PURPOSE: Benign prostatic hyperplasia (BPH) is the most common prostate disease in aging men. Microseminoprotein-beta (MSMB) is abundant in semen. In this study, we investigated association between single nucleotide polymorphisms (SNPs) at the promoter of the MSMB gene and the risk for developing BPH in a Korean population. METHODS: We genotyped two promoter polymorphisms (rs12770171, -184C/T and rs10993994, -2C/T) of the MSMB gene by direct sequencing. Ninety-five BPH patients and 78 control subjects were recruited for this study. SNPStats and Haploview version 4.2 were used for genetic analyses. Multiple logistic regression models (codominant, dominant, recessive, and log-additive models) were applied to determine the odds ratio (OR), 95% confidence interval (CI), and P-value. RESULTS: Genotype frequency of the rs12770171 SNP showed significant difference between BPH patients and controls (OR, 2.14; 95% CI, 1.07-4.27; P=0.032 in the codominant 1 model; OR, 2.31; 95% CI, 1.19-4.47; P=0.011 in the dominant model; and OR, 2.05; 95% CI, 1.17-3.61; P=0.009 in the log-additive model). Moreover, the SNP also showed association between the two groups (OR, 2.05; 95% CI, 1.19-3.52; P=0.009). The rs10993994 SNP was not associated with BPH. In haplotype analysis, CC and TT haplotypes were associated with BPH (P<0.05). CONCLUSIONS: This result indicates that a promoter polymorphism (rs12770170, -184C/T) in the MSMB gene may be associated with BPH development in a Korean population.
Aging ; Genotype ; Haplotypes ; Humans ; Logistic Models ; Male ; Odds Ratio ; Polymorphism, Single Nucleotide ; Prostate ; Prostatic Hyperplasia* ; Risk Factors* ; Semen

Background: Resin-based dental materials release residual monomers or other substances from incomplete polymerization intothe oral cavity, thereby causing adverse biological effects on oral tissue. 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP), an acidic monomer containing dihydrogen phosphate and methacrylate groups, is the most commonly used component of resin-based dental materials, such as restorative composite resins, dentin adhesives, and resin cements. Although previous studies have reported the cytotoxicity and biocompatibility in various cultured cells, the effects of resin monomers on cellular aging have not been reported to date. Therefore, this study aimed to investigate the effects of the resin monomer 10-MDP on cellular senescence and inflamm-aging in vitro. Methods: After stimulation with 10-MDP, MC3T3-E1 osteoblast-like cells were examined for cell viability by WST-8 assay andreactive oxygen species (ROS) production by flow cytometry. The protein and mRNA levels of molecular markers of aging were determined by western blotting and RT-PCR analysis, respectively. Results: Treatment with 0.05 to 1 mM 10-MDP for 24 hours reduced the survival of MC3T3-E1 cells in a concentration-dependentmanner. The intracellular ROS levels in the 10-MDP-treated experimental group were significantly higher than those in the control group. 10-MDP at a concentration of 0.1 mM increased p53, p16, and p21 protein levels. Additionally, an aging pattern was observed with blue staining due to intracellular senescence-associated beta-galactosidase activity. Treatment with 10-MDP increased the levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8, however their expression was decreased by mitogen-activated-protein-kinase (MAPK) inhibitors. Conclusion Taken together, these results suggest that the exposure of osteoblast-like cells to the dental resin monomer 10-MDP,increases the level of cellular senescence and the inflammatory response is mediated by the MAPK pathway.

Abnormal HLA-G expression occurs in various diseases such as melanoma, renal cell carcinoma, asthma, and classic Hodgkin's lymphoma. The purpose of this study was to determine whether HLA-G gene is linked with oral squamous cell carcinoma (OSCC). To investigate the possible link with susceptibility to OSCC, 54 OSCC patients and 120 healthy controls were enrolled in this study. HLA-G 14bp insertion/deletion polymorphism is in 3′-untranslated region of HLA-G gene. HLA-G 14bp insertion/deletion polymorphism was analyzed using the polymerase chain reaction (PCR) method. For the analysis of genetic data, SPSS18.0 program was used. Logistic regression models were performed for odds ratio (OR), 95 percent confidence interval (CI), and P value. There was a significant difference in distribution allele between OSCC patients and control subjects (OR=0.018, 95% CI=0.002-0.131, p<0.001). Our results suggest that HLA-G 14bp insertion/deletion polymorphism may be linked with susceptibility to OSCC in the Korean population.
Alleles ; Asthma ; Carcinoma, Renal Cell ; Carcinoma, Squamous Cell* ; Epithelial Cells* ; Exons* ; HLA-G Antigens* ; Hodgkin Disease ; Humans ; Logistic Models ; Melanoma ; Methods ; Odds Ratio ; Polymerase Chain Reaction

