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▎ Ọdịdị FOXO4-DRI
Isi mmalite: PubChem |
Usoro: LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPPRRRQRRKKRG Ụdị mkpụrụ ndụ: C 228H 388N 86O64 Ibu molekụla: 5358g/mol PubChem CID: 168431240 Ndị otu: EX-A7431 |
▎ FOXO4-DRI Nnyocha
Kedu ihe ndabere nyocha nke FOXO4-DRI?
Nnyocha miri emi na Senescence Cellular:
Site na nyocha miri emi na-aga n'ihu na usoro nke senescence cell, achọpụtara na senescence cellular na-arụ ọrụ dị mkpa n'ọtụtụ usoro physiological yana ihe omume na mmepe nke ọrịa. Mkpụrụ ndụ Senescent ga-agbakọ ma zoo ụdị cytokines dị iche iche na ndị mgbasa ozi na-egbuke egbuke, na-emetụta ọrụ nke sel ndị gbara ya gburugburu, ma si otú a na-eduga na nkwụsị nke anụ ahụ na ọrụ akụkụ ahụ. Ya mere, ịchọta ụzọ iji tinye aka na usoro nke senescence cell aghọwo ebe nyocha.
Nchọpụta nke FOXO4 Protein:
FOXO4 bụ otu n'ime protein igbe ndụdụ O ezinụlọ (FOXO) ma na-arụ ọrụ dị mkpa na usoro ndu dị iche iche dị ka uto cell, ọdịiche, apoptosis, na nzaghachi nrụgide. Nnyocha achọpụtala na FOXO4 nwere njikọ chiri anya na cellular senescence, ọ pụkwara imetụta usoro nhazi nke mkpụrụ ndụ site n'ịhazi okwu nke usoro mkpụrụ ndụ ihe nketa. Dịka ọmụmaatụ, FOXO4 nwere ike ime ka ngosipụta nke ụfọdụ mkpụrụ ndụ ihe nketa antioxidant na mkpụrụ ndụ nrụzi DNA, na-eme ka mkpụrụ ndụ na-eguzogide nrụgide oxidative na mmebi DNA, si otú ahụ na-egbu oge senescence cell.
Nyochaa Obere Ngwakọta Molecule:
Dabere na nghọta nke ọrụ nke protein FOXO4, ndị ọkà mmụta sayensị malitere nyochaa obere ogige molekul nke nwere ike ịhazi ọrụ FOXO4. Ha nwere olile anya ịchọta obere ihe molekul nke nwere ike rụọ ọrụ protein FOXO4 kpọmkwem, si otú a na-egosipụta mmetụta mgbochi ịka nká na ịgwọ ọrịa ndị metụtara ya. Mgbe ọnụ ọgụgụ dị ukwuu nke nyocha nyocha na njikarịcha nyocha, e mechara chọpụta obere ngwongwo molecule FOXO4-DRI. Ọ nwere ike jikọta ya na protein FOXO4, mee ka ụzọ mgbama mgbago ya dị ala, ma rụọ ọrụ n'ịhazi senescence cell na ọrụ physiological metụtara ya.
Gịnị bụ usoro omume nke FOXO4-DRI?
1. Mgbochi ịka nká
FOXO4-DRI nwere ike mee ka protein FOXO4 rụọ ọrụ, wee mezie usoro metabolism nke cell, mmụba, na usoro apoptosis. Protein FOXO4 na-arụ ọrụ nchịkwa dị mkpa na sel. Ọ nwere ike ime ka mkpụrụ ndụ na-eguzogide nrụgide site n'ịhazi okwu nke usoro mkpụrụ ndụ ihe nketa ala, na ibelata senescence na mmebi cellular. Dịka ọmụmaatụ, FOXO4 nwere ike ịkwalite nkwupụta nke enzymes antioxidant ma belata ọkwa nke ikuku oxygen intracellular reactive, si otú a na-ebelata mmebi nke nrụgide oxidative na sel [1, 2] . Tụkwasị na nke ahụ, FOXO4 nwekwara ike ịhazi okwu nke mkpụrụ ndụ ihe nketa metụtara okirikiri cell, na-egbochi ịba ụba cell, ma nọgide na-enwe metabolism nkịtị na ọrụ nke mkpụrụ ndụ.
