▎ Okunoonyereza ku Vilon
Vilon y’akola mu kunoonyereza kuliwa?
1. Obwetaavu obw’amangu obw’okunoonyereza ku kukaddiwa n’endwadde
Olw’okukaddiwa kw’abantu mu nsi yonna okwanguwa, ensonga eziwerako ezikwata ku kukaddiwa, gamba ng’okukaddiwa kw’obutoffaali, okukendeera kw’enkola y’ebitundu by’omubiri, n’endwadde z’abakadde obungi, zifuuse ebizibu eby’amangu eby’obujjanjabi ebirina okugonjoolwa. Okukaddiwa kw’obutoffaali kuwerekerwako okufiirwa mpolampola obusobozi bw’okukuuma homeostasis n’okuddaabiriza ebitundu ebyonooneddwa, ekifuula ekikulu ennyo naddala okuzuula ebintu ebiyinza okulwawo enkola y’okukaddiwa kw’obutoffaali n’okutumbula enkola y’okuddaabiriza ebitundu.
Mu kiseera kye kimu, endwadde ennene nga kookolo, sukaali, endwadde z’emisuwa n’ekibumba ziteeka nnyo obulamu bw’omuntu mu matigga. Enkola z’obujjanjabi ez’ekinnansi zirina obuzibu obumu mu kukola ku ndwadde zino, era waliwo obwetaavu obw’amangu obw’okukola enkola empya ez’obujjanjabi n’eddagala. Ng’ekyokulabirako, abalwadde ba kookolo abakadde tebagumiikiriza bulungi bujjanjabi bwa radiotherapy ne chemotherapy, era ekikolwa ky’obujjanjabi tekimatiza. Kyangu okunoonya enkola z’obujjanjabi ez’obuyambi ezitali za bulabe era ezikola obulungi. Mu mbeera enzibu bwetyo, bannassaayansi bakyusizza amaaso gaabwe ku bioactive peptides, nga basuubira okufuna ekifo eky’okumenyawo, era okunoonyereza ku Vilon ne kutandika.
2. Enkulaakulana ey’amaanyi mu kunoonyereza ku Bioactive Peptides
Ebintu bya peptide bibaawo nnyo mu biramu era byetaba mu nkola nnyingi enkulu ez’omubiri, gamba ng’okulaga obubonero bw’obutoffaali, okulungamya abaserikale b’omubiri, n’okulungamya enkyukakyuka mu mubiri. Mu myaka egiyise, olw’okukulaakulana okw’amangu okwa tekinologiya nga molekyu biology ne biochemistry, enkulaakulana ey’amaanyi ekoleddwa mu kunoonyereza ku bioactive peptides.
Bannasayansi basobola okusengejja obulungi, okwawula, n’okuzuula peptides ez’enjawulo, n’okunoonyereza ennyo ku ngeri gye zikolamu. Okunoonyereza kungi kulaga nti peptides ezirina ensengekera ez’enjawulo zirina emirimu egy’enjawulo egy’ebiramu, ekireeta essuubi eppya ery’okugonjoola ebizibu by’ebyobulamu n’endwadde. Mu nkola eno, abanoonyereza basomye ku muwendo omunene ogwa peptides nga bayita mu nkola nga high-throughput screening n’okukakasa emirimu. Vilon, nga dipeptide erimu ensengekera ey’enjawulo n’emirimu egisobola okukolebwa, mpolampola ezze mu ndowooza y’abantu.
3. Okunoonyereza mu bujjuvu ku nkola z’okuddaabiriza n’okuzza obuggya ebitundu by’omubiri
Okuddaabiriza n’okuzza obuggya ebitundu by’omubiri nkola nkulu mu kukuuma emirimu gya bulijjo egy’omubiri gw’ebiramu n’okuddamu obuvune. Wabula wakyaliwo ebituli bingi mu kutegeera enkola eno mu kiseera kino, era engeri y’okutumbula okuddaabiriza n’okuzza obuggya ebitundu by’omubiri mu ngeri ennungi efuuse ekintu ekikulu mu kunoonyereza. Obutoffaali obusibuka bukola kinene mu kuddaabiriza n’okuzza obuggya ebitundu by’omubiri, era okunoonyereza ku nkola yabwo ey’okukola, okukula, n’okwawukana kufunye okufaayo kungi.
