Association test for rare variants using the hamming distance

Hwangbo, Suhyun,Jang, Jin Young,Oh, Bermseok,Okazaki, Atsuko Imai,Ott, Jurg,Park, Taesung Inderscience Enterprises Ltd. 2018 International journal of data mining and bioinform Vol.21 No.4

Clinicopathologic and protein markers distinguishing the “polymerase epsilon exonuclease” from the “copy number low” subtype of endometrial cancer

Kidong Kim,Suhyun Hwangbo,Hyojin Kim,Yong-Beom Kim,Jae Hong No,Dong Hoon Suh,Taesung Park 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.3

Objective: The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease ( ) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated clinicopathologic and protein markers that distinguish thefrom the copy number (CN)-low subtype in EC. Methods: Ninety-one samples (15 , 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort. Results: Body mass index (BMI) and tumor grade were significantly associated with the subtype. With BMI and tumor grade as covariates, 5 proteins were associated with theEC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683. Conclusion: BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the from the CN-low subtype. Cyclin B1 IHC may replace sequencing in molecular classification of EC.

Discovery of Target Genes for Triple-negative Breast Cancer through Comparative Analysis of Gene Dependency Scores

Bo Kyung KIM,Suhyun HWANGBO,Youngseo KIM,Yebin SON,Jae Yong RYU 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.10

Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods

Seung Mi Lee,Suhyun Hwangbo,Errol R. Norwitz,Ja Nam Koo,Ig Hwan Oh,Eun Saem Choi,Young Mi Jung,Sun Min Kim,Byoung Jae Kim,Sang Youn Kim,Gyoung Min Kim,김원,Sae Kyung Joo,Sue Shin,Chan-Wook Park,Taesung 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.1

Background/Aims: To develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model. Methods: This prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10–14 weeks and screened them for GDM at 24–28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks. Results: Among 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1–4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563–0.697 in settings 1–3 vs. 0.740–0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719– 0.819 in setting 5, P=not significant between settings 4 and 5). Conclusions: We developed an early prediction model for GDM using machine learning. The inclusion of NAFLDassociated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: NCT02276144)

Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome

Park, Chul-Kyu,Kim, Yong Ho,Hwangbo, Suhyun,Cho, Hoonsung Dove Medical Press 2017 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.12 No.-

<P>Photodynamic therapy (PDT) is a promising alternative therapy that could be used as an adjunct to chemotherapy and surgery for cancer, and works by destroying tissue with visible light in the presence of a photosensitizer (PS) and oxygen. The PS should restrict tissue destruction only to the tumor and be activated by light of a specific wavelength; both of these properties are required. Arginine-rich peptides, such as cell-penetrating peptides, have membrane-translocating and nuclear-localizing activities, which have led to their application in various drug delivery modalities. Protamine (Pro) is an arginine-rich peptide with membrane-translocating and nuclear-localizing properties. The reaction of an N-hydroxysuccinimide (NHS) ester of rhodamine (Rho) and clinical Pro was carried out in this study to yield RhoPro, and a demonstration of its phototoxicity, wherein clinical Pro improved the effect of PDT, was performed. The reaction between Pro and the NHS ester of Rho is a solution-phase reaction that results in the complete modification of the Pro peptides, which feature a single reactive amine at the N-terminal proline and a single carboxyl group at the C-terminal arginine. This study aimed to identify a new type of PS for PDT by in vitro and in vivo experiments and to assess the antitumor effects of PDT, using the Pro-conjugated PS, on a cancer cell line. Photodynamic cell death studies showed that the RhoPro produced has more efficient photodynamic activities than Rho alone, causing rapid light-induced cell death. The attachment of clinical Pro to Rho, yielding RhoPro, confers the membrane-internalizing activity of its arginine-rich content on the fluorochrome Rho and can induce rapid photodynamic cell death, presumably owing to light-induced cell membrane rupture. PDT using RhoPro for HT-29 cells was very effective and these findings suggest that RhoPro is a suitable candidate as a PS for solid tumors.</P>

Triterpenoids from <i>Ziziphus jujuba</i> induce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production

Shin, Minna,Lee, Bo-Mi,Kim, Okwha,Tran, Huynh Nguyen Khanh,Lee, Suhyun,Hwangbo, Cheol,Min, Byung-Sun,Lee, Jeong-Hyung The Royal Society of Chemistry 2018 Food & function Vol.9 No.7

