Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice

Kim, Min-Seok,Kim, Sung-Hwan,Jeon, Doin,Kim, Hyeon-Young,Han, Jin-Young,Kim, Bumseok,Lee, Kyuhong Taylor Francis 2018 Journal of toxicology and environmental health. Pa Vol.81 No.11

<P>Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water. Inhalation is an important route of Cd exposure, and lungs are one of the main target organs for metal-induced toxicity. Cd inhalation is associated with an increased risk of pulmonary diseases. The present study aimed to assess the effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following groups: vehicle control (VC), PHMG, cadmium chloride (CdCl2), and PHMG + CdCl2. Animals in the PHMG group exhibited increased numbers of total cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by inflammation and fibrosis in lung tissues. These parameters were exacerbated in mice in the PHMG + CdCl2 group. In contrast, mice in the CdCl2 group alone displayed only minimal inflammation in pulmonary tissue. Expression of inflammatory cytokines and fibrogenic mediators was significantly elevated in lungs of mice in the PHMG group compared with that VC. Further, expression of these cytokines and mediators was enhanced in pulmonary tissue in mice administered PHMG + CdCl2. Data demonstrate that repeated exposure to low-dose Cd may enhance the development of PHMG-induced pulmonary fibrosis.</P>

Hepatotoxicity Induced by Microcystin-LR in Rat

Bumseok Kim,Jae Woo Cho,Hyuk Nyun Kwon,Ivar Blank,Irina Borisova,Sohail Ejaz,Irina Chekarova,Jungkee Kwon,Chae Woong Lim 한국독성학회 2006 Toxicological Research Vol.22 No.4

Microcystin-LR (MC-LR) is a cyanobacterial hepatotoxin mainly produced by Microcystis aeruginosa. The current study examined the effects of a single intraperitoneal dose of MC-LR in rats. Female Sprague-Dawley rats were intraperitoneally injected with MC-LR (100 ㎍/㎏ body weight) and they were sacrificed at 0, 20, 40, 80, 160 min, or 12 h after injection. Clinically, animals showed lethargy and had ruffled hair beginning at 40 min post injection. In the gross findings, liver was enlarged and its color was changed into dark red beginning at 40 min post injection. Microscopically, dissociation of centrilobular hepatocytes and hemorrhage was observed in the hepatic central regions and such pathological changes were then extended to the portal regions of liver by time course manner. Interestingly at 80 min after MC-LR injection, the entrapped eosinophilic materials that may be necrotic fragments of dissociated hepatocytes were found in the capillaries of lung and renal glomerulus. Ultrastructurally, microvilli of the hepatocytes were disrupted or lost at all time points. Furthermore, the Disse space and gap junctions were widened beginning at 40 min post injection. These results suggest that liver is the major target organ of MC-LR and isolated hepatocytes by the effects of such hepatotoxin may secondarily reduce the physiological function of lung and kidney.

A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder.

Kim, Chang Yoon,Chung, Seockhoon,Lee, Joon-Noh,Kwon, Jun Soo,Kim, Do Hoon,Kim, Chul Eung,Jeong, Bumseok,Jeon, Yang-Whan,Lee, Min-Soo,Jun, Tae-Youn,Jung, Hee-Yeon Clinical Neuroscience Publishers 2009 International clinical psychopharmacology Vol.24 No.4

<P>The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigator's Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56+/-1.29 (95% confidence interval: 3.39-3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigator's Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.</P>

Effects of cigarette smoke extracts on cell cycle, cell migration and endocrine activity in human placental cells

Kim, Cho-Won,Lee, Hae-Miru,Lee, Kyuhong,Kim, Bumseok,Lee, Moo-Yeol,Choi, Kyung-Chul Elsevier 2017 Reproductive toxicology Vol.73 No.-

