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1.
Int J Cancer ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479522

RESUMO

Cetuximab and panitumumab bind the human epidermal growth factor receptor (EGFR). While the chimeric cetuximab (IgG1) triggers antibody-dependent-cellular-cytotoxicity (ADCC) of EGFR positive target cells, panitumumab (a human IgG2) does not. The inability of panitumumab to trigger ADCC reflects the poor binding affinity of human IgG2 Fc for the FcγRIII (CD16) on natural killer (NK) cells. However, both human IgG1 and IgG2 bind the FcγRII (CD32A) to a similar extent. This study compares the ability of T cells, engineered with a novel low-affinity CD32A131R -chimeric receptor (CR), and those engineered with the low-affinity CD16158F -CR T cells, in eliminating EGFR positive epithelial cancer cells (ECCs) in combination with cetuximab or panitumumab. Following T cell transduction, the percentage of CD32A131R -CR T cells was 74 ± 10% while the percentage of CD16158F -CR T cells was 46 ± 15%. Only CD32A131R -CR T cells bound panitumumab. CD32A131R -CR T cells combined with the mAb 8.26 (anti-CD32) and CD16158F -CR T cells combined with the mAb 3 g8 (anti-CD16) eliminated colorectal carcinoma (CRC), HCT116FcγR+ cells, in a reverse ADCC assay in vitro. Cross-linking of CD32A131R -CR on T cells by cetuximab or panitumumab and CD16158F -CR T cells by cetuximab induced elimination of triple negative breast cancer (TNBC) MDA-MB-468 cells, and the secretion of IFNγ and TNFα. Neither cetuximab nor panitumumab induced Fcγ-CR T anti-tumor activity against KRAS-mutated HCT116, non-small-cell-lung-cancer, A549 and TNBC, MDA-MB-231 cells. The ADCC of Fcγ-CR T cells was associated with the over-expression of EGFR on ECCs. In conclusion, CD32A131R -CR T cells are efficiently redirected by cetuximab or panitumumab against BC cells overexpressing EGFR. This article is protected by copyright. All rights reserved.

2.
EBioMedicine ; 47: 33-43, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31466914

RESUMO

BACKGROUND: The dismal survival of glioblastoma (GBM) patients urgently calls for the development of new treatments. Chimeric antigen receptor T (CAR-T) cells are an attractive strategy, but preclinical and clinical studies in GBM have shown that heterogeneous expression of the antigens targeted so far causes tumor escape, highlighting the need for the identification of new targets. We explored if B7-H3 is a valuable target for CAR-T cells in GBM. METHODS: We compared mRNA expression of antigens in GBM using TCGA data, and validated B7-H3 expression by immunohistochemistry. We then tested the antitumor activity of B7-H3-redirected CAR-T cells against GBM cell lines and patient-derived GBM neurospheres in vitro and in xenograft murine models. FINDINGS: B7-H3 mRNA and protein are overexpressed in GBM relative to normal brain in all GBM subtypes. Of the 46 specimens analyzed by immunohistochemistry, 76% showed high B7-H3 expression, 22% had detectable, but low B7-H3 expression and 2% were negative, as was normal brain. All 20 patient-derived neurospheres showed ubiquitous B7-H3 expression. B7-H3-redirected CAR-T cells effectively targeted GBM cell lines and neurospheres in vitro and in vivo. No significant differences were found between CD28 and 4-1BB co-stimulation, although CD28-co-stimulated CAR-T cells released more inflammatory cytokines. INTERPRETATION: We demonstrated that B7-H3 is highly expressed in GBM specimens and neurospheres that contain putative cancer stem cells, and that B7-H3-redirected CAR-T cells can effectively control tumor growth. Therefore, B7-H3 represents a promising target in GBM. FUND: Alex's Lemonade Stand Foundation; Il Fondo di Gio Onlus; National Cancer Institute; Burroughs Wellcome Fund.

