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1.
Ann Rheum Dis ; 82(10): 1328-1340, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37487609

RESUMO

OBJECTIVES: The protective role of sodium glucose cotransporter 2 (SGLT2) inhibitors in renal outcomes has been revealed by large cardiovascular outcome trials among patients with type 2 diabetes. However, the effect of SGLT2 inhibitors on lupus nephritis (LN) and its underlying mechanisms remain unknown. METHODS: We applied empagliflozin treatment to lupus-prone MRL/lpr mice to explore the renal protective potential of SGLT2 inhibitors. An SGLT2 knockout monoclonal podocyte cell line was generated using the CRISPR/Cas9 system to examine the cellular and molecular mechanisms. RESULTS: In MRL/lpr mice treated with empagliflozin, the levels of mouse anti-dsDNA IgG-specific antibodies, serum creatinine and proteinuria were markedly decreased. For renal pathology assessment, both the glomerular and tubulointerstitial damages were lessened by administration of empagliflozin. The levels of SGLT2 expression were increased and colocalised with decreased synaptopodin in the renal biopsy samples from patients with LN and MRL/lpr mice with nephritis. The SGLT2 inhibitor empagliflozin could alleviated podocyte injury by attenuating inflammation and enhanced autophagy by reducing mTORC1 activity. Nine patients with LN treated with SGLT2 inhibitors with more than 2 months of follow-up showed that the use of SGLT2 inhibitors was associated with a significant decrease in proteinuria from 29.6% to 96.3%. Moreover, the estimated glomerular filtration rate (eGFR) was relatively stable during the treatment with SGLT2 inhibitors. CONCLUSION: This study confirmed the renoprotective effect of SGLT2 inhibitors in lupus mice, providing more evidence for non-immunosuppressive therapies to improve renal function in classic autoimmune kidney diseases such as LN.


Assuntos
Diabetes Mellitus Tipo 2 , Nefrite Lúpica , Podócitos , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Camundongos , Autofagia , Imunoglobulina G/metabolismo , Inflamação/patologia , Rim/patologia , Nefrite Lúpica/tratamento farmacológico , Camundongos Endogâmicos MRL lpr , Podócitos/patologia , Proteinúria , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Humanos
2.
Front Pharmacol ; 14: 1038457, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37201027

RESUMO

Introduction: Kidney cancer is one of the most common and lethal urological malignancies. Discovering a biomarker that can predict prognosis and potential drug treatment sensitivity is necessary for managing patients with kidney cancer. SUMOylation is a type of posttranslational modification that could impact many tumor-related pathways through the mediation of SUMOylation substrates. In addition, enzymes that participate in the process of SUMOylation can also influence tumorigenesis and development. Methods: We analyzed the clinical and molecular data which were obtanied from three databases, The Cancer Genome Atlas (TCGA), the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC), and ArrayExpress. Results: Through analysis of differentially expressed RNA based on the total TCGA-KIRC cohort, it was found that 29 SUMOylation genes were abnormally expressed, of which 17 genes were upregulated and 12 genes were downregulated in kidney cancer tissues. A SUMOylation risk model was built based on the discovery TCGA cohort and then validated successfully in the validation TCGA cohort, total TCGA cohort, CPTAC cohort, and E-TMAB-1980 cohort. Furthermore, the SUMOylation risk score was analyzed as an independent risk factor in all five cohorts, and a nomogram was constructed. Tumor tissues in different SUMOylation risk groups showed different immune statuses and varying sensitivity to the targeted drug treatment. Discussion: In conclusion, we examined the RNA expression status of SUMOylation genes in kidney cancer tissues and developed and validated a prognostic model for predicting kidney cancer outcomes using three databases and five cohorts. Furthermore, the SUMOylation model can serve as a biomarker for selecting appropriate therapeutic drugs for kidney cancer patients based on their RNA expression.

3.
Ann Noninvasive Electrocardiol ; 27(4): e12966, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35567783

RESUMO

BACKGROUND: Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear. METHODS: We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R') wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms). RESULTS: Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350-8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238-3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005-1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531-3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104-1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006-1.041; p = 0.007), and class I or III anti-arrhythmic drug use (OR, 10.534; 95% CI, 7.090-15.651; p < 0.001) were associated with AF. CONCLUSION: Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.


