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Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).
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BACKGROUND: Previous studies reported that compared to conventional dual antiplatelet therapy (DAT; aspirin + clopidogrel), triple antiplatelet therapy (TAT), involving the addition of cilostazol to DAT, had better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the optimal duration of TAT is yet to be determined. METHODS: In total, 985 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) were prospectively enrolled in 15 PCI centers in South Korea and China. We randomly assigned patients into 3 groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for 6 months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, recurrent myocardial infarction, stroke, or repeat revascularization. RESULTS: The primary endpoint did not differ among the 3 groups (8.8% in DAT, 11.0% in TAT 1M, and 11.6% in TAT 6M; hazard ratio for TAT 1M vs DAT, 1.302; 95% confidence interval [CI], 0.792-2.141; P = .297; hazard ratio for TAT 6M vs DAT, 1.358; 95% CI, 0.829-2.225; P = .225). With respect to in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs 4.7% vs 2.6%, P = .029), with no significant differences in major bleeding events. Additionally, the TAT group had a higher incidence of headaches (0% vs 1.6% vs 2.6%, P = .020). CONCLUSIONS: The addition of cilostazol to DAT did not reduce the incidence of 1-year MACEs compared with DAT alone. Instead, it may be associated with an increased risk of drug intolerance and side effects, including in-hospital bleeding and headaches.
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BACKGROUND: Hair loss occurs due to various biological and environmental causes, which can have psychosocial consequences. The Wnt/ß-catenin signaling is well-known for its role in hair growth and regeneration, as it induces the proliferation and differentiation of hair cells. When the leucine-rich G protein-coupled receptor 5 (Lgr5) interacts with the R-spondins, the frizzled receptor (FZD), a Wnt receptor, becomes stabilized, resulting in an increased ß-catenin activity. AIM: We investigated whether the octapeptide that binds to Lgr5 enhances proliferation and differentiation of human primary hair cells through the activation of Wnt/ß-catenin signaling. METHODS: The binding affinity of the octapeptide to Lgr5 was evaluated using surface plasmon resonance (SPR). We confirmed changes in proliferation and related factors like ß-catenin activation and growth factors (GFs) expression in human hair follicle dermal papilla cells (HHFDPCs). Additionally, we observed the proliferation and the expression of differentiation markers in human hair follicle outer root sheath cells (HHFORSCs), human hair follicle germinal matrix cells (HHFGMCs), and human hair follicle stem cells (HHFSCs). We used three-dimensional HHFDPC spheroid culture treated with dihydrotestosterone (DHT) to create in vitro conditions that mimic androgenetic alopecia, and we studied the effects of octapeptide on Wnt expression and HHFSC differentiation. RESULTS: The binding of the octapeptide to Lgr5 was confirmed using SPR analysis. In HHFDPCs, treatment with octapeptide resulted in a concentration-dependent increase in proliferation. We also observed increased nuclear translocation of ß-catenin and increased expression of its downstream targets. HHFDPCs treated with octapeptide exhibited increased expression of growth factors and phosphorylation of Akt and ERK. In addition, we confirmed that octapeptide increased proliferation and induced differentiation in HHFORSCs, HHFGMCs, and HHFSCs. Under the HHFDPC spheroid culture conditions, we found that octapeptide restored the inhibition of Wnt-5a and Wnt-10b expressions by DHT. In HHFSCs treated with HHFDPC spheroid culture media, we observed that octapeptide recovered the inhibition of differentiation by DHT. CONCLUSION: We found that octapeptides activated the Wnt/ß-catenin signaling and induced the proliferation and differentiation of human primary hair cells by acting as an exogenous ligand for Lgr5. In addition, octapeptides recovered inhibited hair regeneration characters by DHT in androgenetic alopecia-mimic in vitro model. These findings suggest that octapeptides may be a promising therapeutic option for treating hair loss.
