1kits (Ebipipa 10) .
| Ebiriwo: | |
|---|---|
| Omuwendo: | |
▎ TB4 kye ki?
TB4, kwe kugamba, analog ya Thymosin Beta-4 (Tβ4) ey’obutonde, ye polypeptide erimu emirimu emigazi egy’ebiramu. Nga etereeza emyenkanonkano y’amaanyi eya actin, etumbula okutambula kw’obutoffaali, okukula, n’okwawukana, bwe kityo ne kikola kinene nnyo mu kuddaabiriza n’okuzza obuggya ebitundu.
TB4 esobola okwanguya okuggalawo ebiwundu by’olususu, okwongera ku kuzimba kwa kolagini, n’okukendeeza ku kutondebwa kw’enkovu. Mu kiseera kino, kikendeeza ku kuzimba mu ndwadde ng’ekibumba eky’amasavu n’okuzimba amawuggwe. Ate era, oluvannyuma lw’okusannyalala kw’omusuwa gw’omutima, kikuuma obutoffaali bw’omutima, kitumbula emisuwa emipya, era kiyamba omutima okukola obulungi.
Okugatta ku ekyo, TB4 erimu obulungi obw’amaanyi, ekola emirimu mingi, n’okukwatagana obulungi n’ebiramu. Kiyinza okukola butereevu ku bitundu ebyonooneddwa, ne kisinga ku bujjanjabi ate nga kikendeeza ku kukwatibwa kw’enkola.
Ng’ekintu ekipya mu ddagala erizza obuggya, TB4 etuwa ebipya ebisoboka mu kujjanjaba endwadde ez’enjawulo. Obusobozi bwayo mu kuddaabiriza emisuwa gy’omutima, okukuuma obusimu, okujjanjaba endwadde z’amaaso, n’okuddukanya okuzimba okutambula obutasalako kigifudde ekifo eky’okunoonyereza ennyo mu by’eddagala erizza obuggya, ekivuga enkulaakulana y’eddagala erizza obuggya okutuuka ku nkola z’obujjanjabi entuufu era ennungi.
▎ Enzimba ya TB4
Ensibuko: PubChem |
Omutendera: LKKTETQ Ensengekera ya molekyu: C 38H 68N 10O14 Obuzito bwa molekyu: 889.0 g/mol Ennamba ya CAS: 885340-08-9 PubChem CID: 62707662. Omuntu w’abantu Ebigambo ebifaanagana: QHK6Z47GTG |
▎ Okunoonyereza ku TB4
Ensibuko y’okunoonyereza ku TB4 eri etya?
TB4 ye peptide entono ekolebwa okuva mu kifo ekikola ekya thymosin β4. Thymosin β4 erina obusobozi bw’okuzza obuggya ebitundu by’omubiri, okulwanyisa okuzimba, n’okuddaabiriza amangu, era TB4 nayo yasikira eby’obugagga bino. Mu kusooka, mu kunoonyereza ku thymosin β4, kyazuulibwa nti erina emirimu mingi egy’ebiramu, ng’ekola emirimu emikulu mu bintu ng’okutambula kw’obutoffaali, okuddaabiriza ebitundu by’omubiri, n’okulungamya okuzimba. TB4 kye kitundu ekikola ekya thymosin β4. Abanoonyereza basuubira nti okuyita mu kunoonyereza ku TB4, basobola okufuna okutegeera okw’amaanyi ku nkola yaayo n’okunoonyereza oba esobola okukolebwa n’efuuka eddagala eririna ebigendererwa ebitongole eby’obujjanjabi.
Mu by’okuddaabiriza ebiwundu n’okwonooneka kw’ebitundu by’omubiri ebiva ku ndwadde ezitawona, enkola z’obujjanjabi ez’ekinnansi zirina we zikoma. Olw’obusobozi bwayo okutumbula okutambula kw’obutoffaali n’okuddaabiriza ebitundu by’omubiri, TB4 efuuse ekifo eky’okunoonyereza, era abantu basuubira nti ejja kuwa ebirowoozo n’enkola empya ez’okujjanjaba endwadde zino. Okugeza, mu kunoonyereza ku ndwadde nga okuzimba emisuwa gy’omutima n’okulumwa obusimu, okunoonyereza kukolebwa okunoonyereza oba TB4 esobola okutumbula okuddaabiriza ebitundu ebyonooneddwa n’okuzzaawo emirimu gyabyo.
