• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.189-195
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• 2021

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca2+]cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 μM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca2+ accumulation in COV434 cells. Only the highest concentrations of FLX (5-10 μM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.

• Korean Journal of Veterinary Research
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• v.36 no.1
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• pp.93-99
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• 1996

This study was designed to investigate the effect of estrogen(Est) on the progestcrone(Prog) target cells by autoradiography. The spayed 16 mice(ICR, approximately 18~25g) were randomly alloted into 3 groups. $^3H$-Prog-treated group were injected with $40{\mu}Ci$ of $^3H$-Prog/mouse/day for 1 day, Est + $^3H$-Prog-treated group with $20{\mu}Ci$ of $17{\beta}$-Est/mouse/day for 3 days and then with $40{\mu}Ci$ of $^3H$-Prog/mouse at 4th day, and Est+$^3H$-thymidine(TdR)-treated group with $20{\mu}g$ of $17{\beta}$-Est/mouse/day for 3 days and then $80{\mu}Ci$ of $^3H$-TdR/mouse at 4th days. 1. Mice uteri of both Est+$^3H$-Prog-treated group and Est+$^3H$-TdR-treated group were hypemophied in gross finding and the endometrium and myometrium were thickened in microscopic findings. These findings were confirmed that Est enlarged the uteri of mice. 2. Cryo-preparations of mice organs were processed for autoradiography using Kodak NTB-2 emulsion following Kodak D-19 developer and hematoxylin counterstain. In each group, the number values of silver grain distribution appeared to be higher in the $^3H$-Prog-treated group than in the Est+$^3H$-Prog-treated group. It was considered that Est and Prog inhibit each other in action. 3. In both $^3H$-Prog-treated group and Est+$^3H$-Prog-treated group, the uteri have highest distribution rates of silver grains than in other organs, and the cerebral neurons, hepatocytes, bronchiolar epithelial cells and splenic reticular cells also contained some silver grains. 4. The orders of the cell types with more number of silver grains in the uteri were stromal cells, glandular epithelial cells, luminal surface cells and muscular cells and also were as above orders in distribution of proliferating cell type by $^3H$-TdR.

• Interdisciplinary Bio Central
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• v.5 no.2
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• pp.3.1-3.7
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• 2013

Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.

• The Journal of the Institute of Internet, Broadcasting and Communication
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• v.15 no.1
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• pp.179-186
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• 2015

This paper proposes the target path detection algorithm using statistical characteristics of an activated time lag along a moving path of target from a neighboring sensor in PDR(Pulse Doppler Radar) sensor node environment based on USN(Ubiquitous Sensor Network) with a limitation detecting only an existence of moving target. In the proposed algorithm, detection and non-detection time lag obtained from the experimental data are used. The experimental data are through repetitive action of each 500 times about three path scenarios such as passing in between two sensors, moving parallel to two sensors, and turning through two sensors. From this experiments, error detection percentages of three path scenarios are 5.67%, 5.83%, and 7.17%, respectively. They show that the proposed algorithm can exactly detect a target path using the limited PDR sensor nodes.

• Herbal Formula Science
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• v.31 no.4
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• pp.295-313
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• 2023

Objectives : While treatments for cancer are advancing, the development of effective treatments for cancer metastasis, the main cause of cancer patient death, remains insufficient. Recent studies on Dichroae Radix have revealed that its active ingredients have the potential to inhibit cancer metastasis. This study aimed to investigate the cancer metastasis inhibitory effect of Dichroae Radix using network pharmacological analysis. Methods : The active compounds of Dichroae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : In total, 25 active compounds and their 62 non-redundant targets were selected through the TCMSP database and analysis platform. The target genes underwent gene ontology and pathway enrichment analysis. The gene list applied to the gene ontology analysis revealed associations with various biological processes, including signal transduction, chemical synaptic transmission, G-protein-coupled receptor signaling pathways, response to xenobiotic stimulus, and response to drugs, among others. A total of eleven genes, including HSP90AB1, CALM1, F2, AR, PAKACA, PTGS2, NOS2, RXRA, ESR1, ESR2, and NCOA1, were found to be associated with biological pathways related to cancer metastasis. Furthermore, nineteen of the active compounds from Dichroae Radix were confirmed to interact with these genes. Conclusions : The results provide valuable insights into the mechanism of action and molecular targets of Dichroae Radix. Notably, Berberine, the main active ingredient of Dichroae Radix, plays a significant role in degrading AR proteins in advanced prostate cancer. Further studies and validations can provide crucial data to advance cancer metastasis prevention and treatment strategies.

