Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier.

BACKGROUND: Natural products are often friendly and can be used on children's skin after systematic and careful research. Therefore, in this study, the Royal Oji Complex (ROC), a product with natural ingredients, was used to study their effectiveness on keratinocytes taken from the skin of children from 0 to 3 years old. METHOD: Normal human epidermal keratinocytes and tissue-isolated keratinocytes (TIKC) from young donors were treated with three different concentrations of ROC: 0.1, 1, and 10 ppm. The mRNA expression of the epidermal barrier's essential genes, such as hyaluronic acid synthase 3 (Has3), involucrin (IVL), loricrin (LOR), and claudin-1 (CLD1) was investigated using qRT-PCR. Ceramide content was measured by ELISA, with retinoic acid (R.A.) and amarogentin (AMA) serving as positive controls. RESULTS: ROC significantly elevated HAS3 gene expression in HEKn cells, especially at 10 ppm, indicating potential advantages for skin hydration in young infants. IVL increased at first but decreased as ROC concentrations increased. LOR was upregulated at lower ROC concentrations but reduced at higher doses. CLD1 gene expression increased considerably in HEKn but reduced with increasing ROC doses. Ceramide concentration increased somewhat but not significantly at 10 ppm. CONCLUSION: ROC shows potential in altering keratinocyte gene expression, with unique responses in HEKn and TIKC from young donors. While changes in ceramide content were insignificant, these results help to comprehend ROC's multiple effects on young children's skin.

Alternative Assembly of α-Synuclein Leading to Protein Film Formation and Its Application for Developing Polydiacetylene-Based Sensing Materials.

Understanding the self-assembly process of amyloidogenic protein is valuable not only to find its pathological implication but also to prepare protein-based biomaterials. α-Synuclein (αS), a pathological component of Parkinson's disease, producing one-dimensional (1D) amyloid fibrils, has been employed to generate two-dimensional (2D) protein films by encouraging an alternative self-assembly process. At a high temperature of 50 °C, αS molecules self-assembled into 2D films instead of 1D amyloid fibrils, whereas the fibrils were the major product at 37 °C. Based on circular dichroism and Fourier transform infrared spectroscopy analyses, the film was produced via a structural transition from the initial random to still undefined but mostly the turn or loop structure, which was distinctive from the ß-sheet formation observed with the amyloid fibrils. The αS 2D film was also routinely prepared at the oil-water interface and used as a matrix to produce polydiacetylene-based sensing materials. 10,12-Pentacosadiynoic acids (PCDA) were aligned on the film and photopolymerized to form a π-conjugated molecular assembly yielding a blue color. Its colorimetric transition to red was induced by increasing the temperature. This functionalized protein film increased its height from 40 to 55 nm upon PCDA immobilization and exhibited enhanced physical and chemical stability. In addition, the modified film showed remarkably high electrical conductivity only in the red state. This film, therefore, can be considered as a robust protein-based hybrid biomaterial capable of simultaneously recognizing various external stimuli (heat, pH, and solvents) with changes in color and conductivity, and it is expected to be utilized as a basic material for the development of biocompatible sensors.

Robust polydiacetylene-based colorimetric sensing material developed with amyloid fibrils of α-synuclein.

Robust polydiacetylene-based colorimetric sensing material has been developed with amyloid fibrils of α-synuclein in the presence of 10,12-pentacosadiynoic acid (PCDA) by taking advantage of the specific fatty acid interaction of α-synuclein and structural regularity of the self-assembled product of amyloid fibrils. PCDA facilitated not only self-oligomerization of α-synuclein but also its fibrillation into the fibrils with increased thickness. Upon UV irradiation, the PCDA-containing amyloid fibrils (AF-PCDAs) turned blue, which then became red following heat treatment. The blue-to-red color transition was also observed with other stimuli of pH and ethanol. AF-PCDAs were demonstrated to be mechanically stable since not only the individual colors of blue and red but also their colorimetric transition were not affected by a number of sonications which readily disrupted the polydiaceylene (PDA) vesicles with the instant loss of color. Therefore, AF-PCDA can be considered to be a novel PDA-based colorimetric sensing material with high mechanical strength, which has the potential to be employed in various areas involving advanced sensing technologies.

