• Title/Summary/Keyword: p53gene

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Gene Expression Patterns of Spleen, Lung and Brain with Different Radiosensitivity in C57BL6 Mice

  • Majumder Md. Zahidur Rahman;Lee, Woo-Jung;Lee, Su-Jae;Bae, Sang-Woo;Lee, Yun-Sil
    • Journal of Radiation Protection and Research
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    • v.30 no.4
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    • pp.197-208
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    • 2005
  • Although little information is available on the underlying mechanisms, various genetic factors have been associated with tissue-specific responses to radiation. In the present study, we explored the possibility whether organ specific gene expression is associated with radiosensitivity using samples from brain, lung and spleen. We examined intrinsic expression pattern of 23 genes in the organs by semi-quantitative RT-PCR method using both male and female C57BL/6 mice. Expression of p53 and p21, well known factors for governing sensitivity to radiation or chemotherapeutic agents, was not different among the organ types. Both higher expression of sialyltransferase, delta7-sterol reductase, leptin receptor splice variant form 12.1, and Cu/Zn superoxide dismutase (SOD) and lower expression of alphaB crystalline were specific for spleen tissue. Expression level of glutathione peroxidase and APO-1 cell surface antigen gene in lung tissue was high, while that of Na, K-ATPase alpha-subunit, Cu/ZnSOD, and cyclin G was low. Brain, radioresistant organ, showed higher expressions of Na, K-ATPase-subunit, cyclin G, and nucleolar protein hNop56 and lower expression of delta7-sterol reductase. The result revealed a potential correlation between gene expression patterns and organ sensitivity, and Identified genes which might be responsible for organ sensitivity.

Distribution of Beneficial Bacteria in the Intestines after Enzamin Ingestion of Bacillus subtilis AK Strain Fermentation (Bacillus subtilis AK균 발효액(Enzamin)의 섭취 후 장내 유익세균의 분포조사)

  • Ryu, Seo Won;Lee, Hyung H.
    • Journal of Naturopathy
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    • v.7 no.2
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    • pp.27-38
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    • 2018
  • Purpose: The purpose of this study was to investigate whether intestinal proliferation is promoted in beneficial intestinal bacteria or decreased in harmful bacteria before and after ingesting Bacillus fermentation broth (ENM) for 8 weeks in the 16 subjects. Method: Intestinal bacteria were identified by PCR amplification using specific 16S rRNA primers. Results: The Bifidobacterium gene index(%)(gi%) increased to 58.92% in the control group and 69.53% in the test group after the ingestion of ENM, but there was no significant difference. Lactobacillus gi% increased significantly (49.37% in the control and 66.43% in the test) (p<.029). Clostridium gi% was significantly decreased after treatment (83.16% in the control and 67.76% in the test) (p<.077). Bacteroides gi% increased significantly (12.58% in the control and 20.87% in the test) after ingesting (p<.095). Prevotella gi% increased significantly (7.55% in the control and 17.28% in the test) after ingesting (p<.005). After ingesting, the median bacteria increased significantly in the control (20.06%) and the test (35.88%) (p<.001). Conclusions: After ingestion of the ENM, the number of beneficial bacteria increased and the number of harmful bacteria Clostridium tended to decrease. This suggests that ingestion of the Bacillus fermented beverage ENM has an effect on the proliferation of intestinal bacteria.

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Association between ITGB2 Genetic Polymorphisms and Tuberculosis (ITGB2 유전자 다형성과 결핵 사이의 연관성 연구)

  • Jin, Hyun-Seok;Lee, Sang-In;Park, Sangjung
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.118-125
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    • 2018
  • Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), but the genes associated with the host immune system can be attributed to the development of TB. The ITGB2 gene encodes the integrin beta 2 chain CD18 protein and is present on chromosome 21. The integrin beta 2 chain is an integrin expressed in leukocytes and plays a very important role in leukocyte maturation and attachment. ITGB2 plays an important role in the phagocytosis of MTB and the aggregation of leukocytes in MTB infections. This study examined the genetic polymorphisms of the ITGB2 gene between the TB case and normal control using Korean genomic and epidemiologic data. As a result, a statistically significant correlation was confirmed in 10 SNPs. The most significant SNP was rs113421921 (OR=0.69, CI: 0.53~0.90, $P=5.8{\times}10^{-3}$). In addition, rs173098, one of the significant 10 SNPs, is possibly located in a binding motif with the transcription factor cofactor p300, and can affect ITGB2 gene expression. These findings suggest that the pathogenesis of TB may be influenced by a range of genetic factors related to the immune function of the host, e.g., the reactions associated with the recruitment and attachment of leukocytes. The results of this study could be used to predict the infection control for tuberculosis in a patient-tailored manner.

