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1.
J Integr Plant Biol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995105

RESUMO

Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis, the interaction between the membrane and cytoskeleton is poorly understood. Cotton fibers are extremely elongated single cells, which makes them an ideal model for studying cell development. Here, we used the sphingolipid biosynthesis inhibitor, fumonisin B1 (FB1), and found that it effectively suppressed the myeloblastosis (MYB) transcription factor GhMYB86, thereby negatively affecting fiber elongation. A direct target of GhMYB86 is GhTUB7, which encodes the tubulin protein, the major component of the microtubule cytoskeleton. Interestingly, both the overexpression of GhMYB86 and GhTUB7 caused an ectopic microtubule arrangement at the fiber tips, and then leading to shortened fibers. Moreover, we found that GhMBE2 interacted with GhMYB86 and that FB1 and reactive oxygen species induced its transport into the nucleus, thereby enhancing the promotion of GhTUB7 by GhMYB86. Overall, we established a GhMBE2-GhMYB86-GhTUB7 regulation module for fiber elongation and revealed that membrane sphingolipids affect fiber elongation by altering microtubule arrangement.

2.
Biochem Biophys Res Commun ; 660: 73-81, 2023 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-37068391

RESUMO

Cardiac fibrosis is a common pathological feature of cardiac remodelling process with disordered expression of multiple genes and eventually lead to heart failure. Emerging evidence suggests that long noncoding RNAs (lncRNAs) have emerged as critical regulators of various biological processes. However, the exact mechanisms of lncRNAs as mediators in cardiac fibrosis have not been fully elucidated. This study aimed to profile the lncRNA expression pattern in human cardiac fibroblasts (HCFs) with cardiac fibrosis. We treated HCFs with transforming growth factor-ß (TGF-ß) to induce their activation. Then, strand-specific RNA-seq was performed to profile and classify lncRNAs; and perform functional analysis in HCFs. We study the transformation of HCFs with molecular and cell biology methods. Among all identified lncRNA candidates, 176 and 526 lncRNAs were upregulated and downregulated respectively in TGF-ß-stimulated HCFs compared with controls. Functional analyses revealed that the target genes of differentially expressed lncRNAs were mainly related to focal adhesion, metabolic pathways, Hippo signaling pathway, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy. As a representative, novel lncRNAs NONHSAG005537 and NONHSAG017620 inhibited the proliferation, migration, invasion, and transformation of HCFs induced by TGF-ß. Collectively, our study established the expression signature of lncRNAs in cardiac fibrosis and demonstrated the cardioprotective role of NONHSAG005537 and NONHSAG017620 in cardiac fibrosis, providing a promising target for anti-fibrotic therapy.


Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fibrose , Fibroblastos/metabolismo , Fator de Crescimento Transformador beta/metabolismo
3.
Echocardiography ; 40(1): 57-60, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36514962

RESUMO

Abernethy malformation, also known as congenital extrahepatic shunt, is a rare anomaly, which is characterized by partial or complete diversion of the portal blood into the systemic venous circulation. The clinical manifestations of Abernethy malformation during childhood include neonatal cholestasis, failure to thrive, mental retardation, and other congenital defects. We report a case of Abernethy malformation Type II in a 9-year-old boy, whose left ventricle was slightly enlarged because of several major aortopulmonary collateral arteries (MAPCAs) but laboratory examinations were normal 5 years earlier. The characteristics of congenital heart disease in patients with Abernethy malformation are discussed. We propose that physicians should be aware of the possibility of Abernethy malformation in children with enlargement of the left ventricular due to systemic-pulmonary collateral circulation.


Assuntos
Cardiopatias Congênitas , Malformações Vasculares , Masculino , Criança , Humanos , Recém-Nascido , Veia Porta/anormalidades , Malformações Vasculares/diagnóstico , Malformações Vasculares/diagnóstico por imagem , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem
4.
Cell Mol Biol (Noisy-le-grand) ; 68(5): 207-212, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36029488

