• The Plant Pathology Journal
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• v.24 no.3
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• pp.289-295
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• 2008

RNA-RNA interactions and the dynamic RNA conformations are important regulators in virus replication in several RNA virus systems and may also involved in the regulation of many important virus life cycle phases, including translation, replication, assembly, and switches in these important stages. The 5' non-translated region of Potato virus X(PVX) contains multiple cis-acting elements that facilitate various viral processes. It has previously been proposed that RNA-RNA interactions between various RNA elements present in PVX RNA genome are required for PVX RNA accumulation(Hu et al., 2007; Kim and Hemenway, 1999). This model was based on the potential base-pairing between conserved sequence elements at the upstream of subgenomic RNAs(sgRNAs) and at the 5' and 3' end of RNA genome. We now provide more evidence that RNA-RNA base-pairing between elements present at the 5' end and upstream of each sgRNA is required for efficient replication of genomic and subgenomic plus-strand RNA accumulation. Site-directed mutations introduced at the 5' end of plus-strand RNA replication defective mutant(${\Delta}12$) increasing base-pairing possibility with conserved sequence elements located upstream of each sgRNAs restored genomic and subgenomic plus-strand RNA accumulation and caused symptom development in inoculated Nicotiana benthamiana plants. Serial passage of a deletion mutant(${\Delta}8$) caused more severe symptoms and restored wild type sequences and thus retained possible RNA-RNA base-pairing. Altogether, these results indicate that the RNA element located at the 5' end of PVX genome involved in RNA-RNA interactions and play a key role in high-level accumulation of plus-strand RNA in vivo.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.28 no.2A
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• pp.80-85
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• 2003

This paper proposes Galois Field Arithmetic Unit(GFAU) whose structure does addition, multiplication and division in GF(2m). GFAU can execute maximum two additions, or two multiplications, or one addition and one multiplication. The base architecture of this GFAU is a divider based on modified Euclid's algorithm. The divider was modified to enable multiplication and addition, and the modified divider with the control logic became GFAU. The GFAU for GF(2193) was implemented with Verilog HDL with top-down methodology, and it was improved and verified by a cycle-based simulator written in C-language. The verified model was synthesized with Samsung 0.35um, 3.3V CMOS standard cell library, and it operates at 104.7MHz in the worst case of 3.0V, 85$^{\circ}C$, and it has about 25,889 gates.

• 한국균학회소식:학술대회논문집
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• 2016.05a
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• pp.41-41
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• 2016

Influenza viruses are RNA viruses that belong to the Orthomyxoviridae family, and those can be divided into three types; A, B, and C, which based on the differences of the inner nucleoproteins and genomic structures. All three genera differ in their genomic structure and nucleoprotein content, they are further classified into various serotypes based on the two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). These glycoproteins play crucial roles in viral infection and replication. Hemagglutinin mediates binding of virions to sialic acid receptors on the surfaces of target cells at the initial stage of infection. Neuraminidase cleaves the glycosidic bonds of sialic acids from the viral and cell surfaces to release the mature virions from infected cells, after viral replication. Because NA plays an important role in the viral life cycle, it is considered an attractive therapeutic target for the treatment of influenza. The methanolic extracts of Phellinus baumii and Phellinus igniarius exhibited significant activity in the neuraminidase inhibition assay. Polyphenolic compounds were isolated from the methanolic extracts. The structures of these compounds were determined to be hispidin, hypholomine B, inoscavin A, davallialactone, phelligridin D, phelligridin E, and phelligridin G by spectroscopic methods. Compounds inhibited the H1N1 neuraminidase activity in a dose-dependent manner with $IC_{50}$ values of 50.9, 22.9, 20.0, 14.2, 8.8, 8.1 and $8.0{\mu}M$, respectively. Moreover, these compounds showed anti-influenza activity in the viral cytopathic effect (CPE) reduction assay using MDCK cells. These results suggests that the polyphenols from P. baumii and P. igniarius are promising candidates for prevention and therapeutic strategies against viral infection.

• Applied Biological Chemistry
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• v.43 no.3
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• pp.174-178
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• 2000

To search CDK4/Cyclin D1 enzyme inhibition materials, methanol extracts of native eighty seven plant species in thirty seven families were screened in vitro for their inhibiting activities against CDK4/Cyclin D1 enzyme which are control to the normal cell division cycle in human body. Extracts of Paeonia suffruticosa, Saurus chinensis, Sanguisorba officinalis and Celastrus orbiculatus among them significantly inhibited above fifty percent $(in\;5\;{\mu}g/ml)$ against CDK4/ Cyclin D1 enzyme. Especially, the extracts of P. suffruticosa and S. officinalis showed moderately strong inhibition. Also, cryptotanshinone was identified as active compound from a extracts of Salvia mitiorrhiza by spectroscopic analyses including 2D NMR experiments.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.54-65
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• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.2
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• pp.115-122
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• 1998

