Dichloromethane fraction from <i>Gardenia jasminoides</i>: DNA topoisomerase 1 inhibition and oral cancer cell death induction

Lim, WonBong,Kim, OkSu,Jung, JinAn,Ko, YoungJong,Ha, JooWon,Oh, HeeKyun,Lim, HoiSoon,Kwon, HyukIl,Kim, InAe,Kim, Jisun,Kim, MiSook,Kim, SeoYune,Kim, Byung-kuk,Kim, SunMi,Kang, Byung-Cheol,Choi, HongRa Informa Healthcare 2010 PHARMACEUTICAL BIOLOGY Vol.48 No.12

<P><I>Context:</I> A growing body of evidence shows that compounds of plant origin have the ability to prevent cancer. The fruit of gardenia, <I>Gardenia jasminoides</I> Ellis (Rubiaceae), has long been used as a food additive and herbal medicine, and its pharmacological actions, such as protective activity against oxidative damage, cytotoxic effect, and anti-inflammatory and anti-tumor activity, have already been reported.</P><P><I>Objective:</I> The purpose of the present study was to investigate the presence of DNA topoisomerase 1 inhibitor in various solvent fractions of <I>Gardenia</I> extract and examine the induction of oral cancer cell death upon treatment with <I>Gardenia</I> extract.</P><P><I>Materials and methods:</I> The methanol extract of <I>Gardenia</I> was partitioned with <I>n-</I>hexane, dichloromethane, ethyl acetate, <I>n-</I>butanol, and water.</P><P><I>Results:</I> In the DNA topoisomerase 1 assay, <I>n-</I>hexane and dichloromethane fractions inhibited topoisomerase 1 and led to a decrease in the cell viability of KB cells. The dichloromethane fraction (0.1 mg/mL) also showed 77% inhibition of cell viability in KB cells compared with HaCaT cells. Treatment with dichloromethane fraction led to apoptotic cell death as evidenced by flow cytometric analysis and morphological changes. In addition, treatment with <I>Gardenia</I> extract dichloromethane fraction led to the partial increase of caspase-3, caspase-8 and caspase-9 activities and the cleavage of poly (ADP-ribose) polymerase.</P><P><I>Conclusion:</I> Taken together, these results suggest that the dichloromethane fraction from <I>Gardenia</I> extract induces apoptotic cell death by DNA topoisomerase 1 inhibition in KB cells. These findings suggest the possibility that <I>Gardenia</I> extract could be developed as an anticancer modality.</P>

Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells

Kim, Sang Bum,Kim, Hye Rim,Park, Min Chul,Cho, Seongmin,Goughnour, Peter C.,Han, Daeyoung,Yoon, Ina,Kim, YounHa,Kang, Taehee,Song, Eunjoo,Kim, Pilhan,Choi, Hyosun,Mun, Ji Young,Song, Chihong,Lee, Sang Rockefeller University Press 2017 The Journal of cell biology Vol.216 No.7

<P>Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.</P>

Association of urinary phthalate metabolites and phenolics with adipokines and insulin resistance related markers among women of reproductive age

Lee, Inae,Kim, Sunmi,Park, Suhyeon,Mok, Sori,Jeong, Yunsun,Moon, Hyo-Bang,Lee, Jangwoo,Kim, Sungkyoon,Kim, Hai-Joong,Choi, Gyuyeon,Choi, Sooran,Kim, Su Young,Lee, Aram,Park, Jeongim,Choi, Kyungho Elsevier BV 2019 Science of the Total Environment Vol.688 No.-

<P><B>Abstract</B></P> <P>Chemicals such as phthalates and phenolics have been associated with metabolic markers in humans. However, most studies have only looked at a limited number of chemicals, and little is known about their potential effects on adipokines in humans. In the present study, the associations between dozens of urinary chemicals, including phthalate metabolites and phenolics, and markers related to insulin resistance as well as major adipokines, were assessed among the women of reproductive age (<I>n</I> = 459, between 20 and 48 years of age) recruited from major cities in Korea between 2015 and 2016. Adipokines such as adiponectin and leptin, and insulin resistance related markers such as glucose and insulin, were analyzed in serum. Associations between urinary chemicals and the adipokines or insulin resistance related markers were assessed in two steps. First, ordinary least squares (OLS) regression was used to assess the association of each urinary chemical with the adipokines or insulin resistance related markers (single-pollutant model). Second, several chemicals were selected using elastic net regression and were subsequently analyzed with OLS regression model (multi-pollutant model), considering simultaneous exposure to multiple chemicals. In both single- and multi-pollutant models, several urinary chemicals consistently showed significant associations with adipokines or the insulin resistance related markers. The sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHPm) and ethyl paraben (EtP) were associated with increased serum adiponectin levels. Urinary ΣDEHPm levels also showed positive associations with fasting glucose. Moreover, urinary mono-methyl phthalate (MMP), mono-isobutyl phthalate (MiBP), and bisphenol S (BPS) levels showed positive associations with the homeostasis model assessment for insulin resistance (HOMA-IR). Interestingly, urinary propyl paraben (PrP) levels showed a negative association with HOMA-IR, in both models. Our observations show that among many consumer chemicals, phthalates may affect serum adipokines, and thus glucose, and insulin resistance in adult females. Further confirmation is warranted in other populations.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Urinary chemicals and metabolism related markers were measured in women of reproductive age. </LI> <LI> Multiple chemicals were considered in statistical models for adipokines and insulin resistance. </LI> <LI> Sum of DEHP metabolites and EtP were positively associated with serum adiponectin levels. </LI> <LI> Sum of DEHP metabolites was significantly associated with increased fasting glucose. </LI> <LI> MiBP was significantly associated with for increased HOMA-IR. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

분산 환경에서 서브 그래프 탐색을 위한 경로 질의 기반 그래프 처리 기법

김민영(Minyoung Kim),최도진(Dojin Choi),김민수(Minsoo Kim ),박재열(Jaeyeol Park),김이나(Ina Kim),김연동(Yeondong Kim ),임종태(Jongtae Lim),복경수(Kyoungsoo Bok),유재수(Jaesoo Yoo) 한국정보과학회 2018 한국정보과학회 학술발표논문집 Vol.2018 No.6

Current status of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) exposure among mothers and their babies of Korea-CHECK cohort study

Choi, Sooran,Kim, Hai-joong,Kim, Sunmi,Choi, Gyuyeon,Kim, Sungjoo,Park, Jeongim,Shim, Soon-sup,Lee, Inae,Kim, Sungkyoon,Moon, Hyo-Bang,Choi, Kyungho,Lee, Jeong Jae,Kim, Su Young Elsevier 2018 Science of the Total Environment Vol.618 No.-

<P><B>Abstract</B></P> <P>Despite the global ban, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been a persistent and significant environmental health issue worldwide. Prenatal exposure to these persistent organic pollutants (POPs) has been identified as a major route of exposure among developing fetuses and newborn infants. Among Children's Health and Environmental Health of Korea (CHECK) cohort population, pregnant females (<I>n</I> =148) and their matching newborn infants (<I>n</I> =117) recruited from four cities of Korea in 2011 were investigated. The blood serum and cord blood serum were sampled at delivery, and measured for 19 OCPs and 19 PCBs. In addition, a questionnaire regarding demographic characteristics, and dietary habits were conducted. The most frequently detected POPs in both maternal blood and cord blood were <I>p,p</I>′-dichlorodiphenyl dichloroethylene (DDE) (99% detection in maternal, and 98% in cord blood serum) and PCB153 (95% in maternal, 74% in cord blood serum). The levels of dichlorodiphenyl trichloroethanes (DDTs) in both maternal (average 82.5ng/g lw) and cord blood serum (average 77.5ng/g lw) were comparable to or greater than those reported in Japan about a decade ago. Approximately two thirds of the pregnant women and newborn infants showed the <I>p,p</I>′-DDE concentrations exceeding the biological equivalent (BE) corresponding to 10<SUP>−6</SUP> excess cancer risk. In addition, less chlorinated PCBs were detected higher in both maternal and cord serum. Less chlorinated PCBs also showed greater transplacental ratio. Dairy consumption among the subjects was positively associated, and tea consumption was negatively associated with serum levels of several POPs. Our results show that the exposure to legacy POPs, especially DDTs, among pregnant women and newborn infants is still prevailing, thus warrants measures for exposure mitigation among these vulnerable populations.</P> <P><B>Highlights</B></P> <P> <UL> <LI> OCPs and PCBs were measured in serum of Korean mothers and their matching newborns. </LI> <LI> Levels of most OCPs in maternal and cord serum are correlated. </LI> <LI> Less chlorinated PCBs are detected higher in cord serum than maternal serum. </LI> <LI> DDTs are of potential health concern, with 67% of subjects potentially at risk. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

