• Title/Summary/Keyword: BIOMARKER

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Drug Interaction between Ginseng Extract (GE) and Sorafenib (쏘라페닙과 홍삼추출물간의 약물상호작용)

  • Lee, Nam-Hee;Park, Ho-Jae;Rho, Ja-Sung;Kim, Mi-Kyung;Lee, Yu-Kyoung;Cho, Eun-A;Heo, Jeong;Cho, Mong;Hwang, Tae-Ho
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1518-1525
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    • 2011
  • Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

Comparison of Serum Osteopontin Levels in Patients with Stable and Chronic Obstructive Pulmonary Disease and Exacerbation (안정된 만성 폐쇄성 폐질환환자와 급성 악화상태의 혈중 Osteopontin 농도 비교)

  • Ma, Jeong-Eun;Lee, Seung-Hun;Kim, Yu-Eun;Lim, Su-Jin;Lee, Seung-Jun;Jeong, Yi-Yeong;Kim, Ho-Cheol;Lee, Jong-Deog;Hwang, Young-Sil;Cho, Yu-Ji
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.3
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    • pp.195-201
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    • 2011
  • Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding. However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD). Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD. Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects ($62.4{\pm}51.9ng/mL$, $36.9{\pm}11.1ng/mL$, $30{\pm}11ng/mL$, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission ($45{\pm}52.1ng/mL$, $62.4{\pm}51.9ng/mL$, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker ($23{\pm}5.7ng/mL$, $35.5{\pm}17.6ng/mL$, $58.6{\pm}47.8ng/mL$, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second ($FEV_1$%) predicted in healthy controls and stable COPD patients (r=-0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

Effect of Dietary Protein and Calcium Levels on Calcium Metabolism of the Rat (식이단백질과 칼슘 수준이 흰쥐의 칼슘대사에 미치는 영향)

  • Yoon, Gun-Ae;Hwang, Hye-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.2
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    • pp.176-180
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    • 2005
  • This study was conducted to examine effect dietary protein and calcium levels on calcium metabolism of the rat. Weaned 6-week old male rats were divided into 4 groups and were fed experimental diets for six weeks. Experimental groups were HPNC group-high protein normal calcium (protein: 400 g/kg diet, calcium: 0.5%), HPLC group-high protein low calcium (protein: 400 g/kg diet, calcium: 0.1%), NPNC group-normal protein normal calcium (protein: 200 g/diet, calcium: 0.5%), NPLC group-normal protein low calcium (protein: 200 g/diet, calcium: 0.1%). The calcium excretion in urine was higher in high protein group than in normal protein group, and it was highest in HPLC group. The activation of alkaline phophatase had a tendency to low in normal calcium group, and the concentration of parathyroid hormone (PTH) was the lowest in HPLC group. The deoxypyridinoline (DPD) concentration of urine was investigated as the highest in HPLC group and it was significantly lower in HPNC group that consumed normal calcium. The bone density of the femur was the highest in NPNC group and the lowest in NPLC group. As the results of this study, calcium excretion in urine and DPD density were the highest and the bone density was the lowest in HPLC group. It may suggest that the deficiency of calcium causes adversely effect in calcium metabolism upon consuming high protein diet. Therefore, it should be emphasized to consume enough calcium to prevent the hindrance of skeletal metabolism caused by deficiency of calcium upon consuming high protein diet.

Molecular Phylogenetic Study of the Endangered Land Snail Satsuma myomphala Based on Metallothionein Gene. (Metallothionein 유전자를 기초로 한 멸종위기 육상 달팽이 Satsuma myomphala (거제외줄달팽이) 의 분자계통학적 연구)

