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.
Okwu mmalite
Site na mmepe nke sayensị ndụ na-aga n'ihu, nyocha n'ime usoro nke ịka nká na-abawanyewanye nke ọma, na ịchọta ụzọ mgbochi ịka nká nke ọma aghọwo isiokwu dị mkpa na mpaghara sayensị. Telomeres, dị ka ihe nchebe na njedebe nke chromosomes, nwere njikọ chiri anya na ịka nká cellular. Epitalon, peptide dị mkpụmkpụ sịntetị nwere mmetụta mgbochi ịka nká, dọtara uche n'afọ ndị na-adịbeghị anya.
Ọdịnaya metụtara Telomere na-agbatịkwu
(1) Ọdịdị na ọrụ nke Telomeres
Telomeres bụ usoro nucleotide ugboro ugboro na-echekwa nke ọma na nsọtụ chromosomes, nke mejupụtara DNA tandem dị mfe usoro ikwugharị na protein ndị metụtara ya. Telomeres na-arụ ọrụ dị mkpa n'ịkwado iguzosi ike n'ezi ihe nke usoro mkpụrụ ndụ ihe nketa na nkwụsi ike chromosomal. N'oge nkewa sel ọ bụla, telomeres na-eji nwayọọ nwayọọ na-ebelata n'ihi njedebe nke usoro mmegharị DNA. Mgbe telomeres na-ebelata ruo n'ókè ụfọdụ, mkpụrụ ndụ na-abanye n'ogo senescence ma ọ bụ apoptosis, n'ihi ya, a na-akpọ telomeres n'ụzọ ihe atụ dị ka 'elekere cellular nke ndụ.'
Ọgụgụ 1 Epitalon belatara ọkwa ROS intracellular.
(2) Ụzọ nke Telomere Ịgbatị
Telomerase ụzọ
Telomerase bụ mgbagwoju ribonucleoprotein nwere ọrụ transcriptase ntụgharị. Ọ nwere ike iji RNA nke ya dị ka ndebiri iji megharịa telomere ikwugharị usoro ma tinye ha na nsọtụ chromosomes, si otú ahụ na-ejigide ogologo telomere. N'ime sel mmadụ nkịtị, ọrụ telomerase dị obere ma ọ bụ na-anọghị ya, telomeres na-eji nwayọọ nwayọọ na-ebelata site na nkewa sel ọ bụla. Otú ọ dị, n'ọtụtụ mkpụrụ ndụ tumor, telomerase na-emegharịghachi, na-eme ka mkpụrụ ndụ tumo gbasaa ruo mgbe ebighị ebi ma nweta anwụghị anwụ. Na medulloblastoma nke mbụ metastatic ụmụaka, ụfọdụ mkpụrụ ndụ etuto na-achịkwa elongation telomere site na ịgbalite telomerase. Ihe dị ka 10.7% nke medulloblastomas metastatic na-ebute telomerase activation site na mgbanwe mgbanwe TERT na UTSS hypermethylation, si otú ahụ na-enweta elongation telomere.
Usoro nke ALT
Na mgbakwunye na ụzọ telomerase, enwere usoro telomerase na-adabere na ya nke a maara dị ka ụzọ ntụgharị ogologo nke telomeres (ALT). Ụzọ a bụ isi na-ebute site na nkwụsị ATRX ma na-arụ ọrụ dị mkpa na ụfọdụ mkpụrụ ndụ tumo. Na medulloblastoma nke mbụ metastatic nke ụmụaka, ihe dịka 32.1% nke ikpe na-enweta telomere elongation site na usoro ALT, yana 30% nke ihe atụ na-egosipụta nhichapụ nuklia ATRX, si otú a na-eme ka ụzọ ALT rụọ ọrụ.
