• Journal of Life Science
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• v.27 no.2
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• pp.149-154
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• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Journal of Life Science
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• v.32 no.12
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• pp.979-988
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• 2022

Halophytes have been reported to possess a variety of physiological activities, such as anti-cancer, anti-oxidant, anti-diabetes, anti-inflammatory, and anti-obesity. Studies on the roots of the halophyte Rosa rugosa, in particular, have shown a variety of physiological activities and are known to be effective for nursing diabetic complications in traditional Korean medicine. In this study, the effect of R. rugosa on adipogenesis was investigated in 3T3-L1 pre-adipocytes treated with crude extract and solvent fractions (H₂O, n-BuOH, 85% aq. MeOH, and n-Hex) obtained from R. rugosa roots. Treatment with extract and the solvent fractions inhibited the formation of intracellular lipid droplets in differentiated 3T3-L1 adipocytes compared to the untreated group. In particular, n-BuOH and 85% aq. MeOH fractions effectively decreased the expression of adipogenic transcription factors: peroxisome proliferator activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP1c) in both mRNA and protein levels. In conclusion, these results suggest that R. rugosa contains anti-adipogenic molecules that can be utilized as a nutraceutical against obesity. Further refining of n-BuOH and 85% aq. MeOH fractions and analysis of their action mechanisms could yield potential therapeutic agents with anti-adipogenic effects.

• Journal of the Korean Chemical Society
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• v.54 no.1
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• pp.77-87
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• 2010

Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, Various N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i) and N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide from (5.a-5.i) to (10.a-10.i) were synthesized using appropriate synthetic route. The entire test compounds (4.a-4.i) and from (5.a-5.i) to (10.a-10.i) were assayed in vitro against s. aureus strain. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial activity against the strains used, when tested in vitro. In general, p-hydroxybenzohydrazide ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 6.f, 7.g, 9.f and 10.f, 10 i were found to be most potent. The test compounds were found nontoxic upto the dose level of 2000 ${\mu}g$/mL. The intact compounds were then subjected for 3D-QSAR studies. 3D-QSAR study based on the principal of alignment of pharmacophoric features by Schrodinger PHASE module. The 3D-QSAR study allowed us to confirm the preferential binding mode of p-hydroxybenzohydrazide inside the active site.

• Nutrition Research and Practice
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• v.8 no.6
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• pp.655-661
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• 2014

BACKGROUND/OBJECTIVES: The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on adipogenesis in 3T3-L1 cells. Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on adiposity were examined. MATERIALS/METHODS: 3T3-L1 cells were treated with arctiin (12.5 to $100{\mu}M$) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce obesity, and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks. RESULTS: Arctiin treatment to 3T3-L1 pre-adipocytes markedly decreased adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key adipogenic regulators $PPAR{\gamma}$ and $C/EBP{\alpha}$, and also significantly inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral adipose tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal adipose tissue. CONCLUSIONS: Arctiin inhibited adipogenesis in 3T3-L1 adipocytes through the inhibition of $PPAR{\gamma}$ and $C/EBP{\alpha}$ and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing obesity.

• Korean Journal of Food Science and Technology
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• v.47 no.1
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• pp.111-118
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• 2015

In the present study, the phenolic compound level, antioxidant activity, and inhibition of lipid accumulation in Aspergillus oryzae-fermented water extracts of the Platycodon grandiflorum (PG) root and the Curcuma longa (CL) root were determined. Total polyphenol and flavonoid contents were decreased after fermentation. However, the flavonoid content of the fermented PG (FPG) was increased by 2.9-fold that of the PG before fermentation. In addition, the antioxidant activities were significantly decreased following fermentation. The potential anti-obesity activity was assessed by determining lipid accumulation and mRNA expression of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) in 3T3-L1 cells. Aspergillus-fermented extracts of PG and CL roots decreased lipid accumulation, and mRNA expression of SREBP-1c and $PPAR{\gamma}$ in 3T3-L1 cells. These results indicate that Aspergillus fermentation augments the anti-obesity activity of PG and CL by regulating the expression of the genes involved in lipid accumulation and cell differentiation of 3T3-L1 cells.

• Development and Reproduction
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• v.2 no.2
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• pp.165-171
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• 1998

p62 is a novel cytoplsmic protein that binds to SH2 domain of p56$^{lck}$, lymphocyte-specific protein tyrosine kinase, and the expression of p62 was observed in most tissues. In addition p62 interacts with various proteins including ubiquitin and atypical PKC isoform, indicating its diverse biological role in different tissues. However, little is known about functional connection between p62 and its binding proteins. In the present study, a novel cellular protein, p62 has been shown to bind to 14-3-3 $\tau$ isoform that is specific for T cells. Moreover, overexpression of p62 in T cells caused to delay onset of UV-induced apoptosis characterized by DNA fragmentation and breakdown of poly (ADP-ribose) polymerase (PARP). Lately, 14-3-3 proteins have been shown to mediate survival signal via interacting proapoptotic Bad protein in the Iymphocyte. These results suggested the presence of p62-mediated regulatory mechanism during apoptosis in T cells, in which activation-induced apoptotic signal could be interfered by p62 and 14-3-3 protein.n.

