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Biomedical subjects

Hyun-Chul Kim

Publications and source records attributed to Hyun-Chul Kim.

15 recordsLinked to original sources

Characterization of aquatic humic substances to DBPs formation in advanced treatment processes for conventionally treated water.

An advanced water treatment demonstration plant consisted of ozone/granular activated carbon processes was operated to study feasibility of the processes. Natural organic matter (NOM) from raw and process waters at the demonstration plant was isolated into humic and non-humic fractions by physicochemical fractionation method to investigate characteristics of humic fraction (i.e., humic substances, HS) as a predominant haloform reactant. Ozone did not significantly oxidize the carboxylic fraction (from 39.1 to 35.9%), while GAC removed some of the carboxylic fraction (from 35.9 to 29.1%). Formation potential of trihalomethanes (THMs) as compared to haloacetic acids formation potential (HAAFP) was highly influenced by HS. Higher yields of THMs resulted from chlorination of HS with a higher phenolic content and phenolic fraction in the HS gradually decreased from 60.5% to 15.8% through the water treatment. The structural and functional changes of HS were identified by elemental, Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance ((1)H NMR) analyses, and these results were mutually consistent. The functional distribution data obtained by using A-21 resin could be used to support the interpretation of data obtained from the spectroscopic analyses. Decreases in ratio of UV absorbance at 253 nm and 203 nm (A(253)/A(203)) and DBPFPs/DOC showed consistent trends, therefore, A(253)/A(203) ratio may be a good indicator for the disinfection by-product formation potentials (DBPFPs).

Chlorine↗

The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis.

Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-beta1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-beta1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta1 siRNAs reduced the expression of TGF-beta1 in the livers of CCl(4) injection compared with those of control group, and the expression of type I collagen and alpha-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta1 siRNAs inhibit TGF-beta1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human.

Actins↗

A new monoterpene glycoside and antibacterial monoterpene glycosides from Paeonia suffruticosa.

Antibacterial activity-guided fractionation of the CHCI3-MeOH (1:1) extract of Paeonia suffruticosa root bark furnished three monoterpene glycosides, 6-O-vanillyoxypaeoniflorin (1), mudanpioside-H (2), and galloyl-oxypaeoniflorin (3). Of the isolated compounds, compound 1 is a new compound. All isolated compounds showed broad, but moderate, antibacterial activity with minimum inhibitory concentration (MIC) values in the range of 100 to 500 microg/mL against eighteen pathogenic microorganisms of concern for public health or zoonosis.

Anti-Bacterial Agents↗

Bayesian Gaussian process classification with the EM-EP algorithm.

Gaussian process classifiers (GPCs) are Bayesian probabilistic kernel classifiers. In GPCs, the probability of belonging to a certain class at an input location is monotonically related to the value of some latent function at that location. Starting from a Gaussian process prior over this latent function, data are used to infer both the posterior over the latent function and the values of hyperparameters to determine various aspects of the function. Recently, the expectation propagation (EP) approach has been proposed to infer the posterior over the latent function. Based on this work, we present an approximate EM algorithm, the EM-EP algorithm, to learn both the latent function and the hyperparameters. This algorithm is found to converge in practice and provides an efficient Bayesian framework for learning hyperparameters of the kernel. A multiclass extension of the EM-EP algorithm for GPCs is also derived. In the experimental results, the EM-EP algorithms are as good or better than other methods for GPCs or Support Vector Machines (SVMs) with cross-validation.

Algorithms↗

The inhibitory effect of siRNAs on the high glucose-induced overexpression of TGF-beta1 in mesangial cells.

Diabetic nephropathy is characterized by an expansion of the glomerular mesangium, caused by mesangial cell proliferation and an excessive accumulation of extracellar matrix (ECM) proteins, which eventually leading to glomerulosclerosis. TGF-beta1 was found to play an important role in the accumulation of ECM in the kidney. In this study, TGF-beta1 RNA interference was used as an effective therapeutic strategy. The inhibitory effect of TGF-beta1 small interfering RNAs (siRNAs) on the high glucose-induced overexpression of TGF-beta1 in rat mesangial ceys (RMCs). A high levels of glucose induces TGF-beta1 mRNA and protein, and TGF-beta1 siRNAs reduce the ability of high glucose to stimulate their expression. We also examined the inhibitory effect of TGF-beta1 siRNAs on the expression of plasminogen activator inhibitor (PAI)-1 and Collagen Type I which are down-regulators of TGF-beta1. The expression of TGF-beta1, PAI-1 and Collagen Type I was increased in RMCs that were stimulated by 30 mM glucose. TGF-beta1 siRNAs reduces high glucose-induced TGF-beta1, PAI-1, and Collagen Type I mRNA and protein expression in a dose-dependent manner. In conclusion, the present study demonstrates that TGF-beta1 siRNAs effectively inhibits TGF-beta1 mRNA and protein expression in RMCs. These suggest that TGF-beta1 siRNAs through RNAi may be a useful tool for developing new therapeutic applications for the treatment of diabetic nephropathy.

