FOX04 DRI 10mg

▎ Enzimba ya FOXO4-DRI

Ensibuko: PubChem

Omutendera: LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG Ensengekera ya molekyu: C 228H 388N 86O64 Obuzito bwa molekyu: 5358g/mol PubChem CID: 168431240. Enkola y’okukuuma eddagala lino Ebigambo ebifaanagana: EX-A7431

▎ Okunoonyereza ku FOXO4-DRI

Kiki ekiva mu kunoonyereza ku FOXO4-DRI?

Okunoonyereza okw’obwegendereza ku kukaddiwa kw’obutoffaali: 

Olw’okunoonyereza okw’obwegendereza okugenda mu maaso ku nkola y’okukaddiwa kw’obutoffaali, kizuuliddwa nti okukaddiwa kw’obutoffaali kukola kinene mu nkola nnyingi ez’omubiri awamu n’okubeerawo n’okukula kw’endwadde. Obutoffaali obukaddiye bujja kukuŋŋaanya era bufulumya cytokines ez’enjawulo n’abatabaganya okuzimba, ne kikosa emirimu gy’obutoffaali obugyetoolodde, era bwe kityo ne kiviirako emirimu gy’ebitundu n’ebitundu by’omubiri okukendeera. N’olwekyo, okuzuula enkola ez’okuyingira mu nkola y’okukaddiwa kw’obutoffaali kifuuse ekifo eky’okunoonyereza.

Okuzuula obutoffaali bwa FOXO4: 

FOXO4 mmemba mu famire ya forkhead box protein O (FOXO) era ekola kinene mu nkola ez’enjawulo ez’ebiramu nga okukula kw’obutoffaali, okwawukana, okufa, n’okuddamu ku situleesi. Okunoonyereza kuzudde nti FOXO4 ekwatagana nnyo n’okukaddiwa kw’obutoffaali, era esobola okukosa enkola y’okukaddiwa kw’obutoffaali ng’etereeza okwolesebwa kw’obuzaale obuddiriŋŋana. Okugeza, FOXO4 esobola okukola okwolesebwa kw’obuzaale obumu obuziyiza obuwuka obuleeta obulwadde n’obuzaale obuddaabiriza DNA, n’eyongera ku buziyiza bw’obutoffaali eri situleesi y’okwokya n’okwonooneka kwa DNA, bwe kityo ne kilwawo okukaddiwa kw’obutoffaali.

Okukebera ebirungo bya molekyu entono: 

Okusinziira ku kutegeera enkola ya puloteyina ya FOXO4, bannassaayansi baatandika okwekenneenya ebirungo bya molekyu entonotono ebisobola okulung’amya emirimu gya FOXO4. Baali basuubira okufuna ekirungo kya molekyu entono ekiyinza okukola mu ngeri ey’enjawulo puloteyina ya FOXO4, bwe kityo ne kikozesa amaanyi gaakyo ag’okulwanyisa okukaddiwa n’okujjanjaba endwadde ezikwatagana nabyo. Oluvannyuma lw’okugezesa okungi n’okulongoosa, ekirungo kya molekyu entono FOXO4-DRI kyasembayo okuzuulibwa. Kisobola okwesiba mu ngeri ey’enjawulo ku puloteyina ya FOXO4, okukola ekkubo lyayo ery’obubonero wansi, n’okukola kinene mu kulungamya okukaddiwa kw’obutoffaali n’emirimu gy’omubiri egyekuusa ku nsonga eno.

Enkola ya FOXO4-DRI ekola ki?

