Publications by authors named "Hee-Seop Lee"

13 Publications

  • Page 1 of 1

Adverse effect of polystyrene microplastics (PS-MPs) on tube formation and viability of human umbilical vein endothelial cells.

Food Chem Toxicol 2021 Aug 19;154:112356. Epub 2021 Jun 19.

Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, 20742, USA. Electronic address:

Environmental contamination by microplastics (MPs) is an emerging concern in recent years due to associated adverse impacts of MPs on potential human health problems. Endothelial dysfunction is a condition in which the endothelial layer fails to form normally, and is associated with impaired vascular function. Despite the fact that MPs are known to enter the circulation system through intestinal epithelium, little has been known whether MPs impact the normal function of endothelial cells and the formation of vasculature. In the current study, we investigated the effect of polystyrene microplastics (PS-MPs) on tube formation and cytotoxicity in human umbilical vein endothelial cells (HUVECs). Our study showed that the treatment of HUVECs with PS-MPs significantly decreased cell viability, with intracellular accumulation occurring in a dose- and size-dependent manner. Moreover, significant dose-dependent inhibition of angiogenic tube formation was observed in HUVECs treated with 0.5 μm PS-MPs; this effect was accompanied by suppression of angiogenic signaling pathways and inhibitory activity against wound healing and cell migration. Regarding the mechanism of decreased viability, we observed increased autophagic and necrotic cell death. These results indicate that 6-h exposure of endothelial cells to PS-MPs represses tube-forming capacity, while 48-h exposure leads to autophagy and necrosis-mediated cytotoxicity.
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http://dx.doi.org/10.1016/j.fct.2021.112356DOI Listing
August 2021

AWP1 Restrains the Aggressive Behavior of Breast Cancer Cells Induced by TNF-α.

Front Oncol 2021 18;11:631469. Epub 2021 Mar 18.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

TNF-α plays a crucial role in cancer initiation and progression by enhancing cancer cell proliferation, survival, and migration. Even though the known functional role of AWP1 (zinc finger AN1 type-6, ZFAND6) is as a key mediator of TNF-α signaling, its potential role in the TNF-α-dependent responses of cancer cells remains unclear. In our current study, we found that an AWP1 knockdown using short hairpin RNAs increases the migratory potential of non-aggressive MCF-7 breast cancer cells with no significant alteration of their proliferation in response to TNF-α. A CRISPR/Cas9-mediated AWP1 knockout in MCF-7 cells led to mesenchymal cell type morphological changes and an accelerated motility. TNF-α administration further increased this migratory capacity of these AWP1-depleted cells through the activation of NF-κB accompanied by increased epithelial-mesenchymal transition-related gene expression. In particular, an AWP1 depletion augmented the expression of Nox1, reactive oxygen species (ROS) generating enzymes, and ROS levels and subsequently promoted the migratory potential of MCF-7 cells mediated by TNF-α. These TNF-α-mediated increases in the chemotactic migration of AWP1 knockout cells were completely abrogated by an NF-κB inhibitor and a ROS scavenger. Our results suggest that a loss-of-function of AWP1 alters the TNF-α response of non-aggressive breast cancer cells by potentiating ROS-dependent NF-κB activation.
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http://dx.doi.org/10.3389/fonc.2021.631469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012775PMC
March 2021

Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells.

Oxid Med Cell Longev 2020 2;2020:2890536. Epub 2020 Oct 2.

Agricultural Research Service, U.S. Department of Agriculture, Center for Grain and Animal Health Research, Manhattan, KS 66502, USA.

Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.
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http://dx.doi.org/10.1155/2020/2890536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556115PMC
May 2021

Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review.

Int Immunopharmacol 2020 Dec 8;89(Pt A):107056. Epub 2020 Oct 8.

Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA. Electronic address:

Patchouli alcohol (PA), a tricyclic sesquiterpene, is a dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). Diverse beneficial activities have been reported, including anti-influenza virus, anti-depressant, anti-nociceptive, vasorelaxation, lung protection, brain protection, anti-ulcerogenic, anti-colitis, pre-biotic-like, anti-inflammatory, anti-cancer and protective activities against metabolic diseases. However, detailed mechanistic studies are required to explore the possibility of developing PA as a functional food material or promising drug for the prevention and treatment of human diseases. This review highlights multiple molecular targets and working mechanisms by which PA mediates health benefits.
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http://dx.doi.org/10.1016/j.intimp.2020.107056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543893PMC
December 2020

Preventive Effect of Fermented Chestnut Inner Shell Extract on Obesity-Induced Hepatic Steatosis.

Prev Nutr Food Sci 2020 Mar;25(1):32-40

Deptartment of Food and Biotechnology, Korea University, Sejong 30019, Korea.

This study aimed to investigate the effects of the gallic acid-enriched fermented chestnut inner shell extract (FCCE) by on a high fat diet (HFD)-induced obesity and hepatic steatosis mouse model. Mice feeding FCCE exhibited reduced body weight gain compared to those in the HFD-fed group, and showed lower abdominal fat pad weight including epididymal, retroperitoneal, and mesenteric adipose tissue. Further, FCCE administration decreased adipocyte size by suppressing adipogenic factors such as peroxisome proliferator activated receptor γ and CCAAT/ enhancer-binding protein α, and lipogenic factors such as sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl CoA desaturase-1. Moreover, FCCE decreased levels of lipids in serum and liver as well as serum alanine aminotransferase and aspartate aminotransferase levels, markers of liver injury. Histological observations of the liver showed that FCCE significantly attenuated HFD-induced hepatic steatosis. The effect of FCCE on hepatic lipid regulatory factors may be partly associated with adenosine monophosphate-activated protein kinase activation. These results suggest that gallic acid-enriched FCCE has potential to be a promising functional food for prevention of obesity and obesity-related fatty liver disease.
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http://dx.doi.org/10.3746/pnf.2020.25.1.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143010PMC
March 2020

Effects of teriparatide on fusion rates in patients undergoing complex foot and ankle arthrodesis.

Foot Ankle Surg 2020 Oct 16;26(7):766-770. Epub 2019 Oct 16.

Department of Orthopaedic Surgery, Korea University Ansan Hospital, Ansan-si, South Korea. Electronic address:

Background: Here, we determined whether teriparatide treatment would increase fusion rates after foot and ankle arthrodesis by comparing treatment results between patients with high-risk factors for nonunion who received teriparatide against those who did not.

Methods: We retrospectively reviewed 66 consecutive patients who underwent foot and ankle arthrodesis. The inclusion criterion was the presence of at least one of the following risk factors for nonunion after previous foot and ankle arthrodesis: deformity, bone defects, avascular necrosis, and nonunion. Sixteen patients were finally enrolled and divided into 2 groups: 8 patients received teriparatide treatment after fusion surgery (PTH group), and 8 patients did not (control group).

Results: The fusion rate was significantly greater in the PTH group than in the control group (100% vs 50%). Four patients in the control group developed nonunion, 3 of whom underwent revision fusion; however, all patients received the teriparatide treatment after revision surgery and subsequently achieved union. No significant differences in demographics, fusion sites, and complication rates were found.

Conclusion: Though the sample size was small, the current study suggests that teriparatide administration may improve fusion rates in patients with high-risk factors for nonunion after foot and ankle arthrodesis.
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http://dx.doi.org/10.1016/j.fas.2019.10.002DOI Listing
October 2020

The Upregulation of Toll-Like Receptor 3 via Autocrine IFN-β Signaling Drives the Senescence of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Through JAK1.

Front Immunol 2019 23;10:1659. Epub 2019 Jul 23.

Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Although mesenchymal stromal cells (MSCs) are among the most promising cell sources for cell-based therapies and regenerative medicine, the decline in their function with age due to cellular senescence limits their therapeutic applications. Unveiling the underlying mechanism of MSC senescence is therefore of substantial interest with regard to advancing MSC-based cell therapies. We here show that the induction of human umbilical cord blood-derived MSC (UCB-MSC) senescence causes the predominant upregulation of Toll-like receptor 3 (TLR3). Subsequent TLR3 activation by polyinosinic-polycytidylic acid triggers the prominent features of senescence. Using a clustered regularly interspaced short palindromic repeats/Cas9 library screening system, we identified Janus kinase 1 (JAK1) as the candidate regulatory factor for TLR3-mediated MSC senescence. A JAK1 deficiency blocked the MSC senescence phenotype upon TLR3 activation and TLR3 induction. Targeting the JAK1 pathway using chemical JAK1 inhibitors also significantly suppressed TLR3-mediated MSC senescence. Importantly, we further observed that UCB-MSC senescence is driven by a senescence-associated secretory phenotype (SASP) and that interferon-β (IFN-β) is a component of TLR3-dependent SASP, whereby its autocrine actions upregulate TLR3 and suppress cell proliferation. A JAK1 depletion significantly interrupted these effects of IFN-β, indicating that JAK1 is a signaling mediator linking IFN-β activity to TLR3 expression and the process of MSC senescence. Collectively, our findings provide new mechanistic insights into UCB-MSC senescence by revealing the role of an autocrine regulatory loop of SASP evoked by TLR3 activation.
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http://dx.doi.org/10.3389/fimmu.2019.01659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6665952PMC
November 2020

Fermented Castanea crenata Inner Shell Extract Increases Fat Metabolism and Decreases Obesity in High-Fat Diet-Induced Obese Mice.

J Med Food 2019 Mar 23;22(3):264-270. Epub 2019 Jan 23.

1 Food R&D Center, SK Bioland Co., Ltd., Ansan, Korea.

The anti-obesity effects of fermented Castanea crenata inner shell extract (FCCE) were investigated using high-fat diet (HFD)-induced obese mice. In the FCCE intake groups, body weight gain and adipocyte area were significantly reduced, especially body weight gain in the 250 mg/kg FCCE group (G4) decreased by 37%, respectively, compared with negative control group (G2, HFD group). After oral administration of the FCCE, the increase of serum low-density lipoprotein (LDL)-cholesterol induced by HFD was suppressed significantly, as well as the level of aspartate aminotransferase, and alanine aminotransferase, which are markers of hepatitis induced by obesity. Serum leptin in G4 group was significantly decreased to less than that of G2 group. Also, in G4 and 500 mg/kg FCCE group (G5), enzymes-related lipogenesis, citrate synthase, and ATP citrate lyase were decreased, whereas the level of enoyl-CoA hydratase used for β-oxidation was significantly increased in comparison with normal diet group. Furthermore, the FCCE stimulated the expression of lipolytic regulators, especially AMP-activated protein kinase. In conclusion, we suggest that the FCCE may ameliorate in diet-induced obesity by regulating lipid metabolism.
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http://dx.doi.org/10.1089/jmf.2018.4240DOI Listing
March 2019

Antiobesity Effect of Garlic Extract Fermented by Lactobacillus plantarum BL2 in Diet-Induced Obese Mice.

J Med Food 2016 Sep;19(9):823-9

1 Department of Food and Biotechnology, Korea University , Sejong City, Republic of Korea.

Obesity is viewed as a serious public health problem. This study aimed to investigate the antiobesity effects of fermented garlic extract by lactic acid bacteria (LAFGE) on obesity. Male C57BL/6J mice were fed with high-fat diet (HFD) to induce obesity. The HFD-induced obese mice were orally administrated with 250 or 500 mg/kg LAFGE for 8 weeks. Feeding HFD-fed mice with 250 or 500 mg/kg LAFGE reduced body weight by 14% and 18%, respectively, compared to HFD. HFD-fed mice with 500 mg/kg LAFGE administration had lower epididymal, retroperitoneal, and mesenteric adipose tissue mass by 36%, 44%, and 63%, respectively, compared to HFD. The concentration of plasma triacylglyceride and total cholesterol was significantly lower in the HFD-fed mice with LAFGE administration. Moreover, LAFGE supplementation suppressed adipogenesis by downregulation in mRNA and protein expression of PPARγ, C/EBPα, and lipogenic proteins, including SREBP-1c, FAS, and SCD-1. Based on these findings, LAFGE may ameliorate diet-induced obesity by inhibiting adipose tissue hypertrophy by suppressing adipogenesis.
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http://dx.doi.org/10.1089/jmf.2016.3674DOI Listing
September 2016

Clinical comparison of the two-stranded single and four-stranded double Krackow techniques for acute Achilles tendon ruptures.

Knee Surg Sports Traumatol Arthrosc 2017 Jun 9;25(6):1878-1883. Epub 2016 Aug 9.

Department of Orthopaedic Surgery, Korea University Ansan Hospital, Ansan-si, South Korea.

Purpose: Several different Krackow stitch configurations have been used for acute Achilles tendon rupture repair. Although several biomechanical studies compared different Krackow stitch configurations, to our knowledge, no previous studies compared the clinical outcome of these different suture methods. Therefore, in this study, we aimed to compare the clinical outcomes and complications of the two-stranded single and four-stranded double Krackow techniques.

Methods: Sixty-eight consecutive patients who underwent open repair by using the four-stranded double Krackow (33 patients, group A) or the two-stranded single Krackow (35 patients, group B) techniques between September 2011 and August 2014 were reviewed retrospectively. The isokinetic strength of plantar flexion and dorsiflexion of both ankles was assessed on a Cybex dynamometer 3 and 6 months after surgery. Clinical outcomes were evaluated 3, 6, and 12 months post-operatively.

Results: No significant differences were found between the groups regarding patient demographics or activity levels prior to treatment. Significant differences in the Achilles tendon Total Rupture Score, the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot score, or the four-point Boyden scale were not found at any time during follow-up. Rerupture occurred only in one patient from group A. No significant differences were observed between the groups regarding the isokinetic plantar flexion and dorsiflexion strength at any time or any test speed.

Conclusion: Equally favourable clinical outcomes and isokinetic muscle strength and a low complication rate were achieved with the two-stranded single Krackow technique as compared with the four-stranded double Krackow technique for acute Achilles tendon rupture repair.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-016-4265-0DOI Listing
June 2017

Hepatoprotective effects of lactic acid-fermented garlic extract against acetaminophen-induced acute liver injury in rats.

Food Sci Biotechnol 2016 30;25(3):867-873. Epub 2016 Jun 30.

2Deptartment of Food and Biotechnology, Korea University, Sejong, 30019 Korea.

The aim of the present study was to investigate the protective effect of fermented garlic extract by lactic acid bacteria (LAFGE) against acetaminophen (AAP)-induced acute liver injury in rats. Here we demonstrated that rats treated with LAFGE exhibit resistance to AAP-induced liver injury accompanied by lowered plasma alanine amino transferase levels and decreased proinflammatory responses. This function of LAFGE is linked to its capacity of suppressing AAP-induced apoptosis in the liver, partly via the inhibition of MAPK phosphorylation as well as down-regulation of p53. Our findings reveal that LAFGE modulates the signaling pathways involved in hepatic apoptosis through cellular redox control, as indicated by the inhibition of lipid peroxidation, glutathione and ATP depletion, and the elevation of antioxidant enzyme activities. Taken together, these findings indicate that LAFGE ameliorates AAP-induced liver injury by preventing oxidative stress-mediated apoptosis, thereby establishing LAFGE as a potential supplement in the treatment of AAP-induced liver injury.
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http://dx.doi.org/10.1007/s10068-016-0143-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049174PMC
June 2016

Germinated waxy black rice extract inhibits lipid accumulation with regulation of multiple gene expression in 3T3-L1 adipocytes.

Food Sci Biotechnol 2016 30;25(3):821-827. Epub 2016 Jun 30.

2Department of Food and Biotechnology, Korea University, Sejong, 30019 Korea.

The aim of this study was to investigate the anti-obesity effects of germinated waxy black rice (GWBR) extract in 3T3-L1 adipocytes. The inhibitory effect of GWBR extract against adipocyte differentiation was evaluated using Oil Red O staining and glycerol-3-phosphate dehydrogenase (GPDH) assay. GWBR extract inhibited adipocyte differentiation, but was not found to elicit any cytotoxicity. The mRNA levels of adipogenic transcriptional factors such as C/EBP-α and -β, PPAR-γ, and SREBP-1c, as well as adipogenic enzymes, including aP2, LPL, and FAS were significantly downregulated by treatment with GWBR extract compared to untreated control cells. However, mRNA levels of lipolytic genes such as HSL and ATGL, β-oxidation related genes CPT1, and UCP2 involved in thermogenesis were significantly up-regulated by treatment with GWBR extract. These data suggest that GWBR extract may be a potential functional food, and may have pharmacological applications in both the prevention and treatment of obesity.
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http://dx.doi.org/10.1007/s10068-016-0137-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049167PMC
June 2016

Germinated Waxy Black Rice Suppresses Weight Gain in High-Fat Diet-Induced Obese Mice.

J Med Food 2016 Apr 29;19(4):410-7. Epub 2016 Mar 29.

1 Department of Food and Biotechnology, Korea University , Sejong, Korea.

This study was performed to investigate the antiobesity effect of germinated waxy black rice (GWBR) in high-fat diet (HFD)-induced obese mice. The mice were divided into a normal diet (ND) group, HFD group, and 2 test groups for 8 weeks: 2.5% GWBR-supplemented (GWBR-2.5) group and 5% GWBR-supplemented (GWBR-5) group. Supplementing with GWBR significantly reduced body weight gain and lipid accumulation in the liver and adipose tissue compared to the HFD control group. Triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol levels in serum were decreased by GWBR supplementation, whereas high-density lipoprotein-cholesterol level significantly increased. In addition, mRNA levels of transcriptional factors, such as peroxisome proliferator-activated receptor-γ, CCAAT enhancer-binding protein (C/EBP)-α, C/EBP-β, sterol regulatory element-binding protein-1c, and related genes, including adipocyte fatty acid-binding protein, fatty acid synthase, and lipoprotein lipase, were significantly lower in the GWBR groups. However, lipolytic enzymes, such as hormone-sensitive lipase, adipose TG lipase, and carnitine palmitoyltransferase-1, and uncoupling protein 2 mRNA levels were significantly higher in GWBR-supplemented mice. These results suggest that GWBR exerts antiobesity effects by decreasing lipid accumulation and promoting lipolysis in HFD-induced obese mice.
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http://dx.doi.org/10.1089/jmf.2015.3590DOI Listing
April 2016