Publications by authors named "Hye Eun Lee"

94 Publications

Genotyping by Sequencing-Based Discovery of SNP Markers and Construction of Linkage Map from F Population of Pepper with Contrasting Powdery Mildew Resistance Trait.

Biomed Res Int 2021 15;2021:6673010. Epub 2021 Mar 15.

Department of Vegetable Crops, Korea National College of Agriculture and Fisheries, Jeonju 54874, Republic of Korea.

Powdery mildew (PM) is a common fungal disease infecting pepper plants worldwide. Molecular breeding of pepper cultivars with powdery mildew resistance is desirable for the economic improvement of pepper cultivation. In the present study, 188 F population derived from AR1 (PM resistant) and TF68 (PM sensitive) parents were subjected to high-throughput genotyping by sequencing (GBS) for the identification of single nucleotide polymorphism (SNP) markers. Further, the identified SNP markers were utilized for the construction of genetic linkage map and QTL analysis. Overall read mapping percentage of 87.29% was achieved in this study with the total length of mapped region ranging from 2,956,730 to 25,537,525 bp. A total of 41,111 polymorphic SNPs were identified, and a final of 1,841 SNPs were filtered for the construction of a linkage map. A total of 12 linkage groups were constructed corresponding to each chromosome with 1,308 SNP markers with the map length of 2506.8 cM. Further, two QTLs such as and were identified in chromosomes 2 and 5, respectively, for the PM resistance. Overall, the outcomes of the present endeavor can be utilized for the marker-assisted selection of pepper with powdery mildew-resistant trait.
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http://dx.doi.org/10.1155/2021/6673010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987414PMC
March 2021

Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy.

Cells 2021 Mar 4;10(3). Epub 2021 Mar 4.

BK21 PLUS Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea.

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)--glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl--glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.
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http://dx.doi.org/10.3390/cells10030558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001732PMC
March 2021

Impact of Long Working Hours and Shift Work on Perceived Unmet Dental Need: A Panel Study.

Int J Environ Res Public Health 2021 Mar 13;18(6). Epub 2021 Mar 13.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

This study investigates whether workers with long working hours as well as shift workers perceive higher unmet dental care needs, and whether there is a gender difference in the associations. We used the Korea Health Panel (2009, 2011-2014) involving 20,451 person-wave observations from 5567 individuals. Perceived unmet dental care needs was defined when the participants reported that they perceived a need for dental treatment or check-up but had failed to receive dental care services during the past year. Fixed effects logit models were applied to examine how changes in weekly working hours or shift work status were linked to changes in perceived unmet dental needs within each individual. Among participants, 15.9-24.7% reported perceived unmet dental needs and the most common reason was time scarcity. We found that long working hours (>52 h/week) was significantly associated with perceived unmet dental needs due to time scarcity in both men (OR = 1.42, 95% CI 1.13-1.78) and women (OR = 1.35, 95% CI 1.03-1.79) compared workers working 40-52 h per week. Shift work was also a significant risk factor, but only in women (OR = 1.57, 95% CI 1.06-2.32). These findings provide evidence for labor policies to reduce working hours in order to improve access to dental care services.
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http://dx.doi.org/10.3390/ijerph18062939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001453PMC
March 2021

QTL Mapping for Gummy Stem Blight Resistance in Watermelon ( spp.).

Plants (Basel) 2021 Mar 8;10(3). Epub 2021 Mar 8.

Department of Horticulture, Institute of Agricultural Science & Technology, Jeonbuk National University, Jeonju 54896, Korea.

Watermelon () is an economically important fruit crop worldwide. Gummy stem blight (GSB) is one of the most damaging diseases encountered during watermelon cultivation. In the present study, we identified quantitative trait loci (QTLs) associated with GSB resistance in an F population derived from a cross between maternal-susceptible line '920533' () and the paternal-resistant line 'PI 189225' (). The resistance of 178 F plants was assessed by two different evaluation methods, including leaf lesion (LL) and stem blight (SB). To analyze the QTLs associated with GSB resistance, a linkage map was constructed covering a total genetic distance of 1070.2 cM. QTL analysis detected three QTLs associated with GSB resistance on chromosome 8 and 6. Among them, two QTLs, and on chromosome 8 identified as major QTLs, explaining 10.5 and 10.0% of the phenotypic variations localizing at same area and sharing the same top markers for both LL and SB traits, respectively. A minor QTL, , explains 9.7% of phenotypic variations detected on chromosome 6 only for the SB trait. High-throughput markers were developed and validated for the selection of resistant QTLs using watermelon accessions, and commercial cultivars. Four potential candidate genes were predicted associated with GSB resistance based on the physical location of flanking markers on chromosome 8. These findings will be helpful for the development of watermelon cultivars resistant to GSB.
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http://dx.doi.org/10.3390/plants10030500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999335PMC
March 2021

How Framed Messages Influence Depression Assessment Intentions: Interactivity of Social Media as a Moderator.

Int J Environ Res Public Health 2021 Feb 12;18(4). Epub 2021 Feb 12.

School of Communication and Media, Ewha Womans University, Seoul 03760, Korea.