3.
Int J Biol Sci ; 15(7): 1533-1545, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337982

RESUMO

Aims: Berberine (BBR) improves beta-cell function in Type 2 diabetes (T2D) because of its anti-apoptotic activity, and our laboratory developed a new preparation named Huang-Gui Solid Dispersion (HGSD) to improve the oral bioavailability of BBR. However, the mechanism by which BBR inhibits beta-cell apoptosis is unclear. We hypothesized that the Group VIA Ca2+-Independent Phospholipase A2 (iPLA2ß)/Cardiolipin(CL)/Opa1 signaling pathway could exert a protective role in T2D by regulating beta-cell apoptosis and that HGSD could inhibit ß-cell apoptosis through iPLA2ß/CL/Opa1 upregulation. Methods: We examined how iPLA2ß and BBR regulated apoptosis and insulin secretion through CL/Opa1 in vivo and in vitro. In in vitro studies, we developed Palmitate(PA)-induced apoptotic cell death model in mouse insulinoma cells (MIN6). iPLA2ß overexpression and silencing technology were used to examine how the iPLA2ß/CL/Opa1 interaction may play an important role in BBR treatment. In in vivo studies, db/db mice were used as a diabetic animal model. The pancreatic islet function and morphology, beta-cell apoptosis and mitochondrial injury were examined to explore the effects of HGSD. The expression of iPLA2ß/CL/Opa1 was measured to explore whether the signaling pathway was damaged in T2D and was involved in HGSD treatment. Results: The overexpression of iPLA2ß and BBR treatment significantly attenuated Palmitate- induced mitochondrial injury and apoptotic death compared with Palmitate-treated MIN6 cell. In addition, iPLA2ß silencing could simultaneously partly abolish the anti-apoptotic effect of BBR and decrease CL/Opa1 signaling in MIN6 cells. Moreover, HGSD treatment significantly decreased beta-cell apoptosis and resulted in the upregulation of iPLA2ß/CL/Opa1 compared to those of the db/db mice. Conclusion: The results indicated that the regulation of iPLA2ß/CL/Opa1 by HGSD may prevent beta-cell apoptosis and may improve islet beta-cell function in Type 2 diabetic mice and in palmitate-treated MIN6 cells.

4.
J Mol Endocrinol ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247591

RESUMO

The prevalence of obesity is dramatic increased and strongly associated with cardiovascular disease. Adipokines, secreted from adipose tissues, are critical risk factors for the development of cardiomyopathy. Present study aimed to investigate the pathophysiological role of autotaxin in obesity-related cardiomyopathy. In high fat diet-fed mice, autotaxin was mainly synthesized and secreted from adipocytes. The increased accumulation of cardiac autotaxin was positively associated with cardiac dysfunction in obese mice. Interestingly, specific blockage of adipose tissue autotaxin effectively protected against high fat diet-induced cardiac structural disorders, left ventricular hypertrophy and dysfunction. Inhibition of autotaxin further improved high fat diet-induced cardiac fibrosis and mitochondrial dysfunction, including improvement of mitochondrial structure, mass and activities. Our findings demonstrated intervention of adipose tissue biology could influence cardiac modification in obese mice, and adipocyte-derived autotaxin was a potential diagnostic marker and therapeutic target for obesity-related cardiomyopathy.

5.
Cancer Cell ; 35(2): 221-237.e8, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30753824

RESUMO

The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. We also found that 4-1BB co-stimulation promotes lower PD-1 expression in B7-H3.CAR-Ts, and superior antitumor activity when targeting tumor cells that constitutively expressed PD-L1. We took advantage of the cross-reactivity of the B7-H3.CAR with murine B7-H3, and found that B7-H3.CAR-Ts significantly controlled tumor growth in a syngeneic tumor model without evident toxicity. These findings support the clinical development of B7-H3.CAR-Ts.

