Bya Cocer Peptides 
omwezi gumu emabega
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okutwalira awamu
TB 500, era emanyiddwa nga Thymosin Beta-4, ye peptide erimu amino acids 43. Kikola kinene nnyo mu nkola ez’enjawulo ez’omubiri mu mubiri gw’omuntu naddala mu kudda engulu kw’ebinywa. TB 500 yasooka kwawulwa okuva mu bitundu bya thymus, era okunoonyereza kulaga nti erina emirimu emikulu egy’okulungamya mu kutambula kw’obutoffaali, okukola emisuwa, n’okuddaabiriza ebitundu.
Okusinziira ku ndowooza y’ensengekera ya molekyu, omutendera gwa amino asidi ogw’enjawulo ogwa TB 500 guwa emirimu egy’enjawulo egy’ebiramu. Okutebenkera kw’enzimba yaayo kugisobozesa okukuuma emirimu mu mbeera ez’enjawulo ez’omubiri, okussaawo omusingi gw’omulimu gwayo mu kudda engulu kw’ebinywa. Peptide eno esaasaanidde nnyo mu mubiri gwonna, nga erimu obungi obw’amaanyi mu bitundu by’ebinywa, ekiraga akakwate n’emirimu gy’omubiri gw’ebinywa.
Ekifaananyi 1 Obujjanjabi bwa TB4 oluvannyuma lw’okusiba coronary ligation bulongoosa enkola y’emisuwa gy’omutima mu vivo. Ensaasaanya y’okukendeera kw’ekitundu ky’omusuwa gwa kkono (FS).
Enkola TB 500 gy’eyamba okutumbula ebinywa
(1)Enkola y’okusenguka kw’obutoffaali n’okuzza obuggya
Okutumbula okusenguka kw’ebitundu by’omubiri ebiyitibwa myoblast
Oluvannyuma lw’okulumwa ebinywa, okusenguka kw’obutoffaali obukola omubiri (myoblast migration) kikulu nnyo mu kuddaabiriza ekifo ekyonoonese. TB 500 esobola okwesiba ku bikwata ebitongole ku luwuzi lw’obutoffaali, okukola amakubo g’obubonero mu butoffaali, n’okutumbula okusenguka kwa myoblast okugenda mu kifo ekifunye obuvune. Okunoonyereza kulaga nti okugezesa obutoffaali mu vitro, okugattako TB 500 kwanguyiza nnyo sipiidi y’okutambula kwa myoblast era kyongera ku bbanga ly’okusenguka. Enkola eno erimu okuddamu okukola amagumba g’obutoffaali, era TB 500 esobola okulungamya okukola polimeeri n’okuggya polimeeri ya actin, okusobozesa myoblasts okutambula obulungi mu kitundu ky’ebinywa ebyonooneddwa n’okuwa ensibuko y’obutoffaali eyeetaagisa okuddamu okukola ebinywa.
Okukola n’Okwawula Obutoffaali bwa Satellite
Obutoffaali bwa setilayiti butoffaali busibuka mu bitundu by’ebinywa obuyinza okukozesebwa ne bwawulwamu ne bufuuka myoblasts nga ebinywa bifunye obuvune, oluvannyuma ne bikwatagana ne bikola ebinywa ebipya. TB 500 eyongera ku bubonero bw’okukola kw’obutoffaali bwa setilayiti, okutumbula enkyukakyuka yabwo okuva mu mbeera ey’okusirika okudda mu mbeera ey’okukula. Kitereeza okwolesebwa kw’ensonga z’okuwandiika ezikwatagana, nga MyoD ne Myf5, okulungamya obutoffaali bwa setilayiti okutuuka ku njawulo ya myoblast. Mu kugezesa ebisolo, okukuba empiso ya TB 500 mu kitundu mu binywa ebyalumizibwa kyavaamu okweyongera okw’amaanyi mu muwendo gw’obutoffaali bwa setilayiti obukola, awamu n’okulongoosa obungi n’omutindo gw’ebiwuzi by’ebinywa ebipya ebikoleddwa, ekiraga nti TB 500 ekola kinene nnyo mu kutumbula okuddamu okukola kw’ebinywa okutambulizibwa obutoffaali bwa setilayiti.
