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1kits (10Vials) .
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▎ TKPV ƒe Dɔwɔɖoɖo
Dzɔtsoƒe:PubChem |
IUPAC si wotsɔ ƒo ƒui:H-Lys-Pro-Val-OH Molekyulãwo ƒe Mɔfiame: C 16H 30N 4O4 Molekyulã ƒe Kpekpeme: 342.43g/mol CAS ƒe xexlẽdzesi: 67727-97-3 PubChem ƒe CID: 125672 Nya siwo sɔ kple wo nɔewo: Msh (11-13);alfa-Msh (11-13);ACTH-(11-13) |
▎ KPV Numekuku
Nukae nye numekuku si wowɔ le KPV ŋu?
KPV nye peptide etɔ̃ si wokpɔ tso α-melanocyte-stimulating hormone (α-MSH) me. α-MSH nye polypeptide lãmetsi si wɔa dɔ vovovowo le nugbagbeŋutinunya me, si wɔa akpa vevi aɖe le ŋutigbalẽ ƒe amadede, dɔlélenutsiŋutete ƒe ɖoɖowɔwɔ, kple akpa bubuwo dzi kpɔkpɔ me. Abe α-MSH ƒe akpa aɖe ene la, woɖe KPV ɖe vovo eye wosrɔ̃ nu tso eŋu tsitotsito. Togbɔ be wowɔ ŋgɔyiyi aɖewo le atikewɔwɔ me le ƒe ʋɛ siwo va yi me hã la, atikewɔmɔnu siwo woate ŋu azã na dɔgbo ƒe dɔléle (IBD) medzea ame ŋu haɖe o, eye amekoko ƒe agbɔsɔsɔ gakpɔtɔ le dzidzim ɖe edzi. Eyata atikewɔwɔmɔnu yeye siwo wɔa dɔ nyuie didi va zu dɔ si hiã kpata. IBD lɔ dɔgbo ƒe dɔléle si nye abi, Crohn ƒe dɔléle, kple bubuawo ɖe eme, siwo ƒe dzesi enye dɔgbo ƒe dɔdzẽ si nɔa anyi didi eye wògblẽa nu le dɔnɔwo ƒe agbenɔnɔ ƒe nyonyome ŋu vevie. Dɔdamɔnu siwo wozãna fifia dometɔ aɖewoe nye atikewo zazã kple amekoko, gake seɖoƒe aɖewo le wo ame evea siaa ŋu. Le ƒe ʋɛ siwo va yi me la, woƒo nu tso melanocortin peptidewo abe α-MSH ene ƒe dɔlékuiwutikewo ŋu le dextran sulfate sodium (DSS) dɔdzẽ me le sisiblisiwo me. Esia naa kpeɖodzi aɖe si dzi woato asrɔ̃ nu tso ŋutete si le KPV ŋu be wòatsi dɔdzẽ nu ŋu. Dɔwɔwɔwo le α-MSH ŋu abe dɔlélenutsiŋutete ƒe ɖoɖowɔwɔ kple dɔdzẽ dzi ɖeɖe kpɔtɔ ene, eye wobu tripeptide KPV si wokpɔ tso eme hã be ɖewohĩ dɔlélenutsiŋutete ƒe ŋutete mawo tɔgbe le esi.
Nukae nye KPV ƒe dɔwɔwɔ ƒe mɔnu?
Mɔnu si wɔa dɔ le dɔdzẽ si me abi le me
Liƒo ƒe liƒo kple dɔgbo me dodo na ame ƒe nyonyo:
KPV (Lys-Pro-Val) nye tripeptide si woɖe tso α-MSH (α-melanocyte-stimulating hormone) me eye wòtsia dzodzodzoetsitsi nu ɖe dɔgbo ƒe dɔléle ŋu. Gake KPV-tikea meli ke kura le edodo ɖe dɔgboa me o, si kpɔa ŋusẽ ɖe eƒe atikewɔwɔ ƒe ŋusẽkpɔɖeamedzi dzi. Le numekukua me la, wowɔ γ-polyglutamic acid (SH-PGA) si wodo cysteamine to cysteamine kple γ-PGA ƒe carboxyl ƒuƒoƒoa tsɔtsɔ ƒo ƒui me. Womezã atike si ƒoa ƒu ɖe wo nɔewo ŋu o la, wowɔ SH-PGA hydrogel si me polymer le 4% to sulfhydryl ƒuƒoƒowo ƒe wo ɖokui tsɔtsɔ ƒo ƒui me. KPV/SH-PGA hydrogel ɖe elastic modulus (G') si kɔ wu viscous modulus (G'') si sɔ kplii fia le 0.01-10 Hz, si ɖe mɔ̃ɖaŋununya ƒe liƒo nyui kple shear thinning nuwɔna fia, si ɖea vi na rectal dodo. Le ɣeyiɣi ma ke me la, wodzi KPV ƒe liƒo le SH-PGA hydrogel me ɖe edzi ŋutɔ. KPV ƒe 30% koe do tso KPV/SH-PGA hydrogel me le miniti 20 me, eye emegbe woɖe asi le eŋu atraɖii ƒe nuwɔna [1]..