RESUMO

The study aimed to explore the correlations of the results of the high-frequency ultrasound evaluation of the brachial artery endothelial dilatation and carotid atherosclerosis with glucose and lipid metabolism, inflammatory cytokines, the severity of coronary artery disease (CAD) and vascular endothelial function in elderly patients. 78 elderly patients with CAD in Beijing Anzhen Hospital were selected. The high-frequency ultrasonography was carried out to observe the flow-mediated dilatation (FMD) and intima-media thickness (IMT) and to analyze their correlations with inflammatory cytokines [C-reactive protein (CRP) and plasminogen activator inhibitor (PAI-1)], endothelial function [nitric oxide (NO) and endothelin-1 (ET-1)], glycolipid metabolism [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and fasting blood glucose (FBG)] and the severity of CAD. FMD, NO and HDL-C: patients with single-vesselCAD> those with double-vessel CAD>those with multi-vessel CAD. IMT, CRP, PAI-1, FBG, ET-1, TC and TG: patients with single-vesselCAD< those with double-vessel CAD

Assuntos
Doenças das Artérias Carótidas , Doença da Artéria Coronariana , Idoso , Artéria Braquial , Proteína C-Reativa , Artérias Carótidas , Espessura Intima-Media Carotídea , Colesterol , Citocinas , Dilatação , Endotélio Vascular , Glucose , Humanos , Metabolismo dos Lipídeos , Inibidor 1 de Ativador de Plasminogênio , Triglicerídeos , Ultrassonografia
5.
Rev Cardiovasc Med ; 22(2): 531-536, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258922

RESUMO

The role of lipocalin 2 (LCN2) in pulmonary hypertension (PH) in pediatric patients with congenital heart disease (CHD) remains unclear. We sought to investigate whether LCN2 could be a potential biomarker for PH in pediatric patients who underwent surgery for CHD. From December 2018 to February 2020, patients undergoing surgical repair for congenital defects with and without PH were identified. Healthy children without CHD and PH served as controls. A mean pulmonary artery pressure (mPAP) >20 mmHg was used as the definition of PH. Blood samples and echocardiograms were obtained in all patients and right heart catheterization was performed in 79 patients. Multivariable logistic regression analysis was used to determine potential predictors for PH. Among 102 patients, the median age was 10 [Interquartile range (IQR) 7.0-13] months, and 37.5% were female. Compared to non-PH patients and controls, PH patients showed elevated levels of LCN2 (P < 0.001). In addition, LCN2 levels positively correlated with the invasive haemodynamic indices of PH. In univariate regression, LCN2 (odds ratio = 2.69 [1.06-5.31], P < 0.001), N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) (OR = 1.91 [1.21-7.56], P = 0.03) and high-sensitive troponin T (hsTnT) (OR = 1.36 [1.01-3.57], P = 0.01) were associated with PH; however, only LCN2 (OR = 1.68 [1.04-4.52], P = 0.03) was significantly associated with PH on multivariate analysis. In conclusion, children with PH had increased LCN2 expression. LCN2 levels positively correlated with invasive indices of PH. These results indicate LCN2 could be a useful biomarker for prediction of PH in pediatric CHD cases.


Assuntos
Cardiopatias Congênitas , Hipertensão Pulmonar , Adolescente , Biomarcadores , Criança , Ecocardiografia , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Lipocalina-2 , Masculino , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos
6.
Echocardiography ; 38(9): 1666-1672, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34505316

RESUMO

Preexcitation cardiomyopathy is a rare cardiac anomaly but it can be life threatening. It may occur in type B preexcitation syndrome. A patients with this condition typically has an enlarged left ventricle and reduced systolic function without tachycardia-associated cardiomyopathy. Echocardiography plays an important role in diagnosis in identifying this condition by revealing the "rebounce" movement of the inter-ventricular septum (IVS). We report echocardiographic findings of five pediatric patients with preexcitation cardiomyopathy. All of them had a radiofrequency catheter ablation (RFCA) and recovered during the follow-up.


