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1.
Int J Nanomedicine ; 14: 8499-8507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695377

RESUMO

Background: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. Methods: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. Results: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. Conclusion: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.


Assuntos
Compostos Férricos/química , Imagem por Ressonância Magnética , Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Tamanho da Partícula , Polietilenoglicóis/química , Animais , Sobrevivência Celular , Meios de Contraste/química , Células Hep G2 , Humanos , Fígado/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura
2.
Front Neurol ; 10: 520, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214103

RESUMO

Background: The rupture risk of anterior communicating artery aneurysms (ACoAAs) has been known to be higher than that of aneurysms at other locations. Thus, the aim of this study is to investigate the clinical and morphological characteristics associated with risk factors for the rupture of ACoAAs. Methods: In total, 361 consecutive patients with 361 ACoAAs between August 2011 and December 2017 were retrospectively reviewed. Patients and ACoAAs were divided into ruptured and unruptured groups. In addition to clinical characteristics, ACoAA characteristics were evaluated by CT angiography (CTA). A multiple logistic regression analysis was used to identify the independent risk factors associated with ACoAA rupture. The assignment score of these variables depends on the ß coefficient. A receiver operating characteristic (ROC) curve analysis was used to calculate the optimal thresholds. Results: The multiple logistic regression model revealed that A1 dominance [odds ratio (OR) 3.034], an irregular shape (OR 3.358), and an aspect ratio ≥1.19 (AR; OR 3.163) increased the risk of rupture, while cerebral atherosclerosis (OR 0.080), and mean diameters ≥2.48 mm (OR 0.474) were negatively correlated with ACoAA rupture. Incorporating these five factors, the ROC analysis revealed that the threshold value of the multifactors was one, the sensitivity was 88.3%, and the specificity was 66.0%. Conclusions: The scoring model is a simple method that is based on A1 dominance, irregular shape, aspect ratio, cerebral atherosclerosis, and mean diameters from CTA and is of great value in the prediction of the rupture risk of ACoAAs.

3.
Front Hum Neurosci ; 13: 107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001097

RESUMO

Background: Patients with ulcerative colitis (UC) usually display cognitive impairments, such as memory loss, attention deficits, and declining executive functions, particularly during the active stage of the disease. However, the potential neurological mechanisms of these symptoms remain unclear. Method: Forty-one patients with mildly to moderately active UC, as well as 42 matched healthy controls, were recruited for an examination using psychological scales, cognitive function tests and resting-state functional magnetic resonance imaging (rs-fMRI). Seed points were identified via analysis of amplitude of low-frequency fluctuation (ALFF), and functional connectivity (FC) was calculated between these seed regions and other voxels in the whole brain. Correlation analyses were performed among clinical indexes, neuropsychological assessments and neuroimaging data. Result: Compared with the healthy controls, patients with UC exhibited lower ALFF values in the bilateral hippocampal/parahippocampal (HIPP/ParaHIPP) region and higher ALFF values in the left posterior cingulate cortex (PCC.L) and left middle frontal gyrus (MFG.L). With HIPP/ParaHIPP as the seed point, the strengths of the FC in the bilateral middle frontal gyri (MFG), anterior cingulate cortex (ACC), and left caudate nucleus (CAU.L) increased; using the PCC.L as the seed point, the strengths of the FC in the middle cingulate cortex (MCC) and the left angular gyrus (AUG.L) increased. These abnormal brain regions were mainly located in the limbic system. By analyzing the correlations between these brain regions and behavioral data, we observed a close correlation between decreased HIPP/ParaHIPP activity and memory loss; increased PCC activity and strength of FC with the AUG.L were related to dysfunction of executive function and attention network in patients with UC. Conclusion: Based on these results, the limbic lobe might be the core of the brain-gut axis (BGA) and play an important role in cognitive impairments, suggesting potential mechanisms for cognitive impairment in patients with UC in the active stage of the disease.

