• Molecules and Cells
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• v.40 no.8
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• pp.567-576
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• 2017

The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.3
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• pp.527-533
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• 2002

In the screening of Korean traditional tea sources for the cellular lysosomal enzyme activity of peritoneal macrophage from mice, CT-0, a cold-water extract from Carthamus tinctorius L., showed the highest macro-phage-stimulating activity. CT-1-IIa-2-1, a purified macrophage-stimulation polysaccharide was obtained by a series of purification steps such as anion exchage chromatography with DEAE-Toyopearl 650M, gel permeation chromatography with Sepharose CL-6B, Sephacryl S-200, and HPLC with Superdex G-75. The molecular weight of homogeneous purified polysaccharide was estimated about 68 kDa. CT-1-IIa-2-1 consisted of xylose 27.44%, arabinose 16.14%, mannose 15.92% and glucose 14.47%. To measure acute toxicity, dose of 50, 100, 500, and 1000 mg/kg were intraperitoneally injected to ICR mice. The LD$\_$50/ was about 397 mg/kg.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.223-230
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• 2001

Melatonin, a pineal gland hormone, is believed to act as an antioxidant via the stimulation of radical detoxifying enzymes and scavenging of free radicals. In this study, effects of in vitro and in vivo treatments of melatonin on the cisplatin-induced lipid peroxidation, LDH release and plasma creatinine were determined in rabbit renal cortical cells. The level of malondialdehyde (MDA) was assayed as an index of lipid peroxidation and the level of LDH release as an indicator of cellular damage. In in vitro studies, cisplatin increased the levels of MDA and LDH release in a concentration-and time-dependent manner. Melatonin inhibited the cisplatin-induced lipid peroxidation and LDH release in a concentration-dependent manner. The minimal effective concentration of melatonin that significantly reduced the $300\;{\mu}M$ cisplatin-induced lipid peroxidation and LDH release was 1 mM. In in vivo studies, the levels of lipid peroxidation and LDH release in renal cortical cells increased significantly 24 or 48 hours after a single injection of cisplatin (6 mg/kg). When the cisplatin-injected rabbits were pretreated with 10 mg/kg of melatonin, a significant reduction in both lipid peroxidation and LDH release was observed. The plasma creatinine level increased from $0.87{\pm}0.07$ mg/dl in control to $6.33{\pm}0.54$ mg/dl in cisplatin-injected rabbits (P＜0.05). Melatonin partially prevented the increase in serum creatinine level $(1.98{\pm}0.11\;mg/dl)$ by cisplatin (P＜0.05). In the proximal tubules from cisplatin-treated group, tubular cells had microvilli of variable heights. Necrotic debris was seen in tubular lumens. In most of cells, the mitochondria and lysosomes were increased in frequency. The endocytic vacuoles were not prominent and distribution of the brush border was irregular and shortened. These cisplatin-induced morphological changes were moderate in the melatonin-pretreated group. These results suggest that the toxicity of cisplatin is associated with the generation of reactive oxygen free radicals and that melatonin is a powerful antioxidant, which prevents some of the adverse effects of cisplatin.

• Korean Journal of Medicinal Crop Science
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• v.21 no.5
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• pp.361-371
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• 2013

This study was performed to determine the antimelanogenic effect and tyrosinase inhibitory activities of anthocyanin rich fraction (AN-SLP) from Liriope platyphylla Wang et Tang seeds. Anthocyanins isolated from L. platyphylla seeds revealed the presence of four major anthocyanin components, which were tentatively identified as delphinidin-3-Oglucoside, delphinidin-3-O-rutinoside, petunidin-3-O-rutinoside, and malvidin-3-O-rutinoside using semipreparative HPLC, $^1H$-NMR, $^{13}C$ NMR, FAB-MS and LC/ES-MS. The inhibitory effect of AN-SLP on tyrosinase activity was studied using in vitro (against mushroom tyrosinase) and ex vivo (against B16 melanoma cell tyrosinase) models. Cellular tyrosinase activity was decreased by AN-SLP treatment in B 16 melanoma cells through dose dependent manner, but AN-SLP did not inhibit mushroom tyrosinase and L-DOPA oxidation directly. AN-SLP showed melanin inhibition by 53.2% at 50 ${\mu}g/m{\ell}$ which was 0.7 times more efficient than the antimelanogenic effect of commercial arbutin and kojic acid (36.5%) also did not show cell toxicity. Additionally, AN-SLP inhibited the activity of ${\alpha}$-glucosidase and the glycosylation of tyrosinase in melanoma cell. The resulting unsaturated glycosylation of tyrosinase makes it unstable and disturb correct transportation. From theses results, we conclude that AN-SLP could be used as anti-melanogenic agent for skin whitening.