Assuntos
Fibrilação Atrial , Bloqueio de Ramo , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Bloqueio de Ramo/complicações , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/epidemiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
4.
BMC Cardiovasc Disord ; 21(1): 587, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876011

RESUMO

BACKGROUND: In patients with atrial fibrillation (AF) and functional mitral regurgitation (MR), catheter ablation reduces the severity of MR and improves cardiac remodeling. However, its effects on prognosis are uncertain. METHODS: This retrospective study included 151 consecutive patients with AF and functional MR, 82 (54.3%) of whom were treated by catheter ablation (Ablation group) and 69 (45.7%) with drug therapy without ablation (Non-ablation group). Forty-three pairs of these patients were propensity matched on the basis of age, CHA2DS2-VASc scores, and left ventricular ejection fraction. The primary outcome evaluated was severity of MR, cardiac remodeling and the combined incidence of subsequent heart failure-related hospitalization and strokes/transient ischemic attacks. RESULTS: Patients in the Ablation group showed a significant decrease in the severity of MR (p < 0.001), a significant decrease in the left atrial diameter (p = 0.010), and significant improvement in the left ventricular ejection fraction (p = 0.015). However, patients in the Non-ablation group showed only a significant decrease in the severity of MR (p = 0.004). The annual incidence of the studied events was 4.9% in the Ablation group and 16.7% in the Non-ablation group, the incidence being significantly lower in the ablation than Non-ablation group (p = 0.026) according to Kaplan-Meier curve analyses. According to multivariate Cox regression analysis, catheter ablation therapy (hazard ratio [HR] 0.27, 95% confidence interval [CI] 0.09-0.84; p = 0.024) and heart failure at baseline (HR 3.84, 95% CI 1.07-13.74; p = 0.038) were independent predictors of the incidence of the studied events. CONCLUSIONS: Among patients with AF and functional MR, catheter ablation was associated with a significantly lower combined risk of heart failure-related hospitalization and stroke than in a matched cohort of patients receiving drug therapy alone.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/fisiopatologia , Potenciais de Ação , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Frequência Cardíaca , Humanos , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Recuperação de Função Fisiológica , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
5.
J Cell Mol Med ; 25(14): 6746-6759, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34132026

RESUMO

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.


Assuntos
Fibrilação Atrial/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteína Smad3/metabolismo , Transativadores/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Angiotensina II/toxicidade , Animais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etiologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Células Cultivadas , Fibrose , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Transativadores/metabolismo
6.
Clin Cardiol ; 43(12): 1511-1516, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33002216

RESUMO

BACKGROUND: Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff-Parkinson-White (WPW) syndrome and paroxysmal AF, in other patients it can recur. HYPOTHESIS: Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. METHODS: We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P-wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12-lead electrocardiography (ECG). RESULTS: During the mean follow-up period of 30.9 ± 9.2 months (range, 3-36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26-1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). CONCLUSIONS: PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12-lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.


Assuntos
Fibrilação Atrial/cirurgia , Fascículo Atrioventricular/fisiopatologia , Ablação por Cateter/métodos , Frequência Cardíaca/fisiologia , Veias Pulmonares/cirurgia , Síndrome de Wolff-Parkinson-White/complicações , Adulto , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Síndrome de Wolff-Parkinson-White/fisiopatologia , Síndrome de Wolff-Parkinson-White/cirurgia
7.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4685-4690, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872665