2. Mechanism of Action in Men Late-Onset Hypogonadism
Mmekọrịta na FOXO4 na p53:
hypogonadism mmalite mmalite nke nwoke bụ ọrịa metụtara afọ, yana usoro ya bụ arụrụ ọrụ nke mkpụrụ ndụ Leydig dị na testis. Achọpụtala na akwụkwọ ndụ forkhead O (FOXO) FOXO4 na-egosipụta kpọmkwem na mkpụrụ ndụ Leydig mmadụ, na ntụgharị ya na nucleus na ndị agadi na-emetụta mbelata nke njikọ testosterone. Dị ka onye na-egbochi FOXO4 kpọmkwem, FOXO4-DRI na-ahọrọ p53 mkpochapụ nuklia na apoptosis na mkpụrụ ndụ Leydig senescent site na imebi mmekọrịta dị n'etiti FOXO4 na p53 [1].
Imelite microenvironment testicular:
N'ime ụmụ oke ndị merela agadi, FOXO4-DRI nwere ike melite microenvironment testicular ma belata ụkọ testosterone metụtara afọ. Nke a na-egosi na FOXO4-DRI nwere ike iweghachi ọrụ nkịtị nke anụ ahụ testicular site n'ịhazi ụzọ mgbaàmà metụtara ịdị ndụ nke mkpụrụ ndụ Leydig, si otú ahụ na-abawanye ọkwa nzuzo nke testosterone [1]..
3. Usoro nke Action na Pulmonary Fibrosis
Mbelata mkpụrụ ndụ Senescent na mbelata nkwupụta SASP:
Fibrosis pulmonary bụ ọrịa ngụgụ na-aga n'ihu na-enwe oke ọgwụgwọ nhọrọ. A na-ewere senescence cellular dị ka otu n'ime ihe ndị na-akpata ọrịa fibrosis nke akpa ume, na mkpochapụ nke mkpụrụ ndụ senescent nwere ike imeziwanye ọrụ ngụgụ. N'ụdị òké nke fibrosis pulmonary nke bleomycin kpatara, FOXO4-DRI, dị ka ọgwụ pirfenidone akwadoro, nwere ike belata mkpụrụ ndụ senescent, mebie okwu nke senescence-metụtara secretory phenotype (SASP), ma belata mgbanwe morphological na ntinye collagen nke bleomy kpatara [2].
Na-emetụta oke nke ụdị cell:
FOXO4-DRI nwere ike ịbawanye ọnụọgụ nke ụdị 2 alveolar epithelial cell (AEC2) na fibroblasts ma belata oke nke myofibroblasts n'ụdị òké nke fibrosis pulmonary na-ebute site na bleomycin. N'ime nnwale in vitro, ma e jiri ya tụnyere òké na ahịrị sel fibroblast ngụgụ mmadụ, FOXO4-DRI nwere ọchịchọ ka ukwuu igbu myofibroblasts kpatara site n'ịgbanwe ihe na-eto eto-β (TGF-β) [2].
Na-ahazi Ụzọ Mmekọrịta Ndị Na-anabata Matrix Extracellular:
Mmetụta inhibitory nke FOXO4-DRI na myofibroblasts na-eduga na mbelata nke usoro mmekọrịta nke extracellular matrix (ECM) na bleomycin na-ebute fibrosis pulmonary. Nke a na-egosi na FOXO4-DRI nwere ike melite usoro pathological nke fibrosis pulmonary site na ịhazi ọgbọ na metabolism nke ECM [2]..
FOXO4-DRI emeliorates bleomycin (BLM) na-ebute fibrosis nke akpa ume (PF). (A) Eserese eserese nke na-egosi nhazi nnwale. (B) Ihe nnochite anya onyonyo nke haematoxylin-eosin (HE) ntụpọ na Masson trichrome-staining nke akụkụ anụ ahụ ngụgụ.
Isi mmalite: PubMed [2]
Kedu ihe bụ ngwa FOXO4-DRI?
