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Biomedical subjects

C S Cho

Publications and source records attributed to C S Cho.

At least 19 recordsLinked to original sources
PubMed2006

Down-regulation of PPARgamma2-induced adipogenesis by PEGylated conjugated linoleic acid as the pro-drug: Attenuation of lipid accumulation and reduction of apoptosis.

This study is designed to evaluate whether the PEGylated conjugated linoleic acid (PCLA) as the pro-drug can have favorable stability, bioavailability, and anti-adipogenic activity in 3T3-L1 cells for anti-obesity when compared with conjugated linoleic acid (CLA) itself. The CLA was simply coupled to poly(ethylene glycol) (PEG) at the melting state without solvents or catalysts through ester linkages between the carboxylic group of CLA and the hydroxyl group of PEG. To confirm of PCLA as the pro-drug, CLA release from PCLA was investigated by using high-performance liquid chromatographic (HPLC), showing that CLA release from PCLA was almost 90% in a nearly continuous fashion over the next 75h. Apoptosis was promoted by both CLA- and PCLA-treatments with increasing concentrations. However, the level of cell apoptosis induced by PCLA was lower than that induced by CLA owing to the biocompatible and hydrophilic properties of PEG. Moreover, the PCLA decreased glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 cells by acting upon major adipocyte marker proteins such as PPARgamma2, C/EBPalpha, and aP2 modulators. Furthermore, either CLA or PCLA stimulated basal, but not isoproterenol-sensitive, lipolysis in our cell model, suggesting that both CLA and PCLA may stimulate lipolysis via hormone sensitive lipase (HSL)-independent mechanisms. These results suggest that the PCLA may prove to be a stable pro-drug to control the deposition of fat in the human body, and that the anti-adipogenic effect of the PCLA on 3T3-L1 cells will offer a challenging approach for anti-obesity.

3T3-L1 Cells↗
PubMed2006

Regulation of adipocyte differentiation by PEGylated all-trans retinoic acid: reduced cytotoxicity and attenuated lipid accumulation.

Obesity is major risk factor for many disorders, including diabetes, hypertension and heart disease. Unfortunately, there is a dearth of therapeutic agents available to clinicians for the treatment of obesity. The principal aim of this study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have favorable stability and biological activity in 3T3-L1 preadipocytes as an antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis, including survival of adipocytes and differentiation to mature adipocytes. The results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200 nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in addition, increased as the level of RA increased from 10 to 20 microM, whereas PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA-NP has potential as an antiobesity drug carrier due to its small particle size and PEGylated core-shell structure. In addition, our results suggest that PRA inhibits the process of adipogenesis and may be developed to treat obesity. Based on these results, PRA is suitable for adipocyte studies, and an enhanced effect of PRA with adipocyte differentiation offers a challenging approach for pharmaceutical applications.

3T3 Cells↗
PubMed2006

Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation.

This study investigated whether or not there is a correlation between the changes in the serum levels of vascular endothelial growth factor (VEGF) and the outcome of allogeneic stem cell transplantation (allo-SCT). Eighty-five patients undergoing allo-SCT were prospectively studied. The serum VEGF levels were measured on days 0, +7 and +14 after transplantation. The VEGF levels decreased significantly on day +7 and recovered on day +14. The highest levels from day +7 through day +14 were categorized by cluster analysis, which were then correlated with the nonrelapse mortality (NRM). There was a significant correlation between a low VEGF level and the occurrence of severe acute graft-versus-host disease (GVHD) including grade III-IV (P=0.029). The 1-year probability of NRM in patients with a low VEGF level was 22.5% compared with 3.5% for those with a high VEGF level (P=0.024). Multivariate analysis revealed clinically defined infections (P=0.011), advanced disease (P=0.014) and a low VEGF cluster (P=0.05) to be significantly associated with the occurrence of NRM in the cohort. In conclusion, low VEGF levels after allo-SCT are associated with NRM with an exacerbated severity of acute GVHD. VEGF monitoring after a transplant might identify those patients at risk of severe transplant-related mortality.

Acute Disease↗
PubMed2005

Galactose-carrying polymers as extracellular matrices for liver tissue engineering.

