Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.     

Enhanced Oral Bioavailability of Ibuprofen in Rats by Poloxamer Gel Using Poloxamer 188 and Menthol

To improve the oral bioavailability of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the ibuprofen-loaded preparations composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed an abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.     

Dissolution kinetics of alumina in molten CaO–Al2O3–FetO–MgO–SiO2 oxide representing the RH slag in steelmaking process

In order to effectively remove alumina inclusions suspending in ultra-low C steel during RH process, the dissolution kinetics of alumina in molten CaO–Al₂O₃–Fe_tO–MgO–SiO₂ oxide was investigated. A crucible dissolution technique was used where the alumina crucible was allowed to dissolve in the slag of various conditions ((% CaO)/(% Al₂O₃), (% Fe_tO), temperature). The obtained data were interpreted using a kinetic mass transport equation to obtain the mass transport coefficient (k_m) in each condition. Increasing (% CaO)/(% Al₂O₃), (% Fe_tO), and temperature increased the dissolution rate as well as the k_m provided that the slag composition is not close to its saturation composition by alumina. In order to simulate the dissolution of alumina inclusion in the RH slag, which cannot be measured by a confocal scanning laser microscopy (CSLM) at present due to the opaqueness of the slag, the modified invariant interface approximation was employed. Along with the obtained k_m, the viscosity of slag, and a reference experiment using the CSLM, the dissolution kinetics of alumina inclusion in the Fe_tO-containing RH slag was predicted. The time required for the dissolution of alumina inclusions from liquid steel to RH slag was discussed.     

Utilisation of spontaneous emulsification to fabricate lutein‐loaded nanoemulsion‐based delivery systems: factors influencing particle size and colour

Factors influencing the formation and properties of lutein‐loaded nanoemulsions fabricated using spontaneous emulsification (SE) were investigated. Nanoemulsion formation depended on oil type: small droplets (diameter ≈ 200 nm) with a narrow monomodal particle size distribution (polydispersity index ≈ 0.23) could be formed using medium‐chain triglycerides (MCT), but not long‐chain triglycerides. Nanoemulsion formation also depended on surfactant type and concentration, with Tween 80 being the most effective surfactant. Optimisation of lutein‐loaded nanoemulsions formed by SE led to systems with a final composition of 10 wt% oil phase (0.12 wt% lutein + 9.88 wt% MCT), 10 wt% Tween 80, and 80 wt% aqueous phase. The nanoemulsions were stable to droplet aggregation when stored at ambient temperature for up to 1 month; however, some colour fading occurred due to lutein degradation. This study indicated the potential of nanoemulsion‐based delivery system fabricated using a low‐energy method for encapsulation and protection of lutein.     

Influence of maltodextrin addition on the freeze-dry stability of β-lactoglobulin-based emulsions with controlled electrostatic and/or steric interactions

Three types of emulsions (β-Lg-, β-Lg-pectin-, and β-Lg-ι-carrageenan-coated emulsions) with controlled electrostatic and/or steric interactions were prepared, and then examined for their freeze-dry stability in the absence or presence of 6% maltodextrin (MD). In the absence of MD, all emulsions were highly unstable to freeze-drying, nevertheless, the β-Lg-pectin-coated emulsions (d ₃₂ =5.37, d ₄₃ =35.11 μm) that were stabilized mostly by steric repulsion showed better stability than the other 2 emulsions (no dried power was obtained). The freeze-dry instability of all emulsions was improved with MD addition, particularly in the β-Lg- (d ₄₃ =1.10 μm) and β-Lg-ι-carrageenan-coated emulsions (d ₄₃ =0.58 μm) that were stabilized by electrostatic repulsive force. In the presence of MD, the β-Lg-ι-carrageenan-coated emulsions showed the highest stability to freeze-drying, which was attributed to the cooperative impact of steric and electrostatic repulsion. This study implicates that the major mechanism for stabilizing emulsions against freeze-drying could be different depending on the absence or presence of MD.     

4-hydroxy-2-alkenals in polyunsaturated fatty acids-fortified infant formulas and other commercial food products.