• BMB Reports
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• v.42 no.10
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• pp.636-641
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• 2009

The penetrating of monoclonal antibodies (mAbs) into solid tumor may be hampered by their large size. The antibody mimetics, composed of two complementarity-determining regions (CDRs) through a cognate framework region (FR), have been demonstrated to have the capacity to penetrate tumors superior to its parental intact IgG. In this study, we used CDR and FR sequences from the humanized anti-HER2 monoclonal antibody trastuzumab to design four antibody mimetics. Then these antibody mimetics were fused to human IgG Fc to generate mimetics-Fc small antibodies. One of the four mimetics-Fc antibodies binds well to HER2-overexpressing SK-BR3 cells and effectively inhibits the binding of trastuzumab. This mimetics-Fc, denoted as HMTI-Fc, was shown to be effective in mediating antibody-dependent cellular cytotoxicity and exhibit an antiproliferative effect in SK-BR3 cells. To our knowledge, the HMTI-Fc antibody shown here is the smallest fully functional antibody and may have a potential for treatment of cancer.

• Korean Journal of Microbiology
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• v.32 no.3
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• pp.215-221
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• 1994

The complete nucleotide sequence of the cloned pga gene encoding the penicillin G acylase of Bacillus megaterium ATCC 14945 and its 5'- and 3'-flanking regions was determined. The sequence revealed only one large open reading frame (2,406 hp) of the penicillin G acylase (pga) gene. Upstream from ATG of the pga gene, there was a putative ribosome binding site, Shine-Dalgarno sequence. The promoter-like structure, - 10 and - 35 sequences, was also found. Following the stop codon, TAG, a structure reminiscent of the E. coli rho-independent transcription terminator was present. The amino acid sequence was deduced from the nucleotide sequence. The molecular mass of the polypeptide was 91,983 Da. There was a potential signal sequence in its amino-terminal region. A comparison of its deduced amino acid sequence with other characterized penicillin G acylases and the result of SDS-polyacrylamide gel electrophoresis of the purified enzyme showed that a precursor polypeptide of 92 kDa was processed into two dissimilar ${\alpha}$ and ${\beta}$-subunits of 25 and 61 kDa.

• Journal of Soil and Groundwater Environment
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• v.10 no.1
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• pp.13-17
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• 2005

Potential for measuring mobile cadmium concentration in sandy soil using polymer magnetic beads with carboxyl groups was investigated. Experiments for extracting cadmium were performed with contaminated soils, de-ionized water and magnetic beads. In this neutral experimental condition, reacting cadmium with magnetic beads indicate total amount of cadmium that can be moved in soil. The results showed that the mobile fraction of cadmium in soil could be combined with magnetic beads in short time. After binding between cadmium and magnetic beads, the beads were separated from soil suspension by outer magnetic force. The bound cadmium was dissolved from magnetic beads by acid solutions, which were then analyzed by atomic absorption spectroscopy (AAS). This method can determine mobile heavy metals in sandy soil effectively than existing method which use pollutant chemicals to environments such as EDTA.

• Korean Journal of Soil Science and Fertilizer
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• v.47 no.1
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• pp.41-47
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• 2014

Agricultural soils surrounding mine areas in South Korea are often contaminated with multiple metals such as Cd, Pb and Zn. It poses potential risks to plants, soil organisms, groundwater, and eventually human health. The aim of this study was to examine the changes in phytoavailability of Cd, Cu, Pb and Zn after application with calcined eggshell (CES; 0, 1, 3, and 5% W/W) in an agricultural soil contaminated by mine tailings. The contents of Cd, Cu, Pb and Zn in soils were 8.79, 65.4, 1602, and $692mgkg^{-1}$ (aqua regia dissolution), respectively. The experiments were conducted with lettuce (Lactuca sativa L. var. longifolia) grown under greenhouse conditions during a 30-d period. $NH_4NO_3$ solution was used to examine the mobile fraction of these metals in soil. The application of CES dramatically increased soil pH and inorganic carbon content in soil due to CaO and $CaCO_3$ of CES. The increased soil pH decreased the mobile fraction of Cd, Pb, Zn: from 3.49 to < $0.01mgkg^{-1}$ for Cd, from 79.4 to $1.75mgkg^{-1}$ for Pb, and from 29.6 to $1.13mgkg^{-1}$ for Zn with increasing treatment of CES from 0 to 5%. In contrast, the mobile fraction of Cu was increased from 0.05 to $3.08mgkg^{-1}$, probably due to the formation of soluble $CuCO_3{^0}$ and Cu-organic complex. This changes in the mobile fraction resulted in a diminished uptake of Cd, Pb and Zn by lettuce and an increased uptake of Cu: from 4.19 to < $0.001mgkg^{-1}$ dry weight (DW) for Cd, from 0.78 to < $0.001mgkg^{-1}$ DW for Pb, and from 133 to $50.0mgkg^{-1}$ DW for Zn and conversely, from 3.79 up to $8.21kg^{-1}$ DW for Cu. The increased contents of Cu in lettuce shoots did not exceed the toxic level of $>25mgkg^{-1}$ DW. The mobile contents of these metals in soils showed a strong relationship with their contents in plant roots and shoots. These results showed that CES effectively reduced the phytoavailability of Cd, Pb, and Zn to lettuce but elevated that of Cu in consequence of the changed binding forms of Cd, Cu, Pb, and Zn in soils. Based on these conclusions, CES can be used as an effective immobilization agent for Cd, Pb and Zn in contaminated soils. However, the CES should be applied in restricted doses due to too high increased pH in soils.