This study examines how the framing and interactivity of messages influence the intentions of individuals to take a depression assessment. An experiment with a 2 (message framing: gain-versus loss-) × 2 (interactivity: low versus high) between-subject design was conducted among 269 Chinese participants ( = 30.70, = 7.34). The results showed that those reading loss-framed messages had a higher intention to take a depression assessment compared to those reading gain-framed messages. Secondly, those reading messages delivered with high interactivity had a higher intention to take a depression assessment than those reading messages delivered with low interactivity. Further, the interaction effect of framed messages and their varying degrees of interactivity was found to influence the intentions of individuals to take a depression assessment as well. Specifically, participants who read the loss-framed message reported stronger intention in the high interactivity group. In contrast, there was no significant difference between the effectiveness of loss-framed and gain-framed messages in promoting the intention to take a depression assessment in the low interactivity condition.
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http://dx.doi.org/10.3390/ijerph18041787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917622PMC
February 2021

Variability in daily or weekly working hours and self-reported mental health problems in Korea, Korean working condition survey, 2017.

Arch Public Health 2021 Feb 27;79(1):25. Epub 2021 Feb 27.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Working hour regulation in Korea is being revised to allow increasing variability in number of working hours. We sought to investigate the association between variability in the number of daily or weekly working hours with or without long working hours (> 52 h/w) and mental health among South Korean workers.

Methods: We used data from 28,345 full-time, non-shift employed workers working more than 30 h per week participating in the Korean Working Condition Survey in 2017. We defined six groups according to variability in daily or weekly working hours (same number vs different number) and weekly working hours (31-40, 41-52, > 52 h per week). Odds ratios (ORs) and confidence intervals (CIs) for self-reported depressive symptoms and anxiety were calculated using workers with same number of working hours/31-40 h per week as the reference.

Results: Variability in number of work hours every day or week combined with > 52 working hours per week showed the highest risk of depressive symptoms (OR = 5.13, 95% CI 3.25-8.11) and anxiety (OR = 3.75, 95% CI 2.39-5.88) compared to the reference group, controlling for age, sex, education, occupation, industry, salary, workers' choice of working hours and overtime payment. Workers working ≤52 h/w were adversely impacted by variable working hours as well.

Conclusions: Variable daily or weekly working hours were associated with poorer self-reported depressive and anxiety symptoms in Korea, among full-time and non-shift workers. Reform of the Korean Labor Standards Act warrants consideration.
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http://dx.doi.org/10.1186/s13690-021-00545-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912832PMC
February 2021

The Relationships among Self-Worth Contingency on Others' Approval, Appearance Comparisons on Facebook, and Adolescent Girls' Body Esteem: A Cross-Cultural Study.

Int J Environ Res Public Health 2021 Jan 21;18(3). Epub 2021 Jan 21.

School of Communication and Media, Ewha Womans University, Seoul 03760, Korea.

The present study examined the relationship between appearance-related social comparison on social networking services (SNSs) and body esteem in a cross-cultural context (three European countries, i.e., Austria, Belgium, and Spain, versus one Asian country, i.e., South Korea). The role of self-worth contingency on others' approval was considered to be a psychological and cultural factor. Utilizing a large-scale cross-national survey of early and middle adolescents in 2017, the responses of female adolescents ( = 981) were analyzed. The results generally support the findings from previous studies but also reveal cultural differences. Appearance comparison on Facebook negatively influenced girls' body esteem in all European countries, but not in South Korea. Self-worth contingency on others' approval negatively influenced girls' body esteem across all four countries. Finally, a positive relationship between self-worth contingency on others' approval and appearance comparison on Facebook was found in all European countries, but not among Korean girls. These findings suggest the importance of self-worth contingency on others' approval and cultural contexts can be used to study the effects of body image-related SNS use.
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http://dx.doi.org/10.3390/ijerph18030901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908083PMC
January 2021

Impact of Decreased Night Work on Workers' Musculoskeletal Symptoms: A Quasi-Experimental Intervention Study.

Int J Environ Res Public Health 2020 12 5;17(23). Epub 2020 Dec 5.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

A possible association between night shift work and musculoskeletal disorder has been suggested. This study aimed to evaluate the impact of decreased night work on musculoskeletal pain. Difference-in-difference estimation was used to compare changes in musculoskeletal pain between shift workers ( = 122) and non-shift workers ( = 170) in a manufacturing company before and after the introduction of a new shift system eliminating overnight work. Musculoskeletal pain was measured by a questionnaire asking if workers had symptoms in specific body parts, including the neck, shoulder, arm/elbow, wrist/hand, back, and leg/foot, over the past year. Generalized estimating equation models were used to estimate changes in pre- versus post-intervention musculoskeletal pain rates between the treated and control group. In the difference-in-difference (DID) models, prevalence of musculoskeletal pain for shoulder (-10.3%), arm (-12.9%), all sites combined (-9.2%), and upper extremity combined (-14.8%) showed significant decreases from pre- to post-intervention among the treated group (shift workers) compared to the control group (non-shift workers) after controlling for age and weekly working hours. Decreasing night work was related to improvement in musculoskeletal pain in shift workers.
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http://dx.doi.org/10.3390/ijerph17239092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730522PMC
December 2020

Versatile Nutraceutical Potentials of Watermelon-A Modest Fruit Loaded with Pharmaceutically Valuable Phytochemicals.

Molecules 2020 Nov 11;25(22). Epub 2020 Nov 11.

Vegetable Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Jeonju 55365, Korea.