(3) Epitalon na usoro nke Telomere Elongation
Mmetụta Epitalon na Telomerase
Epitalon bụ peptide dị mkpụmkpụ sịntetị nke mejupụtara amino acid anọ (alanine, glutamic acid, aspartic acid na glycine), dabere na peptide eke Epithalamion ewepụtara na gland pineal. Nnyocha na-egosi na Epitalon nwere ike imetụta ogologo telomere site na ịkpali ọrụ telomerase. Otu ìgwè ndị nchọpụta Russia chọpụtara na mbụ na 1980 na Epitalon nwere ike kpalie telomerase, enzyme nke na-ahụ maka ichekwa na ịgbatị telomeres na njedebe nke chromosomes. Ọ bụ ezie na ugbu a enweghị ihe akaebe doro anya na Epitalon nwere ike ịgbatị telomeres ozugbo n'ime mmadụ, ụfọdụ nnwale egosila na ọ nwere ike ịbawanye ọrụ telomerase. Mmụba ọrụ telomerase pụtara na enwere ike ịhazi ọtụtụ usoro nkwugharị telomere ma tinye ya na nsọtụ chromosomes, nwere ike ibelata ọnụego telomere dị mkpụmkpụ na ọbụna nweta elongation telomere.
Ọgụgụ 2 Epitalon chebere ọrụ nke mitochondria n'oge post-ovulatory oocyte ịka nká na vitro.
Usoro Epitalon nke ụzọ mgbaàmà intracellular
Ụzọ nrịbama nke intracellular na-etolite netwọk dị mgbagwoju anya nke na-emekọrịta ihe iji chịkwaa usoro cellular dị ka uto, mmụba, na ịka nká. Epitalon nwere ike imetụta elongation telomere n'ụzọ na-edoghị anya site na ịhazi ụzọ mgbaàmà ndị a. Dịka ọmụmaatụ, ọ nwere ike imetụta ụzọ ndị metụtara nhazi usoro okirikiri cell, na-akwalite usoro nchebe maka telomeres n'oge nkewa sel. Na mgbakwunye, dị ka antioxidant, Epitalon na-ebelata mmepụta nke ụdị oxygen na-emeghachi omume (ROS) n'ime sel. Mkpokọta ROS nwere ike imebi DNA, si otú ahụ na-emetụta nkwụsi ike telomere. Site n'iwetu ọkwa ROS, Epitalon na-enyere aka ịnọgide na-enwe nhazi na ọrụ nke telomeres, na-emepụta ọnọdụ dị mma maka elongation telomere.
(4) Ihe akaebe nnwale maka ọrụ Epitalon na Telomere Elongation
Nnwale sel vitro
Nnwale omenala in vitro cell, ịgbakwụnye Epitalon na usoro omenala mere ka ọrụ telomerase dịkwuo elu na ụfọdụ sel. Ndị nchọpụta gbakwunyere Epitalon na ntinye nke 0.1 mM na usoro omenala cell. Mgbe oge ịkọ ihe, a chọpụtara na ọkwa ọkwa nke mkpụrụ ndụ ihe nketa telomerase na sel abawanyela, na-egosi na Epitalon nwere ike ịkwalite njikọ ma ọ bụ ịgbalite telomerase. Na mgbakwunye, nha nke ogologo telomere gosiri na, ma e jiri ya tụnyere ndị na-ahụ maka njikwa na-enweghị Epitalon, ọnụ ọgụgụ mkpirisi telomere dị na otu nnwale ejirila nwayọ nwayọ, na sel ụfọdụ, a hụrụ ntakịrị ogologo telomere.
Nnwale anụmanụ
N'ime nnwale anụmanụ, a na-enye Epitalon n'anụmanụ nnwale (dị ka ụmụ oke) site na ịgba ọgwụ mgbochi ma ọ bụ nchịkwa ọnụ, a na-enyocha mkpụrụ ndụ anụ ahụ ha. Nsonaazụ gosiri na ọrụ telomerase na ụfọdụ anụ ahụ (dị ka imeju na akụrụ) na-eme ka ọ dịkwuo mma, na ogologo telomere ka kwụsiri ike. N'ime ọmụmụ nke mkpụrụ ndụ imeju òké, a chọpụtara na ụmụ oke ejiri Epitalon na-agwọ ọrịa nwere nnukwu ọrụ telomerase dị elu n'ime sel imeju ma e jiri ya tụnyere ndị a na-adịghị agwọ ọrịa, na mgbe nlele anya na-aga n'ihu ruo ọtụtụ ọnwa, ogo nke telomere na-ebelata n'ime sel imeju dị ntakịrị karịa na otu a na-adịghị agwọ ọrịa. Nke a na-egosikwa na Epitalon nwere mmetụta dị mma na elongation telomere na anụmanụ.