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Folículo Piloso , beta Catenina , Humanos , beta Catenina/metabolismo , Cabelo/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Via de Sinalização Wnt , Di-Hidrotestosterona/metabolismo , Alopecia/tratamento farmacológico , Alopecia/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Proliferação de CélulasRESUMO
AIMS: Considering the limited data regarding clinical outcomes of patients with non-ST-segment on the ECG elevation myocardial infarction (NSTEMI), this study compared the outcomes of patients undergoing percutaneous coronary intervention with newer-generation drug-eluting stents stratified by the presence/absence of complex lesions and symptom-to-balloon time (SBT; <48âh or ≥48âh). METHODS: We enrolled 4373 patients with NSTEMI from the Korea Acute Myocardial Infarction Registry-National Institute of Health dataset and stratified them into the complex group (2106 patients; SBTâ<â48âh, nâ=â1365; SBT ≥48âh, nâ=â741) and the noncomplex group (2267 patients; SBTâ<â48âh, nâ=â1573; SBT ≥48âh, nâ=â694). The primary outcome was the 3-year all-cause mortality rate. The secondary outcomes were any major adverse cardiac events (MACE), including cardiac death (CD), recurrent myocardial infarction, and stroke. RESULTS: The incidence of all-cause mortality (adjusted hazard ratio, 0.656; Pâ=â0.009), CD (Pâ=â0.037), and MACE (Pâ=â0.047) in the complex group and of stroke in the noncomplex group (Pâ=â0.020) were significantly lower in patients with SBTâ<â48âh than in those with SBT ≥48âh. Among patients with SBTâ<â48âh, the stroke incidence (Pâ=â0.019) was higher in the complex group than in the noncomplex group, while among patients with SBT ≥48âh, the MACE incidence (Pâ=â0.011) was higher in the former than in the latter. CONCLUSION: SBT reduction effectively decreased the 3-year mortality in patients with NSTEMI in the complex group compared with the noncomplex group.
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Due to limited published data, we investigated 3-year outcomes according to left ventricular ejection fraction (LVEF) in patients older and younger than 75 years with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent successful newer-generation drug-eluting stent (DES) implantation. This research analyzed the data of 4558 patients (1032 older adults [≥75 years] and 3526 younger adults [<75 years]) from the Korea Acute MI Registry-NIH. We further divided the older group based on LVEF: heart failure (HF) with reduced EF (HFrEF, ≤40%, nâ =â 196; group A), HF with mildly reduced EF (HFmrEF, 41-49%, nâ =â 228; group B), and HF with preserved EF (HFpEF, ≥50%, nâ =â 608; group C). Similarly, the younger group was divided into HFrEF (group D, nâ =â 353), HFmrEF (group E, nâ =â 577), and HFpEF (group F, nâ =â 2596). The primary outcome was a composite of major adverse cardiac events (MACE) at 3 years, including all-cause death, recurrent MI, any repeat revascularization, or hospitalization for HF. MACE rates were highest in the HFrEF groups (A and D), followed by the HFmrEF groups (B and E), and lowest in the HFpEF groups (C and F) for both age groups. All-cause death, cardiac death (CD), all-cause death or MI, and hospitalization for HF rates were higher in group A than in groups B and C, and higher in group D than in groups E and F. Across all LVEF categories, MACE, all-cause death, CD, and non-CD, and all-cause death or MI rates were higher in the older group. This multicenter cohort study demonstrates that older patients have higher mortality rates compared to younger patients. Additionally, MACE rates were highest in the HFrEF group, followed by the HFmrEF group, and lowest in the HFpEF group across both age groups. Further research is needed to confirm these findings.