  • Sang, Min Kyu;Kang, Se Won;Hwang, Hee-Ju;Chung, Jong Min;Song, Dae Kwon;Min, Hye Rin;Park, Jie Eun;Ha, Hee Cheol;Lee, Hyun Jun;Hong, Chan Eui;Ahn, Young Mo;Park, So Young;Park, Young-Su;Park, Hong Seog;Han, Yeon Soo;Lee, Jun Sang;Lee, Yong Seok
    • The Korean Journal of Malacology
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    • v.32 no.4
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    • pp.263-268
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    • 2016
  • Metallothionein (MT) family of metal-binding proteins are involved in maintaining homeostasis and heavy metal poisoning. Recently, MT has been considered as a biomarker that can identify a particular species, very similar to the use of cytochrome oxidase I (COI) gene. Satsuma myomphala species of land snails have been reported from North-East Asia, including South Korea and Japan. In particular, the land snail species have been known from only a limited area of Geoje Island, Gyeongsangnam-do province of South Korea. Genetic studies of S. myomphala has been limited with only 6 nucleotide, 2 protein registered on the NCBI server. For elucidating the genetic information of S. myomphala, we conducted RNA sequencing analysis using Illumina HiSeq 2500 next-generation platform. We screened the MT gene from the RNA-Seq database to confirm the molecular phylogenetic relationship. After sequencing, the de novo analysis and clustering generated 103,774 unigenes. After annotation against PANM database using BLAST program, we obtained MT sequence of 74 amino acid residues containing the coding region of 222 bp. Based on this sequence, we found about 53 sequences using the BLAST program in NCBI nr database. Using ClustalX alignment, Maximum-Likehood Tree of MEGA program, we confirmed the molecular phylogenetic relationships that showed similarity with mollusks such as Helix pomatia and H. aspersa, Megathura crenulata.

The GSTT1 Genotype as A Marker for Susceptibility to Lung Cancer in Korean Female Never-Smokers (한국인 비흡연 여성에서 폐암의 유전적 감수성 표지자로서의 GSTT1 유전자형)

  • Jang, Sang Soo;Jung, Chi Young;Lee, Sin Yeob;Lee, Jae Hee;Jeon, Hyo-Sung;Park, Sun Ha;Son, Ji-Woong;Lee, Eung Bae;Kim, Chang Ho;Kam, Sin;Park, Rang Woon;Kim, In-San;Jung, Tae Hoon;Park, Jae Yong
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.5
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    • pp.485-494
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    • 2003
  • Background : Most previous studies regarding the role of GSTMl and GSTT1 on lung cancer risk have been focused mainly on male smokers. However, epidemiological characteristics, histologic types and risk factors are different in female and male lung cancers, we investigated the association between these genotypes and lung cancer risk in males and females separately. Materials and Methods : The study population consisted of 253 lung cancer (153 males and 100 females) and 243 controls (140 males and 103 females). GSTM1 and GSTT1 genotypes were determined by a multiplex PCR. Results : In the male population, neither GSTM1 nor GSTT1 null genotype showed significant difference between cases and controls. In the female population, the frequencies of GSTM1 null genotype showed no significant difference between cases and controls. However, the frequencies of GSTT1 null genotype was significantly higher in cases (70.3%) than controls (55.3%, odds ratio (OR)=2.18; 95% confidence interval (CI=l.21-3.93). When the female population was stratified by age and smoking status, the ORs for GSTT1 null genotype were significantly higher in subgroups of ${\leq}60$ years (OR=4.82; 95% CI=l.61-14.4) and never-smokers (OR=4.29; 95% CI=1.94-9.48) but not in subgroups of >60 years or smokers. When stratifying the female never-smokers by age, the ORs for GSTT1 null genotype were significantly higher in both age groups of ${\leq}60$ years (OR=7.64; 95% CI=2.00-29.2) and >60 years (OR=2.89; 95% CI=1.05-7.94). Conclusion : We found that GSTT1 null genotype was associated with an increased risk of lung cancer in Korean female never-smokers. This result suggests that GSTT1 null genotype could be used as a biomarker for genetic susceptibility to lung cancer in Korean female never-smokers.

Reduced Number of Endothelial Progenitor Colony-Forming Units in Patients with Preeclampsia

  • Kim, Shin-Young;Park, So-Yeon;Kim, Jin-Woo;Lee, Mi-Bum;Han, You-Jung;Ahn, Hyun-Kyong;Choi, Jun-Seek;Han, Jung-Yeol;Kim, Moon-Young;Choi, Kyu-Hong;Ryu, Hyun-Mee
    • Journal of Genetic Medicine
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    • v.7 no.2
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    • pp.138-144
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    • 2010
  • Purpose: Endothelial progenitor cells (EPCs), which mediates neovascularization of uterine endometrium may be involved in the neovascularization in the utero-placental circulation. Low numbers of endothelial progenitor colony-forming unit (CFU) in culture are predictive biomarker of vascular disease. The aim of the present study was to evaluate whether the number of CFU in preeclampsia differed from that in normal pregnancy. Materials and Methods: Women with singleton normal (n=26) or preeclamptic (n=20) pregnancies were studied during the third trimester. The number of EPCs was quantified by CFU methodology. Plasma levels of angiogenic factors, vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) were determined by enzyme-linked immunoassay. Results: CFU numbers were significantly decreased in the preeclamptic patients compared with the controls (median, 3; range 1-12 vs. 31; 3-81 CFU/well, P<0.001). A majority of the cells comprising individual colonies were positive for endothelial characteristics (Ulex europaeus lectin staining and acetylated low-density lipoprotein uptake). Plasma levels of the sFlt-1 were highly elevated (P<0.001) in patient with preeclampsia compared to controls, whereas PlGF were highly reduced (P=0.004), but these factors did not associate with CFU numbers. Conclusion: Our results suggest that reduced numbers of CFU obtained from maternal peripheral blood may contribute to the development of preeclampsia.