<P><I>Ziziphus jujuba</I> var. <I>inermis</I> Rehder is an edible fruit-producing species of the Rhamnaceae family. In the present study, we isolated eight triterpenoids (1-8) from the fruits of <I>Z. jujuba</I> var. <I>inermis</I> and evaluated their apoptotic cell-death-inducing activities in human cancer cell lines (A549, PC-3, and MDA-MB-231). The structures of compounds 1-8 were determined by spectroscopic methods. Among these, four isomers of coumaroyl alphitolic acid showed potent cytotoxic activities on these cancer cells: 3-<I>O-cis-p</I>-coumaroyl alphitolic acid (3), 3-<I>O-trans-p</I>-coumaroyl alphitolic acid (4), 2-<I>O-trans-p</I>-coumaroyl alphitolic acid (5), and 2-<I>O-cis-p</I>-coumaroyl alphitolic acid (6). Moreover, compounds 3-6 induced apoptotic cell death in a concentration-dependent manner. We further investigated the apoptosis-inducing effects of compound 4 in PC-3 cells which triggered the cleavage of procaspase-3, procaspase-7, procaspase-8, bid, and PARP. Compound 4 increased both the mitochondrial reactive oxygen species (ROS) production and the phosphorylation of p38 MAPK (mitogen-activated protein kinase), but decreased the mitochondrial membrane potential. Pretreatment with Mito-TEMPO (a specific mitochondrial-targeted antioxidant) or a specific p38 inhibitor (SB203580) attenuated apoptotic cell death triggered by compound 4 which suggests that compound 4 may induce apoptotic cell death in these cancer cells by increasing the mitochondrial ROS production as well as the subsequent p38 MAPK activation. The study findings provide a rational base to use <I>Ziziphus</I> extracts for cancer treatments in traditional oriental medicine.</P>

Identification of anti-osteoclastogenic compounds from <i>Cleistocalyx operculatus</i> flower buds and their effects on RANKL-induced osteoclastogenesis

Tran, Phuong Thao,Ngo, Thi Quynh-Mai,Lee, Suhyun,Kim, Okwha,Tran, Huynh Nguyen Khanh,Hwangbo, Cheol,Min, Byung Sun,Lee, Jeong-Hyung ELSEVIER SCIENCE B.V.; AMSTERDAM 2019 JOURNAL OF FUNCTIONAL FOODS Vol.60 No.-

<P><B>Abstract</B></P> <P> <I>Cleistocalyx operculatus</I> flower buds are used as a main ingredient in various beverages and herbal tea in tropical areas. The present study was conducted to investigate anti-osteoclastogenic effects of ethanol extract of <I>C. operculatus</I> flower buds (ECB) and to identify anti-osteoclastogenic compounds in these buds. ECB significantly inhibited RANKL-induced osteoclast differentiation and decreased RANKL-induced the activation of NFATc1. We isolated nineteen compounds from <I>C. operculatus</I> flower buds and found that eight compounds, including maslinic acid (<B>6</B>) and its two coumaroyl analogs (<B>7</B> and <B>8</B>), significantly inhibited RANKL-induced osteoclast formation. Among these, 3-O-<I>trans</I>-<I>p</I>-coumaroyl maslinic acid (<B>8</B>) showed the most potent inhibitory effect on RANKL-induced osteoclastogenesis via impairment of c-Fos and NF-κB activation, and subsequently, NFATc1 activation. These results suggested that identification of the anti-osteoclastogenic compounds from <I>C. operculatus</I> flower buds may extend our understanding of molecular mechanisms underlying biological activities of <I>C. operculatus</I> flower buds for osteoclast-related diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The anti-osteoclastogenic effect of <I>Cleistocalyx operculatus</I> is demonstrated. </LI> <LI> Ethanol extract of <I>C. operculatus</I> flower buds (ECB) inhibits RANKL-induced osteoclastogenesis. </LI> <LI> Eight compounds are identified as anti-osteoclastogenic compounds from ECB. </LI> <LI> Maslinic acid and its two coumaroyl analogs inhibit RANKL-induced NFATc1 activation. </LI> <LI> The mechanism explains the anti-osteoclastogenic effect of C. operculatus flower buds. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Clinical Characteristics and Outcomes of COVID-19 Cohort Patients in Daegu Metropolitan City Outbreak in 2020

Kim Shin-Woo,Kim Seung-Mee,Kim Yu Kyung,Kim Jong-yeon,Lee Yu-Mi,Kim Bong-Ok,Hwangbo Suhyun,Park Taesung 대한의학회 2021 Journal of Korean medical science Vol.36 No.1

