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1.
Aust J Rural Health ; 28(2): 124-131, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31960537

RESUMO

OBJECTIVE: To study the effect of nurse-led counselling on the anxiety symptoms and the quality of life following percutaneous coronary intervention for stable coronary artery disease. DESIGN: Randomised control trial. SETTING: Rural and remote China. PARTICIPANTS: Rural and remote patients were consecutively recruited from a medical centre located in China between January and December 2014. INTERVENTIONS: The control group received standard pre-procedure information from a ward nurse on the processes of the hospitalisation and percutaneous coronary intervention, and post-procedural care. The intervention group received a structured 30-minute counselling session the day before and 24 hours after the percutaneous coronary intervention, by nurse consultants with qualifications in psychological therapies and counselling. The health outcomes were assessed by a SF-12 scale and the Seattle Angina Questionnaire at 6 and 12 months after percutaneous coronary intervention. The anxiety and depression symptoms were evaluated by a Zung anxiety and depression questionnaire. MAIN OUTCOME MEASURES: Cardiac outcomes, quality of life and mental health status. RESULTS: Eighty patients were randomly divided into control (n = 40) and intervention groups (n = 40). There was a significant increase in the scores of the three domains of Seattle Angina Questionnaire 12 months after percutaneous coronary intervention in the intervention group (P < .01). The mental health and physical health scores also increased (P < .01). In the control group, the mean scores of Zung self-rating anxiety scale 12 months following percutaneous coronary intervention were higher than the baseline scores, and higher than in the intervention group (P < .01). CONCLUSIONS: Counselling by a clinician qualified in psychological therapies and counselling significantly reduces anxiety symptoms and improves quality of life.

2.
Stem Cells Int ; 2019: 6768571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781243

RESUMO

Background/Objectives: Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3η signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 (Cav-1F92A) gene may enhance NO production. This study explored the effect of Cav-1F92A-modified rat bone marrow mesenchymal stem cells (rBMSC/Cav-1F92A) on oxidative stress regulation through CA1/kininogen and SelW/14-3-3η signal transduction in a rat model of monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Method: PAH was induced in rats through the subcutaneous injection of MCT. Next, rBMSC/Vector (negative control), rBMSC/Cav-1, rBMSC/Cav-1F92A, or rBMSC/Cav-1F92A+L-NAME were administered to the rats. Changes in pulmonary hemodynamic and vascular morphometry and oxidative stress levels were evaluated. CA1/kininogen and SelW/14-3-3η signal transduction, endothelial nitric oxide synthase (eNOS) dimerization, and eNOS/NO/sGC/cGMP pathway changes were determined through real-time polymerase chain reaction, Western blot, or immunohistochemical analyses. Results: In MCT-induced PAH rats, rBMSC/Cav-1F92A treatment reduced right ventricular systolic pressure, vascular stenosis, and oxidative stress; downregulated CA1/kininogen signal transduction; upregulated SelW/14-3-3η signal transduction; and reactivated the NO pathway. Conclusions: In a rat model of MCT-induced PAH, rBMSC/Cav-1F92A reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3η signal transduction.