Abazannyi batera okufuna obuvune obw’enjawulo nga batendekebwa n’empaka omuli okunyigirizibwa mu binywa n’okulumwa emisuwa. TB4 kirowoozebwa nti esobola okuyamba okwanguya okuddaabiriza obuvune n’okulongoosa sipiidi y’okuwona obuvune mu mizannyo, n’olwekyo esikiriza abantu okufaayo mu kisaawe ky’eddagala ly’ebyemizannyo. Okunoonyereza okumu kugezaako okunoonyereza ku busobozi bw’okukozesa TB4 mu kuddaabiriza obuvune bw’abazannyi. Wabula mu kiseera kye kimu, era ereeseewo okusika omuguwa oba eyinza okukozesebwa obubi ng’okukozesa ebiragalalagala. Olw’okukulaakulanya eddagala, obwetaavu bw’eddagala eppya bweyongera buli kiseera. Nga ekintu kya peptide ekirina enkola ey’enjawulo ey’okukola, TB4 erina obusobozi okukulaakulanyizibwa okufuuka ekika ky’eddagala ekipya, okuwa eby’okulonda ebisingawo ku bujjanjabi obw’obujjanjabi.
Enkola y’okukola kwa TB4 eri etya?
Okutumbula okuddamu okukola ebitundu by’omubiri:
TB4 ye peptide entono ekolebwa okuva mu kifo ekikola ekya thymosin β4. Thymosin β4 erina obusobozi okutumbula okuddamu okukola kw’ebitundu by’omubiri, era TB4 yasikira eky’obugagga kino. Kiyinza okutumbula okuddamu okukola kw’ebitundu by’omubiri mu ngeri zino wammanga:
Okukola amakubo g’obubonero bw’obutoffaali:
Kiyinza okukola amakubo agamu ag’enjawulo agalaga obubonero bw’obutoffaali okutumbula okukula n’okwawukana kw’obutoffaali. Okugeza, kiyinza okukola amakubo g’obubonero agakwatagana n’okukula n’okuddaabiriza obutoffaali, gamba nga ekkubo ly’obubonero erya PI3K/Akt, n’ebirala, bwe kityo ne kisitula okukula n’okwawukana kw’obutoffaali n’okutumbula okuddamu okukola kw’ebitundu [1]..
Okulungamya ekitundu eky’ebweru w’obutoffaali:
Matrix ey’ebweru w’obutoffaali ekola kinene mu kuzzaawo ebitundu by’omubiri. TB4 eyinza okulungamya okusengejja n’okuvunda kw’ekisenge eky’ebweru w’obutoffaali, okutumbula okunywerera kw’obutoffaali, okusenguka, n’okuddamu okukola ebitundu by’omubiri. Okugeza, kiyinza okwongera ku kusengejja kolagini ne elastin, okulongoosa ensengekera n’enkola y’ebitundu by’omubiri [1]..
Ekiziyiza okuzimba:
Okuzimba kwe kuziyiza omubiri okulumwa n’okukwatibwa yinfekisoni, naye okuzimba okuyitiridde kuyinza okuvaako ebitundu by’omubiri okwonooneka. TB4 erina eddagala eriziyiza okuzimba era esobola okuziyiza okukola ebirungo ebizimba. Abatabaganya okuzimba nga cytokines ne chemokines bakola kinene mu kuddamu kw’okuzimba. TB4 eyinza okuziyiza okukola kw’abatabaganya bano abazimba, bwe kityo ne kikendeeza ku kuddamu kw’okuzimba. Okugeza, kiyinza okuziyiza okukola ensonga ezizimba nga tumor necrosis factor-α (TNF-α) ne interleukin-1β (IL-1β) [1]..
