• Clinical and Experimental Reproductive Medicine
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• v.45 no.4
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• pp.154-162
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• 2018

Objective: The fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated. Methods: The functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings. Results: The production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-${\beta}$ estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C). Conclusion: These results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OEE6/E7 cell line.

• The Korea Journal of Herbology
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• v.24 no.2
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• pp.49-56
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• 2009

Objectives : Inflammation is important event in the development of vascular diseases including hypertension, atherosclerosis, and restenosis. Bodusan (BDS) was a traditional Korean herbal medicine and widely used in treatment of gastrointestinal complaint and stomach ulcer. The aim of this study was to determine whether BDS and its components inhibit production of nitrite, PGE2 and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Methods : Cytotoxic activity of BDS and its components on RAW 264.7 cells was using 5-(3caroboxymcrophages. eth-oxyphenyj)-2H-tetra-zolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were detected by western blot. Results : Our results indicated that BDS and its components significantly inhibited the LPS-induced NO and PGE2 production. Moreover. BDS and its components inhibited iNOS and COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-11${\beta}$, IL-6 and MCP-1 formation in macrophages. Conclusions: These results indicate that BDS and its components have potential as an anti-inflammatory agent.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1099-1104
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• 2014

Aims and Background: Ginsenoside Rh2, which exerts the potent anticancer action both in vitro and in vivo, is one of the most well characterized ginsenosides extracted from ginseng. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between ginsenoside Rh2 and phosphoglucose isomerase/autocrine motility factor (PGI/AMF). Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PGI/AMF was assessed by western blot analysis and reverse transcription- PCR (RT-PCR) assay after transfection of a small interfering (si)-RNA to silence PGI/AMF. The effect of PGI/AMF on proliferation was measured by typan blue assay and antibody array. A cell counting kit (CCK)-8 and flow cytometry (FCM) were adopted to investigate the effects of Rh2 on PGI/AMF. The relationships between PGI/AMF and Rh2 associated with Akt, mTOR, Raptor, Rag were detected by western blot analysis. Results: KG1${\alpha}$ cells expressed PGI/AMF and its down-regulation significantly inhibited proliferation. The antibody array indicated that the probable mechanism was reduced expression of PARP, State1, SAPK/JNK and Erk1/2, while those of PRAS40 and p38 were up-regulated. Silencing of PGI/AMF enhanced the sensibility of $KG1{\alpha}$ to Rh2 by suppressing the expression of mTOR, Raptor and Akt. Conclusion: These results suggested that ginsenoside Rh2 suppressed the proliferation of $KG1{\alpha}$, the same as down-regulation of PGI/AMF. Down-regulation of PGI/AMF enhanced the pharmacological effects of ginsenoside Rh2 on KG1${\alpha}$ by reducing Akt/mTOR signaling.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7433-7436
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• 2014

Background: Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients. Materials and Methods: Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers. Results: Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were $80{\mu}g/L$, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86). Conclusions: Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas.

• Molecules and Cells
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• v.38 no.2
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• pp.156-162
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• 2015

Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

• Journal of Genetic Medicine
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• v.5 no.2
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• pp.105-110
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• 2008

Purpose: Preecalmpsia is a pregnancy-specific disorder that reflects widespread endothelial dysfunction resulting from increases of adhesion molecule expression. Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenetic mechanisms responsible for preeclampsia, and ICAM-1 plasma levels and/or function is genetically influenced. Therefore, we evaluated the distribution of ICAM-1 gene K469E polymorphism in pregnant Korean women with preeclampsia and evaluated the association between this polymorphism and preeclampsia. Methods: The K469E polymorphism was analyzed in peripheral blood samples from 197 preeclamptic pregnancies and 193 normotensive pregnancies by a SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results: Genotypic and allelic frequencies of ICAM-1 gene polymorphism (K469E) did not differ between preeclamptic and normotensive pregnancies. The distributions of the KK, KE, and EE genotypes were 40.6%, 43.7%, and 15.7%, respectively, in preeclamptic pregnancies and 38.9%, 45.1%, and 16.1%, respectively, in normotensive pregnancies. The frequencies of K and E alleles were 0.62 and 0.38, respectively, in preeclamptic pregnancies and 0.61 and 0.39, respectively, in normotensive pregnancies. By multiple logistic regression analysis, there was no increased risk of preeclampsia in subjects with ICAM-1 KE (OR, 1.08; P=0.74) or EE (OR, 1.07; P=0.88) genotypes. Conclusion: This study suggests that the ICAM-1 gene K469E polymorphism does not associate with an increased risk of preeclampsia in pregnant Korean women.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.56-61
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• 2009

