• Journal of Ginseng Research
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• v.45 no.1
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• pp.149-155
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• 2021

Background: We have reported that internal deletions in the nef, gag, and pol genes in HIV-1-infected patients are induced in those treated with Korean Red Ginseng (KRG). KRG delays the development of resistance mutations to antiretroviral drugs. Methods: The vif-vpr genes over 26 years in 20 hemophiliacs infected with HIV-1 from a single source were sequenced to investigate whether vif-vpr genes were affected by KRG and KRG plus highly active antiretroviral therapy (ART) (hereafter called GCT) and compared the results with our previous data. Results: A significantly higher number of in-frame small deletions were found in the vif-vpr genes of KRG-treated patients than at the baseline, in control patients, and in ART-alone patients (p < 0.001). These were significantly reduced in GCT patients (p < 0.05). In contrast, sequences harboring a premature stop codon (SC) were more significant in GCT patients (10.1%) than in KRG-alone patients, control (p < 0.01), and ART-alone patients (p = 0.078 for peripheral blood mononuclear cells). The proportion of SC in Vpr was similar to that in Vif, whereas the proportion of sequences revealing SC in the env-nef genes was significantly lower than that in the pol-vif-vpr genes (p < 0.01). The genetic distance was 1.8 times higher in the sequences harboring SC than in the sequences without SC (p < 0.001). Q135P in the vif gene is significantly associated with rapid progression to AIDS (p < 0.01). Conclusion: Our data show that KRG might induce sD in the vif-vpr genes and that vif-vpr genes are similarly affected by lethal mutations.

• BMB Reports
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• v.40 no.5
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• pp.814-824
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• 2007

Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

• Biomedical Science Letters
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• v.19 no.2
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• pp.164-167
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• 2013

Osteoclasts are originated from hemopoietic progenitors of the monocyte/macrophage lineage and resorb mineralized tissues. Elevated osteoclast numbers and activity result in bone disease such as osteoporosis, Paget's disease, and tumor osteolysis. In order to identify the genes that are involved in osteoclast differentiation, microarray was performed after treated with RANKL for 12 h and 24 h in osteoclast precursors. The genes that changed by RANKL treatment were grouped by biological process or molecular function. Among them, the number of genes involved in signal transduction and nucleic acid binding was 6065 and 3066, respectively. When analyzed the number of genes changed more than 1.5 fold in the cells treated with RANKL for 12 h or 24 h compared to when RANKL was not treated, 83 and 62 genes were up-regulated; 56 and 62 genes were downregulated, respectively. To verify the microarray results, real-time RT-PCR for Cxcl1 and Slfn1genes that have not been reported yet related to osteoclast differentiation, as well as Ccl2 gene associated with osteoclast differentiation were carried out. Both experiments showed a similar result of more than 1.5 fold induction of these genes by RANKL treatment. These results suggest the possibility that Cxcl1 and Slfn1 may associate with osteoclastogenesis and provide that microarray is a useful tool to analyze the profile of genes changed during osteoclast differentiation by RANKL. Moreover, this gene profile contributes to understand the regulatory mechanisms involved in osteoclast differentiation and the pathogenesis, thus developing therapeutics of bone diseases such as osteoporosis.

• Mycobiology
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• v.42 no.3
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• pp.241-248
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• 2014

NADPH oxidases (Noxes), transmembrane proteins found in most eukaryotic species, generate reactive oxygen species and are thereby involved in essential biological processes. However, the fact that genes encoding ferric reductases and ferric-chelate reductases share high sequence similarities and domains with Nox genes represents a challenge for bioinformatic approaches used to identify Nox-encoding genes. Further, most studies on fungal Nox genes have focused mainly on functionality, rather than sequence properties, and consequently clear differentiation among the various Nox isoforms has not been achieved. We conducted an extensive sequence analysis to identify putative Nox genes among 34 eukaryotes, including 28 fungal genomes and one Oomycota genome. Analyses were performed with respect to phylogeny, transmembrane helices, di-histidine distance and glycosylation. Our analyses indicate that the sequence properties of fungal Nox genes are different from those of human and plant Nox genes, thus providing novel insight that will enable more accurate identification and characterization of fungal Nox genes.

• Journal of the Korea Society of Computer and Information
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• v.21 no.3
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• pp.65-71
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• 2016

To reduce the expenses for development a novel drug, systems biology has been studied actively. Target prediction, a part of systems biology, contributes to finding a new purpose for FDA(Food and Drug Administration) approved drugs and development novel drugs. In this paper, we propose a classification model for predicting novel target genes based on relation between target genes and disease related genes. After collecting known target genes from TTD(Therapeutic Target Database) and disease related genes from OMIM(Online Mendelian Inheritance in Man), we analyzed the effect of target genes on disease related genes based on PPI(Protein-Protein Interactions) network. We focused on the distinguishing characteristics between known target genes and random target genes, and used the characteristics as features for building a classifier. Because our model is constructed using information about only a disease and its known targets, the model can be applied to unusual diseases without similar drugs and diseases, while existing models for finding new drug-disease associations are based on drug-drug similarity and disease-disease similarity. We validated accuracy of the model using LOOCV of ten times and the AUCs were 0.74 on Alzheimer's disease and 0.71 on Breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3997-4000
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• 2012

MicroRNAs (miRNAs) play roles in the clinic, both as diagnostic and therapeutic tools. The identification of relevant microRNAs is critically required for ovarian cancer because of the prevalence of late diagnosis and poor treatment options currently. To identify miRNAs involved in the development or progression of ovarian cancer, we analyzed gene expression profiles downloaded from Gene Expression Omnibus. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 508 genes that were commonly up-regulated and 1331 genes that were down-regulated in the cancer specimens. Function annotation of these genes showed that most of the up-regulated genes were related to cell cycling, and most of the down-regulated genes were associated with the immune response. When these differentially expressed genes were mapped to MiRTarBase, we obtained a total of 18 key miRNAs which may play important regulatory roles in ovarian cancer. Investigation of these genes and microRNAs should help to disclose the molecular mechanisms of ovarian carcinogenesis and facilitate development of new approaches to therapeutic intervention.