(2)Enkola y’okuzaala emisuwa
Okuyingiza ensonga y’okukula kw’emisuwa (VEGF) okwolesebwa
Angiogenesis kikulu nnyo mu kuddamu kw’ebinywa, kuba egaba oxygen n’ebiriisa mu bitundu ebifunye obuvune ate nga eggyawo kasasiro w’enkyukakyuka y’emmere. TB 500 esobola okusitula obutoffaali bw’ebinywa n’obutoffaali obutwetoolodde obusimu obuyitibwa mesenchymal cells okulaga vascular endothelial growth factor (VEGF). VEGF ye regulator enkulu ey’okutondebwa kw’emisuwa, etumbula okukula, okusenguka, n’okutondebwa kw’obutoffaali bw’emisuwa. Okunoonyereza kulaga nti mu bitundu by’ebinywa ebijjanjabiddwa ne TB 500, byombi mRNA ne protein expression levels za VEGF ziri waggulu nnyo. Okuyingiza kuno kutuukibwako nga tukola amakubo ag’obubonero ag’enjawulo mu butoffaali, gamba ng’amakubo g’obubonero aga PI3K-Akt ne MAPK. Okukola amakubo gano kitumbula okuwandiika n’okuvvuunula obuzaale bwa VEGF, bwe kityo ne kyongera ku kufulumya VEGF n’okwanguyiza okutondebwa kw’emisuwa emipya, ne kitereeza enkola y’omusaayi eri ebinywa ebifunye obuvune.
Ekifaananyi 2 Enkyukakyuka mu nteekateeka y’okwolesebwa kw’obuzaale bw’embuto, nga zigatta wamu n’okukwatibwa ennyo ensonga z’okunyigirizibwa ez’ebweru n’ez’omunda, zitandika enkyukakyuka ez’enjawulo ez’obulwadde mu mutima gw’omuntu omukulu mu bulamu bwaffe bwonna obw’oluvannyuma lw’okuzaala.
Okutebenkeza ensengekera y’emisuwa emipya
Ng’oggyeeko okuleeta okuzimba emisuwa, TB 500 ekola kinene nnyo mu kutebenkeza ensengekera y’emisuwa emipya. Kitereeza ebitonde n’okuddamu okukola ekitundu ekiyitibwa extracellular matrix (ECM), ekisobozesa emisuwa emipya okwegatta obulungi mu bitundu ebigyetoolodde. TB 500 etumbula okusengejja ebitundu bya ECM nga kolagini ne fibronectin ate nga egerageranya matrix metalloproteinases (MMPs) ne tissue inhibitors zazo (TIMPs), okuziyiza emisuwa emipya okwonooneka olw’okuvunda okuyitiridde. Mu mitendera egy’oluvannyuma egy’okutondebwa kw’emisuwa, ekikolwa kino ekya TB 500 kiyamba okukuuma obulungi n’enkola y’emisuwa emipya, okukakasa nti ebinywa ebifunye obuvune bisigala nga bifuna ebiriisa ebimala n’okutumbula okuddamu kw’ebinywa.
