• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.591-598
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• 2018

Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of genesilencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.292-297
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• 1994

This study was conducted to investigate antigenic potential of DA-3030, a recombinant human granulocyte-colony stimulating factor, in guinea pigs and mice. In the active systemic anaphylaxis test, the guinea pigs sensitized with 1.25 or 12.5 $\mu\textrm{g}$/head of DA-3030 alone did not show any anaphylactic reaction. In the homologous passive cutaneous anaphylaxis reaction, anti-DA-3030 antibody was not detected in guinea pigs sensitized with 1.25 or 12.5 $\mu\textrm{g}$/head of DA-3030 alone. On the other hand, the guinea pigs sensitized with 12.5 $\mu\textrm{g}$/heed of DA-3030 incorporated in Freund's complete adjuvant(FCA) or 1 mg/head of ovalbumin incorporated in FCA showed anaphylactic reaction. Anti-DA-3030 antibody was also detected in those guinea pigs. In immunodiffusion test using the sera sensitized with DA-3030 incorporated in FCA, precipitating antibodies were detected only in the sera sensitized with DA-3030 or DA-3030 incorporated in FCA showed. In 24-hour heterologous PCA reaction with sera of C57BL/6 mice immunized with 1.25 or 12.5 $\mu\textrm{g}$/head of DA-3030 alone, none of the sera showed positive reaction. But sera of the animals immunized with 12.5 $\mu\textrm{g}$/head of DA-3030 incorporated in aluminum hydroxide gel(Alum) or 5 $\mu\textrm{g}$/head of ovalbumin incorporated in alum showed positive PCA reaction. DA-3030 did not cause anaphylactic shock or passive cutaneous anaphylaxis in guinea pigs and mice when given alone although DA-3030 incorporated in FCA or Alum induced anaphylactic shock and passive cutaneous anaphylaxis. From these results, it may be concluded the DA-3030 does not induce systemic allergic reaction when administered alone in its clinical use.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.490-496
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• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• Toxicological Research
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• v.17
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• pp.145-155
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• 2001

Cytochrome P4502C19 (CYP2C19) is one of human polymorphic xenobiotic-metabolizing enzymes. The enzyme has been reported to catalyze more than 70 substrates, involving more than 100 reactions. These include several classes of therapeutic agents (e.g. anti-microbial. cardiovascular, psycho-active, etc.), sex hormones and insecticides. Associations of the CYP2C19 genotype/phenotype with individual differences in drug efficacy (e.g. diazepam, omeprazole, proguanil) and toxicity (e.g. mephenytoin, barbiturates) have been documented by many investigators. At least 11 allelic variants of CYP2C19 gene were reported to date. Most of the mutant alleles found in the poor metabolizer (PM) led to the production of truncated and/or inactive proteins. Except for the exon 6, single-nucleotide mutations were reported in all nine exons of the gene. Genetic polymorphism of CYP2C19 shows marked interethnic variation with the population frequencies of PM phenotype ranging from 1∼2% up to more than 50%. The prevalence of CYP2C19 PM tends to be higher in Asian and certain Pacific Islanders than other race or ethnic specificity. Genotyping results of CYP2C19 also revealed that there are different proportions of individual mutant alleles among ethnic populations. This may, in part, explains the interethnic difference in the metabolism of certain drugs (i.e. diazepam), though they were from the same CYP2C19 phenotype. Recently, our research group has studied the genotype and phenotype of CYP2C19 and found that the PM frequency (7∼8%) in Thais is lower than other Asian populations. Molecular and clinical impacts of this finding warrant to further investigation.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.1
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• pp.18-22
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• 2014

The antibacterial activities of methanol extracts of 19 commercial herbal medicines were measured against the fish pathogens Vibrio ichthyoenteri and Streptococcus iniae, which cause several fish diseases. Rhus javanica showed the strongest antibacterial activity against V. ichthyoenteri and S. iniae. The methanol extract of R. javanica was extracted further using several organic solvents with different polarities. The extract from the ethyl acetate fraction showed strong activity against both fish pathogens. The minimum inhibitory concentration (MIC) of the R. javanica extract was $32{\mu}g/mL$ for V. ichthyoenteri and $128{\mu}g/mL$ for S. iniae. Further purification and isolation of the active compound (s) responsible for these activities and further study of the synergistic effect using combinations of antibiotics against pathogenic bacteria are needed.

• Journal of Veterinary Clinics
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• v.25 no.4
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• pp.236-240
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• 2008

Parathyroid hormone (PTH) regulates calcium (Ca) and phosphate transport. Secondary hyperparathyroidism usually occur in chronic renal failure (CRF), and it is a common complication of CRF in dogs and cats. Twenty one dogs with renal failure were enrolled in this study. Plasma Ca, inorganic phosphorus (iP) and PTH concentrations were measured. Dogs were divided into two groups by the ratio of Ca to iP (Ca/iP$\leq$1; Group I, Ca/iP$\leq$1.5; Group II). The PTH level between sexes ages were not significantly different. The PTH level and Ca/iP between two groups were significantly different (p < 0.0001). In conclusion, The ratio of Ca to iP may be considered as useful surrogator to predict PTH level of dogs with renal failure.