6.
Ecotoxicol Environ Saf ; 171: 813-822, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30660975

RESUMO

Investigating the occurrence of disinfection by-products (DBPs) and identify the related influencing factors in drinking water is essentially important to control DBPs risk. In this study, 64 tap water samples were collected from 8 counties (or county level cities) in Jinhua Region of Zhejiang Province, China. Results showed that the median (range) of trihalomethane (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), haloketones (HKs) and halonitromethanes (HNMs) were 23.2 (9.1-40.9), 15.3 (5.8-38.6), 2.2 (0.7-7.6), 2.1 (0.2-6.4) and 0.7 (0.2-2.9) µg/L, respectively. HAAs, HANs, HKs and HNMs levels were generally higher in summer than in winter or spring, while for THMs in most counties, higher levels occurred in winter than in summer or spring. Spatially, Yongkang, Yiwu and Dongyang had higher DBPs levels than Pujiang, Pan'an, Lanxi, Wuyi and Jinhua, which was generally consistent with their economy development (GDP). Correlation analysis showed that DBPs occurrence in tap water was significantly related with physicochemical parameters. Principle component analysis further suggested that organic matter (DOC and UVA254) are the major factors influencing the occurrence of THMs, HAAs, HANs and HKs in tap water, while for HNMs, both the organic (DOC and UVA254) and inorganic factors (e.g. Temp, NO2--N, pH, Br- and NH4+-N) played important role in its formation.


Assuntos
Desinfetantes/química , Água Potável/química , Poluentes Químicos da Água/química , Acetatos/análise , Acetonitrilos/análise , China , Hidrocarbonetos Halogenados/análise , Cetonas/análise , Estações do Ano , Trialometanos/análise
7.
Cardiovasc Diabetol ; 17(1): 90, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907160

RESUMO

BACKGROUND: Raised hemoglobinA1c (HbA1c) is an indicator of pre-diabetes, which is associated with increased risk of coronary artery disease. However, the detailed morphological characteristics of non-culprit plaques in acute coronary syndrome (ACS) patients remain largely unknown. METHODS: A total of 305 non-culprit plaques from 216 ACS patients were analyzed by intravascular optical coherence tomography. These patients were divided into three groups according to the serum glycosylated hemoglobin level: normal HbA1c (< 5.7%), pre-diabetes with raised HbA1c (5.7-6.4%) and diabetes mellitus (DM). RESULTS: Plaques in patients with raised HbA1c had a longer lipid length (17.0 ± 8.3 mm vs. 13.9 ± 7.2 mm, P = 0.004) and greater lipid index (2775.0 ± 1694.0 mm° vs. 1592.1 ± 981.2 mm°, P = 0.001) than those with normal HbA1c but were similar to DM. The prevalence of calcification in patients with raised HbA1c was significantly higher (38.7% vs. 26.3%, P = 0.048) than normal HbA1c but was similar to DM. The percentage of macrophage infiltration in the DM group was higher than that in the normal HbA1c group (20.5% vs. 7.4%, P = 0.005). CONCLUSIONS: Compared to patients with normal HbA1c, the non-culprit plaques in ACS patients with raised HbA1c had more typical vulnerable features but were similar to DM.

