Korean Byungkyul - Citrus platymamma Hort.et Tanaka flavonoids induces cell cycle arrest and apoptosis, regulating MMP protein expression in Hep3B hepatocellular carcinoma cells

Hong, G. E.,Lee, H. J.,Kim, J. A.,Yumnam, S.,Raha, S.,Saralamma, V. Venkatarame Gowda,Heo, J. D.,Lee, S. J.,Kim, E. H.,Won, C. K. Lychnia 2017 International journal of oncology Vol.50 No.2

<P>Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids. DNA fragmentation was confirmed through agarose gel electrophoresis and TUNEL assay. An increase in the total apoptotic cells and G2/M cell cycle arrest with decreased protein expression of CDC25C, CDK1, cycl in B1 and p21 were observed in Hep3B cells treated with flavonoids of C. platymamma. Further, protein expression of Bcl-XL, Bax, caspase-3 and -9 were also modulated by C. platymamma flavonoids treatment indicating that cell death is through intrinsic apoptotic pathway. Moreover, C. platymamma flavonoids also regulated the phosphorylation of MAPKs, PI3K, and Akt in Hep3B cells. Relevant to inhibiting metastasis, C. platymamma treatment reduced wound closure of Hep3B cells and the protein expression of matrix metalloproteinase-2 and -9 were reduced in C. platymamma treated cells. The results show that C. platymamma flavonoids induce cell cycle arrest and apoptosis following activation of MAPKs and suppression of PI3K/Akt pathway which eventually inhibits cell migration in Hep3B cells. The finding provides evidence on biochemical activities of C. platymamma Hort.et Tanaka, which would be an essential agent for hepatocellular carcinoma (HCC) treatment.</P>

The essential oils of Chamaecyparis obtusa promote hair growth through the induction of vascular endothelial growth factor gene

Lee, G.S.,Hong, E.J.,Gwak, K.S.,Park, M.J.,Choi, K.C.,Choi, I.G.,Jang, J.W.,Jeung, E.B. Inverni Della Beffa S.p.A ; Elsevier Science 2010 Fitoterapia Vol.81 No.1

Chamaecyparis obtusa (C. obtusa) is a conifer in the cypress family Cupressaceae, native to northeast Asia. The essential oils of C. obtusa have antibacterial and antifungal effects and several products such as hygienic bands, aromatics, and shampoos contain these oils as a natural source of antimicrobial/antifungal agents. Interestingly, some consumers suffering from baldness and/or other forms of hair loss have reported a hair growth promoting effect of shampoos containing these oils. In the present study, the hair growth promoting effect of C. obtusa oils was elucidated in an animal model. C. obtusa oils promoted the early phase of hair growth in shaved mice. In addition, we examined the molecular effect of C. obtusa oils on the regulation of hair morphogenesis and hair growth using the human keratinocyte cell line HaCaT. In the current study of hair growth regulating genes, the expressions of vascular endothelial growth factor (VEGF), transforming growth factor (TGFβ1), and keratinocyte growth factor(KGF) have been analyzed by real-time PCR in HaCaT cells. The essential oils of C. obtusa were divided into seven fractions for treatment of HaCaT cells. VEGF transcripts were induced by fractions 6 and 7; however, TGFβ1 and KGF mRNA levels were unchanged by C. obtusa oils or fractions. Fraction 7 was separated into seven sub-fractions and studied further. Sub-fractions E and D significantly increased VEGF and KGF gene expression without up-regulating the hair growth inhibition factor, TGFβ1. The components of the two sub-fractions were further analyzed by gas chromatography and mass spectrometry. Cuminol, eucarvone, and calamenene were common to these two sub-fractions, although the effects of these individual components were not determined. Taken together, these results suggest that C. obtusa oils promote hair growth in an animal model and a positive regulator of hair growth, VEGF, was induced by particular components of these oils.

Gender differences in coronary plaque components in patients with acute coronary syndrome: Virtual histology-intravascular ultrasound analysis

Hong, Y.J.,Jeong, M.H.,Choi, Y.H.,Ma, E.H.,Cho, S.H.,Ko, J.S.,Lee, M.G.,Park, K.H.,Sim, D.S.,Yoon, N.S.,Youn, H.J.,Kim, K.H.,Park, H.W.,Kim, J.H.,Ahn, Y.,Cho, J.G.,Park, J.C.,Kang, J.C. Japanese College of Cardiology 2010 Journal of cardiology Vol.56 No.2

