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1kits (Ebipipa 10) .
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▎ Enzimba ya Tesamoreli
Ensibuko: PubChem |
Omutendera: YADAI F TNSY RKVL GQLS A RK L LQDI M SRQ QGE S NQ E RGA R ARL Ensengekera ya molekyu: C 221H 366N 72O 67S Obuzito bwa molekyu: 5136 g/mol Ennamba ya CAS: 218949-48-5 PubChem CID: 16137828. Enkola y’okukuuma eddagala lino Ebigambo ebifaanagana: Egrifta |
▎ Okunoonyereza ku Tesamoreli
Tesamoreli yali akola ki?
Obusimu bw’okukula bw’omuntu obuyitibwa recombinant human growth hormone (rhGH) bwe bukozesebwa mu kujjanjaba obuzibu bw’obusimu obukula (GH), wadde nga buba n’obulungi mu bujjanjabi, era buwerekerwako ebizibu eby’enjawulo. Embeera eno ereetedde okukola eddagala eriyitibwa human growth hormone-releasing factor (GFR), kubanga liyinza okuba n’okugumira obulungi. Tesamoreli ye GFR ey’obutonde ekoleddwa ng’eddagala eriyinza okujjanjaba endwadde ez’enjawulo eziyinza okuba nga zeekuusa ku bbula lya GH, omuli n’obulwadde bw’amasavu obukwatagana ne siriimu.
Enkola ya Tesamoreli ekola ki?
Enkola y’okukola ku bulwadde bw’ekibumba obutali bwa masavu obukwatagana ne siriimu (NAFLD) .
Okulungamya okulaga kw’obuzaale:
Mu NAFLD ekwatagana ne siriimu, okuyita mu kwekenneenya okugaggawaza ensengekera y’obuzaale, kyazuulibwa nti Tesamoreli yayongera okwolesebwa kw’ensengekera y’obuzaale ey’omukono ekwatagana n’okufuuka oxidative phosphorylation mu kibumba, ate ng’akendeeza ku kwolesebwa kw’obuzaale obukwatagana n’okuzimba, okuddaabiriza ebitundu, n’okugabanya obutoffaali [1] . Okusingira ddala, Tesamoreli yakendeeza ku buzaale bw’ekibumba obukwatagana n’okuzimba, okuddaabiriza ebitundu, n’okugabanya obutoffaali, ekiraga nti ekola ekikolwa kyayo nga etereeza okwolesebwa kw’obuzaale buno.
Okuziyiza abatabaganya abakulu:
Tesamoreli esobola okuziyiza okukola emisuwa emikulu, fibrosis, n’abatabaganya abayamba okuzimba. Okugeza, kiyinza okukendeeza ennyo ku miwendo gy’ensonga y’okukula kw’emisuwa A (VEGFA), ensonga y’okukula kw’emisuwa β1 (TGFB1), n’ensonga 1 (CSF1) ey’okusitula ekibinja ky’obutoffaali obunene (macrophage colony-stimulating factor 1). Mu beetabye mu kugezesebwa abafuna obujjanjabi bwa Tesamoreli, okukendeera mu plasma VEGFA ne CSF1 kwakwatagana n’okukendeera mu bubonero bw’emirimu gy’obulwadde bw’ekibumba egy’amasavu obutali bwa mwenge, ate okukendeera mu TGFB1 ne CSF1 kwakwatagana n’okukendeera mu bubonero bwa fibrosis ku ddaala ly’obuzaale [2] . Nga omulungamya okuwandiika n’okukola kwa monocyte, CSF1 eyinza okufuuka ekigendererwa eky’obujjanjabi ekiyiiya eri NAFLD ekwatagana ne siriimu.
Enkola y’okukola ku buvune bw’obusimu obw’okumpi:
Mu kujjanjaba obuvune bw’obusimu obw’okumpi, Tesamoreli kirowoozebwa nti ayongera ku kuzzaawo obusimu obuyitibwa axonal regeneration, okukendeeza ku kukendeera kw’ebinywa, n’okulongoosa ebiva mu nkola. Okunoonyereza okuliwo kati kulaga nti Tesamoreli ayinza okukozesa ekikolwa kyayo ng’atumbula enkola y’okuzza obuggya obusimu n’okuddaabiriza. Enkola entongole ey’okukola tennategeerekeka bulungi, naye eyinza okuzingiramu okulungamya ensonga z’okukula kw’obusimu, okutumbula okukula kw’obusimu, n’okukola myelination, n’ebirala [3].