RESUMO

To investigate the protective effect and mechanism of curcumin on aorta in rats with metabolic syndrome,72 SD rats were randomly divided into blank control group,model control group,positive control group,curcumin low,middle and high dose groups.The rat model of metabolic syndrome was established in all groups except the blank control group. After the intervention by curcumin,the blood pressure,blood lipid,blood glucose,serum insulin and insulin sensitivity index were measured. The contents of serum leptin(LP),adiponectin(ADP) and tumor necrosis factor-α(TNF-α) in rat aorta were detected by enzyme-linked immunosorbent assay(ELISA),and the pathological changes of rat thoracic aorta were observed by HE staining and electron microscope scanning. Western blot assay was used to detect the expression of inducible nitric oxide synthase(i NOS) and endothelial nitric oxide synthase(e NOS) in rats. The results showed that the blood lipid level,fasting blood glucose,fasting insulin,insulin sensitivity index,systolic blood pressure,LP,TNF-α and intima/media thickness ratio in the model control group were significantly higher than those in the blank control group. As compared with the model control group,the levels of blood lipids,fasting blood glucose,fasting insulin,insulin sensitivity index,systolic blood pressure,LP,TNF-α and intima/media thickness ratio were significantly decreased in positive control group,low,middle and high dose curcumin groups. The difference was statistically significant. The results of HE staining showed that the intima of the thoracic aorta in the model group was significantly thickened; the endothelial cell membrane was wrinkled and the organelle was ruptured. The intima of the thoracic aorta in the positive control group was slightly thickened and the structure of endothelial cells was intact,with no foam cells and no abnormality in the adventitia. There was no significant thickening of the thoracic aorta in the low,middle and high dose curcumin groups,and the endothelial cells were still intact. The results of Western blot assay showed that the expression levels of i NOS and e NOS were decreased significantly in the model group,while the expression levels of i NOS and e NOS were increased significantly in the positive control group and curcumin groups. The results indicated that curcumin had a certain protective effect on the aorta of rats with metabolic syndrome and improves the aortic endothelial dysfunction,and its mechanism may be related to the fact that curcumin could reduce the production of oxygen free radicals and up-regulate the expression of i NOS and e NOS in aorta.


Assuntos
Curcumina/farmacologia , Síndrome Metabólica , Substâncias Protetoras/farmacologia , Animais , Aorta , Aorta Torácica , Células Endoteliais , Ratos , Ratos Sprague-Dawley
8.
Clin Cardiol ; 42(9): 806-811, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243791

RESUMO

BACKGROUND: Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur. HYPOTHESIS: We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation. METHODS: This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12-lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P-wave duration of >120 ms and biphasic [±] morphology in the inferior leads. RESULTS: During the mean follow-up period of 30.9 ± 20.0 months (range, 2-71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event-free survival from AF (P < .001). Cox regression analysis with adjustment for the left atrial diameter and CHA2 DS2 -VASc score identified advanced IAB (hazard ratio, 9.18; 95% confidence interval [CI], 2.30-36.72; P = .002) and age > 50 years (hazard ratio, 12.64; 95% CI, 1.33-119.75; P = .027) as independent predictors of AF recurrence. CONCLUSIONS: Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.

9.
Int Heart J ; 59(6): 1261-1265, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30369573

RESUMO

Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS2 scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS2 score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS2 score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS2 score of ≥ 2 with IAB compared with a CHADS2 score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS2 score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS2 score was significantly associated with the development of IAB in this study population.


Assuntos
Técnicas de Apoio para a Decisão , Bloqueio Interatrial/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Bloqueio Interatrial/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Estudos Retrospectivos , Fatores de Risco
10.
Exp Ther Med ; 15(2): 1959-1965, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434790

RESUMO

Oxidative stress and apoptosis serve an essential role in cisplatin-induced cardiotoxicity, which limits its clinical use, and increases the risk of cardiovascular disease. As a natural drug, the antioxidant and antitumor effects of cyanidin have been recognized, but its protective effect on cisplatin-induced cardiomyocyte cytotoxicity remains unclear. H9c2 cells were treated with cisplatin (1-40 µM) in the presence or absence of cyanidin (40-80 µM), subsequently; oxidative stress, apoptosis and mitochondrial function were assessed using several techniques. The results demonstrated that cyanidin was able to dose-dependently reverse cisplatin-induced cell damage and apoptosis, attenuate the accumulation of reactive oxygen species (ROS), and mitochondrial membrane potential depolarization, downregulate the expression of Bcl-2 homologous antagonist/killer, upregulate the expression of apoptosis regulator Bcl-2, and reduce the activation of caspase 3, caspase 9, but not caspase 8. Furthermore, the results revealed that the translocation of apoptosis regulator Bax (Bax) from the cytoplasm to the mitochondrial membrane serves an essential role in cisplatin-induced apoptosis. Cyanidin was able to block the translocation of Bax and reduce the release of cytochrome c from cytoplasm. These data indicate that cyanidin attenuates cisplatin-induced cardiotoxicity by inhibiting ROS-mediated apoptosis, while the mitochondrial and extracellular regulated kinase signaling pathways may also serve important roles.