Extracellular matrix (ECM) plays important roles in tissue engineering because cellular growth and differentiation, in the two-dimensional cell culture as well as in the three-dimensional space of the developing organism, require ECM with which the cells can interact. Especially, the bioartificial liver-assist device or regeneration of the liver-tissue substitutes for liver tissue engineering requires a suitable ECM for hepatocyte culture because hepatocytes are anchorage-dependent cells and are highly sensitive to the ECM milieu for the maintenance of their viability and differentiated functions. Galactose-carrying synthetic ECMs derived from synthetic polymers and natural polymers bind hepatocytes through a receptor-mediated mechanism, resulting in enhanced hepatocyte functions. Attachment and functions of hepatocytes were affected by physico-chemical properties including ECM geometry as well as the type, density and orientation of galactose. Also, cellular environment, medium composition and dynamic culture system influenced liver-specific functions of hepatocytes beside ECM.

Animals↗
PubMed2005

Adsorption behaviors of poly(N-p-vinylbenzyl-4-o-beta-d-galactopyranosyl-[1-->4]-d-gluconamide) by quartz-crystal microbalance.

Adsorption behaviors of amphiphilic poly(N-p-vinylbenzyl-4-o-beta-d-galactopyranosyl-[1-->4]-d-gluconamide) (PVLA) on the polystyrene (PS) surface was studied using 27 MHz quartz-crystal microbalance (QCM). The amount of adsorbed PVLA on PS surface was increased with an increase of PVLA concentration as a Langmuir-type in a monolayer. The saturated mass change (DeltaM(max)) and association constant (K(a)) of PVLA on PS surface were 498.6 ng/cm(2) and 1.93 x 10(7)M(-1), respectively. The adsorbed PVLA on PS surface was specifically recognized by Allo A lectin due to specific interaction between galactose moieties in the PVLA and Allo A. The hydrophobic interaction between hydrophobic main chain of PVLA and hydrophobic surface of PS was reduced in the presence of urea and the diameter of PVLA aqueous solution was decreased with an increase of urea concentration.

Adsorption↗
PubMed2005

Role of E-cadherin molecules in spheroid formation of hepatocytes adhered on galactose-carrying polymer as an artificial asialoglycoprotein model.

The role of E-cadherin in the spheroid formation of hepatocytes adhered on the poly(N-p-vinylbenzyl-D-lactonamide) (PVLA) as a model ligand for asialoglycoprotein receptors (ASGP-R) of hepatocytes was studied. Expression of E-cadherin was increased in round hepatocytes adhered on a high-coating density of PVLA (100 microg/ml), and also in flat ones adhered on a low-coating density of PVLA (1 microg/ml) in the presence of epidermal growth factor (EGF). Hepatocyte spheroids formed on the high-coating density of PVLA in the presence of EGF after 48 h were inhibited by an anti-E-cadherin monoclonal antibody (ECCD-1). From immunofluorescence and confocal laser microscopy, E-cadherin was localized in the intercellular boundaries and concentrated at the inside surface of aggregated cells. As a result, E-cadherin could play an important role in hepatocyte assembly.

Asialoglycoproteins↗
PubMed2005

Release of ciprofloxacin from chondroitin 6-sulfate-graft-poloxamer hydrogel in vitro for ophthalmic drug delivery.

The system was designed to use Poloxamer as a vehicle for ophthalmic drug delivery using in situ gel formation property. To enhance the wound healing and cell adhesion as well as transparency of Poloxamer hydrogel, chondroitin 6-sulfate (C6S) was introduced into Poloxamer. For this purpose, mono amine-terminated Poloxamer (MATP), which was end-capped with ethylene amine group only in one side of terminal hydroxyl groups of Poloxamer, was synthesized. Subsequently, C6S-graft-Poloxamer copolymer (C6S-g-Poloxamer) was prepared by reaction between the amine groups of MATP and carboxyl groups of C6S in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carboimide (EDC). The coupling of MATP with C6S was clarified by 1H-NMR and FT-IR spectroscopy. The gelation temperature of graft copolymers was determined by measuring the temperature at which immobility of the meniscus in each solution was first noted. Release behavior of ciprofloxacin from C6S-g-Poloxamer hydrogel in vitro was investigated as a function of C6S content in the graft copolymer by a spectrophotometric assay at 287 nm using an UV spectrophotometer. Differences in the adhesion and morphology of human lens cell between Poloxamer- and C6S-g-Poloxamer-coated surfaces were also investigated. The gelation temperatures of C6S-g-Poloxamer copolymers were lowered with increasing of the concentration of the copolymer and decreasing of C6S content. The release of ciprofloxacin from the graft copolymer was sustained compared with Poloxamer itself and decreased with increasing the content of C6S in the copolymer due to the in situ gel formation of the copolymer and viscous properties of C6S. Human lens cells (B3) adhered to C6S-g-Poloxamer-coated surface were observed as transformed shapes after 2 days. The bioadhesive and thermally gelling of these graft copolymers will be expected to be an excellent drug carrier for the prolonged delivery to surface of the eye.