Animals↗

Characterization of natural organic matter in conventional water treatment processes for selection of treatment processes focused on DBPs control.

Natural organic matter (NOM) from raw and process waters at a conventional water treatment plant was isolated into hydrophobic and hydrophilic fractions by physicochemical fractionation methods to investigate its characteristics. Formation potential of trihalomethanes (THMs) was highly influenced by the hydrophobic fraction, whereas haloacetic acids formation potential (HAAFP) depended more on the hydrophilic fraction. However the hydrophobic fraction was removed more than the hydrophilic fraction through conventional water treatment. Therefore residual hydrophilic NOM after conventional treatment needs to be removed to reduce HAAFP. Feasible additional processes are required to be evaluated by comparing preferential removal efficiency of hydrophilic NOM through pilot tests. The structural and chemical characteristics of hydrophobic NOM (i.e., humic substances (HS)) were further investigated to know how they are influenced by conventional treatment. The phenolic fraction in the hydrophobic NOM was mainly removed compared to the carboxylic fraction through water treatment, and a higher formation potential of THMs resulted from NOM with a higher phenolic content. The Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance ((1)H-NMR) employed for characterization of NOM through water treatment were insightful revealing that their results were quite close to each other. Decreases of ratio of UV absorbance at 253 and 203 nm, respectively (A(253)/A(203) ratio) and trihalomethane formation potential/dissolved organic carbon (THMFP/DOC) showed consistent trends; therefore, the A(253)/A(203) ratio may be a good indicator of tendency for the formation potential of disinfection by-products (DBPs).

Carbon↗

Hepatoprotective constituents of Cudrania tricuspidata.

Phytochemical investigation of the MeOH extract of the root barks of Cudrania tricuspidata Bureau (Moraceae), as guided by hepatoprotective activity in vitro, furnished four isoprenylated xanthones, cudratricusxanthone A (1), cudraxanthone L (2), cudratricusxanthone E (3), and macluraxanthone B (4). All of these compounds showed the significant hepatoprotective effect on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. Compounds 1, 2, and 4 also exhibited the significant hepatoprotective effect on nitrofurantoin-induced cytotoxicity in human liver-derived Hep G2 cells.

Carcinoma, Hepatocellular↗

Free radical scavenging and hepatoprotective constituents from the leaves of Juglans sinensis.

In the course of searching for hepatoprotective agents from natural products, six compounds were isolated from the MeOH extract of the leaves of Juglans sinensis, as guided by their DPPH free radical scavenging activity. The structures were determined as juglanoside B (1), quercetin 3-O-alpha-L-arabinofuranoside (avicularin, 2), quercetin 3-O-alpha-L-arabinopyranoside (guaijaverin, 3), quercetin 3-O-alpha-L-rhamnopyranoside (quercitrin, 4), (+)-catechin (5) and quercetin 3-O-beta-D-galactopyranoside (hyperin, 6). Compounds 2-6 showed significant DPPH free radical scavenging effects. An evaluation for the hepatoprotective activity of the isolated compounds on drug-induced cytotoxicity was conducted, and compounds 1, 2, and 5 showed protective effects against nitrofurantoin-induced cytotoxicity, and compound 5 also exhibited a moderate protective effect on amiodarone-induced cytotoxicity in Hep G2 cells.

Cell Line↗

A case of pneumonia caused by Ewingella americana in a patient with chronic renal failure.

Though the pathogenic significance and the reservoir of Ewingella americana have not been clarified, this organism has caused several pathogenic infections, especially in immunocompromised patients. We report a pneumonia in a patient with chronic renal failure, who had chronic rejection of transplanted kidney. E. americana was identified to be the pathogen of pneumonia with clinical symptoms and signs and radiological examination. As soon as he was treated with ceftriaxone and isepamicin, clinical improvement was followed with no further growth of E. americana or other pathogenic isolates from sputum culture. This suggests to be the case of pneumonia caused by E. americana for the first time in the Korean literature.

Adult↗

Sp1-decoy oligodeoxynucleotide inhibits high glucose-induced mesangial cell proliferation.

Mesangial expansion caused by cell proliferation and glomerular extracellular matrix accumulation is one of the earliest renal abnormalities observed at the onset of hyperglycemia in diabetes mellitus. Transcription factor Sp1 is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation, and is assumed to play an essential role in mesangial expansion. We have generated a phosphorothioated double-stranded Sp1-decoy oligodeoxynucleotide that effectively blocks Sp1 binding to the promoter region for transcriptional regulation of transforming growth factor-beta1 and plasminogen activator inhibitor-1. The Sp1-decoy oligodeoxynucleotide suppressed transcription of these cytokines and proliferation of primary rat mesangial cells in response to high glucose. These results suggest that the Sp1-decoy oligodeoxynucleotide could be a powerful tool in preventing the pathogenesis of renal hypertrophy.

Animals↗

Inhibition of erythropoietin activity by cyanate.

