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1.  Bupropion for Interferon-Alpha-Induced Depression in Patients with Hepatitis C Viral Infection: An Open-Label Study 
Psychiatry Investigation  2015;12(1):142-145.
Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.
PMCID: PMC4310912
Interferon-induced depression; Bupropion; Antidepressant; Hepatitis C viral infection
2.  Interfacial atomic structure analysis at sub-angstrom resolution using aberration-corrected STEM 
Nanoscale Research Letters  2014;9(1):578.
The atomic structure of a SiGe/Si epitaxial interface grown via molecular beam epitaxy on a single crystal silicon substrate was investigated using an aberration-corrected scanning transmittance electron microscope equipped with a high-angle annular dark-field detector and an energy-dispersive spectrometer. The accuracy required for compensation of the various residual aberration coefficients to achieve sub-angstrom resolution with the electron optics system was also evaluated. It was found that the interfacial layer was composed of a silicon single crystal, connected coherently to epitaxial SiGe nanolaminates. In addition, the distance between the dumbbell structures of the Si and Ge atoms was approximately 0.136 nm at the SiGe/Si interface in the [110] orientation. The corresponding fast Fourier transform exhibited a sub-angstrom scale point resolution of 0.78 Å. Furthermore, the relative positions of the atoms in the chemical composition line scan signals could be directly interpreted from the corresponding incoherent high-angle annular dark-field image.
PMCID: PMC4240948  PMID: 25426003
Aberration correction; HRTEM; HRSTEM; HAADF; Z contrast; EELS; EDS
3.  Heteroepitaxial growth of TiN film on MgO (100) by reactive magnetron sputtering 
Nanoscale Research Letters  2014;9(1):551.
TiN thin films were deposited on MgO (100) substrates at different substrate temperatures using rf sputtering with Ar/N2 ratio of about 10. At 700°C, the growth rate of TiN was approximately 0.05 μm/h. The structural and electrical properties of TiN thin films were characterized with x-ray diffraction (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Hall measurements. For all deposition conditions, XRD results show that the TiN films can be in an epitaxy with MgO with cube-on-cube orientation relationship of (001)TiN // (001)MgO and [100]TiN // [100]MgO. TEM with selected-area electron diffraction pattern verifies the epitaxial growth of the TiN films on MgO. SEM and AFM show that the surface of the TiN film is very smooth with roughness approximately 0.26 nm. The minimum resistivity of the films can be as low as 45 μΩ cm.
PMCID: PMC4199059  PMID: 25324706
Heteroepitaxial TiN; MgO (100); High quality; rf sputtering
4.  Effect of In/Al ratios on structural and optical properties of InAlN films grown on Si(100) by RF-MOMBE 
Nanoscale Research Letters  2014;9(1):204.
In x Al1-x N films were deposited on Si(100) substrate using metal-organic molecular beam epitaxy. We investigated the effect of the trimethylindium/trimethylaluminum (TMIn/TMAl) flow ratios on the structural, morphological, and optical properties of In x Al1-x N films. Surface morphologies and microstructure of the In x Al1-x N films were measured by atomic force microscopy, scanning electron microscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM), respectively. Optical properties of all films were evaluated using an ultraviolet/visible/infrared (UV/Vis/IR) reflection spectrophotometer. XRD and TEM results indicated that In x Al1-x N films were preferentially oriented in the c-axis direction. Besides, the growth rates of In x Al1-x N films were measured at around 0.6 μm/h in average. Reflection spectrum shows that the optical absorption of the In x Al1-x N films redshifts with an increase in the In composition.
PMCID: PMC4012525  PMID: 24855462
InAlN; In/Al ratios; RF-MOMBE
5.  Aqueous Extract of Gracilaria tenuistipitata Suppresses LPS-Induced NF-κB and MAPK Activation in RAW 264.7 and Rat Peritoneal Macrophages and Exerts Hepatoprotective Effects on Carbon Tetrachloride-Treated Rat 
PLoS ONE  2014;9(1):e86557.