Dɔdzẽ ƒe dzesiwo dzi ɖeɖe kpɔtɔ:
To dodokpɔ siwo wowɔ le sisiblisi siwo ŋu abi ƒe dɔdzẽ si 2,4,6-trinitrobenzene sulfonic acid (TNBS) hena vɛ ŋu me la, woɖo kpe atikewɔwɔ ƒe ŋusẽkpɔɖeamedzi si dzi ɖe edzi si KPV/SH-PGA hydrogel kpɔna ɖe dɔdzẽ dzi dzi. Le KPV/SH-PGA hydrogel dodo ɖe dɔgboa me megbe la, woɖe dɔgbo ƒe dzesi siwo dometɔ aɖewoe nye lolo dzi ɖeɖe kpɔtɔ kple dɔléle ƒe dɔwɔwɔ ƒe dzesi ƒe dzesiwo dzi kpɔtɔ ŋutɔ. Tsɔ kpe ɖe eŋu la, atikewɔwɔ kple KPV/SH-PGA hydrogel xe mɔ na dɔgboa ƒe kpuiƒe le sisiblisi siwo wodo TNBS na me eye wòɖe dɔgboa me myeloperoxidase ƒe agbɔsɔsɔ dzi kpɔtɔ. Esi wotsɔ KPV/SH-PGA hydrogel da dɔ nɛ vɔ la, wogakpɔ dɔgboa ƒe nɔnɔme, si me lãmenugbagbeviwo ƒe mɔxenu, crypts, kple goblet cells siwo me gblẽ o hã le. Le ɣeyiɣi ma ke me la, KPV/SH-PGA hydrogel ɖe pro-inflammatory cytokines abe tumor necrosis factor α kple interleukin 6 ƒe ɖeɖefia dzi kpɔtɔ [1]..
Mɔnu si wɔa dɔ le sisiblisi ƒe kpɔɖeŋu siwo wowɔ le dɔgbo ƒe dɔléle si naa dɔdzẽ me
DSS dɔdzẽ ƒe kpɔɖeŋu: Le DSS dɔdzẽ ƒe kpɔɖeŋu me la, atikewɔwɔ kple KPV na wòhaya kaba eye wòna eƒe kpekpeme gahaya ŋutɔ. Le lãmenugbagbeviwo ŋuti nunya gome la, dɔdzẽ ƒe gege ɖe sisiblisi siwo wotsɔ KPV da dɔe me dzi ɖe kpɔtɔ ŋutɔ, si ŋu woɖo kpee to myeloperoxidase (MPO) ƒe dɔwɔwɔ dzi ɖeɖe kpɔtɔ ŋutɔ le dɔgbo ƒe lãkusi me le KPV zazã vɔ megbe [2] ..
CD45RB (hi) ƒe dɔlékuiwo ƒe ʋuʋu ƒe kpɔɖeŋu:
Esi míeɖo kpe nusiwo ŋu woke ɖo le etame dzi la, KPV-dɔdamɔnu na dɔgbo ƒe dɔléle si wotsɔ yi teƒe bubu na dɔlélea gahaya, eƒe kpekpeme gahaya, eye wòɖe dɔdzẽ ƒe tɔtrɔwo dzi kpɔtɔ le lãmenugbagbeviwo ƒe nukpɔsusu nu [2]..
