Biomedical subjects

Jong-Gu Park

Publications and source records attributed to Jong-Gu Park.

16 recordsLinked to original sources

PubMed2006

A novel comonomer-free light-cured glass-ionomer cement for reduced cytotoxicity and enhanced mechanical strength.

OBJECTIVE: The objective of this study was to develop a novel comonomer-free light-cured glass-ionomer system based on the 4-arm star-shape poly(acrylic acid). The mechanical strengths and in vitro cytotoxicity of the formed system were evaluated and compared with those of several representative commercial glass-ionomer cements. MATERIALS AND METHODS: The 4-arm poly(acrylic acid) was synthesized using ATRP and tethered with glycidyl methacrylate (GM). The GM-tethered polymer was formulated with water, photo-initiators, and Fuji II LC filler. Fuji II, Fuji II LC and Vitremer were used for comparison. Compressive strength (CS) and MTT assay were used as tools to evaluate the mechanical strengths and in vitro cytotoxicity of the cements, respectively. RESULTS: The experimental cement exhibited significantly high compressive, diametral tensile and flexural strengths as compared to commercial glass-ionomer cements, Fuji II, Fuji II LC and Vitremer. The effects of polymer/water (P/W) ratio, GM-grafting ratio, glass powder/polymer liquid (P/L) ratio and aging in water on strengths were significant. Similar to conventional glass-ionomer cement Fuji II, the eluates from the experimental cement showed little in vitro cytotoxicity to Balb/c mouse fibroblast cells, as compared to Fuji II LC and Vitremer that contain HEMA as a comonomer. CONCLUSIONS: It appears that this novel comonomer-free light-cured glass-ionomer cement will be a promising dental restorative because it demonstrated significantly improved mechanical strengths and almost no in vitro cytotoxicity as compared to current commercial light-cured glass-ionomer cements.

Acrylic Resins↗

PubMed2006

Novel injectable and in situ curable glycolide/lactide based biodegradable polymer resins and composites.

Novel in situ polymerizable liquid three-arm biodegradable oligomeric polyesters based upon glycolic acid (GA), L-lactic acid (LLA), and their copolymers are synthesized and characterized. Injectable and in situ curable polymer neat resins and their composites formulated with bioabsorbable beta-tricalcium phosphate are prepared at room temperature using photo- and redox-initiation systems, respectively. The cured neat resins show the initial compressive yield strength (YCS, MPa), modulus (M, MPa), ultimate compressive strength (UCS, MPa), and toughness (T, kN mm), ranging from 4.0 to 20.1, 201.5 to 730.2, 82.7 to 310.5, and 1.02 to 3.93. The cured composites show the initial YCS, M, UCS and T, ranging from 27.7 to 56.4, 1440 to 4870, 81.6 to 158.9, and 0.94 to 1.97. Increasing GA/LLA ratio increases all the initial compressive strengths of both neat resins and composites. Increasing filler content increases YCS and M but decreases UCS and T. A diametral tensile strength test shows the same trend as a compressive strength test. There seems to be an optimal flexural strength for the composite at the filler content around 43%. An increasing molar ratio increases curing time but decreases the degree of conversion (DC). An increasing filler content increases curing time but decreases exotherm and DC. During the course of degradation, all the materials show a burst degradation behavior within 24 h, followed by an increase in CS. The poly(glycolic acid) neat resin completely loses its strength at around Day 45. The composites completely lose their strengths at different time intervals, depending on their molar ratio and filler content. The degradation rate is found to be molar ratio and filler-content dependent.

Absorbable Implants↗

PubMed2006

Synthesis and preparation of novel 4-arm star-shape poly(carboxylic acid)s for improved light-cured glass-ionomer cements.