Background: The aim of this study was to evaluate the gender differences in plaque components in acute coronary syndrome (ACS) patients. Methods: We used virtual histology-intravascular ultrasound to evaluate the plaque components in culprit lesions in 362 ACS patients (254 men, 108 women). Results: Women were more likely to be diabetic (34% vs 23%, p=0.030), had greater percentage necrotic core (%NC) volume (19.0+/-12.7% vs 16.8+/-11.9%, p=0.040), and had trends toward higher high-sensitivity C-reactive protein (hs-CRP) (0.85+/-1.28mg/dl vs 0.53+/-0.48mg/dl, p=0.063), and higher incidence of thin-cap fibroatheroma (TCFA) (62% vs 52%, p=0.078) compared with men. %NC volume was significantly greater in diabetic patients compared with nondiabetic patients (20.4+/-10.2% vs 16.0+/-8.9%, p<0.001) and was significantly greater in patients with elevated hs-CRP (>=0.2mg/dl) compared with those with normal hs-CRP (<0.2mg/dl) (18.8+/-8.9% vs 16.6+/-9.7%, p=0.021). However, there were no differences in plaque components between diabetic women and men, and between women and men with elevated hs-CRP levels. Diabetes [odds ratio (OR): 2.44, 95% confidence interval (CI): 1.35-3.82, p=0.003] and hs-CRP (OR: 1.54, 95% CI: 1.08-2.65, p=0.032), but not female gender, were the independent predictors of TCFA. Conclusions: Although it seems likely that female ACS patients have more vulnerable plaque components compared with male ACS patients, these findings may result not from true gender differences in plaque components but higher prevalence of diabetes and hs-CRP elevation in women.

Early Pheromone Experience Modifies a Synaptic Activity to Influence Adult Pheromone Responses of <i>C. elegans</i>

Hong, Myeongjin,Ryu, Leesun,Ow, Maria C.,Kim, Jinmahn,Je, A Reum,Chinta, Satya,Huh, Yang Hoon,Lee, Kea Joo,Butcher, Rebecca A.,Choi, Hongsoo,Sengupta, Piali,Hall, Sarah E.,Kim, Kyuhyung Current Biology Ltd 2017 Current Biology Vol.27 No.20

<P><B>Summary</B></P> <P>Experiences during early development can influence neuronal functions and modulate adult behaviors []. However, the molecular mechanisms underlying the long-term behavioral effects of these early experiences are not fully understood. The <I>C. elegans</I> ascr#3 (asc-ΔC9; C9) pheromone triggers avoidance behavior in adult hermaphrodites []. Here, we show that hermaphrodites that are briefly exposed to ascr#3 immediately after birth exhibit increased ascr#3-specific avoidance as adults, indicating that ascr#3-experienced animals form a long-lasting memory or imprint of this early ascr#3 exposure []. ascr#3 imprinting is mediated by increased synaptic activity between the ascr#3-sensing ADL neurons and their post-synaptic SMB motor neuron partners via increased expression of the <I>odr-2</I> glycosylated phosphatidylinositol (GPI)-linked signaling gene in the SMB neurons. Our study suggests that the memory for early ascr#3 experience is imprinted via alteration of activity of a single synaptic connection, which in turn shapes experience-dependent plasticity in adult ascr#3 responses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Early pheromone exposure modulates behavioral responses to the pheromone as adults </LI> <LI> Pheromone experience is imprinted as increased synaptic activity </LI> <LI> The <I>odr-2</I> GPI-linked signaling protein mediates pheromone imprinting </LI> </UL> </P>

Formulation and Evaluation of a Self-microemulsifying Drug Delivery System Containing Bortezomib

Hong, E.-P.,Kim, J.-Y.,Kim, S.-H.,Hwang, K.-M.,Park, C.-W.,Lee, H.-J.,Kim, D.-W.,Weon, K.-Y.,Jeong, S. Y.,Park, E.-S. PHARMACEUTICAL SOCIETY OF JAPAN 2016 Chemical & pharmaceutical bulletin Vol.64 No.8

<P>The purposes of the present study were to develop a self-microemulsifying drug delivery system (SMEDDS) containing bortezomib, a proteasome inhibitor. The solubility of the drug was evaluated in 15 pharmaceutical excipients. Combinations of oils, surfactants and cosurfactants were screened by drawing pseudo-ternary phase diagrams. The system exhibiting the largest region of microemulsion was considered optimal. Bortezomib SMEDDS spontaneously formed a microemulsion when diluted with an aqueous medium with a median droplet size of approximately 20-30 nm. In vitro release studies showed that the SMEDDS had higher initial release rates for the drug when compared with the raw drug material alone. Measurement of the viscosity, size, and ion conductivity indicated that a phase inversion from water in an oil system to oil in a water system occurred when the weight ratio of the water exceeded 30% of the entire microemulsion system. In a pharmacokinetics study using rats, the bortezomib microemulsion failed to improve the bioavailability of the drug. The reason was assumed to be degradation of the drug in the microemulsion in the gastrointestinal tract. However, bortezomib in Labrasol (R) solution (an aqueous solution containing 0.025% Labraso (R)) showed significantly increased area under the curve from 0-24h (AUC(0-24h)) and maximum plasma concentration (C-max) values compared to the drug suspension. The findings of this study imply that oral delivery of a bortezomib and colloidal system containing Labrasol (R) could be an effective strategy for the delivery of bortezomib.</P>

