• Journal of Korean Neurosurgical Society
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• v.65 no.1
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• pp.4-12
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• 2022

Objective : We reported the differentially methylated genes in patients with subarachnoid hemorrhage (SAH) using bioinformatics analyses to explore the biological characteristics of the development of delayed cerebral ischemia (DCI). Methods : DNA methylation profiles obtained from 40 SAH patients from an epigenome-wide association study were analyzed. Functional enrichment analysis, protein-protein interaction (PPI) network, and module analyses were carried out. Results : A total of 13 patients (32.5%) experienced DCI during the follow-up. In total, we categorized the genes into the two groups of hypermethylation (n=910) and hypomethylation (n=870). The hypermethylated genes referred to biological processes of organic cyclic compound biosynthesis, nucleobase-containing compound biosynthesis, heterocycle biosynthesis, aromatic compound biosynthesis and cellular nitrogen compound biosynthesis. The hypomethylated genes referred to biological processes of carbohydrate metabolism, the regulation of cell size, and the detection of a stimulus, and molecular functions of amylase activity, and hydrolase activity. Based on PPI network and module analysis, three hypermethylation modules were mainly associated with antigen-processing, Golgi-to-ER retrograde transport, and G alpha (i) signaling events, and two hypomethylation modules were associated with post-translational protein phosphorylation and the regulation of natural killer cell chemotaxis. VHL, KIF3A, KIFAP3, RACGAP1, and OPRM1 were identified as hub genes for hypermethylation, and ALB and IL5 as hub genes for hypomethylation. Conclusion : This study provided novel insights into DCI pathogenesis following SAH. Differently methylated hub genes can be useful biomarkers for the accurate DCI diagnosis.

• Journal of Periodontal and Implant Science
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• v.52 no.4
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• pp.282-297
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• 2022

Purpose: To explore differences in the subgingival microbiome according to the presence of periodontitis and/or type 2 diabetes mellitus (T2D), a metagenomic sequencing analysis of the subgingival microbiome was performed. Methods: Twelve participants were divided into 4 groups based on their health conditions (periodontitis, T2D, T2D complicated with periodontitis, and generally healthy). Subgingival plaque was collected for metagenomic sequencing, and gingival crevicular fluids were collected to analyze the concentrations of short-chain fatty acids. Results: The shifts in the subgingival flora from the healthy to periodontitis states were less prominent in T2D subjects than in subjects without T2D. The pentose and glucuronate interconversion, fructose and mannose metabolism, and galactose metabolism pathways were enriched in the periodontitis state, while the phosphotransferase system, lipopolysaccharide (LPS) and peptidoglycan biosynthesis, bacterial secretion system, sulfur metabolism, and glycolysis pathways were enriched in the T2D state. Multiple genes whose expression was upregulated from the red and orange complex bacterial genomes were associated with bacterial biofilm formation and pathogenicity. The concentrations of propionic acid and butyric acid were significantly higher in subjects with periodontitis, with or without T2D, than in healthy subjects. Conclusions: T2D patients are more susceptible to the presence of periodontal pathogens and have a higher risk of developing periodontitis. The pentose and glucuronate interconversion, fructose and mannose metabolism, galactose metabolism, and glycolysis pathways may represent the potential microbial functional association between periodontitis and T2D, and butyric acid may play an important role in the interaction between these 2 diseases. The enrichment of the LPS and peptidoglycan biosynthesis, bacterial secretion system, and sulfur metabolism pathways may cause T2D patients to be more susceptible to periodontitis.