Trends in metabolic risk factors among patients with diabetes mellitus according to income levels: the Korea National Health and Nutrition Examination Surveys 1998~2014 (성인 당뇨병 환자의 소득수준에 따른 혈당, 당화혈색소, 혈압, 및 혈중지질 지표의 변화 추이 : 국민건강영양조사 1998~2014 분석 결과)

  • Cho, Sukyung;Park, Kyong
    • Journal of Nutrition and Health
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    • v.52 no.2
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    • pp.206-216
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    • 2019
  • Purpose: Management of the metabolic risk factors in diabetes patients is essential for preventing or delaying diabetic complications. This study compared the levels of the metabolic risk factors in diabetes patients according to the income levels, and examined the secular trends in recent decades. Methods: The data from the Korea National Health and Nutrition Examination Survey 1998 ~ 2014 were used. The diabetes patients were divided into three groups based on their household income levels. General information was obtained through self-administered questionnaires, and the blood biomarkers and blood pressure data were obtained from a health examination. Multivariable linear regression models were used to compare the metabolic biomarker levels according to the household income levels, adjusting for potential confounding factors. Results: The fasting blood glucose, hemoglobin A1c, and blood lipid (total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride) levels were similar in the three groups. During the survey period of 16 years, the blood pressure showed a significant decreasing trend with time in all groups (p < 0.001). In contrast, the fasting blood glucose (p = 0.004), total cholesterol (p < 0.001), and LDL-cholesterol levels (p = 0.007) decreased significantly, and the HDL-cholesterol level (p < 0.001) increased significantly in the highest-income groups. In the lowest-income group, the fasting blood glucose (p = 0.02), total cholesterol (p < 0.001), and triglyceride (p = 0.003) levels showed a significant decreasing trend over time. On the other hand, the middle-income group showed no significant change in any of the metabolic risk factors except for blood pressure. Conclusion: The level of management of metabolic risk factors according to the income level of Korean diabetes patients was similar. On the other hand, the highest- and lowest-income groups showed positive trends of management of these factors during 16 years of observation, whereas the middle-income group did not show any improvement.

Physicochemical properties of deposited particles on surface of pine leaves as biomarker for air pollution (솔잎가지 표면에 침착된 입자상 물질의 물리화학적 특성 및 대기오염 지표로서의 가능성 고찰)

  • Chung, David;Choi, Jeong-Heui;Lee, Jang-Ho;Lee, Soo-Yong;Lee, Ha-Eun;Park, Ki-Wan;Shim, Kyu-Young;Lee, Jong-Chun
    • Analytical Science and Technology
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    • v.31 no.6
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    • pp.247-258
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    • 2018
  • The purpose of the present study was to investigate whether the degree of air pollution can be evaluated via examination of local plants. Selected sites included two parks in an industrial area, as well as two parks in an urban area. Selected plant samples comprised one-year-old pine shoot leaves. Leaves growing over 2 m from the ground were collected from over 10 pine trees. Leaf surface was analyzed for deposition of 14 trace elements and 16 polycyclic aromatic hydrocarbons (PAHs), including particle size and mass, surface imaging, precipitation-mediated particle removal rate, and concentration. Particle size ranged from 0.4 to $200{\mu}m$, and the volume percentage of particles ${\leq}10$ was 20 %. Deposited particle mass ranged from 0.450-0.825 mg, and precipitation-mediated removal rate ranged from 10.0-27.6 %. Trace element concentration, as measured by ICP/MS after microwave acid digestion, was 18.8-26.3 mg/kg As, 0.08-0.13 mg/kg Be, 0.06-0.08 mg/kg Cd, 4.91-17.8 mg/kg Cr, 5.26-405 mg/kg Cu, 1,930-2,670 mg/kg Fe, 3.03-28.1 mg/kg Pb, 26.9-42.8 mg/kg Mn, 2.66-10.4 mg/kg Ni, 4,560-8,730 mg/kg Al, 2,500-6,120 mg/kg Ba, 5.27-17.8 mg/kg Rb, 40.9-95.3 mg/kg Sr, and 4,030-8,260 mg/kg Zn. Concentration of PAHs, as analyzed by GC/MS/MS after liquid-liquid extraction and purification of deposited particles, ranged from 1.17 to 12.378 mg/kg for ${\Sigma}PAH_{16}$ and from 1.17 to 12.378 mg/kg for ${\Sigma}PAH_7$.

