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1.
Respir Res ; 20(1): 121, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200778

RESUMO

BACKGROUND: Abnormal sympathetic hyperactivity has been shown to lead to pulmonary arterial hypertension (PAH) deterioration. The purpose of this study was to examine whether the transection of the cervical sympathetic trunk (TCST) can inhibit the progression of PAH in a monocrotaline (MCT)-induced PAH model and elucidate the underlying mechanisms. METHODS: Rats were randomly divided into four groups, including a control group, an MCT group, an MCT + sham group and an MCT + TCST group. After performing haemodynamic and echocardiographic measurements, the rats were sacrificed for the histological study, and the norepinephrine (NE) concentrations and protein expression level of tyrosine hydroxylase (TH) were evaluated. The protein expression levels of extracellular signal-regulated kinase (ERK)-1/2, proliferating cell nuclear antigen (PCNA), cyclin A2 and cyclin D1 in pulmonary artery vessels and pulmonary arterial smooth muscle cells (PASMCs) were determined. RESULTS: Compared with the MCT + sham group, TCST profoundly reduced the mean pulmonary arterial pressure (mPAP) (22.02 ± 4.03 mmHg vs. 31.71 ± 2.94 mmHg), right ventricular systolic pressure (RVSP) (35.21 ± 5.59 mmHg vs. 48.36 ± 5.44 mmHg), medial wall thickness (WT%) (22.48 ± 1.75% vs. 46.10 ± 3.16%), and right ventricular transverse diameter (RVTD) (3.78 ± 0.40 mm vs. 4.36 ± 0.29 mm) and increased the tricuspid annular plane systolic excursion (TAPSE) (2.00 ± 0.12 mm vs. 1.41 ± 0.24 mm) (all P < 0.05). The NE concentrations and protein expression levels of TH were increased in the PAH rats but significantly decreased after TCST. Furthermore, TCST reduced the increased protein expression of PCNA, cyclin A2 and cyclin D1 induced by MCT in vivo. We also found that NE promoted PASMC viability and activated the ERK-1/2 pathway. However, the abovementioned NE-induced changes could be suppressed by the specific ERK-1/2 inhibitor U0126. CONCLUSION: TCST can suppress pulmonary artery remodelling and right heart failure in MCT-induced PAH. The main mechanism may be that TCST decreases the NE concentrations in lung tissues, thereby preventing NE from promoting PASMC proliferation mediated by the ERK-1/2 signalling pathway.


Assuntos
Vértebras Cervicais , Progressão da Doença , Sistema de Sinalização das MAP Quinases/fisiologia , Hipertensão Arterial Pulmonar/cirurgia , Nervos Espinhais/fisiologia , Simpatectomia/métodos , Animais , Masculino , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/prevenção & controle , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/cirurgia
2.
Mol Med Rep ; 20(2): 931-938, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173254

RESUMO

Vascular remodeling induced by long­term hyperglycaemia is the main pathological process in diabetic vascular complications. Thus, vascular remodeling may be a potential therapeutic target in diabetes mellitus (DM) with macrovascular disease. The present study aimed to investigate the effect of RING finger protein 10 (RNF10) on vascular remodeling under conditions of chronic hyperglycaemia stimulation. We found that overexpression of RNF10 clearly decreased intimal thickness and attenuated vascular remodeling in DM. TUNEL staining showed that apoptosis was clearly inhibited, an effect that may be mediated by decreases in Bcl­2 protein expression. Quantitative analysis demonstrated that overexpression of RNF10 could suppress inflammation by reducing the levels of TNF­α, and MCP­1 mRNA and NF­κB protein. Meanwhile, overexpression of RNF10 prevented vascular smooth muscle cell (VSMC) hyperproliferation through the downregulation of cyclin D1 and CDK4 proteins. Notably, short hairpin RNF10 (shRNF10) greatly aggravated the pathological responses of diabetic vascular remodeling. These outcomes revealed that the differential expression of RNF10 had a completely opposite effect on vascular damage under hyperglycaemia, further displaying the core function of RNF10 in regulating vascular remodeling induced by diabetes. Consequently, RNF10 could be a novel target for the treatment of diabetic vascular complications.


Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Experimental/genética , Angiopatias Diabéticas/genética , Hiperglicemia/genética , Miócitos de Músculo Liso/metabolismo , Proteínas do Tecido Nervoso/genética , Animais , Apoptose/genética , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Resistência à Insulina/genética , Masculino , Miócitos de Músculo Liso/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
Skeletal Radiol ; 48(12): 1915-1924, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31127357

RESUMO

OBJECTIVE: A systematic review and meta-analysis to compare the diagnostic performance of prostate-specific membrane antigen (PSMA)-PET/CT, choline-PET/CT, Sodium Fluoride (NaF) PET/CT, MRI, and bone scintigraphy (BS) in detecting bone metastases in patients with prostate cancer. METHODS: We searched PubMed and Embase for articles published between January 1990 and September 2018. Two evaluators independently extracted the sensitivity, specificity, the numbers of true and false positives, and true and false negatives. We calculated the pooled sensitivity, specificity, and 95% confidence intervals (CI) for each method. We calculated the tests' diagnostic odds ratios (DOR); drew the summary receiver operating characteristic (SROC) curves; and obtained the areas under the curves (AUC), Q* values, and 95% CIs. RESULTS: The per-patient pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and BS were 0.97, 0.87, 0.96, 0.91, and 0.86, respectively. The pooled specificities were 1.00, 0.99, 0.97, 0.96, and 0.95, respectively. The pooled DOR values were 504.16, 673.67, 242.63, and 114.44, respectively. The AUC were 1.00, 0.99, 0.99, 0.98, and 0.95, respectively. The per-lesion pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone imaging were 0.88, 0.80, 0.97, 0.81 and 0.68, respectively. CONCLUSIONS: According to the meta-analysis, PSMA-PET/CT had the highest per-patient sensitivity and specificity in detecting bone metastases with prostate cancer. The sensitivities of NaF-PET/CT and MRI were better than those for choline-PET/CT and BS. The specificity of PSMA-PET/CT was significantly better than BS. Others were similar. For per-lesion, NaF-PET/CT had the highest sensitivity, PSMA-PET/CT had higher sensitivity than choline-PET/CT and MRI, and BS had the lowest sensitivity.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Imagem por Ressonância Magnética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Cintilografia , Colina , Humanos , Masculino , Glicoproteínas de Membrana , Compostos Organometálicos , Compostos Radiofarmacêuticos , Fluoreto de Sódio
4.
Toxicology ; 422: 1-13, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31005592

RESUMO

Myocarditis is a serious hazard to human life and is difficult to treat due to the proliferation of inflammatory lesions in the myocardium. Leonurine (LE) is a plant phenolic alkaloid extracted from Herba leonuri that has demonstrated cardioprotective effects in many preclinical experiments. However, whether LE can be used for myocarditis therapy has not been reported. We aimed to investigate the cardioprotective effects of LE on lipopolysaccharide (LPS)-induced myocarditis in vivo and vitro. The possible mechanism involved was also further elucidated. In vivo, C57BL/6 mice were exposed to LPS with or without LE. We found out that LE effectively improved cardiac function and attenuated cardiomyocyte apoptosis in mice with myocarditis. In addition, LPS-induced inflammatory and oxidative injuries in the myocardium were also reduced by LE administration. In vitro, LPS simultaneously induced apoptosis and reduced the H9c2 cells viability, followed by elevation of intracellular reactive oxygen species (ROS) generation. However, the abnormalities mentioned were preventable by LE pretreatment in a dose-dependent manner. Both in vivo and in vitro, LPS activated the nuclear factor kappa B (NF-кB) signaling pathway in myocarditis, and LE inhibited the increased expression of phosphorylated iκBα and p65 (p-iκBα, p-p65). Furthermore, the nuclear translocalization and nuclear protein expression of p65 in LPS-injured H9c2 cells were also suppressed by LE. Our results demonstrated that LE exerts potent cardioprotective effects against myocarditis via anti-inflammatory and antioxidative mechanisms, possibly through blocking the activation of NF-кB pathway.


