Anti­angiogenic effect of mountain ginseng in vitro and in vivo: Comparison with farm­cultivated ginseng.

Mountain ginseng (Panax ginseng) has been used for cancer patient therapy in Northeast Asia. Although it is well known that cancer cells are able to induce angiogenesis, the effect of mountain ginseng on angiogenesis is still unknown. In the present study, we investigated whether ethanolic extract of mountain ginseng (MGE) could inhibit angiogenesis in in vitro and in vivo models. In comparison with farm­cultivated ginseng extract (FGE), MGE more strongly inhibited cell migration and formation of capillary­like network within non­cytotoxic ranges in SVEC4­10 cells. In addition, MGE dose­dependently suppressed Transwell cell migration of the cells. Moreover, MGE reduced the phosphorylation and expression of VEGF­R2 as well as the phosphorylation of FAK, Src, Akt and ERK, the intermediate proteins in the VEGF­R2 signaling cascade, in the cells. As expected, MGE dramatically decreased hemoglobin content in Matrigel plugs in mice. In conclusion, MGE possesses stronger anti­angiogenic properties than FGE in vascular endothelial cells. Such effect of MGE is correlated with inhibition of activation of the VEGF­R2 signaling pathway. Therefore, the novel features of MGE may be helpful for understanding its anticancer mechanism for the treatment of cancer patients.

Mountain ginseng inhibits skeletal muscle atrophy by decreasing muscle RING finger protein-1 and atrogin1 through forkhead box O3 in L6 myotubes.

ETHNOPHARMACOLOGICAL RELEVANCE: Mountain ginseng (Panax ginseng C.A. Meyer) is a medicinal herb with immune effects, muscle damage protection and energy metabolism effects. However, the pharmacological role of mountain ginseng in dexamethasone (DEXA)-induced muscle atrophy through the forkhead box O (FOXO) family is not understood. Therefore, we hypothesized that mountain ginseng inhibits skeletal muscle atrophy by decreasing muscle RING finger protein-1 (MuRF1) and atrogin1 through FOXO3 in L6 myotubes. METHODS: Rat myoblast (L6) cells or Sprague-Dawley (SD) rats were exposed to DEXA and mountain ginseng. The expressions of muscle atrophy targets such as MuRF1, atrogin1, MyHC (myosin heavy chain), HSP90, p-Akt, Akt, p-ERK1/2, ERK, FOXO3a, FOXO1, myostatin, and follistatin were analyzed by using Western blot analysis or real-time PCR. The diameter of myotubes was measured. Recruitment of glucocorticoid receptor (GR) or FOXO3a was analyzed by performing a chromatin immunoprecipitation (ChIP) assay. RESULTS: Mountain ginseng treatment reduced muscle weight loss and collagen deposition in DEXA-induced rats. Mountain ginseng treatment led to decreases in MuRF1, atrogin1, p-ERK1/2, FOXO3a, FOXO1, and myostatin. Also, mountain ginseng treatment led to increases in the diameter of myotubes, MyHC, HSP90, p-Akt, and follistatin. Treatment with mountain ginseng reduced enrichment of GR, FOXO3a, and RNA polymerase II on the promoters. CONCLUSIONS: These results suggest that mountain ginseng inhibits skeletal muscle atrophy by decreasing MuRF1 and atrogin1 through FOXO3a in L6 myotubes.

Anticancer Effect of Mountain Ginseng on Human Breast Cancer: Comparison with Farm-Cultivated Ginseng.

