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1kits (Ebipipa 10) .
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▎ Enzimba ya TKPV
Ensibuko:PubChem |
IUPAC Ekifunze:H-Lys-Pro-Val-OH Ensengekera ya molekyu: C 16H 30N 4O4 Obuzito bwa molekyu: 342.43g/mol Ennamba ya CAS: 67727-97-3 PubChem CID: 125672. Enkola y’okukuuma eddagala lino Ebigambo ebikwatagana: Msh (11-13);alpha-Msh (11-13);ACTH-(11-13) |
▎ Okunoonyereza kwa KPV
Kiki ekiva mu kunoonyereza kwa KPV?
KPV ye tripeptide eggibwa mu α-melanocyte-stimulating hormone (α-MSH). α-MSH busimu bwa polypeptide obulina emirimu mingi egy’ebiramu, nga bukola kinene mu kulungamya langi y’olususu, okulungamya abaserikale b’omubiri, n’ebintu ebirala. Ng’ekitundu kya α-MSH, KPV ebadde eyawuddwamu era n’esomeseddwa nnyo. Wadde nga waliwo enkulaakulana ekoleddwa mu by’obusawo mu myaka egiyise, obujjanjabi obuyinza okukozesebwa ku bulwadde bw’ekyenda obuzimba (IBD) bukyali tebumatiza, era omuwendo gw’abalongoosebwa gukyali waggulu. N’olwekyo, okuzuula enkola empya era ennungi ez’obujjanjabi kifuuse omulimu ogw’amangu. IBD mulimu obulwadde bw’olubuto obuyitibwa ulcerative colitis, Crohn’s disease, n’ebirala, ebimanyiddwa olw’okuzimba ekyenda okutambula obutasalako era nga bikosa nnyo omutindo gw’obulamu bw’abalwadde. Enkola z’obujjanjabi eziriwo kati mulimu okujjanjaba eddagala n’okulongoosa, naye zombi zirina we zikoma. Mu myaka egiyise, ebikolwa eby’okulwanyisa okuzimba ebya melanocortin peptides nga α-MSH byogerwako mu dextran sulfate sodium (DSS) colitis mu mbeba. Kino kiwa ekisumuluzo ky’okunoonyereza ku busobozi bwa KPV obuziyiza okuzimba. α-MSH erina emirimu nga okulungamya abaserikale b’omubiri n’okukendeeza ku kuzimba, era tripeptide KPV eggibwamu nayo etwalibwa ng’eyinza okuba n’ebintu ebifaanagana eby’okulwanyisa okuzimba.
Enkola y’okukola kwa KPV eri etya?
Enkola y’okukola mu bulwadde bw’olubuto obuyitibwa ulcerative colitis
Okulongoosa okutebenkera n’okunyanguyiza okugaba mu nseke:
KPV (Lys-Pro-Val) ye tripeptide eggibwa mu α-MSH (α-melanocyte-stimulating hormone) era erina ebikolwa ebiziyiza okuzimba ku bulwadde bw’olubuto. Wabula, ekisengejjero kya KPV tekinywevu nnyo mu kiseera ky’okuweebwa mu nseke, ekikosa enkola yaakyo ey’obujjanjabi. Mu kunoonyereza kuno, asidi wa γ-polyglutamic acid (SH-PGA) eyasimbibwa mu cysteamine yakolebwa nga bagatta cysteamine n’ekibinja kya carboxyl ekya γ-PGA. Nga tetukozesezza kirungo kya cross-linking agent, 4% polymer content SH-PGA hydrogel yakolebwa okuyita mu self-cross-linking of sulfhydryl groups. KPV/SH-PGA hydrogel yalaga modulus ya elastic (G’) esinga modulus ya viscous (G'') ekwatagana ku 0.01-10 Hz, nga eraga okutebenkera okulungi okw’ebyuma n’enneeyisa y’okugonza okusala, eky’omugaso mu kugaba mu nseke. Mu kiseera kye kimu, okutebenkera kwa KPV mu SH-PGA hydrogel kwayongezebwa nnyo. Ebitundu 30% byokka ebya KPV bye byafulumizibwa okuva mu KPV/SH-PGA hydrogel mu ddakiika 20, ne bigobererwa enneeyisa y’okufulumya obutasalako [1]..