Okulungamya enkola y’obutoffaali bw’abaserikale b’omubiri:
Obutoffaali bw’abaserikale bukola kinene mu kuddamu okuzimba. TB4 eyinza okulungamya enkola y’obutoffaali obuziyiza endwadde, gamba ng’okulungamya emirimu gya macrophages ne lymphocytes, bwe kityo ne kikendeeza ku kuddamu kw’okuzimba. Okugeza, kiyinza okutumbula enkyukakyuka ya macrophages mu phenotype anti-inflammatory phenotype era ne kiziyiza okukola n’okukula kw’obutoffaali obuyitibwa lymphocytes [1]..
Okwanguya okukula kw’obutoffaali n’okwawukana:
Nga ekola amakubo g’obutoffaali obulaga obubonero n’okulungamya ekitundu eky’ebweru w’obutoffaali, TB4 esobola okwanguya okukula kw’obutoffaali n’okwawukana, okutumbula okuddaabiriza ebitundu ebyonooneddwa [1]..
Okukendeeza ku kuddamu kw’okuzimba:
Okuddamu kw’okuzimba kujja kulwawo okuddaabiriza ebitundu, era ekikolwa eky’okulwanyisa okuzimba ekya TB4 kisobola okukendeeza ku kuddamu kw’okuzimba, ne kireetawo embeera ennungi ey’okuddaabiriza ebitundu [1]..
Okutumbula okuzimba emisuwa:
Angiogenesis kikulu nnyo mu kuddaabiriza ebitundu by’omubiri. TB4 eyinza okutumbula okutondebwa kw’emisuwa, okwongera omusaayi mu bitundu ebyonooneddwa, okuwa ebiriisa n’omukka gwa oxygen eri obutoffaali, n’okutumbula okuddaabiriza ebitundu [1]..

Okulungamya MMP/TIMP ku bulwadde bw’ekibumba.
Ensibuko:PubMed [3] .
TB4 etereeza etya okusengejja n’okuvunda kw’ekisenge eky’ebweru w’obutoffaali?
Enzikiriziganya wakati w’okusengejja n’okuvunda kw’ekitundu eky’ebweru w’obutoffaali (ECM) kyetaagisa nnyo okukuuma ensengekera n’enkola ya bulijjo ey’ebitundu by’omubiri. TB-500 eyinza okukosa okusengejja kwa matrix ey’ebweru w’obutoffaali mu ngeri zino wammanga:
Okutumbula okuteekebwa kwa kolagini:
TB-500 kirowoozebwa nti esobola okutumbula okuteekebwa kwa kolagini, era kolagini kitundu kikulu nnyo mu matrix ey’ebweru w’obutoffaali. Enkola entongole ey’okukola eyinza okuzingiramu okulungamya amakubo g’obubonero bw’obutoffaali agakwatibwako mu kukola kolagini. Okugeza, kiyinza okutumbula okwolesebwa kw’obuzaale bwa kolagini nga kikola ensonga ezimu ez’okukula oba ensonga eziwandiika, bwe kityo ne kyongera ku kusengejja kolagini [2]..
Okutumbula okwawukana kw’obutoffaali bw’omubiri (endothelial cell differentiation) n’okutondebwa kw’emisuwa:
Obutoffaali bw’omubiri (endothelial cells) bufulumya ebitundu eby’enjawulo eby’omubiri (extracellular matrix components) mu nkola y’okutondebwa kw’emisuwa. TB-500 etumbula okwawukana kw’obutoffaali bw’omubiri (endothelial cell differentiation) n’okutondebwa kw’emisuwa mu bitundu by’olususu, ebiyinza okutumbula obutatereevu okusengejja kw’obutoffaali obw’ebweru w’obutoffaali. Emisuwa emipya egyakolebwa gyetaaga obuwagizi bwa matrix ey’ebweru w’obutoffaali, ekiyinza okusitula obutoffaali okukola ebitundu by’omubiri ebisingawo eby’ebweru w’obutoffaali [2]..
