Woon-Seob Shin

Chitosan oligosaccharides, dp 2–8, have prebiotic effect on the Bifidobacterium bifidium and Lactobacillus sp.

In order to investigate the prebiotic potential of chitosan oligosaccharide (COS), prepared by enzymatic hydrolysis of fully deacetylated chitosan polymer, the effect of COS on bacterial growth was studied. The degree of polymerization (dp) of COS was determined by MALDI-ToF mass spectrometry, and the COS was found to be composed of dimer (33.6%), trimer (16.9%), tetramer (15.8%), pentamer (12.4%), hexamer (8.3%), heptamer (7.1%), and octamer (5.9%). The minimum inhibitory concentrations (MIC) of chitosan polymer against lactic acid bacteria and bifidobacteria were below 0.31%. However, this only applied to two strains, the other bacteria tested grew on MRS broth containing 5% COS. The effects of COS on the growth of bifidobacteria and lactic acid bacteria were compared with those of fructo-oligosaccharide (FOS). FOS was found to have a growth stimulatory effect on only three strains: Bifidobacterium bifidium, B. infantis and Lactobacillus casei. However, COS stimulated the growth of most Lactobacillus sp. and B. bifidium KCTC 3440. The amount of the growth and the specific growth rate of B. bifidium increased with increasing COS concentration. The cultivation time required to obtain maximum growth was reduced to about 25% in MRS broth supplemented with 0.2-0.4% COS. These results demonstrate that COS has considerable bifidogenic potential. Both cell growth and specific growth rates of L. brevis in MRS broth supplemented with 0.1% COS increased by 25%. The present study shows that COS stimulates the growth of some enteric bacteria, and that COS has potential use as a prebiotic health-food.

Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation

Emodin (1,3,8‐trihydroxy‐6‐methylanthraquinone), an active component in the root and rhizome of Rheum palmatum, is a tyrosine kinase inhibitor with a number of biological activities, including antitumor effects. Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)‐A‐induced angiogenesis, both in vitro and in vivo. In vitro, emodin dose‐dependently inhibits proliferation, migration into the denuded area, invasion through a layer of Matrigel and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated with VEGF‐A. Emodin also inhibits basic fibroblast growth factor‐induced proliferation and migration of HUVECs and VEGF‐A‐induced tube formation of human dermal microvascular endothelial cells. Specifically, emodin induces the cell cycle arrest of HUVECs in the G0/G1 phase by suppressing cyclin D1 and E expression and retinoblastoma protein phosphorylation, and suppresses Matrigel invasion by inhibiting the basal secretion of matrix metalloproteinase‐2 and VEGF‐A‐stimulated urokinase plasminogen activator receptor expression. Additionally, emodin effectively inhibits phosphorylation of VEGF‐A receptor‐2 (KDR/Flk‐1) and downstream effector molecules, including focal adhesion kinase, extracellular signal‐regulated kinase 1/2, p38 mitogen‐activated protein kinase, Akt and endothelial nitric oxide synthase. In vivo, emodin strongly suppresses neovessel formation in the chorioallantoic membrane of chick and VEGF‐A‐induced angiogenesis of the Matrigel plug in mice. Our data collectively demonstrate that emodin effectively inhibits VEGF‐A‐induced angiogenesis in vitro and in vivo. Moreover, inhibition of phosphorylation of KDR/Flk‐1 and downstream effector molecules is a possible underlying mechanism of the anti‐angiogenic activity of emodin. Based on these data, we propose that an interaction of emodin with KDR/Flk‐1 may be involved in the inhibitory function of emodin toward VEGF‐A‐induced angiogenesis in vitro and responsible for its potent anti‐angiogenic in vivo.

Synthesis of 10-substituted triazolyl artemisinins possessing anticancer activity via Huisgen 1,3-dipolar cylcoaddition

Most of the 10-substituted triazolylartemisinin synthesized via the Huisgen 1,3-dipolar cylcoaddition of diastereomeric 10-azidoartemisinin (5, 6, and 7) with various alkynes (a-h) exhibit strong growth inhibition activity, even at sub-micromolar concentrations, against various cancer cell lines such as DLD-1, U-87, Hela, SiHa, A172, and B16. In particular, 10b and 10f showed a highly strong cytotoxicity.

Rapid differentiation of Candida albicans from other Candida species using its unique germ tube formation at 39° C

In this study, we found that no Candida species other than C. albicans is able to form germ tubes at 39° C in serum‐free YEPD (1% (w/v) yeast extract, 2% (w/v) peptone and 2% (w/v) dextrose) media, which makes it easy to identify C. albicans from other Candida species. When cultivated in rabbit serum for at least 2 h at 37° C, more than 60% of C. albicans cells generated germ tubes. In YEPD, however, germ tubes began to appear from C. albicans cells within 30 min at 39° C, and more than 60% of C. albicans cells formed the germ tubes after 1 h at 39° C. Standard Candida strains (ATCC, CBS), three C. albicans and two C. dubliniensis strains were cultured in serum at 37° C for 2 h and in YEPD at 39° C for 1 h. All of the three C. albicans formed germ tubes at 39° C. The two C. dubliniensis strains formed germ tubes in serum at 37° C, but grew as a yeast form in YEPD at 39° C. All of the clinically isolated C. albicans strains in our laboratory formed germ tubes in YEPD at 39° C for 1 h, and none of the clinically isolated Candida species other than C. albicans generated germ tubes in YEPD at 39° C. Thus, the unique germ tube formation of C. albicans induced by high temperature (39° C) in YEPD could be applied to a protocol for the rapid and convenient identification of C. albicans in clinical laboratories. Copyright

Selective vasodilatation effect of sargahydroquinoic acid, an active constituent of Sargassum micracanthum, on the basilar arteries of rabbits.