Watermelon () is an important horticultural crop which belongs to the Curcubitaceae family. The nutraceutical potential of watermelon has been illustrated by several researchers, which makes it a better choice of functional food. Watermelon has been used to treat various ailments, such as cardio-vascular diseases, aging related ailments, obesity, diabetes, ulcers, and various types of cancers. The medicinal properties of watermelon are attributed by the presence of important phytochemicals with pharmaceutical values such as lycopene, citrulline, and other polyphenolic compounds. Watermelon acts as vital source of l-citrulline, a neutral-alpha amino acid which is the precursor of l-arginine, an essential amino acid necessary for protein synthesis. Supplementation of l-citrulline and lycopene displayed numerous health benefits in in vitro and in vivo studies. Similarly, the dietary intake of watermelon has proven benefits as functional food in humans for weight management. Apart from the fruits, the extracts prepared from the seeds, sprouts, and leaves also evidenced medicinal properties. The present review provides a comprehensive overview of benefits of watermelon for the treatment of various ailments.
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http://dx.doi.org/10.3390/molecules25225258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698065PMC
November 2020

Expression of Colorectal Cancer Antigenic Protein Fused to IgM Fc in Chinese Cabbage ().

Plants (Basel) 2020 Oct 30;9(11). Epub 2020 Oct 30.

Vegetable Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Wanju-gun 55365, Korea.

The epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen and a potential target for tumor vaccine. The EpCAM is a cell-surface glycoprotein highly expressed in colorectal carcinomas. The objective of the present study is to develop an edible vaccine system through -mediated transformation in Chinese cabbage (). For the transformation, two plant expression vectors containing genes encoding for the EpCAM recombinant protein along with the fragment crystallizable (Fc) region of immunoglobulin M (IgM) and Joining (J)-chain tagged with the KDEL endoplasmic reticulum retention motif (J-chain K) were constructed. The vectors were successfully transformed and expressed in the Chinese cabbage individually using . The transgenic Chinese cabbages were screened using genomic polymerase chain reaction (PCR) in T transgenic plant lines generated from both transformants. Similarly, the immunoblot analysis revealed the expression of recombinant proteins in the transformants. Further, the T transgenic plants were generated by selfing the transgenic plants (T) carrying EpCAM-IgM Fc and J-chain K proteins, respectively. Subsequently, the T plants generated from EpCAM-IgM Fc and J-chain K transformants were crossed to generate F plants carrying both transgenes. The presence of both transgenes was validated using PCR in the F plants. In addition, the expression of Chinese cabbage-derived EpCAM-IgM Fc × J-chain K was evaluated using immunoblot and ELISA analyses in the F plants. The outcomes of the present study can be utilized for the development of a potential anti-cancer vaccine candidate using Chinese cabbage.
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http://dx.doi.org/10.3390/plants9111466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693566PMC
October 2020

-phenylenediamine, an oxidative hair dye ingredient, increases thymic stromal lymphopoietin and proinflammatory cytokines causing acute dermatitis.

Toxicol Res 2020 Oct 21;36(4):329-336. Epub 2020 Feb 21.

BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon, 14662 Korea.

Due to high consumption of cosmetics in modern society, people are always exposed to the risk of skin damage and complications. -phenylenediamine (P-PD), an ingredient of hair dye, has been reported to cause allergic contact dermatitis. However, the mechanism has not been well elucidated. Here, we identify that P-PD causes dermatitis by increasing thymic stromal lymphopoietin (TSLP) and inflammatory cytokines. Topical application of P-PD to mouse ear skin in consecutive 5 days resulted in dermatitis symptoms and increased ear thickness. TSLP production in skin was upregulated by P-PD treatment alone. In addition, P-PD-induced TSLP production was potentiated by MC903, which is an in vivo TSLP inducer. P-PD increased TSLP production in keratinocytes (KCMH-1 cells and phorbol 12-myristate 13-acetate-stimulated PAM212 cells). The production of proinflammatory cytokines such as IL-1β, IL-6, IFN-γ, and CCL2, was upregulated by P-PD treatment together with MC903. The results show that repeated exposure to P-PD causes acute contact dermatitis mediated by increasing the expression of TSLP and proinflammatory cytokines.
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http://dx.doi.org/10.1007/s43188-020-00041-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494699PMC
October 2020

Occupational disparities in survival in Korean women with cancer: a nationwide registry linkage study.

BMJ Open 2020 09 10;10(9):e039259. Epub 2020 Sep 10.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Objectives: We sought to examine occupational disparities in survival among Korean women diagnosed with cancer.

Design: Population-based, registry-linkage study.

Setting: South Korea.

Participants: Our study population comprised female workers registered in the Korean national employment insurance programme during 1995-2000 and diagnosed with cancer between 1995 and 2008. A total of 61 110 women with cancer diagnoses was included in analysis. The occupation was categorised into four groups: (1) managers, professionals and technical workers, (2) clerks, (3) service/sales workers and (4) blue-collar workers.

Primary And Secondary Outcome Measure: Study population were linked to the national death registry until 2009. HRs for mortality adjusting for age and year of diagnosis were calculated in the study sample and subgroups with 10 specific cancer sites including thyroid, breast, stomach, cervix, colon or lung cancer using managers, professionals and technical workers as the reference.