(3) Enkola z’okulwanyisa okuzimba n’okulungamya abaserikale b’omubiri
Okuziyiza Okwolesebwa kw’Ebintu Ebizimba
Obuvune bw’ebinywa buleeta okuddamu okuzimba, era okuzimba okuyitiridde kuyinza okwongera okwonooneka kw’ebitundu by’ebinywa. TB 500 erina obusobozi obuziyiza okuzimba, okuziyiza okulaga ensonga ez’enjawulo ezizimba nga tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), ne interleukin-6 (IL-6). Mu kiseera ky’okuzimba, TB 500 esobola okwesiba ku bikwata ku ngulu w’obutoffaali bw’abaserikale, okukola amakubo g’obubonero obuziyiza okuzimba mu butoffaali, n’okuziyiza okuwandiika n’okuvvuunula obuzaale bwa cytokine obuzimba. Mu bikolwa by’okuzimba ebisolo, oluvannyuma lw’okukozesa TB 500, emiwendo gya TNF-α, IL-1β, ne IL-6 mu bitundu by’ebinywa gyakendeera nnyo, era n’okuyingira kw’obutoffaali obuzimba nakyo kyakendeera. Kino kiraga nti TB 500 ekendeeza ku kuddamu kw’okuzimba oluvannyuma lw’okulumwa ebinywa ng’eziyiza okwolesebwa kw’ensonga ezizimba, bwe kityo n’etumbula okuddamu kw’ebinywa.
Okulungamya enkola y’obutoffaali bw’abaserikale b’omubiri
TB 500 era esobola okulungamya enkola y’obutoffaali bw’abaserikale b’omubiri, okutumbula enkola y’abaserikale b’omubiri esinga okwagala okuddaabiriza ebitundu by’omubiri. Kiyinza okukwata ku polarization ya macrophages, ekizireetera okukyuka okuva ku kika kya M1 ekiyamba okuzimba okudda mu kika kya M2 ekiziyiza okuzimba n’okuddaabiriza. Macrophages ez’ekika kya M2 zisobola okufulumya ensonga ez’enjawulo ez’okukula ne cytokines, nga insulin-like growth factor-1 (IGF-1) ne transforming growth factor-β (TGF-β), eziyamba okutumbula okukula kw’obutoffaali bw’ebinywa n’okuddaabiriza. Okugatta ku ekyo, TB 500 esobola okulungamya enkola ya T lymphocyte, okuziyiza abaserikale b’omubiri okuyitiridde okuziyiza okwonooneka kw’ebinywa by’omubiri gwennyini. Nga ekyusakyusa enkola y’obutoffaali bw’abaserikale, TB 500 ekwasaganya enkola y’abaserikale b’omubiri oluvannyuma lw’okulumwa ebinywa, bwe kityo n’etumbula okuddaabiriza n’okudda engulu kw’ebinywa.
Omulimu gwa TB 500 mu kuddamu okukola ebinywa
(1) Okwanguya Okuddaabiriza Obuvune bw’Ebinywa
Okufunza Obudde bw’Okuddaabiriza
Ka kibeere okunyigirizibwa kw’ebinywa okw’amaanyi oba okukoowa kw’ebinywa okutambula obutasalako, TB 500 esobola okukendeeza ennyo ku budde bw’okuddaabiriza ebinywa okwonooneka. Mu kugezesa ebisolo, oluvannyuma lw’okwonooneka kw’ebinywa, ekibinja ky’okugezesa ekyajjanjabwa ne TB 500 kyalaga omutindo gw’okuwona ogw’amangu ennyo mu kifo ebinywa we byayonooneka. Okwekenenya ebitundu by’omubiri (histological analysis) kwalaga nti ekibinja ky’okugezesa kyalaga ebinywa ebipya bingi n’emisuwa mu bbanga ttono, era okuyingira kw’obutoffaali obuzimba nakyo kyakendeera mangu. Mu kunoonyereza ku bantu, ku bannabyamizannyo abalina okunyigirizibwa kw’ebinywa okuva ku kutendekebwa okw’amaanyi, oluvannyuma lw’okukuba empiso mu kitundu oba okuweebwa mu nkola ya TB 500, abalwadde baategeeza nti emabegako bawummudde obulumi bw’ebinywa n’okukendeeza ennyo ku budde obwetaagisa okuddamu okukola emirimu gy’ebinywa, ne kibasobozesa okudda mu kutendekebwa n’okuvuganya amangu.