Enkola ki entongole Tesamoreli gy’akozesa okukendeeza amasavu mu bitundu by’omubiri n’amasavu mu kibumba mu bantu abalina akawuka ka siriimu?
Enkola y’okulungamya ku busimu bw’okukula
Okusitula okufulumya obusimu bw’okukula:
Tesamoreli busimu obukola obusimu bw’okukula (GHRH), obusobola okusitula okufulumya obusimu bw’okukula. Mu bantu abalina akawuka ka siriimu, okufulumya obusimu bw’okukula kuyinza okukosebwa, era Tesamoreli asobola okutumbula okufulumya obusimu bw’okukula okuva mu nseke y’omu maaso ng’akoppa ekikolwa kya GHRH [4-6]..
Okulungamya enkyukakyuka y’amasavu:
Obusimu obuyamba okukula bukola kinene mu nkyukakyuka y’amasavu. Kiyinza okutumbula okumenya amasavu, okwongera ku oxidation ya fatty acids, n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu. Nga asitula okufulumya obusimu bw’okukula, Tesamoreli ayinza okutereeza mu ngeri etali butereevu enkyukakyuka y’amasavu n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu mu bitundu by’omubiri n’amasavu mu kibumba [4-6]..
Enkosa ku kwolesebwa kw’obuzaale bw’ekibumba
Okukyusa amakubo g’obuzaale:
Okunoonyereza kuzudde nti Tesamoreli asobola okwongera ku kwolesebwa kw’ekibinja ky’obuzaale eky’omukono ekikwatagana n’okufuuka oxidative phosphorylation mu kibumba, ate nga akendeeza ku kwolesebwa kw’ensengekera z’obuzaale ezikwatagana n’okuzimba, okuddaabiriza ebitundu, n’okugabanya obutoffaali [1]..
Okukosa obuzaale obukwatagana n’okuteebereza kookolo w’obutoffaali bw’ekibumba:
Tesamoreli era esobola okulungamya ensengekera z’obuzaale ezikwatagana n’okuteebereza kookolo w’ekibumba, okulinnyisa ensengekera z’obuzaale ezikwatagana n’okuteebereza okulungi n’okukkakkanya ensengekera z’obuzaale ezikwatagana n’okuteebereza okubi, okusinziira ku [1] . Enkyukakyuka zino mu kwolesebwa kw’obuzaale ziyinza okuba nga zeekuusa ku ngeri Tesamoreli gy’ekola ku kukendeeza amasavu mu kibumba.
Enkolagana n’obubonero bw’obuzaale obukwata ku fibrosis:
Mu beetabye mu kugezesebwa abajjanjabwa ne Tesamoreli, enkyukakyuka zino mu kwolesebwa kw’ekibumba zaali zikwatagana n’okulongoosa mu bubonero bw’obuzaale obukwata ku fibrosis. Kino kiraga nti Tesamoreli eyinza okulongoosa embeera y’obuwuzi bw’ekibumba ng’etereeza okulaga kw’obuzaale bw’ekibumba, bwe kityo n’akendeeza ku masavu g’ekibumba [1]..
Enkosa ku puloteyina za plasma
Okuziyiza abatabaganya abakulu:
Tesamoreli esobola okukendeeza ennyo ku miwendo gya puloteyina za plasma nga vascular endothelial growth factor A (VEGFA), transforming growth factor beta 1 (TGFB1), ne macrophage colony-stimulating factor 1 (CSF1) [1] . Proteins zino zeekuusa ku angiogenesis, fibrosis, n’okuzimba, era okuziziyiza Tesamoreli kiyinza okuyamba okukendeeza ku masavu g’ekibumba n’okuzimba.
Enkolagana n’obubonero bw’obulwadde:
Mu beetabye mu kujjanjabwa ne Tesamoreli, okukendeera mu plasma VEGFA ne CSF1 kwakwatagana n’okukendeera mu bubonero bw’emirimu gy’obulwadde bw’ekibumba obutali bwa masavu (NAFLD), ate okukendeera mu TGFB1 ne CSF1 kwakwatagana n’okukendeera mu bubonero bwa fibrosis ku ddaala ly’obuzaale [1] . Kino kiraga nti okulungamya obutoffaali buno mu plasma nga Tesamoreli kuyinza okuba nga kwekuusa ku kulongoosa embeera z’obulwadde bw’ekibumba.