Enkola ku kuvunda kwa matrix ey’ebweru w’obutoffaali:
Kiyinza okulungamya emirimu gya matrix metalloproteinases (MMPs) n’ebiziyiza zo (TIMPs):
Okuvunda kwa matrix ey’ebweru w’obutoffaali okusinga kufugibwa matrix metalloproteinases n’ebiziyiza zo. Wadde nga mu kiseera kino tewali bujulizi butereevu bulaga nti TB-500 etereeza emirimu gya MMPs ne TIMPs, okusinziira ku kuba nti TB-500 erina ebikolwa eby’okutumbula okutambula kw’obutoffaali n’okuwona ebiwundu, era enkola z’okutambula kw’obutoffaali n’okuwona ebiwundu zitera okuwerekerwako okuddamu okukola matrix ey’ebweru w’obutoffaali, kino kiyinza okuzingiramu okulungamya MMPs ne TIMPs. Okugeza, mu kunoonyereza ku fibrosis y’ekibumba, matrix metalloproteinases n’ebiziyiza byabwe ebitongole (kwe kugamba, ebiziyiza ebitundu by’omubiri ebya metalloproteinases, TIMPs) bikola kinene mu kukola n’okusaanuuka kwa kolagini. Nga tuzzaawo bbalansi wakati wa MMPs ne TIMPs, okukuŋŋaanyizibwa kw’ekitundu eky’ebweru w’obutoffaali kuyinza okuziyizibwa, bwe kityo ne kikendeeza ku fibrosis y’ekibumba [3]..
Okulung’amya mu ngeri etali butereevu okuvunda kw’ekisenge eky’ebweru w’obutoffaali nga kikosa enneeyisa y’obutoffaali:
TB-500 esobola okutumbula okutambula kw’obutoffaali obuyitibwa keratinocyte. Mu nkola y’okusenguka kw’obutoffaali, obutoffaali bwetaaga okulungamya okuvunda kw’ekisenge eky’ebweru w’obutoffaali okusobola okugogola ekkubo. Kino kiyinza okuzingiramu okufulumya enziyiza oba ensonga ezimu obutoffaali okulung’amya okuvunda kw’ekisenge eky’ebweru w’obutoffaali. Okugeza, mu nkola ezimu ez’omubiri n’obulwadde, obutoffaali bufulumya matrix metalloproteinases okuvunda matrix ey’ebweru w’obutoffaali okusobola okusenguka [2]..
Mu ngeri ki TB4 gy’ekwataganamu n’ebiramu okutumbula okuddamu okukola kw’ebinywa?
Okufulumya molekyu ezikola ebiramu:
Ebirungo ebiramu bisobola okukola ng’abasitula era ne bikola nga bikwatagana ne TB4 okufulumya molekyu ezikola ebiramu, okutumbula okuddamu okukola kw’ebinywa. Okugeza, ebiramu ebimu bisobola okufulumya ebintu ebikola nga ensonga ezikula. Ebintu bino bikolagana ne TB4 okusitula okukula n’okwawukana kw’obutoffaali bw’ebinywa. TB4 yennyini erina ebiva mu kutumbula okutambula kw’obutoffaali n’okutondebwa kw’emisuwa. Bw’ogattako molekyu ezikola ezifulumizibwa ebiramu, esobola bulungi okutumbula okuddamu okukola kw’ebinywa [4, 5]..
Omulimu gw’ebintu ebikoppa ebiramu:
Ebintu ebikoppa ebiramu bikoppa ensengekera y’obutonde n’enkola y’ebitundu by’ebinywa, ne biwa embeera entonotono entuufu eri TB4. Ebintu nga bino ebikoppa ebiramu bisobola okukwatagana obulungi n’ebitundu by’ebinywa, ne bitumbula ekikolwa kya TB4 mu kifo ekyonoonese. Okugeza, ebintu ebikoppa ebiramu ebirina ensengekera y’obutuli entongole bisobola okuwa obuwagizi eri okukula kw’obutoffaali, era mu kiseera kye kimu, bisobozesa TB4 okusaasaana n’okukola obulungi [4]..