Okukendeeza ku bubonero bw’obulwadde bw’olubuto:
Okuyita mu kugezesa ku nvunza ezirina obulwadde bw’amabwa obw’olubuto obuleetebwa 2,4,6-trinitrobenzene sulfonic acid (TNBS), enkola y’obujjanjabi eyongezeddwa eya KPV/SH-PGA hydrogel ku bulwadde bw’olubuto yakakasibwa. Oluvannyuma lw’okuweebwa KPV/SH-PGA hydrogel mu nseke, obubonero bw’obulwadde bw’olubuto omuli okugejja n’obubonero bw’omuwendo gw’emirimu gy’obulwadde bwakendeezebwa nnyo. Okugatta ku ekyo, okujjanjaba n’ekirungo kya KPV/SH-PGA hydrogel kyalemesa okukendeera kw’ekyenda ekinene mu nvunza ezaafukibwako TNBS era ne kikendeeza ku mutindo gwa myeloperoxidase mu kyenda. Oluvannyuma lw’okujjanjabwa n’ekirungo kya KPV/SH-PGA hydrogel, enkula y’ekyenda ekinene, omuli ekiziyiza eky’omubiri ekiyitibwa epithelial barrier, crypts, n’obutoffaali bwa goblet obutafudde, yakomezebwawo. Mu kiseera kye kimu, KPV/SH-PGA hydrogel yakendeeza ku kwolesebwa kwa cytokines eziyamba okuzimba nga tumor necrosis factor α ne interleukin 6 [1]..
Enkola y’okukola mu bikolwa by’ebibe eby’obulwadde bw’ekyenda obuzimba
DSS colitis model: Mu DSS colitis model, obujjanjabi ne KPV bwavaako okuwona amangu era ne kwongera nnyo ku kudda engulu mu buzito. Mu by’obutonde, okuyingira kw’okuzimba mu mbeba ezajjanjabwa KPV kwakendeera nnyo, ekyakakasibwa okukendeera okw’amaanyi mu mirimu gya myeloperoxidase (MPO) mu bitundu by’ekyenda ekinene oluvannyuma lw’okujjanjabwa KPV [2]..
CD45RB (hi) okutambuza obulwadde bw’olubuto model:
Okuwagira ebizuuliddwa waggulu, obujjanjabi bwa KPV obw’obulwadde bw’olubuto obukyusiddwa bwaleetawo obulwadde okuwona, okuwona obuzito, n’okukendeeza ku nkyukakyuka mu kuzimba okuva mu ndowooza y’ebitundu by’omubiri [2]..
Omuze gw'ebibe ogwa MC1Re/e:
Mu mbeba eziraga ekirungo ekitakola melanocortin-1 receptor (MC1Re/e), obujjanjabi bwa KPV bwataasa ebisolo byonna mu kibinja ky’obujjanjabi okuva mu kufa mu kiseera ky’obulwadde bw’olubuto bwa DSS. Kino kiraga nti ekikolwa ekiziyiza okuzimba ekya KPV kirabika nga waakiri ekitundu kyetongodde ku bubonero bwa MC1R [2]..
Enkola y’okukola mu kuzimba kw’obutoffaali bw’omubiri obuyitibwa bronchial epithelial cell inflammation
I nhibiting NF-κB obubonero:
Mu butoffaali bw’ennyindo z’omuntu obutafa, peptide eyeekuusa ku melanocortin KPV ne agonist α-MSH eya epithelium y’emikutu gy’empewo (MC3R) byaziyiza NF-κB signaling nga biziyiza okuyingiza kwa nuclear kwa p65RelA n’okukola epithelial MC3R, mu kulondako. Okusingira ddala, ekikolwa kya KPV kikwatagana n’okuyingiza kwayo mu nyukiliya, ekiyinza okuziyiza okukyusakyusa kwa nyukiliya kwa p65RelA ewandiikiddwa ne YFP. Mu kiseera kye kimu, ebifo ebisiba KPV ne Imp-α/β biri ku p65RelA, nga kiyinzika okuba nga kizingiramu okuziyiza importin-α armadillo domains 7 ne 8 [3]..