3.
J Cell Physiol ; 234(11): 20392-20407, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30997675

RESUMO

Enhancing differentiation of mesenchymal stem cells (MSCs) to endothelial cells may improve their ability to vascularize tissue and promote wound healing. This study describes a novel role for nitric oxide (NO) in reprogramming MSCs towards an endothelial lineage and highlights the role of Wnt signaling and epigenetic modification by NO. Rat MSCs were transduced with lentiviral vectors expressing endothelial nitric oxide synthase (pLV-eNOS) and a mutated caveolin gene (pLV-CAV-1F92A ) to enhance NO generation resulting in increased in vitro capillary tubule formation and endothelial marker gene expression. An exogenous source of NO could also stimulate CD31 expression in MSCs. NO was associated with an arterial-specific endothelial gene expression profile of Notch1, Dll4, and Hey2 and significantly reduced expression of venous markers. Wnt signaling associated with NO was evident through increased gene expression of Wnt3a and ß-catenin protein, and expression of the endothelial marker Pecam-1 could be significantly reduced by treatment with the Wnt signaling inhibitor Dkk-1. The role of NO as an epigenetic modifier was evident with reduced gene expression of the methyltransferase, DNMT1, and bisulfite sequencing of the endothelial Flt1 promoter region in NO-producing MSCs showed significant demethylation compared to control cells. Finally, subcutaneous implantation of NO-producing MSCs seeded in a biomaterial scaffold (NovoSorb®) resulted in survival of transplanted cells and the formation of blood vessels. In summary, this study describes, NO as a potent endothelial programming factor which acts as an epigenetic modifier in MSCs and may provide a novel platform for vascular regenerative therapy.

4.
J Cell Physiol ; 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30779123

RESUMO

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague-Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP-ADMSCs, and CLP-sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2'-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP-ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP-sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

5.
Stem Cell Res Ther ; 10(1): 55, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760312

RESUMO

BACKGROUND: Despite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; however, this approach remains controversial. The aim of this systematic review and meta-analysis is to assess the potential efficacy of SC therapy for PAH. METHODS: The Medline, EMBASE, Cochrane Library, and Web of Science databases were searched from inception to August 12, 2018. Preclinical studies that evaluated the use of SC therapy for PAH were included. The primary outcome was pulmonary haemodynamics, as assessed by measurement of the right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and/or mean right ventricle pressure (mRVP). The secondary outcomes included the weight ratio of the right ventricle to the left ventricle plus septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW), the percentage of pulmonary arteriole area index (WA), and/or the percentage of medial wall thickness of the pulmonary arteriole (WT). The quality of outcomes was evaluated using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool. The inverse-variance method with random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Statistical analysis was performed with STATA 14.0. RESULTS: Twenty-eight eligible articles (722 animals) were included. SC therapy reduced the pooled WMDs (95% CIs) of RVSP, mPAP, mRVP, RV/LV+S, RV/BW, WA, and WT for animals with PAH, with values of - 14.12 (- 14.63, - 13.61), - 11.86 (- 12.35, - 11.36), - 17.33 (- 18.10, - 16.56), - 0.10 (- 0.10, - 0.09), 0.23 (0.21, 0.24), - 13.66 (- 15.71, - 11.62), and - 7.96 (- 7.99, - 7.93), respectively. CONCLUSIONS: SC therapy is effective for PAH in preclinical studies. These results may help to standardise preclinical animal studies and provide a theoretical basis for clinical trial design in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( http://www.crd.york.ac.uk/PROSPERO ).


Assuntos
Hipertensão Arterial Pulmonar/terapia , Transplante de Células-Tronco , Arteríolas/fisiopatologia , Arteríolas/transplante , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/transplante , Hemodinâmica , Humanos , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/transplante
6.
Heart Lung Circ ; 28(10): 1587-1597, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30262154