Ekikolwa ky’okukyusa obusimu obuziyiza endwadde:
Ebirungo ebiramu bisobola okutumbula okuddamu okukola kw’ebinywa nga bitereeza abaserikale b’omubiri, nga bikwatagana ne TB4. Okunoonyereza kulaga nti ebiramu bisobola okulung’amya polarization ya macrophages, bwe bityo ne bifuga okuddamu kw’abaserikale b’omubiri n’okutondawo embeera ennungi ey’okuddamu okukola ebinywa. TB4 eyinza okwongera okutumbula enkola eno ey’okukyusa obusimu obuziyiza endwadde nga ekosa emirimu gy’obutoffaali bw’abaserikale b’omubiri. Okugeza, okuyita mu immunomodulation etabaganyizibwa biomaterials, polarization ya macrophages esobola okulung’amibwa okutumbula soft tissue regeneration of the musculoskeletal system, era TB4 eyinza okukola omulimu ogw’okukwatagana mu nkola eno [5]..
Okugatta obutoffaali obusibuka n’ebiramu:
Obutoffaali obusibuka bukola kinene mu kuzzaawo ebinywa. Okugatta wamu n’ebirungo ebiramu ne TB4 kiyinza okuwa enkola y’obujjanjabi ennungi. Ebika by’obutoffaali obusibuka bungi, gamba ng’obutoffaali obusibuka mu mesenchymal n’obutoffaali obusibuka mu masavu, byenyigira mu kuzzaawo ebinywa. Ebirungo ebiramu bisobola okuwa obuwagizi n’obulagirizi eri obutoffaali obusibuka, ate TB4 esobola okutumbula okusenguka, okuwangaala, n’okwawukana kw’obutoffaali obusibuka. Ebisatu bino bwe bigattibwa awamu bisobola okuvvuunuka obuzibu obuli mu kubikozesa byokka ne bitumbula ebinywa okuddamu okukola.
Okutumbula okuddamu okukola kw’obusimu:
Okuzza obuggya obusimu obw’okumpi nakyo kikola kinene mu kuzzaawo ebinywa. Ebirungo ebiramu bisobola okuwa omukutu gw’enzimba okutumbula okuddamu okukola kw’obusimu, era TB4 eyinza okwongera okutumbula okuddamu okukola kw’obusimu n’okuddamu okukola kw’ebinywa nga ekosa okulaga kw’obuzaale okukwatagana n’okutondebwa kw’obusimu. Okugeza, okunoonyereza okumu kuzudde nti ensengekera z’obuzaale ezikwatagana n’okutondebwa kw’obusimu ziteekebwa waggulu, ekiraga omulimu gw’okuzza obuggya obusimu obw’okumpi mu kutabaganya okuddamu amaanyi g’ebinywa, era ebiramu ne TB4 biyinza awamu okutumbula enkola eno [6]..
Okukozesa ebiramu ebiddamu magineeti:
Ebiramu ebipya ebiddamu magineeti bisobola okutumbula okuddamu okukola kw’ebinywa nga bivaako okuweebwa eddagala n’obutoffaali. TB4 esobola okukozesebwa nga egattibwa wamu n’ebiramu ng’ebyo okulongoosa enkola y’okuddaabiriza ebinywa ebyonooneddwa. Okugeza, biphasic iron gel scaffold esobola okukozesebwa okutuusa obutoffaali n’ensonga z’okukula, precisely timing in vivo okutumbula functional muscle regeneration mu kiseera ky’okuzimba. TB4 eyinza okukola mu ngeri ey’okukwatagana n’ekintu kino eky’ebiramu okwongera okutumbula okuddamu okukola kw’ebinywa [7]..