Background: A coronavirus disease 2019 (COVID-19) outbreak started in February 2020 and was controlled at the end of March 2020 in Daegu, the epicenter of the coronavirus outbreak in Korea. The aim of this study was to describe the clinical course and outcomes of patients with COVID-19 in Daegu. Methods: In collaboration with Daegu Metropolitan City and Korean Center for Diseases Control, we conducted a retrospective, multicenter cohort study. Demographic, clinical, treatment, and laboratory data, including viral RNA detection, were obtained from the electronic medical records and cohort database and compared between survivors and non-survivors. We used univariate and multi-variable logistic regression methods and Cox regression model and performed Kaplan–Meier analysis to determine the risk factors associated with the 28-day mortality and release from isolation among the patients. Results: In this study, 7,057 laboratory-confirmed patients with COVID-19 (total cohort) who had been diagnosed from February 18 to July 10, 2020 were included. Of the total cohort, 5,467 were asymptomatic to mild patients (77.4%) (asymptomatic 30.6% and mild 46.8%), 985 moderate (14.0%), 380 severe (5.4%), and 225 critical (3.2%). The mortality of the patients was 2.5% (179/7,057). The Cox regression hazard model for the patients with available clinical information (core cohort) (n = 2,254) showed the risk factors for 28-day mortality: age > 70 (hazard ratio [HR], 4.219, P = 0.002), need for O2 supply at admission (HR, 2.995; P = 0.001), fever (> 37.5°C) (HR, 2.808; P = 0.001), diabetes (HR, 2.119; P = 0.008), cancer (HR, 3.043; P = 0.011), dementia (HR, 5.252; P = 0.008), neurological disease (HR, 2.084; P = 0.039), heart failure (HR, 3.234; P = 0.012), and hypertension (HR, 2.160; P = 0.017). The median duration for release from isolation was 33 days (interquartile range, 24.0–46.0) in survivors. The Cox proportional hazard model for the long duration of isolation included severity, age > 70, and dementia. Conclusion: Overall, asymptomatic to mild patients were approximately 77% of the total cohort (asymptomatic, 30.6%). The case fatality rate was 2.5%. Risk factors, including older age, need for O2 supply, dementia, and neurological disorder at admission, could help clinicians to identify COVID-19 patients with poor prognosis at an early stage.

Ganomycin I from <i>Ganoderma lucidum</i> attenuates RANKL-mediated osteoclastogenesis by inhibiting MAPKs and NFATc1

Tran, Phuong Thao,Dat, Nguyen Tien,Dang, Nguyen Hai,Van Cuong, Pham,Lee, Suhyun,Hwangbo, Cheol,Van Minh, Chau,Lee, Jeong-Hyung Elsevier 2019 Phytomedicine Vol.55 No.-

<P><B>ABSTARCT</B></P> <P><B>Background</B></P> <P>Many bone-related diseases such as osteoporosis and rheumatoid arthritis are commonly associated with excessive activity of the osteoclast. Ganomycin I (GMI), a meroterpenoid isolated from Vietnamese mushroom <I>Ganoderma lucidum</I>, possesses a variety of beneficial effects on human health. However, its impact and underlying mechanism on osteoclastogenesis remain unclear. In the present study, we investigated the effect of GMI on RANKL-induced osteoclast formation in mouse BMMs and RAW264.7 cells.</P> <P><B>Methods</B></P> <P>BMMs or RAW264.7 cells were treated with GMI followed by an evaluation of cell viability, RANKL-induced osteoclast differentiation, actin-ring formation, and resorption pits activity. Effects of GMI on RANKL-induced phosphorylation of MAPKs as well as the expression levels of NFATc1 and c-Fos were evaluated by Western blot analysis. Expression levels of osteoclast marker genes were evaluated by Western blot analysis and reverse transcription-qPCR.</P> <P><B>Results</B></P> <P>GMI significantly inhibited RANKL-induced osteoclast differentiation by decreasing the number of osteoclasts, osteoclast actin–ring formation, and bone resorption in a dose-dependent manner without affecting cell viability. At molecular level, GMI inhibited the RANKL-induced phosphorylation of ERK, JNK, and p38 MAPKs, as well as the expression levels of c-Fos and NFATc1, which are known to be crucial transcription factors for osteoclast formation. In addition, GMI decreased expression levels of osteoclastogenesis specific marker genes including c-Src, CtsK, TRAP, MMP-9, OSCAR, and DC-STAMP in RANKL-stimulated BMMs.</P> <P><B>Conclusion</B></P> <P>Our findings suggest that GMI can attenuate osteoclast formation by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and the anti-osteoclastogenic activity of GMI may extend our understanding of molecular mechanisms underlying biological activities and pharmacological use of <I>G. lucidum</I> as a traditional anti-osteoporotic medicine.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>