8.
Theranostics ; 8(8): 2171-2188, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721071

RESUMO

The mechanism by which adipocyte-derived endocrine factors promote insulin resistance in skeletal muscle are not fully understood. MiR-27a is highly expressed in sera of obese individuals with prediabetes and T2DM, and mainly derived by adipose tissues. Thus, miR-27a secreted into circulation by adipose tissue may regulate insulin resistance in skeletal muscle. Methods: The association between miR-27a and insulin resistance in skeletal muscle was determined in obese children, high-fat diet-induced miR-27a knockdown obese mice, db/db mice and C2C12 cells overexpressing miR-27a. The crosstalk mediated by exosomal miR-27a between adipose tissue and skeletal muscle was determined in C2C12 cells incubated with conditioned medium prepared from palmitate-treated 3T3-L1 adipocytes. Results: We showed that serum miR-27a level correlated positively with obesity and insulin resistance in obese children, and that elevated serum miR-27a levels correlated with insulin resistance in leptin receptor-deficient db/db mice, and with obesity and insulin resistance in high-fat diet-fed C57BL/6J mice. MiR-27a released from adipocytes of high-fat diet-fed C57BL/6J mice was associated with triglyceride accumulation. MiR-27a derived from these adipocytes induced insulin resistance in C2C12 skeletal muscle cells through miR-27a-mediated repression of PPARγ and its downstream genes involved in the development of obesity. Conclusions: These results identify a novel crosstalk signaling pathway between adipose tissue and skeletal muscle in the development of insulin resistance, and indicate that adipose tissue-derived miR-27a may play a key role in the development of obesity-triggered insulin resistance in skeletal muscle.

9.
Comput Methods Programs Biomed ; 160: 43-49, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29728245

RESUMO

BACKGROUND AND OBJECTIVE: Relative location prediction in computed tomography (CT) scan images is a challenging problem. Many traditional machine learning methods have been applied in attempts to alleviate this problem. However, the accuracy and speed of these methods cannot meet the requirement of medical scenario. In this paper, we propose a regression model based on one-dimensional convolutional neural networks (CNN) to determine the relative location of a CT scan image both quickly and precisely. METHODS: In contrast to other common CNN models that use a two-dimensional image as an input, the input of this CNN model is a feature vector extracted by a shape context algorithm with spatial correlation. Normalization via z-score is first applied as a pre-processing step. Then, in order to prevent overfitting and improve model's performance, 20% of the elements of the feature vectors are randomly set to zero. This CNN model consists primarily of three one-dimensional convolutional layers, three dropout layers and two fully-connected layers with appropriate loss functions. RESULTS: A public dataset is employed to validate the performance of the proposed model using a 5-fold cross validation. Experimental results demonstrate an excellent performance of the proposed model when compared with contemporary techniques, achieving a median absolute error of 1.04 cm and mean absolute error of 1.69 cm. The time taken for each relative location prediction is approximately 2 ms. CONCLUSION: Results indicate that the proposed CNN method can contribute to a quick and accurate relative location prediction in CT scan images, which can improve efficiency of the medical picture archiving and communication system in the future.


Assuntos
Redes Neurais (Computação) , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Algoritmos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pescoço/anatomia & histologia , Pescoço/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Análise de Regressão
10.
Medicine (Baltimore) ; 97(16): e0518, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29668639

RESUMO

PURPOSE: Previous studies have indicated that stent implantation could alter the vessel geometry, which may impact the neointimal healing process. Curvature is an important parameter for evaluating vessel geometry. The purpose of our study was to investigate the relationship between vessel curvature and neointimal healing after stent implantation. METHODS: Fifty-nine patients with acute coronary syndrome (ACS) who underwent stent implantation were enrolled in the study. According to the post-percutaneous coronary intervention vessel curvature measured by quantitative coronary angiography, patients were divided into high (n = 30) and low (n = 29) curvature groups. Neointimal thickness and area together with the neointimal type were assessed by optical coherence tomography at a 6-month follow-up. RESULTS: Baseline clinical characteristics were comparable between the 2 groups. The vessel curvature at pre- and 6-month follow-up was significantly higher in the high curvature group than the low curvature group. At 6-month follow-up, neointimal thickness (0.22 [0.08-0.32] mm vs. 0.10 [0.07-0.16] mm, P = .043) and neointimal area (1.86 [0.66-2.66] vs. 0.82 [0.60-1.41] mm, P = .030) were significantly higher in the high curvature group than the low curvature group. In the high curvature group, the incidence of the heterogeneous neointimal type was higher than that in the low curvature group (50.00% vs. 17.20%, respectively, P = .004), whereas the frequency of the homogeneous neointimal type was lower (43.30% vs. 82.80%, respectively, P = .004) in the high curvature group than the low curvature group. CONCLUSION: Higher vessel curvature after stent implantation may potentially have an impact on the neointimal healing with a higher incidence of heterogeneous neointimal.