Okugatta ku ekyo, ensonga nga okusengejja n’okuvunda kwa matrix ey’ebweru w’obutoffaali n’obubonero wakati w’obutoffaali nabyo birina kinene kye bikola ku kuddaabiriza ebitundu by’omubiri. Mu nkola y’okunoonyereza ku nkola z’okuddaabiriza n’okuzza obuggya ebitundu by’omubiri, abanoonyereza bakizudde nti peptides ezimu zisobola okulungamya enkola zino enkulu. Okusinziira ku kino, okunoonyereza ku peptides ezirina obusobozi okulung’amya okuddaabiriza n’okuzza obuggya ebitundu by’omubiri kubadde kweyongera buli kiseera. Vilon efuuse ekintu ekikulu eky’okunoonyereza mu mulimu guno olw’ebiyinza okuvaamu mu kuwagira okukola n’okukula kw’obutoffaali obusibuka n’okulungamya emirimu gya fibroblast.
Enkola ya Vilon ekola ki?
1. Ebikosa Chromosomes ne Gene Expression
Okutumbula okusumululwa kwa Heterochromatin: Okunoonyereza kulaga nti Vilon esobola okuleeta okusumululwa (deheterochromatization) kwa heterochromatin yonna mu lymphocytes ezikuziddwa ez’abakadde [1] . Kino kitegeeza nti esobola okukola enkola y’okusengejja obuzaale bwa ribosomal obuva ku deheterochromatization y’ekitundu ekitegeka nucleolar n’okufulumya obuzaale obuziyizibwa olw’okusengejja kw’ekitundu kya euchromatin okukola facultative heterochromatin. Mu kiseera kye kimu, Vilon tereeta kusumululwa kwa heterochromatin ekola okwetoloola centromere. Ebivuddemu biraga nti Vilon ejja kukola mpolampola facultative heterochromatin (deheterochromatization) n’emyaka [1]..
2. Emirimu mu Kujjanjaba Endwadde
Obujjanjabi obujjuvu eri abalwadde ba kookolo: Mu kujjanjaba abalwadde ba kookolo abakadde, Vilon eyingizibwa mu nteekateeka y’obujjanjabi ng’ekirungo ekikyusa obusimu obuziyiza endwadde. Ebivudde mu kunoonyereza okusooka biraga nti okukozesa Vilon kuyinza okulongoosa omuwendo gw’abalwadde abawangaala emyaka 2, okuziyiza ebizibu ebiva mu kulongoosebwa, ebizibu eby’ewala, okuddamu, n’okusaasaana kw’ekizimba, n’okulongoosa omutindo gw’obulamu oluvannyuma lw’okujjanjabibwa mu ngeri ey’amaanyi [2]..
Antitumor Effect: Mu kugezesa mu vitro, Vilon erina ekikolwa ekiziyiza okusinziira ku ddoozi ku kukula kw’obutoffaali bw’ekizimba obw’ebika bisatu, okuli kookolo w’olubuto n’omumwa gwa nnabaana gw’omuntu LOVO, kookolo w’olubuto lw’omuntu MKN45, ne kookolo w’ekibumba ky’omuntu QGY7703, naye terina kikolwa kya kuziyiza kya lwatu ku butoffaali obweru obwa bulijjo obw’omuntu [3] . Okugezesa okuziyiza ebizimba mu vivo kulaga nti Vilon erina ekikolwa ekiziyiza okukula kwa kookolo w’ekibumba ky’ebibe H22, era ddoozi ennungi eri 15mg・Kg-1. Bwe bakozesa ddoozi enkulu eya 30mg・Kg-1, omuwendo gw’okuziyiza ebizimba ogwa kookolo w’ekibumba w’ekizimba H22 eyasimbibwa mu mbeba gutuuka ku bitundu ebisukka mu 60% [3]..