1. Okulwanyisa okukaddiwa

FOXO4-DRI esobola okukola puloteyina ya FOXO4, n’oluvannyuma n’etereeza enkola y’obutoffaali, okukula, n’okufa. Puloteeni ya FOXO4 ekola omulimu omukulu ogw’okulungamya mu butoffaali. Kiyinza okutumbula okuziyiza kw’obutoffaali ku situleesi nga kitereeza okwolesebwa kw’obuzaale obuddiriŋŋana wansi, n’okukendeeza ku kukaddiwa kw’obutoffaali n’okwonooneka. Okugeza, FOXO4 esobola okutumbula okwolesebwa kw’enziyiza eziziyiza obuwuka obuleeta obulwadde n’okukendeeza ku mutindo gw’ebika bya oxygen ebikola mu butoffaali, bwe kityo ne kikendeeza ku kwonooneka kw’okunyigirizibwa okw’okwokya eri obutoffaali ^{[1, 2]} . Okugatta ku ekyo, FOXO4 era esobola okulungamya okwolesebwa kw’obuzaale obukwatagana n’enzirukanya y’obutoffaali, okuziyiza okukula kw’obutoffaali okuyitiridde, n’okukuuma enkyukakyuka y’obutoffaali eya bulijjo n’enkola y’obutoffaali.

2. Enkola y’Ekikolwa mu bulwadde bw’ekisajja obutandika ekikeerezi (Late-Onset Hypogonadism).

Enkolagana ne FOXO4 ne p53: 

Obulwadde bw’ekisajja obutandika ekikeerezi bulwadde obuva ku myaka, era enkola yaago enkulu y’obutakola bulungi bw’obutoffaali bwa Leydig obukaddiye mu nseke. Kizuuliddwa nti forkhead box O (FOXO) transcription factor FOXO4 eraga mu ngeri ey’enjawulo mu butoffaali bwa Leydig obw’omuntu, era okukyusibwa kwayo mu nucleus mu bakadde kukwatagana n’okukendeera kw’okusengejja testosterone. Nga FOXO4 blocker eyeetongodde, FOXO4-DRI esunsulamu okuleeta p53 nuclear exclusion ne apoptosis mu senescent Leydig cells nga etaataaganya enkolagana wakati wa FOXO4 ne p53 ^[1]..

Okulongoosa embeera y’ensigo entonotono: 

Mu mbeba ezikaddiye mu butonde, FOXO4-DRI esobola okulongoosa embeera y’ensigo entonotono n’okukendeeza ku bbula ly’obusimu obuyitibwa testosterone obuva ku myaka. Kino kiraga nti FOXO4-DRI eyinza okuzzaawo enkola eya bulijjo ey’ebitundu by’ensigo nga etereeza ekkubo ly’obubonero erikwatagana n’okukaddiwa kw’obutoffaali bwa Leydig, bwe kityo n’eyongera ku mutindo gw’okufulumya obutoffaali bw’ensigo ^[1]..

3. Enkola y’Ekikolwa mu bulwadde bw’amawuggwe

Okukendeeza ku butoffaali obukaddiye n’okukendeeza ku kwolesebwa kwa SASP: 

Obulwadde bw’amawuggwe obuyitibwa pulmonary fibrosis bulwadde bw’amawuggwe obugenda mu maaso mu bitundu by’omubiri (interstitial lung disease) nga bujjanjabi butono. Okukaddiwa kw’obutoffaali kutwalibwa ng’ekimu ku bintu ebirwaza obulwadde bw’amawuggwe, era okuggyawo obutoffaali obukaddiye kiyinza okulongoosa enkola y’amawuggwe. Mu nkola y’ebibe ey’obulwadde bw’amawuggwe obuleetebwa bleomycin, FOXO4-DRI, okufaananako n’eddagala erikkirizibwa erya pirfenidone, esobola okukendeeza ku butoffaali obukaddiye, okukendeeza ku kwolesebwa kw’ekikula ky’ekyama ekikwatagana n’okukaddiwa (SASP), n’okukendeeza ku nkyukakyuka mu nkula n’okuteekebwa kwa kolagini okuleetebwa bleomycin ^[2]..