11.
Exp Ther Med ; 14(3): 2335-2340, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28962164

RESUMO

Atherosclerosis is a chronic inflammatory disease, which is associated with the increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). Cordycepin is one of the major bioactive components of Ophiocordyceps sinensis that has been demonstrated to exert anti-atherogenic activity; however, its molecular mechanisms are poorly understood. The aim of the present study was to examine the in vitro effects of cordycepin on the tumor necrosis factor (TNF)-α-induced suppression of adhesion molecule expression. The results of the present study demonstrated that cordycepin markedly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in TNF-α-stimulated human aortic vascular smooth muscle cells (HA-VSMCs). Cordycepin significantly inhibited the TNF-α-induced mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) activation (P<0.05), markedly inhibited the TNF-α-induced expression level of nuclear factor (NF)-κB p65 and markedly prevented the TNF-α-associated degradation of IκBα in HA-VSMCs. The results of the present study suggest that cordycepin inhibits the expression of VCAM-1 and ICAM-1 in TNF-α-stimulated HA-VSMCs via downregulating the MAPK/Akt/NF-κB signaling pathway. Therefore, cordycepin may have a potential therapeutic application for preventing the advancement of atherosclerotic lesions.

12.
Mol Med Rep ; 16(5): 6354-6359, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28849173

RESUMO

Increased expression of adhesion molecules is thought to serve an important role in the pathogenesis of atherosclerosis. Myricitrin, a bioactive compound of Myrica cerifera, has been demonstrated to exhibit anti­atherogenic effects. However, the effect of myricitrin on the expression of adhesion molecules in vascular smooth muscle cells (VSMCs) remains unknown. Therefore, the aim of the present study was to evaluate the inhibitory effects of myricitrin on tumor necrosis factor­α (TNF­α)­induced expression of adhesion molecules in VSMCs in vitro. The results revealed that myricitrin inhibited the adhesion of human THP­1 monocyte cells to TNF­α­stimulated mouse MOVAS­1 VSMC cells, and reduced the expression of adhesion molecules in TNF­α­stimulated MOVAS­1 cells. In addition, myricitrin significantly inhibited the TNF­α­induced expression of nuclear factor (NF)­κB p65, and prevented the TNF­α­induced degradation of nuclear factor of κ light chain enhancer in B­cells inhibitor α. Furthermore, myricitrin inhibited the production of intracellular reactive oxygen species in TNF­α­stimulated MOVAS­1 cells. In conclusion, the results of the present study indicated that myricitrin inhibits the expression of vascular cell adhesion protein­1 and intercellular adhesion molecule­1 in TNF­α­stimulated MOVAS­1 cells potentially via the NF­κB signaling pathway. Therefore, myricitrin may be an effective pharmacological agent for the prevention or treatment of atherosclerosis.


Assuntos
Antioxidantes/farmacologia , Fármacos Cardiovasculares/farmacologia , Flavonoides/farmacologia , Molécula 1 de Adesão Intercelular/genética , Miócitos de Músculo Liso/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Molécula 1 de Adesão de Célula Vascular/genética , Animais , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Myrica/química , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Células THP-1 , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/antagonistas & inibidores , Molécula 1 de Adesão de Célula Vascular/metabolismo
13.
J Atheroscler Thromb ; 24(2): 176-184, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27301462

RESUMO

AIM: To evaluate the role of CHADS2 and CHA2DS2-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF). METHODS: A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63±10 years) with IAB and without AF. IAB was defined as P-wave duration >120 ms using a 12-lead electrocardiogram. CHADS2 and CHA2DS2-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA. RESULTS: During the mean follow-up period of 4.9±0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2 score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562-0.715; P=0.001] and the CHA2DS2-VASc score (AUC, 0.671; 95% CI, 0.599-0.744; P<0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2 score ≥3 (sensitivity=0.455 and specificity=0.747) and a CHA2DS2-VASc score ≥4 (sensitivity=0.564 and specificity=0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2 [hazard ratio (HR), 1.442; 95% CI, 1.171-1.774; P=0.001] and CHA2DS2-VASc (HR, 1.420; 95% CI, 1.203-1.677; P<0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins. CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.