Enkola y’okukola mu bulwadde bw’omumwa obuva ku ddagala
Ebiziyiza obuwuka, okuzimba, n’okuddaabiriza:
Nga tukozesa PLGA-PEG-PLGA (PPP) ekwata ku bbugumu nga matrix ne epigallocatechin-3-gallate (EGCG) n’enkola ey’obuzaale ey’okulwanyisa obuwuka ng’ekinyweza okunyweza, in-situ mucosal adhesive hydrogel (PPP_E) yategekebwa bulungi. Tripeptide KPV yasaanuusibwa mu solution ennyogovu eya PPP_2% E precursor solution ng’eddagala ery’ekyokulabirako okuteekateeka KPV@PPP_2% E hydrogel. Enkola y’okulwanyisa okuzimba n’obusobozi okutumbula okutambula kw’obutoffaali bwa KPV mu PPP-2% E hydrogel byakuumibwa bulungi. Okugatta ku ekyo, KPV@PPP_2% E yalina amaanyi ag’okulwanyisa obuwuka ku Staphylococcus aureus. KPV@PPP_2% E hydrogel bwe yasiigibwa ku gingival mucosa y’envunza ezirina obulwadde bwa chemotherapy-induced oral mucositis, esobola okukyuka amangu n’efuuka hydrogel n’enywerera ku ngulu w’ekiwundu okumala essaawa 7, okulongoosa ennyo emmere gye balya n’okuzza obuzito bw’envunza. Mu kiseera kye kimu, nga etumbula okwolesebwa kwa CK10 ne PCNA, KPV@PPP_E hydrogel nayo yaddaabiriza bulungi enkula y’ebitundu by’omubiri eby’amabwa. Okugatta ku ekyo, KPV@PPP_2% E hydrogel yaziyiza nnyo cytokines ezizimba omuli IL-1β ne TNF-α, era mu kiseera kye kimu n’etereeza IL-10 [4]..
Ensibuko:PubMed [5] .
Misango ki egy’okukozesa eddagala lya KPV mu bujjanjabi?
Obujjanjabi bw’obulwadde bw’olubuto obuyitibwa ulcerative colitis
Okugaba nga bayita mu hydrogel eyeesalasala:
Mu kunoonyereza, cysteamine-grafted γ-polyglutamic acid (SH-PGA) yasengekebwa n’ekolebwa mu hydrogel okutebenkeza tripeptide KPV [1] . KPV/SH-PGA hydrogel yalaga ebikolwa ebirungi eby’obujjanjabi mu nkola y’envunza ey’obulwadde bw’olubuto obw’amabwa obuleetebwa 2,4,6-trinitrobenzene sulfonic acid (TNBS). Okusingira ddala, oluvannyuma lw’okuweebwa mu nseke, obubonero bw’obulwadde bw’olubuto ng’okugejja n’obubonero bw’omuwendo gw’emirimu gy’obulwadde bwakendeezebwa nnyo, era era kiyinza okuziyiza okukendeera kw’ekyenda ekinene mu nvunza ezaafukibwako TNBS n’okukendeeza ku mutindo gwa myeloperoxidase mu lubuto. Mu kiseera kye kimu, enkula y’ekyenda ekinene, omuli ekiziyiza eky’omubiri ekiyitibwa epithelial barrier, crypts, n’obutoffaali bwa goblet obutakyuse, yakomezebwawo oluvannyuma lw’okujjanjabwa n’ekirungo kya KPV/SH-PGA hydrogel, era hydrogel era yakendeeza ku kwolesebwa kwa cytokines eziyamba okuzimba nga tumor necrosis factor α ne interleukin 6.
