The dietary ingredient, genistein, stimulates cathelicidin antimicrobial peptide expression through a novel S1P-dependent mechanism

Park, K.,Kim, Y.I.,Shin, K.O.,Seo, H.S.,Kim, J.Y.,Mann, T.,Oda, Y.,Lee, Y.M.,Holleran, W.M.,Elias, P.M.,Uchida, Y. Butterworths ; Elsevier Science Ltd 2014 The Journal of nutritional biochemistry Vol.25 No.7

We recently discovered that a signaling lipid, sphingosine-1-phosphate (S1P), generated by sphingosine kinase 1, regulates a major epidermal antimicrobial peptide's [cathelicidin antimicrobial peptide (CAMP)] expression via an NF-κB→C/EBPα-dependent pathway, independent of vitamin D receptor (VDR) in epithelial cells. Activation of estrogen receptors (ERs) by either estrogens or phytoestrogens also is known to stimulate S1P production, but it is unknown whether ER activation increases CAMP production. We investigated whether a phytoestrogen, genistein, simulates CAMP expression in keratinocytes, a model of epithelial cells, by either a S1P-dependent mechanism(s) or the alternate VDR-regulated pathway. Exogenous genistein, as well as an ER-β ligand, WAY-200070, increased CAMP mRNA and protein expression in cultured human keratinocytes, while ER-β antagonist, ICI182780, attenuated the expected genistein- and WAY-200070-induced increase in CAMP mRNA/protein expression. Genistein treatment increased acidic and alkaline ceramidase expression and cellular S1P levels in parallel with increased S1P lyase inhibition, accounting for increased CAMP production. In contrast, siRNA against VDR did not alter genistein-mediated up-regulation of CAMP. Taken together, genistein induces CAMP production via an ER-β→S1P→NF-κB→C/EBPα- rather than a VDR-dependent mechanism, illuminating a new role for estrogens in the regulation of epithelial innate immunity and pointing to potential additional benefits of dietary genistein in enhancing cutaneous antimicrobial defense.

<i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms

Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. ‐,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. ‐,K.,Yoon, Y. ‐,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4

<P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>

Pharmacodynamic Effect of Cilostazol Plus Standard Clopidogrel Versus Double-Dose Clopidogrel in Patients With Type 2 Diabetes Undergoing Percutaneous Coronary Intervention

Jeong, Young-Hoon,Tantry, Udaya S.,Park, Yongwhi,Kwon, Tae Jung,Park, Jeong Rang,Hwang, Seok-Jae,Bliden, Kevin P.,Koh, Eun-Ha,Kwak, Choong Hwan,Hwang, Jin-Yong,Kim, Sunjoo,Gurbel, Paul A. American Diabetes Association 2012 Diabetes care Vol.35 No.11

<P><B>OBJECTIVE</B></P><P>To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (<I>CYP2C19*2/*3</I>, <I>CYP3A5*3)</I>and ATP-binding cassette subfamily B1(<I>ABCB1 C3435T</I>) genetic polymorphisms in type 2 diabetes (T2DM) patients.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>T2DM patients were treated with TRIPLE (<I>n</I> = 41) or DOUBLE (<I>n</I> = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-μM ADP-induced maximal platelet aggregation (ΔMPA<SUB>20</SUB>) between baseline and switching values.</P><P><B>RESULTS</B></P><P>TRIPLE versus DOUBLE showed greater ΔMPA<SUB>20</SUB> (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2–16.3]; <I>P</I> < 0.001). Carriage of one (β coefficient, −5.4%; <I>P</I> = 0.162) and two <I>CYP2C19</I> loss-of-function allele(s) (−8.3%; <I>P</I> = 0.007) were associated with lower ΔMPA<SUB>20</SUB> in DOUBLE–treated patients, but not in TRIPLE-treated patients.</P><P><B>CONCLUSIONS</B></P><P>Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.</P>

Reproductive Performance, Milk Composition, Blood Metabolites and Hormone Profiles of Lactating Sows Fed Diets with Different Cereal and Fat Sources

Park, M.S.,Shinde, P.L.,Yang, Y.X.,Kim, J.S.,Choi, J.Y.,Yun, K.,Kim, Y.W.,Lohakare, J.D.,Yang, B.K.,Lee, J.K.,Chae, Byung-Jo Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.2