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Stents Farmacológicos , Infarto do Miocárdio sem Supradesnível do Segmento ST , Volume Sistólico , Humanos , Masculino , Feminino , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Fatores Etários , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , República da Coreia/epidemiologia , Resultado do Tratamento , Sistema de Registros , Função Ventricular Esquerda/fisiologia , Intervenção Coronária Percutânea/métodos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: We assessed left ventricular ejection fraction (LVEF) to compare the effects of renin-angiotensin system inhibitors (RASI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We categorized 4558 patients with NSTEMI as either RASI users (3752 patients) or non-users (806 patients). The 3-year patient-oriented composite outcome (POCO), which included all-cause death, recurrent myocardial infarction, any repeat revascularization, or hospitalization for heart failure (HF), was the primary outcome. To compare clinical outcomes, a multivariable-adjusted hazard ratio (aHR) was calculated after performing multicollinearity tests on all significant confounding variables (P < 0.05). RESULTS: Among RASI users, the aHRs for POCO, all-cause death, and cardiac death were significantly higher in the HF with reduced EF (HFrEF) subgroup than in the HF with mildly reduced EF (HFmrEF) (1.610, 2.120, and 2.489; P < 0.001, <0.001, and <0.001; respectively) and HF with preserved EF (HFpEF) (2.234, 3.920, and 5.215; P < 0.001, <0.001, and <0.001; respectively) subgroups. The aHRs for these variables were significantly higher in the HFmrEF subgroup than the HFpEF subgroup (1.416, 1.843, and 2.172, respectively). Among RASI non-users, the aHRs for these variables were significantly higher in the HFrEF subgroup than the HFmrEF (2.573, 3.172, and 3.762, respectively) and HFpEF (2.425, 3.805, and 4.178, respectively) subgroups. In three LVEF subgroups, RASI users exhibited lower aHRs for POCO and all-cause death than RASI non-users. CONCLUSION: In the RASI users group, the aHRs for POCO and mortality were highest in the HFrEF subgroup, intermediate in the HFmrEF subgroup, and lowest in the HFpEF subgroup.
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The aim of our study was to assess the relationship between serum gamma-glutamyl transferase (GGT) level within the normal range and incident hypertension according to drinking and obesity status in nonhypertensive individuals. We followed up 4783 normotensive adults (mean age = 44 years) who had serum GGT levels within the normal range at baseline for 3 years. Subjects were divided into four GGT quartile groups according to their serum GGT level at baseline. The overall incidence of hypertension was 8.1%, and the incidence increased with increasing GGT quartile (3.8%, 6.9%, 9.0%, and 12.4% in the lowest, second, third, and highest GGT quartiles, respectively; P < .001). In the logistic regression analysis adjusted for age, sex, body mass index, lifestyle factors, glucose, uric acid, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and baseline systolic blood pressure, the odds ratio (ORs) for incident hypertension increased with increasing GGT quartile (P for trend = .030). In the above model, the highest quartile group showed increased ORs compared with those in the lowest quartile group (ORs [95% confidence interval], 2.638 [1.259-5.528]). Subgroup analyses revealed a significant association between GGT quartile and the incidence of hypertension in the drinker and non-overweight groups. Our results indicate that elevated serum GGT levels within the normal range are associated with a higher risk of incident hypertension in Korean adults, particularly, in drinkers and non-overweight individuals, suggesting possible different pathophysiologic mechanisms in the incidence of alcohol- and obesity-related hypertension.
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Hipertensão/enzimologia , Hipertensão/epidemiologia , gama-Glutamiltransferase/sangue , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Povo Asiático , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: Recent studies have suggested that deep-learning models can satisfactorily assist in fracture diagnosis. We aimed to evaluate the performance of two of such models in wrist fracture detection. METHODS: We collected image data of patients who visited with wrist trauma at the emergency department. A dataset extracted from January 2018 to May 2020 was split into training (90%) and test (10%) datasets, and two types of convolutional neural networks (i.e., DenseNet-161 and ResNet-152) were trained to detect wrist fractures. Gradient-weighted class activation mapping was used to highlight the regions of radiograph scans that contributed to the decision of the model. Performance of the convolutional neural network models was evaluated using the area under the receiver operating characteristic curve. RESULTS: For model training, we used 4,551 radiographs from 798 patients and 4,443 radiographs from 1,481 patients with and without fractures, respectively. The remaining 10% (300 radiographs from 100 patients with fractures and 690 radiographs from 230 patients without fractures) was used as a test dataset. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DenseNet-161 and ResNet-152 in the test dataset were 90.3%, 90.3%, 80.3%, 95.6%, and 90.3% and 88.6%, 88.4%, 76.9%, 94.7%, and 88.5%, respectively. The area under the receiver operating characteristic curves of DenseNet-161 and ResNet-152 for wrist fracture detection were 0.962 and 0.947, respectively. CONCLUSION: We demonstrated that DenseNet-161 and ResNet-152 models could help detect wrist fractures in the emergency room with satisfactory performance.
