• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.434-441
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• 2015

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.131-136
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• 2020

Hippocampal synaptic dysfunction is a hallmark of Alzheimer's disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.

• International Journal of Oral Biology
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• v.37 no.4
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• pp.167-173
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• 2012

This study investigated the genes involved in the differentiation of odontoblasts derived from human dental pulp stem cells (hDPSCs). hDPSCs isolated from human tooth pulp were validated by fluorescence activated cell sorting (FACS). After odontogenic induction, hDPSCs were analyzed investigated by Alizaline red-S staining, ALP assay, ALP staining and RT-PCR. Differential display-polymerase chain reaction (DD-PCR) was performed to screen differentially expressed genes involved in the differentiation of hDPSCs. By FACS analysis, the stem cell markers CD24 and CD44 were found to be highly expressed in hDPSCs. When hDPSCs were treated with agents such as ${\beta}$-glycerophosphate (${\beta}$-GP) and ascorbic acid (AA), nodule formation was exhibited within six weeks. The ALP activity of hDPSCs was found to elevate over time, with a detectable up-regulation at 14 days after odontogenic induction. RT-PCR analysis revealed that dentin sialophosphoprotein (DSPP) and osteocalcin (OC) expression had increased in a time-dependent manner in the induction culture. Through the use of DD-PCR, several genes were differentially detected following the odontogenic induction. These results suggest that these genes may possibly be linked to a variety of cellular process during odontogenesis. Furthermore, the characterization of these regulated genes during odontogenic induction will likely provide valuable new insights into the functions of odontoblasts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.236-241
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• 2010

The purpose of this study was to investigate the mechanism of ethanol extract of Agrimonia pilosa Ledeb. (EAP)-reduced melanogenesis and diphenyl-picryl-hydrazyl (DPPH) radical scavenging activity. Agrimonia pilosa Ledeb., a perennial herbaceous plant, has been used as an antihemorrhagic, anthelminntic, and antiinflammatory agents in Chinese herbal medicine. In the present study, we observed that melanin synthesis and tyrosinase activity of B16F10 cells were significantly decreased by EAP. However, EAP could not suppress tyrosinase activity in the cell-free system, whereas kojic acid directly inhibited tyrosinase activity. Furthermore, EAP decreased the protein expression of tyrosinase, tyrosinase-related prootein 1 (TRP-1), and tyrosinase-related prootein 2 (TRP-2). EAP scavenged DPPH radical up to 41% with 100 ${\mu}g/m{\ell}$ concentration. These results suggest that the hypopigmentary effect of EPA was due to regulation of tyrosinase protein.

• Korean Journal of Environmental Agriculture
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• v.14 no.3
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• pp.329-337
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• 1995

The effect of N-(4-chlorophenyl) maleimide(CPMI), plant growth regulators, and alkylating agents on gluathione(GSH) content and glutathione S-transferase(GST) activity was examined with 3-day-old etiolated sorghum(Sorghum bicolor [L.] Moench) seedlings. The GSH content and GST activity of untreated seedlings were higher in shoots than that in roots. Response of GST activity in coleoptile was significantly greater than in other tissues of sorghum seedling. In CPMI-treated seedlings, GSH content was not significantly different from that in untreated seedlings. CPM treatment resulted in 2.3-fold increase in GST activity measured with metolachlor as substrate in the coleoptile region. In contrast, change in GST activity measured with metolachlor as substrate in the coleoptile region. In contrast, change in GST activity measured with 1-chloro-2, 4-dinitrobenzene did not occur. The increase of GST activity was caused by induction of a GST isozyme, which is substrate-specific to metolachlor. Subsequently, two hypotheses related to metolachlor detoxification were evaluated on the basis of regulation of plant growth regulators and substrate induction of GST activity. In coleoptile, GST activity measured with metolachior was increased to 2.1-and 3.4-fold by both 2, 4-dichlorophenoxyacetic acid(2,4-D) and metolachlor treated at the germination stage of sorghum, respectively. Treatments of 2.4-D and metolachlor also induced isozymes exhibiting the activity toward metolachlor. One of the isozymes was co-eluted with that induced by CPMI. These results indicated that increase in GST activity by CPMI may be partially related to auxin regulation and substrate induction.