Ebikosa abalwadde ba sukaali: Mu balwadde ba sukaali ab’ekika kya I abakadde, Vilon, ng’ekitundu ku bujjanjabi obujjuvu, esobola okulongoosa omulimu gw’okuzimba n’okuziyiza omusaayi, okweyoleka ng’okweyongera mu birimu eddagala ery’obutonde eriziyiza okuzimba omusaayi (antithrombin III ne protein C) n’okusikirizibwa fibrinolysis [4] . Mu kiseera kye kimu, mu mbeera ezisinga, Vilon era esobola okukendeeza ku ddoozi ya insulini eyeetaagisa okutebenkeza enkyukakyuka ya carbohydrate. Okugatta ku ekyo, era esobola okukendeeza ku biri mu butoffaali obuyamba T, obutoffaali bwa NK obusinziira ku T n’obutasinziira ku T, okuzza emiwendo gya T lymphocytes ezikola, B lymphocytes, ne IgA mu mbeera eya bulijjo, era kirina ekikolwa ekitebenkeza abaserikale b’omubiri n’omulimu gw’okuziyiza omusaayi [4]..
3. Ebikosa Emirimu gy’Obutoffaali n’Ebitundu by’Ekitundu
Okusitula okuddamu okukola kw’obutoffaali bw’ekibumba: Mu nkola y’envunza ey’obulwadde bw’ekibumba obuleetebwa obutwa bwa kaboni tetrachloride, Vilon erina kye yeekolera ku kuddamu okukola emirimu gy’obutoffaali bw’ekibumba n’okuddamu okukola ekibumba mu nvunza ezirina obulwadde bw’ekibumba. Nga wayise wiiki bbiri oluvannyuma lw’okusiiga eddagala lino, emirimu gya glucose-6-phosphatase (G6P) mu kibumba ky’envunza ezirina obulwadde bw’ekibumba gikendeera, era Vilon asobola okugyongera. Mu nvunza ezitajjanjabiddwa, ebirimu glycogen yonna n’ebitundu byayo n’emirimu gya G6P bikyali ku ddaala erya pre-cirrhosis. Mu kugezesa kwonna, emirimu gya glycogen phosphorylase (GP) ne glycogen synthase (GS) mu kibumba ky’envunza ezirina obulwadde bw’ekibumba mu bibinja byombi tegirina njawulo ku miwendo egy’okufuga. Vilon erina ekikolwa ekinafu eky’okusitula ku kuzzaawo ekibumba mu nvunza ezirina obulwadde bw’ekibumba, nga kyeyolekera nga omugatte gwa puloteyina n’omutindo gwa ploidy mu hepatocytes z’ekibinja ekyokubiri eky’envunza nga 4.7% ne 11.5% waggulu okusinga eby’ekibinja ekisooka [5]..
Ebikosa ebitundu ebikwatagana n’amasannyalaze: Vilon asitula emirimu gy’okukula kw’obutoffaali bwa thymocytes era n’ayongera ku busobozi bw’okukula kw’obutoffaali obusibuka mu byenda, bwe kityo n’esitula okuddamu okukola oluvannyuma lw’obusannyalazo bw’ebitundu ebikulu. Okugeza, okunoonyereza ku nvunza n’envunza ezitaliiko kamogo ezaafuna obusannyalazo bumu obw’omubiri gwonna (6Gy) kuzudde nti Vilon erina kye yeekolera ku nkula y’enkola y’omubiri (functional morphology of the thymus, spleen, and duodenum) [6]..