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by remodelling in vascular smooth muscles, and switching from contractile (differentiated) to synthetic (dedifferentiated) phenotype. This study aimed to investigate the effect of a mutated caveolin-1 (Cav1F92A) gene from bone marrow mesenchymal stem cells (rBMSCs) on phenotypic switching in the smooth muscle cells during PAH. METHODS: Human pulmonary smooth muscle cells (HPASMCs) were treated with monocrotaline (MCT,1µM), and co-cultured with Cav1F92A gene modified rBMSCs (rBMSCs/Cav1F92A). The nitric oxide (NO) production, cell adhesion, cell viability and inflammatory cytokines expression in rBMSCs was measured to evaluate the survival rate of rBMSCs and the changes of inflammatory cytokines. The concentration of NO/cGMP (nitric oxide/Guanosine-3',5'-cyclic monophosphate), the tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-ß1) mRNA, the expression of contractile smooth muscle cells (SMCs) phenotype markers (thrombospondin-1 and Matrix Gla protein, MGP), the synthetic SMCs phenotype markers (H-caldesmon and smooth muscle gene SM22 alpha, SM22α), cell migration and the morphological changes in rBMSCs/Cav1F92A co-cultured HPASMCs were investigated. RESULTS: Cav1F92A increased NO concentration, cell adhesion, cell viability, anti-inflammatory cytokines interleukin-4 (IL-4), and interleukin-10 (IL-10), but decreased the inflammatory cytokines interleukin-1α (IL-1α), interferon-γ (INF-γ) and TNF-α expression in rBMSCs. rBMSCs/Cav1F92A activated the NO/cGMP, down-regulated TNF-α, TGF-ß1, thrombospondin-1 and MGP expression, up-regulated SM22α and H-caldesmon expression, restored cell morphology, and inhibited cell migration in MCT treated HPASMCs. CONCLUSIONS: rBMSCs/Cav1F92A inhibits switching from contractile to synthetic phenotype in HPASMCs. It also inhibits migration and promotes morphological restoration of these cells. rBMSCs/Cav1F92A may be used as a therapeutic modality for PAH.


Assuntos
Caveolina 1/genética , DNA/genética , Hipertensão Pulmonar/genética , Células-Tronco Mesenquimais/metabolismo , Músculo Liso Vascular/metabolismo , Mutação , Artéria Pulmonar/metabolismo , Caveolina 1/metabolismo , Desdiferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Análise Mutacional de DNA , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Células-Tronco Mesenquimais/citologia , Músculo Liso Vascular/patologia , Artéria Pulmonar/patologia
7.
J Transl Med ; 16(1): 331, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30486885

RESUMO

BACKGROUND: The ProCESS, ARISE, and ProMISe trials have failed to show that early goal-directed therapy (EGDT) reduces mortality in patients with severe sepsis and septic shock. Although lactate-guided therapy (LGT) has been shown to result in significantly lower mortality, its use remains controversial. Therefore, we performed a meta-analysis to evaluate EGDT vs. LGT or usual care (UC) in adult patients with severe sepsis and septic shock. METHODS: Relevant randomized controlled trials published from January 1, 2001 to March 30, 2017 were identified in PubMed, EMBASE, Web of Science, and the Cochrane Library. The primary outcome was mortality; secondary outcomes included red cell transfusions, dobutamine use, vasopressor infusion, and mechanical ventilation support within the first 6 h and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. RESULTS: Sixteen studies enrolling 5968 patients with 2956 in EGDT, 2547 in UC, and 465 in LGT were included in this meta-analysis. Compared with UC, EGDT was associated with a lower mortality (10 trials; RR 0.85, 95% CI 0.74-0.97, P = 0.01), and this difference was more pronounced in the subgroup of UC patients with mortality > 30%. In addition, EGDT patients received more red cell transfusions, dobutamine, and vasopressor infusions within the first 6 h. Compared with LGT, EGDT was associated with higher mortality (6 trials; RR 1.42, 95% CI 1.19-1.70, P = 0.0001) with no heterogeneity (P = 0.727, I2 = 0%). CONCLUSION: EGDT seems to reduce mortality in adult patients with severe sepsis and septic shock, and the benefit may primarily be attributed to red cell transfusions, dobutamine administration, and vasopressor infusions within the first 6 h. However, LGT may result in a greater mortality benefit than EGDT.


Assuntos
Objetivos , Ácido Láctico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Séptico/tratamento farmacológico , Adulto , Humanos , Viés de Publicação , Fatores de Risco , Choque Séptico/mortalidade , Resultado do Tratamento
8.
J Biomed Res ; 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30249813

RESUMO

Multivessel coronary artery ectasia with severe calcification is rare among patients with coronary artery disease. A 74-year-old Chinese woman suffered from acute myocardial infarction on a background of 50 years of poorly controlled hypertension secondary to pheochromocytoma, which was surgically removed in June 2012 prior to the presentation. Coronary angiography revealed total occlusion of the proximal left anterior descending artery, and multiple ectasias with severe calcification in the left main, circumflex and right coronary artery. After an aspiration thrombectomy and balloon angioplasty, grade 3 coronary flow was restored in the left descending coronary artery. No cardiac events were found in the 12-month follow-up. We conclude that multivessel coronary artery ectasia and severe calcification may be present in patients with a long-standing history of hypertension secondary to pheochromocytoma.