Mountain ginseng has been used generally as a pharmacopuncture for cancer therapy in clinical practice in Northeast Asia. Nonetheless, there have been few scientific reports for the anticancer action of mountain ginseng. In this study, we investigated whether mountain ginseng extract (MGE) could inhibit the growth of breast cancer in in vitro and in vivo models. MGE showed stronger cytotoxicity than farm-cultivated ginseng extract (FGE) through promoting ROS generation. Also MGE dose-dependently brought about mitochondrial dysfunction in MCF-7 cells. In addition, MGE induced apoptosis through enhancing the activities of caspase-3/7 by regulation of expression of Bcl-2, Bax, cytochrome c, and cleaved caspase-3 in the MCF-7 cells. Consistent with the in vitro results, MGE significantly reduced tumor weights compared with FGE in mice transplanted with MCF-7 cells, and it regulated the expression of apoptosis-related proteins, such as Bcl-2, Bax, cytochrome c, cleaved caspase-3, and cleaved PARP, in the tumor tissues. Additionally, MGE included higher total ginsenoside contents than FGE. In conclusion, MGE, which is richer in ginsenosides, exerts a stronger anticancer action than FGE in breast cancer. The anticancer action of MGE may be closely correlated with caspase-mediated apoptosis through upregulating ROS generation. Therefore, these findings may be helpful for a clinical understanding of the anticancer mechanism of MGE for breast cancer patients.

Exact Boson-Fermion Duality on a 3D Euclidean Lattice.

The idea of statistical transmutation plays a crucial role in descriptions of the fractional quantum Hall effect. However, a recently conjectured duality between a critical boson and a massless two-component Dirac fermion extends this notion to gapless systems. This duality sheds light on highly nontrivial problems such as the half-filled Landau level, the superconductor-insulator transition, and surface states of strongly coupled topological insulators. Although this boson-fermion duality has undergone many consistency checks, it has remained unproven. We describe the duality in a nonperturbative fashion using an exact UV mapping of partition functions on a 3D Euclidean lattice.

Single-Step LRET Aptasensor for Rapid Mycotoxin Detection.

Contamination of foods by mycotoxins is a common yet serious problem. Owing to the increase in consumption of fresh produce, consumers have become aware of food safety issues caused by mycotoxins. Therefore, rapid and sensitive mycotoxin detection is in great demand in fields such as food safety and public health. Here we report a single-step luminescence resonance energy transfer (LRET) aptasensor for mycotoxin detection. To accomplish the single-step sensor, our sensor was constructed by linking a quencher-labeled aptamer through a linker to the surface of upconversion nanoparticles (UCNPs). Our LRET aptasensor is composed of Mn2+-doped NaYF4:Yb3+,Er3+ UCNPs as the LRET donor, and black hole quencher 3 (BHQ3) as the acceptor. The maximum quenching efficiency is obtained by modulating the linker length, which controls the distance between the quencher and the UCNPs. Our distinctive design of LRET aptasensor allows detection of mycotoxins selectively in colored food samples within 10 min without multiple bioassay steps. We believe our single-step aptasensor has a significant potential for on-site detection of food contaminants, environmental pollutants, and biological metabolites.

Input-Specific Plasticity and Homeostasis at the Drosophila Larval Neuromuscular Junction.

Synaptic connections undergo activity-dependent plasticity during development and learning, as well as homeostatic re-adjustment to ensure stability. Little is known about the relationship between these processes, particularly in vivo. We addressed this with novel quantal resolution imaging of transmission during locomotive behavior at glutamatergic synapses of the Drosophila larval neuromuscular junction. We find that two motor input types, Ib and Is, provide distinct forms of excitatory drive during crawling and differ in key transmission properties. Although both inputs vary in transmission probability, active Is synapses are more reliable. High-frequency firing "wakes up" silent Ib synapses and depresses Is synapses. Strikingly, homeostatic compensation in presynaptic strength only occurs at Ib synapses. This specialization is associated with distinct regulation of postsynaptic CaMKII. Thus, basal synaptic strength, short-term plasticity, and homeostasis are determined input-specifically, generating a functional diversity that sculpts excitatory transmission and behavioral function.

The effect of localized surface plasmon resonance on the emission color change in organic light emitting diodes.