4. Emirimu ku Mutendera gwa Molekyulu
Enkola esoboka ey’okusiba ku lususu: Okunoonyereza ku nkola y’enkyukakyuka ya molekyu kulaga nti byombi Vilon (lysylglutamic acid dipeptide) ne thymopoietin (Glu-Trp) birimu ebibanda by’omunnyo mu molekyu mu nsengekera zaabyo, ekikendeeza ku kukyukakyuka kwazo mu nsengekera. Olw’olujegere lw’ebbali olwa aliphatic olwa Lys, Vilon esinga okukyukakyuka. Enkola esoboka ey’okusiba ligand-receptor kwa dipeptide ku luwuzi olusikirizibwa etegeezeddwa, kwe kugamba, okusiba okuyita mu atomu za nayitrojeni ne okisigyeni ezikola omutala gw’omunnyo [7]..
Ebikosa Okwolesebwa kwa Puloteyini mu Kitundu Ekitegeka Nucleolar: Vilon esitula era n’eziyiza okwolesebwa kwa puloteyina za mukenenya mu bitundu ebitegeka nucleolar mu bitundu by’omubiri ebiyitibwa serum tissue ne epithelial cell nuclei, nga zikola oba okukendeeza ku kutondebwa, okukuŋŋaanyizibwa, n’okutambuza ribosomes okutuuka mu cytoplasm, bwe kityo n’esalawo amaanyi g’okusengejja puloteyina mu butoffaali buno. Okugatta ku ekyo, peptide eno era etumbula enkyukakyuka ya thymocytes okufuuka obutoffaali bwa blast obweyongera [8]..
Vilon ekozesebwa ki?
1. Okulwanyisa okukaddiwa
Vilon etwalibwa nga peptide eyinza okuziyiza okukaddiwa eyinza okulwawo okukaddiwa kw’obutoffaali ng’elongoosa enkola y’olubuto, okutumbula enkola y’enziyiza, n’okutumbula okuyingiza ebiriisa. Ng’oggyeeko ekyo, Vilon era kizuuliddwa nti asobola okulongoosa mu ngeri ya kolagini y’olususu n’okukendeeza ku bubonero bw’okukaddiwa kw’olususu. Okunoonyereza kuzudde nti peptide KE (Lys-Glu, Vilon) esobola okwongera ku kitundu eky’okwolesebwa kwa kolagini 1 mu buwangwa bw’ebiwuziwuzi by’olususu ebikaddiye ebitundu 83%; era kyongera ku kitundu ky’okwolesebwa kwa sirtuin 6 mu buwangwa bwa fibroblasts z’olususu ento n’enkadde emirundi 1.6 ne 2.6 [11]..
2. Okuddaabiriza n’okuzza obuggya ebitundu by’omubiri
Vilon eraga obusobozi obw’amaanyi mu kuddaabiriza ebitundu by’omubiri n’okuzza obuggya. Kiyinza okuwagira okukola n’okukula kw’obutoffaali obusibuka, okwanguya okuwona kw’ebiwundu n’okuddaabiriza ebitundu by’omubiri. Okunoonyereza era kuzudde nti Vilon ayinza okutumbula okuddaabiriza olususu, ebyenda n’ebitundu ebirala ng’atereeza emirimu gya fibroblast. Okunoonyereza kulaga nti eddagala eriyitibwa synthetic dipeptide Vilon lyayongerwa mu explant culture medium okuva mu nvunza ez’emyaka egy’enjawulo. Ebivuddemu biraga nti Vilon esobola okuleeta okutebenkera kw’enkula y’ebitundu, okukola okuddamu okukola n’emirimu gy’obutoffaali, era yalina akakwate ak’amaanyi ku explants z’envunza enkadde, ekiraga nti Vilon erina obusobozi mu kuddaabiriza ebitundu [9]..