Ọdịnaya metụtara mgbochi ịka nká
(1) Usoro nke ịka nká
Nchegbu Oxidative na ịka nká
Ka afọ na-abawanye, nguzozi redox n'ime sel na-akụghasị, na-eduga n'ịchịkọta ụdị oxygen na-emeghachi omume (ROS). ROS nwere akụrụngwa oxidative siri ike, nke nwere ike oxidizing biomolecules cellular dị ka protein, lipids, na DNA, na-ebute mmebi n'usoro na ọrụ cellular. Ndị na-edozi oxidized nwere ike ịkwụsị ọrụ ndụ ha nke ọma, lipids oxidized nwere ike imebi mmiri na nkwụsi ike nke akpụkpọ ahụ cellular, na DNA oxidative mmebi nwere ike iduga mmụgharị mkpụrụ ndụ ihe nketa na arụrụ ọrụ cellular, nke niile na-eme ka usoro ịka nká nke mkpụrụ ndụ na akụkụ ahụ dịkwuo elu.
Cellular ịka nká na apoptosis
Senescence cell na apoptosis bụ ihe omume dị mkpa na usoro ịka nká. Mgbe a na-ekpughere mkpụrụ ndụ n'ọnọdụ nrụgide dị iche iche (dịka nrụgide oxidative, mmebi DNA, wdg), ha na-abanye n'ọnọdụ uche. Àgwà nke mkpụrụ ndụ senescent gụnyere njide okirikiri cell, mgbanwe metabolic, na nzuzo nke cytokines kpọmkwem. Ka ọ dị ugbu a, apoptosis bụ usoro ọnwụ cell emebere nke na-arụ ọrụ dị mkpa n'ịkwado homeostasis anụ ahụ. Otú ọ dị, ka afọ na-abawanye, usoro nhazi nke apoptosis nwere ike imebi, ma ọ bụ oke ma ọ bụ ezughị ezu apoptosis nwere ike iduga n'ịda mbà nke anụ ahụ, n'ikpeazụ na-egosipụta dịka ịka nká.
Telomere Shortening na ịka nká
Dịka e kwuru na mbụ, mkpirisi telomere bụ otu n'ime akara ngosi nke ịka nká. Ka mkpụrụ ndụ na-aga n'ihu na-ekewa, telomeres ji nwayọọ nwayọọ na-ebelata. Mgbe telomeres ruru ogologo oge dị oke egwu, sel na-akwụsị nkewa wee banye n'ọnọdụ mmetụta. Mkpirisi Telomere nwekwara ike ịkpalite mmeghachi omume mmeghachi omume DNA n'ime mkpụrụ ndụ, na-eme ka ịka nká na apoptosis dịkwuo elu, si otú ahụ na-emetụta usoro ịka nká nke akụkụ ahụ.
Ọgụgụ 3 Mmetụta Epitalon na mmalite apoptosis na post-ovulatory ịka nká oocytes.
(2) Usoro mgbochi ịka nká nke Epitalon
Ọrụ Antioxidant
Epitalon bụ antioxidant dị irè nwere ikike antioxidant tụnyere melatonin. Ọ nwere ike ịgbawa ROS ozugbo n'ime sel, na-ebelata mmebi oxidative na biomolecules nke ROS kpatara. N'ime nnwale in vitro na-eji oocytes òké, ịgbakwunye 0.1 mM Epitalon na usoro omenala mere ka mbelata dị ukwuu na ọkwa ROS intracellular. Mbelata nke ROS na-enyere aka ịnọgide na-enwe iguzosi ike n'ezi ihe nke akpụkpọ ahụ cell, ọrụ protein nkịtị, na nkwụsi ike DNA, si otú ahụ na-egbu oge ịka nká. Na mgbakwunye, Epitalon nwere ike ịkwalite ikike antioxidant nke cell site na ịhazi ọrụ nke sistemu enzyme antioxidant intracellular (dị ka superoxide dismutase na catalase), si otú ahụ na-ebelata mmebi nke nrụgide oxidative na-akpata.