<P><B>Abstract</B></P> <P>Maternal smoking during pregnancy is known to be related to adverse pregnancy results associated with trophoblast proliferation and cell cycle progression. Moreover, many previous studies have shown that cigarette smoke is correlated with human chorionic gonadotropin beta (hCG-β) subunit produced from syncytiotrophoblasts during pregnancy. Thus, we further investigated whether cigarette smoke extract (CSE) affects the cell proliferation, migration and endocrine hormone activity of JEG-3 human placental cancer cells. JEG-3 cell proliferation was significantly reduced by all CSEs in a concentration-dependent manner. Moreover, CSEs decreased proliferating cell nuclear antigen (PCNA) levels in JEG-3 cells in Western blot. Increased migration or invasion ability of JEG-3 cells following CSE treatment was also confirmed by a scratch or fibronectin invasion assay <I>in vitro</I>. Additionally, protein levels of E-cadherin as an epithelial maker were down-regulated, while the mesenchymal markers N-cadherin, snail and slug were up-regulated in a time-dependent manner. The metastasis marker, cathepsin D, was also down-regulated by CSE. Finally, CSEs significantly reduced the expression of hCG-β protein in JEG-3 cells. Overall, these results indicate that exposure of placental cells to CSE deregulates the cell cycle by altering the expression of cell cycle-related proteins and stimulates cell metastatic ability by altering EMT markers and cathepsin D expression. CSE exposure may also decrease hCG-β production as an endocrine marker, implying that cigarette smoke has adverse effects during pregnancy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CSE exposure deregulated the placental cell growth by altering cell proliferation-related genes. </LI> <LI> CSE exposure stimulated JEG-3 metastatic potential by altering EMT markers and cathepsin D. </LI> <LI> CSE exposure also deregulated the production of human chorionic gonadotropin beta. </LI> <LI> Cigarette smoking may have adverse effects on normal placenta functions during pregnancy. </LI> </UL> </P>

Superstring standard model from &BbbZ;_{12−<i>I</i>} orbifold compactification with and without exotics, and effective <i>R</i>-parity

Kim, Jihn E.,Kim, Ji-Hun,Kyae, Bumseok Institute of Physics Pub 2007 The journal of high energy physics Vol.2007 No.6

We construct a supersymmetric standard model in the context of the &BbbZ;<SUB>12−<I>I</I></SUB> orbifold compactification of the heterotic string theory. The gauge group is SU(3)<SUB>c</SUB> × SU(2)<SUB>L</SUB> × U(1)<SUB>Y</SUB> × U(1)<SUP>4</SUP> × [SO(10) × U(1)<SUP>3</SUP>]′. We obtain three chiral families, 3 × {<I>Q</I>, <I>d</I><SUP><I>c</I></SUP>, <I>u</I><SUP><I>c</I></SUP>, <I>L</I>, <I>e</I><SUP><I>c</I></SUP>, ν<SUP><I>c</I></SUP>}, and Higgs doublets. There are numerous neutral singlets many of which can have VEVs so that low energy phenomenology on Yukawa couplings can be satisfied. In one assignment (Model E) of the electroweak hypercharge, we obtain the string scale value of sin <SUP>2</SUP> θ<SUB><I>W</I></SUB><SUP>0</SUP> = (3/8) and another exactly massless <I>exphoton</I> (in addition to the photon) coupling to exotic particles only. There are color triplet and anti-triplet exotics, α and &baralpha;, SU(2)<SUB>L</SUB> doublet exotics, δ and &bardelta;, and SU(3)<SUB>c</SUB> × SU(2)<SUB>L</SUB> singlet but <I>Y</I> = 2/3, −1/3, −2/3, 1/3 exotics, ξ, η, &barxi;, &bareta;. We show that all these vector-like exotics achieve heavy masses by appropriate VEVs of neutral singlets. One can find an effective <I>R</I>-parity between light (electroweak scale) particles so that proton and the LSP can live sufficiently long. In another assignment (Model S) of the electroweak hypercharge, there does not appear any exotic particle but sin<SUP>2</SUP> θ<SUB><I>W</I></SUB><SUP>0</SUP> = 3/14.

