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Search Results: 1 - 10 of 132598 matches for " Thuc T. Le "
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Single-Cell Profiling Reveals the Origin of Phenotypic Variability in Adipogenesis
Thuc T. Le, Ji-Xin Cheng
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005189
Abstract: Phenotypic heterogeneity in a clonal cell population is a well-observed but poorly understood phenomenon. Here, a single-cell approach is employed to investigate non-mutative causes of phenotypic heterogeneity during the differentiation of 3T3-L1 cells into fat cells. Using coherent anti-Stokes Raman scattering microscopy and flow cytometry, adipogenic gene expression, insulin signaling, and glucose import are visualized simultaneously with lipid droplet accumulation in single cells. Expression of adipogenic genes PPARγ, C/EBPα, aP2, LP2 suggests a commitment to fat cell differentiation in all cells. However, the lack of lipid droplet in many differentiating cells suggests adipogenic gene expression is insufficient for lipid droplet formation. Instead, cell-to-cell variability in lipid droplet formation is dependent on the cascade responses of an insulin signaling pathway which includes insulin sensitivity, kinase activity, glucose import, expression of an insulin degradation enzyme, and insulin degradation rate. Increased and prolonged insulin stimulation promotes lipid droplet accumulation in all differentiating cells. Single-cell profiling reveals the kinetics of an insulin signaling cascade as the origin of phenotypic variability in drug-inducible adipogenesis.
Uridine Prevents Fenofibrate-Induced Fatty Liver
Thuc T. Le, Yasuyo Urasaki, Giuseppe Pizzorno
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087179
Abstract: Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD) and acyl-CoA oxidase 1 (ACOX1), and induces excessive accumulation of long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA). Uridine co-administration at a daily dosage of 400 mg/kg raises NAD+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.
Uridine Affects Liver Protein Glycosylation, Insulin Signaling, and Heme Biosynthesis
Yasuyo Urasaki, Giuseppe Pizzorno, Thuc T. Le
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099728
Abstract: Purines and pyrimidines are complementary bases of the genetic code. The roles of purines and their derivatives in cellular signal transduction and energy metabolism are well-known. In contrast, the roles of pyrimidines and their derivatives in cellular function remain poorly understood. In this study, the roles of uridine, a pyrimidine nucleoside, in liver metabolism are examined in mice. We report that short-term uridine administration in C57BL/6J mice increases liver protein glycosylation profiles, reduces phosphorylation level of insulin signaling proteins, and activates the HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. Short-term uridine administration is also associated with reduced liver hemin level and reduced ability for insulin-stimulated blood glucose removal during an insulin tolerance test. Some of the short-term effects of exogenous uridine in C57BL/6J mice are conserved in transgenic UPase1?/? mice with long-term elevation of endogenous uridine level. UPase1?/? mice exhibit activation of the liver HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. UPase1?/? mice also exhibit impaired ability for insulin-stimulated blood glucose removal. However, other short-term effects of exogenous uridine in C57BL/6J mice are not conserved in UPase1?/? mice. UPase1?/? mice exhibit normal phosphorylation level of liver insulin signaling proteins and increased liver hemin concentration compared to untreated control C57BL/6J mice. Contrasting short-term and long-term consequences of uridine on liver metabolism suggest that uridine exerts transient effects and elicits adaptive responses. Taken together, our data support potential roles of pyrimidines and their derivatives in the regulation of liver metabolism.
Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis
Thuc T Le, Terry B Huff, Ji-Xin Cheng
BMC Cancer , 2009, DOI: 10.1186/1471-2407-9-42
Abstract: Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments.CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells.Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis.Excess lipid in the body has been shown to aggravate cancer. Animal studies showed that high fat diets and obesity enhanced cancer metastasis [1]. In human, a body mass index above 30 kg/m2 is strongly correlated with increased risk for various types of cancer [2]. It is generally accepted that diet and obesity are accountable for 30% of preventable causes of cancer [2]. Indeed, diet, nutrition, and physical activity are widely promoted as effective means for cancer prevention by the World Cancer Research Fund and the American Institute for Cancer Research [3]. Nonetheless, the relationship between diet and cancer incidence and mortality in huma
Label-free Evaluation of Hepatic Microvesicular Steatosis with Multimodal Coherent Anti-Stokes Raman Scattering Microscopy
Thuc T. Le, Amy Ziemba, Yasuyo Urasaki, Steven Brotman, Giuseppe Pizzorno
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051092
Abstract: Hepatic microvesicular steatosis is a hallmark of drug-induced hepatotoxicity and early-stage fatty liver disease. Current histopathology techniques are inadequate for the clinical evaluation of hepatic microvesicular steatosis. In this paper, we explore the use of multimodal coherent anti-Stokes Raman scattering (CARS) microscopy for the detection and characterization of hepatic microvesicular steatosis. We show that CARS microscopy is more sensitive than Oil Red O histology for the detection of microvesicular steatosis. Computer-assisted analysis of liver lipid level based on CARS signal intensity is consistent with triglyceride measurement using a standard biochemical assay. Most importantly, in a single measurement procedure on unprocessed and unstained liver tissues, multimodal CARS imaging provides a wealth of critical information including the detection of microvesicular steatosis and quantitation of liver lipid content, number and size of lipid droplets, and lipid unsaturation and packing order of lipid droplets. Such information can only be assessed by multiple different methods on processed and stained liver tissues or tissue extracts using current standard analytical techniques. Multimodal CARS microscopy also permits label-free identification of lipid-rich non-parenchymal cells. In addition, label-free and non-perturbative CARS imaging allow rapid screening of mitochondrial toxins-induced microvesicular steatosis in primary hepatocyte cultures. With its sensitivity and versatility, multimodal CARS microscopy should be a powerful tool for the clinical evaluation of hepatic microvesicular steatosis.
Imaging Immune and Metabolic Cells of Visceral Adipose Tissues with Multimodal Nonlinear Optical Microscopy
Yasuyo Urasaki, Mary G. Johlfs, Ronald R. Fiscus, Thuc T. Le
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038418
Abstract: Visceral adipose tissue (VAT) inflammation is recognized as a mechanism by which obesity is associated with metabolic diseases. The communication between adipose tissue macrophages (ATMs) and adipocytes is important to understanding the interaction between immunity and energy metabolism and its roles in obesity-induced diseases. Yet visualizing adipocytes and macrophages in complex tissues is challenging to standard imaging methods. Here, we describe the use of a multimodal nonlinear optical (NLO) microscope to characterize the composition of VATs of lean and obese mice including adipocytes, macrophages, and collagen fibrils in a label-free manner. We show that lipid metabolism processes such as lipid droplet formation, lipid droplet microvesiculation, and free fatty acids trafficking can be dynamically monitored in macrophages and adipocytes. With its versatility, NLO microscopy should be a powerful imaging tool to complement molecular characterization of the immunity-metabolism interface.
A Comparative Study of Fat Storage Quantitation in Nematode Caenorhabditis elegans Using Label and Label-Free Methods
Kelvin Yen,Thuc T. Le,Ankita Bansal,Sri Devi Narasimhan,Ji-Xin Cheng,Heidi A. Tissenbaum
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012810
Abstract: The nematode Caenorhabditis elegans has been employed as a model organism to study human obesity due to the conservation of the pathways that regulate energy metabolism. To assay for fat storage in C. elegans, a number of fat-soluble dyes have been employed including BODIPY, Nile Red, Oil Red O, and Sudan Black. However, dye-labeled assays produce results that often do not correlate with fat stores in C. elegans. An alternative label-free approach to analyze fat storage in C. elegans has recently been described with coherent anti-Stokes Raman scattering (CARS) microscopy. Here, we compare the performance of CARS microscopy with standard dye-labeled techniques and biochemical quantification to analyze fat storage in wild type C. elegans and with genetic mutations in the insulin/IGF-1 signaling pathway including the genes daf-2 (insulin/IGF-1 receptor), rict-1 (rictor) and sgk-1 (serum glucocorticoid kinase). CARS imaging provides a direct measure of fat storage with unprecedented details including total fat stores as well as the size, number, and lipid-chain unsaturation of individual lipid droplets. In addition, CARS/TPEF imaging reveals a neutral lipid species that resides in both the hypodermis and the intestinal cells and an autofluorescent organelle that resides exclusively in the intestinal cells. Importantly, coherent addition of the CARS fields from the C-H abundant neutral lipid permits selective CARS imaging of the fat store, and further coupling of spontaneous Raman analysis provides unprecedented details including lipid-chain unsaturation of individual lipid droplets. We observe that although daf-2, rict-1, and sgk-1 mutants affect insulin/IGF-1 signaling, they exhibit vastly different phenotypes in terms of neutral lipid and autofluorescent species. We find that CARS imaging gives quantification similar to standard biochemical triglyceride quantification. Further, we independently confirm that feeding worms with vital dyes does not lead to the staining of fat stores, but rather the sequestration of dyes in lysosome-related organelles. In contrast, fixative staining methods provide reproducible data but are prone to errors due to the interference of autofluorescent species and the non-specific staining of cellular structures other than fat stores. Importantly, both growth conditions and developmental stage should be considered when comparing methods of C. elegans lipid storage. Taken together, we confirm that CARS microscopy provides a direct, non-invasive, and label-free means to quantitatively analyze fat storage in living C. elegans.
