Faculty Profiles - KIM Hye-Sook

Papers - KIM Hye-Sook

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Anti-Diabetic Potential of Sargassum horneri and Ulva australis Extracts In Vitro and In Vivo Reviewed

Young-Hyeon Lee, Hye-Ran Kim, Min-Ho Yeo, Sung-Chun Kim, Ho-Bong Hyun, Young-Min Ham, Yong-Hwan Jung, Hye-Sook Kim, Kyung-Soo Chang

Current Issues in Molecular Biology 45 ( 9 ) 7492 - 7512 2023.9

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources that cause environmental and economic problems when entering or multiplying the coastal waters of Jeju Island. We analyzed their anti-diabetic efficacy to assess their reusability as functional additives. The alpha-glucosidase inhibitory activity of SH and UA extracts was confirmed, and the effect of UA extract was higher than that of SH. After the induction of insulin-resistant HepG2 cells, the effects of the two marine extracts on oxidative stress, intracellular glucose uptake, and glycogen content were compared to the positive control, metformin. Treatment of insulin-resistant HepG2 cells with SH and UA resulted in a concentration-dependent decrease in oxidative stress and increased intracellular glucose uptake and glycogen content. Moreover, SH and UA treatment upregulated the expression of IRS-1, AKT, and GLUT4, which are suppressed in insulin resistance, to a similar degree to metformin, and suppressed the expression of FoxO1, PEPCK involved in gluconeogenesis, and GSK-3β involved in glycogen metabolism. The oral administration of these extracts to rats with streptozotocin-induced diabetes led to a higher weight gain than that in the diabetic group. Insulin resistance and oral glucose tolerance are alleviated by the regulation of blood glucose. Thus, the SH and UA extracts may be used in the development of therapeutic agents or supplements to improve insulin resistance.

DOI： 10.3390/cimb45090473

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Extract of Torreya nucifera Pericarps Exhibits a Parasiticidal Effect on the Nematode Parasite, Trichinella spiralis Reviewed

Mi Jin Jeong, Shin Ae Kang, Sun Nyoung Yu, Soon Cheol Ahn, Shin-ichi Miyoshi, Hye-Sook Kim, Hak Sun Yu

Journal of Medicinal Food 26 ( 9 ) 624 - 630 2023.9

Evaluating the activity of N-89 as an oral antimalarial drug Reviewed

Nagwa S. M. Aly, Hiroaki Matsumori, Thi Quyen Dinh, Akira Sato, Shin-ichi Miyoshi, Kyung-Soo Chang, Hak Sun Yu, Takaaki Kubota, Yuji Kurosaki, Duc Tuan Cao, Gehan A. Rashed, Hye-Sook Kim

Parasites, Hosts and Diseases 61 ( 3 ) 282 - 291 2023.8

Authorship：Corresponding author Publishing type：Research paper (scientific journal) Publisher：Korean Society for Parasitology

Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

DOI： 10.3347/phd.23044

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Evaluation of schistosomula lung antigen preparation and soluble egg antigen vaccines on experimental schistosomiasis mansoni Reviewed

Nagwa S. M. Aly, Hye-Sook Kim, Maysa A. Eraky, Asmaa A. El Kholy, Basma T. Ali, Shin-ichi Miyoshi, Rabab E. Omar

Parasites, Hosts and Diseases 61 ( 3 ) 251 - 262 2023.8

Publishing type：Research paper (scientific journal) Publisher：Korean Society for Parasitology

Schistosomiasis causes significant morbidity and mortality worldwide. This study aimed to assess the effect of schistosomula lung antigen preparation (SLAP) and soluble egg antigen (SEA) on a murine schistosomiasis mansoni model. Ninety laboratory-bred male Swiss albino mice were divided into 6 groups. Two doses of the vaccine were given at 2-week intervals. All mice were subcutaneously infected with 80±10 Schistosoma mansoni cercariae 2 weeks after the last vaccination dose. They were sacrificed 7 weeks post-infection. Parasitological and histopathological studies were conducted to assess the effect of inoculated antigens (single or combined). The results showed that the combination of SLAP and SEA (combination group) led to a significant reduction in worm burden (65.56%), and liver and intestine egg count (59% and 60.59%, respectively). The oogram pattern revealed a reduction in immature and mature eggs (15±0.4 and 10±0.8, respectively) and an increased number of dead eggs in the combination group (P<0.001). In terms of histopathological changes, the combination group showed notably small compact fibrocellular egg granuloma and moderate fibrosis in the liver. A high percentage of destroyed ova was observed in the intestine of the combination group. This study demonstrates for the first time the prophylactic effect of combined SLAP and SEA vaccine. The vaccine induced a significant reduction in the parasitological and pathological impacts of schistosomiasis mansoni in hepatic and intestinal tissues, making it a promising vaccine candidate for controlling schistosomiasis.

