Institute for Medical science

Jeonju, South Korea

Institute for Medical science

Jeonju, South Korea
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Lee J.-H.,Chonbuk National University | Kwon Y.-B.,Institute for Medical Science | Kim D.-K.,Chonbuk National University | Kim D.-S.,Central Research and Development | Jo H.-K.,Central Research and Development
Journal of the Korean Society of Food Science and Nutrition | Year: 2015

Traditional herbs, such as Lonicera japonica, Arctii Fructus, and Scutellariae Radix have been used as traditional drug due to their anti-inflammatory and anti-oxidant activities. The aim of this study was to investigate the anti-inflammatory effects of extract mixture (YG-1) in a model of lipopolysaccharide (LPS)-induced acute inflammation in both macrophage (RAW 264.7) cells and Sprague-Dawley rats. YG-1 did not show specific cellular toxicity in RAW 264.7 cells until a concentration of 100 μg/mL. YG-1 reduced various markers related to inflammation such as IL-1β, COX-2, and iNOS caused by LPS in RAW 264.7 cells. Consistent with these results, YG-1 exerted significant anti-inflammatory effects in an acute inflammation rat model. Acute fever and high concentration of IL-1β in serum induced by LPS were significantly reduced by YG-1. These results were similar to flubiprofen, a commercial anti-inflammatory and anti-febrile drug. Therefore, these results indicate that YG-1 has beneficial effects on LPS-induced acute inflammation and suggest that YG-1 can serve as an effective anti-inflammatory and anti-febrile drug. © 2015, Korean Society of Food Science and Nutrition. All rights reserved.


Hwang H.,Institute for Medical science | Hwang H.,Chonbuk National University | Kwon J.,Institute for Medical science | Kwon J.,Chonbuk National University | And 15 more authors.
Radiology | Year: 2014

Purpose: To determine whether chitosan hydrogel nanoparticles loaded with vascular endothelial growth factor (VEGF) peptides (81-91 fragments) capable of targeting the ischemic myocardium enhance angiogenesis and promote therapeutic effects and whether radionuclide image-guided dosage control is feasible.Materials and Methods: Experimental procedures and protocols were approved by the Institutional Animal Care and Use Committee. Rats (n = 32, eight per group) were subjected to myocardial ischemia (control group) and received chitosan hydrogel nanoparticles with VEGF165 proteins (chitosan VEGF) or VEGF81-91 peptides (chitosan peptides) via apical puncture. Ischemic hearts receiving chitosan without angiogenic factors served as the chitosan control. Myocardial perfusion was examined 7 days after surgery by using technetium 99m (99mTc) tetrofosmin (37 MBq) autoradiography, and changes in vascular density with immunohistochemical staining were reviewed. Kruskal-Wallis test and Bonferroni corrected Mann-Whitney U test were used for multiple comparisons. Wilcoxon signed rank test was used to compare myocardial retention of 99mTc chitosan.Results: Thirty minutes of myocardial ischemia resulted in perfusion defects (median, 54%; interquartile range [IQR], 41%-62%). Chitosan VEGF decreased perfusion defect extent (median, 68%; IQR, 63%-73%; P = .006 vs control) and increased vascular density (median, 81 vessels per high-power field; IQR, 72-100; P = .009 vs control). Administration of chitosan peptides reduced the degree of perfusion defects (median, 66%; IQR, 62%-73%; P = .006 vs control) and increased vascular density (median, 82 vessels; IQR, 78-92; P = .006 vs control). The effects of chitosan peptides on perfusion and vascular density were comparable to those seen with chitosan VEGF proteins (P = .713 and P = .833, respectively). Chitosan radiolabeled with 99mTc was administered twice at reperfusion with a 1-hour interval to determine whether image-guided dosage control is feasible. The hearts initially retained 4.6% (IQR, 4.1%-5.0%) of 99mTc chitosan administered and 9.2% (IQR, 6.6%-12.7%; P = .068) with subsequent injection.Conclusion: VEGF peptides have angiogenic potential and resulted in therapeutic effectiveness. Adjunct use of single photon emission computed tomography was also demonstrated for individualized treatment of myocardial ischemia by further tailoring the therapeutic dosing. © RSNA, 2014.


