• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10513-10524
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• 2015

Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5147-5152
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• 2016

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.1
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• pp.5-17
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• 2000

To evaluate the possible therapeutic effects of growth hormone and vitamin C on multiorgan failure, a rat model was developed for LPS-induced sepsis. Using this model, the effects of growth hormone and vitamin C on tissue damages, catalase and i-NOS activities, and MDA levels were examined in the lung and liver. The level of TNF- in plasm was also examined. Male, Sprague-Dawley rats were injected with LPS intraperitoneally then divided into 3 groups : positive controls injected with LPS only, the ones injected with growth hormone or vitamin C immediately after the LPS injections. The lung and the liver were then isolated, blood samples were collected at 24 or 48 hours after the LPS injection, then examined for histopathological and biochemical changes. The results obtained were as follows. 1. LPS induced sinusoid vasodilation and mild destruction of lobular structure in the liver. In the lung, alveolar structure appeared to be thickened and interstitial edema was observed. The levels of MDA in the liver and the lung was increased by LPS, while the activity of catalase was decreased. The activity of i-NOS of those tissues was also increased, which was more pronounced at 24 hr. The level of TNF- in plasm was increased by LPS 2. In the lung, vitamin C suppressed lymphocyte and neutrophil infiltration, alveolar wall thickening and interstitial edema. In the liver, vitamin C protected against the destruction of the lobular structure. The activity of catalase reduced by LPS was reversed partly by vitamin C. The activity of i-NOS enhanced by LPS was also reversed by vitamin C. The level of TNF- in plasm reduced in some animals by vitamin C, which however was not significant statistically(p<0.05). 3. Growth hormone showed similar protective effects against inflammation and damages in the liver and lung tissues. Growth hormone reversed partly the LPS effects on the level of MDA, the activity of catalase and i-NOS induction in the liver and the lung. Growth hormone reduced plasma level of TNF-${\alpha}$ substantially, which contrasted from vitamin C. Besides this, overall protective effects of growth hormone against LPS-induced experimental sepsis were similar to those of vitamin C. From this results, the mechanism of growth hormone on suppression of LPS-induced tissue damage might be associated with production of antioxidative enzyme and suppression of plasma TNF- level.

• The Korea Journal of Herbology
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• v.35 no.1
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• pp.45-55
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• 2020

Objectives : The purpose of this study is to determine whether Rhus verniciflua Stokes with Latin name Lacca Sinica Exsiccata, and Eucommia ulmoides Oliver with Latin name Eucommiae Cortex Extract Combination (ILF-RE) improves laboratory test results in participants with liver function disorder. Methods : This study was conducted at Woosuk university Korean medicine hospital where participants with high serum alanine transaminase (ALT) levels from 45 to 135 U/L were enrolled. Subjects received ILF-RE 3.6 g (1.2 g/day as ILF-RE) or placebo 3.6 g for 12 weeks. It was confirmed that urushiol was not detected in ILF-RE. The primary outcomes were the decrement degree of serum ALT and gamma-glutamyl transferase (GGT) levels between two groups. The secondary outcomes were the decrement degree of serum aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LD), total bilirubin, total cholesterol, triglyceride (TG) and fatty liver index (FLI) levels between two groups. Adverse events, skin prick tests, laboratory tests, and vital signs were observed and analyzed to confirm the safety of ILF-RE.1) Results : In the ILF-RE group, the liver function index ALT, GGT, lipid metabolism index TG, and fatty liver index FLI were significantly decreased compared to the placebo group. There was no significant difference in ILF-RE group in terms of adverse events, severe adverse events, skin prick test, laboratory test, and vital signs compared with placebo group. Conclusions : ILF-RE was found to be effective in improving liver function. In addition, no clinically significant adverse events or body changes were observed during this study.

• Journal of Oriental Neuropsychiatry
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• v.3 no.1
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• pp.3-24
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• 1992