4.
Nano Lett ; 19(5): 3011-3018, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30971089

RESUMO

Magnetic/plasmonic hybrid nanoparticles are highly desirable for multimodal bioimaging and biosensing. Although the synthesis of heterodimeric nanoparticles has been reported, the products are usually hydrophobic so that post-treatment procedures are required to transfer them into water which are often difficult to perform and cause damages to the structures. Direct synthesis of hydrophilic hybrid nanostructures has remained a grand challenge albeit its immediate advantage of biocompatibility. Herein we report a general seed-mediated approach to the synthesis of hydrophilic and biocompatible M-Fe3O4 (M = Au, Ag, and Pd) heterodimers, in which the size of metals and Fe3O4 can be independently regulated in a wide range. Benefiting from the aqueous synthesis, this approach can be further extended to design more complex heterodimeric structures such as AgPtalloy-Fe3O4, Aucore@Pdshell-Fe3O4, and Aushell-Fe3O4. The hydrophilic nature of our heterodimers makes them readily useful for biomedical applications without the need of additional ligand exchange processes in contrast to those prepared in nonpolar solvents. These nanoscale magnetic/plasmonic heterostructures were shown to be ideally suited for integrated biomedical diagnoses, such as magnetic resonance imaging, photoacoustic imaging, optical coherence tomography, and computed tomography, in virtue of their biocompatibility and combined tunable magnetic and plasmonic properties.


Assuntos
Meios de Contraste/farmacologia , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Imagem Multimodal/métodos , Meios de Contraste/química , Ouro/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Tomografia Computadorizada por Raios X , Água/química
5.
Eur J Radiol ; 112: 88-92, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30777225

RESUMO

PURPOSE: To study the association of the enhancement ratio (ER) of aneurysmal wall enhancement (AWE) with symptomatic intracranial aneurysms (IAs), we hypothesized that the ER of AWE would be stronger in symptomatic IAs than in asymptomatic IAs, as assessed by high-resolution magnetic resonance imaging (HRMRI). MATERIALS AND METHODS: Between February 2016 and February 2018, 80 consecutive patients with 89 unruptured IAs were reviewed. Patients and IAs were divided into symptomatic and asymptomatic groups. In addition to the clinical characteristics, the IA features (e.g., size, shape) were evaluated via computed tomography angiography, while the ER and enhanced patterns were evaluated by HRMRI. Multiple logistic regression analysis was performed to determine the independent risk factors for symptomatic IAs. Receiver operating characteristic curve analysis was used for the final model to obtain the optimal thresholds. RESULTS: Multiple logistic regression analysis indicated that only the ER was associated with symptomatic IAs. The threshold value of the ER was 60.5%. CONCLUSIONS: A higher ER was more frequently identified in symptomatic IAs. More attention should be paid to this factor in the management of IAs.


Assuntos
Aneurisma Intracraniano/patologia , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Curva ROC , Estudos Retrospectivos , Fatores de Risco
6.
Acad Radiol ; 26(10): e292-e297, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30567638

RESUMO

RATIONALE AND OBJECTIVES: To identify the relationship between enhancement ratio (ER) of aneurysm walls and degrees of inflammation. MATERIALS AND METHODS: Twenty-five white rabbits were used in this study; all underwent surgery to isolate the right common carotid artery (RCCA). Twenty rabbits underwent an aneurysm creation procedure, and 5 underwent a control procedure. In the aneurysm creation procedure, there was surgical exposure of the origin of RCCA and temporary occlusion with an aneurysm clip. The distal RCCA was ligated, and the trapped segment was infused with elastase for 20 minutes, after which the clip was removed. In the control procedure, the trapped segment was infused with saline. High-resolution magnetic resonance imaging was performed at weeks 2, 3, 4, and 5 after the procedure, and wall ER was calculated. After MRI, aneurysms were harvested and stained with hematoxylin-eosin. Pearson correlation analysis and scatter plots were used to evaluate the relationship between wall ER and the degree of inflammation. The relationships between the wall ER, the number of inflammatory cells and time were analyzed by linear graphs. RESULTS: Wall ER positively correlated with inflammatory cell count of the aneurysm wall (r = 0.877, p < 0.001). The relationships between wall ER, the number of inflammatory cells, and time increased and then decreased according linear graphs. CONCLUSION: In this study, the aneurysm wall ER was confirmed to be associated with the degree of inflammation on the rabbit aneurysm model.