• Toxicological Research
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• v.35 no.1
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• pp.45-63
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• 2019

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.4
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• pp.437-445
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• 2018

In this study, we analyzed two components, sulforaphane and PF-3758309 to prove that the mixed composition of them has more effective antioxidant and whitening functions compared to each component. We analyzed the cellular toxicity of each component and also the mixed composition to find the safe concentration level for cell viability. From the single component treatment, we discovered that sulforaphane was safe up to $10{\mu}M$, and PF-3758309 up to 100 nM. Combination treatment of $10{\mu}M$ sulforaphane and 1 nM PF-3758309 did not affect the cell viability. The LPS-stimulated NO generation was significantly reduced by the mixed composition of sulforaphane and PF-3758309. Melanogenesis by ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH) was also inhibited by the mixed composition. In order to confirm the possibility as the cosmetic material, we carried out clinical studies for the mixed composition samples. Skin safety evaluation using patch test was judged to be unstimulated, skin whitening effect was increased, and melanin deposition was suppressed by treatment of mixed composition samples. These results provide us with the opportunity for applying it into the development of new functional cosmetics.

• Korean Journal of Environmental Biology
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• v.37 no.1
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• pp.72-81
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• 2019

Bisphenol A (BPA), a representative endocrine disrupting chemicals, has adverse effects on growth, development and reproduction in aquatic organisms. The object of this study was to investigate the modulation of antioxidant enzyme-coding genes using quantitative real time RT-PCR (qRT-PCR), enzyme activity and total protein content, to understand oxidative stress responses after exposure to BPA for 48 h in brackish water flea Diaphanosoma celebensis. The BPA ($3mg\;L^{-1}$) significantly upregulated the expression of Cu/Zn-SOD, Mn-SOD, and catalase (CAT) mRNA. Three GST isoforms (GST-kappa, GST-mu, and GST-theta) mRNA levels significantly increased at the rate of $0.12mg\;L^{-1}$ of BPA. In particular, GST-mu showed the highest expression level, indicating its key role in antioxidant response to BPA. SOD activity was induced with a concentration-dependent manner, and total protein contents was reduced. These findings indicate that BPA can induce oxidative stress in this species, and these antioxidants may be involved in cellular protection against BPA exposure. This study will provide a better understanding of molecular mode of action of BPA toxicity in aquatic organisms.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.31 no.3
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• pp.202-212
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• 2021

Objectives: The reproductive health of female workers has been extensively investigated in South Korea and other countries worldwide. However, few studies have discussed the reproductive health of male workers. In this study, we reviewed the recent literature that reports on the effects of occupational exposure on the reproductive health of male workers and the health of their children. Methods: In May 2020 we used the PubMed search engine to search the literature over the last 10 years and chose case-control, cohort, and cross-sectional studies and reviews. We selected epidemiological studies that investigated the association between pre-pregnant occupational exposure and the reproductive health of male workers and the health of their children. We excluded case reports, non-epidemiological studies (animal experiments, cellular-level experiments, and similar articles), and studies that described postnatal occupational exposure. Results: We eventually selected 23 studies. The studies that included exclusively male workers reported that those employed in the agricultural sector or those exposed to pesticides showed lower blood levels of reproductive hormones and a high risk of lympho-hematopoietic system cancer in their children. Male workers exposed to complex organic solvents and organic compounds showed a high risk of poor semen quality, increased time to pregnancy, decreased blood levels of reproductive hormones, and a high risk of lympho-hematopoietic system cancer in their children. Male workers employed in occupations that involved significant social contact, or in the leather and livestock industries, and in occupations with high levels of exposure to lead and organic solvents showed a high risk of malignancies, including lympho-hematopoietic system cancer, neuroblastoma, and central nervous system tumors in their children. Studies that investigated both male and female workers reported that children of male smelters showed a high risk of premature birth, and children of male workers exposed to metals showed a high risk of hypospadias and cryptorchidism. Children of male welders and workers employed in the glass, ceramic, and tile industries showed a high risk of premature birth. Conclusion: The findings of this study will serve as basic data for further research on male workers' reproductive health and provide a scientific basis for the development of strategies to protect the reproductive health of males employed in high-risk occupations. Moreover, the results of this study may provide guidelines to improve the understanding of and knowledge on male workers' reproductive health.