9.
Oncol Rep ; 39(3): 1269-1275, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328466

RESUMO

Immature colon carcinoma transcript 1 (ICT1), a human mitochondrial translation release factor, is a ribosome-dependent codon-independent peptidyl-tRNA hydrolase. ICT1-deficiency has been recognized as a cell growth inhibitor of hepatoblastoma and glioblastoma multiforme. To explore the role of ICT1 in human leukemia, 2 short hairpin RNAs (shRNAs) targeting ICT1 sequences were designed in leukemia U937 cells. The successful infection of ICT1 in the U937 cells was observed under a fluorescence microscope and further quantified by western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tetrazolium dye (MTT) assay revealed a significant decrease in proliferation of ICT1-knockdown U937 cells on the fourth and fifth day as compared with the control. Depletion of ICT1 resulted in an increase in S phase and sub-G1 (representing cell apoptosis) fractions. Annexin V-APC/7-AAD staining assay confirmed that knockdown of ICT1 played a crucial role in boosting early and late apoptotic programs in U937 cells. Downregulation of ICT1 also altered cyclin A2 transcription expression, caspase-3 activity and p21 protein expression. Additionally, decreased levels of heat shock protein 27 (HSP27) phosphorylation at Ser78 was correlated with knockdown of ICT1 in U937 cells. Thus, we concluded that the regulatory role of ICT1 in leukemia may be used as a potential therapeutic target for the treatment of leukemia.


Assuntos
Biomarcadores Tumorais/metabolismo , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Leucemia/patologia , Proteínas/antagonistas & inibidores , Fase S , Apoptose , Biomarcadores Tumorais/genética , Humanos , Leucemia/genética , Leucemia/metabolismo , Proteínas/genética , Proteínas Ribossômicas , Células Tumorais Cultivadas
10.
Biomed Pharmacother ; 99: 1-8, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29324307

RESUMO

BACKGROUND: Cell based therapy has been heralded as a novel, promising therapeutic strategy for cardiovascular diseases including pulmonary arterial hypertension (PAH). However, the low survival rate after transplantation due to cell death via anoikis is a major obstacle in stem cell therapy. Cells adhesion via Integrin alpha5beta1 (ITGA5B1) has a tendency to exert higher maximum forces. The present study aimed to evaluate the potential protective effect of ITGA5B1 on rat bone marrow mesenchymal stem cells (rBMSCs) from anoikis. METHODS: Mononuclear cells were isolated by density gradient centrifugation with Ficoll, and rBMSCs cell surface markers were evaluated by flow cytometry. Osteogenic and adipocyte differentiation was determined by Alizarin Red S and Oil Red O staining respectively. The expression of Integrin A5 (ITGA5), Integrin B1 (ITGB1), eNOS and actived-caspase-3 mRNA or protein was confirmed by qPCR and western-blot. Cell adhesion, cell viability, anoikis and the migration of rBMSCs were also evaluated. Nitric oxide (NO) production was detected by the greiss assay. RESULTS: Co-infected with Integrin A5 and B1 lentivirus to rBMSCs increased ITGA5 and ITGB1 mRNA and protein expression. ITGA5B1 enhanced the cell adhesion, cell viability, cell migration and NO production but reduced the cell anoikis in rBMSCs/ITGA5B1 groups. CONCLUSION: Transduction of rat rBMSCs with ITGA5B1 lentivirus could prevent cell anoikis and increase NO production.