7.
Front Cell Neurosci ; 12: 454, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30534056

RESUMO

Background: Early postmenopausal women frequently suffer from cognitive impairments and emotional disorders, such as lack of attention, poor memory, deficits in executive function and depression. However, the underlying mechanisms of these impairments remain unclear. Method: Forty-three early postmenopausal women and forty-four age-matched premenopausal controls underwent serum sex hormone analysis, neuropsychological testing and resting-state functional magnetic resonance imaging (rs-fMRI). Degree centrality (DC) analysis was performed to confirm the peak points of the functionally abnormal brain areas as the centers of the seeds. Subsequently, the functional connectivity (FC) between these abnormal seeds and other voxels across the whole brain was calculated. Finally, the sex hormone levels, neuroimaging indices and neuropsychological data were combined to detect potential correlations. Results: Compared with the premenopausal controls, the early postmenopausal women exhibited significantly higher serum follicle-stimulating hormone (FSH) levels, more severe climacteric and depressive symptoms, worse sleep quality and more extensive cognitive impairments. Concurrently, the neuroimaging results showed elevated DC values in the left amygdala (AMYG.L), reduced DC values in the left middle occipital gyrus (MOG.L) and right middle occipital gyrus (MOG.R). When we used the AMYG.L as the seed point, FC with the left insula (INS.L), bilateral prefrontal cortex (PFC) and right superior frontal gyrus (SFG.R) was increased; these regions are related to depressive states, poor sleep quality and decreased executive function. When bilateral MOG were used as the seed points, FC with left inferior parietal gyrus (IPG.L), this area closely associated with impaired memory, was decreased. Conclusion: These results illuminated the regional and network-level brain dysfunction in early postmenopausal women, which might provide information on the underlying mechanisms of the different cognitive impairments and emotional alterations observed in this group.

8.
Brain Imaging Behav ; 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30259292

RESUMO

This study investigated the aberrant connectivity of the salience network (SN) and default mode network (DMN) and the relevance between these abnormalities and symptom improvement in hyperthyroid patients using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based functional connectivity (FC) analyses were performed on state fMRI data to reveal possible differences in critical node connectivity in the SN and DMN between 41 new-onset, untreated hyperthyroid patients and 41 healthy controls. Subsequently, follow-up data were available for 25 patients treated with methimazole for one month. Compared with the healthy controls, the patients exhibited abnormal internetwork FC from the SN to the DMN and the executive control network (ECN) and decreased intra-network FC within the SN. Relative to the hyperthyroid state, the antithyroid therapy induced reversible connectivity of the left insula to the dorsal anterior cingulate cortex(dACC)and ECN, and persistently increased connectivity between the SN and DMN in patients with improved thyroid function. Finally, Pearson's correlation analyses were performed among the abnormal FC, neuropsychological assessment and serum free triiodothyronine(FT3)level data. The results indicated that aberrant intra- and internetwork FC in the SN and DMN might underlie the pathogenesis of hyperthyroidism, and antithyroid treatment could regulate the FC of certain key brain regions within the SN and DMN in hyperthyroid patients.

9.
World Neurosurg ; 115: e27-e32, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29567291

RESUMO

OBJECTIVE: To evaluate risk factors for instability in intracranial aneurysms (IAs) using computed tomography angiography (CTA). METHODS: A total of 614 consecutive patients diagnosed with 661 IAs between August 2011 and February 2016 were reviewed. Patients and IAs were divided into stable and unstable groups. Along with clinical characteristics, IA characteristics were evaluated by CTA. Multiple logistic regression analysis was used to identify the independent risk factors associated with unstable IAs. Receiver operating characteristic (ROC) curve analysis was performed on the final model, and optimal thresholds were obtained. RESULTS: Patient age (odds ratio [OR], 0.946), cerebral atherosclerosis (CA; OR, 0.525), and IAs located at the middle cerebral artery (OR, 0.473) or internal carotid artery (OR, 0.512) were negatively correlated with instability, whereas IAs with irregular shape (OR, 2.157), deep depth (OR, 1.557), or large flow angle (FA; OR, 1.015) were more likely to be unstable. ROC analysis revealed threshold values of age, depth, and FA of 59.5 years, 4.25 mm, and 87.8°, respectively. CONCLUSIONS: The stability of IAs is significantly affected by several factors, including patient age and the presence of CA. IA shape and location also have an impact on the stability of IAs. Growth into an irregular shape, with a deep depth, and a large FA are risk factors for a change in IAs from stable to unstable.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia por Tomografia Computadorizada/normas , Aneurisma Intracraniano/diagnóstico por imagem , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Fatores de Risco
10.
J Neurointerv Surg ; 10(10): 995-998, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29437934