The Induction of ROS-dependent Autophagy by Particulate Matter 2.5 and Hydrogen Peroxide in Human Lung Epithelial A549 Cells (미세먼지와 산화적 스트레스에 의한 인간 폐 상피 A549 세포에의 ROS 의존적 자가포식 유도)

  • Park, Beom Su;Kim, Da Hye;Hwangbo, Hyun;Lee, Hyesook;Hong, Su Hyun;Cheong, Jaehun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.32 no.4
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    • pp.310-317
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    • 2022
  • Recently, interest in the harmful factors of particulate matter (PM), a major component of air pollution, has been increasing. In particular, PM2.5 with a diameter of less than 2.5 ㎛ is well known to induce oxidative stress accompanied by autophagy in human lung epithelial cells. However, studies on whether PM2.5 increases autophagy under oxidative stress and whether this process is reactive oxygen species (ROS)-dependent are insufficient. Therefore, in this study, we investigated whether PM2.5 promotes autophagy through the generation of ROS in human alveolar epithelial A594 cells. According to our results, cells co-treated with PM2.5 and hydrogen peroxide (H2O2) showed a lower cell viability than cells treated with each alone, which was associated with increased total and mitochondrial ROS production. The co-treatment of PM2.5 and H2O2 also increased autophagy induction, which was confirmed through Cyto-ID staining, and the expression of autophagy biomarker proteins increased. However, when ROS generation was artificially blocked by N-acetyl-L-cysteine pretreatment, the reduction in cell viability and induction of autophagy by PM2.5 and H2O2 co-treatment were markedly attenuated. Therefore, the present results suggest that PM2.5-induced ROS generation may play a critical role in autophagy induction in A549 cells.

Fecal Microbiota Profiling of Holstein and Jersey, in South Korea : A Comparative Study (국내에서 사육되는 Holstein 젖소과 Jersey 젖소의 대변 미생물 분석 : 비교연구)

  • Gwangsu Ha;Ji-Won Seo;Hee Gun Yang;Se Won Park;Soo-Young Lee;Young Kyoung Park;RanHee Lee;Do-Youn Jeong;Hee-Jong Yang
    • Journal of Life Science
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    • v.33 no.7
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    • pp.565-573
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    • 2023
  • In light of the complex interactions between the host animal and its resident gut microbiomes, studies of these microbial communities as a means to improve cattle production are important. This study was conducted to analyze the intestinal microorganisms of Holstein (HT) and Jersey (JS), raised in Korea and to clarify the differences in microbial structures according to cattle species through next-generation sequencing. The alpha-diversity analysis revealed that most species richness and diversity indices were significantly higher in JS than in HT whereas phylogenetic diversity, which is the sum of taxonomic distances, is not significant. Microbial composition analysis showed that the intestinal microbial community structure of the two groups differed. In the both groups, a significant correlation was observed among the distribution of several microbes at the family level. In particular, a highly significant correlation (p<0.0001) among a variety of microbial distributions was found in JS. Beta-diversity analyis was to performed to statistically verify whether a difference exists in the intestinal microbial community structure of the two groups. Principal coordinate analysis and unweighted pair group method with arithmetic mean (UPGMA) clustering analysis showed separation between the HT and JS clusters. Meanwhile, permutational multivariate analysis of variance (PERMANOVA) revealed that their microbial structures are significantly different (p<0.0001). LEfSe biomarker analysis was performed to discover the differenc microbial features between the two groups. We found that several microbes, such as Firmicutes, Bacilli, Moraxellaceae and Pseudomonadales account for most of the difference in intestinal microbial community structure between the two groups.