Assuntos
Anoikis , Integrina alfa5beta1/metabolismo , Células-Tronco Mesenquimais/metabolismo , Óxido Nítrico/biossíntese , Animais , Adesão Celular , Movimento Celular , Sobrevivência Celular , Células Cultivadas , Masculino , Células-Tronco Mesenquimais/citologia , Ratos , Transdução Genética , Cicatrização
11.
Oncol Lett ; 14(5): 5591-5596, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29113187

RESUMO

Zinc-finger protein 750 (ZNF750) encodes a putative C2H2 zinc finger protein and is typically mutated or deleted in squamous cell carcinoma. The role of ZNF750 in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the present study was to investigate the effects of ZNF750 overexpression in CAL-27 cells. Cell viability, and the expression of genes associated with proliferation, differentiation and the epithelial-mesenchymal transition were investigated in CAL-27 cells following ZNF750 overexpression, using Cell Counting kit-8, reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. In addition, scratch wound, invasion and migration assays were performed. Cell viability, matrix metalloproteinase 28 expression, cyclin B1 expression and mesenchymal marker neural cadherin expression were decreased following ZNF750 overexpression compared with the control groups. ZNF750 overexpression induced the differentiation-associated genes late cornified envelope 3A and small proline-rich protein 1A and upregulated the expression of late epidermal differentiation factor Kruppel-like factor 4. Overexpression of ZNF750 in CAL-27 cells resulted in inhibition of cell invasion and migration. Taken together, these data suggest that ZNF750 may inhibit the metastasis of OSCC.

12.
Biomed Pharmacother ; 90: 8-14, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28340379

RESUMO

The spindle and kinetochore-associated complex subunit 1(SKA1) is a newly discovered gene, which has been associated with mitosis and tumorigenesis. However, its role insalivary adenoid cystic carcinoma (SACC) is still unknown, and the invasive and metastatic mechanism in SACC is still unclear. To explore the molecular mechanism of SKA1 in the process of malignant proliferation and metastasis in adenoid cystic cancer (ACC) cells, we employed lentivirus-mediated short hairpin RNA to knockdown SKA1 in SACC-83 cells. The results demonstrated that the lentivirus-mediated shRNA-targeting SKA1 lead to a significant down-regulation of SKA1 expression. Knockdown of SKA1 inhibited cell proliferation, cell invasion, migration and the cell cycle arrest. Furthermore, knockdown of SKA1 reduced the Ndc80, CDK4, Cyclin D1, Cyclin E1, Cyclin B1 and matrix metalloproteinase-9 (MMP-9) protein expression, but increased the p27 protein expression. These findings indicated that SKA1 might be a promising target for cancer gene therapy in human ACC.


Assuntos
Carcinoma Adenoide Cístico/genética , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/genética , Metástase Neoplásica/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes/métodos , Humanos , Lentivirus/genética , RNA Interferente Pequeno/genética
13.
Vasa ; 46(4): 283-290, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28304220

RESUMO

BACKGROUND: This study aimed to utilize high-resolution magnetic resonance imaging (MRI) to investigate the characteristics of stable and vulnerable carotid arteriosclerotic plaques, with correlations to histopathological findings. PATIENTS AND METHODS: High-resolution MRI was performed in 817 patients, using three-dimensional magnetic resonance angiography. Plaque composition was evaluated by measuring the areas occupied by calcification, a lipid-rich necrotic core, intra-plaque haemorrhage, and fibrous cap rupture. Plaque morphology was analysed by measuring vessel wall area, thickness, and luminal area at the bifurcation of the common carotid artery. Plaque tissues were sampled during carotid endarterectomy and examined using haematoxylin-eosin, Oil Red O, Masson trichrome staining, and immunohistochemical staining for CD68. RESULTS: Patients were divided into stable plaque group (n = 462) and vulnerable plaque group (n = 355), based on intraoperative observations and postoperative histopathological findings. Compared to the stable plaque group, the vulnerable plaque group exhibited increased vessel wall areas and thickness, and decreased mean luminal areas (P < 0.001). The vulnerable plaque group also had a lower collagen content, a higher lipid content, and higher CD68 expression in plaque tissues on histological examinations (P < 0.01). Incidences of lipid-rich necrotic core (38.1 % vs. 34.3 %), intra-plaque haemorrhage (26.9 % vs. 22.8 %), plaque calcification (45.2 % vs. 40.9 %), and fibrous cap rupture (36.0 % vs 39.8 %) in the plaques were concordant with MRI observations and histopathological findings (p > 0.05). CONCLUSIONS: Stable and vulnerable carotid plaques had different morphologies and compositions. High-resolution MRI can assess such differences qualitatively and quantitatively in vivo and provide guidance for risk stratification and management.