Reappraisal of serum alpha-foetoprotein as a surveillance test for hepatocellular carcinoma during entecavir treatment.

BACKGROUND & AIMS: The aim of this study was to re-evaluate the diagnostic performance of alpha-foetoprotein (AFP) as a surveillance test for hepatocellular carcinoma (HCC) in patients with hepatitis B virus-related chronic liver disease who were treated with entecavir (ETV). METHODS: Between January 2007 and August 2012, we analysed 373 treatment-naïve patients with HBV-related chronic hepatitis (n = 229) or cirrhosis (n = 144) who were candidates for surveillance test, and were treated with ETV (0.5 mg/day) for longer than 12 months. To minimize the effect of AFP elevation caused by hepatitis activity, serum AFP levels were measured 12 months after the initiation of ETV treatment. RESULTS: Hepatocellular carcinoma developed in 28 patients (7.5%) during a median follow-up period of 48.0 months (IQR = 40.5-57.3 months). The area under the receiver operating characteristic curve for AFP was 0.71 (95% CI = 0.59-0.84). The optimal AFP cut-off value was 13 ng/ml, leading to a sensitivity of 50.0%, specificity of 98.8%, positive predictive value of 77.8% and negative predictive value of 96.1%. In multivariate Cox analysis, an older age, the presence of cirrhosis and AFP levels of ≥20 ng/ml at 12 months after treatment were found to be significantly associated with an increased incidence of HCC. CONCLUSIONS: The role of serum AFP as a surveillance test should be re-evaluated in patients with HBV-related chronic liver diseases who were treated with antiviral therapy.

α-Synuclein-mediated defense against oxidative stress via modulation of glutathione peroxidase.

In this report, mutual effect of α-synuclein and GPX-1 is investigated to unveil their involvement in the PD pathogenesis in terms of cellular defense mechanism against oxidative stress. Biochemical and immunocytochemical studies showed that α-synuclein enhanced the GPX-1 activity with Kd of 17.3nM and the enzyme in turn markedly enhanced in vitro fibrillation of α-synuclein. Transmission electron microscopy revealed the fibrillar meshwork of α-synuclein containing GPX-1 located in locally concentrated islets. The entrapped enzyme was demonstrated to be protected in a latent form and its activity was fully recovered as released from the matrix. Therefore, novel defensive roles of α-synuclein and its amyloid fibrils against oxidative stress are suggested as the GPX-1 stimulator and the active depot for the enzyme, respectively.

Device-Algorithm Co-Optimization for an On-Chip Trainable Capacitor-Based Synaptic Device with IGZO TFT and Retention-Centric Tiki-Taka Algorithm.

Analog in-memory computing synaptic devices are widely studied for efficient implementation of deep learning. However, synaptic devices based on resistive memory have difficulties implementing on-chip training due to the lack of means to control the amount of resistance change and large device variations. To overcome these shortcomings, silicon complementary metal-oxide semiconductor (Si-CMOS) and capacitor-based charge storage synapses are proposed, but it is difficult to obtain sufficient retention time due to Si-CMOS leakage currents, resulting in a deterioration of training accuracy. Here, a novel 6T1C synaptic device using only n-type indium gaIlium zinc oxide thin film transistor (IGZO TFT) with low leakage current and a capacitor is proposed, allowing not only linear and symmetric weight update but also sufficient retention time and parallel on-chip training operations. In addition, an efficient and realistic training algorithm to compensate for any remaining device non-idealities such as drifting references and long-term retention loss is proposed, demonstrating the importance of device-algorithm co-optimization.

Exchange-induced electron transport in heavily phosphorus-doped si nanowires.