Ensibuko:PubMed [1] .
Tesamoreli ekozesebwa ki?
Ebikosa abantu abalina akawuka ka siriimu
Okukendeeza amasavu mu bitundu by’omubiri n’amasavu mu kibumba:
Okunoonyereza okumu kulaga nti mu bantu abalina akawuka ka siriimu abafuna obujjanjabi bwa integrase inhibitor (INSTIs), okweyongera kw’ebitundu by’amasavu eby’omu lubuto (VAT) kyeraliikiriza, kubanga VAT ekwatagana n’endwadde ezikwatagana wansi ng’obulwadde bw’ekibumba obutali bwa masavu (NAFLD). Tesamoreli, ekirungo ekiyitibwa growth hormone-releasing hormone analog, eragiddwa okukendeeza ku VAT mu bantu abalina akawuka ka siriimu abalina lipohypertrophy ebitundu ebisukka mu 15% mu myezi 6 [7] . Mu kugezesebwa okwafugibwa placebo ku bantu 61 abalina NAFLD ekwatagana ne siriimu, okwekenneenya okwakolebwa oluvannyuma lw’abantu ssekinnoomu abafuna obujjanjabi bwa INSTIs kwazuula nti oluvannyuma lw’emyezi 12, VAT mu kibinja kya placebo yeeyongera ebitundu 10.8%, ate VAT mu kibinja ky’abajjanjabi Tesamoreli yakendeera ebitundu 8.3% okutwalira awamu. Okugatta ku ekyo, ekitundu ky’amasavu mu kibumba (HFF) mu kibinja ekyajjanjabwa Tesamoreli kyakendeera ebitundu 31% okusinziira ku ntandikwa, nga kino kyali kisinga nnyo ku ekyo mu kibinja eky’obujjanjabi bwa placebo [7]..
Okulongoosa omutindo gw’amasavu:
Mu bantu abalina akawuka ka siriimu, mu balwadde abalina omugejjo ogw’omu makkati abakozesa Tesamoreli, density y’amasavu g’omu bitundu by’omubiri (VAT) n’amasavu agali wansi w’olususu (SAT) yeeyongera, era okweyongera kuno kwali kwetongodde ku nkyukakyuka mu bungi bw’amasavu, ekiraga nti Tesamoreli era esobola okulongoosa omutindo gwa VAT ne SAT mu kibinja ky’abalwadde kino [8]..
Enkosa ku nkola y’abaserikale b’omubiri:
Okukozesa Tesamoreli okumala ebbanga eddene kiyinza okukendeeza ku bubonero bw’emirimu gy’obutoffaali bwa T ne monocyte/macrophage mu ntambula y’omusaayi gw’abantu abalina akawuka ka siriimu n’okukendeeza ku makubo g’abaserikale b’omubiri mu kibumba. Okusingira ddala, bw’ogeraageranya n’eddagala eriyitibwa placebo, Tesamoreli yakendeeza ku bungi bw’obutoffaali 13 obutambula, omuli chemokines nnya, cytokines bbiri, molekyu nnya ezikwatagana n’obutoffaali bwa T, awamu ne arginase-1, galectin-9, ne hepatocyte growth factor. Okwekenenya emikutu kwalaga nti waliwo enkolagana ey’okumpi wakati w’amakubo g’obuzaale agavunaanyizibwa ku kukendeeza ku puloteyina zino, era targeted transcriptomics yakakasa downregulation signal y’amakubo g’abaserikale b’omubiri mu kibumba [9]..