• Fisheries and Aquatic Sciences
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• v.25 no.11
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• pp.579-586
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• 2022

Research on the potential biological activity of red alga Symphyocladia spp. has been limited to Symphyocladia latiuscula, which is widely used as a food ingredient in Korea. Here, we examined the biological activity of another species, Symphyocladia linearis, which is found in Korea and was reported as a new species in 2013. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antibacterial properties of a 70% ethanol extract of S. linearis. Antioxidant activity, which was evaluated using radical scavenging assays, revealed half maximal inhibitory concentration values for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) of 34.57 and 11.70 ㎍/mL algal extract, respectively. Anti-inflammatory activity of the S. linearis ethanolic extract was evaluated using RAW 264.7 cells by measuring the inhibition of lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. The potential cytotoxicity of NO and PGE₂ was first examined, confirming no toxicity at concentrations ranging from 10-100 ㎍/mL. NO production was inhibited 61.1% and 78.0% at 50 and 100 ㎍/mL S. linearis extract, respectively; and PGE₂ production was inhibited 69.1%, 83.2%, and 94.8% at 25, 50, and 100 ㎍/mL S. linearis extract, respectively. Thus, the S. linearis extract showed very strong efficacy against PGE₂ production. The cellular production of reactive oxygen species, measured using 2',7'-dichlorofluorescin diacetate fluorescence, was inhibited 48.8% by the addition of 100 ㎍/mL S. linearis extract. Antibacterial activity was evaluated using the disc diffusion method and minimum inhibitory concentration (MIC). S. linearis was effective only against gram-positive bacteria, exhibiting antibacterial activity against Staphylococcus aureus with a MIC of 256 ㎍/mL extract and against Bacillus cereus with a MIC of 1,024 ㎍/mL extract. Based on these results, we infer that a 70% ethanolic extract of S. linearis possesses strong anti-inflammatory properties, and therefore has the potential to be used in the prevention and treatment of inflammatory and immune diseases.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.53-61
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• 2022

This study aimed to increase the targeting ability against PSMA in cell therapy using metabolic glycoengineering and biorthogonal chemistry and to visualize cell trafficking using PET imaging. Cellular membranes of THP-1 cells were decorated with azide(-N₃) using Ac₄ManNAz by metabolic glycoengineering. Engineered THP-1 cells were conjugated with DBCO-bearing fluorophore (ADIBO-Cy5.5) for 1 h at different concentrations and analyzed by confocal fluorescence microscopy and flow cytometry. For PSAM ligand conjugation to THP-1 cells, Ac₄ManNAz treated THP-1 cells were incubated with DBCO-PSMA ligand (ADIBO-GUL) at a final concentration with 100 µM for 1 h. To evaluate the effect on cell recognition, PSMA ligand conjugated THP-1 cells(as effectors) were co-cultured with PSMA positive 22RV1 (as target cells) at 3 : 1 a effector-to-target cell (E/T) ratio. The interaction between THP-1 and 22RV1 was monitored by confocal fluorescence microscopy. For preparing the radiolabeled THP-1, the cells were treated at the activity of ~ 740 kBq of [⁸⁹Zr]Zr(oxinate)₄/5 × 10⁶ cells. Radiolabeled cells were analyzed for determination of cell-associated radioactivity by gamma counting and viability using MTS assay. In the cytotoxicity assay, THP-1 cells did not have any cytotoxicity even when the Ac₄ManNAz concentration was 100 µM. In confocal microscopy and flow cytometry, THP-1 cells were efficiently labeled ADIBO-Cy5.5 in a dose-dependent manner, and the dose of 100 µM was the optimal concentration for the following experiments. The clusters of PSMA ligand-conjugated THP-1 cells and 22RV1 cells were identified, indicating cell-cell recognition over the cell surface between two types of cells. Cell radiolabeling efficiency was 54.5 ± 17.8%. THP-1 labeled with 0.09 ± 0.03 Bq/cell showed no significant cytotoxicity compared to unlabeled THP-1 up to 7 days. We successfully demonstrated that Ac₄ManNAz treated cells were efficiently conjugated with ADIBO-GUL for preparing the PSMA-targeting cells, and [⁸⁹Zr]Zr(oxinate)₄ could be used to label cells without toxicity. It suggested that PSMA-ligand conjugated cell therapy could be improved cell targeting and be monitored by PET imaging.