Anti-Neuroinflammatory Effects of Arecae pericarpium on LPS-Stimulated BV2 Cells.

Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways.

8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells.

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Quantitative Photothermal Characterization with Bioprinted 3D Complex Tissue Constructs for Early-Stage Breast Cancer Therapy Using Gold Nanorods.

Plasmonic photothermal therapy (PPTT) using gold nanoparticles (AuNPs) has shown great potential for use in selective tumor treatment, because the AuNPs can generate destructive heat preferentially upon irradiation. However, PPTT using AuNPs has not been added to practice, owing to insufficient heating methods and tissue temperature measurement techniques, leading to unreliable and inaccurate treatments. Because the photothermal properties of AuNPs vary with laser power, particle optical density, and tissue depth, the accurate prediction of heat generation is indispensable for clinical treatment. In this report, bioprinted 3D complex tissue constructs comprising processed gel obtained from porcine skin and human decellularized adipose tissue are presented for characterization of the photothermal properties of gold nanorods (AuNRs) having an aspect ratio of 3.7 irradiated by a near-infrared laser. Moreover, an analytical function is suggested for achieving PPTT that can cause thermal damage selectively on early-stage human breast cancer by regulating the heat generation of the AuNRs in the tissue.

Comparative Assessment of Biological Activities of Mistletoes for Cosmetic Applications: Viscum Album Var. Coloratum (Kom.) Ohwi and Loranthus Tanakae Franch. & Sav.

Mistletoes, hemiparasites, contain many components with various biological activities and have been used in cosmetics industry. Loranthacease (1,000 species) and Viscaceae (550 species) have the most dominant species in mistletoes (nearly 1,600 species). It can be expected that the biological activities vary from species to species; therefore, we have tested Viscum album var. coloratum (Kom.) Ohwi (belonging to Santalaceae) and Loranthus tanakae Franch. & Sav. (belonging to Loranthacease) for a comparative study of their cosmetic properties, including antioxidant, antimelanogenic, and antiwrinkle activities. As results, the ethanol extract of L. tanakae had higher phenolic content and showed effective antioxidant activity and elastase inhibition. Meanwhile, the ethanol extract of V. album more effectively inhibited tyrosinase. Comparing with ethanol extracts, the water extracts of both mistletoes showed lower biological efficacy than the ethanol extracts or no significant effect. Thus, these results show that different extracts of mistletoe have different levels of biological activities, presumably because of the differences in their phytochemical profiles and because of the different extraction methods used.

The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo.

BACKGROUND: Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms. METHODS: AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice. RESULTS: We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice. CONCLUSION: These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD.

Complementary and Alternative Medicine Use and Its Association with Emotional Status and Quality of Life in Patients with a Solid Tumor: A Cross-Sectional Study.

OBJECTIVES: Complementary and alternative medicine (CAM) has been used widely in various populations for various purposes, including emotional support and improvement of quality of life (QOL). However, CAM use and purposes for using CAM are less clear among Korean patients with a solid tumor. The purpose of this study was to determine the prevalence and type of CAM use, and the association between CAM use and anxiety, depression, and QOL in patients with a solid tumor. DESIGN: A cross-sectional survey. SETTING: A cancer center in Korea. SUBJECTS: Two hundred and sixteen patients diagnosed with a solid tumor. OUTCOME MEASURES: Standard questionnaires on CAM use, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer QLQ-C30. RESULTS: One hundred thirty one patients (60.6%) reported using CAM. CAM users, compared with non-CAM users, were significantly younger (57.8 vs. 60.9 years, p = 0.05), had higher level of education (p = 0.008), had higher income (p = 0.008), were less likely to seek physician consultation on CAM use (p = 0.002), and had a more advanced stage of tumor (p = 0.003) with more distant metastasis (p = 0.001). The most commonly used CAM was herbal medicine (n = 89, 67.9%). CAM users had significantly lower anxiety (t = 5.21, p < 0.001) and depression (t = 4.90, p < 0.001) than non-CAM users. When the effects of CAM use were tested on anxiety, depression, and QOL, controlling for covariates, CAM use was significantly associated with 8.7% and 8.8% of variance in decreasing anxiety and depression, but there was no unique association of CAM use with variance in QOL. CONCLUSIONS: CAM use is prevalent and younger age, higher education levels, higher income, less physician consultation, and higher cancer stage are significant correlates to CAM use. Controlling for covariates (e.g., gender, BMI), CAM use is significantly associated with lower anxiety and depression compared with those of non-CAM users.

Photonic crystal alloys: a new twist in controlling photonic band structure properties.

We identified new photonic structures and phenomenon that are analogous to alloy crystals and the associated electronic bandgap engineering. From a set of diamond-lattice microwave photonic crystals of randomly mixed silica and alumina spheres but with a well defined mixing composition, we observed that both bandedges of the L-point bandgap monotonically shifted with very little bowing as the composition was varied. The observed results were in excellent agreement with the virtual crystal approximation theory originally developed for electronic properties of alloy crystals. This result signifies the similarity and correspondence between photonics and electronics.

Genome-wide drug-induced haploinsufficient screening of fission yeast for identification of hydrazinocurcumin targets.

Hydrazinocurcumin (HC), a synthetic derivative of curcumin, has been reported to inhibit angiogenesis via unknown mechanisms. Understanding the molecular mechanisms of the drug's action is important for the development of improved compounds with better pharmacological properties. A genomewide drug-induced haploinsufficiency screening of fission yeast gene deletion mutants has been applied to identify drug targets of HC. As a first step, the 50% inhibition concentration (IC50) of HC was determined to be 2.2 microM. The initial screening of 4,158 mutants in 384-well plates using robotics was performed at concentrations of 2, 3, and 4 microM. A second screening was performed to detect sensitivity to HC on the plates. The first screening revealed 178 candidates, and the second screening resulted in 13 candidates, following the elimination of 165 false positives. Final filtering of the condition-dependent haploinsufficient genes gave eight target genes. Analysis of the specific targets of HC has shown that they are related to septum formation and the general transcription processes, which may be related to histone acetyl transferase. The target mutants showed 65% growth inhibition in response to HC compared with wild-type controls, as shown by liquid culture assay.

Yeast-based screening to identify modulators of G-protein signaling using uncontrolled cell division cycle by overexpression of Stm1.

Stm1, a G-protein coupled receptor, which senses nutritional state drives cells to stop the proliferative cell cycle and enter meiosis under nutritionally deficient conditions in Schizosaccharomyces pombe. It was shown that overexpression of Stm1 led growth inhibition and uncontrolled mitotic haploidization presumably by the premature initiation of mitosis. Sty1 and Gpa2 seem to play important roles for Stm1 to deliver starvation signal to induce downstream function. Based on the observation that conversion of diploid to haploid by overexpression of Stm1 can be easily detected as pink or red colonies in the media containing low adenine, HTS drug screening system to identify modulators of GPCR was established and tested using 413 compounds. Four very potent modulators of GPCR including Biochanin A, which possess strong inhibitory activity against uncontrolled cell division, were identified in this screening. This study provides the yeast-based platform that allows robust cellular assays to identify novel modulators of G-protein signaling and MAP kinase pathway.