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Angiografia por Ressonância Magnética , Placa Aterosclerótica , Idoso , Biópsia , Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/cirurgia , China , Colágeno/análise , Endarterectomia das Carótidas , Feminino , Fibrose , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Imuno-Histoquímica , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Necrose , Valor Preditivo dos Testes , Estudos Prospectivos , Ruptura Espontânea , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/patologia
15.
Heart Lung Circ ; 26(1): 94-100, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27425182

RESUMO

BACKGROUND: Degradable collagen-chitosan composite materials have been used to fabricate tissue engineered heart valves. The aims of this study were to demonstrate that the collagen-chitosan composite scaffolds are cytocompatible, and endothelial cells can be differentiated from bone marrow mesenchymal stem cells (BMSCs) when seeded onto the scaffolds. The adhesion and biological activities of the seeded cells were also investigated. METHODS: Collagen-chitosan composite material was used as the cell matrix, and smooth muscle cells, fibroblasts and BMSCs were used as seed cells. After four weeks of in vitro culture, the smooth muscle cells, fibroblasts, and BMSCs were sequentially seeded into the collagen-chitosan composite material. After four weeks in culture, the cellular density and activity were assessed on segments of the tissue engineered heart valve scaffolds to determine the cell viability and proliferation in the collagen-chitosan composite material. RESULTS: The tissue engineered heart valves stained positively for both smooth muscle actin and endothelial cell factor VIII, suggesting that the seeded cells were in fact smooth muscle cells, fibroblasts, and endothelial cells. The 6-ketone prostaglandin content, as measured by radioimmunoassay, of the collagen-chitosan cell culture fluid was higher than that of the serum-free medium (P <0.01). Light and electron microscopy showed that the seeded cells had shapes similar to the morphology of smooth muscle cells, fibroblasts, and endothelial cells. CONCLUSIONS: Endothelial cells can be differentiated from BMSCs when seeded onto the collagen-chitosan composite scaffolds. The seeded cells retained their biological activity after being cultured in vitro and seeded into the collagen-chitosan composite material.


Assuntos
Implantes Absorvíveis , Quitosana/química , Colágeno/química , Fibroblastos/metabolismo , Valvas Cardíacas , Miócitos de Músculo Liso/metabolismo , Engenharia Tecidual , Animais , Células Cultivadas , Fibroblastos/classificação , Miócitos de Músculo Liso/citologia , Coelhos
16.
Stem Cell Res Ther ; 7(1): 182, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27927230

