• Molecules and Cells
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• v.41 no.12
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• pp.1052-1060
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• 2018

Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.675-682
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• 2022

Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

• Journal of Energy Engineering
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• v.24 no.1
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• pp.114-122
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• 2015

In the high convective gas flow condition, irregular shaped water waves from which droplet entrainment occurs are generated under horizontally stratified two-phase flow condition. KAERI proposed a new mechanistic droplet entrainment model based on the momentum balance equation consisting of the shear stress, surface tension, and gravity forces. However, this model requires correlation or experimental data of several physical parameters related to the wave characteristics. In the present study, we tried to measure the physical parameters such as wave slope, wave hypotenuse length, wave velocity, wave frequency, and wavelength experimentally. For this, an experiment was conducted in the horizontal rectangular channel of which width, height, and length are, respectively, 40 mm, 50 mm, and 4.2 m. In the present test, the working fluids are chosen as air and water. The PIV technique was applied not only to obtain images for phase interface waves but also to measure the velocity field of the water flow. Additionally, we developed the parallel wire conductance probe for the confirmation of wave height from PIV image. Finally, we measured the physical parameters to be used in the validation of new droplet entrainment model.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.33 no.4
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• pp.353-359
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• 1988

Variations in photosynthetic capacities of leaves differing in thickness were explained on the basis of relationships between gas exchange and internal leaf structure. The relative importance of gas diffusion and of biochemical processes as limiting for leaf photosynthesis was also determined. Mesophyll cell surface was considered to be the limiting internal site for gas diffusion. and cell volume to be indicative of the sink capacity for CO$_2$ fixation. Increases in cell surface area were assumed to reduce proportionately mesophyll resistance to the liquid phase diffusion of CO$_2$. Increased cell volume was thought to account for a proportional increase in reaction rates for carboxylation, oxygenation. and dark respiration. This assumption was tested using chamber-grown Glycine max (L.) Merr. cv. Amsoy plants. Plants were grown under 200, 400, and 600 ${\mu}$mol photons m$\^$-2/ s$\^$-1/ of PAR to induce development of various leaf thickness. Photosynthetic CO$_2$ uptake rates were measured on the 3rd and 4th trifoliolate leaves under 1000 ${\mu}$mol photons m$\^$-2/ s$\^$-1/ of PAR and at the air temperature of 28 C. A pseudo -mechanistic photosynthesis model was modified to accommodate the concept of cell surface area as well as both cell volume and surface area. Both versions were used to simulate leaf photosynthesis. Computations based on volume and surface area showed slightly better agreement with experimental data than did those based on the surface area only. This implies that any single factor, whether it is photosynthetic model utilized in this study was suitable for relating leaf thickness to leaf productivity.

• BMB Reports
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• v.55 no.6
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• pp.275-280
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• 2022

The treatment of atopic dermatitis (AD) is challenging due to its complex etiology. From epidermal disruption to chronic inflammation, various cells and inflammatory pathways contribute to the progression of AD. As with immunosuppressants, general inhibition of inflammatory pathways can be effective, but this approach is not suitable for long-term treatment due to its side effects. This study aimed to identify a plant extract (PE) with anti-inflammatory effects on multiple cell types involved in AD development and provide relevant mechanistic evidence. Degranulation was measured in RBL-2H3 cells to screen 30 PEs native to South Korea. To investigate the anti-inflammatory effects of Parasenecio auriculatus var. matsumurana Nakai extract (PAE) in AD, production of cytokines and nitric oxide, activation status of FcεRI and TLR4 signaling, cell-cell junction, and cell viability were evaluated using qRT-PCR, western blotting, confocal microscopy, Griess system, and an MTT assay in RBL-2H3, HEK293, RAW264.7, and HaCaT cells. For in vivo experiments, a DNCBinduced AD mouse model was constructed, and hematoxylin and eosin, periodic acid-Schiff, toluidine blue, and F4/80-staining were performed. The chemical constituents of PAE were analyzed by HPLC-MS. By measuring the anti-degranulation effects of 30 PEs in RBL-2H3 cells, we found that Paeonia lactiflora Pall., PA, and Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. show an inhibitory activity of more than 50%. Of these, PAE most dramatically and consistently suppressed cytokine expression, including IL-4, IL-9, IL-13, and TNF-α. PAE potently inhibited FcεRI signaling, which mechanistically supports its basophil-stabilizing effects, and PAE downregulated cytokines and NO production in macrophages via perturbation of toll-like receptor signaling. Moreover, PAE suppressed cytokine production in keratinocytes and upregulated the expression of tight junction molecules ZO-1 and occludin. In a DNCB-induced AD mouse model, the topical application of PAE significantly improved atopic index scores, immune cell infiltration, cytokine expression, abnormal activation of signaling molecules in FcεRI and TLR signaling, and damaged skin structure compared with dexamethasone. The anti-inflammatory effect of PAE was mainly due to integerrimine. Our findings suggest that PAE could potently inhibit multi-inflammatory cells involved in AD development, synergistically block the propagation of inflammatory responses, and thus alleviate AD symptoms.