In addition to the previous investigations of bioactivity of aqueous extract of the edible Gracilaria tenuistipitata (AEGT) against H2O2-induced DNA damage and hepatitis C virus replication, the purpose of this study is to evaluate the potential therapeutic properties of AEGT against inflammation and hepatotoxicity using lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 cells, primary rat peritoneal macrophages and carbon tetrachloride (CCl4)-induced acute hepatitis model in rats. AEGT concentration-dependently inhibited the elevated RNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2, thereby reducing nitric oxide and prostaglandin E2 levels, respectively. Moreover, AEGT significantly suppressed the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. These inhibitory effects were associated with the suppression of nuclear factor-kappa B activation and mitogen-activated protein kinase phosphorylation by AEGT in LPS-stimulated cells. In addition, we highlighted the hepatoprotective and curative effects of AEGT in a rat model of CCl4-intoxicated acute liver injury, which was evident from reduction in the elevated serum aspartate aminotransferase and alanine aminotransferase levels as well as amelioration of histological damage by pre-treatment or post-treatment of AEGT. In conclusion, the results demonstrate that AEGT may serve as a potential supplement in the prevention or amelioration of inflammatory diseases.
PMCID: PMC3903563  PMID: 24475143
6.  Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction 
Upon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of Lindera erythrocarpa Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.
PMCID: PMC3591928  PMID: 23254429
7.  Aqueous Extract of the Edible Gracilaria tenuistipitata Inhibits Hepatitis C Viral Replication via Cyclooxygenase-2 Suppression and Reduces Virus-Induced Inflammation 
PLoS ONE  2013;8(2):e57704.
Hepatitis C virus (HCV) is an important human pathogen leading to hepatocellular carcinoma. Using an in vitro cell-based HCV replicon and JFH-1 infection system, we demonstrated that an aqueous extract of the seaweed Gracilaria tenuistipitata (AEGT) concentration-dependently inhibited HCV replication at nontoxic concentrations. AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment. We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels. Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects. Furthermore, we highlighted the inhibitory effect of AEGT in HCV-induced pro-inflammatory gene expression such as the expression of tumour necrosis factor-α, interleukin-1β, inducible nitrite oxide synthase and COX-2 in a concentration-dependent manner to evaluate the potential therapeutic supplement in the management of patients with chronic HCV infections.
PMCID: PMC3585194  PMID: 23469054
8.  Green Tea Phenolic Epicatechins Inhibit Hepatitis C Virus Replication via Cycloxygenase-2 and Attenuate Virus-Induced Inflammation 
PLoS ONE  2013;8(1):e54466.
Chronic hepatitis C virus (HCV) infection is the leading risk factor for hepatocellular carcinoma (HCC) and chronic liver disease worldwide. Green tea, in addition to being consumed as a healthy beverage, contains phenolic catechins that have been used as medicinal substances. In the present study, we illustrated that the epicatechin isomers (+)-epicatechin and (−)-epicatechin concentration-dependently inhibited HCV replication at nontoxic concentrations by using in vitro cell-based HCV replicon and JFH-1 infectious systems. In addition to significantly suppressing virus-induced cyclooxygenase-2 (COX-2) expression, our results revealed that the anti-HCV activity of the epicatechin isomers occurred through the down-regulation of COX-2. Furthermore, both the epicatechin isomers additively inhibited HCV replication in combination with either interferon-α or viral enzyme inhibitors [2′-C-methylcytidine (NM-107) or telaprevir]. They also had prominent anti-inflammatory effects by inhibiting the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitrite oxide synthase as well as the COX-2 in viral protein-expressing hepatoma Huh-7 cells. Collectively, (+)-epicatechin and (−)-epicatechin may serve as therapeutic supplements for treating HCV-related diseases.
PMCID: PMC3554764  PMID: 23365670
9.  Study of InN epitaxial films and nanorods grown on GaN template by RF-MOMBE 
Nanoscale Research Letters  2012;7(1):468.
This paper reports on high-quality InN materials prepared on a GaN template using radio-frequency metalorganic molecular beam epitaxy. We also discuss the structural and electro-optical properties of InN nanorods/films. The X-ray diffraction peaks of InN(0002) and InN(0004) were identified from their spectra, indicating that the (0001)-oriented hexagonal InN was epitaxially grown on the GaN template. Scanning electron microscopic images of the surface morphology revealed a two-dimensional growth at a rate of approximately 0.85 μm/h. Cross-sectional transmission electron microscopy images identified a sharp InN/GaN interface and a clear epitaxial orientation relationship of [0001]InN // [0001]GaN and ( 2¯110)InN // ( 2¯110)GaN. The optical properties of wurtzite InN nanorods were determined according to the photoluminescence, revealing a band gap of 0.77 eV.