Assuntos
Cardiomiopatias , Síndromes de Pré-Excitação , Síndrome de Wolff-Parkinson-White , Cardiomiopatias/diagnóstico por imagem , Criança , Ecocardiografia , Eletrocardiografia , Humanos , Síndromes de Pré-Excitação/complicações
7.
Pediatr Cardiol ; 42(2): 425-431, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33394115

RESUMO

The impact of reverse left ventricular remodeling (r-LVR) on clinical outcomes after surgical correction of anomalous left coronary artery from the pulmonary artery (ALCAPA) remains unclear. This study aims to examine the prognostic significance of r-LVR in patients with ALCAPA after surgery. We prospectively identified 61 patients undergoing surgical correction for ALCAPA; 54 patients had adequate echocardiographic image quality with quantitative biplane analysis performed both at baseline and at 30-day postoperative follow-up. Postoperative r-LVR was defined as a reduction of ≥ 10% in left ventricular end-diastolic volume index during follow-up. Cox proportional-hazards regression was used to investigate the independent association of r-LVR and all-cause mortality. Among 54 patients (age: 21.2 ± 7 months; 37% females), r-LVR occurred in 35 patients (64.8%) after surgery. Compared to patients with r-LVR, patients without r-LVR had significantly higher level of N-terminal pro B-type natriuretic peptide (NT-proBNP) [2176 (711, 4219) vs 998 (623, 2145) P < 0.001] and lower survival rate (47.3% vs 82.9%, HR = 5.72 [1.96 to 17.20], P < 0.001) at 1-year follow-up. NT-proBNP (OR = 2.27 [1.67 to 18.3], P = 0.02) was an independent predictor of r-LVR in multivariate analysis. Moreover, r-LVR was significantly associated with a lower rate of all-cause mortality (HR = 0.27 [0.08 to 0.98], P = 0.03) in multivariate analysis, even after adjustment for clinical and echocardiographic variables. R-LVR occurred in more than half of patients with ALCAPA undergoing surgical correction and it was associated with better clinical outcomes. NT-proBNP is an independent predictor of r-LVR.


Assuntos
Artéria Coronária Esquerda Anormal/cirurgia , Remodelação Ventricular , Estudos de Casos e Controles , Pré-Escolar , Ecocardiografia/métodos , Feminino , Humanos , Lactente , Masculino , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Artéria Pulmonar
8.
Environ Monit Assess ; 193(8): 484, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241705

RESUMO

Understanding the complexity of catchment-scale human activities, natural factors, and stream water quality is particularly important for basin water resources management. Thorough investigations on how multiple environmental factors quantitatively and simultaneously affect water quality are limited. This study employed Spearman's correlation and ridge regression analysis (RRA) to disentangle the hydraulic geometry and land use contributions to water quality variables (WQVs). Nine and six indicators were used to describe the hydraulic geometry and land use characteristics, respectively, in the Taihu Basin. The results revealed significant correlations between the land use, hydraulic geometry, and stream water quality. Built-up land and cropland negatively impacted the stream water quality, while woodland had the opposite trend. The structure and morphological connectivity of the river network were associated with most WQVs. The hydrologic connectivity characteristics strongly influenced ammonia-nitrogen (NH3-N), permanganate index (CODMn), and dissolved oxygen (DO). Six equations that estimated the stream water quality were established through RRA. Human factors impose a greater impact on the stream water quality than natural factors in the Taihu Basin. Our findings provide quantitative insights to mitigate water pollution via reasonable management and control of the river structure and connectivity and land-use patterns.


Assuntos
Rios , Qualidade da Água , China , Monitoramento Ambiental , Humanos , Poluição da Água/análise
9.
J Interv Cardiol ; 2020: 8242790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177964

RESUMO

OBJECTIVES: This study aimed to explore the selection of views for transthoracic echocardiography-guided transfemoral puncture for the device closure of pediatric atrial septal defect (ASD) without radiation. METHODS: Sixty children (29 males and 31 females) were diagnosed with a central ASD, normal heart function, and no other intracardiac deformity. All procedures were performed in a surgical operating room (without radiological equipment) under basic anesthesia; the femoral vein pathway and guidance by only transthoracic echocardiography were used to complete the device closure of the ASD. The subcostal acoustic window and parasternal aorta short-axis views were used to guide the extra stiff wire and catheter into the left atrium. All procedures were performed under the subcostal biatrial section. The sheath entered the left atrium, and the apical four-chamber view was used to monitor the delivery and release of the occluder. RESULTS: Successful closure of the ASD was achieved in all cases. The operating time from the end of the puncture to the release of the occluder was 10.36 ± 3.57 minutes. No other incisions were needed in 60 cases. No occluders were removed, and no residual shunt or pericardial effusions were detected after the procedures, during the non-ICU stay time. The average hospital stay was 2.19 ± 0.58 days. CONCLUSION: The accurate selection of transthoracic echocardiographic views can better ensure the safety and effectiveness of ASD closure through the femoral vein without radiation in children.


