• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.5
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• pp.831-836
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• 2010

In addition to spice, black pepper (Piper nigrum Linne : PnL) has been used as herbal medicine because of its function in anti-oxidation, anti-inflammation, and anti-carcinogenesis. Recently, it has been reported that piperine, a component of PnL, inhibits adipocyte differentiation by repressing various adipogenic gene expressions. In this study, we determined whether piperine is a major constituent of PnL that confers the anti-adipogenic activity at whole genome level. Differentiation of 3T3-L1 pre-adipocytes was induced in presence of PnL extract or piperine. To compare genes that are regulated by PnL extract or piperine, we performed expression profiling using microarrays (Agilent Mouse 44k 4plex). RNA samples were labeled with Cy3 and Cy5, respectively. Labeled samples were hybridized to the microarrays. Results were filtered and cut off set p<0.05. Genes exhibiting significant differences in expression level were classified into Gene Ontology (GO)-based functional categories (http://www.geneontology.org) and KEGG (http://www.genome.jp/kegg/). Extract of PnL and its component piperine reduced lipid accumulation in 3T3-L1 cells during adipogenesis. Such anti-adipogenic activity appears to result from down-regulation of transcription factor genes involved in adipogenesis, and other genes involved in fatty acid synthesis, transport, triglyceride synthesis, and carbohydrate metabolism. These genome-wide studies lead to conclude that piperine, as a critical component of PnL, plays common role with PnL in anti-adipogenesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.6
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• pp.229-234
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• 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. Indigo Naturalis (IN) is a dark blue powder obtained by processing leaves or stems of indigo plants, its anticancer effects have been reported in several studies. However, the pharmacological mechanism of IN in small cell lung cancer (SCLC) is not elucidated. In this study, to investigate the anticancer efficacy of IN for SCLC, we presented potential active ingredients, SCLC-related targets, and pharmacological mechanisms of IN that are expected to have anticancer activity for SCLC using a network pharmacological analysis. The phytochemical compounds of IN have been collected through TCMSP, SymMap, or HPLC documents. The active ingredients of IN such as indirubin, indican, isatin, and tryptanthrin were selected through ADME parameters or literature investigations for each compound. Using the Compounds, Disease-Target associations Databases, 124 common targets of IN and SCLC were obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis was carried out. GO biological processes are associated with response to xenobiotic stimulus, positive regulation of protein phosphorylation, regulation of mitotic cell cycle, and regulation of apoptotic signaling pathway. KEGG disease pathways included Gastric cancer, Bladder cancer, SCLC, and Melanoma. The main anticancer targets of the IN for SCLC were analyzed in 14 targets, including BCL2, MYC, and TP53. In conclusion, the results of this study based on the network pharmacology of IN can provide important data for the effective prevention and treatment of SCLC.

• Journal of Korean Medical classics
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• v.24 no.5
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• pp.99-105
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• 2011

The medical treatment is process of collecting symptoms, making a diagnosis and treatment for the diagnosis. The remedy and the efficacy are the important hinge that links the diagnosis to the means of medical treatment. Lots of medical data are stored on database or saved as files in these days. The preferential way to find the efficacy related to the remedy is search all efficacy terms match up to the remedy term. To increase the rate of matching remedy terms with efficacy terms, we study the relation between efficacy terms and remedy terms and research the conversion way of the terms into the representative terms. The rate of matching the raw remedy terms with the raw efficacy terms is below 30%. The rate of matching the disaggregate remedy terms with the disaggregate efficacy terms is about 50%. The rate of matching the representative remedy terms with the representative efficacy terms is almost 70%.

• The Journal of Korean Medicine
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• v.45 no.1
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• pp.114-125
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• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.353-360
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• 2017

