• Biomolecules & Therapeutics
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• 제18권1호
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• pp.77-82
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• 2010

Peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR${\gamma}$ agonists, the $\beta$-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR${\gamma}$ agonist. In transactivation assays, SP1818 selectively activated PPAR${\gamma}$, but the degree of PPAR${\gamma}$ stimulation was less than with $1{\mu}M$ rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR${\gamma}$ activated by rosiglitazone but not PPAR${\gamma}$ activated by SP1818.

• 한국유전체학회:학술대회논문집
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• 한국유전체학회 2006년도 The 15th Korean Genome Organization Conference KOGO 2006 Annual Meeting
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• pp.33-33
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• 2006

• Genomics & Informatics
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• 제5권1호
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• pp.24-29
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• 2007

Computational virtual screening has become an essential platform of drug discovery for the efficient identification of active candidates. Moleculardocking, a key technology of receptor-centric virtual screening, is commonly used to predict the binding affinities of chemical compounds on target receptors. Despite the advancement and extensive application of these methods, substantial improvement is still required to increase their accuracy and time-efficiency. Here, we evaluate several advanced structure-based virtual screening approaches for elucidating the rank-order activity of chemical libraries, and the quantitative structureactivity relationship (QSAR). Our results show that the ensemble-average free energy estimation, including implicit solvation energy terms, significantly improves the hit enrichment of the virtual screening. We also demonstrate that the assignment of quantum mechanical-polarized (QM-polarized) partial charges to docked ligands contributes to the reproduction of the crystal pose of ligands in the docking and scoring procedure.

• Journal of Preventive Medicine and Public Health
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• 제53권3호
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• pp.198-204
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• 2020

Objectives: This study aimed to analyze the mortality of heart disease (HD), ischemic heart disease (IHD), and cerebrovascular disease (CeVD) through an age-period-cohort (APC) analysis. Methods: We used data on mortality due to cardiovascular disease from 1995 to 2018 in Japan, as determined by Vital Statistics. Age groups from 0 years to 99 years were defined by 5-year increments, and cohorts were defined for each age group of each year with a 1-year shift. We used Bayesian APC analysis to decompose the changes in the diseases' mortality rates into age, period, and cohort effects. Results: The period effects for all diseases decreased during the analyzed periods for both men and women. The cohort effects for men increased substantially in cohorts born from around 1940 to the 1970s for all types of cardiovascular diseases. The cohort effects of HD decreased in the cohorts born in the 1970s or later for both men and women. Regarding IHD and CeVD, either a non-increase or decrease of cohort effects was confirmed for cohorts born in the 1970s or later for men, but the effects for women showed a continuously increasing trend in the cohorts born in the 1960s or later. Conclusions: The cohort effects for IHD and CeVD showed increasing trends in younger generations of women. This suggests that preventive approaches against cardiovascular diseases are needed, particularly for women.

• 한국건강관리협회지
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• 제3권2호
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• pp.147-164
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• 2005

The purpose of this study was to examine the effects of physical activity on women's health. I conducted literature reviews for meta-analyses and randomized controlled trials with the target diseases including cardiovascular diseases, diabetes, cancers osteoporosis, and pregnancy outcomes. Women who were active had less total mortality and smaller incidence of hypertension, coronary heart diseases, and stroke. Exercise was better than drug therapies in preventing diabetes and effective in preventing colon and breast cancers. Exercise can reduce the risks of falling injury in elderly women. Walking during pregnancy was not harmful to the mothers and their infants, and desirable to prevent the complications of pregnancy or weight gain after pregnancy. Physical activity at work and leisure-time showed similar effects on women's health. Based on these results, moderate-intensity physical activity should be recommended to all women, Resistive, muscle strength, and balance-training exercise also can be recommended. Doctors' advices are effective to make women exercise, especially using handouts or motivational interviewing techniques. It is desirable to recommend to peform other health promotion measures together such as smoking cessation, weight control and diet control.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.370-378
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• 2009

N-myc downstream-regulated gene 2 (NDRG2) has recently been found to be a tumor suppressor gene. Although it has been reported that NDRG2 expression in breast cancer cells decreases cell proliferation by inhibiting STAT3 activation via SOCS1 induction, the molecular mechanism of chemotherapeutic agent-induced apoptosis is not well known. To elucidate the effect of NDRG2 on the apoptotic pathway induced by doxorubicin, we established stable cell lines expressing NDRG2 and investigated the effect of NDRG2 expression on the doxorubicin-induced apoptosis. While STAT3 activation was remarkably inhibited by NDRG2 overexpression, the expression level of p21 was increased by NDRG2 expression. We confirmed that NDRG2-expressing cells treated with doxorubicin suppressed STAT3 activation and upregulated p21 expression. NDRG2 expression considerably enhanced TUNEL positive apoptotic cells, poly-ADP ribose polymerase (PARP) cleavage, release of cytochrome c to cytosol, and caspase-3 activity in doxorubicin-induced apoptosis. Bid expression in a resting state and after treatment with doxorubicin increased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells. Meanwhile, Bcl-$x_L$ expression decreased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells in a resting state and in doxorubicin-treated cells. Collectively, these data suggest that suppression of STAT3 activation by NDRG2 influences the sensitivity to doxorubicin-induced apoptosis of breast cancer cells and this may provide a potential therapeutic benefit to overcome the resistance against doxorubicin in breast cancer.