RESUMO

OBJECTIVE: Patient related clinical factors and intracranial aneurysms (IAs) at different locations may lead to statistical bias when investigating the rupture risk of IAs. Thus the purpose of this study was to identify the morphological parameters that are related to the rupture of mirror posterior communicating artery aneurysms (PComAAs). METHODS: Between August 2011 and July 2017, 68 patients with mirror PComAAs and aneurysmal subarachnoid hemorrhage were diagnosed by CT angiography at three medical centers. Morphological characteristics for PComAAs included bifurcation, shape, neck width, width, depth, maximum size, flow angle, parent vessel diameter, aspect ratio (AR), depth/width ratio, bottleneck factor, and size ratio (SR). Multiple logistic regression analysis was performed to determine the independent risk factors for rupture. Receiver operating characteristic curve analysis was performed to obtain the optimal thresholds. RESULTS: AR (OR 5.623) and SR (OR 5.570) were more commonly observed in the ruptured cohort. The threshold values of AR and SR were 0.98 and 1.21, respectively. CONCLUSIONS: Mirror PComAAs are a useful model to investigate the rupture risk of PComAAs. AR (≥0.98) and SR (≥1.21) are better predictors of ruptured PComAAs.


Assuntos
Aneurisma Roto/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/epidemiologia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Aneurisma Intracraniano/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/epidemiologia
11.
BMC Cancer ; 17(1): 335, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28514957

RESUMO

BACKGROUND: Lymphatic vessel density and lymphovascular invasion are commonly assessed to identify the clinicopathological outcomes in breast cancer. However, the prognostic values of them on patients' survival are still uncertain. METHODS: Databases of PubMed, Embase, and Web of Science were searched from inception up to 30 June 2016. The hazard ratio with its 95% confidence interval was used to determine the prognostic effects of lymphatic vessel density and lymphovascular invasion on disease-free survival and overall survival in breast cancer. RESULTS: Nineteen studies, involving 4215 participants, were included in this study. With the combination of the results of lymphatic vessel density, the pooled hazard ratios and 95% confidence intervals were 2.02 (1.69-2.40) for disease-free survival and 2.88 (2.07-4.01) for overall survival, respectively. For lymphovascular invasion study, the pooled hazard ratios and 95% confidence intervals were 1.81 (1.57-2.08) for disease-free survival and 1.64 (1.43-1.87) for overall survival, respectively. In addition, 29.56% (827/2798) of participants presented with lymphovascular invasion in total. CONCLUSIONS: Our study demonstrates that lymphatic vessel density and lymphovascular invasion can predict poor prognosis in breast cancer. Standardized assessments of lymphatic vessel density and lymphovascular invasion are needed.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Vasos Linfáticos/patologia , Intervalo Livre de Doença , Feminino , Humanos , Linfangiogênese/fisiologia , Metástase Linfática , Invasividade Neoplásica/patologia , Modelos de Riscos Proporcionais
12.
Adv Mater ; 29(26)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28466959

RESUMO

Here, this study reports a novel confined-space thermal dewetting strategy for the fabrication of Au nanocups with tunable diameter, height, and size of cup opening. The nanocup morphology is defined by the cup-shaped void space created by a yolk-shell silica template that spontaneously takes an eccentric configuration during annealing. Thermal dewetting of Au, which is sandwiched between the yolk and shell, leads to the desired nanocup morphology. With strong scattering in near infrared, the Au nanocups exhibit superior efficiency as contrast agents for spectral-domain optical coherence tomography imaging. This confined-space thermal dewetting strategy is scalable and general, and can be potentially extended to the synthesis of novel anisotropic nanostructures of various compositions that are difficult to produce by conventional wet chemical or physical methods, thus opening up opportunities for many new applications.