Jeong H.-S.,Chonbuk National University | Jeong H.-S.,Biomedical Research Institute | Jeong H.-S.,Cyclotron Research Center | Jeong H.-S.,Institute for Medical science | And 29 more authors.
Journal of Liposome Research | Year: 2013

The imaging of sentinel lymph nodes (SLN) has been researched for its role in assessing cancer progression and postsurgical lymphedema. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the Food and Drug Administration. It is known that liposome-encapsulated ICG (LP-ICG) has improved stability and fluorescence signal compared with ICG. We designed mannosylated liposome-encapsulated ICG (M-LP-ICG) as an optical contrast agent for SLN. M-LP-ICG has a higher UV absorbance spectrum and fluorescence intensity than LP-ICG. The stability of M-LP-ICG measured in 50° fetal bovine serum solution by a dialysis method was better than that of LP-ICG. M-LP-ICG demonstrated a high uptake in RAW 264.7 macrophage cell because the density of mannose is high. There were differences between M-LP-ICG and glucosylated liposome-encapsulated ICG (G-LP-ICG), which are geometrical isomers. The result of an inhibition study of M-LP-ICG showed a statistically significant decrease in uptake in RAW 264.7 cells after either co-treatment or pre-treatment with d-(+)-mannose as an inhibitor. Results from an in vitro experiment demonstrated that M-LP-ICG was specifically taken up by macrophage cells through the mannose receptor on its surface. The time-series images acquired from a normal mouse model after subcutaneous injection showed that the signal from M-LP-ICG in SLN and other organs appeared early and disappeared quickly in comparison with signals from LP-ICG. Not only the sentinel but also the draining lymph nodes were observed partly in M-LP-ICG. M-LP-ICG appears to increase the specificity of uptake and retention in macrophages, making it a good candidate contrast agent for an optic imaging system for SLN and the lymphatic system. © 2013 Informa Healthcare USA, Inc. All rights reserved.


Han X.-J.,Institute for Medical Science | Lee M.-J.,Institute for Medical Science | Yu G.-R.,Institute for Medical Science | Lee Z.-W.,Korea Basic Science Institute | And 4 more authors.
Cell Death and Disease | Year: 2012

The ubiquitin hybrid genes Uba80 and Uba52 encode ubiquitin (Ub), which is fused to the ribosomal proteins S27a (RPS27a) and L40 (RPL40), respectively. Here, we show that these genes are preferentially over-expressed during hepatoma cell apoptosis. Experiments using the tet-inducible transgenic system revealed that over-expression of the ubiquitin hybrid genes sensitized the cells to apoptosis. Further analysis suggested that Ub, and not RPS27a or RPL40, was associated with apoptotic cell death. Cleavage-resistant mutation analysis revealed that the N-terminal portion and the last two amino acids (GG) of Ub are critical for cleavage at the junction between the two protein moieties. An apoptogenic stimulus enhances the nuclear targeting and aggregation of Ub in the nucleus, resulting in histone H2A deubiquitylation followed by abnormal ubiquitylation of the nuclear envelope and the lamina. These events accompany the apoptotic nuclear morphology in the late stage of apoptosis. Each fused RP is localized in the nucleoli. These results suggest a role for Ub hybrid proteins in the altered nuclear dynamics of Ub during tumor cell apoptosis induced by apoptogenic stimuli. © 2012 Macmillan Publishers Limited.


Han Y.H.,Institute for Medical science | Park W.H.,Institute for Medical science
Food and Chemical Toxicology | Year: 2010

Pyrogallol (PG) as a polyphenol induces apoptosis in cells. Here, we evaluated the effects of PG on the growth and death of endothelial cells (ECs). PG dose-dependently inhibited the growth of calf pulmonary artery endothelial cells (CPAEC) and human umbilical vein endothelial cells (HUVEC). PG also induced apoptosis in both cells accompanied by the loss of mitochondrial membrane potential (ΔΨm). CPAEC were more sensitive to PG than HUVEC concerning cell growth and death. Caspase inhibitors (pan-caspase, caspase-3, -8 or -9 inhibitor) did not affect the growth inhibition of CPAEC by PG. However, pan-caspase inhibitor (Z-VAD) significantly reduced apoptosis and the loss of ΔΨm in PG-treated CPAEC. PG reduced ROS level and increased GSH depleted cell numbers in CPAEC. While Z-VAD increased ROS levels in PG-treated CPAEC, it decreased GSH depleted cell numbers. In conclusion, PG inhibited the growth of ECs, especially CPAEC via caspase-dependent apoptosis and GSH depletion. © 2009 Elsevier Ltd. All rights reserved.