Purpose: Cognitive impairment is one of the main symptoms of Alzheimer disease and other dementias. Glycyrrhiza uralensis is a natural product that has a protective effect against cognitive impairment. In this study, we investigated whether glycyrrhizic acid, among the main bioactive components of Glycyrrhiza uralensis, has a neuroprotective effect on scopolamine-induced cognitive impairment. Methods: Twenty-week-old male Institute of Cancer Research mice were used in this study. The scopolamine-induced cognitive impairment mice model was used. Glycyrrhizic acid was orally administered to mice once daily for 21 days, while scopolamine (1 mg/kg) treatment was delivered 30 minutes before behavioral tests. Donepezil (2 mg/kg) was used as a positive drug control. To evaluate the effect of glycyrrhizic acid, the following assessments were performed on hippocampal tissue: Y-maze test, acetylcholinesterase activity, antioxidant enzymes’ activity (superoxide dismutase, catalase). Western blotting for phosphor-extracellular signal-regulated kinase, P38, and c-Jun NH2-terminal kinase was conducted. Results: We found that glycyrrhizic acid administration significantly improved scopolamine-induced cognitive impairment in the Y-maze test. The acetylcholinesterase activity, superoxide dismutase, and catalase activity in the glycyrrhizic acid-treated group showed a significant reversal of cognitive impairment compared with the scopolamine-treated group. Conclusions Our results suggest that glycyrrhizic acid has a neuroprotective effect on cognitive function in scopolamine-induced cognitive impairment.

Inflammatory myopathy is characterized by symmetrical proximal muscle weakness, elevated muscle enzyme levels and favorable response to glucocorticoids therapy. Although periorbital edema is a common manifestation of inflammatory myopathy, generalized subcutaneous edema is very rare. We report here a case of a 47-year-old female patient with acute polymyositis/systemic lupus erythematosus overlap syndrome with generalized subcutaneous edema and interstitial lung disease. We aggressively treated the disease with high-dose glucocorticoids, intravenous immunoglobulin, and immunosuppressive agents.
Edema* ; Female ; Glucocorticoids ; Humans ; Immunoglobulins ; Immunosuppressive Agents ; Lung Diseases, Interstitial* ; Middle Aged ; Muscle Weakness ; Muscles ; Myositis

Melatonin, which is the main product of the pineal gland, has well documented antioxidant and immune-modulatory effects. Macrophages produce molecules that are known to play roles in inflammatory responses. We conducted microarray analysis to evaluate the global gene expression profiles in response to treatment with melatonin in lipopolysaccharide (LPS) activated RAW 264.7 macrophage cells. In addition, eight genes were subjected to real-time reverse transcription polymerase chain reaction (RT-PCR) to confirm the results of the microarray. The cells were treated with LPS or melatonin plus LPS for 24 hr. LPS induced the up-regulation of 1073 genes and the down-regulation of 1144 genes when compared to the control group. Melatonin pretreatment of LPS-stimulated RAW 264.7 cells resulted in the down regulation of 241 genes and up regulation of 164 genes. Interestingly, among genes related to macrophage-mediated immunity, LPS increased the expression of seven genes (Adora2b, Fcgr2b, Cish, Cxcl10, Clec4n, Il1a, and Il1b) and decreased the expression of one gene (Clec4a3). These changes in expression were attenuated by melatonin. Furthermore, the results of real-time PCR were similar to those of the microarray. Taken together, these results suggest that melatonin may have a suppressive effect on LPS-induced expression of genes involved in the regulation of immunity and defense in RAW 264.7 macrophage cells. Moreover, these results may explain beneficial effects of melatonin in the treatment of various inflammatory conditions.
Down-Regulation ; Gene Expression ; Macrophages ; Melatonin ; Microarray Analysis ; Pineal Gland ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Transcriptome ; Up-Regulation

Recently, Sun et al (2008) reported that the IL6R polymorphism is associated with schizophrenia. Therefore, to detect the association between polymorphisms of interleukin 31 receptor A (IL31RA) and schizophrenia, we genotyped 9 SNPs [rs9292101 (intron 1), rs1009639 (exon 2, Pro43Pro), rs2161582 (intron 2), rs68761890 (intron 5), rs16884629 (intron 6), rs11956465 (intron 12), rs12153724 (intron 12), and rs16884641 (intron 14)] using the Golden Gate assay on Illumina BeadStation 500 GX. Two hundred eighteen patients with schizophrenia and 379 normal subjects were recruited. Patients with schizophrenia were diagnosed according to DSM-IV, and control subjects without history of psychiatric disorders were selected. We used SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs for the evaluation of genetic data. Of nine polymorphisms, three SNPs (rs9292101, rs1009639, and rs11956465) were associated with schizophrenia. The rs9292101 and rs11956465 showed significant associations with the risk of schizophrenia in the codominant [rs9292101, odds ratio (OR)=0.74, 95% confidence interval (CI)=0.58~0.95, p=0.017] and recessive (rs11956465, OR=0.64, 95% CI=0.42~0.96, p=0.034) models, respectively. The rs1009639 also was statistically related to schizophrenia in both codominant (OR=0.76, 95% CI=0.60~0.97, p=0.025) and dominant (OR=0.66, 95% CI=0.44~0.98, p=0.035) models. Two linkage disequilibrium (LD) blocks were made. In the analysis of haplotypes, a haplotype (GCT) in block 1 and a haplotype (CCACAG) in block 2 showed significant associations between schizophrenia and control groups (haplotype GCT, frequency=0.509, chi square=4.199, p=0.040; haplotype CCACAG, frequency=0.289, chi square=5.691, p=0.017). The results suggest that IL31RA may be associated with risk of schizophrenia in Korean population.
Diagnostic and Statistical Manual of Mental Disorders ; Genes, vif ; Haplotypes ; Humans ; Interleukins ; Lidocaine ; Linkage Disequilibrium ; Odds Ratio ; Polymorphism, Single Nucleotide ; Schizophrenia ; Solar System