Cells, Cultured↗
PubMed2004

Delivery of all trans-retinoic acid (RA) to hepatocyte cell line from RA/galactosyl alpha-cyclodextrin inclusion complex.

All trans-retinoic acid (RA) plays a role in regulation of P450RAI gene expression. In this study, hepatocyte cell line (HepG2) was used to study an effect of RA released from RA/galactosyl alpha-cyclodextrin (GCD) inclusion complex on regulation of P450RAI gene expression. A delivery system composed of RA/GCD inclusion complex was applied because RA is poorly water soluble, and organic solvents used to dissolve it often interfere with cytotoxicity. Solubility of RA in water was increased by forming complex with GCD. Inclusion complex between GCD and RA was checked by (1)H-nuclear magnetic resonance, Fourier transformation infrared (FT-IR) spectroscopy and X-ray diffraction (XRD). The chemical shifts of the interior and exterior GCD protons in the presence of RA indicated that the RA was included within the GCD macrocycle cavity. The carbonyl band of RA and crystalline peak of RA in RA/GCD inclusion complex disappeared from FT-IR and XRD measurements, respectively, indication of inclusion complex between RA and GCD. From the observation of fluorescence micrograph of hepatocytes and flow cytometry measurement of HepG2, the internalization of fluorescein isothiocyanate-GCD by the hepatocyte occurred. Gene expression of P450RAI in HepG2 by delivery of RA from RA/GCD complex was observed.

Cell Line↗
PubMed2003

Release of ciprofloxacin from poloxamer-graft-hyaluronic acid hydrogels in vitro.

Recently, in situ gel formation has extensively been studied to enhance ocular bioavailability and duration of the drug activity. In this study, we report grafting of poloxamer onto the hyaluronic acid for application of tissue engineering oriented ophthalmic drug delivery system. Graft copolymers were prepared by coupling mono amine-terminated poloxamer (MATP) with hyaluronic acid (HA) backbone using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxylsuccinimide (NHS) as coupling agents. The coupling of MATP with HA was clarified by 1H NMR and FT-IR spectroscopy. The gelation temperature of graft copolymers was dependent on the content of HA and the concentration of poloxamer. From drug release studies in vitro, ciprofloxacin was sustainedly released from the poloxamer-g-hyaluronic acid hydrogel due to the in situ gel formation of the copolymer and viscous properties of HA.

Ciprofloxacin↗
PubMed2003

Primer Design Assistant (PDA): A web-based primer design tool.

Primer Design Assistant (PDA) is a web interface primer design service combined with thermodynamic theory to evaluate the fitness of primers. It runs in a Linux-Apache-MySQL-PHP structure on a PC equipped with dual CPU (Intel Pentium III 1.4 GHz) and 512 Mb of RAM. A succinct user interface of PDA is accomplished by built-in parameters setting. Advanced options on 5' GC content, 3' GC content, dimer check and hairpin check are available. The option of covered region constrains the PCR product to cover a user-defined segment. PDA accepts single sequence query or multiple ones in FASTA format. It produces optimal and homogenous primer pairs that meet the need in experimental design with large-scaled PCR amplifications. Considering the system loading, the size of a submitted sequence is limited to 10 kb and the total sequence number in a query is limited to 20. The authors may be contacted regarding other requirements for primer design. The web application can be found at http://dbb.nhri.org.tw/primer/.

DNA Primers↗
PubMed2003

Visualization of transfection of hepatocytes by galactosylated chitosan-graft-poly(ethylene glycol)/DNA complexes by confocal laser scanning microscopy.