DOI： 10.3347/phd.22154

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Maternal and Fetal Effects of Gestational Vitamin D Concentration Reviewed

Ki-Wook Kwon, Young-Hyeon Lee, Min-Ho Yeo, Sang-Hyun Park, Hye-Ran Kim, Hye-Sook Kim, Kyung-Soo Chang

Healthcare 11 ( 16 ) 2325 - 2325 2023.8

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Most (90%) vitamin D synthesis occurs in the skin using sunlight (ultraviolet rays), and 10% is obtained through food. Vitamin D is an essential nutrient for skeletal growth and maintenance, cell proliferation and differentiation, and immune function. This study investigated whether maternal serum vitamin D concentrations induce maternofetal effects. Hematological analysis, serological changes, and precision fetal ultrasound findings were analyzed by maternal vitamin D concentration in gestational weeks 22–25 to ascertain direct effects on fetal growth. Bone density–vitamin D concentration correlation was analyzed. No hematologic or serological effect of maternal vitamin D concentration was detected; however, the sexually transmitted infection and cross-infection rates were inversely proportional to maternal vitamin D concentration. No significant correlation between vitamin D concentration and vertebral and femoral BMD was detected. For fetal growth, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length were analyzed. Humerus (p < 0.05) and femur (p < 0.001) lengths were higher in the vitamin D-sufficient group than in the vitamin D-deficient group. Vitamin D concentration did not positively affect hematologic changes and bone density; maternal vitamin D concentration essentially affected fetal bone growth. Vitamin D inhibits sexually transmitted infections in mothers and promotes fetal bone growth. Prevention of vitamin D deficiency, supplementation, or outdoor activities is recommended.

DOI： 10.3390/healthcare11162325

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Anti-Obesity Potential of Sargassum horneri and Ulva australis Extracts: Study In Vitro and In Vivo Reviewed

Young-Hyeon Lee, Hye-Ran Kim, Min-Ho Yeo, Sung Chun Kim, Ho-Bong Hyun, Young-Min Ham, Yong-Hwan Jung, Hye-Sook Kim, Kyung-Soo Chang

Applied Sciences 13 ( 15 ) 8951 - 8951 2023.8

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Current research highlights the use of natural products or phytochemicals as drugs and functional additives to treat obesity with few side effects. Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources on Jeju Island, Republic of Korea. In this study, we analyzed their antioxidant and anti-obesity efficacies to confirm their potential as functional additives. We prepared SH and UA extracts using 80% ethanol and observed that free radical scavenging activity and total phenol content were high in SH extracts, and total flavonoid content was elevated in UA extracts. Additionally, 3T3-L1 cells were treated with SH and UA extracts, and the ability of the extracts to inhibit adipocyte differentiation was examined using Oil Red O staining and analysis of neutral fat content. We confirmed that the mRNA expression of the C/EBPα, PPARγ, and SREBP1c genes that act on adipocyte differentiation, and of FAS, a fatty acid synthase, was suppressed. Experiments in a mouse model of obesity showed that 12-week administration of a high-fat diet with 1% extract added to drinking water resulted in lower weight gain compared to the high-fat diet alone. These results suggest that SH and UA extracts have antioxidant properties and are effective in obesity prevention. Therefore, the two marine waste resources are potential functional additive candidates for preventing obesity.

DOI： 10.3390/app13158951

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Extracellular Leakage Protein Patterns in Two Types of Cancer Cell Death: Necrosis and Apoptosis Reviewed

Akira Sato, Akira Shimotsuma, Tetsuya Miyoshi, Yui Takahashi, Naoki Funayama, Yoko Ogino, Akiko Hiramoto, Yusuke Wataya, Hye-Sook Kim

ACS Omega 8 ( 28 ) 25059 - 25065 2023.7

Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model Reviewed

Nagwa S. M. Aly, Hiroaki Matsumori, Thi Quyen Dinh, Akira Sato, Shin-Ichi Miyoshi, Kyung-Soo Chang, Hak Sun Yu, Duc Tuan Cao, Hye-Sook Kim

Pathogens 12 ( 3 ) 398 - 398 2023.3

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children.