Pre-B-cell leukemia transcription factor 1 (PBX1), which is located on chromosome 1q23, was recently reported to be associated with type 2 diabetes mellitus. We examined whether single nucleotide polymorphisms (SNPs) of the PBX1 gene are associated with overweight/obesity in a Korean population. We genotyped 66 SNPs in the PBX1 gene and investigated their association with clinical phenotypes found in 214 overweight/obese subjects and 160 control subjects using the Affymetrix Targeted Genotyping chip array. Seven SNPs (g.+75186C>T, g.+78350C>A, g.+80646C>T, g.+138004C>T, g.+185219G>A, g.+191272A>C, and g.+265317T>A) were associated with the risk of obesity in three models (codominant, dominant, and recessive) (P=0.007-0.05). Haplotype 1 (CAC) and 3 (TAC) of block 3 and haplotype 2 (GGAAT) of block 10 were also strongly associated with the risk of obesity. In the control group, subjects that had homozygote for the major allele for both g.+185219G>A and g.+191272A>C showed lower high density lipoprotein-cholesterol (HDL-C) level compared to those possessing the minor allele, suggesting that the association between the homozygote for the major allele for both g.+185219G>A and g.+191272A>C and HDL-C is attributable to the increased risk of obesity. This study suggests that the PBX1 gene is a possible risk factor in overweight/obese patients.
Alleles ; Diabetes Mellitus, Type 2 ; Haplotypes ; Homozygote ; Humans ; Obesity ; Phenotype ; Polymorphism, Single Nucleotide ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Risk Factors ; Transcription Factors

PURPOSE: Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1alpha (HIF-1alpha) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1alpha-induced invasive characteristics. MATERIALS AND METHODS: Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on HIF-1alpha, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1alpha and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1alpha, tissue analysis was done. RESULTS: Hypoxia induces HIF-1alpha expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1alpha via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1alpha with RNA interference suppressed hypoxia-induced HIF-1alpha and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1alpha. These were confirmed in the orthotopic FTC model. CONCLUSION: Hypoxia induced HIF-1alpha, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.
Adenocarcinoma, Follicular/*genetics/metabolism ; Animals ; Anoxia/*genetics ; Cadherins/genetics ; Epithelial-Mesenchymal Transition/*genetics ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism ; Lymphokines ; Mice ; Neoplasm Invasiveness ; Phenotype ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Thyroid Neoplasms/*genetics/metabolism ; Transcriptional Activation ; Twist Transcription Factor/*genetics/metabolism ; Vimentin/metabolism

OBJECTIVE: To determine whether ACE insertion/deletion (I/D) polymorphism is associated with the ossification of the posterior longitudinal ligament (OPLL) of the spine in the Korean population. METHODS: A case-control study was conducted to investigate the association between I/D polymorphism of the angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) gene and OPLL. The 95 OPLL patients and 274 control subjects were recruited. Polymerase chain reaction for the genotyping of ACE I/D polymorphism was performed. The difference between the OPLL patients and the control subjects was compared using the contingency chi2 test and the logistic regression analysis. For statistical analysis, SPSS, SNPStats, SNPAnalyzer, and Helixtree programs were used. RESULTS: The genotype and allele frequencies of ACE I/D polymorphism showed significant differences between the OPLL patients and the control subjects (genotype, p<0.001; allele, p=0.009). The frequencies of D/D genotype and D allele in the OPLL group were higher than those in the control group. In logistic regression analysis, ACE I/D polymorphism was associated with OPLL (dominant model; p=0.002; odd ratio, 2.20; 95% confidence interval, 1.33-3.65). CONCLUSION: These results suggest that the deletion polymorphism of the ACE gene may be a risk factor for the development of OPLL in the Korean population.
Alleles ; Angiotensin I* ; Angiotensins* ; Case-Control Studies ; Gene Frequency ; Genotype ; Humans ; Logistic Models ; Longitudinal Ligaments* ; Peptidyl-Dipeptidase A* ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors ; Spine