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Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.
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Pontos de Checagem do Ciclo Celular/genética , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Células-Tronco Neurais/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Sinapses/metabolismo , Animais , Sequência de Bases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Linhagem da Célula/genética , Movimento Celular/genética , Ontologia Genética , Humanos , Mesencéfalo/embriologia , Camundongos , Células-Tronco Neurais/citologia , Neurogênese/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Doença de Parkinson/genética , Regiões Promotoras Genéticas/genética , Reprodutibilidade dos Testes , Ativação Transcricional/genéticaRESUMO
BACKGROUND: The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. METHODS/DESIGN: The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. DISCUSSION: The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. TRIAL REGISTRATION: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.
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Ligas , Angioplastia com Balão/instrumentação , Ligas de Cromo , Artéria Ilíaca , Doença Arterial Periférica/terapia , Stents Metálicos Autoexpansíveis , Stents , Angioplastia com Balão/efeitos adversos , Protocolos Clínicos , Constrição Patológica , Elasticidade , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/fisiopatologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Desenho de Prótese , Falha de Prótese , República da Coreia , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803).
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Ligas , Angioplastia com Balão/instrumentação , Artéria Femoral , Doença Arterial Periférica/terapia , Artéria Poplítea , Projetos de Pesquisa , Stents , Angioplastia com Balão/efeitos adversos , Aspirina/uso terapêutico , Cilostazol , Protocolos Clínicos , Clopidogrel , Quimioterapia Combinada , Artéria Femoral/fisiopatologia , Humanos , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Inibidores da Agregação Plaquetária/uso terapêutico , Artéria Poplítea/fisiopatologia , Estudos Prospectivos , Desenho de Prótese , Falha de Prótese , Tetrazóis/uso terapêutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Nurr1 is an orphan nuclear receptor best known for its essential role in the development and maintenance of midbrain dopaminergic (DA) neurons. During DA neurogenesis, Nurr1 directly targets human tyrosine hydroxylase (hTH). Here we investigated this targeting to identify the molecular mechanisms by which Nurr1 regulates DA neurogenesis. We previously cloned the hTH promoter and found three consensus elements for Nurr1 binding: NBRE-A, -B, and -C. In the present study, gel retardation and luciferase assays using hTH constructs showed that Nurr1 preferentially bound to NBRE-A, through which it mediated transcriptional activity. Furthermore, Nurr1 displayed dual-function transcriptional activities depending on the cell type. In DA-like SH-SY5Y cells, Nurr1 dose-dependently stimulated hTH-3174 promoter activity by 7- to 11-fold. However, in the human neural stem cell (hNSC) line HB1.F3, Nurr1 strongly repressed transcription from the same promoter. This repression was relieved by mutation of only the NBRE-A element and by nicotinamide [an inhibitor of class III histone deacetylases (HDACs), such as SIRT1], but not by trichostatin A (an inhibitor of class I and II HDACs). SIRT1 was strongly expressed in the nucleus of HB1.F3 cells, while it was localized in the cytoplasm in SH-SY5Y cells. ChIP assays of HB1.F3 cells showed that Nurr1 overexpression significantly increased the SIRT1 occupancy of the NBRE-A hTH promoter region, while low SIRT1 levels were observed in control cells. In contrast, no significant SIRT1 recruitment was observed in SH-SY5Y cells. These results indicate that differential SIRT1 localization may be involved in hTH gene regulation. Overall, our findings suggest that Nurr1 exists in dual transcriptional complexes, including co-repressor complexes that can be remodeled to become co-activators and can fine-tune hTH gene transcription during human DA neurogenesis.