This paper is aimed at finding out the clue to the medical solution to the pathological phenomena of the dehumanizing and demoralizing state of our society by centering around the Chiljeong that originates from Oriental Medicine, Sung Confucianism and Sa-sang Medicine(四象醫學). In these fields,the Chiljeong is based on the theory of Eum-yang and Viscera(陰陽.臟腑論) in Oriental Medicine, on the problems of good and evil in Sung Cunfucianism and on the theory of Sa-sang Visceral Localization(四象.臟局의 理論) in Sa-sang Medicine. The principles of geneation of Chiljeong : In case of Oriental Medicine, Sin(神) controls Chiljeong and of it is stored in five Viscera, it becomes Sin in the Heart, Hon(魂) in the Liver, Sa(思) in the Spleen, Bed-Woo(悲.憂) in the Lung, and Kyeong-Kong(驚.恐) in the Kidney. Then five Viscera react with outer stimuli or Sin, it gives off Chiljeong as Joy(from the Heart), Anger(from the Liver). Thought (from the Spleen), Anxiety and Sorrow(from the Lung) and Surprise and Fear(from the Kidney) In Sung Confucianism, Sim(心) comtrols Seong-jeong(性.情), and at the moment of that Sim gives off Jeong(情), it becomes good when the Li(理) gibes off itself and then Chi(氣) follows Li, or Chi gives off itself and is regulated optimally, out it becomes evil when Li cannot preside over Chi and then shaded by cloudy Chi. The pathology: If the Chiljeong exceeds one's capacity, the corresponding Vicsera will be damaged, and the Passions(喜.怒.哀.樂) that may harm to four types of constitution severly are the Joy and Pleasure(in Tae-eum-in 太陰人 and So-eum-in 少陰人) and Grief and Anger(in Tae-yang-in 太陽人 and So-yang-in 少陽人), so one should be alert on some passions by regrding his constitutional frailty. More over, because of the variations in Sa-sang Visceral Localyzatin there is various ability in human affairs, but as the clumsiness in human affairs may make him hurt by it, so one should be prevented from these passions and human affairs, that is flowing Joy and Participations(黨與) in Tae-yang-in, flowing Pleasure and Dwelings(居處) in So-yang-in, explosive Anger and Companies(交遇) in So-eum-in, explosive Grief and Affairs(事務) in Tae-eum-in. How to clutivate the human nature: The ulitmate purpose in Oriental Medicine is preserving Cheon-Jin(天眞), that is following the Tao(道) by making him be in harmony with the Chi(氣) of the Seasons and by living a simple life. In Sung Confucianism, the way preventing the lustful desire and preserving Cheon-li(天理) is to observate derectly the calm, original place of human nature with reverence, when Sim has nat given off itself yet, and when Sim has already given off, it also is to meditating on one's passion and thought that the principle of good should be researched on or the evil should be cut off according to it's being good or evil. Such like as these various aspects of research on the Chiljeong it will be helpful in understanding human nature by producing the various materials on it, moreover, by doing so, we can lead out appropriate solution on the confusions of judgement value and demoralization.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.61 no.2
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• pp.270-275
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• 2012

This paper presents a portable and compact optical device which can conveniently be used to perform a functional analysis of human liver function. The proposed system employed red/green LEDs, as a light source, and CMOS image sensor, which is commonly used in cellular phones. With this system, several blood serum samples have been evaluated for liver functional analysis by measuring light absorption level through the blood serum samples depending on aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin concentration. The light absorption through the blood serum samples containing AST, ALT, or total bilirubin can provide their concentrations. The green light absorption is more sensitive to the concentration of AST or ALT, and the red light absorption is more sensitive to the total bilirubuin concentration. Additional calibration steps were performed by using a MATLAB program in order to eliminate the light scattering effects from the extraneous particles existing in each blood serum sample. From the blind test, three standard light intensity curves through each enzyme have been obtained and the enzyme concentration values have been compared to those obtained from a commercially available biochemistry analyzer (Toshiba 200 FR). The average percent difference in the obtained concentrations from two systems for AST, ALT, and total bilirubin concentration came out to be 7.79%, 7.98%. and 7.56%, respectively, with the adjusted coefficient of determination (R2) higher than 0.98. This system can possibly lead to a low-cost and simple system that can be used as a point-of-care (POC) system in a condition without advanced equipments.

• Bioinformatics and Biosystems
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• v.1 no.1
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• pp.67-72
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• 2006

The aim of this paper is to discuss the effect of missing values in detecting differentially expressed genes in a cDNA microarray experiment in the context of a one sample problem. We conducted a cDNA micro array experiment to detect differentially expressed genes for the metastasis of colorectal cancer based on twenty patients who underwent liver resection due to liver metastasis from colorectal cancer. Total RNAs from metastatic liver tumor and adjacent normal liver tissue from a single patient were labeled with cy5 and cy3, respectively, and competitively hybridized to a cDNA microarray with 7775 human genes. We used $M=log_2(R/G)$ for the signal evaluation, where Rand G denoted the fluorescent intensities of Cy5 and Cy3 dyes, respectively. The statistical problem comprises a one sample test of testing E(M)=0 for each gene and involves multiple tests. The twenty cDNA microarray data would comprise a matrix of dimension 7775 by 20, if there were no missing values. However, missing values occur for various reasons. For each gene, the no missing proportion (NMP) was defined to be the proportion of non-missing values out of twenty. In detecting differentially expressed (DE) genes, we used the genes whose NMP is greater than or equal to 0.4 and then sequentially increased NMP by 0.1 for investigating its effect on the detection of DE genes. For each fixed NMP, we imputed the missing values with K-nearest neighbor method (K=10) and applied the nonparametric t-test of Dudoit et al. (2002), SAM by Tusher et al. (2001) and empirical Bayes procedure by $L\ddot{o}nnstedt$ and Speed (2002) to find out the effect of missing values in the final outcome. These three procedures yielded substantially agreeable result in detecting DE genes. Of these three procedures we used SAM for exploring the acceptable NMP level. The result showed that the optimum no missing proportion (NMP) found in this data set turned out to be 80%. It is more desirable to find the optimum level of NMP for each data set by applying the method described in this note, when the plot of (NMP, Number of overlapping genes) shows a turning point.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.306-316
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• 2009