1. Mgbochi ịka nká
FOXO4-DRI nwere uru ọ bara n'ịkwalite ọdịda ọrụ metụtara afọ. Site na mmụba nke afọ, akụkụ dị iche iche na usoro nke ahụ ga-enweta ogo dị iche iche nke ịka nká na nkwụsị ọrụ, dị ka mbelata nke ọrụ usoro ahụ ji alụso ọrịa ọgụ, ịda mbà n'obi nke usoro obi obi, na mbelata nke ọrụ usoro ụjọ. Site n'ịgbalite protein FOXO4, FOXO4-DRI nwere ike igbu oge usoro nke senescence nke cellular, melite ume cell na ọrụ, ma si otú a na-enyere aka melite ahụike nke ahụ dum. Dịka ọmụmaatụ, na ụdị òké ochie, ọgwụgwọ na FOXO4-DRI nwere ike imeziwanye ikike mmega ahụ na ọrụ ọgụgụ isi nke ụmụ oke ma belata ihe omume nke ọrịa ndị metụtara afọ [1, 2]..
2. Ọgwụgwọ Ọrịa Neurodegenerative
Mmekọrịta ya na Neuron ịka nká na ọnwụ:
Ọrịa Neurodegenerative dị ka ọrịa Alzheimer na ọrịa Parkinson nwere njikọ chiri anya na ịka nká na ọnwụ nke neurons. N'ime ọrịa ndị a, neuron ga-emebi site na ihe dị iche iche dị ka nrụgide oxidative, nzaghachi mkpali, na nchịkọta protein, na-eduga n'ịkwụsị nwayọọ nwayọọ nke ọrụ neuronal na n'ikpeazụ na-ebute nsogbu ọgụgụ isi na moto. Site n'ịgbalite ụzọ akara ngosi FOXO4, FOXO4-DRI nwere ike ịkwalite ndụ na nrụzi nke neurons ma kwalite nguzogide ha na nrụgide oxidative na akara apoptotic.
The FOXO4 protein nwere ike ịhazi okwu nke ọtụtụ mkpụrụ ndụ ihe nketa na neurons, gụnyere antioxidant enzymes, anti-apoptotic proteins, akwara uto ihe, wdg Nkwalite nke okwu nke mkpụrụ ndụ ihe nketa ndị a nwere ike na-echebe neurons site na mmebi ma kwalite mweghachi na mmezi nke neurons. Dịka ọmụmaatụ, na ụdị òké nke ọrịa Alzheimer, ọgwụgwọ na FOXO4-DRI nwere ike ibelata ntinye nke protein amyloid, melite ọrụ neuronal, ma belata ọganihu nke ọrịa ahụ. N'ụdị ọrịa ọrịa Parkinson, FOXO4-DRI nwekwara ike ichebe neurons dopaminergic ma melite ikike mmega ahụ nke ụmụ oke [3, 4] . Ya mere, a na-atụ anya na FOXO4-DRI na-eji ọgwụgwọ ọrịa neurodegenerative mee ihe iji mee ka ọganihu nke ọrịa ahụ kwụsịlata ma melite ọrụ ọgụgụ isi na moto nke ndị ọrịa.
3. Mgbochi na ọgwụgwọ ọrịa obi
Na-echebe Cardiomyocytes:
Na usoro obi obi, FOXO4-DRI nwere ike ichebe cardiomyocytes site na nrụgide oxidative na mmebi apoptotic. Cardiomyocytes bụ isi mkpụrụ ndụ arụ ọrụ nke obi, na mmebi ha na ọnwụ ha bụ otu n'ime ihe ndị dị mkpa na-ebute ọrịa obi. FOXO4-DRI nwere ike ime ka protein FOXO4 rụọ ọrụ, kwalite okwu nke enzymes antioxidant, belata ọkwa oxygen intracellular reactive na cardiomyocytes, ma belata mmebi nke nrụgide oxidative na cardiomyocytes. N'otu oge ahụ, FOXO4-DRI nwekwara ike ịkwalite nkwupụta nke protin anti-apoptotic, gbochie mmalite nke ụzọ mgbaàmà apoptotic, ma chebe cardiomyocytes site na apoptosis [4]..