• Biomedical Science Letters
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• v.16 no.3
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• pp.179-185
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• 2010

Benzene is known as a ubiquitous air pollutant and has a carcinogenic influence on the human body. Benzene is also metabolized to other volatile organic compounds (VOCs) in the body such as phenol and hydroquinone (HQ). The metabolites are accumulated and further oxidized by myeloperoxidase in bone marrow. They act as toxic agents and cause a variety of diseases, including cancer, atopic dermatitis and asthma. In this study, we examined the effects of benzene and its metabolites on proliferation, differentiation and chemotaxis of EoL-1 cells, the human eosinophilic leukemia cell line. These chemicals had no effect on the proliferation of EoL-1 cells. Benzene decreased the differentiation of EoL-1 cells induced by butyric acid. HQ was induced the cell death during butyric acid-induced EoL-1 cell differentiation. In a chemotaxis experiment, benzene, phenol and HQ enhanced the cell migration induced by Lkn-1 but not by MCP-1, eotaxin, MIP-$1{\alpha}$ and RANTES. These findings provide the effect of VOCs on the regulation of eosinophil-involved immune response.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.2
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• pp.119-124
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• 2022

Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical opportunistic pathogens. Moreover, these bacteria are known to possess multidrug-resistant (MDR) properties. This study investigates the antimicrobial activity of six fermented products, which have varying efficacies against P. aeruginosa, E. coli, and S. aureus. To identify novel candidate genes, differential expression analysis was performed using an annealing control primer. In the disk diffusion method, Fig vinegar (FV) and Diospyros kaki Thunb vinegar (DTV) showed the greatest increase in inhibition compared to other fermented products, whereas fermented Korean traditional nature herb (FKTNH) had no antibacterial effect. This study identified down-regulation of Escherichia coli O157:H7 ompW gene for outer membrane protein W, whereas gene for synthetic construct Lao1 gene for L-amino acid oxidase were up-regulated in E. coli treated with 5% FV. Consuming fermented vinegar helps prevent bacterial infections. Especially, FV and DTV are potentially useful alternative natural products for multidrug resistance. Furthermore, both are expected to be used as effective natural antimicrobial agents, such as disinfectants.

• Nutrition Research and Practice
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• v.14 no.6
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• pp.580-592
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• 2020

BACKGROUND/OBJECTIVES: The present study aimed to further investigate the potential health beneficial effects of long-term seaweed supplementation on lipid metabolism and hepatic functions in DIO mice. MATERIALS/METHODS: Four brown seaweeds (Undaria pinnatifida [UP], Laminaria japonica [LJ], Sargassum fulvellum [SF], or Hizikia fusiforme [HF]) were added to a high fat diet (HFD) at a 5% ratio and supplemented to C57BL/6N mice for 16 weeks. Triglycerides (TGs) and total cholesterol (TC) in the liver, feces, and plasma were measured. Fecal bile acid (BA) levels in feces were monitored. Hepatic insulin signaling- and lipogenesis-related proteins were evaluated by Western blot analysis. RESULTS: Fasting blood glucose levels were significantly reduced in the LJ, SF, and HF groups compared to the HFD group by the end of 16-week feeding period. Plasma TG levels and hepatic lipid accumulation were significantly reduced in all 4 seaweed supplemented groups, whereas plasma TC levels were only suppressed in the UP and HF groups compared to the HFD group. Fecal BA levels were significantly elevated by UP, LJ, and SF supplementation compared to HFD feeding only. Lastly, regarding hepatic insulin signaling-related proteins, phosphorylation of 5'-AMP-activated protein kinase was significantly up-regulated by all 4 types of seaweed, whereas phosphorylation of protein kinase B was up-regulated only in the SF and HF groups. Lipogenesis-related proteins in the liver were effectively down-regulated by HF supplementation in DIO mice. CONCLUSIONS: Brown seaweed consumption showed hypotriglyceridemic effects in the prolonged DIO mouse model. Specifically, combinatory regulation of BA excretion and lipogenesis-related proteins in the liver by seaweed supplementation contributed to the reduction of plasma and hepatic TG levels, which inhibited hyperglycemia in DIO mice. Thus, the discrepant and species-specific functions of brown seaweeds provide novel insights for the selection of future targets for therapeutic agents.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.481-489
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• 2010