Assessment of Biomarkers in Acetaminophen-Induced Hepatic Toxicity by siRNA

  • Kang, Jin-Seok;Yum, Young-Na;Kim, Joo-Hwan;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.438-445
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    • 2009
  • We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

Expression and Characterization of CMCax Having β-1,4-Endoglucanase Activity from Acetobacter xylinum

  • Koo, Hyun-Min;Song, Sung-Hee;Pyun, Yu-Ryang;Kim, Yu-Sam
    • BMB Reports
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    • v.31 no.1
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    • pp.53-57
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    • 1998
  • The CMCax gene from Acetobacter xylinum ATCC 23769 was cloned and expressed in E. coli. With this gene, three gene products - mature CMCax, CMCax containing signal peptide(pre-CMCax), and a glutathione-S-transferase(GST)-CMCax fusion enzyme - were expressed. CMCax and pre-CMCax are aggregated to multimeric forms which showed high CMC hydrolysis activity, whereas GST-CMCax was less aggregated and showed lower activity, indicating that oligomerization of CMCax controbutes to the cellulose hydrolysis activity to achieve greater efficiency. The enzyme was identified to be an $\beta$-1,4-endoglucanase, which catalyzes the cleavage of internal $\beta$-1,4-glycosidic bonds of cellulose. The reaction products, cellobiose and cellotriose, from cellopentaose as a substrate, were identified by HPLC. Substrate specificity of cellotetraose by this enzyme was poor, and the reaction products consisted of glucose, cellobiose, and cellotriose in a very low yield. Theses results suggested that cellopentaose might be the oligosaccharide substrate consisting of the lowest number of glucose. The optimum pH of CMCax and pre CMCax was about 4.5, whereas that of GST-CMCas was rather broad at pH 4.5-8. The physiological significance of cellulose-hydrolyzing enzyme, CMCax, having such low $\beta$-1,4-endoglucanase activity and low optimum pH in cellulose-producing A. xylinum is not clearly known yet, but it seems to be closely related to the production of cellulose.

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Loss of Heterozygosity (LOH) on 17th and 18th Chromosome from Colorectal Carcinoma (대장암에서 17, 18번 염색체의 이형접합성 소실)

  • Lee, Jae-Sik
    • Korean Journal of Clinical Laboratory Science
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    • v.40 no.1
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    • pp.41-47
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    • 2008
  • Colorectal carcinoma is occurred frequently to Korean and so ranked the fourth from various cancers. Due to western dietary life, this cancer has been increased continually. Therefore, the study will be needed to find a candidate gene involved in the development and progression of colorectal carcinoma and to diagnose and treatment helpfully. The striking feature from cancer suppressor genes is known for LOH (loss of heterozygosity), which is the method to find allele genetic loss or mutation of cancer cell. The purpose of this study was designed to find a carcinogenic gene from colon cancer using microsatellite marker on 17th and 18th chromosome from 30 subjects. The LOH was investigated in order of D18S59 57% (17/30), TP53CA 50% (15/30), D18S68 47% (14/30), D18S69 43% (13/30). The genetic mutation depends on loci of colorectal carcinoma was shown higher with 2.44 from colon cancer than with 1.25 from right colorectal carcinoma (p<0.032). The genetic mutation with lymph nodes was investigated higher with 2.69 at mutated group than with 1.14 at non-mutated group (p<0.003). At genetic mutated pattern depends on disease stage, there was higher significant difference at III-IV stage 2.50 than that of I-II stage 1.17, respectively (p=0.015). There was no difference at comparison between histological classification and serological CEA increase. The loss on 18q21 found in this study is highly recurrence loci and was observed 43% for Korean with high recurrence. Therefore, LOH is a very useful tool to detect 18q21 loci in clinical application, prior to the treatment of colorectal carcinoma. After the operation of colorectol carcinoma, the efficient application using LOH at operated part tissue which is designed to protect the recurrence as well as its cure will be needed.

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Genetic Variations of ABCC2 Gene Associated with Adverse Drug Reactions to Valproic Acid in Korean Epileptic Patients

  • Yi, Ji Hyun;Cho, Yang-Je;Kim, Won-Joo;Lee, Min Goo;Lee, Ji Hyun
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.254-262
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    • 2013
  • The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p=0.0057) and the GG genotype (61.0% vs. 39.7%, p=0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p=0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway

  • Long, Zi-Wen;Wu, Jiang-Hong;Hong, Cai;Wang, Ya-Nong;Zhou, Ye
    • Molecules and Cells
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    • v.41 no.6
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    • pp.532-544
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    • 2018
  • Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

Immuno-regulatory and Anti-cancer Effect of Acorus gramineus Solander (석창포(石菖蒲)의 면역조절 및 항암효과)

  • Kim, Nam-Seok;Lee, Kyu-Hee;Kim, Tae-Ho;Bae, Jin-Bum;Kim, Sun-Geun;Jeon, Hoon;Lim, Jong-Phil;Shin, Tae-Yong;Lee, Chang-Hyun;Jeong, Seung-Il;Kwon, Jin;Oh, Chan-Ho
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.869-873
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    • 2007
  • Methanol extracts of Acorus gramineus Solander(AGS) were found to exhibit immuno-regulatory action in BALB/c mice. Oral administration of AGS increased murine splenic T lymphocytes, especially $T_H$ and $T_C/T_S$ subpopulations were increased significantly. Treatment of AGS exerted strong cytotoxicity against U937 and HL60 human leukemia cells. Also, AGS induced apoptosis of U937 leukemia cells in a dose dependent manner. Nitric oxide(NO) production and iNOS gene expression were also increased in AGS-treated RAW264.7 cells. Treatment of AGS increased the expression of p53 gene and decreased the expression of PCNA protein in cultured U937 cells. These data suggest that AGS are effective on the immuno-regulatory action and anti-cancer properties.

Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal

  • Thongdee, Pimwan;Kuesap, Jiraporn;Rungsihirunrat, Kanchana;Dumre, Shyam Prakash;Espino, Effie;Noedl, Harald;Na-Bangchang, Kesara
    • Parasites, Hosts and Diseases
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    • v.53 no.2
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    • pp.227-232
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    • 2015
  • Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required.