Okufuga Ekitundu ky’Ebika by’Obutoffaali: 

FOXO4-DRI esobola okwongera ku kitundu ky’obutoffaali bw’amawuggwe obw’ekika kya 2 (AEC2) ne fibroblasts n’okukendeeza ku kitundu kya myofibroblasts mu muze gw’ebibe ogw’obulwadde bw’amawuggwe obuleetebwa bleomycin. Mu kugezesa mu vitro, bw’ogeraageranya ne layini z’obutoffaali bw’amawuggwe g’amawuggwe g’ebibe n’omuntu, FOXO4-DRI erina omuze omunene ogw’okutta myofibroblasts ezireetebwa transforming growth factor-β (TGF-β) ^[2]..

Okulungamya ekkubo ly’enkolagana ya Extracellular Matrix Receptor: 

Enkola y’okuziyiza eya FOXO4-DRI ku myofibroblasts ereeta okukka wansi w’ekkubo ly’enkolagana y’ebikwata eby’ebweru w’obutoffaali (ECM) mu bulwadde bw’amawuggwe obuleetebwa bleomycin. Kino kiraga nti FOXO4-DRI eyinza okulongoosa enkola y’obulwadde bw’okuzimba amawuggwe ng’etereeza omulembe n’enkyukakyuka ya ECM ^[2]..

FOXO4-DRI etereeza obulwadde bw’amawuggwe obuleetebwa bleomycin (BLM) (PF). (A) Ekifaananyi ekiraga enteekateeka y’okugezesa. (B) Ebifaananyi ebikiikirira ebya sikaani eby’okusiiga haematoxylin-eosin (HE) n’okusiiga Masson trichrome-okusiiga ebitundu by’ebitundu by’amawuggwe.

Ensibuko:PubMed ^{[2] .}

Biki ebikozesebwa mu kukola FOXO4-DRI?

1. Okulwanyisa okukaddiwa

FOXO4-DRI erina omugaso oguyinza okubaawo mu kulongoosa okukendeera kw’emirimu okwekuusa ku myaka. Ng’emyaka gyeyongera, ebitundu by’omubiri n’enkola ez’enjawulo bijja kufuna diguli ez’enjawulo ez’okukaddiwa n’okukendeera kw’emirimu, gamba ng’okukendeera kw’enkola y’abaserikale b’omubiri, okunafuwa kw’enkola y’emisuwa gy’omutima, n’okukendeera kw’enkola y’obusimu. Nga ekola puloteyina ya FOXO4, FOXO4-DRI esobola okulwawo enkola y’okukaddiwa kw’obutoffaali, okulongoosa obulamu n’enkola y’obutoffaali, era bwe kityo n’eyamba okulongoosa obulamu bw’omubiri okutwalira awamu. Okugeza, mu model y’ebibe eby’emyaka, obujjanjabi ne FOXO4-DRI busobola okulongoosa ennyo obusobozi bw’okukola dduyiro n’enkola y’okutegeera kw’ebibe n’okukendeeza ku kubeerawo kw’endwadde ezeekuusa ku myaka ^{[1, 2].}.

2. Obujjanjabi bw’endwadde z’obusimu

Enkolagana n’okukaddiwa kw’obusimu n’okufa: 

Endwadde ezikendeeza ku busimu nga Alzheimer’s disease ne Parkinson’s disease zikwatagana nnyo n’okukaddiwa n’okufa kw’obusimu obuyitibwa neurons. Mu ndwadde zino, obusimu bujja kwonoonebwa ensonga ez’enjawulo nga oxidative stress, inflammatory response, ne protein aggregation, ekivaako okufiirwa mpolampola enkola y’obusimu era okukkakkana nga kireese obuzibu mu kutegeera n’enkola y’enkola y’emirimu. Nga ekola ekkubo ly’obubonero bwa FOXO4, FOXO4-DRI esobola okutumbula obulamu n’okuddaabiriza obusimu obuyitibwa neurons n’okutumbula okuziyiza kwabwo eri oxidative stress ne apoptotic signals.