13.
Sci Rep ; 7: 40364, 2017 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-28067327

RESUMO

The status of lymph node involvement is an important prognostic factor for breast cancer. However, the presence of intratumoral lymphatic vessels in primary tumor lesions and the relationship between lymphatic vessel density (LVD) and lymph node metastasis (LNM) have not been firmly established. Therefore, we performed a meta-analysis study to investigate these issues. According to the pre-established inclusion and exclusion criteria, 13 studies, involving 1029 breast cancer patients, were included in this study. Using immunohistochemical staining, intratumoral lymphatic vessels were detected in 40.07% of breast cancer patients (240/599), and peritumoral lymphatics were detected in 77.09% (397/515). All studies demonstrated that peritumoral LVD was higher than intratumoral LVD, with a pooled standard mean difference and 95% confidence interval (95% CI) of 1.75 (1.28 to 2.21). Both intratumoral LVD and peritumoral LVD positively correlated with LNM, with correlation coefficients of 0.14 (95% CI 0.05 to 0.23) and 0.31 (95% CI 0.13 to 0.49), respectively. In summary, our study reports the overall detection rate of intratumoral lymphatics and demonstrates the associations between intratumoral LVD, peritumoral LVD, and LNM in breast cancer. Additionally, controlled studies with a larger number of subjects are needed to establish these relationships.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Viés de Publicação
14.
Oncotarget ; 8(2): 2863-2873, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27926511

RESUMO

Lymph node status is one of the key parameters used for determining the stage of breast cancer progression. The relationship of lymphatic vessel density (LVD), lymphovascular invasion (LVI), and lymph node metastasis (LNM) has not been clearly demonstrated yet. Databases of PubMed, Embase, and Web of Science were searched from inception up to 25 May 2016. Spearman correlation coefficient (r) and 95% confidence interval (CI) were used to determine the relationship within each group. Based on pre-established inclusion criteria, 28 studies involving 2920 breast cancer patients were included in this study. The r values of LVD-LVI, LVD-LNM, and LVI-LNM were 0.45 (95% CI: 0.31 to 0.57), 0.32 (95% CI: 0.23 to 0.40), and 0.24 (95% CI: 0.19 to 0.28), respectively. Compared with intratumoral LVD, peritumoral LVD showed more robust correlation with LVI (r = 0.53, 95% CI: 0.27 to 0.72) and LNM (r = 0.33, 95% CI: 0.18 to 0.46). The patients in LNM positive group presented with higher LVI detection rate of 45.85%, while in LNM negative group with detection rate of 23.85%. The results describe a triangle relationship between LVD, LVI, and LNM in breast cancer. Both LVD and LVI are indicated to be valuable predictors of LNM occurrence. Compared with intratumoral lymphatic vessels, peritumoral lymphatics might be the main disseminate route for breast tumor cells.


Assuntos
Neoplasias da Mama/patologia , Vasos Linfáticos/patologia , Neovascularização Patológica , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Invasividade Neoplásica , Viés de Publicação
15.
Int J Nanomedicine ; 11: 4051-63, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27578974

RESUMO

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM(-1) s(-1), which was much higher than that of MnFe2O4 nanoparticles (67.5 mM 1 s(-1)). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn(2+) ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.


Assuntos
Meios de Contraste/química , Compostos Férricos/química , Imagem por Ressonância Magnética , Compostos de Manganês/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Lactonas/química , Microscopia Eletrônica de Transmissão , Sondas Moleculares , Neoplasias/diagnóstico , Neovascularização Patológica , Poliésteres/química , Polietilenoglicóis/química , Sensibilidade e Especificidade
16.
Eur Radiol ; 26(11): 4089-4097, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26960542