Heavily phosphorus-doped silicon nanowires (Si NWs) show intriguing transport phenomena at low temperature. As we decrease the temperature, the resistivity of the Si NWs initially decreases, like metals, and starts to increase logarithmically below a resistivity minimum temperature (T(min)), which is accompanied by (i) a zero-bias dip in the differential conductance and (ii) anisotropic negative magnetoresistance (MR), depending on the angle between the applied magnetic field and current flow. These results are associated with the impurity band conduction and electron scattering by the localized spins at phosphorus donor states. The analysis on the MR reveals that the localized spins are coupled antiferromagnetically at low temperature via the exchange interaction.

Large-scale assembly of highly flexible low-noise devices based on silicon nanowires.

Recently, integrated flexible devices based on silicon nanowires (Si-NWs) have received significant attention as high performance flexible devices. However, most previous assembly methods can generate only specifically-shaped devices and require unconventional facilities, which has been a major hurdle for industrial applications. Herein, we report a simple but very efficient method for assembling Si-NWs into virtually generally-shape patterns on flexible substrates using only conventional microfabrication facilities, allowing us to mass-produce highly flexible low-noise devices. As proof of this method, we demonstrated the fabrication of highly bendable top-gate transistors based on Si-NWs. These devices showed typical n-type semiconductor behaviors, and exhibited a much lower noise level compared to previous flexible devices based on organic conductors or other nanowires. In addition, the gating behaviors and low-noise characteristics of our devices were maintained, even under highly bent conditions.

Morphological Evaluation of Meta-stable Oligomers of α-Synuclein with Small-Angle Neutron Scattering.

Amyloidogenesis of α-synuclein (αS) is considered to be a pathological phenomenon related to Parkinson's disease (PD). As a key component to reveal the fibrillation mechanism and toxicity, we have investigated an oligomeric species of αS capable of exhibiting the unit-assembly process leading to accelerated amyloid fibril formation. These oligomers previously shown to exist in a meta-stable state with mostly disordered structure and unable to seed the fibrillation were converted to either temperature-sensitive self-associative oligomers or NaCl-induced non-fibrillating oligomeric species. Despite their transient and disordered nature, the structural information of meta-stable αS oligomers (Meta-αS-Os) was successfully evaluated with small-angle neutron scattering (SANS) technique. By fitting the neutron scattering data with polydisperse Gaussian Coil (pGC) model, Meta-αS-O was analyzed as a sphere with approximate diameter of 100 Å. Its overall shape altered drastically with subtle changes in temperature between 37 °C and 43 °C, which would be responsible for fibrillar polymorphism. Based on their bifurcating property of Meta-αS-Os leading to either on-pathway or off-pathway species, the oligomers could be suggested as a crucial intermediate responsible for the oligomeric diversification and multiple fibrillation processes. Therefore, Meta-αS-Os could be considered as a principal target to control the amyloidogenesis and its pathogenesis.

EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of α-Synuclein.

(-)-Epigallocatechin gallate (EGCG), the major component of green tea, has been re-evaluated with α-synuclein (αS), a pathological constituent of Parkinson's disease, to elaborate its therapeutic value. EGCG has been demonstrated to not only induce the off-pathway 'compact' oligomers of αS as suggested previously, but also drastically enhance the amyloid fibril formation of αS. Considering that the EGCG-induced amyloid fibrils could be a product of on-pathway SDS-sensitive 'transient' oligomers, the polyphenol effect on the transient 'active' oligomers (AOs) was investigated. By facilitating the fibril formation and thus eliminating the toxic AOs, EGCG was shown to suppress the membrane disrupting radiating amyloid fibril formation on the surface of liposomal membranes and thus protect the cells which could be readily affected by AOs. Taken together, EGCG has been suggested to exhibit its protective effect against the αS-mediated cytotoxicity by not only producing the off-pathway 'compact' oligomers, but also facilitating the conversion of 'active' oligomers into amyloid fibrils.