Assuntos
Síndrome Coronariana Aguda , Vasos Coronários , Stents Farmacológicos/efeitos adversos , Neointima , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias , Tomografia de Coerência Óptica/métodos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/patologia , Síndrome Coronariana Aguda/cirurgia , Adulto , Assistência ao Convalescente/métodos , Idoso , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neointima/diagnóstico por imagem , Neointima/etiologia , Neointima/patologia , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Túnica Íntima/diagnóstico por imagem
11.
Mol Med Rep ; 16(3): 2915-2924, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28713962

RESUMO

The present study aimed to identify key genes and signaling pathways associated with myocardial infarction (MI) following telomerase activation, and investigate the possible underlying molecular mechanisms involved in this process. Array data of GSE62973 was downloaded, including 11 samples from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed in infarct vs. control, infarct + telomerase vs. control, and infarct + telomerase vs. infarct with the Linear Models for Microarray and RNA­Seq Data package. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for upregulated and downregulated genes by the Database for Annotation, Visualization and Integrated Discovery. Sub network modules of 3 protein­protein interaction (PPI) networks were analyzed by Clustering with Overlapping Neighbourhood Expansion, and genes associated with telomerase were analyzed. Proto­oncogene tyrosine­protein kinase Src (Src) and proto­oncogene tyrosine­protein kinase Fyn (Fyn) were the hub nodes of the greatest degree in the PPI network for the infarct + telomerase vs. control comparison group and infarct + telomerase vs. infarct comparison group, respectively. Olfactory receptor gene family associated genes, including olfactory receptor 10 were significantly enriched in the sub network modules of the 3 comparison groups. In addition, olfactory transduction was a significantly enriched pathway by downregulation of DEGs in the infarct vs. control comparison group, and was additionally a significantly enriched pathway by upregulated DEGs in infarct + telomerase vs. infarct comparison group. Olfactory transduction was a significant pathway enriched by genes associated with telomerase. Telomerase activation may serve an important role in MI, in part, via the regulation of Src, Fyn and olfactory receptor family associated genes.


Assuntos
Ativação Enzimática , Infarto do Miocárdio/genética , Telomerase/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Genômica , Humanos , Infarto do Miocárdio/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transdução de Sinais , Telomerase/genética
12.
Eur J Endocrinol ; 177(2): 195-205, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28566441

RESUMO

OBJECTIVE: We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD). DESIGN: Phase II and III, multicenter, open-label, randomized controlled trials. METHODS: 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored. RESULTS: The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment (P < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment (P < 0.05). Adverse event rates and treatment compliance were comparable between the two groups. CONCLUSION: Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.


Assuntos
Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Polietilenoglicóis/administração & dosagem , Adolescente , Criança , Preparações de Ação Retardada/administração & dosagem , Nanismo Hipofisário/sangue , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Masculino , Proteínas Recombinantes/administração & dosagem
13.
Int J Biomed Imaging ; 2017: 9604178, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28487724

RESUMO

Compressed sensing (CS) has been applied to accelerate magnetic resonance imaging (MRI) for many years. Due to the lack of translation invariance of the wavelet basis, undersampled MRI reconstruction based on discrete wavelet transform may result in serious artifacts. In this paper, we propose a CS-based reconstruction scheme, which combines complex double-density dual-tree discrete wavelet transform (CDDDT-DWT) with fast iterative shrinkage/soft thresholding algorithm (FISTA) to efficiently reduce such visual artifacts. The CDDDT-DWT has the characteristics of shift invariance, high degree, and a good directional selectivity. In addition, FISTA has an excellent convergence rate, and the design of FISTA is simple. Compared with conventional CS-based reconstruction methods, the experimental results demonstrate that this novel approach achieves higher peak signal-to-noise ratio (PSNR), larger signal-to-noise ratio (SNR), better structural similarity index (SSIM), and lower relative error.