• Genomics & Informatics
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• 제6권4호
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• pp.210-222
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• 2008

Due to the polygenic nature of cancer, it is believed that breast cancer is caused by the perturbation of multiple genes and their complex interactions, which contribute to the wide aspects of disease phenotypes. A systems biology approach for the identification of subnetworks of interconnected genes as functional modules is required to understand the complex nature of diseases such as breast cancer. In this study, we apply a 3-step strategy for the interpretation of microarray data, focusing on identifying significantly perturbed metabolic pathways rather than analyzing a large amount of overexpressed and underexpressed individual genes. The selected pathways are considered to be dysregulated functional modules that putatively contribute to the progression of disease. The subnetwork of protein-protein interactions for these dysregulated pathways are constructed for further detailed analysis. We evaluated the method by analyzing microarray datasets of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Using the strategy of microarray analysis, we selected several significantly perturbed pathways that are implicated in the regulation of progression of breast cancers, including the extracellular matrix-receptor interaction pathway and the focal adhesion pathway. Moreover, these selected pathways include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting interesting perturbed pathways that putatively play a role in the progression of breast cancer and provides an improved interpretability of networks of protein-protein interactions.

• Journal of Dairy Science and Biotechnology
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• 제38권1호
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• pp.19-26
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• 2020

Allergic diseases, including atopic dermatitis, asthma, allergic rhinitis, and food allergies, could be caused by dysbiosis that results in an immune system imbalance. The incidence of allergic diseases has been increasing and they are now one of the most common diseases throughout the world. Recently, probiotics have been suggested as an alternative intervention for the prevention and treatment of allergic diseases. Probiotics are endogenous microflora with functional effects within hosts. They have various clinical and immunological capacities and have recently been considered as a supplement for the treatment and prevention of allergic diseases. Probiotic bacteria modulate immune cells such as Th1, Th2, and regulatory T cells that are correlated with protection against atopic dermatitis, however, safety concerns for the use of probiotics have been raised. Therefore, further research is needed to clarify the efficacy and safety of probiotics in the treatment of allergic diseases.

• Genomics & Informatics
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• 제11권4호
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• pp.224-229
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• 2013

Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that is able to bind several different ligands, including advanced glycation endproducts, high-mobility group protein (B)1 (HMGB1), S-100 calcium-binding protein, amyloid-${\beta}$-protein, Mac-1, and phosphatidylserine. Its interaction is engaged in critical cellular processes, such as inflammation, proliferation, apoptosis, autophagy, and migration, and dysregulation of RAGE and its ligands leads to the development of numerous human diseases. In this review, we summarize the signaling pathways regulated by RAGE and its ligands identified up to date and demonstrate the effects of hyper-activation of RAGE signals on human diseases, focused mainly on renal disorders. Finally, we propose that RAGE and its ligands are the potential targets for the diagnosis, monitoring, and treatment of numerous renal diseases.

• BMB Reports
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• 제39권4호
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• pp.441-447
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• 2006

Abuse of drugs can elicit compulsive drug seeking behaviors upon repeated administration, and ultimately leads to the phenomenon of addiction. We developed a procedure for the standardization of microarray gene expression data of rat brain in drug addiction and stored them in a single integrated database system, focusing on more effective data processing and interpretation. Another characteristic of the present database is that it has a systematic flexibility for statistical analysis and linking with other databases. Basically, we adopt an intelligent SQL querying system, as the foundation of our DB, in order to set up an interactive module which can automatically read the raw gene expression data in the standardized format. We maximize the usability of this DB, helping users study significant gene expression and identify biological function of the genes through integrated up-to-date gene information such as GO annotation and metabolic pathway. For collecting the latest information of selected gene from the database, we also set up the local BLAST search engine and non-redundant sequence database updated by NCBI server on a daily basis. We find that the present database is a useful query interface and data-mining tool, specifically for finding out the genes related to drug addiction. We apply this system to the identification and characterization of methamphetamine-induced genes' behavior in rat brain.