Several human diseases have been associated with mitochondrial voltage-dependent anion channel-1 (VDAC1) due to its role in calcium ion transportation and apoptosis. Recent studies suggest that VDAC1 may interact with endothelium-dependent nitric oxide synthase (eNOS). Decreased VDAC1 expression may limit the physical interaction between VDAC1 and eNOS and thus impair nitric oxide production, leading to cardiovascular diseases, including pulmonary arterial hypertension (PAH). In this report, we conducted meta-analysis of genome-wide expression data to identify VDAC1 influenced genes implicated in PAH pathobiology. First, we identified the genes differentially expressed between wild-type and Vdac1 knockout mouse embryonic fibroblasts in hypoxic conditions. These genes were deemed to be influenced by VDAC1 deficiency. Gene ontology analysis indicates that the VDAC1 influenced genes are significantly associated with PAH pathobiology. Second, a molecular signature derived from the VDAC1 influenced genes was developed. We suggest that, VDAC1 has a protective role in PAH and the gene expression signature of VDAC1 influenced genes can be used to i) predict severity of pulmonary hypertension secondary to pulmonary diseases, ii) differentiate idiopathic pulmonary artery hypertension (IPAH) patients from controls, and iii) differentiate IPAH from connective tissue disease associated PAH.

• Journal of Pharmacopuncture
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• v.27 no.2
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• pp.162-171
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• 2024

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.221-228
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• 2011

Rodent malaria parasites, such as Plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. Exploiting the available genetic sequence information, we constructed a cDNA library from the erythrocytic stages of P. berghei and analyzed the expressed sequence tag (EST). A total of 10,040 ESTs were generated and assembled into 2,462 clusters. These EST clusters were compared against public protein databases and 48 putative new transcripts, most of which were hypothetical proteins with unknown function, were identified. Genes encoding ribosomal or membrane proteins and purine nucleotide phosphorylases were highly abundant clusters in P. berghei. Protein domain analyses and the Gene Ontology functional categorization revealed translation/protein folding, metabolism, protein degradation, and multiple family of variant antigens to be mainly prevalent. The presently-collected ESTs and its bioinformatic analysis will be useful resources to identify for drug target and vaccine candidates and validate gene predictions of P. berghei.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.2
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• pp.1-9
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• 2023

Objectives : This study used a network pharmacology approach to analyze the treatment mechanisms of Yijin-tang on Meniere's disease, and comparative analysis the treatment mechanisms of drugs recommended in the Meniere's disease treatment guidelines. Methods : We collected information on the recommended drugs from the Meniere's disease treatment guidelines and their target proteins were screened via the STITCH database. The intersection targets were obtained through Venny 2.1.0. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed using ClueGO. Results : The 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were associated with both Yijin-tang and Meniere's disease related genes. The 10 proteins(AQP2, KCNE1, AQP1, AVP, ACE, HRH1, HRH3, NOS1, CA1, CFTR) were associated with both the recommended drugs in the guidelines and Meniere's disease related genes. The 2 proteins(CFTR, NOS1) were common across all three groups. Further, GO/KEGG pathway analysis of the collected proteins revealed that the common mechanisms of action between Yijin-tang and the recommended drugs in the guidelines were related to pathways involving immune dysfunction and disturbances in lymphatic fluid homeostasis. In addition, the recommended drugs in the guidelines appeared to act through mechanisms that improve blood flow through vasodilation. Conclusions : Pharmacological network analysis can help to explain the treatment mechanisms of Yijin-tang on Meniere's disease.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.121-129
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• 2011

Objective: The propose of this study is to build a conceptual framework for representing clinical findings in Traditional East Asian Medicine(TEAM). As the existing standard models have been developed without considering features of Traditional Medicine, in this study we introduced unique characteristics for the TEAM. Method: This study was composed of three steps. First, we analyzed whether the existing clinical information models are suitable for representing clinical findings. Second, we analyzed ISO/TS 22789 model which is a ISO medical informatics standard, to find out the problem by applying clinical findings of TEAM into the model. Finally, we defined semantic links and a concept hierarchy in our model based on the analyzed results. The model includes the concepts for clinical findings and terms, and the semantic links can be regarded as relations between concepts, so that the representating clinical findings are completed by connecting concepts with other concepts. Results: Our framework was developed by removing unnecessary semantic links, and adding some necessary ones based on ISO/TS 22789 model. The ISO/TS 22789 model has a simple concept hierarchy, but in this study we subdivided the hierarchy and also considered interoperability with other terminological systems and standard models. Conclusions: This research needs more discussions, but is meaningful as proposing a way how to develop Traditional Medicine terminological systems. This study shows the limitations of existing models in describing clinical findings for TEAM, and what should be considered to represent Traditional Medicine knowledge, and propose a solution to improve the problem.

• Korean Circulation Journal
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• v.54 no.8
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• pp.468-481
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• 2024

Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.