Puloteeni ya FOXO4 esobola okulung’amya okwolesebwa kw’obuzaale obuwerako mu busimu obuyitibwa neurons, omuli enziyiza eziziyiza obuwuka obuleeta obulwadde, puloteyina eziziyiza okufa, ensonga ezikula kw’obusimu, n’ebirala Okulinnyisa okwolesebwa kw’obuzaale buno kuyinza okukuuma obusimu obutafuna kwonooneka n’okutumbula okuddamu okukola n’okuddaabiriza obusimu obuyitibwa neurons. Okugeza, mu nkola y’ebibe ey’obulwadde bwa Alzheimer, obujjanjabi ne FOXO4-DRI busobola okukendeeza ku kuteekebwa kwa puloteyina za amyloid, okulongoosa enkola y’obusimu, n’okukendeeza ku kukula kw’obulwadde. Mu nkola y’obulwadde bwa Parkinson, FOXO4-DRI era esobola okukuuma obusimu obukola dopaminergic n’okulongoosa obusobozi bw’okukola dduyiro bw’ebibe ^{[3, 4]} . N’olwekyo, FOXO4-DRI esuubirwa okukozesebwa mu kujjanjaba endwadde z’obusimu okukendeeza ku kukula kw’obulwadde n’okulongoosa enkola y’okutegeera n’enkola y’emirimu gy’abalwadde.

3. Okuziyiza n’okujjanjaba endwadde z’emisuwa

Okukuuma Cardiomyocytes: Omutima: 

Mu nkola y’emisuwa gy’omutima, FOXO4-DRI esobola okukuuma cardiomyocytes okuva ku oxidative stress n’okwonooneka kwa apoptotic. Cardiomyocytes bwe butoffaali obukulu obukola ku mutima, era okwonooneka n’okufa kwabwo kye kimu ku bikulu ebivaako endwadde z’emisuwa. FOXO4-DRI esobola okukola puloteyina ya FOXO4, okulinnyisa okwolesebwa kw’enziyiza eziziyiza obuwuka obuleeta obulwadde, okukendeeza ku mutindo gw’ebika bya oxygen ebikola mu butoffaali mu myocytes, n’okukendeeza ku kwonooneka kwa oxidative stress eri cardiomyocytes. Mu kiseera kye kimu, FOXO4-DRI era esobola okutumbula okwolesebwa kwa puloteyina ezilwanyisa apoptotic, okuziyiza okukola kw’ekkubo ly’obubonero bw’okufa, n’okukuuma cardiomyocytes okuva ku apoptosis ^[4]..

Okutumbula Enkola y’obutoffaali bw’emisuwa: 

FOXO4-DRI era esobola okutumbula enkola eya bulijjo ey’obutoffaali bw’emisuwa n’okukuuma obutebenkevu n’obugumu bw’emisuwa. Obutoffaali bw’emisuwa kitundu kikulu nnyo mu bbugwe w’emisuwa, era enkola yaago etali ya bulijjo ejja kuleetera okubeerawo kw’endwadde z’emisuwa ng’okweyongera okuyita mu misuwa, okuzimba omusaayi, n’okuzimba emisuwa. FOXO4-DRI esobola okukola puloteyina ya FOXO4, okulungamya okwolesebwa kw’obuzaale obuwerako mu butoffaali bw’emisuwa, okutumbula okukula, okusenguka, n’okuddaabiriza obutoffaali bw’emisuwa, n’okukuuma emirimu gya bulijjo egy’emisuwa. Okugeza, FOXO4-DRI esobola okulinnyisa okwolesebwa kw’ensonga y’okukula kw’emisuwa (VEGF), okutumbula okukula kw’obutoffaali bw’emisuwa n’okutondebwa kw’emisuwa; era esobola okutumbula okwolesebwa kw’endothelial nitric oxide synthase (eNOS), okutumbula okukola kwa nitric oxide, okugaziya emisuwa, n’okukendeeza puleesa ^[4]..

