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1.  Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays 
Journal of Radiation Research  2014;55(2):277-282.
The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage.
PMCID: PMC3951079  PMID: 24508645
lactoferrin; radioprotection; sub-lethal X-ray irradiation; mice
2.  Downregulation of Angiotensin II-Induced 12-Lipoxygenase Expression and Cell Proliferation in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats by CCL5 
Angiotensin II (Ang II) plays an important role in vascular hypertension. The role of the chemokine CCL5 on Ang II-induced activities in vascular smooth muscle cells (VSMCs) has not been studied. In this study, we elucidated the effect of CCL5 on Ang II-induced 12-lipoxygenase (LO) expression and cell proliferation in spontaneously hypertensive rats (SHR) VSMCs. CCL5 decreased Ang II-induced 12-LO mRNA expression and protein production, and it increased Ang II type 2 (AT2) receptor expression in SHR VSMCs. The inhibitory effect of CCL5 on Ang II-induced 12-LO mRNA expression was mediated through the AT2 receptor. Although treatment of CCL5 alone induced SHR VSMCs proliferation, CCL5 inhibited Ang II-induced VSMCs proliferation and PD123,319, an AT2 receptor antagonist, blocked the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation. Phosphorylation of p38 was detected in VSMCs treated with Ang II or CCL5 alone. But, decrease of p38 phosphorylation was detected in VSMCs treated with Ang II and CCL5 simultaneously (Ang II/CCL5) and PD123,319 increased p38 phosphorylation in VSMCs treated with Ang II/CCL5. Therefore, these results suggest that the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation is mediated by the AT2 receptor via p38 inactivation, and CCL5 may play a beneficial role in Ang II-induced vascular hypertension.
PMCID: PMC2776900  PMID: 19915702
Angiotensin II; Angiotensin II type 2 receptor; Cell proliferation; Chemokine CCL5; 12-lipoxygenase
3.  Successful treatment of myelodysplastic syndrome and Behcet colitis after allogeneic hematopoietic stem cell transplantation 
PMCID: PMC3932385  PMID: 24574844
Myelodysplastic syndromes; Behcet syndrome; Hematopoietic stem cell transplantation
4.  Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-κB/AP-1 Pathways 
Biomolecules & Therapeutics  2013;21(5):332-337.
Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer’s disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.
PMCID: PMC3825195  PMID: 24244819
Microglia; Kalopanaxsaponin A; Anti-inflammation; JNK; NF-κB; AP-1
5.  Prevalence of and Risk Factors for Gastrointestinal Diseases in Korean Americans and Native Koreans Undergoing Screening Endoscopy 
Gut and Liver  2013;7(5):539-545.
In South Korea, health check-ups are readily accessible to the public. We aimed to compare the prevalence of upper gastrointestinal (GI) and lower GI diseases in Korean Americans and native Koreans to determine differences and risk factors.
In total, 1,942 subjects who visited Gangnam Severance Hospital from July 2008 to November 2010 for a health check-up were enrolled. Basic characteristics and laboratory data for the subjects were collected. Esophagogastroduodenoscopy and colonoscopy were performed. In total, 940 Korean Americans (group 1) and 1,002 native Koreans (group 2) were enrolled.
The overall prevalence of GI diseases for each group (group 1 vs group 2) were as follows: reflux esophagitis (RE) (9.65% vs 7.9%), gastric ulcer (2.8% vs 3.4%), duodenal ulcer (2.3% vs 3.6%), gastric cancer (0.4% vs 0.3%), colorectal polyp (35.9% vs 35.6%), colorectal cancer (0.5% vs 0.5%), and hemorrhoids (29.4% vs 21.3%). The prevalence of hemorrhoids was significantly higher in group 1 than in group 2 (p=0.001). In the multivariable analysis of group 1, male sex, age over 50 years, hypercholesterolemia and hypertriglyceridemia predicted colorectal polyps. Male sex and high fasting glucose levels were associated with RE.
Our study showed that the prevalence of GI diseases (except hemorrhoids) in Korean Americans was similar to that observed in native Koreans. Therefore, the Korean guidelines for upper and lower screening endoscopy may be applicable to Korean Americans.
PMCID: PMC3782668  PMID: 24073311
Korean Americans; Screening endoscopy
6.  Differential expression of thymic DNA repair genes in low-dose-rate irradiated AKR/J mice 
Journal of Veterinary Science  2013;14(3):271-279.