Assuntos
Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Ácido Gálico/análogos & derivados , Miocardite/tratamento farmacológico , NF-kappa B/metabolismo , Animais , Linhagem Celular , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Miocardite/induzido quimicamente , Miocardite/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
5.
IUBMB Life ; 71(5): 632-642, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30597731

RESUMO

Vascular smooth muscle cell (VSMC) hyperproliferation is the main pathological process in various cardiovascular diseases, such as vascular restenosis. This process may be repressed by RING finger protein 10 (RNF10) in metabolic syndrome (MetS) rats. The aim of this study is to evaluate the inhibitory effects and molecular mechanisms of RNF10 on VSMC hyperproliferation. Neointimal hyperplasia in MetS and high-glucose-induced VSMC hyperproliferation were measured after infection with adenoviruses encoding RNF10 (Ad-RNF10), short hairpin RNF10 (Ad-shRNF10), or green fluorescent protein (Ad-GFP). In vivo and in vitro, we found that overexpression of RNF10 significantly affected neointima formation and VSMC proliferation, and displayed further inhibitory activity by promoting mesenchyme homeobox 2 (Meox2) and suppressing activating protein 1 (AP-1). In contrast, Ad-shRNF10 had an opposite effect on neointimal hyperplasia and VSMC hyperproliferation in vivo and in vitro. Our study indicated that RNF10 inhibited the hyperproliferation with the activities of Meox2 and AP-1 proteins. RNF10 may be a next drug target for treating vascular restenosis and other related cardiovascular diseases. © 2018 IUBMB Life, 71(5):632-642, 2019.


Assuntos
Proteínas de Transporte/metabolismo , Proliferação de Células , Reestenose Coronária/prevenção & controle , Hiperplasia/prevenção & controle , Síndrome Metabólica/fisiopatologia , Músculo Liso Vascular/citologia , Neointima , Proteínas do Tecido Nervoso/metabolismo , Adenoviridae/fisiologia , Infecções por Adenoviridae/virologia , Angioplastia Coronária com Balão/efeitos adversos , Animais , Proteínas de Transporte/genética , Movimento Celular , Células Cultivadas , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Dieta Hiperlipídica/efeitos adversos , Hiperplasia/etiologia , Hiperplasia/patologia , Masculino , Síndrome Metabólica/etiologia , Músculo Liso Vascular/metabolismo , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
6.
Genes Dis ; 5(4): 335-341, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30591935

RESUMO

To assess the efficacy and short-term outcomes of adherence to statin therapy among coronary heart disease (CHD) patients following their hospital discharge, we enrolled 615 CHD patients who were prescribed statins from The First Affiliated Hospital of Chongqing Medical University in China between February 1st and October 31st of 2013. Statin adherence was evaluated by identifying the proportion of patients who remained adherent or became non-adherent to statin therapy over 4-8 months post-discharge from the hospital. The composite outcomes included all-cause mortality and re-hospitalization with cardiovascular disease. We found that 15.9% patients were non-adherent to their statin therapies and that coronary artery stenosis<75% (OR = 3.433, 95% CI: 2.191-5.380, p < 0.001) and adverse effects (OR = 2.542, 95% CI: 1.327-4.869, p = 0.005) both clearly contributed to poor adherence. The primary self-reported reasons for non-adherence included a lack of knowledge about the benefits of statin therapy (36.7%), the treatment being halted at the advice of their doctor (19.4%), and the difficulty in obtaining statins (12.2%). Non-adherence to statin therapy was significantly associated with an increased risk of cardiovascular events (OR = 1.741, 95% CI: 1.035-2.929, p = 0.037). In conclusion, CHD patients with moderate stenosis or adverse effects tended to have poor statin adherence, and this was significantly associated with increased cardiovascular events. We should strengthen education of the importance of statin therapy for both patients and doctors and facilitate the ability of patients to obtain their statin medication. Clinical Study Register Code: ChiCTR-EPC-16007839.

7.
Life Sci ; 208: 325-332, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29723537

RESUMO

AIMS: Vascular restenosis and neointimal hyperplasia are enhanced in metabolic syndrome (MetS). Vascular smooth muscle cell (VSMC) proliferation is a key step during restenosis and is suppressed by RING finger protein 10 (RNF10). However, the effect of RNF10 on neointimal hyperplasia is unknown. In the present study, we explored whether RNF10 over-expression prevents neointimal hyperplasia in a MetS rat model and in cultured VSMCs exposed to high glucose. MAIN METHODS: An adenovirus encoding RNF10 (Ad-RNF10) or control green fluorescent protein (Ad-GFP) was delivered to balloon-injured carotid arteries in MetS rats and cultured rat VSMCs exposed to high glucose. Neointimal hyperplasia was measured, and the apoptosis index in the neointima was evaluated. The protein levels of RNF10, caspase-3, Bcl-2 and Bax in the injured vessels and VSMCs were determined. KEY FINDINGS: Ad-RNF10 prevented the development of neointimal hyperplasia in balloon-injured vessels. Furthermore, an increase in the apoptosis index and cleaved caspase-3 protein expression and a decrease in Bcl-2 expression were detected in the injured vessels after Ad-RNF10 treatment. Meanwhile, increased caspase-3 protein expression and decreased Bcl-2 expression were detected in VSMCs treated with Ad-RNF10. SIGNIFICANCE: RNF10 over-expression strongly suppresses neointimal hyperplasia via increased apoptosis, constituting a promising new therapeutic target for vascular restenosis.