DOI： 10.3390/pathogens12030398

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Diagnosis of Toxoplasmosis Using Surface Antigen Grade 1 Detection by ELISA, Nano-Gold ELISA, and PCR in Pregnant Women Reviewed

Nagwa SM Aly, Hye-Sook Kim, Yasmin M Marei, Azza S Elhamshary, Ibrahim R Bayoumi, Rabab E Omar, Dina A Mohammed, Shin-Ichi Miyoshi, Gehan A Rashed

International Journal of Nanomedicine Volume 18 1335 - 1345 2023.3

Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice Reviewed

Nagwa S. M. Aly, Hiroaki Matsumori, Thi Quyen Dinh, Akira Sato, Shin-Ichi Miyoshi, Kyung-Soo Chang, Hak Sun Yu, Fumie Kobayashi, Hye-Sook Kim

Parasites, Host and Diseases (The Korean Journal of Parasitology) 61 ( 1 ) 33 - 41 2023.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Korean Society for Parasitology

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

DOI： 10.3347/phd.22119

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Formulation and evaluation of the antimalarial N-89 as a transdermal drug candidate Reviewed

Nagwa S.M. Aly, Hiroaki Matsumori, Thi Quyen Dinh, Akira Sato, Shin-Ich Miyoshi, Kyung-Soo Chang, Hak Sun Yu, Hye-Sook Kim

Parasitology International 93 102720 - 102720 2022.12

Synthesis of 1,5-diaryl-2-fluoro-6,7-dioxabicyclo[3.2.2]nonanes with high antimalarial activity utilizing photoinduced electron-transfer oxygenation reactions Reviewed

Masaki Kamata, Rie Maeda, Jun Hayakawa, Hye-Sook Kim

Tetrahedron Letters 96 153752 - 153752 2022.4

Comparison of Microbial Detection of Hemodialysis Water in Reasoner’s 2A Agar (R2A) and Trypticase Soy Agar (TSA) Reviewed

Sang-Hyun Park, Young-Hyeon Lee, Min-Ho Yeo, Hi-Ryun Lee, Hye-Sook Kim, Kyung-Soo Chang

Journal of Bacteriology and Virology 51 ( 2 ) 79 - 88 2021.6

Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis. Reviewed International journal

Akira Sato, Akihiro Yamamoto, Akira Shimotsuma, Yoko Ogino, Naoki Funayama, Yui Takahashi, Akiko Hiramoto, Yusuke Wataya, Hye-Sook Kim

FEBS open bio 10 ( 11 ) 2417 - 2426 2020.11

Language：English Publishing type：Research paper (scientific journal)

MicroRNAs (miRNAs) are small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the mRNA or inhibit translation. Such miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanisms regulating cell death (necrosis in original F28-7 cells and apoptosis in their variant F28-7-A cells) in the mouse mammary tumor cell line FM3A using the anticancer agent floxuridine (FUdR). We previously reported that inhibition of heat-shock protein 90 by the specific inhibitor geldanamycin (GA) in F28-7 cells causes a shift from necrosis to apoptosis. In this study, we investigated the intracellular miRNA expression profiles of FUdR-treated F28-7 cells (necrotic condition), GA plus FUdR-treated F28-7 cells (apoptotic condition), and FUdR-treated F28-7-A cells (apoptotic condition) through miRNA microarray analysis. In addition, we knocked down Dicer, a key molecule for the expression of mature miRNAs, in F28-7 cells to examine whether it modulates FUdR-induced cell death. Our analysis revealed that the miRNA expression patterns differ significantly between these cell death conditions. Furthermore, we identified miRNA candidates that regulate cell death. Knockdown of Dicer in FUdR-treated necrosis-fated cells caused a partial shift from necrosis to apoptosis. These findings suggest that modulation of miRNA expression patterns influences the decision of cell death fate toward necrosis or apoptosis. Our findings may serve as a basis for further study of the functions of miRNAs in cell death mechanisms.

DOI： 10.1002/2211-5463.12995

PubMed

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Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. Reviewed International journal

Akira Sato, Akiko Hiramoto, Hye-Sook Kim, Yusuke Wataya

International journal of molecular sciences 21 ( 16 ) 2020.8

Language：English Publishing type：Research paper (scientific journal)

Cell death can be broadly characterized as either necrosis or apoptosis, depending on the morphological and biochemical features of the cell itself. We have previously reported that the treatment of mouse mammary carcinoma FM3A cells with the anticancer drug floxuridine (FUdR) induces necrosis in the original clone F28-7 but apoptosis in the variant F28-7-A. We have identified regulators, including heat shock protein 90, lamin-B1, cytokeratin-19, and activating transcription factor 3, of cell death mechanisms by using comprehensive gene and protein expression analyses and a phenotype-screening approach. We also observed that the individual inhibition or knockdown of the identified regulators in F28-7 results in a shift from necrotic to apoptotic morphology. Furthermore, we investigated microRNA (miRNA, miR) expression profiles in sister cell strains F28-7 and F28-7-A using miRNA microarray analyses. We found that several unique miRNAs, miR-351-5p and miR-743a-3p, were expressed at higher levels in F28-7-A than in F28-7. Higher expression of these miRNAs in F28-7 induced by transfecting miR mimics resulted in a switch in the mode of cell death from necrosis to apoptosis. Our findings suggest that the identified cell death regulators may play key roles in the decision of cell death mechanism: necrosis or apoptosis.