4-Hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) were determined using selected ion-monitoring gas chromatography-mass spectrometry (GC-MS) in 56 kinds of commercially available PUFA-fortified foods including infant formulas and baby foods. HHE and HNE, each specifically coming from the oxidation of n-3 and n-6 polyunsaturated fatty acids (PUFA), were observed at <10-77 and 41-132 microg kg(-1) in the infant formulas (n = 12) and at <10-52 and 36-116 microg kg(-1) in the baby foods (n = 7), respectively. 4-Hydroxy-2-alkenals in infant formulas and baby foods were further determined at 10 and 30 days after opening in an attempt to examine the time dependence of the levels of 4-hydroxy-2-alkenals. The values of HHE and HNE had increased appreciably to <10-220 and 79-792 microg kg(-1) in infant formulas and to <10-112 and 135-572 microg kg(-1) in baby foods, respectively, at 10 days and decreased, although statistically not significant, in most of the tested samples after 30 days, which suggested that the reactive compounds might interact with other constituents like proteins in the samples to form adducts or be decomposed with time. Based on the current study, it was calculated that 3-month to 1-year-old babies maintained exclusively on these commercially available PUFA-fortified infant formulas or baby foods could be exposed to a maximum of 20.2 microg kg(-1) body weight day(-1) of 4-hydroxy-2-alkenals, which is two orders of magnitude higher than the exposure of Korean adults estimated in a previous study of the authors' (2005). The present study may trigger future studies investigating the physiological influence of 4-hydroxy-2-alkenals originating from the diet on man at an early stage of development.     

Variable block-based deblocking filter for H.264/AVC on low-end and low-bit rates terminals

H.264/AVC supports variable block motion compensation, multiple reference frames, 1/4-pixel motion vector accuracy, and in-loop deblocking filter, compared with previous video coding standards. While these coding techniques are major functions for video compression improvement, they lead to high computational complexity at the same time. For the H.264 video coding techniques to be actually applied on low-end/low-bit rates terminals more extensively, it is essential to improve the coding efficiency. Currently the H.264 deblocking filter, which can improve the subjective quality of video, is hardly used on low-end terminals due to computational complexity.In this paper, we propose an enhanced method of deblocking filter that efficiently reduces the blocking artifacts occurring during the low-bit rates video coding. In the ‘variable block-based deblocking filter (VBDF)’ proposed in this paper, the temporal and spatial characteristics of moving pictures are extracted using the variable block-size information of motion compensation, the filter mode is classified into four different modes according to the moving-picture characteristics, and the adaptive filtering is executed in the separate modes. The proposed VBDF can reduce the blocking artifacts, prevent excessive blurring effects, and achieve about 30–40% computational speedup at about the same PSNR compared with the existing methods.     

Suppression of mouse skin tumor promotion and induction of apoptosis in HL-60 cells by Alpinia oxyphylla Miquel (Zingiberaceae)

There have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Many components from dietary or medicinal plants have been identified that possess substantial chemopreventive properties. An example is curcumin (Curcuma longa Linn., Zingiberaceae), which has been shown to inhibit tumor promotion in experimental carcinogenesis. Alpinia oxyphylla Miquel, another plant of the ginger family used in oriental herbal medicine, contains diarylheptanoids whose structures are analogous to that of curcumin. In the present study, we have tested A.oxyphylla for its ability to suppress tumor promotion. Thus, topical application of the methanolic extract of dried fruits of A.oxyphylla significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumor promotion as well as ear edema in female ICR mice. In another study, treatment of HL-60 cells with the methanolic extract of A.oxyphylla significantly reduced the viability of the cells and also inhibited DNA synthesis. Microscopic examination of the treated cells showed characteristic morphology of apoptosis. Furthermore, cells treated with the extract of A.oxyphylla exhibited internucleosomal DNA fragmentation in time- and concentration-dependent manners. TPA-stimulated generation of superoxide anion in differentiated HL-60 cells was also blunted by A.oxyphylla. Taken together, these findings suggest that A.oxyphylla possesses potential chemopreventive and antitumorigenic activities.     

T-cell apoptosis detected in situ during positive and negative selection in the thymus

Because of positive and negative selection to molecules of the major histocompatibility complex (MHC), only a small proportion of the massive numbers of T cells generated in the thymus are selected for export. Immature thymocytes have a rapid turnover, and it has long been assumed that most thymocytes die in situ, presumably from apoptosis. This has yet to be proved, however, and conventional staining techniques have shown only minimal evidence of cell death in the normal thymus. Using a method for detecting cells with DNA strand breaks, we now present direct evidence for apoptosis in the normal thymus. In sections of thymus from adult mice, apoptotic cells are scattered throughout the cortex and are engulfed locally by F4/80+ macrophages. Apoptosis in the thymic cortex is not reduced in MHC-deficient mice, which suggests that T-cell death is primarily a reflection of lack of positive selection rather than negative selection. Direct evidence for apoptosis due to negative selection was obtained by crossing a V beta 5 transgenic line to I-E+ and I-E- mice: I-E+ mice are known to eliminate V beta 5+ T cells in the thymus whereas I-E- mice do not. In marked contrast to I-E- mice, the medulla of I-E+ V beta 5 transgenic mice contains dense aggregates of apoptotic cells; these cells are engulfed by a distinct population of F4/80- MAC-3+ macrophages. Negative selection of V beta 5+ cells is thus restricted to the medulla.