Three primary colors, cyan, yellow, and green, are obtained from Ag nano-dot embedded organic light emitting diodes (OLEDs) by localized surface plasmon resonance (LSPR). By changing the thickness of the Ag film, the size and spacing of Ag nano-dots are controlled. The generated light from the emissive layer in the OLEDs interacts with the free electrons near the surface of the Ag nano-dots, which leads to LSPR absorption and scattering. The UV-visible absorption spectra of glass/ITO/Ag nano-dot samples show intense peaks from 430 nm to 520 nm with an increase of Ag nano-dot size. And also, the Rayleigh scattering spectra results show the plasmon resonance wavelength in the range of 470-550 nm. The effect of the LSPR of Ag nano-dots on the change of emission color in OLEDs is demonstrated using 2 dimensional finite-difference time-domain simulations. The intensity of the electro-magnetic field in the sample with 5 nm-thick Ag is low at the incident wavelength of 500 nm, but it increases with the incident wavelength. This provides evidence that the emission color change in OLEDs originates from LSPR at the Ag nano-dots. As a result, the emission peak wavelength of OLEDs shifted toward longer wavelengths, from cyan to yellow-green, with the increase of Ag nano-dot size.

Rapid Optical Cavity PCR.

Recent outbreaks of deadly infectious diseases, such as Ebola and Middle East respiratory syndrome coronavirus, have motivated the research for accurate, rapid diagnostics that can be administered at the point of care. Nucleic acid biomarkers for these diseases can be amplified and quantified via polymerase chain reaction (PCR). In order to solve the problems of conventional PCR--speed, uniform heating and cooling, and massive metal heating blocks--an innovative optofluidic cavity PCR method using light-emitting diodes (LEDs) is accomplished. Using this device, 30 thermal cycles between 94 °C and 68 °C can be accomplished in 4 min for 1.3 µL (10 min for 10 µL). Simulation results show that temperature differences across the 750 µm thick cavity are less than 2 °C and 0.2 °C, respectively, at 94 °C and 68 °C. Nucleic acid concentrations as low as 10(-8) ng µL(-1) (2 DNA copies per µL) can be amplified with 40 PCR thermal cycles. This simple, ultrafast, precise, robust, and low-cost optofluidic cavity PCR is favorable for advanced molecular diagnostics and precision medicine. It is especially important for the development of lightweight, point-of-care devices for use in both developing and developed countries.

Design of red, green, blue transparent electrodes for flexible optical devices.

Controlling the wavelength of electrodes within a desirable region is important in most optoelectronic devices for enhancing their efficiencies. Here, we investigated a full-color flexible transparent electrode using a wavelength matching layer (WML). The WMLs were able to adjust the optical-phase thickness of the entire electrode by controlling refractive indices and were capable of producing desirable colors in the visible band from 470 to 610 nm. Electrodes with tungsten oxide (WO(3)) having a refractive index of 1.9 showed high transmittance (T = 90.5%) at 460 nm and low sheet resistance (R(s) = 11.08 Ω/sq), comparable with those of indium tin oxide (ITO, T = 86.4%, R(s) = 12 Ω/sq). The optimum structure of electrodes determined by optical simulation based on the characteristic matrix method agrees well with that based on the experimental method. Replacing the ITO electrode with the WO(3) electrode, the luminance of blue organic light-emitting diodes (λ = 460 nm) at 222 mA/cm(2) increased from 7020 to 7200 cd/m(2).

Hemolysis-free blood plasma separation.

Hemolysis, involving the rupture of red blood cells (RBCs) and release of their contents into blood plasma, is a major issue of concern in clinical fields. Hemolysis in vitro can occur as a result of errors in clinical trials; in vivo, hemolysis can be caused by a variety of medical conditions. Blood plasma separation is often the first step in blood-based clinical diagnostic procedures. However, inhibitors released from RBCs due to hemolysis during plasma separation can lead to problems in diagnostic tests such as low sensitivity, selectivity and inaccurate results. In particular, a general lack of simple and reliable blood plasma separation methods has been a major obstacle for microfluidic-based point-of-care (POC) diagnostic devices. Here we present a hemolysis-free microfluidic blood plasma separation platform. A membrane filter was positioned on top of a vertical up-flow channel (filter-in-top configuration) to reduce clogging of RBCs by gravity-assisted cells sedimentation. With this device, separated plasma volume was increased approximately 4-fold (2.4 µL plasma after 20 min with 38% hematocrit human whole blood), and hemoglobin concentration in separated plasma was decreased approximately 90% due to the prevention of RBCs hemolysis, when compared to conventional filter-in-bottom configuration blood plasma separation platforms. On-chip plasma contained ~90% of protein and ~100% of nucleic acids found in off-chip centrifuged plasma, confirming comparable target molecule recovery efficiency. This simple and robust on-chip blood plasma separation device integrates with downstream detection modules to ultimately create sample-to-answer microfluidic POC diagnostics devices.