Assuntos
Fibrilação Atrial , Bloqueio Cardíaco/complicações , Medição de Risco/métodos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Idoso , Técnicas de Apoio para a Decisão , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos
14.
Oncotarget ; 8(12): 20371-20379, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27901494

RESUMO

We sought to comprehensively assess the efficacy of Intermittent Pneumatic Compression (IPC) in patients undergoing gynecologic surgery. A computerized literature search was conducted in Pubmed, Embase and Cochrane Library databases. Seven randomized controlled trials involving 1001 participants were included. Compared with control, IPC significantly lowered the deep vein thrombosis (DVT) risk [risk ratio (RR) = 0.33, 95% confidence interval (CI): 0.16 - 0.66]. The incidence of DVT in IPC and drugs group was similar (4.5% versus. 3.99%, RR = 1.19, 95% CI: 0.42 - 3.44). With regards to pulmonary embolism risk, no significant difference was observed in IPC versus control or IPC versus drugs. IPC had a lower postoperative transfusion rate than heparin (RR = 0.53, 95% CI: 0.32 - 0.89), but had a similar transfusion rate in operating room to low molecular weight heparin (RR = 1.06, 95% CI: 0.69 - 1.63). Combined use of IPC and graduated compression stockings (GCS) had a marginally lower risk of DVT than GCS alone (RR = 0.38, 95% CI: 0.14 - 1.03). In summary, IPC is effective in reducing DVT complications in gynecologic surgery. IPC is neither superior nor inferior to pharmacological thromboprophylaxis. However, whether combination of IPC and chemoprophylaxis is more effective than IPC or chemoprophylaxis alone remains unknown in this patient population.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Dispositivos de Compressão Pneumática Intermitente , Tromboembolia Venosa/prevenção & controle , Feminino , Humanos
15.
Int Heart J ; 57(5): 580-5, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27593538

RESUMO

Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS2 score, an AF-related risk score for ischemic stroke, with new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 ± 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS2 score as ≥ 2 points. During the mean follow-up period of 4.8 ± 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS2 score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS2 score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS2 score compared with no IAB and a low CHADS2 score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS2 score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS2 score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.


Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Eletrocardiografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Função Atrial/fisiologia , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia
16.
J Cardiol ; 68(4): 352-6, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26611936

RESUMO

BACKGROUND: It has been demonstrated that advanced interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF); however, the impact of advanced IAB on recurrence of paroxysmal AF after catheter ablation is not clear. METHODS: 204 consecutive patients with paroxysmal AF who underwent index circumferential pulmonary vein (PV) isolation were prospectively enrolled. In all patients, a resting electrocardiogram in sinus rhythm was evaluated for the presence of advanced IAB, defined as a P-wave duration >120ms and biphasic (±) morphology in the inferior leads. Advanced IAB was detected in 20.1% of patients. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30s beyond 3 months after the catheter ablation in the absence of any antiarrhythmic treatment. RESULTS: During the mean follow-up period of 13.9±6.2 months (range, 3-27 months), 62 patients (30.4%) developed recurrence of AF. The recurrence rate was higher in patients with advanced IAB than those without advanced IAB (46.3% vs. 26.4%, p=0.006). Cox regression analysis with adjustment for age, P-wave duration, CHADS2 score, and PV isolation identified advanced IAB (hazard ratio, 2.111; 95% confidence interval, 1.034-4.308; p=0.040) and left atrial diameter (hazard ratio, 1.051; 95% confidence interval, 1.004-1.100; p=0.034) as two independent predictors of recurrence of AF. CONCLUSIONS: Patients with advanced IAB were at an increased risk of AF recurrence after catheter ablation.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Átrios do Coração , Bloqueio Cardíaco/diagnóstico , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/cirurgia , Recidiva
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