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Células-Tronco Neurais/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Sirtuína 1/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Sequência de Bases , Biomarcadores/metabolismo , Linhagem Celular , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/genética , Histona Desacetilases/metabolismo , Humanos , Modelos Biológicos , Dados de Sequência Molecular , Células-Tronco Neurais/efeitos dos fármacos , Niacinamida/farmacologia , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/química , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECTIVE: Although several studies have reported an association between microalbuminuria and pulse wave velocity in patients with hypertension or diabetes, there have been no reports of their significance in apparently healthy individuals. METHODS: Microalbuminuria and brachial-ankle PWV (baPWV) were investigated in a sample of 3826 nonhypertensive, nondiabetic individuals (3598 men, mean age 50 ± 11.3 years) at Kangbuk Samsung Health Promotion Center between 2006 and 2009. The patients were classified into two groups according to urinary albumin-creatinine ratio (UACR) in morning urine specimens: normoalbuminuria (<30 µg/mg) and microalbuminuria (30-300 µg/mg). RESULTS: The prevalence of prehypertension (preHT) and microalbuminuria was 52.5 and 4%, respectively. Abnormal baPWV and microalbuminuria each has unfavorable cardiometabolic profile. The absolute values of baPWV were correlated with those of UACR (r = 0.220, P < 0.001). In multivariate regression analysis, the microalbuminuria group showed an independent association of increasing baPWVs irrespective of potential confounders, compared with the normoalbuminuria group (standard ß = 0.049, P < 0.001). In the subspecified analyses, category III (preHT + normoalbuminuria) and IV (preHT + microalbuminuria) had higher odds ratio (ORs) [95% confidence interval (CI)] for the abnormal baPWV group, compared with category I (normal BP + normoalbuminuria) [2.345 (2.010-2.735) and 3.822 (2.367-6.171), respectively]. CONCLUSION: These findings demonstrate epidemiologic evidence for an independent association between arterial stiffness and microalbuminuria, indices of subclinical target organ damage in nonhypertensive, nondiabetic individuals, which suggests the possibility of a similar pathophysiologic mechanism involved in these two indices of subclinical target organ damage.
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Albuminúria/complicações , Pressão Sanguínea , Rigidez Vascular , Tornozelo/fisiopatologia , Antropometria/métodos , Velocidade do Fluxo Sanguíneo/fisiologia , Determinação da Pressão Arterial , Artéria Braquial/fisiologia , Creatinina/metabolismo , Creatinina/urina , Feminino , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Valores de Referência , Resistência VascularRESUMO
BACKGROUND: Cardiovascular events are known to occur more frequently in patients with a high morning surge in blood pressure (BP), but the correlation between a morning BP surge and corrected QT dispersion (QTc) has not been confirmed to date. METHODS AND RESULTS: The correlation between the morning BP surge and QTc was studied in 82 patients recently diagnosed with high BP (47 males, 35 females). Twenty-four-hours BP monitoring was conducted to classify patients into dipper (n=45) or nondipper (n=37) groups according to the degree of nocturnal BP reduction. QTc was found to be significantly longer in the nondippers compared with the dippers (36.1+/-17.2 vs 47.6+/-20.7, p<0.001). In addition, there was a significant increase in the end-diastolic interventricular septum thickness (IVSd), left ventricular posterior wall thickness in diastole (PWT) and left ventricular mass index (LVMI) in the nondippers vs the dippers (respectively, 0.93+/-0.09 vs 1.03+/-0.05, p<0.001, 0.94+/-0.09 vs 1.01+/-0.04, p<0.01, 109.7+/-12.8 vs 129.1+/-20.9, p<0.001). QTc had a significant positive correlation with nighttime BP, IVSd, PWT, and LVMI, but negatively correlated with the nocturnal BP reduction rate. These results were maintained even after adjusting for age and gender. However, a significant correlation between the morning BP surge and QTc was not confirmed. CONCLUSION: In the present nondipper hypertensive patients, QTc, nighttime BP, LVMI, and wall thickness were significantly greater than in the dipper patients. However, there was no significant correlation between the morning BP surge and QTc.