• Molecules and Cells
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• v.21 no.3
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• pp.436-442
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• 2006

Different proliferation of neuroblast 6-4 (NB6-4) in the thorax and abdomen produces segmental specific expression pattern of several neuroblast marker genes. NB6-4 is divided to form four medialmost cell body glia (MM-CBG) per segment in thorax and two MM-CBG per segment in abdomen. As homeotic genes determine the identities of embryonic segments along the A/P axis, we investigated if temporal and specific expression of homeotic genes affects MM-CBG patterns in thorax and abdomen. A Ubx loss-of-function mutation was found to hardly affect MM-CBG formation, whereas abd-A and Abd-B caused the transformation of abdominal MM-CBG to their thoracic counterparts. On the other hand, gain-of-function mutants of Ubx, abd-A and Abd-B genes reduced the number of thoracic MM-CBG, indicating that thoracic MM-CBG resembled abdominal MM-CBG. However, mutations in Polycomb group (PcG) genes, which are negative transregulators of homeotic genes, did not cause the thoracic to abdominal MM-CBG pattern transformation although the number of MM-CBG in a few percent of embryos were partially reduced or abnormally patterned. Our results indicate that temporal and spatial expression of the homeotic genes is important to determine segmental-specificity of NB6-4 daughter cells along the anterior-posterior (A/P) axis.

• Journal of fish pathology
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• v.22 no.3
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• pp.383-389
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• 2009

Analysis of expressed sequence tags (ESTs) is an efficient approach for gene discovery, expression profiling, and development of resources useful for functional genomics studies. As part of studies on the immune system of olive flounder, a total of 251 EST sequences from gill cDNA library were generated to identify and characterize important genes in the immune machanisms of olive flounder. Of the 251 clones, 126 clones (50.2%) were identified as orthologues of known genes from olive flounder and other organisms. Among the 126 EST clones, 16 clones (12.7%) were representing 9 unique genes identified as homologous to the previously reported olive flounder ESTs, 100 clones (79.4%) representing 103unique genes were identified as orthologs of known genes from other organisms. We also identified several kinds of immune associated proteins, indicating EST as a powerful method for identifying immune related genes of fish as well as identifying novel genes. Further studies using cDNA microarrays are needed to identify the differentially expressed transcripts after disease infection.

• Animal cells and systems
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• v.9 no.1
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• pp.1-7
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• 2005

Class I and class II MHC genes have been identified in most of the jawed vertebrate taxa. In all investigated bony fish species, unlike mammals, the classical class I and class II MHC genes are not linked and even are found on different chromosomes. Linking and clustering of the class I and class II MHC genes is not the only phenomenon clearly detected in the evolution of immune system from cartilaginous to mammals. In all non-mammalian classes the LMP/TAP genes are highly conserved within class I genes region, while these genes are conserved within class II genes region only in mammals. Today we know that LMP/TAP genes in mammals have a crucial role in peptide processing for presentation within class I molecules, as well as in anti-tumor immunity. For these reasons, differences in clustering of LMP/TAP/MHC genes can be responsible for the differences in mechanisms and efficacy of anti-tumor immunity in non-mammalian vertebrates compared to same mechanisms in mammals. Also, the differences in cytokine network and anti-tumor antigens presentation within classes of vertebrates can be explained by toe peculiarity of LMP/TAP/MHC gene clustering.

• Proceedings of the Botanical Society of Korea Conference
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• 1996.07a
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• pp.26-38
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• 1996

To investigate the regulation of plant histone H2A gene expression, we isolated two H2A genes (TH254 and TH274) from wheat, which encode different types of variants. Both genes had an intron in the coding region. In the promoters, some characteristics sequences, such as Oct and Nona motifs, which are conserved among plant histone genes were also found, and they were located in a short region (about 120 bp) upstream from the putative TATA box. Analyses of promoter activity with H2A-GUS fusion genes in the transient system using tobacco protoplasts revealed novel types of positive cis-acting sequences in the TH254 promoter: a direct repeat of a 13-bp sequence (AGTTACATTATTG) and a stretch composed of an AT-rich sequence (ATATAGAAAATTAAAA) and a G-box (CACGTG). A quantitative S1 assay of the mRNA amounts from the TH254/GUS and TH274/GUG chimeric genes in stably transformed and cell cycle-synchronized tobacco cell lines showed that the promoters of both genes contained at least one cis-acting element responsible for S phase-specific expression. Histochemical analysis of transgenic tobacco plants carrying the chimeric genes showed that the promoters of the two H2A genes were both active in developing seedlings and flower organs but regulated in different manner.