Assessment of Chitosan-Affected Metabolic Response by Peroxisome Proliferator-Activated Receptor Bioluminescent Imaging-Guided Transcriptomic Analysis

Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR), a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB) and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo

Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity

<p>Abstract</p> <p>Background</p> <p>Sodium/iodide symporter (NIS) mediates the active transport and accumulation of iodide from the blood into the thyroid gland. His-226 located in the extracellular region of NIS has been demonstrated to be critical for iodide transport in our previous study. The conserved charged amino acid residues in the extracellular region of NIS were therefore characterized in this study.</p> <p>Methods</p> <p>Fourteen charged residues (Arg-9, Glu-79, Arg-82, Lys-86, Asp-163, His-226, Arg-228, Asp-233, Asp-237, Arg-239, Arg-241, Asp-311, Asp-322, and Asp-331) were replaced by alanine. Iodide uptake abilities of mutants were evaluated by steady-state and kinetic analysis. The three-dimensional comparative protein structure of NIS was further modeled using sodium/glucose transporter as the reference protein.</p> <p>Results</p> <p>All the NIS mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However, these mutants, except R9A, displayed severe defects on the iodide uptake. Further kinetic analysis revealed that mutations at conserved positively charged amino acid residues in the extracellular region of NIS led to decrease NIS-mediated iodide uptake activity by reducing the maximal rate of iodide transport, while mutations at conserved negatively charged residues led to decrease iodide transport by increasing dissociation between NIS mutants and iodide.</p> <p>Conclusions</p> <p>This is the first report characterizing thoroughly the functional significance of conserved charged amino acid residues in the extracellular region of NIS. Our data suggested that conserved charged amino acid residues, except Arg-9, in the extracellular region of NIS were critical for iodide transport.</p

High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P &lt; 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P &lt; 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis

Associations of obesity and malnutrition with cardiac remodeling and cardiovascular outcomes in Asian adults:A cohort study

BackgroundObesity, a known risk factor for cardiovascular disease and heart failure (HF), is associated with adverse cardiac remodeling in the general population. Little is known about how nutritional status modifies the relationship between obesity and outcomes. We aimed to investigate the association of obesity and nutritional status with clinical characteristics, echocardiographic changes, and clinical outcomes in the general community.Methods and findingsWe examined 5,300 consecutive asymptomatic Asian participants who were prospectively recruited in a cardiovascular health screening program (mean age 49.6 ± 11.4 years, 64.8% male) between June 2009 to December 2012. Clinical and echocardiographic characteristics were described in participants, stratified by combined subgroups of obesity and nutritional status. Obesity was indexed by body mass index (BMI) (low, ≤25 kg/m2 [lean]; high, >25 kg/m2 [obese]) (WHO-recommended Asian cutoffs). Nutritional status was defined primarily by serum albumin (SA) concentration (low, ConclusionsIn our cohort study among asymptomatic community-based adults in Taiwan, we found that obese individuals with poor nutritional status have the highest comorbidity burden, the most adverse cardiac remodeling, and the least favorable composite outcome

Effects of HIP Treatment on the Microstructure of Cr50-Si50 Target

Hot Isostatic Pressing (HIP) is a process that uniquely combines higher pressure and temperature to produce materials and parts with substantially better properties than those fabricated by other methods. Commercial as-hp (hot pressing) treated Cr50-Si50 targets are used throughout this study. The aim of this paper is to discuss the methods and to find a suitable HIP treatment for the as-hp treated Cr50-Si50 target. Otherwise, we also to find the effects of microstructure on the mechanical properties of HIP treated Cr50-Si50 target. To evaluate the effects on microstructure and properties of the Cr50-Si50 target by HIP process, SEM, TEM and porosity, density inspections were performed. The experiment results show that HIP treatment at 1373 K under the pressure of 175 MPa and 4 hours for Cr50-Si50 target is the optimum condition. In this study, HIP treatment reduced the porosity of the target about 60%

Fabrication and Characterization of High-Sensitivity Underwater Acoustic Multimedia Communication Devices with Thick Composite PZT Films

This paper presents a high-sensitivity hydrophone fabricated with a Microelectromechanical Systems (MEMS) process using epitaxial thin films grown on silicon wafers. The evaluated resonant frequency was calculated through finite-element analysis (FEA). The hydrophone was designed, fabricated, and characterized by different measurements performed in a water tank, by using a pulsed sound technique with a sensitivity of −190 dB ± 2 dB for frequencies in the range 50-500 Hz. These results indicate the high-performance miniaturized acoustic devices, which can impact a variety of technological applications

Fabrication and Characterization of High-Sensitivity Underwater Acoustic Multimedia Communication Devices with Thick Composite PZT Films

This paper presents a high-sensitivity hydrophone fabricated with a Microelectromechanical Systems (MEMS) process using epitaxial thin films grown on silicon wafers. The evaluated resonant frequency was calculated through finite-element analysis (FEA). The hydrophone was designed, fabricated, and characterized by different measurements performed in a water tank, by using a pulsed sound technique with a sensitivity of −190 dB ± 2 dB for frequencies in the range 50–500 Hz. These results indicate the high-performance miniaturized acoustic devices, which can impact a variety of technological applications