RESUMO

BACKGROUND: Nitric oxide (NO) plays a role in a number of physiological processes including stem cell differentiation and osteogenesis. Endothelial nitric oxide synthase (eNOS), one of three NO-producing enzymes, is located in a close conformation with the caveolin-1 (CAV-1WT) membrane protein which is inhibitory to NO production. Modification of this interaction through mutation of the caveolin scaffold domain can increase NO release. In this study, we genetically modified equine adipose-derived stem cells (eASCs) with eNOS, CAV-1WT, and a CAV-1F92A (CAV-1WT mutant) and assessed NO-mediated osteogenic differentiation and the relationship with the Wnt signaling pathway. METHODS: NO production was enhanced by lentiviral vector co-delivery of eNOS and CAV-1F92A to eASCs, and osteogenesis and Wnt signaling was assessed by gene expression analysis and activity of a novel Runx2-GFP reporter. Cells were also exposed to a NO donor (NONOate) and the eNOS inhibitor, L-NAME. RESULTS: NO production as measured by nitrite was significantly increased in eNOS and CAV-1F92A transduced eASCs +(5.59 ± 0.22 µM) compared to eNOS alone (4.81 ± 0.59 µM) and un-transduced control cells (0.91 ± 0.23 µM) (p < 0.05). During osteogenic differentiation, higher NO correlated with increased calcium deposition, Runx2, and alkaline phosphatase (ALP) gene expression and the activity of a Runx2-eGFP reporter. Co-expression of eNOS and CAV-1WT transgenes resulted in lower NO production. Canonical Wnt signaling pathway-associated Wnt3a and Wnt8a gene expressions were increased in eNOS-CAV-1F92A cells undergoing osteogenesis whilst non-canonical Wnt5a was decreased and similar results were seen with NONOate treatment. Treatment of osteogenic cultures with 2 mM L-NAME resulted in reduced Runx2, ALP, and Wnt3a expressions, whilst Wnt5a expression was increased in eNOS-delivered cells. Co-transduction of eASCs with a Wnt pathway responsive lenti-TCF/LEF-dGFP reporter only showed activity in osteogenic cultures co-transduced with a doxycycline inducible eNOS. Lentiviral vector expression of canonical Wnt3a and non-canonical Wnt5a in eASCs was associated with induced and suppressed osteogenic differentiation, respectively, whilst treatment of eNOS-osteogenic cells with the Wnt inhibitor Dkk-1 significantly reduced expressions of Runx2 and ALP. CONCLUSIONS: This study identifies NO as a regulator of canonical Wnt/ß-catenin signaling to promote osteogenesis in eASCs which may contribute to novel bone regeneration strategies.


Assuntos
Adipócitos/fisiologia , Caveolina 1/metabolismo , Diferenciação Celular/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Osteogênese/fisiologia , Células-Tronco/fisiologia , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Adipócitos/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Células HEK293 , Cavalos , Humanos , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo
17.
Biomed Pharmacother ; 84: 1705-1710, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27847204

RESUMO

This study was designed to investigate the inhibition activity of polysaccharide extract from Laminaria japonica against RSV. The polysaccharide from Laminaria japonica was isolated by ethanol precipitation. HEK293 cells were infected with RVS, and the antiviral activity of polysaccharide extract against RSV in host cells was tested. By using ELISA and western blot assay, the expression level of IFN-α and IRF3 and their functional roles in polysaccharide-mediated antiviral activity against RSV were investigated. The polysaccharide extract from Laminaria japonica had low toxicity to HEK293 cell. The TC50 to HEK293 cells was up to 1.76mg/mL. Furthermore, the EC50 of polysaccharide extract to RSV was 5.27µg/mL, and TI was 334. The polysaccharide extract improved IRF-3 expression which promoted the level of IFN-α. IN CONCLUSION: Polysaccharide extract from Laminaria japonica elicits antiviral activity against RSV by up-regulation of IRF3 signaling-mediated IFN-α production.


Assuntos
Antivirais/farmacologia , Laminaria , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Antivirais/isolamento & purificação , Antivirais/toxicidade , Western Blotting , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Etanol/química , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Fator Regulador 3 de Interferon/metabolismo , Interferon-alfa/metabolismo , Laminaria/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Vírus Sinciciais Respiratórios/crescimento & desenvolvimento , Vírus Sinciciais Respiratórios/patogenicidade , Transdução de Sinais/efeitos dos fármacos , Solventes/química , Regulação para Cima , Replicação Viral/efeitos dos fármacos
18.
Vasc Endovascular Surg ; 50(7): 470-474, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27681172