OBJECTIVE: The objective of this study was to synthesize and characterize novel 4-arm star-shape poly(acrylic acid)s (poly(AA)s) via atom-transfer radical polymerization (ATRP) technique, tether in situ light-curable methacrylate functionalities onto the poly(AA) backbone, use these star-shape poly(AA)s to formulate the light-cured glass-ionomer cements (LCGICs), and evaluate the mechanical strengths of the formed cements. MATERIALS AND METHODS: The 4-arm poly(AA)s were synthesized using ATRP and tethered with either 2-isocyanatoethyl methacrylate (IEM) or glycidyl methacrylate (GM). The polymers were formulated with 2-hydroxyethyl methacrylte (HEMA) or methacryloyl beta-alanine (MBA), water, initiators, and Fuji II LC filler. Compressive strength (CS) was used as a tool to evaluate the formed cements. The specimens were conditioned in distilled water at 37 degrees C for 24h prior to testing. RESULTS: The 4-arm poly(AA) showed a lower viscosity as compared to its linear counterpart. Both IEM-tethered and GM-tethered 4-arm poly(AA) constructed LCGICs showed significantly high mechanical strengths. Both types of co-monomer and grafting agent dramatically affected the mechanical strengths. The MBA-containing poly(AA) cements exhibited much higher CS than the HEMA-containing cements. The IEM-tethered poly(AA) cements showed much higher CS and DTS than the GM-tethered cements. CONCLUSIONS: This study developed a novel light-curable 4-arm star-shape poly(AA) system. The system was 13% in CS, 178% in DTS and 123% in FS, compared to Fuji II LC.

Acrylic Resins↗

PubMed2006

Novel amino acid-constructed polyalkenoates for dental glass-ionomer restoratives.

Several methacrylate or acrylate derivatives of natural amino acids were synthesized and characterized. Based upon these derivatives, novel amino acid-constructed polyalkenoic acids were prepared and used to formulate glass-ionomer cements (GICs) with Fuji II glass filler. The effects of type of derivatives, molar ratio, molecular weight, and powder/liquid ratio were investigated. The results show that amino acid-constructed polyalkenoic acids can be formed only from amino acid methacrylate derivatives or by copolymerization of methacrylate with acrylate derivatives. Strong hydrogen bond interactions failed the polymer formation from acrylate derivatives. The cement composed of poly(methacryloyl glutamic acid-co-acryloyl beta-alanine) with the molar ratio of 8:2 demonstrated the best mechanical strengths along with a workable viscosity. By using the powder/liquid ratio of 3.0/1, the experimental cement exhibited a significantly higher FS (27.7 MPa), and nearly the same CS (198.5 MPa) and DTS (11.8 MPa), as compared to Fuji II (18.9 for FS, 189.1 for CS, and 11.4 MPa for DTS). During aging, the cement showed a significant increase in strength over 24 h, followed by a slow increase over 6 months.

Amino Acids↗

PubMed2006

Preparation, formulation and evaluation of novel photo-cured glass ionomers based on co-polymers of (meth)acrylated amino acids.

A novel photo-cured amino-acid-constructed glass-ionomer cement system has been developed. Glutamic acid- and beta-alanine-based methacrylate and acrylate derivatives were synthesized, characterized and used to construct the polyalkenoic acids and formulated with water and Fuji II glass filler to form self-cured cement. Compressive strength (CS) of the cement and viscosity of the liquid were used as tools for evaluation. The effects of molar ratio and molecular weight (MW) were studied. The optimized co-polymer was further modified with glycidyl methacrylate (GM) and formulated with water, acrylic acid and Fuji II LC filler to form photo-cured cement. The effects of MW, GM tethering ratio, polymer liquid ratio and glass filler powder/polymer liquid (P/L) ratio were investigated. CS, flexural strength (FS) and viscosity were used as screening tools to find the optimal formulation. All the specimens were conditioned in distilled water at 37 degrees C for either 24 h or 7 days prior to testing. The results show that amino-acid-constructed polyalkenoic acids can be formed only from amino acid methacrylate derivatives or by co-polymerization of methacrylate with acrylate derivatives. Among the numerous co-polymers synthesized, poly(methacryloyl glutamic acid-co-acryloyl beta-alanine) or poly(MGA-co-ABA) with the molar ratio of 8:2 and MW of 19.5 kg/mol contributed the highest mechanical strengths and lower working viscosity to the cement. For photo-cured system, the effects of GM tethering ratio, polymer content and P/L ratio were significant. It is found that an appropriate ratio balance between these parameters is very important. The effect of molecular weight was not significant. The self-cured experimental cement was 32% higher in FS than Fuji II and the same in CS and DTS as Fuji II. The photo-cured experimental cement was 19%, 47% and 176% higher in CS, DTS and FS than Fuji II LC.

