Biomedical subjects
Publications and source records attributed to Youngjin Choi.
GV01 is one of the most effective acupoints to treat diarrhea in humans and animals. The present study showed that skin on the GV01 acupoint reveals tenderness and neurogenic inflammation in colonic inflammatory states, but not in normal healthy states.
Systematic computational work for a series of 13 disaccharides was performed to provide an atomic-level insight of unique biochemical role of the alpha,alpha-(1-->1)-linked glucopyranoside dimer over the other glycosidically linked sugars. Superior osmotic and cryoprotective abilities of trehalose were explained on the basis of conformational and hydration characteristics of the trehalose molecule. Analyses of the hydration number and radial distribution function of solvent water molecules showed that there was very little hydration adjacent to the glycosidic oxygen of trehalose and that the dynamic conformation of trehalose was less flexible than any of the other sugars due to this anisotropic hydration. The remarkable conformational rigidity that allowed trehalose to act as a sugar template was required for stable interactions with hydrogen-bonded water molecules. Trehalose made an average of 2.8 long-lived hydrogen bonds per each MD step, which was much larger than the average of 2.1 for the other sugars. The stable hydrogen-bond network is derived from the formation of long-lived water bridges at the expense of decreasing the dynamics of the water molecules. Evidence for this dynamic reduction of water by trehalose was also established based on each of the lowest translational diffusion coefficients and the lowest intermolecular coulombic energy of the water molecules around trehalose. Overall results indicate that trehalose functions as a 'dynamic reducer' for solvent water molecules based on its anisotropic hydration and conformational rigidity, suggesting that macroscopic solvent properties could be modulated by changes in the type of glycosidic linkages in sugar molecules.
Human acute myeloid leukemias with the t(8;21) translocation express the AML1-ETO fusion protein in the hematopoietic stem cell compartment and show impairment in erythroid differentiation. This clinical finding is reproduced in multiple murine and cell culture model systems in which AML1-ETO specifically interferes with erythroid maturation. Using purified normal human early hematopoietic progenitor cells, we find that AML1-ETO impedes the earliest discernable steps of erythroid lineage commitment. Correspondingly, GATA-1, a central transcriptional regulator of erythroid differentiation, undergoes repression by AML1-ETO in a nonconventional histone deacetylase-independent manner. In particular, GATA-1 acetylation by its transcriptional coactivator, p300/CBP, a critical regulatory step in programming erythroid development, is efficiently blocked by AML1-ETO. Fusion of a heterologous E1A coactivator recruitment module to GATA-1 overrides the inhibitory effects of AML1-ETO on GATA-1 acetylation and transactivation. Furthermore, the E1A-GATA-1 fusion, but not wild-type GATA-1, rescues erythroid lineage commitment in primary human progenitors expressing AML1-ETO. These results ascribe a novel repressive mechanism to AML1-ETO, blockade of GATA-1 acetylation, which correlates with its inhibitory effects on primary erythroid lineage commitment.
Molecular dynamics simulations were performed to explain the conformational effect of an alpha-(1-->6)-glycosidic linkage upon the cyclic osmoregulated periplasmic glucan (OPG) produced by Xanthomonas campestris pv. citri. We suggest that a single alpha-(1-->6)-glycosidic linkage in cyclic OPG functions as a novel entropic regulator, which reduces the conformational entropy of cyclic OPG and increases the motional entropy of solvent water molecules.
The chromosomal translocation t(8;21), generating the AML1-ETO fusion protein, is frequently associated with French-American-British (FAB) type M2 acute myeloid leukemia (AML). t(8;21) fuses the runt domain from the hematopoietic transcription factor RUNX1 with almost the entire transcriptional repressor ETO. AML1-ETO inhibits normal definitive hematopoiesis and blocks erythroid differentiation. Several mechanistic models for the role of AML1-ETO in leukemia development have emerged over the last decade. Most of these models have emphasized the capacity of the fusion protein to redirect repressive cofactors, such as histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), to RUNX target genes, thereby reversing the hematopoietic transcriptional program activated by wild-type RUNX1a phenomenon referred to collectively in this review as the "classical" corepressor model. Because erythropoiesis occurs in a RUNX-independent manner, this dominant-negative "classical" model cannot explain the prominent repression of red-cell development by AML1-ETO. This review will consider the clinical and mechanistic significance of erythroid inhibition by AML1-ETO. Additional models to account for this mysterious oncogenic function are proposed.