High-Density Single-Layer Coating of Gold Nanoparticles onto Multiple Substrates by Using an Intrinsically Disordered Protein of α-Synuclein for Nanoapplications.

Functional graffiti of nanoparticles onto target surface is an important issue in the development of nanodevices. A general strategy has been introduced here to decorate chemically diverse substrates with gold nanoparticles (AuNPs) in the form of a close-packed single layer by using an omni-adhesive protein of α-synuclein (αS) as conjugated with the particles. Since the adsorption was highly sensitive to pH, the amino acid sequence of αS exposed from the conjugates and its conformationally disordered state capable of exhibiting structural plasticity are considered to be responsible for the single-layer coating over diverse surfaces. Merited by the simple solution-based adsorption procedure, the particles have been imprinted to various geometric shapes in 2-D and physically inaccessible surfaces of 3-D objects. The αS-encapsulated AuNPs to form a high-density single-layer coat has been employed in the development of nonvolatile memory, fule-cell, solar-cell, and cell-culture platform, where the outlying αS has played versatile roles such as a dielectric layer for charge retention, a sacrificial layer to expose AuNPs for chemical catalysis, a reaction center for silicification, and biointerface for cell attachment, respectively. Multiple utilizations of the αS-based hybrid NPs, therefore, could offer great versatility to fabricate a variety of NP-integrated advanced materials which would serve as an indispensable component for widespread applications of high-performance nanodevices.

Supramolecular self-assembled aggregates formed by pentacosa-10,12-diynyl amidomethyl-ß-cyclodextrin.

Mono[6-deoxy-6-(pentacosa-10,12-diynyl amidomethyl)]-ß-cyclodextrin was successfully synthesized by reacting mono-6-amino-6-deoxy-ß-cyclodextrin with N-hydroxysuccinimide ester of 10,12-pentacosadiynoic acid in DMF. The modified ß-cyclodextrin self-assembled and aggregated to form a worm-like supramolecular structure, and the novel supramolecular aggregates were studied using 2D nuclear magnetic resonance spectroscopy, X-ray powder diffraction, thermogravimetry, and electron microscopy. Interestingly, the synthesized pentacosa-10,12-diynyl amidomethyl-ß-cyclodextrin formed columnar type self-aggregates and it was clearly differentiated from cage-like structure of native ß-cyclodextrin.

Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma.

BACKGROUND/AIMS: The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored. RESULTS: The interleukin-1-ß-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues. CONCLUSIONS: The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.

A large-sized phytobezoar located on the rare site of the gastrointestinal tract.

Bezoars are concretions of undigested material and are most often observed in the stomach. They can occur at any site in the gastrointestinal tract; however, duodenal localization is very rare. We report the case of a 71-year-old male who had undergone subtotal gastrectomy with gastroduodenostomy and experienced severe epigastric discomfort, abdominal pain, and vomiting for a few days. An approximately 7×8 cm-sized mass was found on an abdominal computed tomography scan. On following endoscopy, a large bezoar was revealed in the duodenum and was removed using an endoscopic removal technique, assisted by a large amount of Coca-Cola infusion.

Radiating amyloid fibril formation on the surface of lipid membranes through unit-assembly of oligomeric species of α-synuclein.

BACKGROUND: Lewy body in the substantia nigra is a cardinal pathological feature of Parkinson's disease. Despite enormous efforts, the cause-and-effect relationship between Lewy body formation and the disorder is yet to be explicitly unveiled. METHODOLOGY/PRINCIPAL FINDINGS: Here, we showed that radiating amyloid fibrils (RAFs) were instantly developed on the surface of synthetic lipid membranes from the ß-sheet free oligomeric species of α-synuclein through a unit-assembly process. The burgeoning RAFs were successfully matured by feeding them with additional oligomers, which led to concomitant dramatic shrinkage and disintegration of the membranes by pulling off lipid molecules to the extending fibrils. Mitochondria and lysosomes were demonstrated to be disrupted by the oligomeric α-synuclein via membrane-dependent fibril formation. CONCLUSION: The physical structure formation of amyloid fibrils, therefore, could be considered as detrimental to the cells by affecting membrane integrity of the intracellular organelles, which might be a molecular cause for the neuronal degeneration observed in Parkinson's disease.

