• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.2
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• pp.138-144
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• 2017

The pharmacological rationale of Agastache rugosa (AR) or Pogostemon cablin (PC), which have been used in traditional Korean medicine to treat dampness pattern or syndrome in gastrointestinal tract, was investigated on the gastrointestinal disorders. In-vivo model studies that examined the effect on the gastrointestinal disorders of AR or PC were collected. They were classified into disease-induced in-vivo models or non-disease in vivo models. The target disease, animal species, induction method, administration, and outcomes (changes in morphological and histological parameter, or blood and fluid) of each study were analyzed. The therapeutic mechanism of AR or PC extract was evaluated by the induced diseases and the changes in outcomes. There were contradictory reports on gastrointestinal motility of AR or PC in disease non-disease in-vivo model. AR or PC inhibited gastrointestinal motility in disease model of increased gastrointestinal motility, while promoted motility in disease model of decreased gastrointestinal motility. AR or PC also inhibited inflammatory changes in gastrointestinal inflammation model. These results suggest that the bidirectional regulation of gastrointestinal motility and the improvement of gastrointestinal inflammatory disorders might underpin traditional therapeutic effect of AR or PC, that is effect to resolve dampness of gastrointestinal tract.

• Genomics & Informatics
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• v.13 no.1
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• pp.15-24
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• 2015

Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that plays a critical role in lipogenesis. This lipogenic enzyme has gained importance beyond its physiological role due to its implications in several clinical conditions-cancers, obesity, and diabetes. This has made FASN an attractive pharmacological target. Here, we have attempted to predict the theoretical models for the human enoyl reductase (ER) and ${\beta}$-ketoacyl reductase (KR) domains based on the porcine FASN crystal structure, which was the structurally closest template available at the time of this study. Comparative modeling methods were used for studying the structure-function relationships. Different validation studies revealed the predicted structures to be highly plausible. The respective substrates of ER and KR domains-namely, trans-butenoyl and ${\beta}$-ketobutyryl-were computationally docked into active sites using Glide in order to understand the probable binding mode. The molecular dynamics simulations of the apo and holo states of ER and KR showed stable backbone root mean square deviation trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of residues in the most favorable region for ER and 90.3% for the KR domain, respectively. Thus, the predicted models yielded significant insights into the substrate binding modes of the ER and KR catalytic domains and will aid in identifying novel chemical inhibitors of human FASN that target these domains.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.490-495
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• 2004

Brain cells produce cytokines and chemokines during the inflammatory process of many neuronal diseases both in animal models and in patients. Inflammatory cytokines are the main responsible for the onset of inflammatory cascade. During the past decade, a growing corpus of evidence has indicated an important role of these cytokines in the development of brain damage. ZhenganXifeng-tang (ZGXFT) is a Korean herbal prescription, which has been successfully applied for the treatment of various neuronal diseases. However, its effect in experimental models remains unknown. Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in inflammatory disease. An inflammatory response associated with β-amyloid (Aβ) and interleukin (IL)-1β is responsible for the pathology of inflammation disease. To investigate the biological effect of ZGXFT, the author examined cytotoxicity, effect of cytokines (IL-6 and IL-8) secretion and expression of cyclooxygenase-2 (COX-2) on human astrocytoma cell line U373MG stimulated with IL-1β plus M fragment 25-35 (Aβ [25-35]). ZGXFT by itself had no effect on cell viability on human astrocytoma cells. The secretion of IL-6 and IL-8 was inhibited by pre-treatment with ZGXFT in human astrocytoma cells. In addition, the expression of COX-2 was induced by IL-1β plus AB[25-35] and was partially inhibited by treatment with ZGXFT. The author demonstrates the regulatory effects of inflammatory reactions by ZGXFT in human astrocytes for the first time and suggest the anti-inflammatory effect of ZGXFT may reduce and delay pathologic events of inflammatory disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.404-409
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• 2006