Amino Acids↗

PubMed2006

Leptomycin B, a metabolite of Streptomyces, inhibits the expression of inducible nitric oxide synthase in BV2 microglial cells.

Overexpression of inducible nitric oxide synthase (iNOS) and the resultant overproduction of NO has been implicated in neuronal inflammatory diseases. Leptomycin B (LMB), a metabolite of Streptomyces, has been identified as a specific inhibitor of CRM1 nuclear export receptor. In this study, we evaluated the effect of LMB on lipopolysaccharide (LPS)-induced iNOS expression in BV2 cells, a murine microglial cells and the associated mechanisms. LMB strongly inhibited LPS-induced iNOS protein and mRNA expressions in BV2 cells in which 10 ng/ml of LMB (18 nM) was sufficient to greatly down-regulate iNOS by LPS, suggesting the potency of LMB to inhibit iNOS. The data of iNOS promoter-driven luciferase assay further suggested that the LMB inhibitory effect was in part due to inhibition of iNOS transcription. However, LPS-induced activation of various intracellular signaling proteins, such as nuclear factor-kappaB (NF-kappaB), extracellular signal-regulated kinases (ERKs), p38s, and c-Jun N-terminal kinases (JNKs), whose activations are known to be important for iNOS expression by LPS in BV2 cells, were not affected in the presence of LMB. Together, these results suggest that LMB inhibits iNOS expression in response to LPS in BV2 microglia, and the inhibition seems to be associated with blockage of CRM1-mediated iNOS mRNA nuclear export and also in part transcriptional down-regulation of iNOS, but not through modulation of NF-kappaB and the mitogen-activated protein kinase signaling pathways.

Active Transport, Cell Nucleus↗

PubMed2005

Inhibitory modulation of ATP-sensitive potassium channels by gallate-ester moiety of (-)-epigallocatechin-3-gallate.

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenolic substance found in green tea, is well recognized to be beneficial for human health. However, it is still controversial as to what dose of this compound is indeed good for human health. Though some recent studies have interestingly reported various beneficial effects of EGCG in cell culture system, however, plasma levels of EGCG attainable by oral regular intake in humans are normally in nanomolar range. However, potential side effects of EGCG when administered parenterally at higher concentration have not been thoroughly tested. Here, we evaluated the effect of EGCG on ATP-sensitive potassium (K(ATP)) channels expressed in Xenopus oocytes. EGCG inhibited the activity of the Kir6.2/SUR1 and Kir6.2DeltaC36 channels with IC(50) of 142+/-37 and 19.9+/-1.7microM, respectively. Inhibition of EGCG was also observed in Kir6.2/SUR2A or Kir6.2/SUR2B channels. Notably, (-)-epicatechin-3-gallate (ECG), another major polyphenolic substance in green tea, was found to reduce the channel activity with greater potency than EGCG. In contrast to EGCG and ECG, which have the gallic acid-ester moiety in their own structures, (-)-epigallocatechin and (-)-epicatechin exhibited very weak inhibition of the K(ATP) channel. Collectively, these results suggest that the gallate-ester moiety of epicatechins may be critical for inhibiting the K(ATP) channel activity via the pore-forming subunit Kir6.2 and this may be a possible mechanism by which green tea extracts or EGCG may cause unexpected side effects at micromolar plasma level.