Han Y.H.,Institute for Medical science | Moon H.J.,Institute for Medical science | You B.R.,Institute for Medical science | Park W.H.,Institute for Medical science
Food and Chemical Toxicology | Year: 2010

Pyrogallol (PG) as a polyphenol compound can generate superoxide anion (O2{radical dot} -). Here, we investigated the effects of PG and/or MAPK inhibitors on Calu-6 lung cells in relation to cell growth, cell death, reactive oxygen species (ROS) and GSH levels. PG inhibited the growth of Calu-6 cells and induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). While general ROS were decreased in PG-treated Calu-6 cells at 72 h, intracellular O2{radical dot} - level including mitochondrial O2{radical dot} - was increased. PG also increased GSH depleted cell number in Calu-6 cells. MEK inhibitor slightly prevented cell growth inhibition, cell death and GSH depletion by PG. JNK inhibitor did not affect cell growth, cell death, MMP (ΔΨm) loss, ROS level and GSH deletion in PG-treated Calu-6 cells but p38 inhibitor mildly enhanced MMP (ΔΨm) loss, O2{radical dot} - level and GSH depletion in these cells. Conclusively, MEK inhibitor slightly prevented growth inhibition and death in PG-treated Calu-6 cells. Growth inhibition and death in Calu-6 cells by PG and/or MAPK inhibitors were partially related to O2{radical dot} - level and GSH content changes. © 2009 Elsevier Ltd. All rights reserved.


Han Y.H.,Institute for Medical science | Moon H.J.,Institute for Medical science | You B.R.,Institute for Medical science | Yang Y.M.,Chonbuk National University | And 3 more authors.
International Journal of Molecular Medicine | Year: 2010

Propyl gallate (PG) as a synthetic antioxidant exerting a variety of effects on tissue and cell functions. We evaluated the effects of PG on the growth of endothelial cells, especially calf pulmonary artery endothelial cells (CPAEC) in relation to apoptosis. PG dose-dependently inhibited the growth of CPAEC and human umbilical vein endothelial cells (HUVEC) at 24 h. The susceptibility of CPAEC to PG was higher than that of HUVEC. PG induced apoptosis in CPAEC, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm). The tested caspase inhibitors (pan-caspase, caspase-3, -8 or -9 inhibitor) did not rescue CPAEC from PG-induced cell death but instead slightly enhanced the cell death. PG increased reactive oxygen species (ROS) level in CPAEC. The caspase inhibitors did not significantly change the ROS level. Furthermore, PG increased the GSH depleted cell number and decreased GSH level in CPAEC. The tested caspase inhibitors did not significantly change the number in PG-treated CPAEC. Each caspase inhibitor differently alters GSH levels in CPAEC. In conclusion, PG inhibited the growth of endothelial cells, especially CPAEC via caspase-independent apoptosis. PG-induced CPAEC death was accompanied by ROS increase and GSH depletion.


Park J.-Y.,Ajou University | Jang Y.H.,Daegu University | Kim Y.-S.,Institute for Medical science | Sohn S.,Ajou University | Kim Y.C.,Ajou University
European Journal of Dermatology | Year: 2013

Background: Photo aging is defined as premature aging of the skin induced by ultraviolet (UV) irradiation. Photodynamic therapy (PDT) has been shown to be a non-invasive but effective technique for photo aged skin. Objective: We observed histological and ultra-structural changes of photo aging and photorejuvenating effects of 5-aminolevulinic acid (ALA)-PDTinaUV-irradiated mice model. Methods: A total of 20 mice were divided into a control (group A) group and a UV-irradiated (photo aging) group. The photo aging group was divided according to the following interventions: photo aging only (group B), ALA application only (group C), light-emitting diode (LED) irradiation only (group D), and ALA-PDT with a light dose of 20 J/cm2 (group E). Serial skin biopsies were performed from day 2 to day 21, and transmission electron microscopic (TEM) studies were performed. Results: After UV irradiation, the amount of dermal collagen fibers decreased, and the quantity of elastotic materials increased. Following ALA-PDT application, the amount of collagen fibers increased from day 2 to day 21 and the increased elastotic materials during the photo aging period were normalized. With TEM, the decreased collagen fibers during photo aging were restored after PDT application. Also, distended dermal fibroblasts with distended endoplasmic reticulum by UV irradiation were normalized after PDT application. Conclusion: This study provides histologic evidence of the beneficial effects of ALA-PDT, even in photo damaged skin. ALA-PDT induces deposition of collagen in the dermis, normalizes elastotic materials which were induced by photo aging and may even have a direct effect on the normalization of the morphology of fibroblasts.