Assuntos
Ecocardiografia/métodos , Comunicação Interatrial , Implantação de Prótese , Dispositivo para Oclusão Septal , Cirurgia Assistida por Computador/métodos , Cateterismo Periférico/métodos , Criança , Pré-Escolar , Feminino , Veia Femoral/cirurgia , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/cirurgia , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos
10.
Echocardiography ; 37(12): 2139-2143, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33070402

RESUMO

Shone's syndrome is a rare congenital heart disease that includes 4 cardiovascular anomalies: supravalvular mitral ring, parachute mitral valve, subaortic stenosis, and coarctation of the aorta. Early diagnosis and treatment result in better outcomes. Echocardiography plays an important role in the diagnosis and is the optimal examination for detecting this disease. Pressure gradients are often unreliable and inaccurate; thus, careful anatomical observation of the left ventricular inflow and outflow tracts, particularly the mitral valve, is vital for accurate diagnosis and planning appropriate management. Herein, we describe 9 cases of Shone's syndrome, diagnosed with echocardiography and treated surgically.


Assuntos
Coartação Aórtica , Cardiopatias Congênitas , Estenose da Valva Mitral , Coartação Aórtica/diagnóstico por imagem , Ecocardiografia , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Estenose da Valva Mitral/diagnóstico por imagem , Síndrome
11.
J Cell Biochem ; 120(3): 3709-3715, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30368869

RESUMO

Acute statin treatment has been reported to be critical in protecting the cardiac cells against ischemia/reperfusion injury by activating PI3K/Akt signal pathway. In vitro rat myocardial ischemia/reperfusion model, chronic statin treatment led to upregulation of phosphatase and tensin homolog (PTEN). This has been potentially indicated the correlation in PTEN and protective effect of statin on myocardium. In this current study, we evaluated the role of sodium orthovanadate a nonspecific inhibitor to PTEN and its correlation with atorvastatin on protecting myocardium against ischemia/reperfusion injury. We found a long-term statin treatment could increase the PTEN level, and this process was counteracted in the presence of sodium orthovanadate. However, the phosphotyrosine level was not affected by this statin. Besides, this process was mediated by Akt signaling since phosphorylated Akt level was altered by statin and sodium orthovanadate treatment. In a conclusion, this study showed a potential mechanism underlying PTEN-induced attenuation in long-term statin's therapeutic effect, which provided the new insight into the synergic role of PTEN and atorvastatin in protecting cardiac cells against ischemia/reperfusion injury.


Assuntos
Atorvastatina/efeitos adversos , Regulação para Baixo/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/enzimologia , PTEN Fosfo-Hidrolase/biossíntese , Vanadatos/farmacologia , Animais , Atorvastatina/farmacologia , Masculino , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/enzimologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley
12.
J Cell Biochem ; 120(7): 10972-10977, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30891810

RESUMO

OBJECTIVE: This study was designed to explore the protective effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) against ischemia/reperfusion (I/R) injury-induced cardiomyocytes apoptosis. METHODS: The H9c2 cell I/R injury model was induced by simultaneous shortage of nutrients and oxygen. TSG administration (0.10, 0.25, and 0.50 mM) was performed before and during I/R stimulation. Cell apoptosis was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Expression of cell-related proteins was detected to assess the effect of TSG on cell apoptosis. RESULTS: I/R injury induced significant cell apoptosis. Significantly decreased Bcl-2 and increased Bax, caspase-3, and p-Akt expression ( P < 0.01) was detected in the cell model of I/R injury. In contrast, TSG administration eliminated all the changes induced by I/R injury in a dose-dependent manner. Compared with the H9c2 cell model of I/R injury, the H9c2 cells treated with 0.50 mM TSG showed the lowest cell apoptosis percentage, the highest expression of Bcl-2, and the lowest expression of Bax, caspase-3, and p-Akt ( P < 0.01). CONCLUSION: We confirmed that the protective effect of TSG against I/R injury-induced cell apoptosis in H9c2 in vitro was associated with the Bcl-2/Bax ratio, caspase-3, and Akt activation.