Different dietary cereal sources and fat types in the lactation diet were evaluated to investigate their effects on reproductive performance, milk composition, blood metabolites and hormones in multiparous sows. Twenty-four sows were randomly assigned to one of four treatments according to a 2${\times}$2 factorial arrangement of treatments. Each treatment had 6 replicates comprising 1 sow. Two cereal (corn or wheat) and two fat (tallow or soybean oil) sources were used to prepare iso-caloric and iso-nitrogenous diets. Sows fed corn-based diets lost less body weight (p = 0.003) and backfat thickness (p = 0.034), consumed more feed (p = 0.032) and had shorter wean-to-estrus interval (p = 0.016) than sows fed wheat-based diets. Fewer piglets and lower body weight of piglets (p<0.05) at weaning were noted in sows fed wheat-based diets than in sows fed corn-based diets. However, no significant effects (p>0.05) of dietary fat source and its interaction with dietary cereal source on sow body condition and reproductive performance were observed during lactation. Feeding of a corn-based diet improved (p<0.05) sow milk total solid, protein and fat, increased blood urea nitrogen (p = 0.032) and triglyceride (p = 0.018), and decreased blood creatinine (p = 0.011) concentration at weaning when compared with sows fed wheatbased diets. Sows fed corn-based diets had higher concentration of insulin (p = 0.048) and LH (p<0.05) at weaning than sows fed wheatbased diets. The results indicate that feeding corn-based diets to lactating sows improved sow body condition and reproductive performance compared with wheat-based diets regardless of fat sources.

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

Westhovens, R,Robles, M,Ximenes, A C,Nayiager, S,Wollenhaupt, J,Durez, P,Gomez-Reino, J,Grassi, W,Haraoui, B,Shergy, W,Park, S-H,Genant, H,Peterfy, C,Becker, J-C,Covucci, A,Helfrick, R,Bathon, J BMJ Group 2009 Annals of the Rheumatic Diseases Vol.68 No.12

<P><B>Objectives:</B></P><P>To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors.</P><P><B>Methods:</B></P><P>In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout.</P><P><B>Results:</B></P><P>At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone.</P><P><B>Conclusions:</B></P><P>In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.</P>

Hierarchical 3D ZnIn₂S₄/graphene nano-heterostructures: their <i>in situ</i> fabrication with dual functionality in solar hydrogen production and as anodes for lithium ion batteries

Kale, Sayali B.,Kalubarme, Ramchandra S.,Mahadadalkar, Manjiri A.,Jadhav, Harsharaj S.,Bhirud, Ashwini P.,Ambekar, Jalinder D.,Park, Chan-Jin,Kale, Bharat B. The Royal Society of Chemistry 2015 Physical Chemistry Chemical Physics Vol.17 No.47

<P>Hierarchical 3D ZnIn2S4/graphene (ZnIn2S4/Gr) nano-heterostructures were successfully synthesized using an in-situ hydrothermal method. The dual functionality of these nano-heterostructures i.e. for solar hydrogen production and lithium ion batteries has been demonstrated for the first time. The ZnIn2S4/Gr nano-heterostructures were optimized by varying the concentrations of graphene for utmost hydrogen production. An inspection of the structure shows the existence of layered hexagonal ZnIn2S4 wrapped in graphene. The reduction of graphene oxide (GO) to graphene was confirmed by Raman and XPS analyses. The morphological analysis demonstrated that ultrathin ZnIn2S4 nanopetals are dispersed on graphene sheets. The optical study reveals the extended absorption edge to the visible region due to the presence of graphene and hence is used as a photocatalyst to transform H2S into eco-friendly hydrogen using solar light. The ZnIn2S4/Gr nano-heterostructure that is comprised of graphene and ZnIn2S4 in a weight ratio of 1 : 99 exhibits enhanced photocatalytically stable hydrogen production i.e. B6365 mmole h(-1) under visible light irradiation using just 0.2 g of nano-heterostructure, which is much higher as compared to bare hierarchical 3D ZnIn2(S4). The heightened photocatalytic activity is attributed to the enhanced charge carrier separation due to graphene which acts as an excellent electron collector and transporter. Furthermore, the usage of nano-heterostructures and pristine ZnIn2S4 as anodes in lithium ion batteries confers the charge capacities of 590 and 320 mA h g(-1) after 220 cycles as compared to their initial reversible capacities of 645 and 523 mA h g(-1), respectively. These nano-heterostructures show high reversible capacity, excellent cycling stability, and high-rate capability indicating their potential as promising anode materials for LIBs. The excellent performance is due to the nanostructuring of ZnIn2S4 and the presence of a graphene layer, which works as a channel for the supply of electrons during the charge-discharge process. More significantly, their dual functionality in energy generation and storage is quite unique and commendable.</P>

국내이용 말사료의 영양적 가치와 YEAST CULTURE 첨가시 소화율 , 광물질 이용율 및 혈액성상에 미치는 영향

김성민(S . M . Kim),김종민(C . M . Kim),이현기(H . K . Lee),박원표(W . P . Park),임영재(Y . J . Lim),김병진(B . J . Kim),정태영(T . Y . Chung) 한국영양사료학회 1991 韓國營養飼料學會誌 Vol.15 No.5