Adenosine Triphosphate↗

PubMed2005

Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR.

Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.

Animals↗

PubMed2005

Gene knockdown by large circular antisense for high-throughput functional genomics.

Single-stranded genomic DNA of recombinant M13 phages was tested as an antisense molecule and examined for its usefulness in high-throughput functional genomics. cDNA fragments of various genes (TNF-alpha, c-myc, c-myb, cdk2 and cdk4) were independently cloned into phagemid vectors. Using the life cycle of M13 bacteriophages, large circular (LC)-molecules, antisense to their respective genes, were prepared from the culture supernatant of bacterial transformants. LC-antisense molecules exhibited enhanced stability, target specificity and no need for target-site searches. High-throughput functional genomics was then attempted with an LC-antisense library, which was generated by using a phagemid vector that incorporated a unidirectional subtracted cDNA library derived from liver cancer tissue. We identified 56 genes involved in the growth of these cells. These results indicate that an antisense sequence as a part of single-stranded LC-genomic DNA of recombinant M13 phages exhibits effective antisense activity, and may have potential for high-throughput functional genomics.

Animals↗

PubMed2005

Catalase induced expression of inflammatory mediators via activation of NF-kappaB, PI3K/AKT, p70S6K, and JNKs in BV2 microglia.

Catalase induces COX-2 or iNOS expression in some type of cells, but the mechanism remains unclear. Here we investigated the effect of catalase on COX-2 and iNOS expression in BV2 microglia and the inductive mechanism associated. Exposure of catalase to BV2 microglia induced expression of COX-2 and iNOS that was related with transcriptional up-regulation. Importantly, catalase-induced COX-2 and iNOS expression needed activations of NF-kappaB, PI3K/AKT, and JNKs, which were important for the transcriptional up-regulation of COX-2 and iNOS. Notably, rapamycin inhibition of p70S6K led to down-regulation of COX-2 and iNOS protein expression, but not steady-state mRNA expression and transcription, induced by catalase, suggesting that p70S6K is involved in increased COX-2 and iNOS mRNA translation by catalase. Interestingly, there was PI3K-dependent activation of AKT, p70S6K, JNKs, and NF-kappaB in response to catalase. These data collectively suggest catalase-induced COX-2 and iNOS expression in BV2 microglia is, in part at least, mediated through activation of multiple signaling proteins.

Animals↗

PubMed2005

Novel amino acid modified zinc polycarboxylates for improved dental cements.

OBJECTIVE: The objective of this study was to develop a novel amino acid modified zinc/calcium polycarboxylate cement system, formulate the cements, and evaluate their mechanical strengths. MATERIALS AND METHODS: Acrylate and methacrylate derivatives of four amino acids were synthesized and characterized using FT-IR and 1HNMR spectroscopy. The derivatives were formulated with polymer having pendent methacrylate group, water, and synthesized novel filler. Compressive (CS) as well as flexural strengths (FS) and viscosities of the resin liquids were used as tools to evaluate the formulations and formed cements. The specimens for CS and FS tests were conditioned in distilled water at 37 degrees C for 24 h and 7 d, respectively, prior to testing. RESULTS: The measured CS and FS of the cements was in the decreasing order of methacryloyl beta-alanine > acryloyl glutamic acid = acryloyl beta-alanine > methacryloyl glutamic acid > 2-hydroxyethyl methacrylate. Methacryloyl beta-alanine was selected for further formulations due to its relatively low solution viscosity and high CS as well as FS. Effects of polymer content, P/L ratio, tartaric acid and initiator concentration were significant. During aging, the cement showed a constant increase in CS for up to 1 month and then kept constant for up to 3 months. CONCLUSIONS: This study developed a novel amino acid modified zinc/calcium polycarboxylate cement system. This system was 85% higher in CS, 98% higher in DTS and 183% higher in FS, compared to Durelon.