Okulongoosa omutindo gw’okuddaabiriza
TB 500 tekoma ku kwanguyiza sipiidi ya kuddaabiriza buvune mu binywa wabula era etumbula omutindo gw’okuddaabiriza. Okuyita mu nkola nga okutumbula okutambula kwa myoblast, okukola n’okwawukana kw’obutoffaali bwa satellite, n’okutondebwa kw’emisuwa, TB 500 efuula ebitundu by’ebinywa ebiddaabiriziddwa mu nsengeka n’emirimu okumpi n’ebinywa ebya bulijjo. Ebiwuzi by’ebinywa ebiddaabiriziddwa bitegekebwa mu ngeri y’emu, era amaanyi g’ebinywa agakonziba n’okugumiikiriza biddamu bulungi. Oluvannyuma lw’okukozesa TB 500 okuddaabiriza ebinywa ebifunye obuvune, enjawulo mu maanyi agasinga obunene ag’okukonziba n’obudde bw’okugumiikiriza obukoowu wakati w’ebinywa ebiddaabiriziddwa n’ebitali bifunye buvune ntono, ekiraga nti TB 500 erongoosa bulungi omutindo gw’okuddaabiriza obuvune bw’ebinywa era n’ekendeeza ku buzibu obw’ekiseera ekiwanvu obw’obuvune bw’ebinywa ku nkola y’enkola y’emirimu gy’omubiri.
(2) Okukendeeza ku bukoowu bw’ebinywa
Enkola y’okulungamya enkyukakyuka y’amasoboza
Okukoowa kw’ebinywa kukwatagana nnyo n’obuzibu bw’okukyusakyusa amaanyi. TB 500 esobola okulungamya enkola z’okukyusakyusa amaanyi mu butoffaali bw’ebinywa, okulongoosa enkola y’okugaba amaanyi era bwe kityo n’ekendeeza ku bukoowu bw’ebinywa. Kitumbula ensengekera y’ebiramu n’enkola ya mitochondrial, okwongera ku muwendo gwa mitochondrial n’emirimu, okusobozesa obutoffaali bw’ebinywa okukola okussa okw’omukka mu ngeri ennungi n’okukola adenosine triphosphate (ATP) nnyingi. Okugatta ku ekyo, TB 500 esobola okulung’amya emirimu gy’enziyiza ezenyigira mu nkyukakyuka ya glucose n’enkyukakyuka ya asidi w’amasavu, okulongoosa enkozesa y’ebirungo ebikola amaanyi. Mu kiseera ky’okukola dduyiro, TB 500 esobola okutumbula okumenyaamenya kwa asidi z’amasavu mu oxidative, okuwa ebinywa amaanyi amangi, okukendeeza ku kukuŋŋaanyizibwa kwa lactic acid, n’okulwawo okutandika kw’obukoowu bw’ebinywa.
Okulungamya ku situleesi ya oxidative
Mu kiseera ky’okukola dduyiro, omuwendo omunene ogw’ebika bya oxygen ebikola (ROS) bikolebwa, ekivaako okunyigirizibwa okw’okwokya (oxidative stress), nga kino kye kimu ku bisinga okuvaako ebinywa okukoowa. TB 500 erina eby’obutonde ebiziyiza obuwuka obuleeta obulwadde, okutumbula emirimu gy’enziyiza eziziyiza obuwuka obuleeta obulwadde mu butoffaali nga superoxide dismutase (SOD) ne glutathione peroxidase (GPx), okukendeeza ku kukuŋŋaanyizibwa kwa ROS, n’okukendeeza ku kwonooneka kw’obutoffaali bw’ebinywa obuva ku situleesi y’okwokya. Mu kugezesa ebisolo, ebisolo ebyasooka okujjanjabwa ne TB 500 byalaga obubonero bwa oxidative stress markers obutono ennyo mu binywa n’obukoowu bw’ebinywa obutono bw’ogeraageranya n’ekibinja ekifuga oluvannyuma lw’okukola dduyiro okumala ebbanga. Okunoonyereza kuno kulaga nti TB 500 ekendeeza ku kwonooneka kw’obutoffaali bw’ebinywa n’okukendeeza ku bukoowu bw’ebinywa ng’etereeza okuddamu kw’okunyigirizibwa okw’okwokya (oxidative stress responses), bwe kityo n’ekuuma enkola y’ebinywa eya bulijjo.