MC1Re/e mouse ƒe kpɔɖeŋu:
Le mi siwo ɖea melanocortin-1 xɔla si mewɔa dɔ o (MC1Re/e) fiana me la, KPV zazã ɖe lã siwo katã le atikewɔwɔ ƒe ƒuƒoƒoa me tso ku me le DSS dɔdzẽ me. Esia ɖee fia be edze abe KPV ƒe ŋusẽkpɔɖeamedzi si tsia dzodzodzoetsitsi nu ƒe akpa aɖe ya teti le eɖokui si le MC1R ƒe dzesiwo gbɔ ene [2]..
Mɔnu si wɔa dɔ le aɖuɖɔtoe me lãmenugbagbeviwo ƒe dɔdzẽ me
I nhibiting NF-κB dzesiwo:
Le amegbetɔ ƒe aɖuɖɔtoe me lãmenugbagbevi siwo mekuna o me la, peptide si do ƒome kple melanocortin si nye KPV kple agonist α-MSH si nye yaƒoƒomɔ̃ ƒe lãkusi (MC3R) xe mɔ na NF-κB ƒe dzesiwo to mɔxexe ɖe p65RelA ƒe nuklia ƒe tsɔtsɔ yi duta nu kple lãmenugbagbeviwo ƒe MC3R ƒe dɔwɔwɔ me. Etɔxɛe la, KPV ƒe ŋusẽkpɔɖeamedzi do ƒome kple eƒe nuklia tsɔtsɔ yi duta, si ate ŋu axe mɔ ɖe p65RelA si wotsɔ YFP de dzesii ƒe nuklia ƒe ʋuʋu nu. Le ɣeyiɣi ma ke me la, KPV kple Imp-α/β ƒe kadodoƒewo le p65RelA dzi, ɖewohĩ esia lɔ mɔxexe ɖe importin-α armadillo domenyinyi 7 kple 8 nu ɖe eme [3]..
Mɔnu si dzi wòtona wɔa dɔ le nu me ƒe ʋumenugbagbeviɣidɔ si atikewɔmɔnu hena vɛ me
Dɔlékuiwutikewo, dɔlékuiwutikewo, kple wo dzadzraɖo ƒe ŋusẽkpɔɖeamedziwo:
Esi wozã PLGA-PEG-PLGA (PPP) si sea dzoxɔxɔ nu abe matrix ene eye epigallocatechin-3-gallate (EGCG) si me dɔlékuiwutikewo ƒe dɔwɔwɔ le dzɔdzɔme nu le abe nusi doa ŋusẽ nulénu ene la, wodzra in-situ mucosal adhesive hydrogel (PPP_E) ɖo dzidzedzetɔe. Wotsɔ tripeptide KPV la ƒo ɖe PPP_2% E ŋgɔdonya ƒe tsi fafɛ me abe kpɔɖeŋutike ene tsɔ dzra KPV@PPP_2% E hydrogel ɖo. Wolé dɔlékuiwutike ƒe dɔwɔwɔ kple ŋutete si le esi be wòado lãmenugbagbeviwo ƒe ʋuʋu ɖe ŋgɔ le KPV me le PPP-2% E hydrogel me la me nyuie. Tsɔ kpe ɖe eŋu la, KPV@PPP_2% E la kpɔ dɔlékuiwutike sesẽ aɖe ɖe Staphylococcus aureus ŋu. Ne wotsɔ KPV@PPP_2% E hydrogel la de sisiblisi siwo ŋu atikewɔmɔnu ƒe nu me ʋumenugbagbeviɣidɔ le ƒe aɖuɖɔtoe me la, ate ŋu atrɔ kabakaba azu hydrogel eye wòalé ɖe abi la ƒe anyime gaƒoƒo 7, si ana sisiblisiwo ƒe nuɖuɖu kple woƒe kpekpeme ƒe hayahaya nanyo ɖe edzi ŋutɔ. Le ɣeyiɣi ma ke me la, to CK10 kple PCNA ƒe ɖeɖefia dodo ɖe ŋgɔ me la, KPV@PPP_E hydrogel la dzra gingiva si me abi le ƒe lãmenugbagbeviwo ƒe nɔnɔme hã ɖo nyuie. Gakpe ɖe eŋu la, KPV@PPP_2% E hydrogel xe mɔ ɖe dɔdzẽ ƒe cytokines siwo dometɔ aɖewoe nye IL-1β kple TNF-α nu vevie, eye le ɣeyiɣi ma ke me la, edo IL-10 ɖe dzi [4]..