14.
Biomed Eng Online ; 16(1): 53, 2017 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-28449672

RESUMO

BACKGROUND: The challenge of reconstructing a sparse medical magnetic resonance image based on compressed sensing from undersampled k-space data has been investigated within recent years. As total variation (TV) performs well in preserving edge, one type of approach considers TV-regularization as a sparse structure to solve a convex optimization problem. Nevertheless, this convex optimization problem is both nonlinear and nonsmooth, and thus difficult to handle, especially for a large-scale problem. Therefore, it is essential to develop efficient algorithms to solve a very broad class of TV-regularized problems. METHODS: In this paper, we propose an efficient algorithm referred to as the fast linearized preconditioned alternating direction method of multipliers (FLPADMM), to solve an augmented TV-regularized model that adds a quadratic term to enforce image smoothness. Because of the separable structure of this model, FLPADMM decomposes the convex problem into two subproblems. Each subproblem can be alternatively minimized by augmented Lagrangian function. Furthermore, a linearized strategy and multistep weighted scheme can be easily combined for more effective image recovery. RESULTS: The method of the present study showed improved accuracy and efficiency, in comparison to other methods. Furthermore, the experiments conducted on in vivo data showed that our algorithm achieved a higher signal-to-noise ratio (SNR), lower relative error (Rel.Err), and better structural similarity (SSIM) index in comparison to other state-of-the-art algorithms. CONCLUSIONS: Extensive experiments demonstrate that the proposed algorithm exhibits superior performance in accuracy and efficiency than conventional compressed sensing MRI algorithms.


Assuntos
Algoritmos , Artefatos , Compressão de Dados/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Modelos Lineares , Imagem por Ressonância Magnética/métodos , Humanos , Imagem por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
ACS Appl Mater Interfaces ; 9(11): 10266-10275, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28240859

RESUMO

Coexistence of antibiotics and heavy metals is typically detected in water containing both organic and inorganic contaminants. In this work, a flocculation method using a reusable thermoresponsive chitosan-based flocculant (CS-g-PNNPAM) was applied for separation and sequential recovery of tetracycline (TC) and Cu(II) from water. High synergistic removal rates of both TC and Cu(II) from water (>90%) were reached. Interactive effects among targeted water temperature (T1), stock solution temperature (T2), and flocculant dosage on flocculation performance were assessed using response surface methodology. To optimize flocculation, operation strategies of adjusting T2 and dosage according to T1 based on the interactive effects were given through mathematical analyses. The flocculation mechanism as well as interfacial interactions among CS-g-PNNPAM, TC, and Cu(II) were studied through experimental investigations (floc size monitoring, X-ray photoelectron spectroscopy, and UV spectra) and theoretical calculations (density functional theory and molecular dynamics simulations). Coordination of Cu(II) with TC and the flocculant promoted flocculation; switchable interactions (H bonds and hydrophobic association) of the TC-flocculant at different temperatures were key factors affecting operation strategies. When these interactions were weakened step by step, TC and Cu(II) were sequentially recovered from flocs using certain solutions. Meanwhile, the flocculant in flocs was regenerated and found reusable with high flocculation efficiency.

16.
Oncotarget ; 8(3): 4234-4244, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27992371

RESUMO

Atherosclerosis often leads to myocardial infarction and stroke. We examined the influence of baseline plaque characteristics on subsequent vascular remodeling in response to changes in plaque size. Using optical coherence tomography (OCT) and intravascular ultrasound (IVUS), we examined 213 plaques from 138 patients with acute coronary syndrome at baseline and repeated IVUS at the 12-month follow-up. The change in external elastic membrane (EEM) area for each 1 mm2 change in plaque area (i.e., the slope of the regression line) was calculated as a measure of vascular remodeling capacity. In plaques with static positive remodeling, the slope was smaller than in plaques without static positive remodeling. In addition, the slope of the regression line for lesions with a large plaque burden was much smaller than that for lesions with a small plaque burden. Multivariate linear regression analysis showed that diabetes, calcification and static positive remodeling were inversely and independently associated with the level of change in EEM area/change in plaque area. Lesions with a large plaque burden, calcifications or static positive remodeling had less remodeling capacity, and calcification and static positive remodeling were independent predictors of reduced subsequent remodeling. Therefore, calcifications and static positive remodeling could be used as morphological biomarkers to predict decreased subsequent arterial remodeling.


Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ultrassonografia de Intervenção , Remodelação Vascular
17.
J Biomed Mater Res B Appl Biomater ; 105(5): 977-988, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-26873608

RESUMO

The natural vitreous is a biological hydrogel consisting primarily of a collagen and anionic hyaluronate. It is surgically removed in many ocular diseases and replaced with fluids, gases, or silicone oils. We have been interested in developing synthetic hydrogels as vitreous substitutes. In this study, we combined the stiffness and hydrophobicity of polymethacrylamide (PMAM) and the anionic nature of polymethacrylate (PMAA) to make copolymers that would mimic the natural vitreous. We used bis-methacryloyl cystamine (BMAC) to introduce thiol groups for reversible crosslink. The Mn of copolymers ranged from ∼100 k to ∼200 k Da (polydisperisty index of 1.47-2.63) and their composition as determined by titration, 1 H NMR and disulfide test were close to the feed ratio. The reactivities of monomers were as follows: MAM > MAA ∼ BMAC. Copolymers with higher MAA contents gelled faster, swelled more, and had higher storage modulus (1.5 to 100 Pa) comparable to that of the natural vitreous. We evaluated the biocompatibility of copolymers by electric cell-substrate impedance sensing (ECIS) using human retinal pigment epithelial cells, primary porcine retinal pigmented epithelial cells, human microvascular endothelial cells adult dermis, and a fibroblast line 3T3. The biocompatibility decreases as the content of BMAC increases. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 977-988, 2017.


Assuntos
Células Epiteliais/metabolismo , Hidrogéis , Teste de Materiais , Ácidos Polimetacrílicos , Epitélio Pigmentado da Retina/metabolismo , Corpo Vítreo , Animais , Células Epiteliais/citologia , Humanos , Hidrogéis/síntese química , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Células NIH 3T3 , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Epitélio Pigmentado da Retina/citologia , Suínos
18.
Coron Artery Dis ; 27(8): 658-666, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27580090

RESUMO

OBJECTIVE: Some plaques grow slowly in a linear manner, whereas others undergo a rapid phasic progression. However, the detailed in-vivo relationship between plaque characteristics and plaque progression pattern has not been reported. The current study aimed to investigate the plaque progression patterns with serial intravascular ultrasound (IVUS) examinations, and to correlate baseline plaque characteristics assessed by optical coherence tomography and IVUS with plaque progression patterns. METHODS: A total of 248 coronary lesions from 157 patients were identified and imaged by both optical coherence tomography and IVUS at baseline. IVUS examination was repeated at 6 and 12 months. Plaque progression was defined as greater than or equal to 5% increase in percent atheroma volume by IVUS. The progression patterns were divided into three groups: no progression, rapid phasic progression, and gradual progression. RESULTS: Among 248 lesions, 190 (77%) showed no progression. Among 58 lesions with progression, 20 (34%) showed gradual progression, whereas 38 (66%) showed rapid phasic progression. Multivariate analysis indicated that thin-cap fibroatheroma [odds ratio (OR)=5.24, 95% confidence interval (CI) 2.04-13.4; P=0.001], microvessel (OR=2.20, 95% CI 1.10-4.79; P=0.045), and positive remodeling (OR=2.64, 95% CI 1.19-5.81; P=0.016) were associated independently with rapid phasic progression. CONCLUSION: Three-quarters of coronary plaques did not progress over time with contemporary medical treatment. Among the lesions with progression, one-third showed a gradual pattern and two-thirds showed a rapid phasic pattern. The presence of thin-cap fibroatheroma, microvessel, and positive remodeling were the independent predictors for rapid phasic pattern progression of coronary atherosclerotic plaques.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica , Tomografia de Coerência Óptica , Ultrassonografia de Intervenção , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Estenose Coronária/patologia , Estenose Coronária/terapia , Vasos Coronários/patologia , Progressão da Doença , Feminino , Fibrose , Humanos , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Remodelação Vascular
19.
Meta Gene ; 9: 120-3, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27331016