Molecular dynamics (MD) simulations were performed for the prediction of chiral discrimination of N-acetylphenylalanine enantiomers by cyclomaltoheptaose (beta-cyclodextrin, beta-CD). Binding free energies and various conformational properties were obtained using by the MM-PBSA (molecular mechanics Poisson-Boltzmann/surface area) approach. The calculated relative difference (DeltaDeltabinding) of binding free energy was in fine agreement with the experimentally determined value. The difference of rotameric distributions of guest N-acetylphenylalanine enantiomers complexed with the host, beta-CD, was observed after the conformational analyses, suggesting that the conformational changes of guest captured within host cavity would be a decisive factor for enantiodifferentiation at a molecular level.
Carboxymethylated cyclosophoraoses (CM-Cys) were synthesized by chemical modification of a family of neutral cyclosophoraoses isolated from Rhizobium leguminosarum biovar trifolii. Structural analyses of the CM-Cys were carried out using NMR and FTIR spectroscopies, and the molecular weight distributions were confirmed with MALDI-TOF mass spectrometry. Based on structural characterization, native cyclosophoraoses were successfully substituted with carboxymethyl groups at the OH-4 and OH-6 of the glucose residues with degrees of substitution (DS) ranging from 0.012 to 0.290. CM-Cys was also used as a host for the inclusion complexation with hydrobenzoin (HB) and N-acetyltryptophan (N-AcTrp) as guest molecules. NMR spectroscopic analyses of the complexes showed that the CM-Cys induced chemical shifts of some protons of the guest molecules upon the complexation. Phase solubility studies of the guest molecules by CM-Cys were performed using HPLC, and the results were compared with those of native cyclosophoraoses. The solubility of HB and N-AcTrp was enhanced by the CM-Cys about 5.1- and 299-fold, respectively.
Cyclosophoraoses isolated from Rhizobium meliloti, as an NMR chiral shift agent, were used to discriminate propranolol enantiomers. Continuous variation plot made from the complex of cyclosophoraoses with propranolol showed that the diastereomeric complex had predominantly 1:1 stoichiometry through UV spectroscopic analysis. The chiral recognition of propranolol enantiomers by cyclosophoraoses was investigated through the determination of binding constant based on the (13)C NMR chemical shift changes. The averaged K(obs) values from the plots were 55.7 M(-1) for (R)-(+)-propranolol and 36.6 M(-1) for (S)-(-)-propranolol, respectively. Enantioselectivity (alpha = K(R+)/K(S(-)) of 1.52 was then obtained. Computational calculation also revealed that (R)-(+) propranolol was more tightly bound with cyclosophoraose than (S)-(-)-propranolol due to the enhanced van der Waals interaction.
A study has been performed to examine the effect of temperature and ethanolic stresses on the coulombic efficiency of a microbial fuel cell. The conventional-type fuel cell containing Gram-negative bacteria, Proteus vulgaris, was investigated as a model system. From current output measurements, it was found that the coulombic yields were altered by environmental stresses such as temperature shock or ethanol treatment to the bacteria. While high-temperature or ethanolic shock led to a remarkable decrement in coulombic output, the low-temperature shock induced a slight increase in microbial fuel cell efficiency. These results indicate that the membrane fluidity is affected considerably by environmental stress, which in turn affects the electron transfer process through the bacterial cell membrane to and from the electrode. This interpretation was confirmed by the cyclic voltammetric study of a mediator on an electrode surface modified with the lipids extracted from the membrane of P. vulgaris under the given stress. Markedly different electrochemical behaviors were observed depending on the environmental stress. A reciprocal relationship between coulomb output and the ratio of saturation/unsaturation of fatty acids has been observed. This is the first report, to our knowledge, that the structural adaptation of membrane fatty acids in response to the environmental shock can regulate the coulombic efficiency of a microbial fuel cell.