Objectives : This study was performed to investigate the anti-fibrogenic effect of Curcumae Longae Radix on human hepatic stellate cells. Materials and Methods: Hepatic stellate cells (LX-2) were treated with various concentrations of Curcumae Longae Radix extract for 24, 48, and 72 hours. It was extracted with distilled water. After the treatment, cell viability, proliferation, cell cycle analysis, procollagen levels and the mRNA of the ASMA, TIMPl, TIMP2, MMP2, collagen type la, PDGF-receptor-beta and TGF-beta were measured by using MTT assay, BrdU assay, RT-PCR, and procollagen type 1 C-peptide EIA kit. Results : The viability of HSCs decreased in the 48 hours group, and proliferation of HSCs decreased as the concentration increased. In the cell cycle analysis, Curcumae Longae Radix decreased the ratio of M phase, and increased the ratio of apoptosis, G0/G1 and S phase. In the RT-PCR, the mRNA expression of the collagen type la and ASMA decreased with the Curcumae Longae Radix treatment. The production of procollagen by the HSCs was decreased by the treatment of Curcumae Longae Radix with high dose. Conclusion : These results suggest that Curcumae Longae Radix is helpful in the treatment of liver fibrosis as well as liver cirrhosis.

• Korean Journal of Veterinary Research
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• v.48 no.3
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• pp.347-355
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• 2008

Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, is persistent organic pollutants widely spread throughout the environment and human population. But little is known about the adverse biological effects of the PFOA. In the present study, the toxicological effects of PFOA were investigated in rats. Sprague-Dawley rats (N = 10 in each group) were orally administered with PFOA in drinking water for 4 weeks (0, 100, 200, or 400 ppm in male, and 0, 200, 400, or 800 ppm in female). Three female rats given 800 ppm died during the study. PFOA treatment decreased the body weight gain and increased the liver weights in both genders. Serum biochemical investigations revealed significant increases in the aspartate aminotransferase, alanine transaminase, alkaline phosphatase, blood urea nitrogen, total cholesterol, and total bilirubin in male but in female. Serum estradiol (E2) levels were increased in all treated rats. Histopathologically, hepatocellular hypertrophy around central vein was noted in the liver of treated rats. No significant histopathological changes were noted in other organs. In conclusion, PFOA induced toxicological changes in the liver and increased serum E2 level which was not related to histopathological changes of endocrine and reproductive system.

• Journal of Korean Biological Nursing Science
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• v.2 no.1
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• pp.49-63
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• 2000

Aflatoxin $B_1(AFB_1)$ is a potent hepatotoxic and hepatocarcinogenic mycotoxin in human beings. It is accumulated in animal tissues and injured cell through variable metabolic pathway. This study was conducted to determine the effect of antioxidant vitamins on liver function enzymes and hepatic damage of $AFB_1$ treated mice. The 6 weeks old male ICR mice were randomly separated 6 groups, vehicle solvent or vitamin C(10 mg/kg/day) and vitamin E(63.8 mg/kg/day) were administered by intraperitoneal(i.p.) injection and 1 hr later, vehicle solution(DMSO) or $AFB_1$(0.4 mg/kg) were injected. The results obtained as follow ; The levels of liver function enzymes such as GOT, GPT, LDH, and alkaline phosphatase, in sera of mice were remarkably elevated by treatment with $AFB_1$ only. However, those enzymes were significantly alleviated by co-treatment with antioxidant vitamins(p<0.01). Especially the levels of LDH and ALK phosphatase were similar to those of control groups(p<0.01). The transmission electron microscopy(TEM) image of intracellular microrganelles on the liver cell of mice was also degenerated extremely by treatment with $AFB_1$, but vitamin C and vitamin E gave good effects on cellular deformation. The intracellular microrganelles such as mitochondria, endoplasmic reticulum, nucleus and nucleic membrane were nearly disappeared the cellular deformation by antioxidant vitamins co-administration. With above results, we could estimated that antioxidant vitamins blocked AFB1 induced hepatic cell damage.