• Journal of Haehwa Medicine
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• v.24 no.1
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• pp.47-60
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• 2015

Objective : The aim of this review is to analyze the study tendency in papers on Gyejibokryeong-hwan had been published in Korea from 1990 to 2014. Methods : We searched the four electronic database(NSDL, RISS, Korean traditional knowledge portal, OASIS) and checked relevant Korean journals from 1990 to 2014. We classified the papers by publication date, speciality, study method, and field of study, and analysed the study tendency. Results : After analyzing the papers, these results are revealed : 1. 2.12 papers were published annually on average. 2. As for the speciality of the journal, most of the papers were published in Traditional Korean Medicine, and a few were in Pharmacology. 3. As for the study method, in vitro was 32%, in vivo was 30%, and clinical case was 21%, 4. As for the subject of the studies, beneficial effect was 86%, toxicity was 8%, safety, stability and qualitative analysis was 2% each. 5. As for the studies about effectiveness on the diseases, 30% at gynecologic disease and 30% at vascular disease like arteriosclerosis. There were new studies for a variety of fields like cancer, urologic, and musculoskeletal diseases. Conclusions : These results suggest that Gyejibokryeong-hwan can be used as cure medicine, but there are not sufficient evidence based papers, so there should be further studies in order to establish Gyejibokryeong-hwan as a cure medicine.

• Advances in Traditional Medicine
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• v.5 no.1
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• pp.1-15
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• 2005

Ginseng is a popular medicinal plant highly valued throughout the world. Asian ginseng is one of the most common species of ginseng. It has long occupied a significant position in oriental medicine and has been justified its name as the 'king herb'. As a nutritional supplement, ginseng is an extremely common and popular herbal medicine in the United States and Canada in recent decades. The multiple constituents of ginseng possess equally multifaceted pharmacological actions as demonstrated by numerous studies. Ginseng root and its constituents influenced the central nervous system, endocrine, cardiovascular, gastrointestinal system, sexual, renal organ and immune system, etc. One important action is its anti-hyperglycemic effect. Previous studies on ginseng demonstrate that only the root of ginseng has been used in the treatment of diabetes, while the other parts of ginseng plant were always neglected. Recently, we analyzed the constituents of ginseng berry, leaf and discovered that ginseng berry, leaf extracts and its total ginsenosides have the ability to reduce hyperglycemia and body weight and increase the peripheral glucose utilization in obese or diabetic ob/ob or db/db mice. Our data suggest that all parts of ginseng plant, including root, berry, leaf and stem exhibit potent anti-hyperglycemic and anti-obese effects and may provide an opportunity to develop a novel class of anti-diabetic agents.

• Advances in Traditional Medicine
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• v.6 no.4
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• pp.286-292
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• 2006

In this study, we evaluated the antiproliferative effects of Panax notoginseng, ginsenoside Rb1, and notoginsenoside R1 in the human breast carcinoma MCF-7 cell line. Our results indicated that both Panax notoginseng radix extract (NRE) and Panax notoginseng rhizoma extract (NRhE) possess significant antiproliferative activities in MCF-7 cells. Compared to control group (100%), at the concentrations of 0.05, 0.5, and 1.0 mg/ml NRE, cell growth was concentration-dependently reduced to 81.0 ${\pm}$ 6.1 (P < 0.01), 34.2 ${\pm}$ 4.8 (P < 0.001), and 19.3 ${\pm}$ 1.9 (P < 0.001), respectively. Similar results with NRhE at concentrations of 0.5 and 1.0 mg/ml were obtained in these MCF-7 cells. To identify the responsible chemical constituent, we tested the antiproliferation effects of two representative saponins, ginsenoside Rb1 and notoginsenoside R1, on the MCF-7 cells. The data showed that ginsenoside Rb1 was endowed with antiproliferative properties, while notoginsenoside R1 did not have an inhibitory effect in the concentrations tested. Our studies provided evidence that Panax notoginseng extracts and ginsenoside Rb1 may be beneficial, as adjuvants, in the treatment of human breast carcinoma.

• Journal of Periodontal and Implant Science
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• v.50 no.5
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• pp.313-326
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• 2020

Purpose: This study was conducted to analyze specific RNA expression profiles in gingival tissue and saliva samples in periodontitis patients and healthy individuals, and to determine their correlations in light of the potential use of microarray-based analyses of saliva samples as a periodontal monitoring tool. Methods: Gingival tissue biopsies and saliva samples from 22 patients (12 with severe periodontitis and 10 with a healthy periodontium) were analyzed using transcriptomic microarray analysis. Differential gene expression was assessed, and pathway and clustering analyses were conducted for the samples. The correlations between the results for the gingival tissue and saliva samples were analyzed at both the gene and pathway levels. Results: There were 621 differentially expressed genes (DEGs; 320 upregulated and 301 downregulated) in the gingival tissue samples of the periodontitis group, and 154 DEGs (44 upregulated and 110 downregulated) in the saliva samples. Nine of these genes overlapped between the sample types. The periodontitis patients formed a distinct cluster group based on gene expression profiles for both the tissue and saliva samples. Database for Annotation, Visualization and Integrated Discovery analysis revealed 159 enriched pathways from the tissue samples of the periodontitis patients, as well as 110 enriched pathways In the saliva samples. Thirty-four pathways overlapped between the sample types. Conclusions: The present results indicate the possibility of using the salivary transcriptome to distinguish periodontitis patients from healthy individuals. Further work is required to enhance the extraction of available RNA from saliva samples.