Results: Women in service/sales (HR 1.25, 95% CI 1.15 to 1.35) and blue-collar occupations (HR 1.34, 95% CI 1.25 to 1.44) had poorer survival for all cancer sites combined, while blue-collar workers showed poorer survival for lung (HR 1.41, 95% CI 1.14 to 1.77), breast (HR 1.28, 95% CI 1.06 to 1.54), cervical cancer (HR 1.42, 95% CI 1.02 to 2.06) and non-Hodgkin's lymphoma (HR 1.69, 95% CI 1.09 to 2.77) compared with women in professional and managerial positions.

Conclusion: We found substantial and significant inequalities in overall survival by the occupational group among Korean women with cancer, even in the context of universal access to cancer screening and treatment.
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http://dx.doi.org/10.1136/bmjopen-2020-039259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485248PMC
September 2020

Genome Editing of in Tomato Confers Resistance to Pepper Mottle Virus.

Front Plant Sci 2020 24;11:1098. Epub 2020 Jul 24.

Department of Plant Science and Plant Genomics and Breeding Institute, College of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.

Many of the recessive virus-resistance genes in plants encode eukaryotic translation initiation factors (eIFs), including eIF4E, eIF4G, and related proteins. Notably, and its isoform are pivotal for viral infection and act as recessive resistance genes against various potyviruses in a wide range of plants. In this study, we used Clustered Regularly Interspaced Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated targeted mutagenesis to test whether novel sequence-specific mutations at in (tomato) cv. Micro-Tom could confer enhanced resistance to potyviruses. This approach produced heritable homozygous mutations in the transgene-free E generation. Sequence analysis of from E transgenic plants expressing and transcripts identified chimeric deletions ranging from 11 to 43 bp. Genotype analysis of the -edited lines in E, E, and E transgenic tomato plants showed that the mutations were transmitted to subsequent generations. When homozygous mutant lines were tested for resistance to potyviruses, they exhibited no resistance to tobacco etch virus (TEV). Notably, however, several mutant lines showed no accumulation of viral particles upon infection with pepper mottle virus (PepMoV). These results indicate that site-specific mutation of tomato successfully conferred enhanced resistance to PepMoV. Thus, this study demonstrates the feasibility of the use of CRISPR/Cas9 approach to accelerate breeding for trait improvement in tomato plants.
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http://dx.doi.org/10.3389/fpls.2020.01098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396686PMC
July 2020

Genome Editing of in Tomato Confers Resistance to Pepper Mottle Virus.

Front Plant Sci 2020 24;11:1098. Epub 2020 Jul 24.

Department of Plant Science and Plant Genomics and Breeding Institute, College of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.

Many of the recessive virus-resistance genes in plants encode eukaryotic translation initiation factors (eIFs), including eIF4E, eIF4G, and related proteins. Notably, and its isoform are pivotal for viral infection and act as recessive resistance genes against various potyviruses in a wide range of plants. In this study, we used Clustered Regularly Interspaced Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated targeted mutagenesis to test whether novel sequence-specific mutations at in (tomato) cv. Micro-Tom could confer enhanced resistance to potyviruses. This approach produced heritable homozygous mutations in the transgene-free E generation. Sequence analysis of from E transgenic plants expressing and transcripts identified chimeric deletions ranging from 11 to 43 bp. Genotype analysis of the -edited lines in E, E, and E transgenic tomato plants showed that the mutations were transmitted to subsequent generations. When homozygous mutant lines were tested for resistance to potyviruses, they exhibited no resistance to tobacco etch virus (TEV). Notably, however, several mutant lines showed no accumulation of viral particles upon infection with pepper mottle virus (PepMoV). These results indicate that site-specific mutation of tomato successfully conferred enhanced resistance to PepMoV. Thus, this study demonstrates the feasibility of the use of CRISPR/Cas9 approach to accelerate breeding for trait improvement in tomato plants.
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http://dx.doi.org/10.3389/fpls.2020.01098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396686PMC
July 2020

Comparative analysis of lead content during food processing.

Food Sci Biotechnol 2020 Aug 30;29(8):1063-1069. Epub 2020 Mar 30.

Food Contaminants Division, Department of Food Safety Evaluation, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong-eup, Heungdeok-gu, Cheongju-si, 28159 South Korea.

Heavy metals in groups 3-16 in periods 4 and greater. They exist naturally in the earth's crust. People are exposed to heavy metals by the inhalation of polluted air and via the intake of contaminated food. People are exposed to lead (Pb), one of heavy metals, by consuming foods that are contaminated from the environment. Pb is ubiquitous in the environment and accumulates in plants and animals that eat contaminated plants. The Pb in foods before and after processing were analyzed via Inductively coupled plasma with mass spectrometry to determine the effects of the procedures on the Pb migration and residue. This analytical method was verified to have a limit of detection of 0.011-0.859 µg/kg, acceptable linearity with the regression coefficient of 0.999, relative recoveries of 78.1-89.9% and repeatability of 1.4-7.7%. The amount of Pb was reduced during the following processes: more than 79.6% by extracting ginseng, extracting red ginseng and balloon flower roots via alcohol, more than 47.9% by blanching Chwinamul, more than 18.2% by brewing coffee with cold and hot water, more than 22.2% by extracting juices from fruits and peeling fruits. Therefore, proper cooking and food processing can be advantageous in terms of reducing exposure to Pb.
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http://dx.doi.org/10.1007/s10068-020-00756-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347731PMC
August 2020

Evaluation of Manassantin A Tetrahydrofuran Core Region Analogues and Cooperative Therapeutic Effects with EGFR Inhibition.