Introduction: TLR-5, a member of the toll-like receptor (TLR) family, is a element of the type I transmembrane receptors, which are characterized by an intracellular signaling domain homolog to the interleukin-1 receptor. These receptors recognize microbial components, particularly bacterial flagellin. All-trans retinoic acid (atRA, tretinoin), a natural metabolite of vitamin A, acts as a growth and differentiation factor in many tissues, and is also needed for immune functions. In this study, THP-1 human macrophage-monocytes were used to examine the mechanisms by which atRA regulated the expression of TLR-5. Because the molecular mechanism underlying this regulation at the transcriptional level is also unclear, this study examined which putative transcription factors are responsible for TLR-5 expression by atRA in immune cells. Materials and Methods: This study examined whether atRA induces the expression of TLR-5 in THP-1 cells using reverse transcription-polymerase chain reaction (RT-PCR), and which transcription factors are involved in regulating the TLR-5 promoter in RAW264.7 cells using a reporter assay system. Western blot analysis was used to determine which signal pathway is involved in the expression of TLR-5 in atRA-treated THP-1 cells. Results: atRA at a concentration of 10 nM greatly induced the expression of TLR-5 in THP-1 cells. Human TLR-5 promoter contains three Sp-1/GC binding sites around -50 bp and two NF-kB binding sites at -380 bp and -160 bp from the transcriptional start site of the TLR-5 gene. Sp-1/GC is primarily responsible for the constitutive TLR-5 expression, and may also contribute to NF-kB at -160 bp to induce TLR-5 after atRA stimulation in THP-1 cells. The role of NF-kB in TLR-5 expression was further confirmed by inhibitor pyrrolidine dithiocarbamate (PDTC) experiments, which greatly reduced the TLR-5 transcription by 70-80%. Conclusion: atRA induces the expression of the human TLR-5 gene and NF-kB is a critical transcription factor for the atRA-induced expression of TLR-5. Accordingly, it is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents of infectious diseases. atRA and various synthetic retinoids have been used therapeutically in human diseases, such as leukemia and other cancers due to the antiproliferative and apoptosis inducing effects of retinoids. Therefore, understanding the molecular regulatory mechanism of TLR-5 may assist in the design of alternative strategies for the treatment of infectious diseases, leukemia and cancers.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.3
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• pp.139-153
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• 2012

Objectives : NK cells are spontaneously cytotoxic lymphocytes. These are not only important parts in the first line of defence against bacterial and viral infections of outside, but they may also play a critical role in chronic viral diseases. NK cells kill their targets spontaneously, without the need for prior sensitization and class I MHC restriction by the regulation of cytolytic functions and secretion of a variety of cytokines, such as interleukin-12(IL-12), MCP-1, IL-6, TNF-${\alpha}$, IFN-${\gamma}$. In addition, macrophage and NK cells cooperate through the production of cell mediates. These cooperation and modulation are one of major factors to prevent for evading immune surveillance of cancer. Hence, it could be assumed that if any candidate to enhance activities of macrophage and NK cell, it is considered as a potentially useful agents against cancer. Methods : In our study, to investigate effect of fermented soybean extracts by Lactic acid bacteria (SFE, soybean fermented extracts) work on intestinal immune cell to maintain general immune modulating and anti-cancer activity. We analyzed NK cytotoxicity assay and gene expressions of cytokine related with macrophage and NK cell activity. Results : In vitro experiment, SFE was verified as safety material for cell toxicicty to tumor cell strain without any toxicity of tumor growth inhibition and various cell strain. Effects of macrophage activity stimulating directly by SFE measured induced cytokine. The studies showed that IL-12 production by stimulation of SFE depended on concentration from 0.16mg/mL to 0.63mg/mL with non toxicity to cell, and it was the best activity at 0.63mg/mL. Besides, the effective concentration of SFE producing TNF-${\alpha}$ is similar to IL-12, but it was the best activity at 1.25mg/mL. The level of MCP-1, IL-6 and IFN-${\gamma}$ depended on concentration from 0.16mg/mL to 10mg/mL, IFN-${\gamma}$ showed the best activity at the effective concentration of 0.63mg/mL. With the result of NK cell activity measurement, the spleen cell of mouse injected SFE had 1.5 times higher killing effect than non injected cell. Conclusions : The result of this studies is that Soybean fermetated extracts(SFE) has possibility to immune aided material for the function not only inhibition of microbial infection to macrophage but also activity of adaption immune and cellular immune system.