OBJECTIVE: Increased urea concentration is a measure of advanced renal failure and the adequacy of renal replacement therapy in end-stage renal disease (ESRD). Altered biologic activity due to changes in protein structure occurs when cyanate, formed spontaneously from urea, reacts with proteins. Carbamylation results in impaired erythropoietin (EPO) activity when high concentrations of cyanate react with EPO. In this study, the activity of carbamylated EPO (C-EPO), formed at a cyanate concentration which may occur in vivo, was studied in Sprague-Dawley rats. MATERIAL AND METHODS: The extent of carbamylation, causing loss of free amino groups, was monitored using trinitrobenzenesulfonic acid. Erythrocyte, hemoglobin, hematocrit and leukocyte levels were measured after either EPO, incubated EPO, C-EPO, physiologic saline or cyanate (1.5 microM; 0.2 ml) were injected subcutaneous twice weekly for 3 weeks in rats. RESULTS: In vitro carbamylation of EPO was time- and concentration-dependent. C-EPO concentration increased as the duration of exposure to cyanate increased from 6 to 72 h, or as cyanate concentration increased from 15 nM to 1.5 microM. Injections of EPO caused significant increases in vivo in all erythropoietic measures. In contrast, injections of C-EPO, physiologic saline or 1.5 microM cyanate caused no change from baseline. CONCLUSIONS: These results demonstrated diminished biologic activity in healthy rats by C-EPO formed in vitro at cyanate concentrations that may be found in vivo. C-EPO and high urea-derived cyanate levels may contribute to suboptimal erythropoietic responses to EPO therapy for chronic renal failure and ESRD, and may provide another measurement indicating inadequate dialysis.

Animals↗

Inhibitory effects of novel E2F decoy oligodeoxynucleotides on mesangial cell proliferation by coexpression of E2F/DP.

Proliferation of glomerular mesangial cells (MCs) is an important feature of several forms of glomerulonephritis. The transcription factor E2F coordinately regulates expression of genes required for cell proliferation, thereby mediating cell growth control. Here we investigated the role of E2F1 and E2F4 expression, with or without co-expression of DP1 or DP2, on cell proliferation in transiently transfected primary rat MCs. In transfected cells, cell proliferation induced by over-expression of E2F was significantly enhanced by co-expression of DP proteins. Previous studies showed that the transfection of decoy oligodeoxynucleotides (ODNs) corresponding to E2F binding sites inhibits cell proliferation. Here we have developed a Ring-E2F (R-E2F) decoy ODN with a circular dumbbell structure and compared its effects with those of a phosphorothioated E2F decoy (PS-E2F decoy) ODN. The R-E2F decoy ODN showed enhanced stability in the presence of nucleases and sera, and inhibited E2F/DP-dependent promoter activity of cell cycle genes more effectively than the PS-E2F decoy ODN. Transfection of R-E2F decoy ODN resulted in strong inhibition of cell cycle gene expression and MC proliferation. Our data suggest that E2F/DP complexes play a critical role in the MC proliferation and that the R-E2F decoy ODN may be a powerful tool for inhibiting cell proliferation.

Animals↗

Modulation of Sp1-dependent transcription by a cis-acting E2F element in dhfr promoter.

The dihydrofolate reductase (dhfr) promoter contains cis-acting elements for Sp1 and E2F. Here we examined the cooperative regulation of dhfr gene transcription by Sp1 and E2F in human osteosarcoma cells, U2OS. Trichostatin A, an inhibitor of histone deacetylases, markedly stimulated dhfr promoter activity, a response that was enhanced by the deletion of an E2F element. In contrast, deletion of the dhfr Sp1 binding sites completely abolished promoter stimulation by trichostatin A. Cotransfection assays showed that activation of dhfr transcription by expression of E2F1/DP1 requires the reiterated Sp1 elements, whereas activation by Sp1 was enhanced by the deletion of the E2F element. Expression of HDAC1 with Sp1 suppressed promoter activity and suppression was not alleviated by coexpression of E2F1/DP1. These results suggest that HDAC1 acts through Sp1 to repress dhfr promoter activity, and that the E2F element modulates the activity of Sp1 at the dhfr promoter through a cis-acting mechanism.

Base Sequence↗

Structural basis for the NAD-dependent deacetylase mechanism of Sir2.

The NAD-dependent histone/protein deacetylase activity of Sir2 (silent information regulator 2) accounts for its diverse biological roles including gene silencing, DNA damage repair, cell cycle regulation, and life span extension. We provide crystallographic evidence that 2'-O-acetyl ADP-ribose is the reaction product that is formed at the active site of Sir2 from the 2.6-A co-crystal structure of 2'-O-acetyl-ADP-ribose and Sir2 from Archaeoglobus fulgidus. In addition, we show that His-116 and Phe-159 play critical roles in the catalysis and substrate recognition. The conserved Ser-24 and Asp-101 contribute to the stability for NAD binding rather than being directly involved in the catalysis. The crystal structures of wild type and mutant derivatives of Sir2, in conjunction with biochemical analyses of the mutants, provide novel insights into the reaction mechanism of Sir2-mediated deacetylation.

Adenosine Diphosphate Ribose↗