• The Korean Journal of Pesticide Science
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• v.5 no.3
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• pp.1-11
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• 2001

New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1241-1245
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• 2014

Cinobufacin is used clinically to treat patients with many solid malignant tumors. However, the mechanisms underlying action remain to be detailed. Our study focused on miRNAs involved in cinobufacin inhibition of GC cell proliferation. miRNA microarray analysis and real time PCR identified miR-494 as a significant cinobufacin-associated miRNA. In vivo, ectopic expression of miR-494 inhibited the proliferation and induced apoptosis of BGC-823 cells on CCK-8 and flow cytometry analysis. Further study verified BAG-1 (anti-apoptosis gene) to bea target of miR-494 by luciferase reporter assay and Western blotting. In summary, our study demonstrated that cinobufacin may inhibit the proliferation and promote the apoptosis of BGC-823 cells. Cinobufacin-associated miR-494 may indirectly be involved in cell proliferation and apoptosis by targeting BAG-1, pointing to use as a potential molecular target of cinobufacin in gastric cancer therapy.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.158-158
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• 1998

The non-mevalonate pathway is a newly discovered isoprenoid biosynthetic pathway in some bacteria, cyanobacteria, algae and plants. Because isoprenoid metabolites (ubiquinone, menaquinone, undecaprenol) are essential for bacterial growth, this pathway may represent a novel target for antibacterial agents. Antibiotics with a unique mechanism of action are needed to combat the risk of antibiotic resistance that is a current worldwide problem. In order to study this pathway as viable target, it was necessary to verify use of the pathway in our model system, the bacterium Bacillus subtilis. Incubation experiments with [6,6-$^2$H$_2$]-D-glucose and [l-$^2$H$_3$]-deoxy-D-xylulose were conducted to provide labeled menaquinone-7 (MK -7), the most abundant isoprenoid in B. subtilis. $^2$H-NMR analysis of the MK-7 revealed labeling patterns that strongly support utilization of the non-mevalonate pathway. Another approach to study the pathway is by structure activity relationships of proposed inhibitors of the pathway. Fosmidomycin is a phosphonic acid with antibacterial activity known to inhibit isoprenoid biosynthesis in susceptible bacteria and may act by inhibiting the non-mevalonate pathway. Fosmidomycin and an N-methyl analog were synthesized and tested for antibacterial activity. Fosmidomycin was active against Escherichia coli and B. subtilis, while N-formyl-N-methyl-3-amino-propylphosphonic acid was inactive.

• Journal of Biomedical Engineering Research
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• v.40 no.3
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• pp.97-104
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• 2019

To examine different types of influenza diagnostic test kits automatically, automated rapid influenza diagnostic test method based on image recognition is proposed in this paper. First, the proposed methods classify a variety of the rapid influenza diagnostic test kit based on support vector machine that analyzes the kits' feature point. Then, to improve the accuracy of test, the proposed methods match the histogram of both the target image of influenza kit and the input image of influenza kit for minimizing the effect of environment factors, such as lighting and exposure variations. And, to minimize the effect from composition of the hand-helds devices, the proposed methods extract the feature point and match point-by-point between target image of influenza kit and input image of influenza kit. Experimental results of 124 experimental group show that the proposed methods significantly have effectiveness, which shows 90% accuracy in moderate antigen, for the preliminary examination of influenza, and provides the opportunity for taking action against influenza.

• Journal of Embryo Transfer
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• v.13 no.2
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• pp.179-190
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• 1998

Prolactin (PRL) surge in cycling rats at proestrous afternoon has previously been reported as an inducer of apoptotic cell death of luteal cells. This death-inducing action of PRL seeins unusual, because PRL can he categorized as a cell-survival factor, if other known physiological functions of PRL are taken into account. In this study, the apoptotic action of PRL was assessed in cultured cells prepared from rat luteal tissue and underlying molecular /cellular mechanism of PRL-induced luteolysis was analyzed. The latest crop of corpora lutea (CLs) were enucleated from rat ovaries at 18:00 h on the proestrous day before the next ovulation. Donor rats were pretreated with CB154, a dopamine agonist, in order to he exempted from the endogenous PRL surge. The harvested GLs were dispersed and cultured with or without PRL (2$\mu$g /ml) for 24 or 48 h. An addition of PRL to the culture medium changed the parameters indicative of cell death via apoptosis: a decrease in cell viability (MTT) and an increase in chromatin condensation. Most of the DNA breakdown in nuclei induced by PRL occurred in steroidogenic cells which were identified by 3$\beta$-HSD activity staining, and the number of 3$\beta$-HSD-positivecells were significantly decreased. Interestingly, most of the cells with an apoptotic nucleus adhered to one or more intact and seemingly non-steroidogenic cells. Because the expression of Fas has heen shown to be abundant in murine ovary, and Fas is known to have an exact physiological role in occurrence of apoptotic cell death, the membrane form-Fas ligand (rnFasL) was quantified in the cell lysate. An addition of PRL increased expression of mFasL. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, in place of PRL, enhanced the apoptotic parameters. Cumulatively, the apoptotic PRL action was addressed to cells unknown than steroidogenic lute~ cells. The most prohable candidate for the direct target cells is Tcells in the luteal tissue that can express mFasL in response to PRL.