Na-achịkwa ọrụ mitochondrial
Mitochondria bụ ụlọ ike nke mkpụrụ ndụ, na ọnọdụ ọrụ ha nwere njikọ chiri anya na ịka nká cellular. N'ime afọ, ọrụ mitochondrial ji nwayọọ nwayọọ na-agbada, na-egosipụta site na mbelata akpụkpọ anụ mitochondrial, mbelata mmepụta ATP, yana mmụba ROS ọgbọ. Epitalon nwere ike ịbawanye ikike nke mitochondrial na mitochondrial DNA oyiri nọmba, si otú ahụ kwalite ọrụ mitochondrial. N'ime nnwale ịka nká nke in vitro site na iji oocytes òké, oocytes emeso ya na Epitalon gosipụtara ikike nke mitochondrial membrane dị elu nke ukwuu yana mụbaa ọnụọgụ DNA mitochondrial mgbe awa 12 na 24 nke ịka nká gasịrị ma e jiri ya tụnyere ndị a na-agwọghị ya. Nke a na-egosi na Epitalon nwere ike ịnọgide na-arụ ọrụ mitochondrial nkịtị ma belata ịka nká nke cellular nke mitochondrial dysfunction kpatara. Ọrụ mitochondrial emelitere na-enyekwa aka ịnọgide na-enwe nguzozi ike nke cellular, na-enye ume zuru oke maka mmemme physiological nkịtị yana igbu oge ịka nká.
Na-egbochi apoptosis
Cell apoptosis na-arụ ọrụ dị mkpa na usoro ịka nká. Oke cell apoptosis nwere ike iduga mbelata nke anụ ahụ na ọrụ akụkụ ahụ. Epitalon na-ahazi ụzọ mgbaàmà metụtara apoptosis intracellular iji belata ihe omume apoptosis cell. N'ime nnwale ịka nká nke in vitro na-eji òké oocytes, mgbe awa 24 nke ịka nká in vitro gasịrị, ọnụ ọgụgụ apoptosis nke oocytes n'ime ìgwè a na-agwọ Epitalon dị obere karịa nke ahụ na-adịghị agwọ ọrịa. Enwere ike ịsị na nke a bụ ikike Epitalon iji gbochie mmalite nke akara apoptosis site na usoro dịka ibelata ọkwa ROS na imeziwanye ọrụ mitochondrial, si otú ahụ belata apoptosis na inyere aka ịnọgide na-arụ ọrụ anụ ahụ nkịtị na akụkụ ahụ, na igbu oge ịka nká.
(3) Ihe akaebe nnwale nke mmetụta mgbochi ịka nká nke Epitalon
Mmetụta nchebe na oocytes
N'ime nyocha nyocha mmetụta Epitalon na ogo oocyte, a chọpụtara na Epitalon na-echebe nke ọma oocytes site na mmebi metụtara ịka nká mgbe ovulation gasịrị. Ka oge post-ovulation na-abawanye, ikike mmepe nke oocytes na-ebelata nke nta nke nta. Mgbe agbakwunyere 0.1 mM Epitalon na usoro omenala, a na-enyocha ogo oocyte mgbe awa 6, 12 na 24 nke omenala gasịrị. Nsonaazụ gosiri na ọgwụgwọ Epitalon belatara nke ukwuu ugboro nke ntụpọ spindle na nkesa nke cortical granules na-adịghị mma, ebe ọ na-abawanye ikike nke mitochondrial na mitochondrial DNA oyiri nọmba, yana ibelata apoptosis oocyte. Nke a na-egosi na Epitalon nwere ike igbu oge usoro ịka nká in vitro nke oocytes, jikwaa ịdịmma ha na ikike mmepe ha, ma nye ọkwa ọkwa cell nke mmetụta mgbochi ịka nká nke Epitalon.