Synthesis of silica nanoparticles from Vietnamese rice husk by sol--gel method
Van Hai Le, Chi Nhan Thuc and Huy Ha Thuc
Nanoscale Research Letters , 2013, DOI: 10.1186/1556-276X-8-58
Abstract: Silica powder at nanoscale was obtained by heat treatment of Vietnamese rice husk following the sol--gel method. The rice husk ash (RHA) is synthesized using rice husk which was thermally treated at optimal condition at 600[degree sign]C for 4 h. The silica from RHA was extracted using sodium hydroxide solution to produce a sodium silicate solution and then precipitated by adding H2SO4 at pH = 4 in the mixture of water/butanol with cationic presence. In order to identify the optimal condition for producing the homogenous silica nanoparticles, the effects of surfactant surface coverage, aging temperature, and aging time were investigated. By analysis of X-ray diffraction, scanning electron microscopy, and transmission electron microscopy, the silica product obtained was amorphous and the uniformity of the nanosized sample was observed at an average size of 3 nm, and the BET result showed that the highest specific surface of the sample was about 340 m2/g. The results obtained in the mentioned method prove that the rice husk from agricultural wastes can be used for the production of silica nanoparticles.
Preparation of 2,5-Bis(Aminomethyl)Furan by Direct Reductive Amination of 2,5-Diformylfuran over Nickel-Raney Catalysts  [PDF]
Ngoc-Thuc Le, Areum Byun, Yohan Han, Kee-In Lee, Hyungrok Kim
Green and Sustainable Chemistry (GSC) , 2015, DOI: 10.4236/gsc.2015.53015
Abstract: The direct reductive amination of 2,5-diformylfuran (DFF) with ammonia to 2,5-bis(aminomethyl)furan (BAF) was demonstrated, for the first time, over the commercial type Nickel-Raney and acid treated Nickel-Raney catalysts. The effects of reaction parameters such as reaction medium, temperature and hydrogen pressure were described. The acid treated Nickel-Raney catalyst exhibited the highest BAF yield in the THF-water mixed reaction medium. The relatively higher Ni0 species composition and larger surface area of the acid treated Nickel-Raney catalyst with specific reaction conditions contributed greatly to the BAF formation. The oligomeric species, such as furanic imine trimers and tetramers confirmed by MALDI-MS analysis were presented as the intermediates of DFF reductive amination.
Diversity Characterization of Optimized Two-Antenna Systems for UMTS Handsets
A. Diallo,P. Le Thuc,C. Luxey,R. Staraj
EURASIP Journal on Wireless Communications and Networking , 2008, DOI: 10.1155/2007/37574
Abstract: This paper presents the evaluation of the diversity performance of several two-antenna systems for UMTS terminals. All the measurements are done in a reverberation chamber and in a Wheeler cap setup. First, a two-antenna system having poor isolation between its radiators is measured. Then, the performance of this structure is compared with two optimized structures having high isolation and high total efficiency, thanks to the implementation of a neutralization technique between the radiating elements. The key diversity parameters of all these systems are discussed, that is, the total efficiency of the antenna, the envelope correlation coefficient, the diversity gains, the mean effective gain (MEG), and the MEG ratio. The comparison of all these results is especially showing the benefit brought back by the neutralization technique.
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