Morphological and Molecular Phylogenetic Position of Prorocentrum micans sensu stricto and Description of Prorocentrum koreanum sp. nov. from Southern Coastal Waters in Korea and Japan

Han, M.S.,Wang, P.,Kim, J.H.,Cho, S.Y.,Park, B.S.,Kim, J.H.,Katano, T.,Kim, B.H. G. Fischer 2016 PROTIST -JENA- Vol.167 No.1

Prorocentrum micans is an extremely variable dinoflagellate species, with many different local forms reported worldwide. Because of this morphological diversity, it is important to establish whether these various forms belong to P. micans sensu stricto. For this study, P. micans-like specimens were isolated from several localities in the southern coastal waters of Korea and Japan. The morphological characteristics and the molecular signatures of P. micans were re-examined. Moreover, a new Prorocentrum species, Prorocentrum koreanum sp. nov. was established through detailed light microscopy and scanning electron microscopy observations. Examination of the periflagellar platelets revealed that P. koreanum sp. nov. differs from P. micans. Furthermore, P. koreanum and P. micans exhibited different distribution patterns of trichocyst pores. Through molecular phylogeny analysis of small subunit (SSU) rRNA, internal transcribed spacer (ITS), and large subunit (LSU) rRNA sequence, we found P. koreanum to be more closely related to P. mexicanum and P. rhathymum than to P. micans. Additionally, ITS2 compensatory base changes also provide strong evidence to support P. koreanum and P. micans being separate species.

Effects of Deletion of Ca Supplement (limestone) on Growth and Beef Quality in Hanwoo Finishing Steers

Lee, C. E.,Park, N. K.,Seong, P. N.,Jin, S. H.,Park, B. Y.,Kim, K. I. 한국동물자원과학회 2003 한국축산학회지 Vol.45 No.3

이 연구는 소 비육후기에 칼슘제(석회석)를 첨가하지 않은 사료의 급여가 성장율, 근내지방도 및 혈청 1,25-dihydroxy vitamin D_3(1,25(OH)_2D_3) 함량에 미치는 영향을 구명하기 위하여 수행되었다. 거세 한우 24두(20~24개월령)를 12두씩 대조구(석회석 2.5% 함유 농후사료)와 칼슘제 무첨가구(석회석 0%)로 배치하여 223일 동안 사료(농후사료 및 오차드그라스 건초)와 물을 무제한 급여하였고, 사양시험이 완료된 후 도축하여 육질을 평가하였다. 혈청 Ca^2+, Ca 및 P 함량에는 처리 간 차이가 없었으나 (P>0.05), 1,25(OH)_2D_3 함량은 시험 시작후 2 또는 6개월째 모두 칼슘제 무첨가구가 대조구보다 (각각 78.3 vs 51.7 또는 80.3 vs 51.1pg/mL) 높았다 (P<0.01). 칼슘제를 첨가하지 않은 사료를 급여한 비육우가 대조구보다 농후사료 섭취량은 증가하고 건초 섭취량은 감소하는 경향을 보였다. 일당증체량은 대조구보다 칼슘제 무첨가구에서 높았다(P<0.01). 등심단면적(82.8 vs 77.2㎠), 근내지방도(5.1 vs 2.2) 및 지방 함량(10.2 vs 6.7%)이 칼슘제 무첨가구가 대조구보다 높았고 (P<0.05), 수분 함량 (67.6 vs 70.4%)은 낮았다 (P<0.05). 등심 육색, pH 및 보수력에서는 처리 간 차이가 없었으나 전단력에서는 칼슘제 무첨가구에서 (2.9 vs 3.2 kg/1.27-㎝ diameter core), 약간 낮게 (P = 0.08) 나타났다. 관능평가에서는 칼슘제 무첨가구가 대조구보다 연도 (4.9 vs 4.5) 및 향미 (4.9 vs 4.6)가 약간 개선되었으나 (P<0.05) 다즙성에서는 처리간 차이가 없었다 (P<0.05) 다즙성에서는 처리간 차이가 없었다 (P<0.05). 본 연구결과는 비육후기에 칼슘제(석회석)를 첨가하지 않은 사료의 급여는 에너지 섭취의 증가 또는 1,25(OH)_2D_3의 합성 촉진을 통하여, 근내지방합성이 증가되어 성장율 및 근내지방도를 개선한다는 것을 제시하였다. A study was conducted to determine the effects of feeding a diet containing no Ca supplement (limestone) during the late finishing period on growth, marbling and serum 1,25-dihydroxy vitamin D_3 level in Korean native cattle. Twenty-four steers (20~24 mo of age) were divided into two groups of 12 each: one group assigned to a control diet (concentrates containing 2.5% limestone) and the other to a diet containing no calcium supplement. They were allowed to have free access to diets (concentrates and orchard grass hay) and water during the entire feeding period (223 d). Serum Ca^2-, Ca and P concentrations were not influenced by diets, but serum 1,25-dihydroxy vitamin D_3 concentrations determined 2 or 6 mo after the beginning of feeding the experimental diets were higher (P<0.01) in steers fed the diet without Ca supplement than in those fed the control diet (78.3 vs 51.7 and 80.3 vs 51.1 pg/mL, respectively). Steers fed the diet without Ca supplement tended to have a higher intake of concentrates, but a lower intake of hay, compared to those fed the control diet. Average daily gain was higher (P<0.05) in steers fed the diet without Ca supplement than in those fed the control diet. Feeding the diet without Ca supplement remarkably (P<0.01) increased the marbling score (5.1 vs 2.2) and the muscle (M. longissimus dorsi) fat content (10.2 vs 6.7%) with a concomitant decrease in moisture content (67.6 vs 70.4%), compared to feeding the compared to feeding the control diet. Ribeye area was increased (77.2 vs 82.8 ㎤) with the diet without Ca supplement, compared to the control diet (P<0.05). Meat color, pH and water-holding capacity in longissimus muscle were not different between the two groups. The Warner-Brazler Shear (WBS) force of the longissimus muscle was slightly (P=0.08) lower in steers fed the diet without Ca supplement than in steers fed the control diet (2.9 vs 3.2 ㎏/1.27-㎝ diameter core). Sensory evaluation showed that feeding the diet without Ca supplement slightly (P<0.05) improved tenderness (4.9 vs 4.5) and flavor (4.9 vs 4.6), compared to feeding the control diet, but juiciness was not affected by diets. Results showed that deletion of Ca supplement fro finishing diets is beneficial, increasing growth and marbling partly through an increased energy intake and induced 1,25-dihydroxy vitamin D_3 synthesis that may increase intracellular Ca^2+ concentration and in turn fat synthesis.