PMCID: PMC3492109  PMID: 22908859
RF-MOMBE; InN; nanorods
10.  Complex distribution patterns of voltage-gated calcium channel α-subunits in the spiral ganglion 
Hearing research  2011;278(1-2):52-68.
As with other elements of the peripheral auditory system, spiral ganglion neurons display specializations that vary as a function of location along the tonotopic axis. Previous work has shown that voltage-gated K+ channels and synaptic proteins show graded changes in their density that confers rapid responsiveness to neurons in the high frequency, basal region of the cochlea and slower, more maintained responsiveness to neurons in the low frequency, apical region of the cochlea. In order to understand how voltage-gated calcium channels (VGCCs) may contribute to these diverse phenotypes, we identified the VGCC α-subunits expressed in the ganglion, investigated aspects of Ca2+-dependent neuronal firing patterns, and mapped the intracellular and intercellular distributions of seven VGCC α-subunits in the spiral ganglion in vitro.
Initial experiments with qRT-PCR showed that eight of the ten known VGCC α-subunits were expressed in the ganglion and electrophysiological analysis revealed firing patterns that were consistent with the presence of both LVA and HVA Ca2+ channels. Moreover, we were able to study seven of the α-subunits with immunocytochemistry, and we found that all were present in spiral ganglion neurons, and that three of them were neuron-specific (CaV1.3, CaV2.2, and CaV3.3). Further characterization of neuron-specific α-subunits showed that CaV1.3 and CaV3.3 were tonotopically-distributed, whereas CaV2.2 was uniformly distributed in apical and basal neurons. Multiple VGCC α-subunits were also immunolocalized to Schwann cells, having distinct intracellular localizations, and, significantly, appearing to distinguish putative compact0 (CaV2.3, CaV3.1) from loose (CaV1.2) myelin.
Electrophysiological evaluation of spiral ganglion neurons in the presence of TEA revealed Ca2+ plateau potentials with slopes that varied proportionately with the cochlear region from which neurons were isolated. Because afterhyperpolarizations were minimal or absent under these conditions, we hypothesize that differential density and/or kinetics of one or more of the VGCC α-subunits could account for observed tonotopic differences. These experiments have set the stage for defining the clear multiplicity of functional control in neurons and Schwann cells of the spiral ganglion.
PMCID: PMC3223918  PMID: 21281707
Spiral ganglion neurons; primary afferents; firing patterns; ion channels; calcium channels; VGCC; myelin; Schwann cells
11.  A simple, innovative way to reduce rhinitis symptoms after sedation during endoscopy 
Supplemental oxygen is routinely given via nasal cannula (NC) to patients undergoing moderate sedation for endoscopy. Some patients complain of profuse rhinorrhea and/or sneezing after the procedure, which results in additional medical costs and patient dissatisfaction.
To determine the causal relationship between the route of oxygen delivery and troublesome nasal symptoms, and to seek possible solutions.
Patients (n=836) were randomly assigned to one of the three following groups: the NC group (n=294), the trimmed NC (TNC) group (n=268) and the nasal mask (NM) group (n=274). All received alfentanil 12.5 μg/kg and midazolam 0.06 mg/kg, and adjunct propofol for sedation. Supplemental oxygen at a flow rate of 4 L/min was used in the NC and TNC groups, and 6 L/min in the NM group. The incidence of nasal symptoms and hypoxia were assessed.
The incidence of rhinitis symptoms was significantly higher in the NC group (7.1%) than in the TNC (0.4%) and NM (0%) groups (P<0.001). The incidence of hypoxia was lower in the NC group (3.1%) (P=0.040). All hypoxia events were transient (ie, less than 30 s in duration). On spirometry, the mean value of the lowest saturation of peripheral oxygen was found to be significantly lower in the NM group (96.8%) than in the NC group (97.7%) (P=0.004).
Trimming the NC or using NMs reduced the incidence of rhinitis symptoms; however, the incidence of hypoxia was higher. Further investigation regarding the efficiency of oxygen supplementation is warranted in the design of novel oxygen delivery devices.
PMCID: PMC3043006  PMID: 21321676
Endoscopy; Nasal cannula; Rhinitis; Supplemental oxygenation

Results 1-11 (11)