Omulimu mu bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge
Okukendeeza amasavu mu kibumba n’okuziyiza obulwadde bwa fibrosis okukula:
Mu bulwadde bw’ekibumba obutali bwa masavu obuva ku siriimu, Tesamoreli ekakasiddwa nti ekendeeza amasavu mu kibumba n’okuziyiza okukula kw’obulwadde bwa fibrosis. Abanoonyereza baakola okwekenneenya okussa essira ku puloteyina za plasma 9 ezikwatagana n’ensengekera z’obuzaale ez’oku ntikko ezikulembedde mu nsengeka z’obuzaale ezifugirwa mu ngeri ey’enjawulo era ne bakizuula nti Tesamoreli yaleetawo okukendeera okw’amaanyi mu nsonga y’okukula kw’emisuwa A (VEGFA), ensonga y’okukula ekyusa β1 (TGFB1), ne macrophage colony-stimulating factor 1 (CSF1). Mu beetabye mu kugezesebwa abajjanjabwa ne Tesamoreli, okukendeera mu plasma VEGFA ne CSF1 kwakwatagana n’okukendeera mu bubonero bw’emirimu gy’obulwadde bw’ekibumba egy’amasavu obutali bwa mwenge, ate okukendeera mu TGFB1 ne CSF1 kwakwatagana n’okukendeera mu bubonero bwa fibrosis ku ddaala ly’obuzaale. Nga omulungamya okuwandiika n’okukola kwa monocyte, CSF1 eyinza okufuuka ekigendererwa eky’obujjanjabi ekiyiiya eri obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge mu siriimu [2]..
Enkosa ku nkola ya transcriptome y’ekibumba:
Nga tukozesa okwekenneenya okugaggawaza ensengekera y’obutonde (gene set enrichment analysis), kyazuulibwa nti Tesamoreli yayongera ku kwolesebwa kw’ekibumba kw’ensengekera y’obuzaale ey’omukono (signature gene set) ekwatagana ne oxidative phosphorylation era n’akendeeza ku kwolesebwa kw’ekibumba kw’obuzaale obukwatagana n’okuzimba, okuddaabiriza ebitundu, n’okugabanya obutoffaali. Okugatta ku ekyo, Tesamoreli era upregulated ne downregulated gene sets ezaalondebwa ezikwatagana n’okuteebereza okulungi n’okubi okwa hepatocellular carcinoma, respectively. Mu beetabye mu kugezesebwa abajjanjabwa ne Tesamoreli, enkyukakyuka zino mu kwolesebwa kw’ekibumba zaali zikwatagana n’okulongoosa mu bubonero bw’obuzaale obukwata ku fibrosis [2]..
Nga synthetic growth hormone-releasing hormone analog, Tesamoreli alaze obusobozi bw’obujjanjabi mu bintu ebiwerako. Mu kumaliriza, okunoonyereza okungi kukakasizza nti esobola bulungi okulung’amya okufulumya obusimu bw’okukula n’okulongoosa enkola y’omubiri gw’omubiri. Mu kujjanjaba endwadde ezeekuusa ku siriimu, kikola kinene ku kukendeeza amasavu agakuŋŋaanyizibwa mu lubuto. Nga esitula okufulumya obusimu bw’okukula n’okulongoosa enkola y’amasavu, ekendeeza ku bungi bw’amasavu mu bitundu by’omubiri awatali kukosa mubiri omugonvu, nga kikola kinene mu kutereeza obutonde bw’omubiri gw’abalwadde. Mu kujjanjaba obulwadde bw’ekibumba obutaliimu masavu, okunoonyereza okumu era kulaga nti busobola okukendeeza ku masavu mu kibumba. Amakulu ga Tesamoreli ga maanyi nnyo. Ku balwadde abalina akawuka ka siriimu, kiwa engeri ennungi ey’okulongoosaamu obuzibu mu nkyukakyuka y’amasavu obuva ku bulwadde n’obujjanjabi, kitereeza omutindo gw’obulamu bw’abalwadde, kiyamba okumalawo puleesa y’eby’omwoyo ereetebwa enkyukakyuka mu ndabika, n’okutumbula okuwulira kwabwe okw’okukwatagana n’abantu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Stanley TL mukenkufu mu Harvard University, akola okunoonyereza n’okusomesa mu matendekero nga Harvard Medical School ne Massachusetts General Hospital. Ebintu by’anoonyerezaako mulimu endocrinology ne metabolism, endwadde ezisiigibwa, immunology, microbiology, n’endya n’emmere. Akoze okunoonyereza okw’obwegendereza mu bintu bino, ng’awa emisingi gy’enzikiriziganya egy’okuzuula, okujjanjaba, n’okuziyiza endwadde ezikwatagana nabyo. Mu kiseera kye kimu, akolagana nnyo n’ebibiina nga Harvard Medical School ne Massachusetts General Hospital for Children, ng’agatta endowooza n’enkola y’obujjanjabi n’okukola ku nsonga z’obusawo. Stanley TL awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [4].
