Eun Joo Roh

Enhanced In Vitro Midbrain Dopamine Neuron Differentiation, Dopaminergic Function, Neurite Outgrowth, and 1-Methyl-4-Phenylpyridium Resistance in Mouse Embryonic Stem Cells Overexpressing Bcl-XL

Embryonic stem (ES) cells provide a potentially unlimited source of specialized cells for regenerative medicine. The ease of inducing stable genetic modifications in ES cells allows for in vitro manipulations to enhance differentiation into specific cell types and to optimize in vivo function of differentiated progeny in animal models of disease. We have generated mouse ES cells that constitutively express Bcl-XL, an antiapoptotic protein of Bcl-2 family. In vitro differentiation of Bcl-XL overexpressing ES (Bcl-ES) cells resulted in higher expression of genes related to midbrain dopamine (DA) neuron development and increased the number of ES-derived neurons expressing midbrain DA markers compared with differentiation of wild-type ES cells. Moreover, DA neurons derived from Bcl-ES cells were less susceptible to 1-methyl-4-phenylpyridium, a neurotoxin for DA neurons. On transplantation into parkinsonian rats, the Bcl-ES-derived DA neurons exhibited more extensive fiber outgrowth and led to a more pronounced reversal of behavioral symptoms than wild-type ES-derived DA neurons. These data suggest a role for Bcl-XL during in vitro midbrain DA neuron differentiation and provide an improved system for cell transplantation in a preclinical animal model of Parkinsons disease.

Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Calcium signaling is important in many signaling processes in cancer cell proliferation and motility including in deadly glioblastomas of the brain that aggressively invade neighboring tissue. We hypothesized that disturbing Ca(2+) signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a panel of small-molecule modulators of Ca(2+) signaling, we identified caffeine as an inhibitor of glioblastoma cell motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca(2+) increase by inositol 1,4,5-trisphospate receptor subtype 3 (IP(3)R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP(3)R3-mediated Ca(2+) release, caffeine inhibited migration of glioblastoma cells in various in vitro assays. Consistent with these effects, caffeine greatly increased mean survival in a mouse xenograft model of glioblastoma. These findings suggest IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma.

Scandium(III) triflate immobilised in ionic liquids: a novel and recyclable catalytic system for Friedel–Crafts alkylation of aromatic compounds with alkenes

Scandium(III) triflate catalysed Friedel–Crafts alkylation of aromatic compounds with alkenes proceeded readily in the hydrophobic ionic liquid solvents based on 1,3-dialkylimidazolium salts with easy catalyst/solvent recycling, whereas these reactions did not occur in common organic solvents, water or hydrophilic ionic liquids at all.

Practical method to recycle a chiral (salen)Mn epoxidation catalyst by using an ionic liquid

A practical recycling procedure for Jacobsen’s chiral (salen)MnIII epoxidation catalyst involving the use of the air- and moisture-stable ionic liquid [bmim][PF6] has been developed.

Prevalence and Management of Dyslipidemia in Korea: Korea National Health and Nutrition Examination Survey during 1998 to 2010

Background Dyslipidemia is a major risk factor of cardiovascular disease. The aim of this study was to investigate the changing trends in the prevalence and management status of dyslipidemia among Korean adults. Methods The prevalence of dyslipidemia and the rates of awareness, treatment, and control of dyslipidemia were investigated in adults aged ≥20 years from the Korea National Health and Nutrition Surveys (KNHANES) 1998 to 2010. The updated National Cholesterol Education Program criteria was used, which define dyslipidemia as having one or more of the following lipid abnormalities: hypercholesterolemia (total cholesterol ≥240 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), hypertriglyceridemia (≥150 mg/dL), hyper-low density lipoprotein (LDL) cholesterolemia (≥160 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), and hypo-high density lipoprotein (HDL)-cholesterolemia (<40 mg/dL in men and <50 mg/dL in women). Results The number of participants was 6,921, 4,894, 5,312, 2,733, 6,295, 6,900, and 5,738 in KNHANES 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Age-standardized prevalence rates of dyslipidemia were 54.0%, 65.8%, 66.5%, 60.6%, 58.7%, 58.9%, and 59.0% in 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Hypertriglyceridemia and hypo-HDL-cholesterolemia were the two most frequent lipid abnormalities. The overall prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased by 1.36- and 1.35-fold in 2010 compared with 2007, respectively. Awareness, treatment, and control rates of dyslipidemia improved over the period of surveys in both sexes. In 2010, about 30% of dyslipidemic patients who received lipid-lowering treatment reached target levels. Conclusion Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.

MONNA, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1.

Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a −NO2 group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC50 < 10 μM. The most potent blocker, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid (MONNA), had an IC50 of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10∼30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.

Osmium tetroxide–(QN)2PHAL in an ionic liquid: a highly efficient and recyclable catalyst system for asymmetric dihydroxylation of olefins

In Os-catalysed asymmetric dihydroxylation using NMO as a co-oxidant, the combination of an ionic liquid and the new bis-cinchona alkaloid 2 generated in situ from (QN)2PHAL during reaction provided a simple and practical approach to the recycling of both catalytic components (osmium tetraoxide and chiral ligand).

Ionic liquids as powerful media in scandium triflate catalysed Diels–Alder reactions: significant rate acceleration, selectivity improvement and easy recycling of catalyst

Ionic liquids act as powerful media (or additives) in scandium triflate catalysed Diels–Alder reactions not only for facilitating of catalyst recovery but also for accelerating reaction rate and improving selectivity.

Polymeric cinchona alkaloids for the heterogeneous catalytic asymmetric dihydroxylation of olefins: The influence of the polymer backbone polarity on the compatibility between polymer support and reaction medium

Abstract Heterogeneous catalytic asymmetric dihydroxylation of olefins using homo- and co-polymeric cinchona alkaloids has been reported. The benzoate type homopolymers 2a, b showed high enantioselectivity in the heterogeneous ADH reactions, but their catalytic efficiency was largely dependent on the solvent system which may relate to the accessibility of the active catalytic site. The influence of polymer backbone polarity on the compatibility with the reaction medium was investigated using copolymers 3a, b and 4 having polar polymer backbone. The reaction rates and optical yields were dramatically increased by increasing the polarity of the polymer backbone in NMO- acetone H 2 O system.

A new synthetic route to (3R,4S)-3-hydroxy-4-phenylazetidin-2-one as a taxol side chain precursor

Abstract A new synthetic route to (3 R ,4 S )-3-hydroxy-4-phenylazetidin-2-one, an important precursor for the paclitaxel side chain, has been developed using intramolecular cyclization of N -( p -methoxyphenyl) (2 S ,3 R )-2-acetoxy-3-bromo-3-phenylpropionamide which can be easily obtained by catalytic asymmetric dihydroxylation of N -( p -methoxyphenyl)- trans -cinnamide, followed by bromoacetylation.