• Journal of Oriental Neuropsychiatry
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• v.30 no.4
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• pp.327-340
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• 2019

Objectives: Alzheimer's disease (AD) is a complex disease accompanied by slow impairment of memory and coordination leading to behavioral changes. To date, the only treatment option is to delay the progress of the disease. The purpose of this study was to investigate the synergistic effects of combination treatment with donepezil and three herbal extracts SIP-3 in the AD mouse model induced by amyloid-β (Aβ). Methods: We tested SIP-3 extracts for the cytotoxicity on Aβ-treated SH-SY5Y cells. Then the synergistic effects of SIP-3 and donepezil were evaluated in the AD mouse model using animal experiments and the next generation sequencing (NGS) study. Results: We found that co-treatment with SIP-3 extracts and donepezil increased the viability in Aβ-treated SH-SY5Y cells. The beneficial effects of the co-treatment were also observed in the Aβ-induced AD mouse model. The NGS study was performed to show that the co-treatment of SIP-3 and donepezil restored the disease phenotype closely to the normal level in the AD mouse model in terms of mRNA expression. However, the phenotypes were only partially restored. Conclusions: This study suggests that the combination treatment has a potential to be used for the treatment of AD. However, longer periods of treatment may be required.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.592-600
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• 2022

Background: Di-(2-ethylhexyl) phthalate (DEHP) is the most common endocrine disrupting chemical used as a plasticizer. DEHP is associated with the development of endometrium-related diseases through the induction of inflammation. The major therapeutic approaches against endometrial cancer and endometriosis involve the suppression of inflammatory response. Korean Red Ginseng (KRG) is a natural product with anti-inflammatory and anti-carcinogenic properties. Thus, the purpose of this study is to investigate the effects of KRG on DEHP-induced inflammatory response in endometrial cancer Ishikawa cells and a mouse model of endometriosis. Methods: RNA-sequencing was performed and analyzed on DEHP-treated Ishikawa cells in the presence and absence of KRG. The effects of KRG on DEHP-induced cyclooxygenase-2 (COX-2) mRNA levels in Ishikawa cells were determined by RT-qPCR. Furthermore, the effects of KRG on the extracellular signal-regulated kinases (ERKs) pathway, COX-2, and nuclear factor-kappa B (NF-kB) p65 after DEHP treatment of Ishikawa cells were evaluated by western blotting. In the mouse model, the severity of endometriosis induced by DEHP and changes in immunohistochemistry were used to assess the protective effect of KRG. Results: According to the RNA-sequencing data, DEHP-induced inflammatory response-related gene expression was downregulated by KRG. Moreover, KRG significantly inhibited DEHP-induced ERK1/2/NF-κB/COX-2 levels in Ishikawa cells. In the mouse model, KRG administration significantly inhibited ectopic endometriosis growth after DEHP-induced endometriosis. Conclusions: Overall, these results suggest that KRG may be a promising lead for the treatment of endometrial cancer and endometriosis via suppression of the inflammatory response.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• Korean Chemical Engineering Research
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• v.45 no.1
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• pp.73-80
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• 2007

This article aims to optimize the nitrogen removal of a sequencing batch reactor (SBR) through the use of the activated sludge model and iterative dynamic programming (IDP). Using a minimum batch time and a maximum nitrogen removal for minimum energy consumption, a performance index is developed on the basis of minimum area criteria for SBR optimization. Choosing area as the performance index makes the optimization problem simpler and a proper weighting in the performance index makes it possible to solve minimum time and energy problem of SBR simultaneously. The optimized results show that the optimal set-point of dissolved oxygen affects both the total batch time and total energy cost. For two different influent loadings, IDP-based SBR optimizations suggest each supervisory control of batch scheduling and set-point trajectory of dissolved oxygen (DO) concentration, and can save 20% of the total energy cost, while meeting the treatment requirements of COD and nitrogen. Moreover, it shows that the re-optimization of IDP within a batch can solve the modelling error problem due to the influent loading changes, or the process faults.

• Tuberculosis and Respiratory Diseases
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• v.84 no.1
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• pp.55-66
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• 2021

Background: Particulate matter 10 (PM₁₀; airborne particles <10 ㎛) inhalation has been demonstrated to induce airway and lung diseases. In this study, we investigate the effects of PM₁₀ inhalation on RNA expression in lung tissues using a murine model. Methods: Female BALB/c mice were affected with PM₁₀, ovalbumin (OVA), or both OVA and PM₁₀. PM₁₀ was administered intranasally while OVA was both intraperitoneally injected and intranasally administered. Treatments occurred 4 times over a 2-week period. Two days after the final challenges, mice were sacrificed. Full RNA sequencing using lung homogenates was conducted. Results: While PM₁₀ did not induce cell proliferation in bronchoalveolar fluid or lead to airway hyper-responsiveness, it did cause airway inflammation and lung fibrosis. Levels of interleukin 1β, tumor necrosis factor-α, and transforming growth factor-β in lung homogenates were significantly elevated in the PM₁₀-treated group, compared to the control group. The PM₁₀ group also showed increased RNA expression of Rn45a, Snord22, Atp6v0c-ps2, Snora28, Snord15b, Snora70, and Mmp12. Generally, genes associated with RNA splicing, DNA repair, the inflammatory response, the immune response, cell death, and apoptotic processes were highly expressed in the PM₁₀-treated group. The OVA/PM₁₀ treatment did not produce greater effects than OVA alone. However, the OVA/PM₁₀-treated group did show increased RNA expression of Clca1, Snord22, Retnla, Prg2, Tff2, Atp6v0c-ps2, and Fcgbp when compared to the control groups. These genes are associated with RNA splicing, DNA repair, the inflammatory response, and the immune response. Conclusion: Inhalation of PM₁₀ extensively altered RNA expression while also inducing cellular inflammation, fibrosis, and increased inflammatory cytokines in this murine mouse model.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.116-126
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• 2023