Purpose: Preeclampsia is a multifactorial disorder with genetic and environmental components. Recently, the STOX1 gene, identified as a candidate gene for preeclampsia in Dutch women, has been shown to be placentally expressed and subject to imprinting with preferential transmission of the maternal allele. The purpose of this study is to investigate whether there is an association between the STOX1 Y153H variation and preeclampsia in Korean pregnant women. Materials and Methods: This study involved 202 preeclamptic and 204 healthy pregnant women who were genotyped for the Y153H variant of the STOX1 gene using a commercially available SNapShot assay kit and an ABI Prism 3730 DNA Analyzer. Results: There were no significant differences in genotype frequencies of the Y153H variant of the STOX1 gene between preeclamptic patients and normal controls (P>0.05). The H allele frequency of the STOX1 Y153H variation was similar in patients with preeclampsia (87.1%) and in normal controls (86.5%). In addition, multiple logistic regression analysis showed that the YH, HH, and YH/HH genotypes were not associated with an increased risk of preeclampsia when compared to the YY genotype. Conclusion: This is the first study to characterize the Y153H variant of the STOX1 gene in Korean patients with preeclampsia. We found no differences in the genotype and allele frequencies between preeclamptic and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the STOX1 Y153H variation is not associated with the development of preeclampsia in Korean pregnant women.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.143-146
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• 2010

Purpose: Insulin is involved in carbohydrate metabolism and also it's very important because it increases storage of glycogen, synthesis of fatty acids, absorption of amino acid, synthesis of protein. Insulin is clinically useful when we evaluate fasting patients in hypoglycemia, classify and predict diabetes, assess the activity of ${\beta}$-cell, research insulin resistance. We are going to increase usability of insulin assay by establishing normal reference value according to statistical analysis. Material & Method: We selected 6,648 patients who visited asan health medical center from May to August in 2008. We set exclusion criteria as family of diabetes, diabetes medication, the past history of blood glucose rise, more than 100 mg/dL in normal fasting blood glucose, outside the scope of BMI 18.5~22.9 $kg/m^2$, and more than HbA1c 6.5%. We determine whether the subgroup is portioned as sex and age or not and establish normal reference value by conducting statistical analysis as Bayesian's method and Hoffman's method. Result: Portioning of subgroup as sex and age is not needed. By statistical analysis of Bayesian method, results 1.5-11.0 uIU/mL. By statistical analysis of Hoffman method, results 1.8~12.8 uIU/mL. Conclusion: We established 1.8~12.8 uIU/mL as Insulin normal reference value by Hoffman method. This is a similar value with reporting reference value 1.7~11.8 uIU/mL in kit. This will enhance the usability of insulin assay by establishing normal reference value.

• The Korean Journal of Nuclear Medicine Technology
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• v.26 no.1
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• pp.42-46
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• 2022

Purpose In the meantime, there have been not many samples that require dilution, and it has been difficult for the examiner to set an appropriate dilution multiple for RIA test item and report the results. Accordingly, it was judged that it was necessary to set the maximum dilution multiple for each test and to verify the upper limit of the clinical reportable range. Therefore, in this study, the maximum dilution multiple for each RIA test was set and the upper limit of the clinical reportable range was verified accordingly Materials and Methods Among all RIA tests conducted at Asan Medical Center, the study treated on 30 types of tests which also conduct the dilution test. Data from March to July 2021 were collected and analyzed. The study was conducted on samples subjected to serial dilutions such as X2, X4 or X10, X10², X10³, X10⁴, X10⁵. Results Among a total of 30 test types, 18 test types have more than 5 N values in the tolerance range of 80~120%. As a result of the verification of maximum dilution multiples, the test set to 10⁴ is 𝛼-fetoprotein and thyroglobulin, and the test set to 10³ is CA-125, CEA, and 𝛽-hCG, and the test set to 10² is Free PSA, PSA, CA15-3, SCC, Ferritin, PTH, Cortisol, and Calcitonin. Tests set to 10 include three categories: 𝛽2-Microglobulin, C-peptide, and Testosterone. Conclusion It is expected that it will contribute to improving the quality of nuclear medicine blood tests as the results of dilution experiments can be reported quickly and accurately through the verification of the clinical reportable range.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.