Cimicifuga racemosa (Black cohosh) has been used as therapeutics for pain and inflammation in Korean folk medicine. The potential effects of cimicifuga racemosa extract on mast cell dependent allergy reaction, however, have not been well elucidated yet. In the present study, we investigated the effect of cimicifuga racemosa extract on the allergy reaction using mast cell dependent in vivo and in vitro models. The oral administration of cimicifuga racemosa extract showed inhibitory potential on the compound 48/80 induced active systemic anaphylactic shock. cimicifuga racemosa extract also significantly inhibited the anti DNP IgE induced passive cutaneous anaphylaxis (PCA) reaction and acetic acid induced vascular permeability. In addition, cimicifuga racemosa extract inhibited the beta hexosaminidase release and TNF alpha and IL 4 mRNA induction by DNP HSA in rat leukemia mast cells, RBL 2H3. but cimicifuga racemosa extract didn't affected to RBL 2H3 cell viability. These results demonstrated that cimicifuga racemosa extract has an anti allergic potential and it may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.362-366
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• 2017

In this study, Banhasasim-tang extracts (BSTE) have an inhibitory effects on cisplatin-induced decrease of body weights in two mouse model. Cisplatin is the most widely used anticancer drug for treatment of various cancer. However, cisplatin treatment to cancer patients leads to many side effects such as nausea, vomiting and body weight decrease. BSTE has been used to decrease digestive disorders in South Korea. We hypothesize that BSTE improve the cisplatin-induced side effects in mouse models. We found that pre- and co-administration of BSTE inhibited decreases of body weights and food intake by cisplatin in mouse models. But BSTE had no synergistic effects for tumor shrinkage by cisplatin in xenograft model. Collectively, our data suggest that BSTE have great potential as a agent for having decrease effects on side effects by cisplatin in cancer patients.

• Korean Journal of Agricultural and Forest Meteorology
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• v.6 no.1
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• pp.61-69
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• 2004

A long-term growth simulation was performed at 99 land units in Yeoncheon county to test the potential adaptability of each land unit for growing soybean cultivars. The land units for soybean cultivation(CZU), each represented by a geographically referenced land patch, were selected based on land use, soil characteristics, and minimum arable land area. Monthly climatic normals for daily maximum and minimum temperature, precipitation, number of rain days and solar radiation were extracted for each CZU from digital climate models(DCM). The DCM grid cells falling within a same CZU were aggregated to make spatially explicit climatic normals relevant to the CZU. A daily weather dataset for 30 years was randomly generated from the monthly climatic normals of each CZU. Growth and development parameters of CROPGRO-soybean model suitable for 2 domestic soybean cultivars were derived from long-term field observations. Three foreign cultivars with well established parameters were also added to this study, representing maturity groups 3, 4, and 5. Each treatment was simulated with the randomly generated 30 years' daily weather data(from planting to physiological maturity) for 99 land units in Yeoncheon to simulate the growth and yield responses to the inter-annual climate variation. The same model was run with input data from the Crop Experiment Station in Suwon to obtain a 30 year normal performance of each cultivar, which was used as a "reference" for evaluation. Results were analyzed with respect to spatial and temporal variation in yield and maturity, and used to evaluate the suitability of each land unit for growing a specific cultivar. A computer program(MAPSOY) was written to help utilize the results in a decision-making procedure for agrotechnology transfer. transfer.

• Journal of Dental Rehabilitation and Applied Science
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• v.18 no.4
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• pp.321-329
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• 2002

Bending moments results from offset overloading of dental implant, which may cause stress concentrations to exceed the physiological capacity of cortical bone and lead to various kinds of mechanical failures. The purpose of this study was to compare the distributing pattern of stress on the finite element models with the different angulated placement of dental implant in mandibular posterior missing areas. The three kinds of finite element model, were designed according to 3 main configurations: Model 1(parallel typed placement of 2 fixtures), Model 2(15. distal angulated placement of one fixture on second molar area), Model 3(15. mesial angulated placement of one fixture on second molar area). The cemented crowns for mandibular first and second molars were made on the two fixtures (4mm 11.5). Three-dimensional finite element models by two fixtures were constructed with the components of the implant and surrounding bone. A 200N vertical static load were applied to the center of central fossa and the point 2mm apart from the center of central fossa on each model. The preprocessing, solving and postprocessing procedures were done by using FEM analysis software NISA/DISPLAY IV Version 10.0((Engineering Mechanics Research Corporation, USA). Von Mises stresses were evaluated and compared in the supporting bone, fixtures, and abutment. The results were as following : (1) Under the point loading at the central fossa, the direction of angulated fixture affected the stress pattern of implants. (2) Under the offset loading, the position of loading affected more on the stress concentration of implants compare to the angulated direction of implants. The results had a tendency to increase the stress on the supporting bone, fixture and screw under the offset loads when the placement angulation of implant fixture is placed toward mesial or distal direction. In designing of the occlusal scheme for angulated placement, placing the occlusal contacts axially during chewing appears to have advantages in a biomechanical viewpoint.