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

• IE interfaces
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• v.13 no.3
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• pp.512-520
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• 2000

An integrated process planning and scheduling model considering outsourcing in manufacturing supply chain is proposed in this paper. The process planning and scheduling considering outsourcing are actually interrelated and should be solved simultaneously. The proposed model considers the alternative process plans for job types, precedence constraints of job operations, due date of production, transportation time and production information for outsourcing. The integrated states include:(1) Operations sequencing, (2) Machine selection, (3) Scheduling with outsourcing under the due date. To solve the model, a heuristic approach based on genetic algorithm(GA) is developed. The proposed approach minimizes the makespan considering outsourcing and shows the best operation-sequences and schedule of all jobs.

• Journal of Korean Society of Environmental Engineers
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• v.31 no.12
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• pp.1075-1080
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• 2009

The partial lipid degradation with the saturation of double-bond at the acidogenesis stage is known to help subsequent methanogenesis during anaerobic digestion. Acidogenic reactions in an anaerobic sequencing batch reactor (ASBR) and a continuously stirred tank reactor (CSTR) were carried out to compare their performances. A mixture of two unsaturated (oleate and linoleate) and two saturated (palmitate and stearate) long-chain fatty acids (LCFAs) was used as a model substrate. Biomass retention in the ASBR contributed to the enhanced performance at hydraulic retention time (HRT) below 15 hr. Biomass retention in the ASBR contributed to the enhanced performance compared to CSTR even at shorter HRT. ASBR would be a proper reactor configuration for the acidogenesis of lipid-containing wastewater.

• Journal of Life Science
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• v.27 no.5
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• pp.524-529
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• 2017

This study was aimed to produce a transgenic zebrafish expressing the human KCNE1 gene. Initially, the entire CDS of the human KCNE1 gene was amplified from a human genomic DNA sample by polymerase chain reaction using a primer set engineered with restriction enzyme sites (EcoRI, BamHI) at the 5' end of each primer. The resultant 402 bp KCNE1 amplicon flanked by EcoR1 and BamH1 was obtained and subsequently cloned into a plasmid vector pPB-CMVp-EF1-GreenPuro. The integrity of the cloned CDS sequence was confirmed by DNA sequencing analysis. Next, the recombinant vector containing the human KCNE1 (pPB-CMVp-hKCNE1-EF1-GreenPuro) was introduced into fertilized eggs of zebrafish by microinjection. Successful expression of the recombinant vector in the eggs was confirmed by the expression of the fluorescence protein encoded in the vector. Finally, in order to assure that the stable expression of the human KCNE1 gene occurred in the transgenic animal, RNAs were extracted from the animal and the presence of KCNE1 transcripts was confirmed by RT-PCT as well as DNA sequencing analysis. The study provides a methodology to construct a useful transgenic animal model applicable to the development of diagnostic technologies for gene therapy of LQTS (Long QT Syndrome) as well as tools for cloning of useful genes in fish.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.3
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• pp.186-192
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• 2004

Purpose: Human tooth proteins are highly heterogeneous, comprising diverse proteins derived from a number of genes. The attempts to identify protein for activity of tooth matrix proteins have been defied by several factors. First, the amount of proteins within teeth is very small relative to many extracellular matrix proteins of other tissues. Second, the bioassay system is tedious and needed for long time. Therefore we tried to find easy techniques, which increase the product rate, and an assay of small proteins, with which amino acid sequence is possible without additional procedures. Materials and Methods: Total protein were extracted from 300 g enamel removed teeth and 600 g teeth with 4 mol/L guanidine HCl and purified by gel chromatography. Aliquot of proteins was implanted into muscle pouches in Sprague-Dawley rats for bioassay. By SDS-PAGE and membrane blotting, molecular weight of each protein was estimated and a partial amino acid sequence was obtained. Each fraction blotted on the membrane was cut out and inserted in rat ectopic model. Results: In dissociative method, total tooth proteins were obtained 1mg/ml from enamel removed teeth and 3.5 mg/ml from teeth. In SDS-PAGE, four clear bands at the sites corresponding to 66, 40, 20 and 18 kD. Especially The 66 kD band was clearly exhibited. Amino acid sequencing from tooth could be possible using PVDF membrane blotting technique. In amino acid sequencing, 66 kD protein was identified as albumin. Conclusion: Compared with conventional method for extraction of teeth protein and bioassay of proteins, the methods in this study were easy, time-saving and more productive technique. The matured tooth proteins omitting additional procedure of mechanical removal of enamel were simply analyzed using blotted PVDF membrane. This method seems to make a contribution as a technique for bioassay and amino acid sequencing of protein.