We previously determined that AKR/J mice housed in a low-dose-rate (LDR) (137Cs, 0.7 mGy/h, 2.1 Gy) γ-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) (137Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice.
PMCID: PMC3788152  PMID: 23820165
AKR/J mice; DNA repair genes; low-dose-rate radiation; thymic lymphoma
7.  Effect of silane activation on shear bond strength of fiber-reinforced composite post to resin cement 
Among the surface treatment methods suggested to enhance the adhesion of resin cement to fiber-reinforced composite posts, conflicting results have been obtained with silanization. In this study, the effects of silanization, heat activation after silanization, on the bond strength between fiber-reinforced composite post and resin cement were determined.
Six groups (n=7) were established to evaluate two types of fiber post (FRC Postec Plus, D.T. Light Post) and three surface treatments (no treatment; air drying; drying at 38℃). Every specimen were bonded with dual-curing resin cement (Variolink N) and stored in distilled water for 24 hours at 37℃. Shear-bond strength (MPa) between the fiber post and the resin cement were measured using universal testing device. The data were analyzed with 1-way ANOVA and by multiple comparisons according to Tukey's HSD (α=0.05). The effect of surface treatment, fiber post type, and the interactions between these two factors were analyzed using 2-way ANOVA and independent sample T-tests.
Silanization of the FRC Postec Plus significantly increased bond strength compared with the respective non-treated control, whereas no effect was determined for the D.T. Light Post. Heat drying the silane coupling agent on to the fiber-reinforced post did not significantly improve bond strength compared to air-syringe drying.
The bond strength between the fiber-reinforced post and the resin cement was significantly increased with silanization in regards to the FRC Postec Plus post. Bond strength was not significantly improved by heat activation of the silane coupling agent.
PMCID: PMC3675281  PMID: 23755334
Post and core technique; Silane; Resin cements; Shear strength; Heat treatment
8.  Anti-Inflammatory Effect of Ginsenoside Rg5 in Lipopolysaccharide-Stimulated BV2 Microglial Cells 
Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-α, IL-1β, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-κB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders.
PMCID: PMC3676815  PMID: 23698769
ginsenoside Rg5; microglia; neuroinflammation; iNOS; cytokine; signaling pathway
9.  Inorganic sulfur reduces cell proliferation by inhibiting of ErbB2 and ErbB3 protein and mRNA expression in MDA-MB-231 human breast cancer cells 
Dietary inorganic sulfur is the minor component in our diet, but some studies suggested that inorganic sulfur is maybe effective to treat cancer related illness. Therefore, this study aims to examine the effects of inorganic sulfur on cell proliferation and gene expression in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Inorganic sulfur significantly decreased proliferation after 72 h of incubation (P < 0.05). The protein expression of ErbB2 and its active form, pErbB2, were significantly reduced at inorganic sulfur concentrations of 50 µmol/L and greater than 25 µmol/L, respectively (P < 0.05). The mRNA expression of ErbB2 was significantly reduced at an inorganic sulfur concentration of 50 µmol/L (P < 0.05). The protein expression of ErbB3 and its active form, pErbB3, and the mRNA expression of ErbB3 were significantly reduced at inorganic sulfur concentrations greater than 25 µmol/L (P < 0.05). The protein and mRNA expression of Akt were significantly reduced at an inorganic sulfur concentration of 50 µmol/L (P < 0.05), but pAkt was not affected by inorganic sulfur treatment. The protein and mRNA expression of Bax were significantly increased with the addition of inorganic sulfur concentration of 50 µmol/L (P < 0.05). In conclusion, cell proliferation was suppressed by inorganic sulfur treatment through the ErbB-Akt pathway in MDA-MB-231 cells.
PMCID: PMC3627935  PMID: 23610600
Inorganic sulfur; epidermal growth factor receptor; apoptosis; cell proliferation; MDA-MB-231 cell
10.  The utility of sperm DNA damage assay using toluidine blue and aniline blue staining in routine semen analysis 
The aim of the present study was to examine the relationship among male age, strict morphology, and sperm chromatin structure and condensation.
Sperm samples from a total of 100 men underwent semen analysis, and sperm chromatin structure and condensation were assessed with toluidine blue (TB) and aniline blue (AB) tests.