A New Technique Using Ultra-slim Endoscopy for High-Grade Crohn's Stricture.

Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown etiology. Most patients with CD will eventually develop a stricturing or penetrating complication. Colonoscopic findings may predict the clinical course in patients with CD. Moreover, since CD patients are at increased risk for developing dysplasia and colorectal cancer, surveillance colonoscopy is necessary for the detection of malignancies. We describe here a CD patient with a high-grade anorectal stricture who successfully underwent a total colon examination with an ultra-slim upper endoscope after an insertion failure with a standard colonoscope and gastroscope.

Ag(I)-cysteamine complex based electrochemical stripping immunoassay: ultrasensitive human IgG detection.

An ultrasensitive electrochemical immunosensor for a protein using a Ag (I)-cysteamine complex (Ag-Cys) as a label was fabricated. The low detection of a protein was based on the electrochemical stripping of Ag from the adsorbed Ag-Cys complex on the gold nanoparticles (AuNPs) conjugated human immunoglobulin G (anti-IgG) antibody (AuNPs-anti-IgG). The electrochemical immunosensor was fabricated by immobilizing anti-IgG antibody on a poly-5,2':5',2''-terthiophene-3'-carboxylic acid (polyTTCA) film grown on the glassy carbon electrode through the covalent bond formation between amine groups of anti-IgG and carboxylic acid groups of polyTTCA. The target protein, IgG was sandwiched between the anti-IgG antibody that covalently attached onto the polyTTCA layer and AuNPs-anti-IgG. Using square wave voltammetry, well defined Ag stripping voltammograms were obtained for the each target concentration. Various experimental parameters were optimized and interference effects from other proteins were checked out. The immunosensor exhibited a wide dynamic range with the detection limit of 0.4 ± 0.05 fg/mL. To evaluate the analytical reliability, the proposed immunosensor was applied to human IgG spiked serum samples and acceptable results were obtained indicating that the method can be readily extended to other bioaffinity assays of clinical or environmental significance.

Removal of intact ß2-microglobulin at neutral ph by using seed-conjugated polymer beads prepared with ß2-microglobulin-derived peptide (58-67).

Removal of ß2-microglobulin (ß2M) from the blood of patients suffering from kidney dysfunction is crucial to protect those individuals from getting the diseased state of dialysis-related amyloidosis. By harnessing the nucleation-dependent fibrillation process of amyloidogenesis, a ß2M removal strategy has been proposed by preparing seed-conjugated polymer beads and assimilating soluble ß2M to the fibrils on the surface at neutral pH. A novel peptide segment of ß2M ranging from residue 58 to residue 67 (Lys-Asp-Trp-Ser-Phe-Tyr-Leu-Leu-Tyr-Tyr), which was capable of being fibrillated at neutral pH was isolated. Charge interaction between the positive N-terminal lysine and the negative C-terminal α-carboxylic group was demonstrated to be critical for the molecular self-assembly leading to the peptide fibril formation by favoring ß-sheet conformation. Because the peptide fibrils were successful to seed intact ß2M at neutral pH, the fibrils were immobilized on polymer beads of HiCore resins, and the resulting seed-conjugated beads were used to accrete intact ß2M in the form of fibrils elongated on the bead surface. Its efficiency of the ß2M removal was improved by placing the seed-immobilized beads in the middle of a continuous flow of the ß2M-containing solution as practiced in the blood circulation during the hemodialysis. Therefore, this ß2M removal system is suggested to exhibit high specificity, high binding capacity, and cost-effectiveness appropriate for eventual clinical application to remove ß2M from the blood of renal failure patients.