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease that has strong contribution of genetic factors to its etiology. We aimed to assess the genetic association between non-HLA genes and T1D in a Chinese case-control cohort recruited from multiple centers consisting of 364 patients with T1D and 719 unrelated healthy children. We genotyped 55 single nucleotide polymorphisms (SNP) markers located in 16 non-HLA genes (VTCN1, PTPN22, CTLA4, SUMO4, CD274, IL2RA, INS, DHCR7, ERBB3, VDR, CYP27B1, CD69, CD276, PTPN2, UBASH3A, and IL2RB) using SNaPshot multiple single-base extension methods. After multivariate analysis and correction for multiple comparisons, we identified the SNP rs2292239 in ERBB3 gene were significantly associated with T1D. The frequency of the major G allele was significantly decreased in patients with T1D (68.8% in T1D vs 77.3% in controls, OR 0.65, 95% CI 0.53-0.79, P = 0.02), and the minor allele T was associated with an increased risk of T1D (OR 1.55, 95% CI 1.26-1.90, P = 0.02). Our haplotype analysis confirmed that rs2292239 was the primary T1D association locus in our current investigation. These results indicated that the ERBB3-rs2292239 was the primary T1D association locus among the investigated 55 SNPs in 16 non-HLA genes in Chinese Han population.

20.
Medicine (Baltimore) ; 94(50): e2246, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26683940

RESUMO

While older age associates with adverse percutaneous coronary intervention (PCI) outcomes, detailed information relating age to stent strut coverage and neointimal characteristics is lacking. One hundred nineteen patients with 123 sirolimus-eluting stents (SESs) were divided into 3 groups: group A (≤55 years), group B (56-65 years), and group C (>65 years). At 6 and 12 months of follow-up, optical coherence tomography was performed to assess strut coverage and neointimal remodeling. At 6 months, the proportion of uncovered struts increased with age: 6.1% in group A versus 7.3% in group B versus 11.7% in group C (P < 0.001) while the proportion of embedded struts decreased: 72.1% versus 57.0% vs. 55.0%, respectively (P < 0.001). Mean neointimal thicknesses were 90  µm versus 60  µm versus 60  µm, respectively (P < 0.001), and neointimal areas were 0.82  mm2 versus 0.52  mm2 versus 0.57  mm2 (P < 0.001). At 12 months, the proportion of uncovered struts increased with age (3.9% vs. 3.3% vs. 4.9 %; P < 0.001), while mean neointimal thicknesses were 100 versus 70 versus 80  µm (P < 0.001) and neointimal areas were 0.87 versus 0.60 versus 0.67  mm2 (P < 0.001). Patients ≤55 years receiving SES showed highest strut coverage and neointimal repair rate compared with the other 2 groups. A "catch-up phenomenon" appeared to occur in the oldest patients, as in the first 6 months the neointima showed lowest endothelial cell coverage and lowest neointimal proliferation rate, whereas from 6 to 12 months, the highest neointimal proliferation rate was seen in the oldest patients.


Assuntos
Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Neointima/diagnóstico , Intervenção Coronária Percutânea , Remodelação Vascular/fisiologia , Fatores Etários , Idoso , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade , Neointima/etiologia , Estudos Retrospectivos , Sirolimo , Tomografia de Coerência Óptica , Resultado do Tratamento
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