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1.  Enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA on human brain metastatic breast cancer 
Scientific Reports  2015;5:8029.
Novel molecularly targeted agents that block the development and metastasis of human brain metastatic breast cancer hold great promise for their translational value. In this study, we constructed a novel targeting composite peptide BRBP1-TAT-KLA comprising of three elements: a brain metastatic breast carcinoma cell (231-BR)-binding peptide BRBP1, a cell penetrating peptide TAT, and a proapoptotic peptide KLA. This composite peptide efficiently internalized in 231-BR cells and consequently induced mitochondrial damage and cellular apoptosis. Exposure of 231-BR cells to BRBP1-TAT-KLA significantly decreased cell viability and increased apoptosis compared with the cells treated with the control peptides. In vivo relevance of these findings was further corroborated in the 231-BR tumor-bearing mice that demonstrated significantly delayed tumor development and metastasis following administration of BRBP1-TAT-KLA compared with those treated with TAT-KLA alone. Interestingly, BRBP1-TAT-KLA inhibited the formation of both large and micro-metastases, while TAT-KLA alone failed to significantly reduce micro-metastases in the breast cancer brain metastasis mice. BRBP1-TAT-KLA selectively homed to the tumors in vivo where it induced cellular apoptosis without significant toxicity on non-tumor tissues. Our findings therefore demonstrated the enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA, providing insights toward development of a potential therapeutic strategy for brain metastatic breast cancer.
doi:10.1038/srep08029
PMCID: PMC4306141  PMID: 25619721
2.  A Rat Brain MRI Template with Digital Stereotaxic Atlas of Fine Anatomical Delineations in Paxinos Space and its Automated Application in Voxel-Wise Analysis 
Human brain mapping  2012;34(6):1306-1318.
This study constructs a rat brain T2-weighted magnetic resonance imaging template including olfactory bulb and a compatible digital atlas. The atlas contains 624 carefully delineated brain structures based on the newest (2005) edition of rat brain atlas by Paxinos and Watson. An automated procedure, as an SPM toolbox, was introduced for spatially normalizing individual rat brains, conducting statistical analysis and visually localizing the results in the Atlas coordinate space. The brain template/atlas and the procedure were evaluated using functional images between rats with the right side middle cerebral artery occlusion (MCAO) and normal controls. The result shows that the brain region with significant signal decline in the MCAO rats was consistent with the occlusion position.
doi:10.1002/hbm.21511
PMCID: PMC4110061  PMID: 22287270
SD rat brain; MRI imaging analysis; SPM; normalization; location; co-registration
3.  Spatial–temporal atlas of human fetal brain development during the early second trimester 
NeuroImage  2013;82:10.1016/j.neuroimage.2013.05.063.
During the second trimester, the human fetal brain undergoes numerous changes that lead to substantial variation in the neonatal in terms of its morphology and tissue types. As fetal MRI is more and more widely used for studying the human brain development during this period, a spatiotemporal atlas becomes necessary for characterizing the dynamic structural changes. In this study, 34 postmortem human fetal brains with gestational ages ranging from 15 to 22 weeks were scanned using 7.0 T MR. We used automated morphometrics, tensor-based morphometry and surface modeling techniques to analyze the data. Spatiotemporal atlases of each week and the overall atlas covering the whole period with high resolution and contrast were created. These atlases were used for the analysis of age-specific shape changes during this period, including development of the cerebral wall, lateral ventricles, Sylvian fissure, and growth direction based on local surface measurements. Our findings indicate that growth of the subplate zone is especially striking and is the main cause for the lamination pattern changes. Changes in the cortex around Sylvian fissure demonstrate that cortical growth may be one of the mechanisms for gyration. Surface deformation mapping, revealed by local shape analysis, indicates that there is global anterior–posterior growth pattern, with frontal and temporal lobes developing relatively quickly during this period. Our results are valuable for understanding the normal brain development trajectories and anatomical characteristics. These week-by-week fetal brain atlases can be used as reference in in vivo studies, and may facilitate the quantification of fetal brain development across space and time.
doi:10.1016/j.neuroimage.2013.05.063
PMCID: PMC3876574  PMID: 23727529
Fetal MRI; Second-trimester; Atlas; Human brain development
4.  Analysis of in situ and ex vivo αVβ3 integrin expression during experimental carotid atherogenesis 
Objective
Mural inflammation has been shown to contribute to the development of plaque, with the αVβ3 integrin highly expressed in atherosclerotic plaques. We herein examined αVβ3 integrin expression as a function of carotid atherosclerosis formation in the apolipoprotein E-deficient (apoE−/−) mouse.
Methods and results
Constrictive collars were placed around the left common carotid arteries of apo E−/− mice maintained on a high-fat diet (n = 14). Before and 21 days following collar placement, in vivo serial magnetic resonance imaging (MRI) measurements of the carotid aortic diameter were performed using a 7T magnetic resonance (MR) scanner. Near- infrared fluorescence (NIRF) imaging was performed (n = 6) using an in vivo imaging system 0–24 hours following administration of 1.0 nmol c(RGDyK)-Cy5.5 via the tail vein. A competition experiment was performed by the co-injection of a saturating dose of bicyclic RGD peptide H-Glu[cyclo(Arg-Gly-Asp-D-Tyr-Lys)]2 (n = 3). Following image acquisition and sacrifice at 24 hours after injection, carotid arteries were harvested for histological analyses. Neointima formation and arterial remodeling in the carotid arteries of apoE−/− mice were induced by the placement of a constrictive collar. Significantly greater fluorescent signals were obtained from constrictive collar left common carotid arteries as compared to uninvolved aortic segments in constrictive collar mice. Binding to stenotic lesions was efficiently blocked in competition experiments. Immunostaining confirmed the presence of mural αVβ3 integrin expression in macrophages in the neointima. Signal intensity increased in a macrophage density-dependent fashion in the stenotic segments.