• Interdisciplinary Bio Central
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• v.4 no.3
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• pp.8.1-8.7
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• 2012

The motor neuron degeneration 2 (mnd2) mice carry a point mutation of A to T nucleotide transversion at the serine 276 residue of high temperature requirement A2 (HtrA2), resulting in losses of an AluI restriction enzyme site (5'AGCT3') and the HtrA2 serine protease activity. Moreover, dysfunctions of HtrA2 are known to be intimately associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Thus, this mnd2 mouse is an invaluable model for understanding the physiological role of HtrA2 and its pathological role in neurodegenerative diseases. Nevertheless, many molecular and cellular biologists in this field have limited experience in working with mutant mouse models due to the necessity of acquired years of the special techniques and knowledges. Herein, using the mnd2 mouse model as an example, we describe easy-to-use standard protocols for web-based analyses of target genes, such as HtrA2, and a novel approach for simple and accurate PCR-AluI-RFLP-based genotype analysis of mnd2 mice. In addition, band resolution of AluI-RFLP fragments was improved in 12% polyacrylamide gel running in 1X Tris-Glycine SDS buffer. Our study indicates that this PCR-AluI-RFLP genotype analysis method can be easily applied by the molecular and cellular biologist to conduct biomedical science studies using the other mutant mouse models.

• Animal cells and systems
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• v.2 no.2
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• pp.249-258
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• 1998

Obesity, one of the most common metabolic diseases in industrial countries is characterized by an increase in the number or size of adipocytes. In an effort to create transgenic mouse models for the study of obesity we developed a novel technique in which adipose tissue can be ablated genetically at will, at any specific developmental stage and/or physiological condition, by the treatment of ganciclovir. We made a series of adipocytespecific expression vectors using minimal regulatory regions of brown adipocyte-specific uncoupling protein (UCP-1) gene and adipocyte-specific aP2 gene, and then analyzed their expression characteristics in cultured cell lines. When both constructs pUCP-LacZ and paP2-LacZ were transfected transiently into differentiating 3T3-L1 (pre-while adipocytes) and HIB-1B (pre-brown adipocytes) cell lines in vitro and then monitored by X-gal staining of cells, these regulatory regions were sufficient to show proper differentiation stage-specific expression in adipocvtes. To confirm that adipocytes expressing HSV-TK controlled by these minimal requlatory elements are sufficient to kill themselves with ganciclovir treatment pUCP-TK and paP2-TK expression constructs were transfected stably into HIB-1B and 3T3-L1 cells, respectively, and their ganciclovir sensitivities were tested during in vitro differentiation of cells. As expected more than 80% of cells were dead by the 7th day of treatment with ganciclovir while negative control cells were not affected at all. The data suqqest that the constructed vectors are suitable for obtaining novel obese transqenic models based on a conditional genetic tissue ablation method.

• Molecules and Cells
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• v.44 no.7
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• pp.500-516
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• 2021

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site. In this study, an integrated approach combining quantitative phosphoproteomics and cell-based functional screening using phosphorylation competition peptides was developed. A pathological cardiac hypertrophy model, junctate-1 transgenic mice and control mice, were analyzed using label-free quantitative phosphoproteomics to identify differentially phosphorylated proteins and sites. A cell-based functional assay system measuring hypertrophic cell growth of neonatal rat ventricle cardiomyocytes (NRVMs) following phenylephrine treatment was applied, and changes in phosphorylation of individual differentially phosphorylated sites were induced by incorporation of phosphorylation competition peptides conjugated with cell-penetrating peptides. Cell-based functional screening against 18 selected phosphorylation sites identified three phosphorylation sites (Ser-98, Ser-179 of Ldb3, and Ser-1146 of palladin) displaying near-complete inhibition of cardiac hypertrophic growth of NRVMs. Changes in phosphorylation levels of Ser-98 and Ser-179 in Ldb3 were further confirmed in NRVMs and other pathological/physiological hypertrophy models, including transverse aortic constriction and swimming models, using site-specific phospho-antibodies. Our integrated approach can be used to identify functionally important phosphorylation sites among differentially phosphorylated sites, and unlike conventional approaches, it is easily applicable for large-scale and/or high-throughput analyses.