Okutwaliza awamu, nga peptide entono erongooseddwa okuva mu kifo ekikola ekya thymosin β4, TB4 eraga obusobozi obw’ekitalo mu kuzzaawo ebitundu by’omubiri, okulwanyisa okuzimba, n’okuddaabiriza amangu. Okunoonyereza kuzudde nti esobola okutumbula okwawukana kw’obutoffaali bw’omubiri (endothelial cell differentiation), okutondebwa kw’emisuwa (angiogenesis), n’okutambula kw’obutoffaali obuyitibwa keratinocyte, era eyinza n’okulungamya okusengejja n’okuvunda kw’ekisenge ky’obutoffaali obw’ebweru w’obutoffaali. Mu nsonga y’okuddaabiriza ebinywa, TB4 eyinza okuleeta essuubi eppya mu kuddaabiriza obuvune mu mizannyo ng’etumbula okukula n’okwawukana kw’obutoffaali obusibuka mu binywa, okulungamya okuddamu kw’okuzimba, n’okukolagana n’ebiramu. TB4 erina obusobozi okufuuka eddagala eddungi erijjanjaba obuyambi ku kwonooneka kw’ebitundu by’omubiri n’endwadde ezikwatagana nabyo.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Ye J munoonyereza mu yunivasite ya Zhejiang era mmemba mu kibiina kya China Orthopedic Regenerative Medicine Group (CORMed). Ebitundu by’anoonyerezaako mulimu yinginiya, ssaayansi w’ebintu, enkola y’okukola otomatiki n’okufuga, bizinensi n’ebyenfuna, n’enkola z’okubala mu sayansi w’embeera z’abantu. Ye J abadde akolagana n’amatendekero n’ebibiina by’ebyenjigiriza eby’enjawulo, nga Opt Clearing Corp, CTC Holdings, University of Illinois Chicago, ne Dalian Institute of Chemical Physics, CAS. Ye J ewandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [5].
▎ Ebiwandiiko Ebikwatagana
[1] Rahaman K, Muresan A, Omwana J, n’abalala. Okukola enkola z’okwekenneenya TB-500 n’ebirungo ebigikyusakyusa nga bakozesa LC-MS/MS[M]. 2022.10.13140/RG.2.2.32176.02564.
[2] Ho ENM, Kwok WH, Lau MY, n’abalala. Okwekenenya okufuga doping kwa TB-500, enkyusa ey’obutonde ey’ekitundu ekikola ekya thymosin β4, mu musulo gw’embalaasi ne plasma nga bakozesa liquid chromatography-mass spectrometry[J]. Ekitabo ky’eby’obutonde A, 2012,1265:57-69.DOI:10.1016/j.chroma.2012.09.043.
[3] Shan L, Wang F, Zhai D, n’abalala. Matrix metalloproteinases zireeta okuvunda kwa matrix okw’ebweru w’obutoffaali okuyita mu makubo ag’enjawulo okukendeeza ku hepatic fibrosis[J]. Eddagala ly’ebiramu n’eddagala, 2023,161.DOI:10.1016/j.biopha.2023.114472.
[4] Carleton MM, Sefton M V. Okutumbula okuddaabiriza okw’omunda okw’ebinywa by’amagumba nga tukozesa ebiramu ebizza obuggya[J]. Journal of Okunoonyereza ku bintu ebikozesebwa mu by’obujjanjabi ekitundu A, 2021,109 (12): 2720-2739.DOI: 10.1002 / jbm.a.37239.
[5] Ye J, Xie C, Wang C, n’abalala. Okutumbula enkola y’ebinywa n’amagumba okuddamu okukola kw’ebitundu ebigonvu nga tuyita mu kukyusakyusa mu macrophage polarization [J]. Ebikozesebwa mu bulamu, 2021,6 (11): 4096-4109.DOI: 10.1016 / j.bioactmat.2021.04.017.
[6] Roberts K, Kim JT, Huynh T, n’abalala. Transcriptome profiling of a synergistic volumetric ebinywa okufiirwa enkola okuddaabiriza[J]. Bmc Obuzibu bw'ebinywa n'amagumba, 2023,24 (1).DOI: 10.1186 / s12891-023-06401-1.
[7] Cezar C A. Ebiramu ebiddamu magineeti okusobola okutumbula okuddamu okukola ebinywa by’amagumba[M]. 2015.https://www.proquest.com/dissertations-theses/ebirungo-ebiramu-ebiddamu-magineeti-ebinywezeddwa/docview/1761573755/se-2.
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu kisenge (in vitro research) (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.