• KSCE Journal of Civil and Environmental Engineering Research
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• v.26 no.1D
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• pp.67-72
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• 2006

Temperature prediction in asphalt pavements is the one of most important factors for estimating the pavement response and predicting the pavement performance in the mechanistic-empirical pavement design. A study on temperature prediction procedure with variation of time and depth in asphalt pavements was conducted using field monitoring data. After selecting the temperature monitoring sections, the temperature sensors have been installed in different depths and the temperature data have been collected in every one hour. The developed pavement temperature prediction model was calibrated using field monitoring temperature data. The predicted temperatures were compared with measured temperatures at different seasons in selected sections. The results showed that the solar absorptivity and emissivity values in the fall is different from the values in other seasons. The predicted temperatures agree well with the measured temperatures at a wide range of temperatures. The temperature differences between each other fall in the range of ${\pm}3^{\circ}C$. It is also found that the regional characteristics did not affect the temperature prediction procedure.

• Journal of Periodontal and Implant Science
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• v.47 no.5
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• pp.292-311
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• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

• Proceedings of the KSEEG Conference
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• 2002.06a
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• pp.81-100
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• 2002

While most of regulatory communities in abroad recognize ' 'natural attenuation " to include degradation, dispersion, dilution, sorption (including precipitation and transformation), and volatilization as governing Processes, regulators prefer "degradation" because this mechanism destroys the contaminant of concern. Unfortunately, true degradation only applies to organic contaminants and short- lived radionuclides, and leaves most metals and long-lived radionuclides. The natural attenuation Processes may reduce the potential risk Posed by site contaminants in three ways: (i)contaminants could be converted to a less toxic form througy destructive processes such as biodegradation or abiotic transformations; (ii) potential exposure levels may be reduced by lowering concentrations (dilution and dispersion); and (iii) contaminant mobility and bioavailability may be reduced by sorption to geomedia. In this review, authors will focus will focul on "sorption" among the natural attenuation processes of hazardous inorganic contaminants including radionuclides. Note though that sorption and transformation processes of inorganic contaminants in the natural setting could be influenced by biotic activities but our discussion would limit only to geochemical reactions involved in the natural attenuation. All of the geochemical reactions have been studied in-depth by numerous researchers for many years to understand "retardation" process of contaminants in the geomedia. The most common approach for estimating retardation is the determination of distrubution coefficiendts ($K_{d}$) of contaminants using parametric or mechanistic models. As typocally used in fate and contaminant transport calculations such as predictive models of the natural attenuation, the $K_{d}$ is defined as the ratio of the contaminant concentration in the surrounding aqueous solution when the system is at equilibrium. Unfortunately, generic or default $K_{d}$ values can result in significant error when used to predict contaminant migration rate and to select a site remediation alternative. Thus, to input the best $K_{d}$ value in the contaminant transport model, it is essential that important geochemical processes affecting the transport should be identified and understood. Precipitation/dissolution and adsorption/desorption are considered the most important geochemical processes affecting the interaction of inorganic and radionuclide contaminants with geomedia at the near and far field, respectively. Most of contaminants to be discussed in this presentation are relatively immobile, i.e., have very high $K_{d}$ values under natural geochemical environments. Unfortunately, the obvious containment in a source area may not be good enough to qualify as monitored natural attenuation site unless owner demonstrate the efficacy if institutional controls that were put in place to protect potential receptors. In this view, natural attenuation as a remedial alternative for some of sites contaminated by hazardous-inorganic components is regulatory and public acceptance issues rather than scientific issue.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4983-4988
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• 2013

Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.