Conclusion
Mural αVβ3 integrin expression, as determined using RGD-Cy5.5 near-infrared optical imaging, was increased in carotid arteries with constrictive collars in experimental mice. This expression can estimate the macrophage-bound inflammatory activity of atherosclerotic lesions.
doi:10.2147/IJN.S28065
PMCID: PMC3278228  PMID: 22334786
near-infrared fluorescence (NIRF); macrophage; αVβ3 integrin; carotid atherogenesis
5.  Ferritin Enhances SPIO Tracking of C6 Rat Glioma Cells by MRI 
Purpose
To investigate the effect of ferritin protein overexpression on superparamagnetic iron oxide (SPIO) particle labeling of C6 rat glioma cells, and track the labeled cells in vivo using magnetic resonance imaging (MRI).
Materials and Methods
A plasmid of H-chain of murine ferritin gene was constructed and transfected into C6 cells. The parental and the transfected C6 cells labeled with SPIO were bilaterally inoculated subcutaneously into nude mice. The mice were imaged by multiple T2-weighted MR scans after C6 cell inoculation. The mice were killed 2 weeks later, and the concentration of iron in the tumor tissue was measured by inductively coupled plasma.
Results
The iron concentration in xenografts derived from SPIO-labeled C6 cells that were transfected with ferritin plasmid was significantly higher than that in xenografts from parental C6 cells that were labeled with SPIO but not transfected (p=0.034, N=5). Ferritin-transfected C6 cells showed an improved T2 contrast in vivo compared with parental cells labeled with SPIO but not transfected.
Conclusion
Coordinating ferritin with SPIO can lead to a longer MRI cellular tracking period.
doi:10.1007/s11307-010-0338-5
PMCID: PMC2966504  PMID: 20440566
Ferritin reporter; Superparamagnetic iron oxide (SPIO) particle; Cell tracking; MRI
6.  Learning and Memory Alterations Are Associated with Hippocampal N-acetylaspartate in a Rat Model of Depression as Measured by 1H-MRS 
PLoS ONE  2011;6(12):e28686.
It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.
doi:10.1371/journal.pone.0028686
PMCID: PMC3237477  PMID: 22194886
7.  Fluorescence Modified Chitosan-Coated Magnetic Nanoparticles for High-Efficient Cellular Imaging 
Nanoscale Research Letters  2009;4(4):287-295.
Labeling of cells with nanoparticles for living detection is of interest to various biomedical applications. In this study, novel fluorescent/magnetic nanoparticles were prepared and used in high-efficient cellular imaging. The nanoparticles coated with the modified chitosan possessed a magnetic oxide core and a covalently attached fluorescent dye. We evaluated the feasibility and efficiency in labeling cancer cells (SMMC-7721) with the nanoparticles. The nanoparticles exhibited a high affinity to cells, which was demonstrated by flow cytometry and magnetic resonance imaging. The results showed that cell-labeling efficiency of the nanoparticles was dependent on the incubation time and nanoparticles’ concentration. The minimum detected number of labeled cells was around 104 by using a clinical 1.5-T MRI imager. Fluorescence and transmission electron microscopy instruments were used to monitor the localization patterns of the magnetic nanoparticles in cells. These new magneto-fluorescent nanoagents have demonstrated the potential for future medical use.
doi:10.1007/s11671-008-9239-9
PMCID: PMC2893437  PMID: 20596545
Magnetic nanoparticle; Fluorescence; Chitosan; Magnetic resonance imaging
8.  Fluorescence Modified Chitosan-Coated Magnetic Nanoparticles for High-Efficient Cellular Imaging 
Nanoscale Research Letters  2009;4(4):287-295.
Labeling of cells with nanoparticles for living detection is of interest to various biomedical applications. In this study, novel fluorescent/magnetic nanoparticles were prepared and used in high-efficient cellular imaging. The nanoparticles coated with the modified chitosan possessed a magnetic oxide core and a covalently attached fluorescent dye. We evaluated the feasibility and efficiency in labeling cancer cells (SMMC-7721) with the nanoparticles. The nanoparticles exhibited a high affinity to cells, which was demonstrated by flow cytometry and magnetic resonance imaging. The results showed that cell-labeling efficiency of the nanoparticles was dependent on the incubation time and nanoparticles’ concentration. The minimum detected number of labeled cells was around 104by using a clinical 1.5-T MRI imager. Fluorescence and transmission electron microscopy instruments were used to monitor the localization patterns of the magnetic nanoparticles in cells. These new magneto-fluorescent nanoagents have demonstrated the potential for future medical use.
doi:10.1007/s11671-008-9239-9
PMCID: PMC2893437  PMID: 20596545
Magnetic nanoparticle; Fluorescence; Chitosan; Magnetic resonance imaging

Results 1-8 (8)