Mmetụta na ịka nká n'ozuzu anụmanụ
N'ime nnwale anụmanụ, mgbe nchịkwa Epitalon ogologo oge gasịrị site na inye nri ma ọ bụ ịgba ọgwụ mgbochi, ahụrụ mmelite n'ọtụtụ ihe na-egosi ịka nká na ụmụ oke. Tụnyere ụmụ oke njikwa na-anaghị agwọ ọrịa, ụmụ oke ndị Epitalon gwọchara gosipụtara denser, ajị na-enwu enwu, mmegharị ahụ emelitere, yana ụfọdụ ogo ogologo ndụ. Nyocha nke pathological nke anụ ahụ òké gosiri na mmebi cellular na ọkwa ịka nká na akụkụ ahụ dị mkpa dị ka imeju na akụrụ nke ụmụ oke Epitalon na-agwọ dị ntakịrị karịa ndị nọ n'òtù njikwa. Nke a na-egosi na Epitalon ọ bụghị nanị na-egosipụta mmetụta mgbochi ịka nká na ọkwa cellular kamakwa ọ na-ebelata usoro ịka nká na ọkwa anụ ahụ, na-eme ka ahụike anụmanụ dịkwuo mma na ndụ ndụ.
Atụmanya ngwa nke Epitalon
Ngwa enwere ike na mpaghara ahụike
Ọgwụ mgbochi ịka nká
Dabere na nchoputa nyocha Epitalon na telomere elongation na mgbochi ịka nká, ọ nwere ike bụrụ ọgwụ ọhụrụ na-egbochi ịka nká. Site n'ọkwawanye nke ịka nká nke ọha mmadụ, ọchịchọ maka ọgwụgwọ mgbochi ịka nká na-eto eto. Epitalon na-egbu oge ịka nká cellular site na ọtụtụ usoro, na-enye nghọta ọhụrụ maka mmepe ọgwụgwọ na-ezubere ọrịa ndị metụtara afọ dịka ọrịa obi na akwara ozi na ọrịa neurodegenerative. Maka ọrịa neurodegenerative, Epitalon nwere ike ichedo neurons site na mmebi nrụgide oxidative ma nọgide na-enwe ogologo telomere, si otú a na-ebelata ịka nká na ọnwụ nke neuronal, na-eme ka mgbaàmà ọrịa dịkwuo mma, na ịkwalite ndụ ndị ọrịa.
Imelite ahụike ọmụmụ
Na ngalaba nke ọgwụ ịmụ nwa, Epitalon nwere mmetụta nchebe ụfọdụ na oocytes. Ka ụmụ nwanyị na-aka nká, ogo oocyte na-ebelata, na-abawanye ohere nke ịmụghị nwa na mmepe nwa ebu n'afọ. Epitalon nwere ike igbu oge oocyte ịka nká ma melite ogo oocyte, na-enye usoro nkwado ọhụrụ maka teknụzụ ọmụmụ enyere aka dị ka in vitro fatịlaịza. Site n'ịgbakwụnye Epitalon n'oge omenala in vitro oocyte, a na-atụ anya na ọ ga-eme ka ọnụego fatịlaịza na ogo nzụlite embrayo na-abawanye, si otú ahụ na-abawanye ọnụego ọganihu nke mmeputakwa enyere aka na inyere ndị di na nwunye aka imezu ọchịchọ ha ịmụ ụmụ.
Mmechi
Epitalon na-egosipụta ikike dị ịrịba ama na telomere elongation na mgbochi ịka nká. Ọ bụ ezie na a ka nwere ụfọdụ okwu na-achọkwu nyocha na mkpebi, ihe ọ pụtara na ma echiche sayensị na ngwa mmekọrịta mmadụ enweghị ike ileghara anya. Ka nyocha na-aga n'ihu na-amụbawanye, a kwenyere na Epitalon ga-ewetakwu ihe ịtụnanya na ọganihu na ngalaba ahụike mmadụ.
Isi mmalite
[1] Teterin O, Gv S. Epitalon[J]. 2023. https://www.researchgate.net/publication/370060637_Epitalon.
[2] Yue X, Liu SL, Guo JN, et al. Epitalon na-echebe megide mmebi ịka nká post-ovulatory nke òké oocytes in vitro[J]. Ịka nká (Albany Ny), 2022,14 (7): 3191-3202.DOI: 10.18632 / ịka nká.204007.
[3] Minasi S, Baldi C, Pietsch T, et al. Telomere elongation site na mgbakwunye ọzọ ịgbatị telomeres (ALT) na telomerase activation na medulloblastoma mbụ metastatic nke nwata [J]. Akwụkwọ akụkọ Neuro-Oncology, 2019,142 (3): 435-444.DOI: 10.1007 / s11060-019-03127-w.
Ngwaahịa dị maka naanị nyocha:
