Publications by authors named "JaeHoon Bae"

30 Publications

  • Page 1 of 1

Current and New Approaches to Predict the Deflections of One-Way Flexural Members with a Focus on Composite Steel Deck Slabs Voided by Circular Tubes.

Materials (Basel) 2021 Jan 16;14(2). Epub 2021 Jan 16.

Technical Research Center, TechSquare Co., Ltd., 1, Gangnam-daero 51-gil, Seocho-gu, Seoul 06628, Korea.

A new type of composite voided slab, the TUBEDECK (TD), which utilizes the structural function of profiled steel decks, has recently been proposed. Previous studies have confirmed that the flexural strength of TD slabs can be calculated based on the full composite contribution of the steel deck, but for long-span flexural members, the deflection serviceability requirement is often dominant. Herein, we derived a novel deflection prediction approach using the results of flexural tests on slab specimens, focusing on TD slabs. First, deflection prediction based on modifications of the current code was proposed. Results revealed that TD slabs exhibited smaller long-term deflections and at least 10% longer maximum span lengths than solid slabs, indicating their greater efficiency. Second, a novel rational method was derived for predicting deflections without computing the effective moment of inertia. The ultimate deflections predicted by the proposed method correlated closely with the deflection under maximum bending moments. To calculate immediate deflections, variation functions for the concrete strain at the extreme compression fiber and neutral axis depth were assumed with predictions in good agreement with experiments. The proposed procedure has important implications in highlighting a new perspective on the deflection prediction of reinforced concrete and composite flexural members.
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http://dx.doi.org/10.3390/ma14020421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829972PMC
January 2021

Fire Design Equation for Steel-Polymer Composite Floors in Thermal Fields Via Finite Element Analysis.

Materials (Basel) 2020 Dec 7;13(23). Epub 2020 Dec 7.

School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 02481, Korea.

Owing to the development of new materials that enhance structural members in the construction field, steel-polymer composite floors have been developed and applied to steel structures. Similar to a sandwich system, steel-polymer composite floors consist of polymers between two steel plates. The structural performance of full-scale composite floors at ambient conditions has been investigated. Additionally, experiments were conducted on analytical models to predict both thermal behavior under fire, including fire resistance based on a small-scale furnace. To evaluate the fire resistance of full-scale steel-polymer composite floors, the thermal behavior and temperature distribution of composite floors should be investigated. Therefore, the temperature distributions of the full-scale composite floors were estimated using the verified analytical model in this study. Furthermore, to determine the fire design equation of steel-polymer composite floors in the thermal field, the correlations between variables were investigated, such as the thickness of top and bottom steel plates and polymers, as well as the fire resistance in the thermal field.
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http://dx.doi.org/10.3390/ma13235573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730457PMC
December 2020

Src Mediates Epigallocatechin-3--Gallate-Elicited Acid Sphingomyelinase Activation.

Molecules 2020 Nov 23;25(22). Epub 2020 Nov 23.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan.

Epigallocatechin-3--gallate (EGCG) is one of the major bioactive compounds known to be present in green tea. We previously reported that EGCG shows selective toxicity through activation of the protein kinase B (Akt)/cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase (ASM) axis via targeting its receptor 67-kDa laminin receptor (67LR), which is overexpressed in cancer. However, little is known about upstream mechanisms of EGCG-elicited ASM activation. In this study we show that the proto-oncogene tyrosine-protein kinase Src, also known as c-src, plays a crucial role in the anticancer effect of EGCG. We showed that EGCG elicits phosphorylation of Src at Tyr 416, a crucial phosphorylation site for its activity, and that the pharmacological inhibition of Src impedes the upstream events in EGCG-induced cell death signaling including upregulation of Akt activity, increase in cGMP levels, and activation of ASM. Moreover, focal adhesion kinase (FAK), which is involved in the phosphorylation of Src, is colocalized with 67LR. EGCG treatment enhanced interaction of FAK and 67LR. Consistent with these findings, pharmacological inhibition of FAK significantly neutralized EGCG-induced upregulation of Akt activity and activation of ASM. Taken together, FAK/Src play crucial roles in the upstream signaling of EGCG.
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http://dx.doi.org/10.3390/molecules25225481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700551PMC
November 2020

Cyclic Load Test and Finite Element Analysis of NOVEL Buckling-Restrained Brace.

Materials (Basel) 2020 Nov 12;13(22). Epub 2020 Nov 12.

School of Civil, Environmental and Architectural Engineering, Korea University, Anamdong, Seongbukgu, Seoul 136713, Korea.

Compared to concrete or mortar-filled Buckling-Restrained Braces (BRBs), all-steel BRBs provide weight and fabrication time reductions. In particular, all-steel buckling braces with H-section cores are gaining attention in cases where large axial strength is required. In this paper, an all-steel BRB, called NOVEL (Noise, CO emission, Vibration, Energy dissipation and Labor), is presented. It comprises an H-section core encased in a square casing, and its behavior was studied through full-scale subassembly and brace tests, followed by a finite element parametric study. Two failure modes were observed: global buckling and flange buckling of the H-section core, which occurred in test specimens with ratios of 1.68 and 4.91, respectively. Global buckling occurred when the maximum moment in the casing reached its yielding moment, although the test specimens had sufficient stiffness to prevent global buckling. Failure by core flange buckling occurred at a core strain of 1.2%. The finite element parametric study indicated that adjusting the width-to-thickness ratio of the core flange is more feasible than stiffening the flange or adjusting the unconstrained-length end stiffeners. The value of 5.06 was the minimum flange slenderness ratio that provided a stable hysteresis to the end of the loading protocol of the American Institute of Steel Construction standard.
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http://dx.doi.org/10.3390/ma13225103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697326PMC
November 2020

Thermal Contact Conductance-Based Thermal Behavior Analytical Model for a Hybrid Floor at Elevated Temperatures.

Materials (Basel) 2020 Sep 24;13(19). Epub 2020 Sep 24.

School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 02481, Korea.

Hybrid floors infilled with polymeric materials between two steel plates were developed as a prefabricated floor system in the construction industry. However, the floor's fire resistance performance has not been investigated. To evaluate this, fire tests suggested by the Korean Standards should be performed. As these tests are costly and time consuming, the number of variables were limited. However, many variables can be investigated in other ways such as furnace tests and finite element analysis (FEA) with less cost and time. In this study, furnace tests on heated surface areas smaller than 1 m were conducted to investigate the thermal behavior of the hybrid floor at elevated temperatures. To obtain the reliability of the proposed thermal behavior analytical (TBA) model, verifications were conducted by FEAs. Thermal contact conductance including interfacial thermal properties between two materials was adopted in the TBA model, and the values at elevated temperatures were suggested based on thermo-gravimetric analyses results and verified by FEA. Errors between the tests and TBA model indicated that the model was adequate in predicting the temperature distribution in small-scale hybrids. Furthermore, larger furnace tests and analysis results were compared to verify the TBA model's application to different sized hybrid floors.
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http://dx.doi.org/10.3390/ma13194257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579247PMC
September 2020

Cyclic Loading Performance of Radius-Cut Double Coke-Shaped Strip Dampers.

Materials (Basel) 2020 Sep 4;13(18). Epub 2020 Sep 4.

School of Civil, Environmental and Architectural Engineering, Korea University, Anamdong, Seongbukgu, Seoul 136713, Korea.

Conventional slit dampers are widely used for the purpose of seismic retrofitting, however, the structure of these dampers is susceptible to fractures, due to stress concentration at the ends of the strips in the event of large earthquakes. To address this issue, a novel radius-cut coke-shaped strip damper featuring improved ductility is proposed herein. This damper was developed based on the moment distribution over the strip when both its ends were constrained. The height-to-width ratio of the strip was increased to induce bending rather than shear deformation, and the reduced beam section method was employed. A radius-cut section was used to intentionally focus the stress to induce the plastic hinge. This reduced the fracture fragility of the specimen, resulting in an increased inelastic deformation capacity. Cyclic loading tests were conducted to verify damping performance against earthquakes. Experiments and finite element analyses proved that the coke-shaped damper exhibits improved ductility. The final fracture occurred in the radius-cut section after sufficient energy dissipation during cyclic loading. The results also indicated further improvements in strength due to the membrane effect under cyclic loading, caused by the tensile resistance of the strip due to its constrained ends.
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http://dx.doi.org/10.3390/ma13183920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557454PMC
September 2020

Procyanidin C1 Inhibits Melanoma Cell Growth by Activating 67-kDa Laminin Receptor Signaling.

Mol Nutr Food Res 2020 04 6;64(7):e1900986. Epub 2020 Mar 6.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan.

Scope: Procyanidin C1 (PC1) is an epicatechin trimer found mainly in grapes that is reported to provide several health benefits. However, little is known about the molecular mechanisms underlying these benefits. The aim of this study is to demonstrate the molecular mechanisms by which PC1 operates.

Methods And Results: A 67-kDa laminin receptor (67LR) is identified as a cell surface receptor of PC1, with a Kd value of 2.8 µm. PC1 induces an inhibitory effect on growth, accompanied by dephosphorylation of the C-kinase potentiated protein phosphatase-1 inhibitor protein of 17 kDa (CPI17) and myosin regulatory light chain (MRLC) proteins, followed by actin cytoskeleton remodeling in melanoma cells. These actions are mediated by protein kinase A (PKA) and protein phosphatase 2A (PP2A) activation once PC1 is bound to 67LR.

Conclusion: It is demonstrated that PC1 elicits melanoma cell growth inhibition by activating the 67LR/PKA/PP2A/CPI17/MRLC pathway.
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http://dx.doi.org/10.1002/mnfr.201900986DOI Listing
April 2020

Epigallocatechin-3-O-gallate induces acid sphingomyelinase activation through activation of phospholipase C.

Biochem Biophys Res Commun 2019 11 1;520(1):186-191. Epub 2019 Oct 1.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395, Japan. Electronic address:

Epigallocatechin-3-O-gallate (EGCG)-induced cyclic guanosine monophosphate (cGMP) plays a crucial role in EGCG-induced cell death in various types of cancer cells. However, little is known regarding the early molecular events after cGMP induction. In this study, we showed that cGMP induction is sufficient to induce the phosphorylation of protein kinase C delta (PKCδ) at Ser664, the crucial kinase for EGCG-induced activation of acid sphingomyelinase (ASM). Using a chemical inhibitor library, we revealed that the inhibitors of the negative regulators of diacylglycerol strongly increase the effect of EGCG. We also showed that EGCG treatment increased phospholipase C (PLC) activity, and the same results were obtained with cGMP inducer treatment. EGCG-induced ASM activation was completely suppressed by pharmacological inhibition of PLC. Collectively, EGCG-induced cGMP activated the cGMP/PLC/PKCδ/ASM signaling axis in multiple myeloma cells.
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http://dx.doi.org/10.1016/j.bbrc.2019.09.102DOI Listing
November 2019

Diallyl disulfide potentiates anti-obesity effect of green tea in high-fat/high-sucrose diet-induced obesity.

J Nutr Biochem 2019 02 3;64:152-161. Epub 2018 Nov 3.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan. Electronic address:

Obesity is a major problem in developed countries and a burden on social health care systems. Several epidemiological studies showed the protective effects of green tea against obesity-related diseases. Cyclic guanosine monophosphate (cGMP) acts as a mediator for the physiological effects of (-)-epigallocatechin-3-O-gallate, the major constituent of green tea. Here, we showed that the level of phosphodiesterase 5, a negative regulator of cGMP, was up-regulated in adipose tissues of high-fat/high-sucrose (HF/HS) diet-fed mice and that this up-regulation was ameliorated by diallyl disulfide (DADS), the major organosulfur in garlic. A green tea extract (GT) and DADS in combination attenuated HF/HS diet-induced adipose increase and triglyceride accumulation in the liver. In these mechanisms, the combination regimen suppressed the HF/HS diet-induced up-regulation of fatty acid synthesis-related enzymes including sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase, and stearoyl-CoA desaturase-1. Moreover, this combination diet up-regulated thermogenesis-related genes including peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha and uncoupling proteins in both white and brown adipose tissues. In conclusion, we identified DADS as an enhancer of the anti-obesity effect of GT accompanied by the suppression of SREBP-1 and activation of PPAR axis. The combination diet is a novel and easily applicable approach against obesity-related diseases.
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http://dx.doi.org/10.1016/j.jnutbio.2018.10.014DOI Listing
February 2019

Saturated fatty acid attenuates anti-obesity effect of green tea.

Sci Rep 2018 07 3;8(1):10023. Epub 2018 Jul 3.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan.

Green tea and its major polyphenol epigallocatechin-3-O-gallate (EGCG) have suppressive effect on dietary obesity. However, it remains unsolved what type of diet on which they exhibit high or low anti-obesity effect. In the present study, we investigated whether anti-obesity effect of green tea differs depending on composition of fats or fatty acids that consist high-fat (HF) diet in mouse model. Green tea extract (GTE) intake dramatically suppressed weight gain and fat accumulation induced by olive oil-based HF diet, whereas the effects on those induced by beef tallow-based HF diet were weak. GTE also effectively suppressed obesity induced by unsaturated fatty acid-enriched HF diet with the stronger effect compared with that induced by saturated fatty acid-enriched HF diet. These differences would be associated with the increasing action of GTE on expression of PPARδ signaling pathway-related genes in the white adipose tissue. Expressions of genes relating to EGCG signaling pathway that is critical for exhibition of physiological effects of EGCG were also associated with the different effects of GTE. Here, we show that anti-obesity effect of GTE differs depending on types of fats or fatty acids that consist HF diet and could be attenuated by saturated fatty acid.
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http://dx.doi.org/10.1038/s41598-018-28338-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030063PMC
July 2018

Removal of a subdermal contraceptive implant (Implanon NXT) that migrated to the axilla by C-arm guidance: A case report and review of the literature.

Medicine (Baltimore) 2017 Dec;96(48):e8627

Department of Plastic and Reconstructive Surgery Department of Obstetrics and Gynecology, Seoul National University College of Medicine Korea Association of Health Promotion Medicheck Department of Plastic and Reconstructive Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul Department of Obstetrics and Gynecology, Jeju National University Hospital, Jeju, Republic of Korea.

Rationale: To report the distant migration of a subdermal contraceptive implant and to suggest that C arm-guided technique is one of the feasible options for removal of the device migrated to the axilla.

Patient Concerns: A 41-year-old multipara with tingling sensation in the left axilla was referred for removal of an Implanon NXT which could not be palpated by physical examination or detected by ultrasound scanning. Finally, the device was detected by computed tomography and found migrating to the left axilla.

Diagnosis: Migration of Implanon NXT to the left axilla abutting the brachial plexus.

Interventions: The device was removed by C arm-guiding.

Outcomes: The patient went home without any procedure-related complications.

Lessons: The incidence of distant migration of a subdermal implant is possible and should be checked up regularly. If the device cannot be palpated or detected by ultrasound at the original implanting site, this should be concerned. Since the single-rod subdermal implant is radiopaque, it can be detected by roentgenography. In this case the distant migration was detected in the axilla, therefore using C arm-guided technique is feasible for the removal of the migrating device. After reviewing the literature, totally 10 cases of distant migration were reported including 2 cases of migration which were advanced further to the pulmonary artery as an embolization.
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http://dx.doi.org/10.1097/MD.0000000000008627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728737PMC
December 2017

Green Tea Polyphenol EGCG Upregulates Tollip Expression by Suppressing Elf-1 Expression.

J Immunol 2017 11 27;199(9):3261-3269. Epub 2017 Sep 27.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan; and

TLR signaling is critical to innate immune system regulation; however, aberrant TLR signaling is involved in several diseases, including insulin resistance, Alzheimer's disease, and tumor metastasis. Moreover, a recent study found that TLR-4 signaling pathway inhibition might be a target for the suppression of chronic inflammatory disorders. In this article, we show that the green tea polyphenol epigallocatechin-3--gallate (EGCG) increases the expression of Toll interacting protein, a strong inhibitor of TLR4 signaling, by suppressing the expression of E74-like ETS transcription factor 1 (Elf-1). A mechanistic study revealed that EGCG suppressed Elf-1 expression via protein phosphatase 2A/cyclic GMP (cGMP)-dependent mechanisms. We also confirmed that orally administered EGCG and a cGMP inducer upregulated Toll interacting protein expression, increased intracellular levels of cGMP in macrophages, and suppressed Elf-1 expression. These data support EGCG and a cGMP inducer as potential candidate suppressors of TLR4 signaling.
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http://dx.doi.org/10.4049/jimmunol.1601822DOI Listing
November 2017

Hydrogen sulphide donors selectively potentiate a green tea polyphenol EGCG-induced apoptosis of multiple myeloma cells.

Sci Rep 2017 07 27;7(1):6665. Epub 2017 Jul 27.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan.

Hydrogen sulphide (HS) is a colourless gas with the odour of rotten eggs and has recently been recognized as a signal mediator in physiological activities related with the regulation of homeostasis, the vascular system and the inflammatory system. Here we show that HS donors, including sodium hydrogen sulphide (NaHS), GYY 4137 and diallyltrisulfide (DATS), synergistically enhanced the anti-cancer effect of a green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) against multiple myeloma cells without affecting normal cells. NaHS significantly potentiated the anti-cancer effect of EGCG and prolonged survival in a mouse xenograft model. In this mechanism, HS enhanced apoptotic cell death through cyclic guanosine monophosphate (cGMP)/acid sphingomyelinase pathway induced by EGCG. Moreover, NaHS reduced the enzyme activity of cyclic nucleotide phosphodiesterase that is known as cGMP negative regulator. In conclusion, we identified HS as a gasotransmitter that potentiates EGCG-induced cancer cell death.
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http://dx.doi.org/10.1038/s41598-017-06879-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532223PMC
July 2017

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma.

Sci Rep 2017 05 15;7(1):1917. Epub 2017 May 15.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan.

Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains to be established. Here we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)-dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly suppressed tumour formation and liver metastasis in vivo. We also found that a synthesized EGCG analog capable of inducing strong cGMP production drastically suppressed the CSC properties of PDAC and extended the survival period in vivo. In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong cGMP inducer could be a potential treatment candidate for the eradication of CSCs of PDAC.
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http://dx.doi.org/10.1038/s41598-017-02162-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432527PMC
May 2017

The FOXO3/PGC-1β signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma.

J Biol Chem 2017 06 15;292(26):10813-10823. Epub 2017 May 15.

From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan and

In 95% of patients with pancreatic ductal adenocarcinoma, recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anticancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knock-in/knockdown experiments, and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ co-activator-1β (PGC-1β)/pyruvate dehydrogenase-A1 pathway is essential for CD44 expression and CSC properties. We observed that patients exhibiting high pyruvate dehydrogenase-A1 expression have a poor prognosis. Systemic PGC-1β knock-out mice are fertile and viable and do not exhibit an overt phenotype under normal conditions. This suggests that cGMP induction and PGC-1β inhibition represent potential strategies for treating patients with pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.1074/jbc.M116.772111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491768PMC
June 2017

Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216.

J Biol Chem 2017 03 1;292(10):4077-4088. Epub 2017 Feb 1.

From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and

Toll-like receptor 4 (TLR4) plays an essential role in innate immunity through inflammatory cytokine induction. Recent studies demonstrated that the abnormal activation of TLR4 has a pivotal role in obesity-induced inflammation, which is associated with several diseases, including hyperinsulinemia, hypertriglyceridemia, and cardiovascular disease. Here we demonstrate that (-)-epigallocatechin-3--gallate, a natural agonist of the 67-kDa laminin receptor (67LR), suppressed TLR4 expression through E3 ubiquitin-protein ring finger protein 216 (RNF216) up-regulation. Our data indicate cyclic GMP mediates 67LR agonist-dependent RNF216 up-regulation. Moreover, we show that the highly absorbent 67LR agonist (-)-epigallocatechin-3--(3--methyl)-gallate (EGCG3″Me) significantly attenuated TLR4 expression in the adipose tissue. EGCG3″Me completely inhibited the high-fat/high-sucrose (HF/HS)-induced up-regulation of tumor necrosis factor α in adipose tissue and serum monocyte chemoattractant protein-1 increase. Furthermore, this agonist intake prevented HF/HS-induced hyperinsulinemia and hypertriglyceridemia. Taken together, 67LR presents an attractive target for the relief of obesity-induced inflammation.
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http://dx.doi.org/10.1074/jbc.M116.755959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354502PMC
March 2017

The Combination of Green Tea Extract and Eriodictyol Inhibited High-Fat/High-Sucrose Diet-Induced Cholesterol Upregulation Is Accompanied by Suppression of Cholesterol Synthesis Enzymes.

J Nutr Sci Vitaminol (Tokyo) 2016 ;62(4):249-256

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University.

Western diets induce obesity associated with an increased risk of hypercholesterolaemia. Indeed, obesity-induced hypercholesterolaemia is correlated with increased coronary cardiovascular disease (CVD) risk. Male C57BL/6J mice were fed a normal diet, high-fat and high-sucrose diet (HF/HS), HF/HS with green tea extract powder diet (HF/HS+GT), HF/HS with eriodictyol diet (HF/HS+Eri), or HF/HS with green tea extract powder and eriodictyol diet (HF/HS+GT+Eri) for 8 wk. Body weight was lower in the HF/HS+GT+Eri group than in the HF/HS group (-8.3%, p<0.01). The HF/HS diet elicited an upregulation of total cholesterol levels (-63%, p<0.001), and low-density lipoprotein (LDL) levels (-89%, p<0.001) were significantly suppressed by the GT+Eri diet. Conversely, no change (p>0.05) was observed in the HF/HS+GT and HF/HS+Eri groups. The HF/HS diet-induced hepatic mRNA increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) was ameliorated (-73%) by the oral administration of green tea extract and eriodictyol. Moreover, the GT+Eri diet suppressed HF/HS diet-induced upregulation of 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS) (-75%, p<0.05). Furthermore, the LDL receptor (LDLR) levels were higher in the HF/HS+GT+Eri group (+50%, p<0.05) than in the HF/HS group. These results suggest that a combination of green tea and eriodictyol decreases cholesterol levels, particularly LDL levels, accompanied by the suppression of HMGCR and HMGCS levels and upregulation of LDLR levels in the liver.
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http://dx.doi.org/10.3177/jnsv.62.249DOI Listing
May 2017

γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein.

Biochem Biophys Res Commun 2016 05 4;473(4):801-807. Epub 2016 Apr 4.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan. Electronic address:

Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein.
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http://dx.doi.org/10.1016/j.bbrc.2016.03.111DOI Listing
May 2016

Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells.

Oncol Rep 2015 Sep 26;34(3):1162-8. Epub 2015 Jun 26.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.

An epidemiological study showed that green tea consumption is associated with a reduced risk of hematopoietic malignancy. The major green tea polyphenol epigallocatechin‑3-O-gallate (EGCG) is reported to have anticancer effects. Chronic myeloid leukemia (CML) is a major hematopoietic malignancy characterized by expansion of myeloid cells. In the present study, we showed EGCG-induced acid sphingomyelinase (ASM) activation and lipid raft clustering in CML cells. The ASM inhibitor desipramine significantly reduced EGCG-induced cell death. Protein kinase Cδ is a well‑known kinase that plays an important role in ASM activation. We observed EGCG-induced phosphorylation of protein kinase Cδ at Ser664. Importantly, EGCG-induced ASM activation was significantly reduced by pretreatment of CML cells with the soluble guanylate cyclase inhibitor NS2028, suggesting that EGCG induced ASM activation through the cyclic guanosine monophosphate (cGMP)-dependent pathway. Indeed, pharmacological inhibition of a cGMP-negative regulator enhanced the anti-CML effect of EGCG. These results indicate that EGCG-induced cell death via the cGMP/ASM pathway in CML cells.
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http://dx.doi.org/10.3892/or.2015.4086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530928PMC
September 2015

Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis.

FEBS Lett 2013 Sep 1;587(18):3052-7. Epub 2013 Aug 1.

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.

(-)-Epigallocatechin-3-O-gallate (EGCG), a polyphenol in green tea, induces apoptosis in acute myeloid leukemia (AML) cells without affecting normal cells. In this study, we observed that cGMP acts as a cell death mediator of the EGCG-induced anti-AML effect through acid sphingomyelinase activation. EGCG activated the Akt/eNOS axis, a well-known mechanism in vascular cGMP upregulation. We also observed that a major cGMP negative regulator, phosphodiesterase 5, was overexpressed in AML cells, and PDE5 inhibitor, an anti-erectile dysfunction drug, synergistically enhanced the anti-AML effect of EGCG. This combination regimen killed AML cells via overexpressed 67-kDa laminin receptors.
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http://dx.doi.org/10.1016/j.febslet.2013.07.041DOI Listing
September 2013

Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α.

Toxicol In Vitro 2012 Feb 13;26(1):42-50. Epub 2011 Oct 13.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.

Evidence suggests anti-tumor activities of glucosamine-hydrochloride (GS-HCl). In the present study, we investigated anti-proliferative, growth suppressive and/or pro-apoptotic effects of GS-HCl on YD-8 human oral squamous cell carcinoma (OSCC) cells. Fundamentally, treatment with GS-HCl strongly inhibited proliferation and induced apoptosis in YD-8 cells, as determined by MTS and DNA fragmentation analyses. Of further note, as measured by Western analyses, GS-HCl treatment led to activation of caspase-3, cytosolic accumulation of cytochrome c, down-regulation of Mcl-1 and HIF-1α, up-regulation of GRP78, an indicator of ER stress, and generation of ROS in YD-8 cells. Importantly, results of pharmacological inhibition studies showed that treatment with z-VAD-fmk, a pan-caspase inhibitor, but not with vitamin E, an anti-oxidant strongly blocked the GS-HCl-induced apoptosis in YD-8 cells. Analyses of additional cell culture works further revealed that GS-HCl had a strong growth suppressive effect on not only YD-8 but also YD-10B and YD-38, two other human OSCC cell lines. These findings collectively demonstrate that GS-HCl has anti-proliferative, anti-survival, and pro-apoptotic effects on YD-8 cells and the effects appear to be mediated via mechanisms associated with the mitochondrial-dependent activation of caspases, down-regulation of Mcl-1, and induction of ER stress. Considering HIF-1α as a tumor angiogenic transcription factor, the ability of GS-HCl to down-regulate HIF-1α in YD-8 cells may further support its anti-cancer property. It is thus suggested that GS-HCl may be used as a potential anti-cancer drug against human OSCC.
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http://dx.doi.org/10.1016/j.tiv.2011.10.005DOI Listing
February 2012

Overexpression of cyclooxygenase-2 in NCI-H292 human alveolar epithelial carcinoma cells: roles of p38 MAPK, ERK-1/2, and PI3K/PKB signaling proteins.

J Cell Biochem 2011 Oct;112(10):3015-24

Department of Medical Genetic Engineering, Keimyung University School of Medicine, 1000 Dalgubeol-daero, Dalseo-gu, Daegu 704-701, Korea.

Evidence suggests overexpression of COX-2 and its role in many human cancers, including lung. However, the regulatory mechanism underlying COX-2 overexpression in lung cancer is not fully understood. We herein investigated whether COX-2 is overexpressed in human airway cancer cell lines, including A549 (lung), Hep-2 (bronchial), and NCI-H292 (alveolar). When grown in cell culture medium containing 10% FBS (serum), of note, there was strong and transient induction of COX-2 protein and mRNA in NCI-H292 cells, but little or low COX-2 expression is seen in A549 or Hep-2 cells. Interestingly, strong and sustained activities of ERK-1/2, JNK-1/2, p38 MAPK, and PKB were also shown in NCI-H292 cells grown in presence of serum. Profoundly, results of pharmacological inhibition studies demonstrated that the serum-dependent COX-2 up-regulation in NCI-H292 cells is attributed to not only the p38 MAPK-, PI3K/PKB-, and ERK-1/2-mediated COX-2 transcriptional up-regulation but also the p38 MAPK- and ERK-1/2-mediated post-transcriptional COX-2 mRNA stabilization. Of further note, it was shown that the ERK-1/2 and PI3K/PKB (but not COX-2, p38 MAPK, and JNK-1/2) activities are necessary for growth of NCI-H292 cells. These findings collectively demonstrate for the first time that COX-2 expression is transiently up-regulated by serum addition in NCI-H292 cells and the serum-induced COX-2 expression is closely linked to the p38 MAPK-, ERK-1/2-, and PI3K/PKB-mediated COX-2 transcriptional and post-transcriptional up-regulation.
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http://dx.doi.org/10.1002/jcb.23226DOI Listing
October 2011

Echinacea in infection.

Am J Clin Nutr 2008 Feb;87(2):488S-92S

The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA 50011, USA.

Ongoing studies have developed strategies for identifying key bioactive compounds and chemical profiles in Echinacea with the goal of improving its human health benefits. Antiviral and antiinflammatory-antipain assays have targeted various classes of chemicals responsible for these activities. Analysis of polar fractions of E. purpurea extracts showed the presence of antiviral activity, with evidence suggesting that polyphenolic compounds other than the known HIV inhibitor, cichoric acid, may be involved. Antiinflammatory activity differed by species, with E. sanguinea having the greatest activity and E. angustifolia, E. pallida, and E. simulata having somewhat less. Fractionation and studies with pure compounds indicate that this activity is explained, at least in part, by the alkamide constituents. Ethanol extracts from Echinacea roots had potent activity as novel agonists of TRPV1, a mammalian pain receptor reported as an integrator of inflammatory pain and hyperalgesia and a prime therapeutic target for analgesic and antiinflammatory drugs. One fraction from E. purpurea ethanol extract was bioactive in this system. Interestingly, the antiinflammatory compounds identified to inhibit prostaglandin E(2) production differed from those involved in TRPV1 receptor activation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262947PMC
http://dx.doi.org/10.1093/ajcn/87.2.488SDOI Listing
February 2008

Synthesis and natural distribution of anti-inflammatory alkamides from Echinacea.

Molecules 2006 Oct 18;11(10):758-67. Epub 2006 Oct 18.

Iowa State University, Department of Chemistry, Ames, IA 50011, USA.

The synthesis of the alkamides 2Z,4E-undeca-2,4-dien-8,10-diynoic acid isobutyl amide (1) and 2Z,4E-undeca-2,4-dien-8,10-diynoic acid isobutyl amide (5) was accomplished by organometallic coupling followed by introduction of the doubly unsaturated amide moiety. The distribution of these two amides in accessions of the nine species of Echinacea was determined.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065760PMC
http://dx.doi.org/10.3390/11100758DOI Listing
October 2006

Phytochemicals from Echinacea and Hypericum: A Direct Synthesis of Isoligularone.

Synth Commun 2007 Jan;37(8):1251-1257

Department of Chemistry, Iowa State University, Ames, IA 50011.

Reaction of trienes with α,β-unsaturated aldehydes produces bicyclic products via a tandem Diels-Alder/ene reaction. The adduct from tiglic aldehyde was converted into isoligularone by conversion to a furan followed by benzylic oxidation.
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http://dx.doi.org/10.1080/00397910701215544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000341PMC
January 2007

The synthesis and natural distribution of the major ketone constituents in Echinacea pallida.

Molecules 2007 Mar 10;12(3):406-14. Epub 2007 Mar 10.

Iowa State University Department of Chemistry, Ames, IA 50011, USA.

The first synthesis of a series of ketones naturally occurring in E. pallida is described. The natural distribution of these ketones among different Echinacea species is also reported.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986633PMC
http://dx.doi.org/10.3390/12030406DOI Listing
March 2007

Echinacea species and alkamides inhibit prostaglandin E(2) production in RAW264.7 mouse macrophage cells.

J Agric Food Chem 2007 Sep 15;55(18):7314-22. Epub 2007 Aug 15.

The Center for Research on Dietary Botanical Supplements, Iowa State University, Ames, Iowa 50011, USA.

Inhibition of prostaglandin E(2) (PGE(2)) production in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells was assessed with an enzyme immunoassay following treatments with Echinacea extracts or synthesized alkamides. Results indicated that ethanol extracts diluted in media to a concentration of 15 microg/mL from E. angustifolia, E. pallida, E. simulata, and E. sanguinea significantly inhibited PGE2 production. In further studies, PGE2 production was significantly reduced by all synthesized alkamides assayed at 50 microM, by Bauer alkamides 8, 12A analogue, and 14, Chen alkamide 2, and Chen alkamide 2 analogue at 25 microM and by Bauer alkamide 14 at 10 microM. Cytotoxicity did not play a role in the noted reduction of PGE2 production in either the Echinacea extracts or synthesized alkamides. High-performance liquid chromatography analysis identified individual alkamides present at concentrations below 2.8 microM in the extracts from the six Echinacea species (15 microg/mL crude extract). Because active extracts contained <2.8 microM of specific alkamide and the results showed that synthetic alkamides must have a minimum concentration of 10 microM to inhibit PGE2, it is likely that alkamides may contribute toward the anti-inflammatory activity of Echinacea in a synergistic or additive manner.
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http://dx.doi.org/10.1021/jf063711aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365466PMC
September 2007

The First Synthesis of a Diynone from Echinacea pallida.

Synthesis (Stuttg) 2005 Dec;2005(20):3502-3504

Department of Chemistry, Iowa State University, Ames IA 50011, USA.

In order to provide an authentic standard and to generate pure material for biological testing, an efficient synthetic route to 1 was developed. This represents the first total synthesis of a major bioactive diynone from E. pallida.
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http://dx.doi.org/10.1055/s-2005-918418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615886PMC
December 2005

Diacetylenic isobutylamides of Echinacea: synthesis and natural distribution.

Phytochemistry 2004 Sep;65(17):2477-84

Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA.

The syntheses of three diacetylenic isobutylamides of Echinacea angustifolia have been achieved by direct synthetic routes by way of a common intermediate. The key step is the alkylation of the anion of the silylated diacetylene. We report the presence of all three diacetylenic isobutylamides in six of the nine Echinacea species: E. angustifolia, E. sanguinea, E. simulata, E. tennesseensis, E. atrorubens and E. laevigata. The accumulation of these amides is sensitive to organ type and age.
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http://dx.doi.org/10.1016/j.phytochem.2004.06.027DOI Listing
September 2004