Prevalence of strict morphology of less than 4%, and abnormal sperm chromatin structure and condensation did not show any statistically significant differences according to male age (p=0.605, p=0.235, and p=0.080). No significant correlation was demonstrated among age of male partners, strict morphology, and abnormal sperm chromatin structure using TB and AB tests. However, abnormal sperm chromatin condensation was positively associated with sperm chromatin structure (r=0.594, p=0.000) and showed negative correlation with strict morphology (r=-0.219, p=0.029).
The tests for sperm chromatin condensation showed a significant association with strict morphology. Further study is needed to elucidate the relationship between clinical outcome and sperm chromatin tests.
PMCID: PMC3630289  PMID: 23614112
Toluidine blue; Aniline blue; Semen analysis; DNA damage; Human
11.  Successful birth with preimplantation genetic diagnosis using single-cell allele-specific PCR and sequencing in a woman with hypochondroplasia due to FGFR3 mutation (c.1620C>A, p.N540K) 
Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.
PMCID: PMC3630293  PMID: 23614116
Hypochondroplasia; Preimplantation genetic diagnosis; Receptor, fibroblast growth factor, type 3
12.  Finite element modeling technique for predicting mechanical behaviors on mandible bone during mastication 
The purpose of this study was to propose finite element (FE) modeling methods for predicting stress distributions on teeth and mandible under chewing action.
For FE model generation, CT images of skull were translated into 3D FE models, and static analysis was performed considering linear material behaviors and nonlinear geometrical effect. To find out proper boundary and loading conditions, parametric studies were performed with various areas and directions of restraints and loading. The loading directions are prescribed to be same as direction of masseter muscle, which was referred from anatomy chart and CT image. From the analysis, strain and stress distributions of teeth and mandible were obtained and compared with experimental data for model validation.
As a result of FE analysis, the optimized boundary condition was chosen such that 8 teeth were fixed in all directions and condyloid process was fixed in all directions except for forward and backward directions. Also, fixing a part of mandible in a lateral direction, where medial pterygoid muscle was attached, gave the more proper analytical results. Loading was prescribed in a same direction as masseter muscle. The tendency of strain distributions between the teeth predicted from the proposed model were compared with experimental results and showed good agreements.
This study proposes cost efficient FE modeling method for predicting stress distributions on teeth and mandible under chewing action. The proposed modeling method is validated with experimental data and can further be used to evaluate structural safety of dental prosthesis.
PMCID: PMC3517960  PMID: 23236574
Mandible; Stress distribution; Mastication; Finite element analysis
13.  The Effect of Red Ginseng Extract on Inflammatory Cytokines after Chemotherapy in Children 
Journal of Ginseng Research  2012;36(4):383-390.
Ginseng has been used as an herbal medicine, widely used in Asian countries, for long time. Recently, beneficial effects for immune functions of Korean red ginseng (KRG) have been reported in adults. This study was performed to investigate the effects of ginseng on immune functions in children after cessation of chemotherapy or stem cell transplantation for advanced cancer. Thirty patients, who were diagnosed and treated for leukemia and solid cancer at the department of pediatrics and adolescence of the Yeungnam University Hospital from June 2004 to June 2009, were enrolled for the study. The study group consisted of 19 patients who received KRG extract (60 mg/kg/d) for 1 yr and 11 patients who did not receive KRG extract were the control group. Blood samples were collected every 6 mo. Immune assays included circulating lymphocyte subpopulation, serum cytokines (IL- 2, IL-10, IL-12, TNF-alpha, and IFN-gamma), and total concentrations of serum IgG, IgA, and IgM subclasses. Age at diagnosis ranged from 2 mo to 15 yr (median 5 yr). Nine patients received stem cell transplantation. The cytokines of the KRG treated group were decreasing more rapidly than that of the control group. Lymphocyte subpopulations (T cell, B cell, NK cell, T4, T8, and T4/ T8 ratio) and serum immunoglobulin subclasses (IgG, IgA, and IgM) did not show significant differences between the study and the control groups. This study suggests that KRG extract might have a stabilizing effect on the inflammatory cytokines in children with cancer after chemotherapy.
PMCID: PMC3659604  PMID: 23717140
Panax ginseng; Korean red ginseng; Cytokine; Childhood cancer
14.  Augmentation of natural cytotoxicity by chronic low-dose ionizing radiation in murine natural killer cells primed by IL-2 
Journal of Radiation Research  2012;53(6):823-829.
The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy in vitro, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to in vivo consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.
PMCID: PMC3483842  PMID: 22915781
Low-dose radiation; natural killer cells; natural cytotoxicity; innate immunity
15.  Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells 
Nutrition Research and Practice  2011;5(5):375-380.