Dzɔtsoƒe:PubMed [5] .
Nukae nye KPV atikewo zazã le atikewɔnyawo me?
Dɔléle si nye abi ƒe dɔdzẽ dada
Ezazã to hydrogel si wotsɔa eɖokui ƒoa ƒui dzi:
Le numekuku aɖe me la, wowɔ γ-polyglutamic acid (SH-PGA) si wotsɔ cysteamine ƒoe eye wowɔe wòzu hydrogel be wòana tripeptide KPV nali ke [1] . KPV/SH-PGA hydrogel ɖe atikewɔwɔ ƒe ŋusẽkpɔɖeamedzi nyuiwo fia le sisiblisi ƒe kpɔɖeŋu si wowɔ le abi ƒe dɔdzẽ si 2,4,6-trinitrobenzene sulfonic acid (TNBS) hena vɛ ŋu. Etɔxɛe la, le dɔgbo me dodo vɔ megbe la, dɔgbo ƒe dɔléle ƒe dzesiwo abe lolo dzi ɖeɖe kpɔtɔ kple dɔléle ƒe dɔwɔwɔ ƒe dzesi ƒe dzesiwo dzi ɖe kpɔtɔ ŋutɔ, eye ate ŋu axe mɔ ɖe dɔgboa ƒe kpuiƒe hã nu le sisiblisi siwo wodo TNBS na me eye wòaɖe dɔgbo me myeloperoxidase ƒe agbɔsɔsɔ dzi akpɔtɔ. Le ɣeyiɣi ma ke me la, wogagbugbɔ dɔgboa ƒe nɔnɔme, si me lãmenugbagbeviwo ƒe mɔxenu, crypts, kple goblet cells siwo me gblẽ o hã le, le atikewɔwɔ kple KPV/SH-PGA hydrogel megbe, eye hydrogel la ɖe pro-inflammatory cytokines abe tumor necrosis factor α kple interleukin 6 hã ƒe ɖeɖefia dzi kpɔtɔ.
Dɔwɔwɔ to dual-network hydrogel dzi:
Numekuku bubu wɔ dual-network hydrogel (PMSP) si wowɔ to maleated γ-polyglutamic acid kple thiolated γ-polyglutamic acid me to thiol-maleimide cross-linking kple self-oxidation of thiols me [5] . Hydrogel sia ate ŋu alé ɖe lãkusi si me dɔdzẽ le ŋu koŋ tsɔ wu be wòalé ɖe lãkusi si le lãmesẽ me ŋu, eye mɔ̃ɖaŋununya ƒe ŋusẽ nyui kple nugbagbeviwo ƒe ƒoƒo ɖe eŋu. KPV, abe kpɔɖeŋutike ene, PMSP léa nu bɔbɔe to elektrikŋusẽ ƒe kadodo me, si wɔnɛ be eƒe nugbagbewo ƒe dɔwɔwɔ nɔa anyi didi wu le dzoxɔxɔ gã ƒe nɔnɔmewo me. Le sisiblisi siwo ŋu dɔgbo ƒe dɔléle si TNBS hena vɛ gome la, le PMSP-KPV dodo ɖe dɔgboa me megbe la, KPV ƒe ŋusẽkpɔɖeamedzi si ɖea dɔgbo ƒe dɔléle dzi kpɔtɔna la nyo ɖe edzi ŋutɔ, eye wogaɖo dɔgboa ƒe lãkusi ƒe mɔxenu la anyi nyuie. Tsɔ kpe ɖe eŋu la, PMSP-KPV hã ɖɔa dɔgboa me numiemiewo ɖo eye wòna nugbagbevi suesue siwo ɖea vi ƒe agbɔsɔsɔ ɖe dɔgboa me dzina ɖe edzi ŋutɔ.