The Research Papers Published in the Journal of the Ergonomics Society of Korea: Research Trends on panel study on people with disabilities

Hyun-Jin Kim(김현진),Hyosun Kweon(권효순),Han Hyun Kyung(한현경),Hyunkyung Kim(김현경),Junho Shin(신준호),Yoon Kim(김윤),Jungwon Hwang(황정원),Eunjoo Kim(김은주),Ahran Kim(김아란),Jimin Han(한지민),Jung Inae(정인애) 대한인간공학회 2022 대한인간공학회 학술대회논문집 Vol.2022 No.10

Inflammatory cytokines are suppressed by light-emitting diode irradiation of P. gingivalis LPS-treated human gingival fibroblasts: inflammatory cytokine changes by LED irradiation.

Choi, HongRan,Lim, WonBong,Kim, InAe,Kim, JiSun,Ko, YoungJong,Kwon, Hyukil,Kim, SangWoo,Kabir, K M Ahsan,Li, Xiaojie,Kim, Oksu,Lee, YoungJoon,Kim, SeoYune,Kim, OkJoon Baillière Tindall ; Springer London 2012 LASERS IN MEDICAL SCIENCE Vol.27 No.2

<P>Human gingival fibroblasts (hGFs) play an important role in the inflammatory reaction to lipopolysaccharide (LPS) from P. gingivalis, which infects periodontal connective tissue. In addition, although light-emitting diode (LED) irradiation has been reported to have biostimulatory effects, including anti-inflammatory activity, the pathological mechanisms of these effects are unclear. This study examined the effects of 635-nm irradiation of P. gingivalis LPS-treated human gingival fibroblasts on inflammatory cytokine profiles and the mitogen-activated protein kinase (MAPK) pathway, which is involved in cytokine production. Gingival fibroblasts treated or not treated with P. gingivalis LPS were irradiated with 635-nm LED light, and cytokine profiles in the supernatant were assessed using a human inflammation antibody array. Expression of cyclooxyginase-2 (COX-2) protein and phosphorylation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun-N-terminal kinase (JNK) were assessed by Western-blot analysis to determine the effects on the MAPK pathway, and prostaglandin E(2) (PGE(2)) in the supernatant was measured using an enzyme-linked immunoassay. COX-2 protein expression and PGE(2) production were significantly increased in the LPS-treated group and decreased by LED irradiation. LPS treatment of gingival fibroblasts led to the increased release of the pro-inflammatory-related cytokines interleukin-6 (IL-6) and IL-8, whereas LED irradiation inhibited their release. Analysis of MAPK signal transduction revealed a considerable decrease in p38 phosphorylation in response to 635-nm radiation either in the presence or absence of LPS. In addition, 635-nm LED irradiation significantly promoted JNK phosphorylation in the presence of LPS. LED irradiation can inhibit activation of pro-inflammatory cytokines, mediate the MAPK signaling pathway, and may be clinically useful as an anti-inflammatory tool.</P>

Cell Death and Intracellular Distribution of Hematoporphyrin in a KB Cell Line

Choi, Hongran,Lim, Wonbong,Kim, Ji-Eun,Kim, Inae,Jeong, Jinan,Ko, Youngjong,Song, Jongwoon,You, Sunyeol,Kim, Doman,Kim, Misook,Kim, Byung-Kuk,Kim, Okjoon Mary Ann Liebert 2009 Photomedicine and laser surgery Vol.27 No.3