• Genomics & Informatics
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• v.21 no.2
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• pp.22.1-22.15
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• 2023

Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.197-197
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• 2022

Wheat is highly susceptible to heat stress, which significantly reduces grain yield. In this study, we used RNA-seq technology to analyze the transcript expression at three different time-points after heat treatment in three cultivars differing in their susceptibility to heat stress: Jopum, Keumkang, and Olgeuru. A total of 11,751, 8850, and 14,711; 10,959,7946, and 14,205; and 22,895,13,060, and 19,408 differentially-expressed genes (log2 fold-change > 1 and FDR (padj) < 0.05) were identified in Jopum, Keumkang, and Olgeuru in the control vs. 6-h, in the control vs. 12-h, and in the 6-h vs. 12-h heat treatment, respectively. Functional enrichment analysis showed that the biological processes for DEGs, such as the cellular response to heat and oxidative stress-and including the removal of superoxide radicals and the positive regulation of superoxide dismutase activity-were significantly enriched among the three comparisons in all three cultivars. Furthermore, we investigated the differential expression patterns of reactive oxygen species (ROS)-scavenging enzymes, heat shock proteins, and heat-stress transcription factors using qRT-PCR to confirm the differences in gene expression among the three varieties under heat stress. This study contributes to a better understanding of the wheat heat-stress response at the early growth stage and the varietal differences in heat tolerancea.

• 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.

• 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 Physiology and Pharmacology
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• v.28 no.1
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• pp.59-72
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• 2024

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

• Korean Journal of Acupuncture
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• v.41 no.1
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• pp.7-15
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• 2024

Objectives : This study aimed to predict the effectiveness and potential of Schizonepeta tenuifolia as an anticancer treatment for non-small cell lung cancer through network-based pharmacology and cellular experiment. Methods : To identify the major bioactive compounds in Schizonepeta tenuifolia, we used the Traditional Chinese Medicine Systems. The target genes for the cancer treatment were selected using the UniProt database and the networked using Cytoscape. We performed functional enrichment analysis based on the Gene Ontology Biological Process and Kyoto Encyclopedia of Genes and Genomes Pathways to predict the mechanisms. To investigate the effect of Schizonepeta tenuifolia on lung cancer cell growth, we treated A549 cells, a lung cancer cell line, with different concentrations of the drug and used the MTT assay for cell viability. Results : Research has shown that the most effective mechanism of active compounds from Schizonepeta tenuifolia is through the pathway of cancer. The results of the network pharmacology analysis indicate that Schizonepeta tenuifolia has potential medicinal value as an adjuvant in anticancer treatment. The concentration-dependent inhibition of cell viability was observed on A549 cells. Furthermore, synergistic anticancer activity with Doxorubicin was also observed. Conclusions : Through a network pharmacological approach, Schizonepeta tenuifolia was predicted to have potential as an anticancer agent, and its efficacy was experimentally demonstrated using A549 cells. These findings suggest that Schizonepeta tenuifolia is a promising candidate for future research.

• Herbal Formula Science
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• v.32 no.1
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• pp.11-28
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• 2024

Objectives : GunRyeong-Tang(GRT) is a traditional herbal prescription that combines Oryeongsan and Sagunja-tang. This study employed network analysis methods on the components of GRT and target genes related to diabetes complications to predict the improvement effects of GRT on diabetes complications. Methods : The collection of active compounds of GRT and related target genes involved the utilization of public databases and the PubChem database. We selected diabetes complication-related genes using GeneCards and confirmed their correlation through comparative analysis with the target genes of GRT. We constructed a network using Cytoscape 3.9.1 and conducted topological analysis. To predict the mechanism, we performed functional enrichment analysis based on Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results : Through network analysis, 234 active compounds and 1361 related genes were collected from GRT. A total of 9,136 genes related to diabetes complications were collected, and 1,039 target genes overlapping with the components of GRT were identified. The core genes of this network were TP53, INS, AKT1, ALB, and EGFR. In addition, GRT significantly reduced the H9c2 cell size and the expression of myocardial hypertrophy biomarkers (ANP, BNP), which were increased by high glucose (HG). Conclusions : Through this study, we were able to predict the activity and mechanism of action of GRT on diabetes and diabetic complications, and confirmed the potential of GRT as a treatment for diabetes complications through the effect of GRT on improving myocardial hypertrophy for diabetic cardiomyopathy.

• 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.