Amino Acids↗

PubMed2005

Prevention of tissue injury by ribbon antisense to TGF-beta1 in the kidney.

Transforming growth factor-beta1 (TGF-beta1) is an important mediator of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. We designed ribbon-type antisense oligos of TGF-beta1, TGF-beta1 RiAS, and combined them with a short peptide of the nuclear localization signal to form a transfection complex of DNA/peptide/liposomes (DPL) for enhanced cellular uptake. When H4IIE cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%. We then examined the ratio of the kidney weight per body weight in rats. Whereas the weight ratio was 0.47% for the normal kidney, the ratio was 0.99% on day 5 after unilateral ureteric obstruction (UUO). The ratios were 0.95% with PBS injection, 1.07% with scrambled RiAS, and 0.68% with TGF-beta1 RiAS. When examined for TGF-beta1 expression in the tissue, the level of TGF-beta1 mRNA was also significantly reduced following treatment with TGF-beta1 RiAS. Further, physical changes such as diminished dilation, atrophy, as well as apoptosis caused by UUO were also found to be markedly reduced by TGF-beta1 RiAS. The results show that ribbon antisense to TGF-beta1 when combined with efficient uptake can effectively block TGF-beta1 expression and preserve tissue integrity in kidneys with UUO.

Animals↗

PubMed2004

Catalase induces the expression of inducible nitric oxide synthase through activation of NF-kappaB and PI3K signaling pathway in Raw 264.7 cells.

It has been reported that macrophages produce substantial amounts of nitrite and nitrate after addition of catalase, but the mechanism associated remains unclear. In present study, we investigated whether catalase modulates the expression of inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide. Exposure of Raw 264.7 macrophages (Raw cells) to catalase induced high expression of iNOS mRNA as well as protein with enzymatic activity. Data of mechanical analyses, such as iNOS promoter-driven luciferase assay and actinomycin D chase experiments demonstrated that the induction was due to increased iNOS transcription and post-transcriptional iNOS mRNA stability. Of interest, catalase-induced iNOS protein expression was abrogated through inactivation of NF-kappaB pathway by MG132 or BAY 11-7085 and PI3K pathway by LY294002 or wortmannin, respectively. In particular, blockage of PI3K pathway by LY294002 down-regulated iNOS transcription and steady-state iNOS mRNA levels as well as iNOS mRNA stability induced by catalase, suggesting regulation of PI3K pathway in catalase-induced iNOS expression at the levels of iNOS transcription, steady-state mRNA status, and mRNA stability. Additional cell culture works in different types of cells indicated that iNOS expression by catalase might be cell type-specific, based on the facts that catalase induced iNOS expression in BV2 microglial macrophage-like cells, but not in HT-29 or A549, human colon or lung cancer epithelial-like cells. Together, these results demonstrate for the first time that catalase induces iNOS expression in Raw cells, which seems to be associated with the increase of iNOS transcription and mRNA stability as well as the activation of NF-kappaB and PI3K signaling pathways.

Animals↗

PubMed2004

Leptomycin B-induced apoptosis is mediated through caspase activation and down-regulation of Mcl-1 and XIAP expression, but not through the generation of ROS in U937 leukemia cells.