Spliceosome-Associated Protein 130 Exacerbates Alcohol-Induced Liver Injury by Inducing NLRP3 Inflammasome–Mediated IL-1β in Mice

Kim, Jong-Won,Roh, Yoon-Seok,Jeong, Hyeneui,Yi, Ho-Keun,Lee, Min-Ho,Lim, Chae-Woong,Kim, Bumseok Elsevier 2018 The American journal of pathology Vol.188 No.4

<P>Excessive alcohol consumption leads to chronic liver diseases. Macrophage-inducible C-type lectin (MincLe) is a C-type lectin receptor that recognizes spliceosome-associated protein 130 (SAP130) known as an endogenous ligand released from dying cells. The aim was to examine the role of Mincle-SAP130 in the pathogenesis of alcoholic liver disease. Alcohol-induced liver injury was induced in wild-type (WT) and Mincle knockout (KO) mice by using a chronic-binge ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis, inflammation with neutrophil infiltration, and fibrosis compared with WT mice after alcohol feeding. In contrast, Mincle activation exacerbated alcohol-induced liver injury. Kupffer cells (KCs) are major sources of Mincle. IL-1 beta expression was significantly down regulated in Mincle KO mice compared with that in WT mice after alcohol consumption. Interestingly, expression and production of IL-1 beta were significantly decreased in SAP130-treated KCs isolated from leucine-rich-containing family pyrin domain containing-3-deficient mice compared with those in WT KCs. Such results were also observed in cells treated with SAP130 plus Syk inhibitor. Furthermore, infiltration of invariant natural killer T cells was decreased in livers of Mincle KO mice. Finally, inhibition of Syk signaling ameliorated alcohol-induced liver injury. Collectively, these results demonstrated that interaction between Mincle and SAP130 may promote the progression of alcoholic Liver disease by IL-1 beta production in KCs and consequently increase inflammatory immune cell infiltration.</P>

Fatal case of Clostridium difficile infection in a neonatal piglet in Korea

Kim, Ha-Young,Jung, Byeong Yeal,Byun, Jae-Won,Lee, Kyung-Hyun,Cho, Ara,Lee, Myoung-Heon,Songer, J. Glenn,Kim, Bumseok PAKISTAN VETERINARY JOURNAL 2015 Pakistan veterinary journal Vol.35 No.2

Evaluating the Influence of Side Stream Cigarette Smoke at an Early Stage of Non-Alcoholic Steatohepatitis Progression in Mice

Kim, Jong Won,Yun, Hyejin,Choi, Seong-Jin,Lee, Sang-Hyub,Park, Surim,Lim, Chae Woong,Lee, Kyuhong,Kim, Bumseok Korean Society of ToxicologyKorea Environmental Mu 2017 Toxicological Research Vol.33 No.1

Side stream cigarette smoke (SSCS) is known to be as harmful and hazardous to human health as is active smoking. In this study, we investigated the relationship between the exposure to SSCS and its stimulatory and subacute effects on the progression of non-alcoholic steatohepatitis (NASH). A methionine and choline-deficient plus high fat (MCDHF) diet was administered to C57BL/6 mice for 6 weeks. During the first three weeks of MCDHF diet feeding, each diet group was exposed to SSCS (0, 20, $40{\mu}g/L$) or fresh air for 2 hrs per day and 5 days per week. Additional experiments were performed by increasing the concentration (0, 30, $60{\mu}g/L$) and exposure time (6 hours per day) of SSCS. According to histopathologic analysis and serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), there were no differences in hepatic fat deposition, fibrosis, apoptosis or liver damage in MCDHF-fed mice based on SSCS exposure. There were also no differences in the expression of inflammation-, oxidative stress- or fibrosis-related genes between MCDHF-fed mice with or without SSCS exposure. Therefore, it is concluded that SSCS with current exposure amounts does not have additive detrimental effects on the early stage of NASH.

Detection of Nitroaromatic Compounds Based on Fluorescent Silafluorene Chemosensors

Bumseok Kim 조선대학교 기초과학연구원 2010 조선자연과학논문집 Vol.3 No.1

The Role of Air Pollutants in Initiating Liver Disease

Kim, Jong Won,Park, Surim,Lim, Chae Woong,Lee, Kyuhong,Kim, Bumseok Korean Society of ToxicologyKorea Environmental Mu 2014 Toxicological Research Vol.30 No.2

Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.