Age-related differences in virtual histology-intravascular ultrasound findings in patients with coronary artery disease

Hong, Y.J.,Jeong, M.H.,Choi, Y.H.,Ma, E.H.,Ko, J.S.,Lee, M.G.,Park, K.H.,Sim, D.S.,Yoon, N.S.,Youn, H.J.,Kim, K.H.,Park, H.W.,Kim, J.H.,Ahn, Y.,Cho, J.G.,Park, J.C.,Kang, J.C. Japanese College of Cardiology 2010 Journal of cardiology Vol.55 No.2

Background: We assessed the age-related differences in pre-intervention virtual histology-intravascular ultrasound (VH-IVUS) findings at target lesion sites in patients with coronary artery disease. Methods: A total of 553 patients who underwent pre-intervention VH-IVUS imaging were grouped according to age: non-elderly (@?70 years, n=429) and elderly (>70 years, n=124); 191 had stable angina and 362 acute coronary syndrome. VH-IVUS classified the tissue into: fibrotic, fibro-fatty, dense calcium (DC), and necrotic core (NC). Results: Overall, the absolute and percent volumes of DC (11.0+/-11.0mm<SUP>3</SUP> vs. 9.7+/-11.9mm<SUP>3</SUP>, P=0.033; 11.7+/-8.1% vs. 9.8+/-7.2%, P=0.014, respectively) and NC (18.5+/-17.6mm<SUP>3</SUP> vs. 16.6+/-18.9mm<SUP>3</SUP>, P=0.020; 18.8+/-8.8% vs. 16.5+/-9.3%, P=0.026, respectively) were significantly greater in the elderly than in the non-elderly. In stable angina patients, the absolute and percent volumes of DC (10.4+/-9.9mm<SUP>3</SUP> vs. 7.2+/-7.6mm<SUP>3</SUP>, P=0.022; 13.4+/-10.0% vs. 9.2+/-6.5%, P=0.011, respectively) and NC (14.8+/-11.2mm<SUP>3</SUP> vs. 12.0+/-11.9mm<SUP>3</SUP>, P=0.035; 19.6+/-8.8% vs. 15.5+/-8.4%, P=0.006, respectively) were significantly greater in the elderly. However, in acute coronary syndrome patients, there were no significant differences in absolute and percent volumes of DC (11.4+/-11.6mm<SUP>3</SUP> vs. 10.9+/-13.4mm<SUP>3</SUP>, P=0.8; 10.7+/-6.5% vs. 10.1+/-7.5%, P=0.5, respectively) and NC (24.1+/-20.3mm<SUP>3</SUP> vs. 23.9+/-21.2mm<SUP>3</SUP>, P=0.9; 22.0+/-8.8% vs. 21.3+/-9.6%, P=0.6, respectively) between the elderly and non-elderly groups. Myocardial infarction (OR: 2.56, 95% CI: 1.45-4.12, P=0.003), diabetes mellitus (OR: 2.23, 95% CI: 1.30-3.53, P=0.009), and high-sensitivity C-reactive protein (OR: 1.44, 95% CI: 1.06-2.45, P=0.042), but not age, were independent predictors of percent NC volume >20% in lesion site. Conclusions: Myocardial infarction, diabetes mellitus, and high-sensitivity C-reactive protein, but not age, were associated with NC-rich lesions. Clinical presentation, risk factors, and inflammatory status, but not age, are important factors for plaque components.

AS-275: Relation Between High-Sensitivity C-Reactive Protein and Coronary Plaque Components in Patients with Acute Coronary Syndrome: Virtual Histology-Intravascular Ultrasound Analysis

Hong, Y.J.,Jeong, M.H.,Choi, Y.H.,Ko, J.S.,Lee, M.G.,Kang, W.Y.,Lee, S.E.,Kim, S.H.,Sim, D.S.,Park, K.H.,Yoon, N.S.,Youn, H.J.,Kim, K.H.,Park, H.W.,Kim, J.H.,Ahn, Y.,Cho, J.G.,Park, J.C.,Kang, J.C. Cahners Pub. Co., etc.] ; Elsevier Science Ltd 2009 The American Journal of Cardiology Vol.103 No.9

Gut-Specific Delivery of T-Helper 17 Cells Reduces Obesity and Insulin Resistance in Mice

