• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8287-8292
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• 2016

Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p=0.8; Controls: D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3 'UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 'UTR is more informative than TSER polymorphism in predicting increased risk.

• Journal of Family Resource Management and Policy Review
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• v.17 no.1
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• pp.139-158
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• 2013

This research aimed to determine how a combined yoga and tea meditation program would affect the happiness of adolescents. The investigation was conducted over a total of 11 sessions held twice a week with 15 female middle-school students. Each session lasted 90 min and comprised preparation for 5 min, Hatha yoga for 50 min, tea meditation for 15 min, the expression of feelings for 15 min, and 5 min were allocated to finishing the program and announcing the next session time. A t-test was performed before and after the program to analyze the effects of the program. A goodness of fit test, which is related to the improvement of happiness, was done through a path analysis. As a result, we were able to determine meaningful changes in the t-test scores of happiness, stress, and quality of life. The scores of mindfulness, physical self-concept, and self efficiency changed positively, but meaningful changes were not shown. To derive a final conclusion, we verified the mediator effect with respect to happiness through a structural model. Consequently, physical self-concept was activated as a promoter for improving self-efficiency and mindfulness. Mindfulness was the key factor that improved the happiness of the adolescent subjects.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.145-149
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• 2003

Background: Apoptosis has been implicated in pathogenesis of various disease. Apo-1/Fas (CD95) is one of the main pathway of apoptosis. To examine the possible relationship between Apo-1/Fas (CD95) and primary knee osteoarthritis, MvaI restriction length polymorphism (RFLP) in human Apo-1/Fas (CD95) gene was assessed. Methods: Genotype and allele frequencies in promoter region in the Apo-1/Fas (CD95) gene were studied by PCR-RFLP in 226 Korean controls and 148 Korean patients with primary knee osteoarthritis. Results: No statistically significant difference in the genotypic distribution and allelic frequencies was found between the control and the knee oateoarthritis patients. But in the severe grade (grade 3, 4) Kellgren-Lawrence score patients, the frequency of $MvaI^*1$ (G) allele was significantly decreased (P=0.0392) and the of $MvaI^*2$ (A) allele frequency was significantly increased (P=0.0473) compared to the normal controls. Conclusion: Apo-1/Fas (CD95) gene polymorphism is a part a determinant factor of severity in knee osteoarthritis, the patients with $MvaI^*2$ (A) allele is more severe radiologic progression. Further substantiation studies are needed in larger patient samples and various other apoptosis related genes to elucidate the mechanism of osteoarthritis, including the Fas ligand gene analysis.

• Genomics & Informatics
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• v.9 no.3
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• pp.114-120
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• 2011

Chronic inflammation has been implicated as one of the important etiological factors in insulin resistance and type 2 diabetes mellitus (T2DM). To investigate the role of anti-inflammatory cytokines in the development of T2DM, we conducted a case-control study to assess the association between IL4/IL4R polymorphisms and disease risk. We firstly identified single nucleotide poly-morphisms (SNP) at IL4 and IL4RA loci by sequencing the loci in Korean participants. Case-control studies were conducted by genotyping the SNPs in 474 T2DM cases and 470 non-diabetic controls recruited from community-based cohorts. Replication of the associated signals was performed in 1,216 cases and 1,352 controls. We assessed effect of IL4 -IL4RA interaction on T2DM using logistic regression method. The functional relevance of the SNP associated with disease risk was determined using a reporter expression assay. We identified a strong association between the IL4 promoter variant rs2243250 and T2DM risk (OR=0.77; 95% CI, 0.67~0.88; p=$1.65{\times}10^{－4}$ in the meta-analysis). The reporter gene expression assay demonstrated that the presence of rs2243250 might affect the gene expression level with ~1.5-fold allele difference. Our findings contribute to the identification of IL4 as a T2D susceptibility locus, further supporting the role of anti-inflammatory cytokines in T2DM disease development.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.636-642
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• 2007

Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.487-496
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• 1995

Previous studies have demonstrated that not all A. actinomycetemcomitans produced significant level of leukotoxic factor and its leukotoxicity have associated with serotype and genetic variation. Our aim was to investigate on the interrelationship between serotype and leukotoxicity of an A. actinomycetemcomitans consisting of 13 clinically well characterized. Korean isolates and to evaluate if particular virulent clonal types of A. actinomycetemcomitans are associated with periodontal disease. For this study, 13 strains of A. actinomycetemcomitans from 6 patients with periodontal disease were isolated and identified by using a selective medium(tryptic soy agar supplemented with 10% serum, $75{\mu}g$ of bacitracin and $5{\mu}g$ of vancomycin per ml) in 10% C02 incubator for 3days with routine Gram staining, colony morphology and biochemical test..For serotyping, antisera were prepared from reference strains of 5 serotypes. (ATCC 29523,Y4, SUNY aB 67, IDH 781, IDH 1705) and then ammonium sulfate precipitation, immunoabsorption and indirect immunofluoroscent procedures were done. For analysis of leukotoxicity, sonic extract of A. actinomycetemcomitans exposed to PMN, and trypan blue was stained for counting the cell viability. Finally Southern blot analyses of genomic DNA digested with the restriction enzyme Tag I was done and the Southern blots were hybridized with the 530bp fragment, termed delta 530, originating from the ltx promoter of strain 652 and deleted from strain JP2. Also ltxA-3.1 and SC2 probe from strain JP2 were hybridized with genomic DNA fragments. Results reveal that strains isolated showed approximately equal proportions of 3 serotypes(b, d, e) and serotype b was not detected. 2 patients harbored 2 different serotypes in the same disease site. The prevalence of leukotoxic strain was 23% and there was no relationship between serotype, leukotoxicity and clinical observations. Especially virulent clonal types of Actinobacillus actinomycetemcomitan (JP2 strain) could not found. Further studies are necessary on the genetic polymorphism of leukotoxin and its relations to clinical status.