The maintenance of a viable pregnancy has long been viewed as an immunological paradox. The deveolping embryo and trophoblast are immunologically foreign to the maternal immune system due to their maternally inherited genes products and tissue-specific differentiation antigens (Hill & Anderson, 1988). Therefore, speculation has arisen that spontaneous abortion may be caused by impaired maternal immune tolerance to the semiallogenic conceptus (Hill, 1990). Loss of recall antigen has been reported in immunosuppressed transplant recipients and is associated with graft survival (Muluk et al., 1991; Schulik et al., 1994). Progesterone $(10^{-5}M)$ has immunosuppressive capabilities (Szekeres-Bartho et al., 1985). Previous study showed that fertile women, but not women with unexplained recurrent abortion (URA), lose their immune response to recall antigens when pregnant (Bermas & Hill, 1997). Therefore, we hypothesized that immunosuppressive doses of progesterone may affect proliferative response of lymphocytes to trophoblast antigen and alloantigen. Proliferative responses using $^3H$-thymidine ($^3H$-TdR) incorporation of peripheral blood mononuclear cells (PBMCs) to the irradiated allogeneic periperal blood mononuclear cells as alloantigen, trophoblast extract and Flu as recall antigen, and PHA as mitogen were serially checked in 9 women who had experienced unexplained recurrent miscarriage. Progesterone vaginal suppositories (100mg b.i.d; Utrogestan, Organon) beginning 3 days after ovulation were given to 9 women with unexplained RSA who had prior evidence of Th1 immunity to trophoblast. We checked proliferation responses to conception cycle before and after progesterone supplementation once a week through the first 7 weeks of pregnancy. All patients of alloantigen and PHA had a positive proliferation response that occmed in the baseline phase. But 4 out of 9 patients (44.4%) of trophoblast antigen and Flu antigen had a positive proliferative response. The suppression of proliferation response to each antigen were started after proliferative phase and during pregnancy cycles. Our data demonstrated that since in vivo progesterone treated PBMCs suppressed more T-lymphocyte activation and $^3H$-TdR incorporation compare to PBMCs, which are not influenced by progesterone. This data suggested that it might be influenced by immunosuppressive effect of progesterone. In conclusion, progesterone may play an important immunological role in regulating local immune response in the fetal-placental unit. Furthermore, in the 9 women given progesterone during a conception cycle, Only two (22%) repeat pregnancy losses occured in these 9 women despite loss of antigen responsiveness (one chemical pregnancy loss and one loss at 8 weeks of growth which was karyotyped as a Trisomy 4). These finding suggested that pregnancy loss due to fetal aneuploidy is not associated with immunological phenomena.

• Korean Journal of Biological Psychiatry
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• v.12 no.1
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• pp.42-61
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• 2005

Objectives:The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. Methods:SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1($80{\mu}M$, $40{\mu}M$, $20{\mu}M$). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. Results:Treatment of SH-SY5Y cells with $80{\mu}M$ ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(${\geq}$3 fold) in Rg1 treated cells and 40 genes were up-regulated(${\geq}$2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1-group. Conclusion:Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.247-256
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• 2017

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

• YAKHAK HOEJI
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• v.50 no.4
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• pp.272-277
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• 2006

This study was undertaken to determine whether the 9 herbal complex induces apoptosis in human breast cancer MCF-7 cells and adriamycin-resistant MCF7/adR cells. Ethanol extracts of Bojungbangamtang (BBTE) and acidic polysaccharide of Red Ginseng (GIN) induced cell death in both MCF-7 and MCF7/adR cells. Ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng also induced $G_2/M$ cell cycle arrest and increased TUNEL positive cells in MCF7/adR cells. In addition, flow cytometric analysis revealed the decreased expression of P-glycoprotein (P-gp) in ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng treated MCF7/adR cells. Similarly, decreased protein levels of P-glycoprotein and multidrug resistance associated proteins-1 were also determined by immunocytometry in ethanol extracts of Bojungbangamtang treated MCF7/adR cells. Taken together these data indicate that ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng inhibit the function of ABC transporters such as multi drug resistance associated proteins (MRPs) and P-glycoprotein as well as induce apoptosis in MCF7/adR cells. Thus, these data suggest that ethanol extracts of Bojungbangamtang and polysaccharide of Red Ginseng can be candidates for the treatment of multidrug-resistant MCF7/adR cells.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.71-77
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• 2019

Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer role of menadione against a range of cancer cell lines. In this study, the anti-cancer effects of menadione and the underlying molecular signaling involved in apoptosis was investigated in gastric cancer cell lines. The menadione treatment decreased the cell viability of MKN45 gastric cancer cells. The decreased cell viability was attributed to the induction of apoptosis, which was confirmed by the results indicating the activation of caspase-3 and -7 and the cleavage of PARP in Western blotting. The upstream regulatory molecules involved in apoptosis were investigated further and it was discovered that menadione reduced the expression of survivin, an inhibitor of upstream apoptosis proteins. In addition, a transcription factor ${\beta}$-catenin, which is known to regulate survivin expression, was down-regulated by menadione. A previous report showed that menadione inhibited XIAP expression to induce apoptosis and induced G2/M cell cycle arrest in AGS cells. This study elucidated another inhibitory mechanism of menadione against gastric cancer cells in a different cell line. Although further studies will be needed, the inhibitory mechanism demonstrated in this study will help better understand the anti-cancer effects of menadione.