Okugaba nga oyita mu haidrogel ow’emikutu ebiri:
Okunoonyereza okulala kwakola dual-network hydrogel (PMSP) ekoleddwa maleated γ-polyglutamic acid ne thiolated γ-polyglutamic acid okuyita mu thiol-maleimide cross-linking ne self-oxidation ya thiols [5] . Hydrogel eno esobola okwekwata mu ngeri ey’enjawulo ku mucosa okuzimba okusinga mucosa omulamu, era erina amaanyi amalungi ag’ebyuma n’okunywerera kw’ebiramu. KPV, ng’eddagala ery’ekyokulabirako, kyangu okukwatibwa PMSP okuyita mu nkolagana y’amasannyalaze, bwe kityo n’ekuuma emirimu gyayo egy’ebiramu okumala ebbanga eddene wansi w’embeera ez’ebbugumu eringi. Mu nvunza ezirina obulwadde bw’olubuto obuleetebwa TNBS, oluvannyuma lw’okuweebwa PMSP-KPV mu nseke, ekikolwa eky’okukendeeza ekya KPV ku bulwadde bw’olubuto kyalongooka nnyo, era ekiziyiza ky’ekyenda ekinene kyaddamu bulungi. Okugatta ku ekyo, PMSP-KPV era yalung’amya ebimera by’ekyenda era n’eyongera nnyo ku bungi bw’obuwuka obw’omugaso mu byenda.
Ku bulwadde bw’okusannyalala kw’omu kamwa obuva ku ddagala
In-situ mucosal adhesive hydrogel (PPP_E) yategekebwa nga ekozesa PLGA-PEG-PLGA (PPP) ekwata ku bbugumu nga matrix ne epigallocatechin-3-gallate (EGCG) nga adhesion enhancer [4] . Tripeptide KPV yasaanuusibwa mu solution ennyogovu eya PPP_2% E precursor solution ng’eddagala ery’ekyokulabirako okuteekateeka KPV@PPP_2% E hydrogel. Hydrogel eno erina eddagala eriziyiza okuzimba, eritta obuwuka, n’okuddaabiriza ku bulwadde bw’omumwa obuva ku ddagala. Okusingira ddala, esobola okukuuma omulimu gw’okulwanyisa okuzimba ogwa KPV n’obusobozi okutumbula okutambula kw’obutoffaali, era erina ekikolwa eky’amaanyi eky’okulwanyisa obuwuka ku Staphylococcus aureus. Oluvannyuma lw’okuweebwa mu nseke z’envunza ezirina obulwadde bw’omumwa obuva ku ddagala, eddagala erisookerwako erya PPP_2% E lyakyuka mangu ne lifuuka hydrogel ne linywerera ku ngulu w’ekiwundu okumala essaawa 7. Obujjanjabi ne KPV@PPP_2% E hydrogel bwalongoosa nnyo emmere n’okuzzaawo obuzito bw’envunza, bwatumbula okwolesebwa kwa CK10 ne PCNA, bwaddaabiriza bulungi enkula y’ebitundu by’omubiri gw’omumwa gwa nnabaana ogulina amabwa, era mu kiseera kye kimu ne buziyiza nnyo obutoffaali obuzimba nga IL-1β ne TNF-α, n’okulinnyisa okwolesebwa kwa IL-10. Hydrogel eno era erina eddagala eritta obuwuka ku biwundu by’amabwa g’omu nnyindo ebirina obulwadde bwa Staphylococcus aureus (MRSA) obuziyiza methicillin, era eziyiza nnyo okuyingira kw’obutoffaali obuzimba mu bitundu by’omubiri ebiri wansi w’omubiri.