Dual-labeled galactosylated chitosan-graft-poly(ethylene glycol) (PEG) (GCP)/DNA complexes were prepared and their hepatocyte-specific delivery and cellular distribution were investigated by confocal laser scanning microscopy (CLSM). The complexes were transfected into hepatocyte through specific interaction of galactose moiety of the GCP and asialoglycoprotein receptors (ASGPR) of the hepatocytes. The GCP/DNA complexes taken up by the hepatocytes were rapidly released into the cytoplasm, but nuclear trafficking of the released complexes was slow and rate-limiting process. The more efficient transfection of the complex occurred in the human-derived HepG2 cells than in primary hepatocytes.

Animals↗
PubMed2003

Galactosylated chitosan (GC)-graft-poly(vinyl pyrrolidone) (PVP) as hepatocyte-targeting DNA carrier. Preparation and physicochemical characterization of GC-graft-PVP/DNA complex (1).

Galactosylated chitosan was conjugated with poly(vinyl pyrrolidone) (PVP) as a hydrophilic group. The complex formation of GC-graft-PVP (GCPVP)/DNA complexes was confirmed by agarose gel electrophoresis. The morphology of the complex observed by atomic force microscopy had a compact and spherical shape, around 40 nm particle sizes at a charge ratio of 3. The binding strength of GCPVP 10K/DNA complex measured by ethidium bromide binding assay was superior to that of the GCPVP 50K/DNA one, probably attributable to its higher flexibility due to the smaller size, whereas the DNase I protection of GCPVP 10K/DNA complex was inferior to that of the GCPVP 50K/DNA one. This indicated that effective complex formation required both higher binding strength and minimal molecular weight of polycation enough to induce the condensation of DNA. The DNA-binding property of GCPVP mainly depended on the molecular weight of chitosan and composition of PVP.

Animals↗
PubMed2003

Acquired activated protein C resistance, high tissue factor expression, and hyper-homocysteinemia in systemic lupus erythematosus.

Activated protein C resistance (APCR), high tissue factor (TF) expression, and hyper-homocysteinemia are associated with thromboembolic diseases. Thromboembolism is a frequent complication of systemic lupus erythematosus (SLE). In this study, we evaluated the prevalence of APCR, high TF, and homocysteine with correlation of the thrombotic tendency in SLE. Ninety-four SLE patients and 28 normal controls were included. APC ratio and TF antigen were measured using commercial kits. Plasma homocysteine level was measured using HPLC. The prevalence of APCR, high TF antigen level, and hyper-homocysteinemia in our SLE patients were 21.3%, 66.0%, and 23.4%, respectively. The median plasma level of TF antigen in SLE patients was 145.23 pg/mL (range, 31.00-778.50 pg/mL), which was significantly higher than the control value of 39.83 pg/mL (range, 1.55-168.50 pg/mL). The median APC ratio in SLE patients was 2.76 (range, 1.48-13.47), which was significantly lower than the control value of 3.59 (range, 0.26-5.66). The plasma level of homocysteine was not significantly different from that of control. A significant association was observed between the presence of APCR (OR = 8.59, P < 0.0001) but not with the presence of high plasma TF antigen level (OR = 1.24, P = 0.67) and thrombotic complications in SLE patients. In conclusion, APCR and high plasma TF levels are common in SLE, but a significant association was observed only between the presence of APCR and thrombosis in SLE patients.

Activated Protein C Resistance↗
PubMed2003

Morphology and metabolism of Ba-alginate-encapsulated hepatocytes with galactosylated chitosan and poly(vinyl alcohol) as extracellular matrices.

Lactobionic acid, bearing a beta-galactose group, was coupled with chitosan to provide synthetic extracellular matrices together with poly(vinyl alcohol) (PVA). The hepatocytes encapsulated in Ba-alginate capsules with galactosylated chitosan (GC) and PVA as extracellular matrices showed aggregation morphologies as the incubation time increased. Ba-alginate-encapsulated hepatocytes with GC exhibited a higher metabolic function in albumin secretion compared to those entrapped in Ba-alginate beads and monolayer-cultured on a collagen-immobilized polystyrene dish. The ammonia removal ability of monolayer-cultured hepatocytes decreased with increasing culture time and disappeared completely after three days. In contrast, the ammonia removal ability of encapsulated and entrapped hepatocytes increased with increasing incubation time in the first seven and five days, respectively. Thereafter, the entrapped hepatocytes lost ammonia removal ability quickly while the encapsulated hepatocytes kept a relatively high ammonia removal ability up to 13 days. The trace amount of GC in the core matrices enabled encapsulated cells to enhance their ammonia removal and albumin secretion ability. The results obtained with 3-(3,4-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) also showed that the capsules incorporated with GC can provide a better microenvironment for cell aggregation along with nutrition and metabolite transfer. Due to the nature of the liquid core, the encapsulated hepatocytes showed very good mobility. This facilitated cell-cell interaction and cell-matrix interaction.