Toward integrated molecular diagnostic system (i MDx): principles and applications.

Integrated molecular diagnostic systems ( iMDx), which are automated, sensitive, specific, user-friendly, robust, rapid, easy-to-use, and portable, can revolutionize future medicine. This review will first focus on the components of sample extraction, preservation, and filtration necessary for all point-of-care devices to include for practical use. Subsequently, we will look for low-powered and precise methods for both sample amplification and signal transduction, going in-depth to the details behind their principles. The final field of total device integration and its application to the clinical field will also be addressed to discuss the practicality for future patient care. We envision that microfluidic systems hold the potential to breakthrough the number of problems brought into the field of medical diagnosis today.

The functional property of egg yolk phosvitin as a melanogenesis inhibitor.

Phosvitin is a phosphoglycoprotein present in egg yolk. More than half of the amino acids in phosvitin molecule are serine, of which >90% are phosphorylated. Therefore, phosvitin has a strong metal binding capability. The aim of this study was to investigate the effect of phosvitin on the inhibition of melanogenesis in melanoma cells. The results showed that phosvitin inhibited the activity of mushroom tyrosinase. Addition of phosvitin at a concentration of 50µg/ml, to B16F10 melanoma cells inhibited tyrosinase activity by approximately 42% and melanin synthesis by 17% compared to those in a control without phosvitin. Phosvitin inhibited the expression of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF) in B16F10 melanoma cells. In addition, phosvitin reduced the cellular cAMP concentration in B16F10 melanoma cells. These results indicate that phosvitin has the potential to be used as a melanogenesis inhibitor in the food and cosmetics industry.

Design rules for highly transparent electrodes using dielectric constant matching of metal oxide with Ag film in optoelectronic devices.

Using dielectric-constant (ε) matching of metal-oxide (MO) with Ag film, highly transparent MO/Ag electrodes are demonstrated. At the large-ε MO/Ag interface, surface-plasmon was suppressed and the film showed increased optical-transmittance (>70%). OLEDs fabricated using large-ε MO/Ag electrodes show 1.38 times greater luminance than that of devices with small-ε MO/Ag.

Enhancement of wall-plug efficiency in vertical InGaN/GaN LEDs by improved current spreading.

We present the enhancement of wall-plug efficiency in vertical InGaN/GaN light-emitting diodes (V-LEDs) by improved current spreading with a novel Al2O3 current blocking layer (CBL). The Al2O3 CBL deposited by electron-beam evaporation shows high transmittance and good corrosion resistance to acidic solutions. V-LEDs with an Al2O3 CBL show similar light output power but lower forward voltage as compared to those with a SiO2 CBL deposited by plasma-enhanced chemical vapor deposition. As a result, the wall-plug efficiency of V-LEDs with an Al2O3 CBL at 500 mA was improved by 5% as compared to those with a SiO2 CBL, and by 19% as compared to those without a CBL.

Design rule of nanostructures in light-emitting diodes for complete elimination of total internal reflection.

Cone-shaped nanostructures with controllable side-wall angle are success- fully fabricated with a SiO(2) nanosphere lithography (NSL) etching mask. Vertical LEDs with cone-shaped nanostructures with a 24.1° side-wall angle provide 6% more light output power compared to those using hexagonal pyramids formed by photochemical etching. This achievement is attributed to effective elimination of total internal reflection by angle-controlled nanostructures.

Potent anti-aging activity of Aruncus dioicus, a native plant of Ulleung-do, South Korea, in CCD-986sk fibroblasts via suppression of matrix metalloproteinases.