RESUMO

OBJECTIVES: Using the human telomerase reverse transcriptase (hTERT) promoter and the modified ferritin heavy chain (Fth) reporter gene, reporter gene expression for MRI was examined in telomerase positive and negative tumour cells and xenografts. METHODS: Activity of the reporter gene expression vector Lenti-hTERT-Fth1-3FLAG-Puro was compared to constitutive CMV-driven expression and to the untransfected parental control in five tumour cell lines: A549, SKOV3, 293T, U2OS and HPDLF. In vitro, transfected cells were evaluated for FLAG-tagged protein expression, iron accumulation and transverse relaxation. In vivo, tumours transduced by lentiviral vector injection were imaged using T2*WI. Changes in tumour signal intensity were validated by histology. RESULTS: Only telomerase positive tumour cells expressed FLAG-tagged Fth and displayed an increase in R2* above the parental control, with a corresponding change in T2*WI. In addition, only telomerase positive tumours, transduced by injection of the reporter gene expression construct, exhibited a change in signal intensity on T2*WI. Tumour histology verified the expression of FLAG-tagged Fth and iron accumulation in telomerase positive tissue. CONCLUSION: Reporter gene expression for MRI, using the Fth reporter and the hTERT promoter, may be a useful strategy for the non-invasive diagnosis of many types of cancer. KEY POINTS: • Modified heavy chain of ferritin can serve as an MR reporter gene • hTERT promoter can direct the expression of reporter gene in cancer cells • MR reporter imaging mediated by hTERT promoter can be used for cancer diagnosis.


Assuntos
Apoferritinas/metabolismo , Imagem Molecular/métodos , Neoplasias/diagnóstico , Telomerase/metabolismo , Análise de Variância , Animais , Apoferritinas/genética , Linhagem Celular Tumoral , Genes Reporter/genética , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética/métodos , Masculino , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas/genética , Telomerase/genética , Transfecção/métodos
17.
J Nanobiotechnology ; 13: 24, 2015 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-25890315

RESUMO

BACKGROUND: GoldMag nanoparticles (GMNPs) possess the properties of colloid gold and superparamagnetic iron oxide nanoparticles, which make them useful for delivery, separation and molecular imaging. However, because of the nanometer effect, GMNPs are highly toxic. Thus, the biosafety of GMNPs should be fully studied prior to their use in biomedicine. The main purpose of this study was to evaluate the nanotoxicity of GMNPs on human umbilical vein endothelial cells (HUVECs) and determine a suitable size, concentration and time for magnetic resonance imaging (MRI). RESULTS: Transmission electron microscopy showed that GMNPs had a typical shell/core structure, and the shell was confirmed to be gold using energy dispersive spectrometer analysis. The average sizes of the 30 and 50 nm GMNPs were 30.65 ± 3.15 and 49.23 ± 5.01 nm, respectively, and the shell thickness were 6.8 ± 0.65 and 8.5 ± 1.36 nm, respectively. Dynamic light scattering showed that the hydrodynamic diameter of the 30 and 50 nm GMNPs were 33.2 ± 2.68 and 53.12 ± 4.56 nm, respectively. The r 2 relaxivity of the 50 nm GMNPs was 98.65 mM(-1) s(-1), whereas it was 80.18 mM(-1) s(-1) for the 30 nm GMNPs. The proliferation, cytoskeleton, migration, tube formation, apoptosis and ROS generation of labeled HUVECs depended on the size and concentration of GMNPs and the time of exposure. Because of the higher labeling rate, the 50 nm GMNPs exhibited a significant increase in nanotoxicity compared with the 30 nm GMNPs at the same concentration and time. At no more than 25 µg/mL and 12 hours, the 50 nm GMNPs exhibited no significant nanotoxicity in HUVECs, whereas no toxicity was observed at 50 µg/mL and 24 hours for the 30 nm GMNPs. CONCLUSIONS: These results demonstrated that the nanotoxicity of GMNPs in HUVECs depended on size, concentration and time. Exposure to larger GMNPs with a higher concentration for a longer period of time resulted in a higher labeling rate and ROS level for HUVECs. Coupled with r 2 relaxivity, it was suggested that the 50 nm GMNPs are more suitable for HUVEC labeling and MRI, and the suitable concentration and time were 25 µg/mL and 12 hours.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dextranos/química , Relação Dose-Resposta a Droga , Ouro/química , Células Endoteliais da Veia Umbilical Humana/química , Humanos , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Microscopia Eletrônica de Transmissão , Neovascularização Fisiológica/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
18.
Pak J Pharm Sci ; 27(4 Suppl): 1089-92, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25016271

RESUMO

Hemsleya sinesis Cogn has a variety of medicinal value. Strain KLXD06 is an endophytic bacteria isolated from H. sinesis exhibited significant inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA). This strain was identified by methods including 16S rDNA sequence homology and phylogenetic analysis morphological, biochemical and physiological characteristics analysis. Ccrude protein from KLXD06 was extracted by ammon ium sulfate salting-out. The results showed that strain KLXD06 was identified as Serratia marcescens. Antibacterial crude protein from KLXD06 was extracted by ammon ium sulfate salting-out, has a thermal stability.