3. Okukuuma emisuwa n’ekibumba
Vilon era alina akakwate akalungi ku bulamu bw’emisuwa n’ekibumba. Kiyinza okulongoosa enkola y’emisuwa gy’omutima nga kikyusa enkola y’okwolesebwa kw’obuzaale n’okutumbula okuyita kw’emisuwa emitonotono mu ndwadde z’ekibumba, okutumbula okulongoosa okuzimba omusaayi.
4. Okukozesebwa mu Bujjanjabi bwa Kookolo
Obujjanjabi obujjuvu eri abalwadde ba kookolo abakadde: Mu bujjanjabi bw’abalwadde ba kookolo abakadde, Vilon eyingizibwa mu nteekateeka y’obujjanjabi ng’ekirungo ekikyusa obusimu obuziyiza endwadde. Okugeza, mu bujjanjabi obw’enjawulo obw’abalwadde abakadde abalina kookolo w’omumwa gwa nnabaana ne kookolo w’olubuto olunene, ebivudde mu kunoonyereza okusooka biraga nti okukozesa Vilon kuyinza okulongoosa omuwendo gw’abalwadde abawangaala emyaka 2, okuziyiza ebizibu ebiva mu kulongoosebwa, ebizibu eby’ewala, okuddamu, n’okusaasaana kw’ekizimba [2]..
Patient Stratification for Multiple Cancers: The Variation of information fused Layers of Networks algorithm (ViLoN) eyatwalibwa Vilon nkola mpya eyesigamiziddwa ku mutimbagano eyinza okukozesebwa okugatta maapu za molekyu eziwera. Mu nsonga z’okugabanya abalwadde, enkola eno ekakasiddwa ku kugatta ebika by’amawulire eby’enjawulo (gene expression, methylation, copy number), era erina okulongoosa okw’amaanyi ku kusengeka abalwadde, era erina okuvuganya okutambula obutakyukakyuka mu mbeera zonna. Mu bibinja ebitono (rectal adenocarcinoma: 90 cases, esophageal cancer: 180 cases), okuyingizaamu okumanya emirimu egy’emabega (KEGG, GO) kikulu nnyo okutuuka ku bivaamu ebirungi [10]..
5. Okukozesebwa mu kujjanjaba endwadde z’ekibumba
Ebikosa ekibumba ky'envunza ezirina obulwadde bw'ekibumba: Ebikolwa by'okuteekateeka dipeptide 'Vilon' ku kuddamu okukola emirimu gy'obutoffaali bw'ekibumba n'okuddamu okukola ekibumba mu nvunza ezirina obulwadde bw'ekibumba byasomesebwa. Envunza ezirina obulwadde bw’ekibumba obuleetebwa obutwa bwa kaboni tetrachloride okumala emyezi 4 zaaweebwa Vilon (1.7 micrograms/kg) ne zifukibwa buli lunaku okumala ennaku 5. Ebyavudde mu kunoonyereza biraga nti oluvannyuma lwa wiiki bbiri ng’eddagala lino lisiigiddwa, emirimu gya glucose-6-phosphatase (G6P), egyakendeera emirundi 1.2 mu bulwadde bw’ekibumba, gyeyongera wansi w’ekikolwa kya Vilon. Vilon erina ekikolwa ekinafu eky’okusitula ku kuzzaawo ekibumba mu nvunza ezirina obulwadde bw’ekibumba, nga kyeyolekera nga omugatte gwa puloteyina n’omutindo gwa ploidy mu hepatocytes z’ekibinja ekyokubiri eky’envunza nga 4.7% ne 11.5% waggulu okusinga eby’ekibinja ekisooka [5]..