J Med Chem 2020 07 24;63(13):6821-6833. Epub 2020 Jun 24.

Department of Chemistry, Duke University, Durham, North Carolina 27708, United States.

Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a validated therapeutic target for cancer. In order to develop new HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural product manassantin A, we synthesized and evaluated manassantin A analogues with modifications in the tetrahydrofuran core region of manassantin A. Our structure-activity relationship study indicated that the α,α'--configuration of the central ring of manassantin A is critical to HIF-1 inhibition. We also demonstrated that a combination of manassantin A with an epidermal growth factor receptor inhibitor shows cooperative antitumor activity (∼80% inhibition for combination vs ∼30% inhibition for monotherapy). Our findings will provide important frameworks for the future therapeutic development of manassantin A-derived chemotherapeutic agents.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00151DOI Listing
July 2020

γ-Glutamylcysteine- and Cysteinylglycine-Directed Growth of Chiral Gold Nanoparticles and their Crystallographic Analysis.

Angew Chem Int Ed Engl 2020 07 25;59(31):12976-12983. Epub 2020 May 25.

Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

Chiral optical metamaterials with delicate structures are in high demand in various fields because of their strong light-matter interactions. Recently, a scalable strategy for the synthesis of chiral plasmonic nanoparticles (NPs) using amino acids and peptides has been reported. Reported herein, 3D chiral gold NPs were synthesized using dipeptide γ-Glu-Cys and Cys-Gly and analyzed crystallographically. The γ-Glu-Cys-directed NPs present a cube-like outline with a protruding chiral wing. In comparison, the NPs synthesized with Cys-Gly exhibited a rhombic dodecahedron-like outline with curved edges and elliptical cavities on each face. Morphology analysis of intermediates indicated that γ-Glu-Cys generated an intermediate concave hexoctahedron morphology, while Cys-Gly formed a concave rhombic dodecahedron. NPs synthesized with Cys-Gly are named 432 helicoid V because of their unique morphology and growth pathway.
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http://dx.doi.org/10.1002/anie.202003760DOI Listing
July 2020

Cancer Incidence by Occupation in Korea: Longitudinal Analysis of a Nationwide Cohort.

Saf Health Work 2020 Mar 31;11(1):41-49. Epub 2019 Dec 31.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: We performed this study to investigate the inequalities in site-specific cancer incidences among workers across different occupations in Korea.

Methods: Subjects included members of the national employment insurance. Incident cancers among 8,744,603 workers were followed from 1995 to 2007. Occupational groups were classified according to the Korean Standard Occupational Classification. Age-standardized incidence rate ratios were calculated.

Results: We found that men in service/sales and blue-collar occupations had elevated rates of esophageal, liver, laryngeal, and lung cancer. Among women, service/sales workers had elevated incidences of cervical cancer. Male prostate cancer, female breast, corpus uteri, and ovarian cancers, as well as male and female colorectal, kidney, and thyroid cancer showed lower incidences among workers in lower socioeconomic occupations.

Conclusions: Substantial differences in cancer incidences were found depending on occupation reflecting socioeconomic position, in the Korean working population. Cancer prevention policy should focus on addressing these socioeconomic inequalities.
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http://dx.doi.org/10.1016/j.shaw.2019.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078566PMC
March 2020

Uniform Chiral Gap Synthesis for High Dissymmetry Factor in Single Plasmonic Gold Nanoparticle.

ACS Nano 2020 Mar 11;14(3):3595-3602. Epub 2020 Mar 11.

Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Synthesis of chiral plasmonic materials has been highlighted for the last decades with their optical properties and versatile potential applications. Recently reported aqueous-based amino acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles with 432 point-group symmetry shows exceptionally high chiroptic response within 100 nm scales. Despite its already excellent chiroptic response, a single-nanoparticle dark field scattering study revealed that full chiroptic potential of chiral gold nanoparticle is limited with its overall synthetic uniformity. Based on this knowledge, we present a multi-chirality-evolution step synthesis method for the enhancement of chiroptic response through an increase in particle uniformity. Detailed time variant study and interrelationship study of reaction parameters allowed the systematic construction of design principles for chiral nanoparticles with exceptional chiroptic response. With the application of precisely controlled growth kinetic to two distinct growth regimes, modified chiral gold nanoparticles showed significantly improved uniformity, achieving an improved dissymmetry factor of = 0.31. We expect that our strategy will aid in precise morphology and property control for chiral nanomaterials, which can be used in various plasmonic metamaterial applications.
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http://dx.doi.org/10.1021/acsnano.9b10094DOI Listing
March 2020

Uniform Chiral Gap Synthesis for High Dissymmetry Factor in Single Plasmonic Gold Nanoparticle.

ACS Nano 2020 Mar 11;14(3):3595-3602. Epub 2020 Mar 11.

Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Synthesis of chiral plasmonic materials has been highlighted for the last decades with their optical properties and versatile potential applications. Recently reported aqueous-based amino acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles with 432 point-group symmetry shows exceptionally high chiroptic response within 100 nm scales. Despite its already excellent chiroptic response, a single-nanoparticle dark field scattering study revealed that full chiroptic potential of chiral gold nanoparticle is limited with its overall synthetic uniformity. Based on this knowledge, we present a multi-chirality-evolution step synthesis method for the enhancement of chiroptic response through an increase in particle uniformity. Detailed time variant study and interrelationship study of reaction parameters allowed the systematic construction of design principles for chiral nanoparticles with exceptional chiroptic response. With the application of precisely controlled growth kinetic to two distinct growth regimes, modified chiral gold nanoparticles showed significantly improved uniformity, achieving an improved dissymmetry factor of = 0.31. We expect that our strategy will aid in precise morphology and property control for chiral nanomaterials, which can be used in various plasmonic metamaterial applications.
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http://dx.doi.org/10.1021/acsnano.9b10094DOI Listing
March 2020

Cysteine-encoded chirality evolution in plasmonic rhombic dodecahedral gold nanoparticles.

Nat Commun 2020 01 14;11(1):263. Epub 2020 Jan 14.

Department of Materials Science and Engineering, Seoul National University, Seoul, 08826, Korea.

Chiral plasmonic nanostructures have opened up unprecedented opportunities in optical applications. We present chirality evolution in nanoparticles focusing on the crystallographic aspects and elucidate key parameters for chiral structure formation. From a detailed understanding of chirality formation, we achieved a morphology (432 Helicoid IV) of three-dimensionally controlled chiral plasmonic nanoparticles based on the rhombic dodecahedral shape. The role of the synthesis parameters, seed, cysteine, cetyltrimethylammonium bromide and ascorbic acid on chiral formation are studied, and based on this understanding, the systematic control of the chiral structure is presented. The relation between the modulated chiral structure factors and optical response is further elucidated by electromagnetic simulation. Importantly, a new optical response is achieved by assembling chiral nanoparticles into a film. This comprehensive study of chiral nanoparticles will provide valuable insight for the further development of diverse chiral plasmonic nanostructures with fascinating properties.
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http://dx.doi.org/10.1038/s41467-019-14117-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959252PMC
January 2020

Occupational Class and Cancer Survival in Korean Men: Follow-Up Study of Nation-Wide Working Population.

Int J Environ Res Public Health 2020 01 1;17(1). Epub 2020 Jan 1.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

: We aimed to describe inequalities in site-specific cancer survival across different occupational classes in Korean men. : Subjects included cancer diagnosed members of the national employment insurance program during 1995-2008. A total of 134,384 male cases were followed by linking their data to the Death registry until 2009. Occupational classes were categorized according to the Korean Standard Occupational Classification (KSOC). Hazard ratio adjusting age and diagnosed year were calculated for each occupation by cancer sites. : Men in service/sales and blue-collar occupations had lower survival of all cancer sites combined and esophagus, stomach, colorectal, liver, larynx, lung, prostate, thyroid cancer and non-Hodgkin's lymphoma than men in professional and managerial positions. Cancer sites with good prognosis like prostate cancer showed wider gap across occupational class. : Considerable inequalities in cancer survival were found by occupation among Korean men. Cancer control policy should more focus on lower socioeconomic occupational class.
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http://dx.doi.org/10.3390/ijerph17010303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981645PMC
January 2020

Chiral Surface and Geometry of Metal Nanocrystals.

Adv Mater 2020 Oct 13;32(41):e1905758. Epub 2019 Dec 13.

Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.

Chirality is a basic property of nature and has great importance in photonics, biochemistry, medicine, and catalysis. This importance has led to the emergence of the chiral inorganic nanostructure field in the last two decades, providing opportunities to control the chirality of light and biochemical reactions. While the facile production of 3D nanostructures has remained a major challenge, recent advances in nanocrystal synthesis have provided a new pathway for efficient control of chirality at the nanoscale by transferring molecular chirality to the geometry of nanocrystals. Interestingly, this discovery stems from a purely crystallographic outcome: chirality can be generated on high-Miller-index surfaces, even for highly symmetric metal crystals. This is the starting point herein, with an overview of the scientific history and a summary of the crystallographic definition. With the advance of nanomaterial synthesis technology, high-Miller-index planes can be selectively exposed on metallic nanoparticles. The enantioselective interaction of chiral molecules and high-Miller-index facets can break the mirror symmetry of the metal nanocrystals. Herein, the fundamental principle of chirality evolution is emphasized and it is shown how chiral surfaces can be directly correlated with chiral morphologies, thus serving as a guide for researchers in chiral catalysts, chiral plasmonics, chiral metamaterials, and photonic devices.
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http://dx.doi.org/10.1002/adma.201905758DOI Listing
October 2020

Occupational disparities in bladder cancer survival: A population-based cancer registry study in Japan.

Cancer Med 2020 02 11;9(3):894-901. Epub 2019 Dec 11.

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Little is known about occupational disparities in bladder cancer survival.

Methods: Using data from a population-based cancer registry (1970-2016), we identified 3593 patients with incident bladder cancer diagnosed during 1970-2011 who completed occupational information. The patients were followed for 5 years (median follow-up time 5.0 years). Their longest-held occupations at incident bladder cancer diagnosis were classified according to a national standardized classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall death were estimated by Cox proportional hazard model, adjusted for age, sex, and year of diagnosis. Clerical workers served as the reference group.