Assuntos
Proteínas de Bactérias/farmacologia , Cucurbitaceae/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Serratia marcescens/química , Filogenia , Serratia marcescens/classificação , Serratia marcescens/isolamento & purificação
19.
Eur J Radiol ; 83(7): 1190-1198, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24832501

RESUMO

OBJECTIVE: To detect tumor angiogenesis in tumor-bearing mice using thiol-PEG-carboxyl-stabilized Fe2O3/Au nanoparticles targeted to CD105 on magnetic resonance imaging (MRI). METHODS: Fe2O3/Au nanoparticles (hybrids) were prepared by reducing Au(3+) on the surface of Fe2O3 nanoparticles. Hybrids were stabilized with thiol-PEG-carboxyl via the Au-S covalent bond, and further conjugated with anti-CD105 antibodies through amide linkages. Characteristics of the hybrid-PEG-CD105 nanoparticles were evaluated. Using these nanoparticles, the labeling specificity of human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. MRI T2-weighted images were obtained at different time points after intravenous administration of the hybrid-PEG-CD105 nanoparticles in the tumor-bearing mice. After MR imaging, the breast cancer xenografts were immediately resected for immunohistochemistry staining and Prussian blue staining to measure the tumor microvessel density (MVD) and evaluate the labeling of blood microvessels by the hybrid-PEG-CD105 nanoparticles in vivo. RESULTS: The mean diameter of the hybrid-PEG-CD105 nanoparticles was 56.6 ± 8.0 nm, as measured by transmission electron microscopy (TEM). Immune activity of the hybrid-PEG-CD105 nanoparticles was 53% of that of the anti-CD105 antibody, as detected by enzyme-linked immunosorbent assay (ELISA). The specific binding of HUVECs with the hybrid-PEG-CD105 nanoparticles was proved by immunostaining and Prussian blue staining in vitro. For breast cancer xenografts, the combination of the hybrid-PEG-CD105 nanoparticles with blood microvessels was detectable by MRI after 60 min administration of the contrast agent. The T2* relative signal intensity (SIR) was positively correlated with the tumor MVD (R(2)=0.8972). CONCLUSION: Anti-CD105 antibody-coupled, thiol-PEG-carboxyl-stabilized core-shell Fe2O3/Au nanoparticles can efficiently target CD105 expressed by HUVECs. Furthermore, the hybrid-PEG-CD105 nanoparticles can be used to detect tumor angiogenesis in vivo.


Assuntos
Neoplasias da Mama/patologia , Ouro , Nanopartículas de Magnetita , Nanoconjugados/química , Neovascularização Patológica/patologia , Polietilenoglicóis/química , Animais , Anticorpos Monoclonais/imunologia , Neoplasias da Mama/imunologia , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Desenho de Drogas , Estabilidade de Medicamentos , Endoglina , Excipientes/química , Ouro/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Nanopartículas de Magnetita/química , Camundongos , Nanoconjugados/ultraestrutura , Neovascularização Patológica/imunologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Compostos de Sulfidrila/química
20.
Molecules ; 16(12): 9775-82, 2011 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-22117168

RESUMO

Phytohemical investigation on the heartwood of Dalbergia odorifera resulted in the isolation of nine flavonoids. Their structures were elucidated as sativanone (1), (3R)-vestitone (2), (3R)-2',3',7-trihydroxy-4'-methoxyisoflavanone (3), (3R)-4'-methoxy-2',3,7-trihydroxyisoflavanone (4), carthamidin (5), liquiritigenin (6), isoliquiritigenin (7), (3R)-vestitol (8), and sulfuretin (9) based on their spectral data. All compounds were evaluated for their inhibitory activity against Ralstonia solanacearum. This is the first report about anti-R. solanacearum activity of the compounds from D. odorifera.


Assuntos
Antibacterianos/farmacologia , Dalbergia/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Ralstonia solanacearum/efeitos dos fármacos , Antibacterianos/química , Flavonoides/química , Testes de Sensibilidade Microbiana
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