Okuziyiza n'okujjanjaba endwadde z'emisuwa: 

Mu bufunze, FOXO4-DRI eyamba okuziyiza n’okujjanjaba endwadde z’emisuwa ng’okuzimba emisuwa gy’omutima, okulemererwa kw’omutima, n’okuzimba emisuwa. Mu nkola y’ebisolo ey’okuzimba emisuwa gy’omutima, obujjanjabi ne FOXO4-DRI busobola okukendeeza ku kufa kw’obutoffaali bw’omutima, okutumbula okuddaabiriza ebitundu by’omusuwa gw’omutima, n’okulongoosa enkola y’omutima. Mu nkola y’okulemererwa kw’omutima, FOXO4-DRI esobola okuziyiza okufa kw’obutoffaali bw’omutima, okutumbula okukonziba kw’emisuwa gy’omutima, n’okulongoosa enkola y’okupampagira omutima. Mu nkola y’okuzimba emisuwa, FOXO4-DRI esobola okukendeeza ku kwonooneka kw’obutoffaali bw’emisuwa, okuziyiza okuddamu kw’okuzimba, n’okukendeeza ku bulabe bw’okuzimba emisuwa ^[4]..

Mu kumaliriza, okuyita mu nkola zaayo ez’okukola, omuli okuleeta apoptosis y’obutoffaali obukaddiye, okulongoosa tissue microenvironment, n’okulwawo enkola y’okukaddiwa, FOXO4-DRI eraga omugaso oguyinza okukozesebwa mu nsonga z’okulwanyisa okukaddiwa, okujjanjaba ensigo obutakola bulungi, radiation-induced pulmonary fibrosis, neurodegenerative diseases, n’okuziyiza n’okujjanjaba endwadde z’emisuwa n’emisuwa.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Han X munoonyereza alina akakwate n’amatendekero ag’ekitiibwa agawerako, omuli Jiangxi Academy of Sciences, Fudan University, Hunan University, Zhengzhou University, University of Geosciences, Sichuan University, National University of Singapore, Minisitule y’ebyobugagga eby’omu ttaka eya People’s Republic of , Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College, Jiang Xi Acad Sci, Guilin Medical University, Tongji University, Medical University, Yunivasite ya Tianjin, ne Yunivasite ya Northeast Normal - . Enkolagana zino ziraga obumanyirivu bwe obw’enjawulo era obw’enjawulo mu by’ensoma.

Okunoonyereza kwe kukwata ku masomo amakulu agawerako. Akola nnyo mu kunoonyereza mu bitundu bya Chemistry, Environmental Sciences & Ecology, Research & Experimental Medicine, Oncology, ne Biochemistry & Molecular Biology. Omulimu gwe gulaga obukugu obugazi n’ebintu ebikulu by’akola mu bintu bino. Han X awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [2].

▎ Ebiwandiiko Ebikwatagana

[1] Zhang C, Xie Y, Chen H, n’abalala. FOXO4-DRI ekendeeza ku myaka egy’obutafulumya testosterone nga etunuulira obutoffaali bwa Leydig obukaddiye mu mbeba ezikaddiye[J]. Okukaddiwa (Albany Ny), 2020,12 (2): 1272-1284.DOI: 10.18632 / okukaddiwa.102682.

[2] Han X, Yuan T, Zhang J, n’abalala. FOXO4 peptide etunuulira myofibroblast etereeza bleomycin-induced pulmonary fibrosis mu mbeba okuyita mu ECM-receptor interaction pathway[J]. Journal of Eddagala ly'obutoffaali ne molekyu, 2022, 26 (11): 3269-3280.DOI: 10.1111 / jcmm.17333.

[3] Theoharides TC, Tsilioni I. Tetramethoxyluteolin okujjanjaba endwadde z’obusimu[J]. Emitwe egy’omulembe mu kemiko w’eddagala, 2018,18 (21): 1872-1882.DOI: 10.2174/ 15680266176 66 18111915424 7.

[4] Aslam DI, Jiyanboyevich Y, Ergashboevna A. Okuziyiza & Okujjanjaba Endwadde z’emisuwa[J]. Ekitabo ky’Amerika ekya Sayansi w’Ebyobujjanjabi n’okunoonyereza ku ddagala, 2021,03:180-188.DOI:10.37547/TAJMSPR/Volume03Issue06-28.

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.