(3) Okutumbula Okukula n’Enkula y’Ebinywa
Okusitula Okukola Protein z’Ebinywa
TB 500 etumbula okukola obutoffaali bw’ebinywa nga ekola ekkubo ly’obubonero bwa mTOR munda mu butoffaali. mTOR ye molekyu enkulu etereeza okusengejja kwa puloteyina, okutumbula ensengekera y’ebiramu mu ribosomal n’emirimu gy’ensonga ezitandika okuvvuunula puloteyina, bwe kityo n’eyongera ku sipiidi y’okusengejja puloteyina mu binywa. TB 500 era etereeza okwolesebwa kw’ensonga z’okuwandiika, omuli NF-κB, ekikwata mu ngeri etali butereevu ku kusengejja obutoffaali bw’ebinywa. Okugezesa okukuza obutoffaali mu vitro kwalaga nti okugattako TB 500 kyayongera nnyo okukola puloteyina mu butoffaali bw’ebinywa. Mu kugezesa ebisolo, ebisolo ebyajjanjabwa ne TB 500 okumala ebbanga eddene byalaga okweyongera okw’amaanyi mu binywa n’amaanyi. TB 500 etumbula okukula n’okukula kw’ebinywa ng’esitula okukola obutoffaali bw’ebinywa.
Okulungamya okukyusa ekika ky’obuwuzi bw’ebinywa
Ebika by’ebinywa byawulwamu ebiwuzi ebinyiga amangu n’ebinyiga mpola, nga bino byawukana mu kukola dduyiro n’engeri y’okukyusakyusa emmere. TB 500 esobola okulung’amya okukyusa ekika ky’obuwuzi bw’ebinywa, n’agilung’amya okugenda mu kkubo erisinga okuyamba okutumbula omutindo gw’emizannyo. Okunoonyereza kulaga nti TB 500 etumbula okwolesebwa kw’obuzaale obukwatagana n’obuwuzi obutambula empola, gamba ng’obuzaale obw’ekika kya myosin heavy chain (MyHC), ate nga buziyiza okwolesebwa kw’obuzaale obukwatagana n’obuwuzi obusika amangu.
Okukozesa TB 500 mu Kuzzaawo Ebinywa
(1) Okukozesa mu Byemizannyo
Okuziyiza n'okuwona obuvune bw'abazannyi
Mu mizannyo egy’okuvuganya, bannabyamizannyo boolekagana n’okutendekebwa okw’amaanyi n’okuvuganya, ekivaamu okulumwa ebinywa. Nga ogaba TB 500 mu ngeri esaanidde nga tonnatendekebwa, okuziyiza ebinywa ku buvune kuyinza okunywezebwa, okukendeeza ku bulabe bw’obuvune ng’okunyigirizibwa kw’ebinywa n’okunyiga. Abazannyi bwe bafuna obuvune mu binywa, okukozesa TB 500 mu budde okujjanjabibwa kiyinza okwanguya okuddaabiriza obuvune, okukendeeza ku budde bw’okuwona, n’okusobozesa bannabyamizannyo okudda amangu mu mpaka. Mu mpaka ezimu ez’emisinde n’omupiira, bannabyamizannyo batandise okugezesa TB 500 okutumbula okuwona obuvune bw’ebinywa era bafunye ebirungi.