Results: Overall prognosis was fair in this population (5-year overall survival, 61.9%). Compared with patients in clerical jobs, survival was poorer for those in professional and managerial jobs (mortality HR 1.36; 95% CI 1.09-1.69), sales and service jobs (HR 1.25, 95% CI 1.01-1.56), construction jobs (HR 1.83, 95% CI 1.40-2.38), and manufacturing jobs (HR 1.32, 95% CI 1.05-1.66), as well as those not actively employed (HR 1.27, 95% CI 1.02-1.58). A similar pattern was observed in the subgroup analyses restricted to male patients as well as additional analyses adjusted for potential prognostic variables (eg, stage) with multiple imputation.

Conclusion: We documented occupational disparities in bladder cancer survival in Japan. However, the pattern of disparity did not favor highest occupational groups.
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http://dx.doi.org/10.1002/cam4.2768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997069PMC
February 2020

Transcriptome sequencing assisted discovery and computational analysis of novel SNPs associated with flowering in in-bred lines for marker-assisted backcross breeding.

Hortic Res 2019 1;6:120. Epub 2019 Nov 1.

Vegetable Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Jeonju, 55365 Republic of Korea.

The sequencing of radish genome aids in the better understanding and tailoring of traits associated with economic importance. In order to accelerate the genomics assisted breeding and genetic selection, transcriptomes of 33 radish inbred lines with diverse traits were sequenced for the development of single nucleotide polymorphic (SNP) markers. The sequence reads ranged from 2,560,543,741 bp to 20,039,688,139 bp with the GC (%) of 47.80-49.34 and phred quality score (Q30) of 96.47-97.54%. A total of 4951 polymorphic SNPs were identified among the accessions after stringent filtering and 298 SNPs with efficient marker assisted backcross breeding (MAB) markers were generated from the polymorphic SNPs. Further, functional annotations of SNPs revealed the effects and importance of the SNPs identified in the flowering process. The SNPs were predominantly associated with the four major flowering related transcription factors such as MYB, MADS box (AG), AP2/EREB, and bHLH. In addition, SNPs in the vital flowering integrator gene (FT) and floral repressors (EMBRYONIC FLOWER 1, 2, and FRIGIDA) were identified among the radish inbred lines. Further, 50 SNPs were randomly selected from 298 SNPs and validated using Kompetitive Allele Specific PCR genotyping system (KASP) in 102 radish inbred lines. The homozygosity of the inbred lines varied from 56 to 96% and the phylogenetic analysis resulted in the clustering of inbred lines into three subgroups. Taken together, the SNP markers identified in the present study can be utilized for the discrimination, seed purity test, and adjusting parental combinations for breeding in radish.
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http://dx.doi.org/10.1038/s41438-019-0200-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823433PMC
November 2019

Methylmercury Determination in Fish by Direct Mercury Analyzer.

J AOAC Int 2020 Jan;103(1):244-249

Ministry of Food and Drug Safety, National Food and Drug Safety Evaluation, Food Safety Evaluation Department, Food Contaminants Division, Osong, Cheongju 28159, Republic of Korea.

Background: There are two methods for quantifying methylmercury (MeHg) in fish using GC-electron capture detection (ECD): AOAC INTERNATIONAL Official Method 988.11 and the Korean Food Code (KFC) method. Both of these methods consume a large amount of chemicals and require long pretreatment times because of several complicated MeHg extraction steps.

Objective: In this study, a new method for the simple and rapid determination of MeHg in fish has been developed. The method is based on the investigation of oxygen combustion-gold amalgamation using a direct mercury analyzer (DMA) after the complete removal of MeHg by organic extraction and back-extraction to an aqueous medium.

Methods: The DMA is suitable for the analysis of both solid and liquid materials and has a good detection limit. The developed method was validated by comparing the MeHg recoveries (%) of both certified reference materials and the market-purchased fish samples with the MeHg concentration obtained using the KFC method.

Results: The following parameters pertaining to the developed method were established: detection limit, 1.02 μg/kg; LOQ, 3.09 μg/kg; linearity (r), 0.9998; range, 0.1-300 μg/kg; and recovery, 95-97%.

Conclusions: Our method is a promising alternative by virtue of its much simpler and faster sample pretreatment procedure, with a MeHg recovery as high as that of the KFC method.

Highlights: The developed method enables the simultaneous analysis of total Hg and MeHg with only DMA equipment.
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http://dx.doi.org/10.5740/jaoacint.18-0254DOI Listing
January 2020

Inhibition of NLRP3 inflammasome in tumor microenvironment leads to suppression of metastatic potential of cancer cells.

Sci Rep 2019 08 22;9(1):12277. Epub 2019 Aug 22.

BK21 PLUS Team, College of Pharmacy, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.