This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 µmol/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P < 0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P < 0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P < 0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.
PMCID: PMC3221821  PMID: 22125673
Inorganic sulfur; invasion; motility; matrix metalloprotease; MDA-MB-231 cells
16.  Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1 
Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cAMP levels and activates protein kinase A, thereby inhibiting vascular smooth muscle cell (VSMC) proliferation. We investigated whether AMP-activated protein kinase (AMPK) activation induced by heme oxygenase-1 (HO-1) is a mediator of the beneficial effects of cilostazol and whether cilostazol may prevent cell proliferation and reactive oxygen species (ROS) production by activating AMPK in VSMC. In the present study, we investigated VSMC with various concentrations of cilostazol. Treatment with cilostazol increased HO-1 expression and phosphorylation of AMPK in a dose- and time-dependent manner. Cilostazol also significantly decreased platelet-derived growth factor (PDGF)-induced VSMC proliferation and ROS production by activating AMPK induced by HO-1. Pharmacological and genetic inhibition of HO-1 and AMPK blocked the cilostazol-induced inhibition of cell proliferation and ROS production.These data suggest that cilostazol-induced HO-1 expression and AMPK activation might attenuate PDGF-induced VSMC proliferation and ROS production.
PMCID: PMC3186921  PMID: 21994478
Cilostazol; Proliferation; ROS; AMPK; HO-1
17.  Impact of Nocturia on Health-Related Quality of Life and Medical Outcomes Study Sleep Score in Men 
To evaluate the impact of nocturia on health-related quality of life and sleep in men.
From January 2008 to December 2008, 284 patients with lower urinary tract symptoms were selected for this study. The participants completed a series of questionnaires on health-related quality of life (the overactive bladder questionnaire, or OAB-q), the Medical Outcomes Study (MOS) sleep scale, and the frequency volume chart.
The patient population had a mean age of 60.0±13.4 years (range, 40 to 79 years). The mean duration of symptoms was 28.8±34.6 months. The mean number of voiding episodes per night was measured as follows: 88 patients (31.0%) reported no nocturia, 60 patients (21.1%) reported 2>voids/night ≥1, 56 patients (19.7%) reported 3>voids/night ≥2, and 80 patients (28.2%) reported ≥3 voids/night. The mean number of nocturia episodes increased with age (P=0.001), and the number of nocturia episodes was significantly associated with the OAB-q symptom score (P=0.001) and symptom bother (P=0.001). Among the categories of the MOS sleep scale, sleep index I (P=0.020), sleep disturbance (P=0.010), adequacy of sleep (P=0.005), and somnolence (P=0.041) were significantly associated with an increased number of nocturia episodes.
The number of nocturia episodes increased with age in men. Nocturia appeared to be associated with further negative effects on sleep quality, health-related quality of life, and symptom bother.
PMCID: PMC3138848  PMID: 21811697
Nocturia; Sleep; Quality of life
18.  Butin (7,3′,4′-Trihydroxydihydroflavone) Reduces Oxidative Stress-Induced Cell Death via Inhibition of the Mitochondria-Dependent Apoptotic Pathway 
Recently, we demonstrated that butin (7,3′,4′-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H2O2)-induced apoptosis by: (1) scavenging reactive oxygen species (ROS), activating antioxidant enzymes such superoxide dismutase and catalase; (2) decreasing oxidative stress-induced 8-hydroxy-2′-deoxyguanosine levels via activation of oxoguanine glycosylase 1, and (3), reducing oxidative stress-induced mitochondrial dysfunction. The objective of this study was to determine the cytoprotective effects of butin on oxidative stress-induced mitochondria-dependent apoptosis, and possible mechanisms involved. Butin significantly reduced H2O2-induced loss of mitochondrial membrane potential as determined by confocal image analysis and flow cytometry, alterations in Bcl-2 family proteins such as decrease in Bcl-2 expression and increase in Bax and phospho Bcl-2 expression, release of cytochrome c from mitochondria into the cytosol and activation of caspases 9 and 3. Furthermore, the anti-apoptotic effect of butin was exerted via inhibition of mitogen-activated protein kinase kinase-4, c-Jun NH2-terminal kinase (JNK) and activator protein-1 cascades induced by H2O2 treatment. Finally, butin exhibited protective effects against H2O2-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G1 hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H2O2-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway.