6. Okukozesebwa mu Bujjanjabi bwa Ssukaali
Ebikosa abalwadde ba sukaali abakadde: Vilon, nga thymic mimetic, ekozesebwa ng’eddagala eriyamba mu kujjanjaba mu bujjuvu abalwadde ba sukaali ab’ekika kya I abakadde. Ebivuddemu biraga nti okukozesa Vilon kulongoosa omulimu gw’okuzimba n’okuziyiza omusaayi, nga kyeyolekera ng’okweyongera mu birimu eddagala ery’obutonde eriziyiza okuzimba omusaayi (antithrombin III ne protein C) n’okusikirizibwa kwa fibrinolysis. Emirundi egisinga, Vilon ekendeeza ku ddoozi ya insulini eyeetaagisa okutebenkeza enkyukakyuka ya carbohydrate. Mu kiseera kye kimu, Vilon era ekendeeza ku biri mu butoffaali obuyamba T, obutoffaali bwa NK obusinziira ku T n’obutasinziira ku T, era n’ezzaawo emiwendo gy’obutoffaali bwa T obukola, obutoffaali bwa B, ne IgA mu mbeera eya bulijjo, ekiraga nti Vilon erina ekikolwa ekitebenkeza abaserikale b’omubiri n’enkola y’okuziyiza omusaayi [4]..
7. Enkozesa mu Bujjanjabi bw’Obuvune bw’Emisanvu
Ebikosa ebitundu ebiwunyiriza amasannyalaze: Ebikosa vilon ne epithalon ku nkula y’emirimu gy’envunza n’envunza ezitaliiko kamogo n’envunza ezaafuna obusannyalazo obumu obwa γ-ray obwa 6Gy mu mubiri gwonna bwasomesebwa. Ebivuddemu biraga nti vilon esitula emirimu gy’okukula kw’obutoffaali obuyitibwa thymocytes era n’eyongera ku busobozi bw’okukula kw’obutoffaali obusibuka mu byenda, bwe kityo n’esitula okuddamu okukola oluvannyuma lw’obusannyalazo bw’ebitundu ebikulu [6]..
Mu kumaliriza, nga dipeptide ey’enjawulo, Vilon esobola okulongoosa enkola y’olubuto, okulwawo okukaddiwa, okuyamba mu kuddaabiriza ebitundu by’omubiri n’okuddamu okukola, n’okukuuma obulamu bw’emisuwa n’ekibumba. Era kikola bulungi mu kujjanjaba kookolo, endwadde z’ekibumba, ssukaali, n’obuvune obuva ku masanyalaze.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal Kańduła MM munoonyereza alina akakwate ku matendekero agawerako ag’ekitiibwa, omuli Janssen Pharmaceuticals, BOKU University, BOKU Vienna, Boston University, ne Johannes Kepler University Linz. Okunoonyereza kwe kukwata ku bintu bingi, nga kino kiraga obukugu bwe mu by’emikono. Mu Biochemistry & Molecular Biology, akoze kinene mu kutumbula okutegeera enkola z’obutoffaali n’enkolagana ya molekyu.
Omulimu gwe mu Cell Biology guzingiramu okunoonyereza ku nsengeka n’enkola y’obutoffaali, ekintu ekikulu ennyo mu kukola enkola empya ez’obujjanjabi. Mu Biotechnology & Applied Microbiology, Kańduła MM anoonyezza enkola eziyiiya ez’okukozesa enkola z’obuwuka obutonotono okugonjoola ebizibu eby’omugaso. Okunoonyereza kwe mu Life Sciences & Biomedicine - Other Topics kulaga nti yeenyigira mu nkola ne tekinologiya ow’omulembe ezisukkulumye ku nsalo za ssaayansi ez’ennono. Ekirala, omulimu gwe mu Yinginiya gulaga obusobozi bwe okukozesa emisingi gya ssaayansi mu nkola. Okuyita mu kunoonyereza kwe okw’enjawulo, Kańduła MM akoze kinene mu kibiina kya ssaayansi, ng’akwata ku nkulaakulana y’enzikiriziganya n’okukozesebwa mu nkola mu busawo n’ebiramu. Kańduła MM ewandiikiddwa mu kiwandiiko ekijuliziddwa [10].