Ịkwalite ọrụ nke mkpụrụ ndụ endothelial vascular:
FOXO4-DRI nwekwara ike ịkwalite ọrụ nkịtị nke sel endothelial vaskụla ma nọgide na-enwe nkwụsi ike na ngbanwe nke arịa ọbara. Mkpụrụ ndụ endothelial vaskụla bụ akụkụ dị mkpa nke mgbidi arịa ọbara, na arụrụ ọrụ ha na-adịghị mma ga-eduga na omume nke ọrịa obi dị ka mmụba nke vaskụla vaskụla, thrombosis, na atherosclerosis. FOXO4-DRI nwere ike ime ka protein FOXO4 rụọ ọrụ, na-edozi okwu nke ọtụtụ mkpụrụ ndụ ihe nketa na sel endothelial vaskụla, na-akwalite mmụba, ịkwaga, na ịrụzi mkpụrụ ndụ endothelial vaskụla, ma nọgide na-arụ ọrụ nkịtị nke arịa ọbara. Dịka ọmụmaatụ, FOXO4-DRI nwere ike imeziwanye okwu nke vascular endothelial growth factor (VEGF), na-akwalite mmụba nke mkpụrụ ndụ endothelial vaskụla na angiogenesis; ọ pụkwara imezi okwu nke endothelial nitric oxide synthase (eNOS), kwalite mmepụta nke nitric oxide, gbasaa arịa ọbara, ma belata ọbara mgbali [4]..
Mgbochi na ọgwụgwọ ọrịa obi:
Na nchịkọta, FOXO4-DRI na-enyere aka igbochi na ịgwọ ọrịa obi dị ka myocardial infarction, nkụda obi, na atherosclerosis. N'ụdị anụmanụ nke infarction myocardial, ọgwụgwọ na FOXO4-DRI nwere ike belata ọnwụ nke cardiomyocytes, kwalite nrụzi anụ ahụ myocardial, ma melite ọrụ obi. N'ụdị ọdịda obi, FOXO4-DRI nwere ike igbochi apoptosis nke cardiomyocytes, kwalite myocardial contractility, ma melite ọrụ mgbapụta nke obi. N'ihe atụ nke atherosclerosis, FOXO4-DRI nwere ike ibelata mmebi nke sel endothelial vaskụla, gbochie nzaghachi mkpali, ma belata ohere nke atherosclerosis [4]..
N'ikpeazụ, site na usoro ya nke ime ihe, gụnyere ime ka apoptosis nke mkpụrụ ndụ senescent dịkwuo mma, meziwanye microenvironment anụ ahụ, na-egbu oge usoro ịka nká, FOXO4-DRI na-egosi uru ngwa ngwa dị n'ọhịa nke mgbochi ịka nká, ọgwụgwọ nke hypofunction testicular, radieshon-induced pulmonary fibrosis, ọrịa neurodegenerative, na mgbochi na ọgwụgwọ nke ọrịa obi.
Banyere Onye dere ya
Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.
Onye ode akwụkwọ akụkọ sayensị
Han X bụ onye nyocha jikọtara ya na ụlọ ọrụ dị iche iche, gụnyere Jiangxi Academy of Sciences, Mahadum Fudan, Mahadum Hunan, Mahadum Zhengzhou, Mahadum Geosciences, Mahadum Sichuan, Mahadum Mba nke Singapore, Ministry of Natural Resources of the People’s Republic of , Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College, Jiang Xiiji University Medical University, Jiang Xiiji University Medical University, Gung Xiijilin S, University Medical University Mahadum, na Northeast Normal University - . Mmekọrịta ndị a na-egosipụta oke mmụta ya na mmụta dị iche iche.
Mmasị nchọcha ya gbasara ọtụtụ isi isiokwu. Ọ na-arụsi ọrụ ike na nyocha n'ime ngalaba Chemistry, Environmental Sciences & Ecology, Research & Experimental Medicine, Oncology, na Biochemistry & Molecular Biology. Ọrụ ya na-egosipụta ọkachamara sara mbara na ntinye aka dị ukwuu na mpaghara ndị a. Edepụtara Han X n'akwụkwọ ntụaka [2].