A plant flavone, luteolin is a well-known inducer of nod genes in the Rhizobium meliloti. Its poor aqueous solubility was greatly enhanced by the complexation with a family of cyclosophoraoses synthesized in R.meliloti. Nuclear magnetic resonance (NMR) spectroscopic analysis showed that the chemical shifts of the aromatic ring moieties of the luteolin were changed greatly by the complexation with cyclosophoraoses. Fourier transform infrared (FTIR) spectroscopic analysis also showed a restricted vibrational pattern in carbonyl stretching region of the luteolin due to the complexation. This effective complex formation of cyclosophoraoses with a plant flavone, luteolin, suggests that rhizobial cyclosophoraoses play an important role as a solubility enhancer of the hydrophobic legume-derived flavonoids.
Conjugated linoleic acid (CLA) is a collective term for a group of positional and geometric conjugated dienoic isomers of linoleic acid. CLA has been shown to have strong inhibitory effects on mammary carcinogenesis both in vitro and in vivo. In this study, we investigated the regulation of human stearoyl-CoA desaturase (SCD, EC 1.14.99.5) expression by CLA in human breast cancer cell lines, MDA-MB-231 and MCF-7. Treatment of the cells with the cis-9,trans-11 and trans-10,cis-12 CLA isomers (45 microM) did not repress SCD mRNA in both MDA-MB-231 and MCF-7 cells. However, the cis-9,trans-11 and trans-10,cis-12 CLA isomers significantly decreased SCD protein levels and SCD activity in MDA-MB-231 cells. In MCF-7 cells, both isomers did not affect protein levels, but they inhibited SCD activity. These results suggest that in MDA-MB-231 cells the cis-9,trans-11 and trans-10,cis-12 CLA isomers regulate human SCD by reducing SCD protein levels, while in MCF-7 cells both isomers have a direct inhibitory effect on SCD enzyme activity.
An electrochemical system consisted of Gluconobacter oxydans as a microorganism and 2-hydroxy-1,4-naphthoquinone (HNQ) as a mediator has been setup to examine the effect of initial carbon sources on the detection of glucose. Catalytic current due to the oxidation of glucose was observed only when both G. oxydans and HNQ were present. From amperometric measurements, it was found that the sensitivity strongly depended on the initial carbon sources. The sensitivity was highest for the cells cultured in a fructose-containing medium and decreased in the order, mannitol > sucrose > glucose > galactose > glycerol. The difference in sensitivity was explained by considering the current rising pattern at an initial stage of a microbial fuel cell constructed with the same components. The rising time, not the fuel cell efficiency, could directly be related to the sensitivity order. A sensor where G. oxydans was confined at the vicinity of the electrode by the semipermeable membrane was constructed. A linear response over a millimolar range of glucose concentration was observed with a cell grown in galactose-containing medium. This work demonstrates that the initial carbon source play an important role on glucose sensoring and should be considered in a real application.
Conjugated linoleic acid (CLA) has shown a wide range of biologically beneficial effects; reduction of incidence and severity of animal carcinogenesis, reduction of the adverse effects of immune stimulation, reduction of severity of atherosclerosis, growth promotion in young rats, and modulation of stearoyl-CoA desaturase (SCD). One of the most interesting aspects of CLA is its ability to reduce body fat while enhancing lean body mass which is associated with the trans-10,cis-12 isomer of CLA. The effects of CLA are unique characteristics that have not been observed with other polyunsaturated fatty acids. In this review, we will focus on the effects of CLA on immune responses, body compositional changes and stearoyl-CoA desaturase.