DOI： 10.3390/ijms21165876

PubMed

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Direct interaction analysis of microRNA-351-5p and nuclear scaffold lamin B1 mRNA by the cell-free in vitro mRNA/miRNA binding evaluation system. Reviewed International journal

Akira Sato, Yoko Ogino, Akira Shimotsuma, Akiko Hiramoto, Hye-Sook Kim, Yusuke Wataya

Nucleosides, nucleotides & nucleic acids 1 - 7 2020.1

Language：English

We previously demonstrated that miR-351-5p regulates nuclear scaffold lamin B1 expression and mediates the anticancer floxuridine-induced necrosis shift to apoptosis in mammalian tumor cells. Notably, it is unknown whether lamin B1 mRNA is a direct target of miR-351-5p. Here, we show that miR-351-5p interacts with a lamin B1 mRNA partial sequence by using the cell-free in vitro miRNA and mRNA binding evaluation system. In addition, the interaction of miR-351-5p/lamin B1 mRNA was suppressed by an miR-351-5p inhibitor. Our findings are important in exploring the functions of miRNAs in cellular processes, including cell death.

DOI： 10.1080/15257770.2019.1702675

PubMed

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Pharmacokinetic analysis of new synthetic antimalarial N-251 Reviewed

Kazuaki Okada, Akira Sato, Akiko Hiramoto, Rena Isogawa, Yuji Kurosaki, Kazutaka Higaki, Shin-Ichi Miyoshi, Kyung-Soo Chang, Hye-Sook Kim

Tropical Medicine and Health 47 ( 1 ) 2019.12

Genomic and biological features of Plasmodium falciparum resistance against antimalarial endoperoxide N-89. Reviewed International journal

Masayuki Morita, Kosuke Hayashi, Akira Sato, Akiko Hiramoto, Osamu Kaneko, Rena Isogawa, Yuji Kurosaki, Shin-Ichi Miyoshi, Kyung-Soo Chang, Yusuke Wataya, Hye-Sook Kim

Gene 716 144016 - 144016 2019.10

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Drug resistance of malaria parasites remains a problem affecting antimalarial treatment and control of the disease. We previously synthesized an antimalarial endoperoxide, N-89, having high antimalarial effects in vitro and in vivo. In this study we seek to understand the resistant mechanism against N-89 by establishing a highly N-89-resistant clone, named NRC10H, of the Plasmodium falciparum FCR-3 strain. We describe gene mutations in the parent FCR-3 strain and the NRC10H clone using whole-genome sequencing and subsequently by expression profiling using quantitative real-time PCR. Seven genes related to drug resistance, proteolysis, glycophosphatidylinositol anchor biosynthesis, and phosphatidylethanolamine biosynthesis exhibited a single amino acid substitution in the NRC10H clone. Among these seven genes, the multidrug resistance protein 2 (mdr2) variant A532S was found only in NRC10H. The genetic status of the P. falciparum endoplasmic reticulum-resident calcium binding protein (PfERC), a potential target of N-89, was similar between the NRC10H clone and the parent FCR-3 strain. These findings suggest that the genetic alterations of the identified seven genes, in particular mdr2, in NRC10H could give rise to resistance of the antimalarial endoperoxide N-89.

DOI： 10.1016/j.gene.2019.144016

PubMed

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A trial for a DNA diagnosis of Plasmodium vivax malaria recently reemerging in the Republic of Korea using microtiter plate hybridization assay. Reviewed

J Y Chai, M D Oh, S H Lee, S M Guk, K H Oh, Y K Park, HS Kim, Y Wataya

The American Journal of Tropical Medicine and Hygiene 63 ( 1 ) 80 - 84 2000.7

The antimalarial activity of transdermal N-89 mediated by inhibiting ERC gene expression in P. berghei-infected mice Reviewed

Hiroaki. Matsumori, Thi Quyen Dinh, Shin-ichi Miyoshi, Masayuki Morita, Hye-Sook Kim

Parasitology International in press 2025

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