RESUMO

OBJECTIVE: To evaluate the safety and outcomes of surgical revascularization for patients with symptomatic kinking of the internal carotid artery (ICA). METHODS: Twenty-five consecutive patients presented with symptomatic kinking of the ICA and a history of transient ischemic attack (TIA) or stroke were prospectively enrolled in this study. All patients were treated with ICA transection and end-to-side reimplantation at the level of the carotid bulb. Patients were followed up for a median of 32 months. RESULTS: There were no deaths or strokes within the 30 days of the treatment. No postprocedural thrombosis or narrowing of the ipsilateral ICA was observed. One (4%) patient had temporary recurrent nerve palsy, which was completely recovered at 4-week follow-up. One (4%) patient had a myocardial ischemic event. At the end of the 32-month follow-up, 1 (4%) patient developed ipsilateral minor stroke. No recurrent stenosis was detected by Doppler ultrasound. CONCLUSION: Surgical treatment for isolated, symptomatic kinking of the ICA and a history of TIA or stroke is safe, and the outcomes are acceptable.


Assuntos
Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Ataque Isquêmico Transitório/etiologia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Endarterectomia das Carótidas , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Reimplante , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
19.
Clin Neurol Neurosurg ; 150: 80-83, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27611985

RESUMO

OBJECTIVE: To investigate the short-term effect of recombinant human erythropoietin (EPO) on patients with severe traumatic brain injury. METHODS: One hundred and fifty-nine patients with severe traumatic brain injury were randomly divided into EPO (n=79) and control group (n=80). EPO group was treated with subcutaneous injection of EPO (100 units/kg) on day 1, 3, 6, 9 and 12 following the brain injury. Glasgow outcome scores (GOS) were used to evaluate the outcomes three months after the treatment. Serum neuron specific enolase (NSE) and S-100ß protein were measured within the first three months after treatment. RESULTS: In the end, 146 patients (75 of the EPO group and 71 of the control group) completed the trial. Three months after the treatment, Good recovery was found in 33.3% of the EPO and 12.6% of the control group patients (p<0.05). Serum NSE and S-100ß protein were decreased gradually in both groups after treatment, but their levels in the EPO group were lower than that of control group (p<0.05). There was no statistically significant difference in blood pressure, hemoglobin levels, pneumonia, sepsis or thromboembolic events between the two groups three months after the treatment (p>0.05). CONCLUSION: Treatment with five doses of recombinant human erythropoietin is associated with an improved functional recovery in patients with severe traumatic brain injury. This treatment does not seem to increase the risk of thromboembolic events or severe infections.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Eritropoetina/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Recuperação de Função Fisiológica , Adulto , Lesões Encefálicas Traumáticas/sangue , Método Duplo-Cego , Eritropoetina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/sangue , Proteínas Recombinantes , Subunidade beta da Proteína Ligante de Cálcio S100/sangue
20.
Biomed Rep ; 5(2): 213-216, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27446544

RESUMO

The aim of the present study was to investigate the effect of Scutellaria baicalensis stem-leaf total flavonoid (SSTF) on the dopaminergic neurons in the substantia nigra in a mouse model of Parkinson's disease (PD). The mouse model was established by intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). SSTF (5 mg/kg) was administered to the mice before or after MPTP injection, and the effects of SSTF on the behavior of the mice and the dopaminergic neurons in the substantia nigra were assessed. In addition, the level of serum malondialdehyde (MDA) was measured. Following injection of MPTP, the number of dopaminergic neurons in the substantia nigra was decreased and the neurons appeared atrophic. In addition, the level of serum MDA in the MPTP mice increased. The mean behavioral scores and the number of dopaminergic neurons in the SSTF treatment groups were significantly higher than in the MPTP group (P<0.05), and the mean serum MDA levels were significantly lower (P<0.05). Thus, SSTF improves the behaviors and the numbers of dopaminergic neurons in the substantia nigra in MPTP-induced PD in mice. These beneficial effects appear to be associated with the reduction in serum MDA.

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