Alginates↗
PubMed2001

Receptor-mediated delivery of all trans-retinoic acid to hepatocyte using poly(L-lactic acid) nanoparticles coated with galactose-carrying polystyrene.

All trans-retinoic acid (RA)-loaded poly(L-lactic acid) (PLA) nanoparticles coated with galactose-carrying polymer, as hepatocyte-specific targeting material using galactose ligands as recognition signals to asialoglycoprotein receptors were prepared by the diafiltration method. Effects of released RA from its loaded nanoparticles on morphology and DNA synthesis of hepatocytes were studied. Receptor-mediated endocytosis of the nanoparticles was checked by fluorescence and confocal laser microscopy. It was found that the shapes of most hepatocytes attached onto polystyrene dish precoated with collagen solution were flat and spreading at low concentration of RA for the RA-loaded nanoparticles, whereas their shapes were round at even low concentration of RA when RA was mixed with the nanoparticles. From the fluorescence and confocal laser microscopic studies, it was suggested that the nanoparticles coated with galactose-carrying polymers were internalized by the hepatocytes through the receptor-mediated mechanism. The RA-loaded nanoparticles were more potent stimulators of hepatocyte DNA synthesis than the free RA system in the presence of epidermal growth factor (EGF) owing to the controlled release of RA from the RA-loaded nanoparticles.

Animals↗
PubMed2001

Galactosylated chitosan-graft-poly(ethylene glycol) as hepatocyte-targeting DNA carrier.

Lactobionic acid bearing galactose group was coupled with chitosan for liver specificity, and poly(ethylene glycol) (PEG) was grafted to galactosylated chitosan (GC) for stability in water and enhanced cell permeability. Complex formation of galactosylated chitosan-graft-PEG (GCP)/DNA complexes was confirmed by agarose gel electrophoresis. Compared to GC/DNA complex, the stability of GCP/DNA complex could be enhanced. Particle sizes of GCP/DNA complexes decreased as the charge ratio of GCP to DNA increased and had a minimum value around 27 nm at the charge ratio of 5. Conformational change of DNA did not occur after complex formation with GCP compared to conformation of DNA itself. GCP/DNA complexes were only transfected into Hep G2 having asialoglycoprotein receptors (ASGR), indicative of specific interaction of ASGR on cells and galactose ligands on GCP.

Chitin↗
PubMed2001

Regulation of asialoglycoprotein receptor expression in the proliferative state of hepatocytes.

It is necessary to proliferate hepatocytes and to increase the number of hepatocytes for development of bioartificial liver (BAL) and reconstitutive therapy. But usually the cell has a precarious balance between proliferation and differentiation: as the cell proliferation increases, functional differentiation decreases. Therefore, it is desirable for the hepatocytes to be functional by differentiation as a material for such clinical use not to be proliferative. In this study, we investigated the background of hepatocyte proliferation for the springboard of control between proliferation and differentiation of hepatocytes, and we focused attention to the asialoglycoprotein receptors (ASGP-R) of the hepatocytes. Partially hepatectomized (PH) rats were used as a model animal. When the isolated hepatocytes were plated onto the artificial extracellular matrix of poly-(N-p-vinylbenzyl-O-beta-d-galactopyranosyl-d-gluconamide) (PVLA) having galactose residues as cell-specific ligand, the rate of adhesion was decreased along with liver regeneration. Interestingly, the release of the ASGP-R from hepatocytes in serum after PH in vivo and reduction of ASGP-R of the hepatocytes in the proliferative state occurred due to cell growth in vitro. It is suggested that the ASGP-R on the hepatocyte surface during the differentiation was released in the proliferative state.

Animals↗