<P>OBJECTIVE: The objective of this study is to investigate the effect of intracellular photosensitizer distribution on tumor cell death after photodynamic therapy (PDT). BACKGROUND DATA: The photosensitizer accumulates in tumor tissue during PDT, and generates intracellular reactive oxygen species (ROS), resulting in tumor cell death. MATERIALS AND METHODS: This study was carried out to elucidate the effects of PDT in a KB oral cancer cell line using hematoporphyrin with irradiation at 635 nm and 5 mW/cm(2). After irradiation, the MTT reduction method, agarose gel electrophoresis, flow cytometry, and Diff-Quick staining were performed. The intracellular ROS level was measured by DCF-DA. Intracellular hematoporphyrin was monitored with a confocal microscope, and Western blot and caspase activity assays were performed. RESULTS: In our study, cell survival was reduced by about 50% after 3 h of hematoporphyrin incubation time. In DNA fragmentation, flow cytometry, and Diff-Quick assay, necrosis was identified within 12 h and apoptosis soon thereafter. Confocal microscopy revealed that hematoporphyrin was localized in the cell membrane, cytoplasm, and nucleus as time passed. The quantities of intracellular ROS correlated with the time of hematoporphyrin accumulation. Additionally, Western blot analysis of Bcl-2/Bax, the release of cytochrome C, and activity of caspase-3 and caspase-9 showed that apoptosis followed the mitochondria-dependent pathway. CONCLUSION: PDT with hematoporphyrin in the KB cell line showed morphological changes of cell necrosis and apoptosis, which were associated with the time of distribution and localization of hematoporphyrin. Also, the apoptosis evoked followed the mitochondria-dependent pathway.</P>

The Korean Cough Guideline: Recommendation and Summary Statement

Rhee, Chin Kook,Jung, Ji Ye,Lee, Sei Won,Kim, Joo-Hee,Park, So Young,Yoo, Kwang Ha,Park, Dong Ah,Koo, Hyeon-Kyoung,Kim, Yee Hyung,Jeong, Ina,Kim, Je Hyeong,Kim, Deog Kyeom,Kim, Sung-Kyoung,Kim, Yong H The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.1

Cough is one of the most common symptom of many respiratory diseases. The Korean Academy of Tuberculosis and Respiratory Diseases organized cough guideline committee and cough guideline was developed by this committee. The purpose of this guideline is to help clinicians to diagnose correctly and treat efficiently patients with cough. In this article, we have stated recommendation and summary of Korean cough guideline. We also provided algorithm for acute, subacute, and chronic cough. For chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered. If UACS is suspicious, first generation anti-histamine and nasal decongestant can be used empirically. In CVA, inhaled corticosteroid is recommended in order to improve cough. In GERD, proton pump inhibitor is recommended in order to improve cough. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, angiotensin converting enzyme inhibitor, habit, psychogenic cough, interstitial lung disease, environmental and occupational factor, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and idiopathic cough can be also considered as cause of chronic cough. Level of evidence for treatment is mostly low. Thus, in this guideline, many recommendations are based on expert opinion. Further study regarding treatment for cough is mandatory.

Tuberculosis Relief Belt Supporting Project (Tuberculosis Patient Management Project for Poverty Group)

Kim, Jae Kyoung,Jeong, Ina,Lee, Ji Yeon,Kim, Jung Hyun,Han, Ah Yeon,Kim, So Yeon,Joh, Joon Sung The Korean Academy of Tuberculosis and Respiratory 2018 Tuberculosis and Respiratory Diseases Vol.81 No.3

Background: The "Tuberculosis Relief Belt Supporting Project (Tuberculosis Patient Management Project for Poverty Groups)" is a national program for socioeconomically vulnerable tuberculosis (TB) patients. We sought to evaluate the clinical and socioeconomic characteristics of poverty-stricken TB patients, and determined the need for relief. Methods: We examined in-patients with TB, who were supported by this project at the National Medical Center from 2014 to 2015. We retrospectively investigated the patients' socioeconomic status, clinical characteristics, and project expenditures. Results: Fifty-eight patients were enrolled. Among 55 patients with known income status, 24 (43.6%) had no income. Most patients (80%) lived alone. A total of 48 patients (82.8%) had more than one underlying disease. More than half of the enrolled patients (30 patients, 51.7%) had smear-positive TB. Cavitary disease was found in 38 patients (65.5%). Among the 38 patients with known resistance status, 19 (50%) had drug-resistant TB. In terms of disease severity, 96.6% of the cases had moderate-to-severe disease. A total of 14 patients (26.4%) died during treatment. Nursing expenses were supported for 12 patients (20.7%), with patient transportation costs reimbursed for 35 patients (60%). In terms of treatment expenses for 31 people (53.4%), 93.5% of them were supported by uninsured benefits. Conclusion: Underlying disease, infectivity, drug resistance, severity, and death occurred frequently in socioeconomically vulnerable patients with TB. Many uninsured treatment costs were not supported by the current government TB programs, and the "Tuberculosis Relief Belt Supporting Project" compensated for these limitations.