• BMB Reports
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• v.36 no.2
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• pp.223-229
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• 2003

The product of a tree (Tabebuia avellanedae) from South America, $\beta$-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells. We observed that the proliferation-inhibitory effect of $\beta$-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that $\beta$-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, $\beta$-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor $p21^{WAF1/CIP1}$ expression in a p53-independent manner, and the p21 proteins that were induced by $\beta$-lapachone were associated with Cdk2. $\beta$-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for $\beta$-lapachone. This may explain some of its anticancer effects.

• Journal of Plant Biotechnology
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• v.42 no.3
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• pp.168-179
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• 2015

We previously identified the rice gene, OsSAP, as an encoder of a highly conserved putative senescence-associated protein that was shown to have anti-apoptotic activity. To confirm the role of OsSAP in inducing abiotic stress tolerance in rice, we introduced OsSAP and AtBI-1, a plant homologue of Bax inhibitor-1, under the control of the CaMV 35S promoter into the rice genome through Agrobacterium-mediated transformation. The OsSAP transformants showed a similar chlorophyll index after salinity treatments with AtBI-1. Furthermore, we compared the effects of salinity stress on leaves and roots by examining the hormone levels of abscisic acid (ABA), jasmonic acid (JA), gibberellic acid (GA3), and zeatin in transformants compared to the control. With the exception of phytohormones, stress-induced changes in hormone levels putatively related to stress tolerance have not been investigated previously. Hormonal level analysis confirmed the lower rate of stress in the transformants compared to the control. The levels of ABA and JA in OsSAP and AtBI-1 transformants were similar, where stress rates increased after one week and decreased after a two week period of drought; there was a slightly higher accumulation compared to the control. However, a similar trend was not observed for the level of zeatin, as the decrease in the level of zeatin accumulation differed in both OsSAP and AtBI-1 transformants for all genotypes during the early period of salinity stress. The GA3 level was detected under normal conditions, but not under salinity stress.

• Molecules and Cells
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• v.43 no.4
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• pp.373-383
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• 2020

Our previous study revealed a novel role of Fas-associated death domain-containing protein (FADD) in islet development and insulin secretion. Insulin-degrading enzyme (IDE) is a zinc metalloprotease that selectively degrades biologically important substrates associated with type 2 diabetes (T2DM). The current study was designed to investigate the effect of FADD phosphorylation on IDE. We found that the mRNA and protein levels of IDE were significantly downregulated in FADD-D mouse livers compared with control mice. Quantitative real-time polymerase chain reaction analysis showed that FADD regulates the expression of IDE at the transcriptional level without affecting the stability of the mRNA in HepG2 cells. Following treatment with cycloheximide, the IDE protein degradation rate was found to be increased in both FADD-D primary hepatocytes and FADD-knockdown HepG2 cells. Additionally, IDE expression levels were reduced in insulin-stimulated primary hepatocytes from FADD-D mice compared to those from control mice. Moreover, FADD phosphorylation promotes nuclear translocation of FoxO1, thus inhibiting the transcriptional activity of the IDE promoter. Together, these findings imply a novel role of FADD in the reduction of protein stability and expression levels of IDE.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7763-7768
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• 2014

Background: Gastritis and gastric cancer are the most common diseases in the Kazakh population. Polymorphisms in genes coding of cytokines have been played important role with gastric disease risk. The risk alleles of cytokines in patients with gastritis can predict the risk of developing gastric cancer. The aim of this study was to investigate cytokine gene polymorphisms as risk factors for the development of gastritis in a case-control study with gastritis patients and healthy individuals from the Kazakh ethnic group, living in North Kazakhstan. Materials and Methods: The polymerase chain reaction followed by direct sequencing were used for detection of two functional polymorphisms in the IL1 gene family, and TaqMan SNP Genotyping Assay Sets were applied for three potentially functional polymorphisms in the IL10 gene, and one in the TNFA promoter. Results: Association analysis of studied allelic variants and the development of gastritis in H. pylori-positive patients showed that IL1B -31C/C, IL1B -511T/T and IL1RN -2/2 allelic variants were associated with development of gastritis (OR=1.8 (1.07-3.16), p=0.025; OR=1.7 (1.04-2.99), p=0.035, and OR=4.92 (2.45-9.85), p<0.001) respectively. Haplotype C-Т that combines both homozygous allelic variants of IL1B gene also had a statistically significant association with slightly higher OR (OR: 1.43, 95% CI: 1.08-1.88). Conclusions: The data from the current study showed that the genotype IL-1B -511Т/-31C-IL1-RN-2 and H. pylori infection increase risk of gastritis in the Kazakh population. That genotype combination might be a factor increasing the risk of developing gastric cancer.