PMCID: PMC3131597  PMID: 21747713
butin; oxidative stress; mitochondria-dependent apoptotic pathway
19.  Age Related Change of Nocturia in Women 
The precise etiology and classification of nocturia in women is not enough. We evaluated age related changes and classified the type of nocturia by age in women.
We included 118 women 20 years or older with nocturia at least one time during night time. Subjects were divided into three groups by the age: group 1, under 40 years; group 2, 40 through 59 years; group 3, 60 years and above. The causes of nocturia and its pattern changed by age in women were evaluated using 3 days frequency volume chart. Nocturia was devided into three types: nocturnal polyuria, decreased nocturnal bladder capacity and mixed type.
The mean age was 57.2±11.8 and the mean nocturnal frequency was 2.7±1.8. In all age group, noctural polyuria was the major cause for noturia (40.8%), followed by low nocturnal bladder capacity (23.7%). As a major cause of nocturia, there was a significant increase of the incidence of nocturnal polyuria in aged people: group 1, 32.4%; group 2, 41.0%; group 3: 47.6% (P<0.04).
Nocturnal polyuria and decreased nocturnal bladder capacity are the major causes of nocturia in women. Nocturnal polyuria was the major cause of nocturia with age over 60 years old. In aged women, nocturnal polyuria should be considered as a main cuase of nocturia and treated based on these result.
PMCID: PMC3021816  PMID: 21253336
Nocturia; Women; Age
20.  The Reliability and Validity of the Korean Version of the Structured Interview for Prodromal Syndrome 
Psychiatry Investigation  2010;7(4):257-263.
The Structured Interview for Prodromal Syndrome (SIPS) from Yale University is intended to diagnose prodromal syndrome of psychosis and to measure the severity of prodromal symptoms. Here, a Korean version of SIPS is presented, and its reliability, validity, and factor structures are examined using a representative Korean sample.
The Korean version of SIPS was administered to 40 participants over a period of 1 year. The inter-rater reliability and internal consistency of the SIPS were then evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was explored using Pearson correlation coefficients with the Positive and Negative Syndrome Scale (PANSS).
Of the 40 subjects, 12.5% developed psychotic disorders during the 1-year follow-up period. Inter-rater reliability was good (intra-class correlations=0.96), and internal consistency was acceptable (Cronbach's alpha=0.83). A three-factor resolution displayed the best simple structure and accounted for 52.6% of all item variance. Factors 1 and 2 showed strong correlations with negative symptoms and cognitive dysfunction, respectively, on the PANSS. Factor 3 was not correlated with any factor on the PANSS.
The Korean version of SIPS is a reliable instrument for the assessment of prodromal symptoms in subjects and may be used to evaluate prodromal psychosis.
PMCID: PMC3022312  PMID: 21253409
The Korean version of the Structured Interview for Prodromal Syndrome; Reliability; Validity; Schizophrenia
21.  Increased Immunoendocrine Cells in Intestinal Mucosa of Postinfectious Irritable Bowel Syndrome Patients 3 Years after Acute Shigella Infection - An Observation in a Small Case Control Study 
Yonsei Medical Journal  2009;51(1):45-51.
Postinfectiously irritable bowel syndrome (PI-IBS) develops in 3-30% of individuals with bacterial gastroenteritis. Recent studies demonstrated increases in inflammatory components in gut mucosa of PI-IBS patients even after complete resolution of infection. We aimed to investigate histological changes in colon and rectum of PI-IBS subjects after long term period of infection.
Materials and Methods
We recruited PI-IBS subjects who had been diagnosed IBS after complete resolution of enteritis caused by shigellosis outbreak 3 years earlier. We compared unmatched four groups, PI-IBS (n = 4), non PI-IBS (n = 7), D-IBS (n = 7, diarrhea predominant type) and healthy controls (n = 10). All of them underwent colonoscopic biopsy at three areas, including descending colon (DC), sigmoid colon (SC) and rectum, which were assessed for 5-hydroxytryptamine (5-HT)/peptide YY (PYY)-containing enterochromaffin (EC) cell, intraepithelial (IEL) and lamina propria T lymphocyte (CD3), CD8 lymphocytes, mast cells and CD68/calprotectin+ macrophages.