Assuntos
Apoptose , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Hiperplasia/patologia , Síndrome Metabólica/fisiopatologia , Músculo Liso Vascular/patologia , Neointima/patologia , Proteínas do Tecido Nervoso/metabolismo , Animais , Proteínas de Transporte/genética , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Hiperplasia/etiologia , Hiperplasia/metabolismo , Técnicas In Vitro , Masculino , Síndrome Metabólica/etiologia , Músculo Liso Vascular/metabolismo , Neointima/etiologia , Neointima/metabolismo , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
8.
Am J Hypertens ; 31(6): 679-686, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29365009

RESUMO

BACKGROUND: The effects of food on the prevalence and control of hypertension are unclear. We aimed to investigate whether a dietary pattern of higher fish, egg, milk, nut, vegetable and fruit consumption, and lower salt intake was associated with hypertension in China. METHODS: A total of 15,303 subjects were recruited from September 2012 to December 2014. Groups with (n = 1,604) and without (n = 13,660) hypertension were formed for a case-control study. The hypertensive participants were classified into the controlled blood pressure (BP) subgroup (n = 397) and the uncontrolled BP subgroup (n = 1,207). Data on the average weekly intake of fish, eggs, milk, nuts, vegetables, fruit, and salt in the past year were collected. Higher intake was defined as greater than or equal to median food intake. RESULTS: Higher fish, egg, milk, nut, vegetable, and fruit intake correlated with lower hypertension prevalence, and fish and fruit intake were the strongest associated factors. Meanwhile, higher fruit intake, the highest quartile of egg or milk intake, and the lowest quartile of salt intake correlated with better BP control. Furthermore, the dietary pattern was associated with lower hypertension prevalence (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.84-0.92; P < 0.001) and better BP control (OR: 1.11, 95% CI: 1.03-1.21; P = 0.011). However, the dietary pattern did not correlate with BP control after excluding fruit intake. CONCLUSIONS: The dietary pattern correlated with lower hypertension prevalence and better BP control, and its association with BP control might be driven by higher fruit consumption.


Assuntos
Comportamento Alimentar , Hipertensão/epidemiologia , Cloreto de Sódio na Dieta/administração & dosagem , Adolescente , Adulto , Idoso , Animais , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Frutas , Humanos , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Leite , Nozes , Prevalência , Alimentos Marinhos , Verduras , Adulto Jovem
9.
Cardiology ; 141(4): 183-189, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30726843

RESUMO

The aims of this study were to investigate the association between different obesity indices and left ventricular mass (LVM) and to develop interventions for obese hypertensive patients to delay the progression of left ventricular hypertrophy (LVH). The association between the visceral adiposity index (VAI) and LVM was explored using multiple regression analysis in all subjects (n = 1,035), the subgroups of patients aged < 65 (n = 713) and ≥65 years (n = 322), and perimenopausal women (n = 319). The VAI was the only obesity index associated with LVH (OR = 1.134; 95% CI 1.025-1.254, p = 0.015). In the subgroup of patients aged < 65 years, both systolic blood pressure and VAI were risk factors for LVH. However, in the subgroup aged ≥65 years, only systolic blood pressure was a risk factor, and there was no association between VAI and LVH (p = 0.13). Perimenopause was an independent risk factor (OR = 1.786; 95% CI 1.125-2.837, p = 0.014). Reducing the VAI rather than the BMI or waist circumference may prevent LVH complications in obese hypertensive patients. For patients aged < 65 years strict control of blood pressure and obesity may be important, and for those aged ≥65 years blood pressure control should be the priority. Estrogen replacement may be useful in postmenopausal women to prevent LVH.


Assuntos
Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Obesidade/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Ecocardiografia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Adulto Jovem
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