Le atikewɔmɔnu ƒe nu me ʋumenugbagbeviɣidɔ ta
Wowɔ in-situ mucosal adhesive hydrogel (PPP_E) tsɔ zã PLGA-PEG-PLGA (PPP) si sea dzoxɔxɔ nu abe matrix ene eye epigallocatechin-3-gallate (EGCG) abe adhesion enhancer ene [4] . Wotsɔ tripeptide KPV la ƒo ɖe PPP_2% E ŋgɔdonya ƒe tsi fafɛ me abe kpɔɖeŋutike ene tsɔ dzra KPV@PPP_2% E hydrogel ɖo. Hydrogel sia tsia dɔlékuiwutikewo, dɔlékuiwutikewo, kple nuwo ɖɔɖɔɖo ƒe ŋusẽkpɔɖeamedzi ɖe nu me ƒe ʋumenugbagbeviɣidɔ si atikewo zazã hena vɛ dzi. Etɔxɛe la, ate ŋu alé KPV ƒe dɔlékuiwutike ƒe dɔwɔwɔ ɖe te kple ŋutete si le esi be wòado lãmenugbagbeviwo ƒe ʋuʋu ɖe ŋgɔ, eye wòakpɔ dɔlékuiwutike ƒe ŋusẽkpɔɖeamedzi sesẽ ɖe Staphylococcus aureus ŋu. Esi wodoe ɖe sisiblisi siwo ŋu atikewɔmɔnu ƒe nu me ʋumenugbagbeviɣidɔ le ƒe aɖuɖɔtoe me vɔ la, PPP_2% E ŋgɔdonya ƒe tsi la trɔ kabakaba zua hydrogel eye wòléna ɖe abi la ŋu gaƒoƒo 7 sɔŋ. KPV@PPP_2% E hydrogel ƒe atikewɔwɔ na lãwo ƒe nuɖuɖu ɖuɖu kple woƒe kpekpeme ƒe hayahaya nyo ɖe edzi ŋutɔ, edo CK10 kple PCNA ƒe ɖeɖefia ɖe ŋgɔ, edzra gingiva si me abi le ƒe lãmenugbagbeviwo ƒe nɔnɔme ɖo nyuie, eye le ɣeyiɣi ma ke me la, exe mɔ ɖe dɔdzẽ ƒe cytokines abe IL-1β kple TNF-α ene nu vevie, eye wòdo IL-10 ƒe ɖeɖefia ɖe dzi. Hydrogel sia kpɔa ŋusẽ ɖe dɔlékuiwutikewo hã dzi le abi siwo le aɖuɖɔtoe me siwo ŋu Staphylococcus aureus (MRSA) si te ŋu nɔa te ɖe methicillin nu hã dzi, eye wòxea mɔ na lãmenugbagbevi siwo naa dɔdzẽ ƒe gege ɖe lãkusi te la me vevie.
Dɔgbo ƒe dɔléle si naa dɔdzẽ dada
Numekuku aɖewo ɖee fia be KPV ateŋu anye atike yeye si woatsɔ ada dɔgbo ƒe dɔléle (IBD) [6] . Le amegbetɔ ƒe dɔgbo ƒe lãmenugbagbeviwo (Caco2-BBE kple HT29-Cl.19A) kple amegbetɔ ƒe T lãmenugbagbeviwo (Jurkat) me la, le ŋusẽdodo kple pro-inflammatory cytokines megbe la, KPV tsɔtsɔ kpe ɖe eŋu ate ŋu axe mɔ ɖe NF-κB kple MAP kinase inflammatory signaling pathways ƒe dɔwɔwɔ nu eye wòaɖe pro-inflammatory cytokines ƒe dodo dzi akpɔtɔ. Numekukua ɖee fia be KPV wɔa dɔ to hPepT1 si woɖena fiana le dɔlélenutsiŋutete kple dɔgbo ƒe lãmenugbagbeviwo me. Tsɔ kpe ɖe eŋu la, le sisiblisi ƒe kpɔɖeŋu siwo wowɔ le dɔgbo ƒe dɔléle si dextran sulfate sodium (DSS) kple TNBS hena vɛ ŋu me la, KPV nono ate ŋu aɖe dɔlékuiwutike siwo doa alɔ dɔdzẽ ƒe ɖeɖefia kple dɔdzẽ ƒe dzɔdzɔ dzi akpɔtɔ.