Shin Y.S.,Chonbuk National University | Kim S.D.,Chonbuk National University | Cha J.S.,Chonbuk National University | Kim M.K.,Chonbuk National University | And 5 more authors.
International Journal of Urology | Year: 2011

Objectives: To assess the clinical significance of immediate urine cytology (IUC) after transurethral resection of bladder tumor (TURBT) for non-muscle invasive bladder cancer (NMIBC). Methods: We reviewed the records of 174 patients who underwent IUC after TURBT for NMIBC. IUC was obtained just before Foley catheter removal after TURBT. The relationship between IUC and tumor stage, grade, size and multiplicity, as well as preoperative urine cytology and immediate intravesical epirubicin therapy, were assessed. The relationship between a positive IUC and cancer recurrence was also assessed. Multivariate Cox proportional hazards regression analysis was carried out, including IUC, tumor stage, tumor grade, tumor size, tumor multiplicity, preoperative urine cytology and immediate intravesical epirubicin therapy. Results: IUC was positive in 76 patients (43.7%) and negative in 98 patients (56.3%). In the positive IUC group, tumor stage and grade were higher (P=0.001, <0.001), tumor size was larger (P=0.001), tumor multiplicity was higher (P=0.002) and positive preoperative cytology was more likely (P=0.006) than in the negative IUC group. In the positive IUC group, the cancer recurrence rate was 72.3% and that of the negative IUC group was 30.6% (P<0.001). In a multivariate Cox proportional hazards regression analysis, positive IUC (HR 1.83, P=0.019), tumor size (HR 1.72, P=0.045), tumor multiplicity (HR 3.63, P=0.015), preoperative urine cytology (HR 1.23, P=0.043) and immediate intravesical epirubicin therapy (HR 0.171, P=0.001) were independent prognostic factors for cancer recurrence. Conclusion: These data suggest that IUC after TURBT for NMIBC can be an independent prognostic factor to predict cancer recurrence. © 2011 The Japanese Urological Association.


Yang S.H.O.,Chonbuk National University | Baek H.A.H.,Chonbuk National University | Lee H.O.J.,Chonbuk National University | Park H.O.S.,Chonbuk National University | And 13 more authors.
Oncology Reports | Year: 2010

Discoidin domain receptors (DDRs) are a novel class of receptor tyrosine kinases that bind to several collagens and facilitate cell adhesion. DDR1 is involved in cancer invasion. However, very limited data are available on the aspect of clinical significance of DDR1 expression in cancer. The aim of this study was to investigate prognostic impact of DDR1 expression in non-small cell lung carcinoma (NSCLC). Tumor tissues from 171 NSCLC, including 86 squamous cell carcinomas, 69 adenocarcinomas, and 16 pure bronchioloalveolar carcinomas (BAC), were analyzed for expression of DDR1 using immunohistochemical staining. In addition, two lung adenocarcinoma cell lines (A549, H358) were transfected with two isoforms of DDR1, DDR1a and DDR1b, and then migration and invasion assays were carried out. DDR1 was expressed in 6 of 16 BAC (38%) and 95 of 155 invasive NSCLC (61%, p=0.065). DDR1 up-regulation tend to be more frequently observed in invasive adenocarcinoma (64%) compared to DDR1 expression in BAC (38%) (p=0.056). In invasive NSCLC, DDR1 expression was significantly correlated with lymph node metastasis (p=0.001). Overexpression of DDR1 in lung cancer cells resulted in a significant increase of cell motility and invasiveness (p<0.001) and the interaction of DDR1 with collagen facilitates the invasiveness of NSCLC cells. DDR1 overexpression produced an activation of MMP-9 in H358 cells. In conclusion, these findings indicate that up-regulation of DDR1 may contribute to the progression and poor prognosis of NSCLC and this effect may be associated with increased invasiveness.

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