Okwongera ku mutindo gw’emizannyo
TB 500 era esobola okutumbula omutindo gw’emizannyo ng’ekendeeza ku bukoowu bw’ebinywa n’okutumbula okukula n’okukula kw’ebinywa. Mu mizannyo egy’okugumiikiriza, TB 500’s regulatory effects on energy metabolism and oxidative stress eyinza okulwawo okutandika kw’obukoowu bw’ebinywa, bwe kityo ne kilongoosa omutindo gw’okugumira embeera z’abazannyi. Mu mizannyo gy’amaanyi, okusitula kwa TB 500 okukola obutoffaali bw’ebinywa n’okulungamya okukyusa ekika ky’obuwuzi bw’ebinywa kiyinza okwongera ku maanyi g’ebinywa n’amaanyi g’okubwatuka.
(2) Okukozesebwa mu ddagala ly’okuddaabiriza
Obujjanjabi bw'okuddaabiriza obuvune mu binywa
Mu ddagala ly’okuddaabiriza, TB 500 esobola okukozesebwa ng’obujjanjabi obw’okugatta ku kuddaabiriza obuvune bw’ebinywa. Ku balwadde abalina obuvune mu binywa obuva ku buvune, okulongoosebwa, oba ensonga endala, okugatta obujjanjabi obwa bulijjo obw’okuddaabiriza n’okukozesa TB 500 kiyinza okutumbula ebiva mu kuddaabiriza. Mu balwadde abalina obuvune mu binywa oluvannyuma lw’okumenya, okukuba empiso mu kitundu oba okugaba TB 500 mu nkola ku mabbali g’obujjanjabi bw’omubiri n’okutendekebwa mu kuddaabiriza kiyinza okwanguya okuddamu amaanyi g’ebinywa n’okukola, bwe kityo ne kikendeeza ku kiseera ky’okuddaabiriza. Abasawo abaddaabiriza basobola okulongoosa enteekateeka z’obujjanjabi bwa TB 500 okusinziira ku mbeera y’omulwadde entongole, omuli ddoozi, emirundi, n’engeri gy’aweebwa, okusobola okutuuka ku bivaamu ebirungi mu kuddaabiriza.
Ekifaananyi 3: Endowooza y‟okukozesa molekyu ezifuluma nga tezinnazaalibwa okuzzaawo enkola y‟ebitundu by‟omubiri mu bakadde.
Obujjanjabi bw’okuzimba ebinywa obukwatagana n’obuzibu bw’obusimu
Endwadde ezimu ez’obusimu, gamba ng’okulumwa omugongo n’obulwadde bwa amyotrophic lateral sclerosis (ALS), ziyinza okuvaako ebinywa okukendeera. TB 500 esobola okukola eky’obujjanjabi ku kukendeera kw’ebinywa okukwatagana n’endwadde z’obusimu ng’etumbula okukula kw’obutoffaali bw’ebinywa n’okuziyiza okufa kw’obutoffaali bw’ebinywa. Mu kugezesa ebisolo, ku bikolwa by’okukendeera kw’ebinywa ebiva ku buvune bw’omugongo, okukozesa TB 500 kwavaamu okulongoosa okw’amaanyi mu ddaala ly’okukendeera kw’ebinywa, ng’obuzito bw’ebinywa n’amaanyi bizzeemu ekitundu.
Mu bufunzi
TB 500 esobola okutumbula ebinywa okuddamu okukola. Okuyita mu nkola nga okutambula kw’obutoffaali n’okuddamu okukola, okukola emisuwa, n’okulungamya okulwanyisa okuzimba n’abaserikale b’omubiri, kikola kinene mu kuddaabiriza obuvune bw’ebinywa, okumalawo obukoowu, n’okukula n’okukula. Mu by’emizannyo, kisobola okuyamba bannabyamizannyo okuziyiza n’okujjanjaba obuvune mu binywa n’okutumbula omutindo gw’emizannyo; mu kisaawe ky’eddagala ly’okuddaabiriza, liyinza okukozesebwa mu kujjanjaba okuddaabiriza obuvune bw’ebinywa n’okujjanjaba okuzimba ebinywa ebikwatagana n’endwadde z’obusimu.
Ensonda
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Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