Le nyataƒoƒo me la, abe atike si wɔa dɔ le nugbagbewo me si ŋu ŋutete gã aɖe le ene la, KPV ɖea viɖe tɔxɛwo fiana le dɔléle vovovowo dada me. Le dɔgbo ƒe dɔléle si naa dɔdzẽ ƒe akpa dzi, eɖanye le sisiblisi ƒe kpɔɖeŋu dodokpɔwo me alo le atikewɔwɔmɔnu vovovowo didi me na abi ƒe dɔdzẽ o, KPV ate ŋu aɖe dɔdzẽ ƒe gege ɖe lãme na ame dzi akpɔtɔ nyuie, ana lãmenugbagbeviwo ƒe nɔnɔme nanyo ɖe edzi, aɖɔ cytokine ƒe ɖeɖefia ɖo, eye wòawɔ dɔ ɖedzesi siwo tsi tre ɖe dɔdzẽ ŋu to mɔnuwo abe PepT1 ƒe tsɔtsɔ yi teƒe bubuwo ene dzi. Le nu me ƒe ʋumenugbagbeviɣidɔ si atikewɔmɔnuwo hena vɛ dada me la, menye ɖeko hydrogel si me KPV le si wodzra ɖo kple matrix kple adhesion enhancer tɔxɛ aɖe ate ŋu alé eƒe dɔlékuiwutike kple lãmenugbagbeviwo ƒe ʋuʋu dodo ɖe ŋgɔ ƒe dɔwɔnawo me ɖe asi ko o, ke ate ŋu alé dɔlékuiwutike ƒe ŋutete sẽŋu aɖe hã le esi, si ana sisiblisiwo ƒe dzesi siwo do ƒome kplii nanyo ɖe edzi ŋutɔ eye wòdoa lãmenugbagbeviwo ɖɔɖɔɖo ɖe ŋgɔ. Togbɔ be KPV ƒe dɔdamɔnu siwo wozãna fifia mesɔ gbɔ o hã la, numekuku siwo li fifia ɖe asixɔxɔ si le eŋu le atikewɔwɔ me fia bliboe. Le etsɔme la, ne woate ŋu akpɔ ŋgɔyiyiwo le numekuku deto siwo ku ɖe atikewo ƒe liƒo kple wo tsɔtsɔ yi na amewo ƒe dɔwɔwɔ nyuie wu, dɔdamɔnu ƒe dzesiwo keke ɖe enu, kple ŋusẽdodo dɔdaƒewo ƒe ŋkuléle ɖe wo ŋu kple wo dzi kpɔkpɔ ŋu me la, wole mɔ kpɔm be KPV ahe atikewɔwɔmɔnu deŋgɔ kple esiwo wɔa dɔ nyuie wu vɛ na dɔnɔ geɖe eye wòawɔ akpa vevi aɖe le atikewɔnyawo me.
Le Agbalẽŋlɔla La Ŋu
Nusiwo míeyɔ ɖe etame la katã nye esiwo ŋu Cocer Peptides wɔ numekuku le, trɔ asi le wo ŋu eye woƒo wo nu ƒu.
Dzɔdzɔmeŋutinunya ƒe Agbalẽŋlɔla
Dalmasso G nye numekula le atikewɔwɔ me, eye numekuku ƒe mɔfiamewo ku ɖe atikewɔwɔ, nugbagbeŋutinunya, kple domenyiŋusẽfianu, kpakple nu bubuwo ŋu. Ewɔ dɔ le dɔwɔƒe xɔŋkɔ geɖewo me, siwo dometɔ aɖewoe nye Universite Clermont Auvergne (UCA), CHU Clermont Ferrand, INRAE, Institut National de la Sante et de la Recherche Medicale (Inserm), Clermont Univ, Georgia Dukɔa ƒe Yunivɛsiti, Emory Yunivɛsiti, Yunivɛsiti Cote d’Azur, kple Universidad Nacional Rio Cuarto. Dɔwɔƒe siawo xɔ ŋkɔ ŋutɔ le woƒe dɔwo me, eye Dalmasso G ƒe nuwɔwɔ aduadu kple wo kpe ɖe nusɔsrɔ̃ siwo do ƒome kplii ƒe ŋgɔyiyi ŋu. Nusiwo ŋu wòkpɔ le numekukua me ate ŋu aɖe vi ŋutɔ na atikewɔwɔ ŋuti dzɔdzɔmeŋutinunya ƒe ŋgɔyiyi, vevietɔ le dɔlélewo dada me tsonu kple dɔnɔwo ƒe agbenɔnɔ ƒe nyonyome dodo ɖe ŋgɔ me. Woŋlɔ Dalmasso G ɖe nyayɔyɔ ƒe numekugbalẽ me [6].