13.
Gynecol Oncol ; 154(3): 583-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31307665

RESUMO

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) in locally advanced cervical cancer (LACC) patients treated with neoadjuvant concurrent chemoradiation (CCRT) or radiation (RT) alone followed by radical surgery (RS). METHODS: In a single-center retrospective study from a prospective database, 275 FIGO Stage IB2-IIIB patients who underwent CCRT/RT + RS were included. HRQOL was prospectively assessed by EORTC QLQ-C30 and EORTC QLQ-CX24 prior to any treatment (baseline) and 6 months after surgery, respectively. RESULTS: A statistically significant and clinically relevant improvement in physical functioning (P < 0.001) and role functioning (P = 0.002, P = 0.031) was observed in patients receiving either CCRT+RS or RT + RS at follow-up. In addition, quality of life (QoL), physical functioning, and social functioning were better in the RT + RS group than the CCRT+RS group after treatment (P = 0.028, P = 0.010, P = 0.014). Symptom scores of fatigue decreased in both groups over time (P < 0.001, P = 0.004) while insomnia decreased only in the RT + RS group (P = 0.042). Worsened menopausal symptoms were documented in both groups at follow-up (P = 0.001, P = 0.047), while lymphedema was deteriorated only in patients receiving CCRT + RS (P < 0.001). Sexuality scores did not differ between groups or over time with the exception of sexual worry, which was deteriorated in patients receiving RT + RS (P = 0.042). CONCLUSIONS: QLQ-C30 functioning and tumor-related symptoms scores improved while lymphedema and menopausal symptoms worsened 6 months after neoadjuvant CCRT or RT alone followed by RS in LACC patients. Patients treated with RT + RS had a generally better HRQOL compared with those receiving CCRT+RS, though further validation with prospective randomized clinical trials is warranted.


Assuntos
Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Qualidade de Vida , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/cirurgia
14.
Heart Fail Rev ; 23(3): 355-361, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28986727

RESUMO

There remains an ongoing controversy regarding the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of developing heart failure (HF). In addition, none of the animal studies suggested a mechanism for the DPP-4 inhibitors and HF risk. To date, advances in pharmacogenomics have enabled the identification of genetic variants in DPP-4 gene. Studies have shown that genetic polymorphisms in the gene encoding DPP-4 may be associated with potential pathways involved in HF risk. This review discusses the contradictory findings of DPP-4 inhibitors and HF and a potential role for pharmacogenomics. Pharmacogenomics of DPP-4 inhibitors is promising, and genetic information from randomized control trials is urgently needed to gain a full understanding of the safety of DPP-4 inhibitors and the risk of HF.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/farmacocinética , Insuficiência Cardíaca/etiologia , Farmacogenética/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Saúde Global , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Fatores de Risco
15.
Med Mycol ; 54(4): 394-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26468549

RESUMO

In our multicenter study, we studied the distribution of Candida species in vulvovaginal candidiasis patients and investigated antifungal susceptibility profile and genotype of Candida albicans in vaginal swab. A total of 115 Candida albicans strains were detected in 135 clinical isolates. Minimum inhibitory concentration determinations showed that 83% and 81% of the 115 Candida albicans strains were susceptible to fluconazole and voriconazole. Randomly amplified polymorphic DNA analysis (RAPD) was applied to identify clonally related isolates from different patients at the local level. All tested strains were classified into genotype A (77.4%), genotype B (18.3%), and genotype C (4.3%). Genotype A was further classified into five subtypes and genotype B into two subtypes.Candida albicans was the dominant pathogen of vulvovaginal candidiasis, the majority belonging to genotype A in this study. Exposure to azoles is a risk factor for the emergence of azole resistance among Candida albicans isolated from VVC patients.


Assuntos
Candida albicans , Candidíase Vulvovaginal/microbiologia , Farmacorresistência Fúngica/genética , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Candida albicans/isolamento & purificação , China , Feminino , Genótipo , Técnicas de Genotipagem , Maternidades , Humanos , Testes de Sensibilidade Microbiana , Técnica de Amplificação ao Acaso de DNA Polimórfico , Estudos Retrospectivos
16.
Exp Cell Res ; 333(1): 60-72, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25724898