All subjects had no structural or gross abnormalities at colonoscopy. In PI-IBS, 5-HT containing EC cells, PYY containing EC cells, IELs, CD3 lymphocytes, CD8 lymphocytes, mast cells, and CD68 + macrophages were increased compared to control (p < 0.05). In D-IBS, PYY containing EC cells, IELs, and CD3 lymphocytes were increased compared to control (p < 0.05). In PI-IBS, 5-HT containing EC cells tended to increase and PYY containing EC cells, CD8 lymphocytes, mast cells, and CD68+ macrophages were increased compared to non PI-IBS (p < 0.05). Calprotectin + marcrophages were decreased in PI-IBS, non PI-IBS and IBS compared to control.
The immunoendocrine cells were sporadically increased in PI-IBS, non PI-IBS and D-IBS compared with control. Our findings in a very small number of patients suggest that mucosal inflammation may play a role in long-term PI-IBS, and that other sub-groups of IBS and larger scale studies are needed to confirm this observation.
PMCID: PMC2799963  PMID: 20046513
Post infectious irritable bowel syndrome; enterochromaffin cell; T lymphocyte; mast cell; macrophage
22.  Compound K, a Metabolite of Ginseng Saponin, Induces Mitochondria-Dependent and Caspase-Dependent Apoptosis via the Generation of Reactive Oxygen Species in Human Colon Cancer Cells 
The objective of this study was to elucidate the cytotoxic mechanism of Compound K, with respect to the involvement of reactive oxygen species (ROS) and the mitochondrial involved apoptosis, in HT-29 human colon cancer cells. Compound K exhibited a concentration of 50% growth inhibition (IC50) at 20 μg/mL and cytotoxicity in a time dependent manner. Compound K produced intracellular ROS in a time dependent fashion; however, N-acetylcysteine (NAC) pretreatment resulted in the inhibition of this effect and the recovery of cell viability. Compound K induced a mitochondria-dependent apoptotic pathway via the modulation of Bax and Bcl-2 expressions, resulting in the disruption of the mitochondrial membrane potential (Δψm). Loss of the Δψm was followed by cytochrome c release from the mitochondria, resulting in the activation of caspase-9, -3, and concomitant poly ADP-ribosyl polymerase (PARP) cleavage, which are the indicators of caspase-dependent apoptosis. The apoptotic effect of Compound K, exerted via the activation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), was abrogated by specific MAPK inhibitors. This study demonstrated that Compound K-mediated generation of ROS led to apoptosis through the modulation of a mitochondria-dependent apoptotic pathway and MAPK pathway.
PMCID: PMC3100836  PMID: 21614182
Compound K; reactive oxygen species; mitochondrial membrane potential; c-Jun NH2-terminal kinase; p38 mitogen-activated protein kinase
23.  Evaluation of proximal contact strength by postural changes 
Proper proximal contact is important for maintaining and stabilizing the dental arch. However, the proximal contact strength (PCS) is not a constant value and can be affected by a variety of factors.
This study examined the influences of postural changes on the posterior PCS.
Twelve adults with a normal occlusion and had not undergone prosthetic treatment or proximal restoration were participated in this study. A metal strip was inserted into the proximal surface and removed at a constant velocity. The contact strength was measured in every contact point between canine to second molar in both arches. The PCSs were obtained initially in the upright position, secondly in the supine position and finally in the upright position again. All measurements were repeated after a 2 hour period. Statistical analysis was carried out using the Friedman test (P < .05).
Generally, a decrease in PCS occurred when the posture was changed from the initial upright to supine position, while it increased when the posture was changed from the supine to upright position. A significant change was observed in all areas except for between the canine-first premolar in the maxilla and between the first molarsecond molar in the mandible areas.
The posterior PCS, which dentists generally believe to be a static feature of occlusion, is affected significantly by posture.
PMCID: PMC2994688  PMID: 21165266
Proximal contact strength; Upright position; Supine position
24.  IL-8/CXCL8 Upregulates 12-Lipoxygenase Expression in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats 
We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC.
Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 (AT1) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [3H]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings.
Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the AT1 receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an AT1 receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor.
These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.
PMCID: PMC2803299  PMID: 20107540
IL-8/CXCL8; 12-lipoxygenase; rat vascular smooth muscle cell
25.  15-Deoxy-Δ12,14-Prostaglandin J2 Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats 
15d-PGJ2 has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR.
Effect and action mechanism of 15d-PGJ2 on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-κB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity.
15d-PGJ2 decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ2 in SHR VSMCs was mediated through PPARγ, and dependent on NF-κB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ2/LPS.
Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARγ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.
PMCID: PMC2803308  PMID: 20107546
15d-PGJ2; IL-8/CXCL8; vascular smooth muscle cells

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