Obujjanjabi bw’obulwadde bw’ekyenda obuzimba
Okunoonyereza okumu kulaga nti KPV eyinza okuba eddagala eppya erijjanjaba obulwadde bw’ekyenda ekizimba (IBD) [6] . Mu butoffaali bw’ekyenda ky’omuntu (Caco2-BBE ne HT29-Cl.19A) n’obutoffaali bwa T obw’omuntu (Jurkat), oluvannyuma lw’okusikirizibwa ne pro-inflammatory cytokines, okugattako KPV kuyinza okuziyiza okukola kw’amakubo g’obubonero obuzimba NF-κB ne MAP kinase n’okukendeeza ku kufuluma kwa pro-inflammatory cytokines. Okunoonyereza kuno kwazudde nti KPV ekola okuyita mu hPepT1 eraga mu butoffaali bw’abaserikale b’omubiri n’obw’ekyenda. Okugatta ku ekyo, mu bikolwa by’ebibe eby’obulwadde bw’olubuto obuleetebwa dextran sulfate sodium (DSS) ne TNBS, okuweebwa KPV mu kamwa kuyinza okukendeeza ku kwolesebwa kwa pro-inflammatory cytokines n’okubeerawo kw’obulwadde bw’olubuto.
Mu kumaliriza, ng’ekintu ekikola ebiramu nga kirina obusobozi bungi, KPV eraga ebirungi eby’enjawulo mu kujjanjaba endwadde ez’enjawulo. Mu kitundu ky’obulwadde bw’ekyenda obuzimba, ka kibeere mu kugezesa okw’ekyokulabirako ky’ebibe oba mu kunoonyereza ku nkola ez’enjawulo ez’okugaba obulwadde bw’olubuto obuzimba, KPV esobola bulungi okukendeeza ku kuyingira kw’okuzimba, okulongoosa enkula y’ebitundu by’omubiri, okulungamya okwolesebwa kwa cytokine, n’okukola ebikolwa eby’amaanyi eby’okulwanyisa okuzimba okuyita mu nkola nga entambula ya PepT1. Mu kujjanjaba obulwadde bw’okusannyalala kw’omu kamwa obuva ku ddagala, hydrogel erimu KPV etegekeddwa ne matrix eyeetongodde n’ekinyweza okunyweza tesobola kukoma ku kukuuma mirimu gyayo egy’okulwanyisa okuzimba n’okutumbula okutambula kw’obutoffaali naye era erina obusobozi obw’amaanyi obw’okulwanyisa obuwuka, okulongoosa ennyo obubonero obukwatagana n’envunza n’okutumbula okuddaabiriza ebitundu. Wadde ng’emisango gy’okukozesa KPV mu bujjanjabi mu kiseera kino gikyali mitono, ebivudde mu kunoonyereza okuliwo biraga mu bujjuvu omugaso gwayo mu bujjanjabi. Mu biseera eby’omu maaso, singa okumenyawo kuyinza okutuukibwako mu kunoonyereza okw’obwegendereza ku kulongoosa okutebenkera kw’eddagala n’obulungi bw’okutuusa, okugaziya ebiraga obujjanjabi, n’okunyweza okulondoola n’okuddukanya obujjanjabi, KPV esuubirwa okuleeta enkola z’obujjanjabi ez’omutindo ogwa waggulu era ennungi eri abalwadde bangi era n’okuzannya ekifo ekikulu ennyo mu bujjanjabi obw’obujjanjabi.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Dalmasso G munoonyereza mu by’obusawo, ng’alina endagiriro z’okunoonyereza ezikwata ku ddagala, biochemistry, n’obuzaale, n’ebirala. Abadde akoze mu matendekero ag’amaanyi agawerako, omuli Universite Clermont Auvergne (UCA), CHU Clermont Ferrand, INRAE, Institut National de la Sante et de la Recherche Medicale (Inserm), Clermont Univ, Yunivasite y’eggwanga eya Georgia, Yunivasite y’e Emory, Yunivasite y’e Cote d’Azur, ne Universidad Nacional Rio Cuarto. Ebitongole bino bimanyiddwa nnyo mu mirimu gyabyo, era enkolagana ya Dalmasso G nabo eyambye okutumbula emisomo egyekuusa ku nsonga eno. Ebizuuliddwa mu kunoonyereza kwe biyinza okuba eby’amakulu mangi mu kukulaakulanya ssaayansi w’obusawo naddala mu kulongoosa ebiva mu bujjanjabi bw’endwadde n’omutindo gw’obulamu bw’abalwadde. Dalmasso G ewandiikiddwa mu kiwandiiko ekijuliziddwa [6].