RESUMO

Cytokine-induced antiapoptotic inhibitor 1 (CIAPIN1) was recently identified as an essential downstream effector of the Ras signaling pathway and has been confirmed to be closely associated with various malignant tumors. However, its potential role in regulating breast cancer metastasis remains unclear. Matrix metalloproteinases (MMPs) are a broad family of zinc-biding endopeptidases that participate in the extracellular matrix (ECM) degradation that accompanies cancer cell invasion, metastasis and angiogenesis. In this study, we found up-regulation of CIAPIN1 by lentiviral expression vector inhibited the migration, invasion and MMPs expression of MDA-MB-231 cells. Further, CIAPIN1 over-expression decreased NHE1 (Na(+)/H(+) exchanger 1) expression and ERK1/2 phosphorylation. Importantly, treating CIAPIN1 over-expressed MDA-MB-231 cells with the NHE1 specific inhibitor, Cariporide, further inhibited the metastatic capacity, MMPs expression and phosphorylated ERK1/2. Treatment with the MEK1 specific inhibitor, PD98059, induced nearly the same suppression of CIAPIN1 over-expression-dependent migration, invasion and MMPs expression as was observed with Cariporide. Further, Cariporide and PD98059 synergistically suppressed migration, invasion and MMPs expression of CIAPIN1 over-expressed MDA-MB-231 cells. Thus, our results revealed the mechanism by which CIAPIN1 targeted NHE1 to mediate migration and invasion of MDA-MB-231 cells through regulation of MMPs via ERK1/2 signaling pathway.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Metaloproteinases da Matriz/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Invasividade Neoplásica , Metástase Neoplásica , Trocador 1 de Sódio-Hidrogênio
17.
Eur Neurol ; 75(1-2): 48-57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26784899

RESUMO

BACKGROUND: Contemporary functional MRI (fMRI) methods can provide a wealth of information about the neural mechanisms associated with primary insomnia (PI), which centrally involve neural network circuits related to spatial working memory. METHODS: A total of 30 participants diagnosed with PI and without atypical brain anatomy were selected along with 30 age- and gender-matched healthy controls. Subjects were administered the Pittsburgh Sleep Quality Index (PSQI), Hamilton Rating Scale for Depression and clinical assessments of spatial working memory, followed by an MRI scan and fMRI in spatial memory task state. RESULTS: Statistically significant differences between PSQI and spatial working memory were observed between PI patients and controls (p < 0.01). Activation of neural networks related to spatial memory task state in the PI group was observed at the left temporal lobe, left occipital lobe and right frontal lobe. Lower levels of activation were observed in the left parahippocampal gyrus, right parahippocampal gyrus, bilateral temporal cortex, frontal cortex and superior parietal lobule. CONCLUSION: Participants with PI exhibited characteristic abnormalities in the neural network connectivity related to spatial working memory. These results may be indicative of an underlying pathological mechanism related to spatial working memory deterioration in PI, analogous to recently described mechanisms in other mental health disorders.


Assuntos
Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Biochim Biophys Acta ; 1842(2): 220-31, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24252614

RESUMO

Mitochondrial dysfunction is an early pathological feature of Alzheimer's disease (AD). The underlying mechanisms and strategies to repair it remain unclear. Here, we demonstrate for the first time the direct consequences and potential mechanisms of mitochondrial functional defects associated with abnormal mitochondrial dynamics in AD. Using cytoplasmic hybrid (cybrid) neurons with incorporated platelet mitochondria from AD and age-matched non-AD human subjects into mitochondrial DNA (mtDNA)-depleted neuronal cells, we observed that AD cybrid cells had significant changes in morphology and function; such changes associate with altered expression and distribution of dynamin-like protein (DLP1) and mitofusin 2 (Mfn2). Treatment with antioxidant protects against AD mitochondria-induced extracellular signal-regulated kinase (ERK) activation and mitochondrial fission-fusion imbalances. Notably, inhibition of ERK activation not only attenuates aberrant mitochondrial morphology and function but also restores the mitochondrial fission and fusion balance. These effects suggest a role of oxidative stress-mediated ERK signal transduction in modulation of mitochondrial fission and fusion events. Further, blockade of the mitochondrial fission protein DLP1 by a genetic manipulation with a dominant negative DLP1 (DLP1(K38A)), its expression with siRNA-DLP1, or inhibition of mitochondrial division with mdivi-1 attenuates mitochondrial functional defects observed in AD cybrid cells. Our results provide new insights into mitochondrial dysfunction resulting from changes in the ERK-fission/fusion (DLP1) machinery and signaling pathway. The protective effect of mdivi-1 and inhibition of ERK signaling on maintenance of normal mitochondrial structure and function holds promise as a potential novel therapeutic strategy for AD.