Sargahydroquinoic acid (2), a major active constituent of Sargassum micracanthum collected from the coast of the East Sea in Korea, showed a selective vasodilatation effect on the basilar arteries of rabbits. Therefore, treatment with sargahydroquinoic acid may selectively accelerate cerebral blood flow through dilatation of the basilar artery without lowering systemic blood pressure.

TiO2 nanorods via one-step electrospinning technique: a novel nanomatrix for mouse myoblasts adhesion and propagation.

This study was aimed at the synthesis and characterization of novel Titania nanorods by sol-gel electrospinning technique. The physicochemical properties of the synthesized nanorods were determined by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray diffraction (XRD) pattern. To examine the in vitro cytotoxicity, mouse myoblast C2C12 cells were treated with different concentrations of as prepared TiO(2) nanorods and the viability of cells was analyzed by Cell Counting Kit-8 assay at regular time intervals. The morphological features of the cells attached with nanorods were examined by Bio-SEM. Cytotoxicity experiments indicated that the mouse myoblast cells could attach to the TiO(2) nanorods after being cultured. We observed that TiO(2) nanorods could support cell adhesion and growth and guide spreading behavior of myoblasts. We conclude that the electrospun TiO(2) nanorods scaffolds with unique morphology had excellent biocompatibility. Thus, the current work demonstrates that the as-synthesized TiO(2) nanorods represent a promising biomaterial to be exploited for various tissue engineering applications.

17-Allylamino-17-Demethoxygeldanamycin Down-Regulates Hyaluronic Acid–Induced Glioma Invasion by Blocking Matrix Metalloproteinase-9 Secretion

Hyaluronic acid (HA) has been implicated in cell adhesion, motility, and tumor progression in gliomas. We previously reported that HA stimulates secretion of matrix metalloproteinase-9 (MMP-9) and induces glioma invasion. However, the molecular mechanism of HA action and therapeutic strategies for blocking HA-induced MMP-9 secretion remain unknown. Here, we report that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) blocks MMP-9 secretion and that HA-induced nuclear factor-κB (NF-κB) activation is mediated by IκB kinase, which phosphorylates the NF-κB inhibitor IκBα and promotes its degradation. In addition, using an RNA interference approach, we show that the focal adhesion kinase plays a critical role in mediating HA-induced NF-κB activation, which resulted in increased MMP-9 expression and secretion, cell migration, and invasion. Importantly, we show that 17-AAG acts by blocking focal adhesion kinase activation, thereby inhibiting IκB kinase–dependent IκBα phosphorylation/degradation, NF-κB activation, and MMP-9 expression. This leads to suppression of HA-induced cell migration and invasion. Based on our data, we propose that 17-AAG is a candidate drug for treatment of highly invasive gliomas resulting from HA-induced, NF-κB–mediated MMP-9 secretion. (Mol Cancer Res 2008;6(11):1657–65)

A study on the synthesis of antiangiogenic (+)-coronarin A and congeners from (+)-sclareolide.

Coronarin A 1, epi-coronarin A 2 and some synthetic intermediates 14a and 14b synthesized from sclareolide exhibit good growth inhibition activities on HUVEC proliferation. In particular, coronarin A 1 and epi-coronarin A 2 effectively suppressed the growth factor induced tube formation of HUVEC at the concentration of 10 micro g/mL.

Acid-catalyzed synthesis of 10-substituted triazolyl artemisinins and their growth inhibitory activity against various cancer cells

A diastereomeric and regioisomeric library of 10-substituted triazolyl artemisinin compounds (6a-6h, 7a-7h, and 8a-8h) with a potent growth inhibitory activities against various cancer cell lines was established. These compounds were synthesized by a reaction with dihydroartemisinin (2) and various substituted triazoles (5a-5h) in methylene chloride using a BF(3)Et(2)O catalyst. Most of the compounds exhibited a strong potency in the submicromolar range, and, in particular, 6f, 7f, and 8f, which have a pentylphenyltriazole moiety, proved to be promising candidates for preclinical trials.

Synthesis of sulfonyl curcumin mimics exerting a vasodilatation effect on the basilar artery of rabbits

In order to discover novel small vasodilatory molecules for potential use in the treatment of vascular disease, we tested the vasodilatation effect of two types of synthetic curcumin mimics, amide type (3) and sulfonyl amide type (4), upon the basilar artery of rabbits. In general, the sulfonyl amide type mimic (4) is more potent than the amide type (3). Curcumin (1) and compounds 12 and 20 effectively dilated the basilar artery of white rabbits.