Aruncus dioicus var. kamtschaticus HARA, also known as goat's beard, is a native plant in Ulleung-do, South Korea. It has been used as a remedy in skin care, detoxification, blood stanching, tonsillitis. High performance liquid chromatography with diode array detection was used for partial validation of bioactive chemicals in A. dioicus ethyl acetate (EtOAc) extract, and EtOAC extract was examined for its effect on ultraviolet (UV)-induced cell aging using CCD-986sk-human skin fibroblast cells. Cells were exposed to UV-B for 1 min before extract treatment. An established viability assay was performed to test cell toxicity of A. dioicus at 5, 10, or 50 µg/ml concentrations, and activities of matrix metalloproteinase (MMP) 1, 2, 3, phosphorylated-p38 (p-p38, an activated form of p38), p38, and c-fos transcription factors were evaluated. A. dioicus extract decreased the amount of mRNA transcripts and total proteins of MMP1, 2, 3 as well as p-p38 and c-fos. The c-fos expression was also confirmed by in vivo fluorescent staining of CCD-986sk cells after UV-B exposure followed by EtOAc extract treatment. The results showed that expression of skin aging related genes encoding MMP1, 2, and 3 was inhibited by reduced transcription factor expression of p-p38 and c-fos by A. dioicus EtOAc extract. The results suggest that A. dioicus extract can be used to reduce UV-B-induced skin aging and is a potential candidate for cosmedical materials.

MgO nano-facet embedded silver-based dielectric/metal/dielectric transparent electrode.

We replace Indium Tin Oxide (ITO) with an MgO nano-facet Embedded WO(3)/Ag/WO(3)(WAW) multilayer for electrodes of high efficiency OLEDs. WAW shows higher values for transmittance (93%) and conductivity (1.3×10(5) S/cm) than those of ITO. Moreover, WAW shows higher transmittance (92.5%) than that of ITO (86.4%) in the blue region (<500 nm). However, due to the large difference in refractive indices (n) of glass (n=1.55) and WO(3) (n=1.95), the incident light has a small critical angle (52°). Thus, the generated light is confined by the glass/WAW interface, resulting in low light outcoupling efficiency (~20%). This can be enhanced by using a nano-facet structured MgO (n=1.73) layer and a ZrO(2) (n=1.84) layer as a graded index layer. Using these optimized electrodes, ITO-free, OLEDs with various emission wavelengths have been produced. The luminance of OLEDs using MgO/ZrO(2)/WAW layers is enhanced by 24% compared to that of devices with ITO.

Fermentation strategies for 1,3-propanediol production from glycerol using a genetically engineered Klebsiella pneumoniae strain to eliminate by-product formation.

We generated a genetically engineered Klebsiella pneumoniae strain (AK-VOT) to eliminate by-product formation during production of 1,3-propanediol (1,3-PD) from glycerol. In the present study, the glycerol-metabolizing properties of the recombinant strain were examined during fermentation in a 5 L bioreactor. As expected, by-product formation was completely absent (except for acetate) when the AK-VOT strain fermented glycerol. However, 1,3-PD productivity was severely reduced owing to a delay in cell growth attributable to a low rate of glycerol consumption. This problem was solved by establishing a two-stage process separating cell growth from 1,3-PD production. In addition, nutrient co-supplementation, especially with starch, significantly increased 1,3-PD production from glycerol during fed-batch fermentation by AK-VOT in the absence of by-product formation.

Suppression of mast-cell-mediated allergic inflammation by Lindera obtusiloba.

Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of Lindera obtusiloba water extract (LOWE) on the mast-cell-mediated allergic inflammation and possible mechanism of action using in vitro and in vivo models. LOWE reduced histamine release from various types of mast cells activated by immunoglobulin E (IgE) or phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of LOWE on histamine release was mediated by calcium signal. LOWE decreased the PMACI-stimulated gene expression of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in human mast cells. The inhibitory effect of LOWE on the proinflammatory cytokines was nuclear factor (NF)-κB dependent. In addition, LOWE suppressed compound 48/80-induced systemic allergic reaction and serum histamine release in mice and IgE-mediated local allergic reactions. Our results indicate that LOWE inhibits mast-cell-derived allergic inflammation and involvement of calcium, histamine, proinflammatory cytokines and NF-κB in these effects.