Tumor microenvironment favors tumor cells to promote their growth and metastasis such as migration, invasion, and angiogenesis. IL-1β, one of the inflammatory cytokines released from myeloid cells in tumor microenvironment, plays an important role in development and progress of tumor. The activation of inflammasome is a critical step to secrete mature IL-1β through stepwise reactions to activate capspase-1. Therefore, we investigated whether the inhibition of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in macrophages regulated the metastatic potential of tumor cells. NLRP3 inflammasome was activated by ATP in bone marrow-derived primary mouse macrophages. The metastatic potential of mouse melanoma cell line (B16F10) was determined by migration and invasion assays with transwell system. ATP-treated wild-type macrophages increased the migration and invasion of melanoma cells. However, NLRP3- or caspase-1-knockout macrophages exhibited greatly diminished ability to promote the migration and invasion of melanoma cells. In addition, treatment with celastrol, an inhibitor of NLRP3 inflammasome, reduced the potency of macrophages to stimulate migration and invasion of melanoma cells. The results demonstrate that inhibition of the NLRP3 inflammasome in macrophages by genetic deficiency or a pharmacological inhibitor is linked to suppression of the metastatic potential of tumor cells. The results would provide a novel anti-cancer strategy to modulate tumor microenvironment by suppressing NLRP3 inflammasome and consequently reducing IL-1β production.
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http://dx.doi.org/10.1038/s41598-019-48794-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706417PMC
August 2019

CCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity.

Elife 2019 08 20;8. Epub 2019 Aug 20.

BK21 Plus KNU Multi-Omics Creative Drug Research Team, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea.

CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell migration patterns were deformed in -knockdown zebrafish embryos. CCN1 activated VEGFR2 and downstream MAPK/PI3K signalling pathways, YAP/TAZ, as well as Rho effector mDia1 to enhance tip cell activity and CCN1 itself. VEGFR2 interacted with integrin αvβ3 through CCN1. Integrin αvβ3 inhibitor repressed tip cell number and sprouting in postnatal retinas from endothelial cell-specific transgenic mice, and allograft tumours in transgenic mice showed hyperactive vascular sprouting. Cancer patients with high expression have poor survival outcomes and positive correlation with and high . Thus, our data underscore the positive feedback regulation of tip cells by CCN1 through integrin αvβ3/VEGFR2 and increased YAP/TAZ activity, suggesting a promising therapeutic intervention for pathological angiogenesis.
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http://dx.doi.org/10.7554/eLife.46012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726423PMC
August 2019

Protective Effect of Biculturalism for Health Amongst Minority Youth: The Case of Pacific Islander Migrant Youths in Hawai'i.

Br J Soc Work 2019 Jun 25;49(4):1003-1022. Epub 2019 Apr 25.

Division of Communication and Fine Arts, UOG Station, University of Guam, Mangilao, Guam.

This study investigates the mechanisms by which biculturalism impacts various health outcomes amongst youth migrants to Hawai'i who are from the US-Affiliated Pacific Islands jurisdictions. Using purposive sampling, 284 males and females (twelve to nineteen years old) of Pacific Islander ethnicities in Hawai'i completed a survey. Results from path analysis showed that biculturalism significantly and positively affected self-esteem that, in turn, improved eating attitude, body satisfaction and perceived well-being. Further, eating attitude increased healthy eating behaviour and body satisfaction that, in turn, positively affected general health perception and body satisfaction. Positive smoking attitudes increased smoking activities, which negatively affect general health perception. The study demonstrated that self-esteem impacted overall health through its influence on enhancing positive perceptions about the importance of healthy eating, body satisfaction and well-being. Biculturalism indirectly led to increased self-esteem, which in turn directly influenced attitudes about healthy eating, body satisfaction and perceived well-being. Our study provides strong evidence that addressing the problem of health disparities for minority populations in the USA has to start with reaffirming the value of diversity and multiculturalism and embracing an individual's historic cultural identity. Specific implications for funding agencies and researchers of minority health programs are discussed.
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http://dx.doi.org/10.1093/bjsw/bcz042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615175PMC
June 2019

Chiral Scatterometry on Chemically Synthesized Single Plasmonic Nanoparticles.

ACS Nano 2019 Aug 15;13(8):8659-8668. Epub 2019 Jul 15.

4th Physics Institute and Research Center SCoPE , University of Stuttgart , Pfaffenwaldring 57 , 70569 Stuttgart , Germany.

Wide-spread applications of nanoparticles require large-scale fabrication techniques. Being intrinsically scalable, bottom-up nanoparticle synthesis shows an ever-growing control over particle morphology, enabling even chirally selective shapes. Significant efforts have been undertaken to refine the synthesis in order to decrease the structural spread of the particles and to purify and maximize the resulting handedness. So far, imaging technologies such as electron microscopy are mostly used to investigate the quality of the synthesis. However, for nanophotonic and plasmonic applications, the optical properties are, in fact, key. In this work, we show that single particle chiral scatterometry holds great potential as a feedback to characterize the (chir-)optical quality of chemically synthesized nanoparticles. The spectra of single helicoid nanoparticles reveal a diverse set of chiroptical responses with hugely varying absolute chiral asymmetry in spite of the well-controlled morphology of the particles. Averaging over the single nanoparticles reproduces the solution ensemble measurement remarkably well. This demonstrates that the single particles, despite their morphological and consequently chiroptical differences, exhibit a clearly pronounced chiral spectral and structural feature. We find that the -factor, that is, the degree of asymmetry of chiral light scattering of single nanoparticles can be up to 4 times larger than that for the ensemble. This proves that chiral scatterometry can be a highly important optical feedback for bottom-up nanoparticle synthesis as it reveals that the asymmetry of the ensemble solution can be further increased and maximized by appropriate refinement methods or by postfabrication purification.
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http://dx.doi.org/10.1021/acsnano.9b04046DOI Listing
August 2019