalon irashobora gutinza gusaza kwa oocyte no kunoza ireme rya oocyte, igatanga ingamba nshya zifasha tekinoloji yimyororokere ifashwa nko gufumbira vitro. Iyo wongeyeho Epitalon mugihe cyumuco wa vitro oocyte, biteganijwe ko uzamura igipimo cy’ifumbire ndetse n’iterambere ry’isoro, bityo bikongerera intsinzi intsinzi y’imyororokere ifasha kandi bigafasha abashakanye benshi batabyara kuzuza icyifuzo cyabo cyo kubyara.
Umwanzuro
Epitalon yerekana ubushobozi bukomeye mukurambura telomere no kurwanya gusaza. Nubwo hakiri ibibazo bimwe bisaba ubundi bushakashatsi no kubikemura, akamaro kacyo haba mubitekerezo bya siyansi no mubikorwa mbonezamubano ntibishobora kwirengagizwa. Mu gihe ubushakashatsi bukomeje kwiyongera, abantu bemeza ko Epitalon izazana ibintu byinshi bitangaje ndetse n’iterambere mu rwego rw’ubuzima bw’abantu.
Inkomoko
[1] Teterin O, Gv S. Epitalon [J]. 2023.
[2] Yue X, Liu SL, Guo JN, n'abandi. Epitalon irinda gusaza nyuma ya ovulatory gusaza biterwa no kwangirika kwa oocytes yimbeba muri vitro [J]. Gusaza (Albany Ny), 2022,14 (7): 3191-3202.DOI: 10.18632 / gusaza.204007.
[3] Minasi S, Baldi C, Pietsch T, n'abandi. Kurambura telomere ukoresheje ubundi buryo bwo kurambura telomereri (ALT) no gukora telomerase muri medulloblastoma metastatic primaire yo mu bwana [J]. Ikinyamakuru cya Neuro-Oncology, 2019,142 (3): 435-444.DOI: 10.1007 / s11060-019-03127-w.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