Hong, C.P.,Park, A.,Yang, B.G.,Yun, C.H.,Kwak, M.J.,Lee, G.W.,Kim, J.H.,Jang, M.S.,Lee, E.J.,Jeun, E.J.,You, G.,Kim, K.S.,Choi, Y.,Park, J.H.,Hwang, D.,Im, S.H.,Kim, J.F.,Kim, Y.K.,Seoh, J.Y.,Surh, C. Elsevier North Holland [etc.] 2017 Gastroenterology Vol.152 No.8

<P>BACKGROUND & AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4(+) T-helper (T-H) cells with obesity and the effects of gut-tropic T(H)17 cells in mice on a high-fat diet (HFD). METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A-deficient HFD were compared with mice fed a vitamin A-sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and T(H)17 cells (wild type or deficient in integrin beta 7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction. RESULTS: Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4(+) T-H cells. Intestinal tissues from obese mice had significant reductions in the proportion of T(H)17 cells but increased proportion of T(H)1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of T(H)17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in vitro-differentiated gut-tropic T(H)17 cells to obese mice reduced these metabolic defects, which required the integrin beta 7 subunit and IL17. Delivery of T(H)17 cells to intestines of mice led to expansion of commensal microbes associated with leanness. CONCLUSIONS: In mice, intestinal T(H)17 cells contribute to development of a microbiota that maintains metabolic homeostasis, via IL17. Gut-homing T(H)17 cells might be used to reduce metabolic disorders in obese individuals.</P>

Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation

Hong, Z. Y.,Lee, C. G.,Shim, H. S.,Lee, E. J.,Song, K. H.,Choi, B. W.,Cho, J.,Story, M. D. SPRINGER VERLAG KG 2016 Lung Vol.194 No.1

<P>Purpose We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury. Methods and MaterialsADFIR was administered to the left lung of mice using a small animal micro-irradiator. Histopathological evaluation and micro-computed tomography (micro-CT) analyses were performed at 1, 2, 6, and 12 weeks after irradiation. Dose responses were tested at doses of 0-90 Gy in C57BL/6 and C3H/HeJCr mice at 6 weeks after irradiation. The volume effect was evaluated with 1-, 3-, and 5-mm diameter collimators at 1-4 weeks after 90-Gy irradiation. ResultsADFIR caused gross local lung injury of the inflated lung in just 1 week, with extensive hyaline material visible in the irradiated area. The fibrosing process was initiated as early as 2 weeks after irradiation. C3H and C57 mice did not show significant differences in dose response. Six weeks after irradiation, the radiation dose-response curve had a sigmoidal shape, where the lag, log, and stationary phases occurred at < 40, 50-70, and > 80 Gy, respectively. ADFIR induced substantial volume-dependent structural and functional damage to the lungs, and the volume changes of lung consolidation on micro-CT correlated inversely with lung fibrosis over time. ConclusionsWe determined the time, dose, and volume responses in our established small animal model, and found that lung injury was substantially accelerated and phenotypically different from that of prior studies using non-ablative hemi-thorax and complete thorax irradiation schemes.</P>

Electrical and Magnetic Properties of <tex> ${\rm Sr}({\rm Ru},{\rm Cr}){\rm O}_{3}$</tex> Thin Films

Ramana, E. Venkata,Park, Hong Woo,Jung, C. U. IEEE 2010 IEEE transactions on magnetics Vol.46 No.6

<P> Cr-doped <TEX>${\rm SrRuO}_{3}$</TEX> (SRCO) thin films were grown on an <TEX>${\rm SrTiO}_{3}$</TEX> (STO) (001) substrate using a pulsed laser deposition method in order to study the effects of the Cr doping. Measurements of the out-of-plane lattice constant and the electrical and magnetic properties indicate that Cr is incorporated into the B-site of the SRO lattice. Magnetic hysteresis measurements reveal a ferromagnetic nature with a saturation magnetization of about 0.75 <TEX>$\mu_{\rm B}/{\rm Ru}$</TEX>. The magnetization measurement of <TEX>${\rm Sr}({\rm Ru}_{0.9}{\rm Cr}_{0.1}){\rm O}_{3}$</TEX> showed a ferromagnetic transition temperature <TEX>$T_{\rm C}=165\ {\rm K}$</TEX>. This <TEX>$T_{\rm C}$</TEX> value is about 13 K higher than that reported for <TEX>${\rm SrRuO}_{3}$</TEX> thin films. The <TEX>$T_{\rm C}$</TEX> enhancement due to Cr doping in <TEX>${\rm SrRuO}_{3}$</TEX> thin film was less than that observed for the bulk sample. Electrical resistivity measurements of the SRCO thin films reveal metallic behavior, with a much larger residual resistivity of <TEX>$\sim 260\ \mu\Omega\ {\rm cm}$</TEX> compared to 26 <TEX>$\mu\Omega$</TEX> cm for <TEX>${\rm SrRuO}_{3}$</TEX> thin films. </P>