Leptomycin B (LMB), which is originally isolated from Streptomyces, possesses anti-tumor properties in vivo and in vitro. Though it was previously reported that LMB induces cell cycle arrest and p53-mediated apoptosis in certain cancer cells, however, the mechanism by which LMB induces apoptosis remains poorly understood. Here, we investigated the mechanisms of apoptosis induced by LMB in U937 cells. Treatment with LMB concentration-dependently induced cytotoxicity and apoptosis in U937 cells that correlated temporally with activation of caspases and down-regulation of Mcl-1 and XIAP. LMB did not change the expressions of Bcl-2 or Bax. A broad spectrum caspase inhibitor, z-VAD-fmk, blocked caspase-3 activation and elevated the survival in LMB-treated U937 cells, suggesting that caspase-3 activation is critical for LMB-induced apoptosis. Interestingly, Bcl-2 overexpression that blocked cytochrome c release by LMB effectively attenuated the apoptotic response to LMB, suggesting that LMB-induced apoptosis is mediated through the mitochondrial pathway. Antioxidants or antioxidant enzymes had no effects on LMB-induced apoptosis. Data of flow cytometry analysis using 2',7'-dichlorofluorescein-diacetate further revealed no reactive oxygen species (ROS) generation by LMB, indicating that apoptosis induced by LMB is ROS-independent. However, the apoptotic response to LMB was not shown in U937 cells pretreated with the sulfhydryl group-containing antioxidant N-acetylcysteine (NAC). Further analysis suggested that NAC directly binds LMB and abolishes the apoptotic effects of LMB. Collectively, these findings suggest that LMB potently induces apoptosis in U937 cells, and LMB-induced apoptosis in U937 cells is related with cytochrome c release, activation of caspases, and selective down-regulation of Mcl-1 and XIAP.

Antibiotics, Antineoplastic↗

PubMed2004

Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathways.

Induction of COX-2 by catalase in smooth muscle cells, endothelial cells, and neuronal cells has been previously reported. However, the mechanism by which catalase up-regulates COX-2 remains poorly understood. In this study, we investigated the effect of catalase on induction of COX-2 in macrophages. The addition of catalase into Raw 264.7 macrophages induced COX-2 expression that was correlated with increased COX-2 transcription and mRNA stability. Catalase also induced activation of NF-kappaB, PI3K, ERKs, p38s, or JNKs. Catalase-induced COX-2 expression was abrogated by treatment of MG-132 (a NF-kappaB inhibitor) or LY294002 (a PI3K inhibitor), but not by treatment of PD98059 (an ERK inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor). Moreover, inhibition of PI3K by LY294002 caused partial decrease of catalase-induced COX-2 transcription and steady-state COX-2 transcript levels, but not COX-2 mRNA stability. Together, these results suggest that catalase induces the expression of COX-2 in Raw 264.7 macrophages, and the induction is related with activation of NF-kappaB transcription factor and PI3K signaling pathway.

Animals↗

PubMed2002

Inhibitory effects of novel AP-1 decoy oligodeoxynucleotides on vascular smooth muscle cell proliferation in vitro and neointimal formation in vivo.

Excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal formation are critical steps in the pathogenesis of atherosclerosis and restenosis after percutaneous transluminal angioplasty. In this study, we investigated the hypothesis that the activator protein-1 (AP-1) plays an important role in neointimal formation after vascular injury. A circular dumbbell AP-1 decoy oligodeoxynucleotide (CDODN) was developed as a novel therapeutic strategy for restenosis after angioplasty. This CDODN was more stable than the conventional phosphorothioate linear decoy ODN (PSODN) and maintained structural integrity on exposure to exonuclease III or serum. Transfection with AP-1 decoy ODNs strongly inhibited VSMC proliferation and migration, as well as glucose- and serum-induced expression of PCNA and cyclin A genes. Administration of AP-1 decoy ODNs in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished neointimal formation after balloon injury to the rat carotid artery. Compared with PSODN, CDODN was more effective in inhibiting the proliferation of VSMCs in vitro and neointimal formation in vivo. Our results collectively indicate that AP-1 activation is crucial for the mediation of VSMC proliferation in response to vascular injury. Moreover, the use of stable CDODN specific for AP-1 activity in combination with the highly effective HVJ-liposome method provides a novel potential therapeutic strategy for the prevention of restenosis after angioplasty in humans.

Angioplasty, Balloon↗