Systems for Production of Calves from Hanwoo(Korean Cattle) IVM/IVF/IVC Blastocyst II. Simple, Efficient and Successful Vitrification of Hanwoo Blastocyst

Kim, E.Y.,Kim, D.I.,Park, N.H.,Weon, Y.S.,Nam, H.K.,Lee, K.S.,Park, S.Y.,Yoon, S.H.,Park, S.P.,Chung, K.S.,Lim, J.H. The Korean Society of Animal Reproduction 1999 Reproductive & developmental biology Vol.23 No.4

The objective of this study was to optimize the freezing/thawing method of in vitro produced Hanwoo blastocysts. Day 7 blastocysts after IVF were vitrified using EFS40 (40% ethylene glycol, 18% ficoll, 0.3 M sucrose and 10% FBS added m-DPBS) as a freezing solution and electron microscope (EM) grid (V-G) or straw (V-S) as an embryo container. In both method, freezing/thawing were treated by 2-step, treatment time was required in V-G method and V-S method, for 2 min / 3 min and 3.5 min / 10 min, respectively. Embryo survival was assessed as re-expanded and hatched rates at 24 h and 48 h after warming, respectively. The results obtained in these experiments were summarized as follows: when the effect of exposure in vitrification solution and chilling injury from freezing procedure on in vitro produced expanded blastocysts were examined, at 24 h after warming, embryo survival in exposure group (100.0%) was not different compared to that in control group (100.0%), although those results were significantly different with two vitrified groups (V-G: 87.8, V-S: 77.8%) (P<0.001). However, at 48 h after warming, hatched rates of V-G group (67.8%) were significantly higher than those of V-S group (53.3%) (P<0.05). In addition, this hatched rate in V-G group was not different with that in exposure group (73.3%). When the effects of embryo developmental stage (early, expanded and early hatching blastocysts) and embryo container (EM grid and straw) to the in vitro survival of vitrified-warmed day 7 Hanwoo blastocysts were simultaneously examined, fast developed embryos were indicated the better resistance to freezing than delayed developed one, irrespective of embryo containers (early; 57.1 & 24.4%, expanded; 84.7 & 60.6%, early hatching; 91.7 & 80.0%) (P<0.001). Especially, in expanded and early hatching blastocysts, embryo survival of V-G group (67.8, 95.0%) was significantly higher than those of V-S group (53.0, 65.0%) at 48 h post warming, respectively (P<0.05, P<0.001). Therefore, this study indicates that Hanwoo blastocysts can be cryopreserved more simple, efficient and successful by vitrification method using EM grid.