Assuntos
Doença de Alzheimer/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Células Híbridas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Antioxidantes/farmacologia , Dinaminas , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Células Híbridas/patologia , Immunoblotting , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Dinâmica Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/genética , Proteínas Mitocondriais/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Mutação , Neurônios/metabolismo , Neurônios/patologia , Probucol/farmacologia , Quinazolinonas/farmacologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
19.
Zhonghua Yi Xue Za Zhi ; 95(37): 3017-22, 2015 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-26814082

RESUMO

OBJECTIVE: To explore the cerebral blood flow (CBF) by three-dimensional arterial spin labeling (3D-ASL) and the standardized uptake value (SUV) of 18F-fluorodeoxyglucose (18F-FDG) in the prefrontal lobe of patients with major depression disorder (MDD), and analyze their correlations with patients' depressive symptoms. METHODS: 3D-ASL and 18F-FDG positron emission tomography/computed tomography (PET/CT) were performed in 17 MDD patients and 16 healthy controls under the resting state. The depressive symptoms were classified into seven factors using Hamilton depression rating scale. Regional cerebral blood flow (CBF) and standardized uptake value (SUV) were compared between the patients and healthy controls using a two-sample t-test, and the correlation between the CBF and SUV with the patient Hamilton scores was examined using Spearman analysis. RESULTS: Decreased regional CBF values were present in the bilateral middle and the right superior frontal gyrus in patients, and decreased regional SUVs were observed in the bilateral superior, middle and inferior frontal gyrus. The significant correlation between the CBF and SUV values with the patients' Hamilton scores was mainly observed in the left middle, right middle and the right inferior frontal gyrus. CONCLUSION: 18F-FDG PET/CT is more sensitive than ASL in identifying the functional abnormalities in the prefrontal lobe. Decreased CBF and SUV in the prefrontal lobe closely correlate with the Hamilton Depression Rating Scale scores. We speculate that the left middle frontal gyrus may be a key responsible functional region in patients with MDD.


Assuntos
Depressão , Transtorno Depressivo Maior , Córtex Pré-Frontal , Circulação Cerebrovascular , Fluordesoxiglucose F18 , Lobo Frontal , Glucose , Humanos , Tomografia por Emissão de Pósitrons , Marcadores de Spin
20.
Zhonghua Yi Xue Za Zhi ; 95(21): 1677-80, 2015 Jun 02.
Artigo em Chinês | MEDLINE | ID: mdl-26675798

RESUMO

OBJECTIVE: To explore abnormal brain activation of spatial working memory in primary insomnia and its potential neuromechanism. METHODS: we recruited 30 cases primary insomnia (PI) patients and 30 cases age, gender matched healthy control (HC) subjects from July 2013 to December 2013, the diagnosis of primary insomnia matched the diagnosis criterion of DSM-IV and Classification and diagnostic criteria of mental disorders in China third edition (CCMD-3). All the subjects attended the tests of PSQI, HAMA, HAMD and index of spatial working memory. And then, we collected the data of routine MRI and spatial working memory task fMRI on 3.0 T MRI scanner. After that, we used SPM8 and REST1.8 to analyze the fMRI data, compared difference of PSQI, HAMA, HAMD, index of spatial working memory and brain activation of spatial working memory between PI group and HC group. RESULTS: There were significant difference between PI group and HC group in PSQI, HAMA, HAMD and index of spatial working memory (P < 0.05). In the spatial working memory related activate brain region, compared with HC group, left temporal lobe, occipital lobe and right frontal lobe activation increased and bilateral parahippocampalis, temporal cortex, frontal cortex and superior parietal lobule activation reduced in PI group. CONCLUSION: Spatial working memory task fMRI revealed the pathological mechanisms of cognitive dysfunction of clinical spatial working memory and emotional disorder in primary insomnia patients.


Assuntos
Transtornos Cognitivos , Memória de Curto Prazo , Distúrbios do Início e da Manutenção do Sono , Encéfalo , China , Cognição , Humanos , Imageamento por Ressonância Magnética
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