KAISO, a critical regulator of p53-mediated transcription of <i>CDKN1A</i> and apoptotic genes

Koh, Dong-In,Han, Dohyun,Ryu, Hoon,Choi, Won-Il,Jeon, Bu-Nam,Kim, Min-Kyeong,Kim, Youngsoo,Kim, Jin Young,Parry, Lee,Clarke, Alan R.,Reynolds, Albert B.,Hur, Man-Wook National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.42

<P><B>Significance</B></P><P>Transcription factor KAISO (POZ/BTB family protein, ZBTB33) expression is induced by genotoxic stress in a tumor suppressor p53-dependent manner. KAISO then interacts with p53 and the acetyltransferase p300 to modulate p300 acetylation of p53 and imposing upon p53 a “code,” i.e., acetylation at K320 and K382, and inhibition of acetylation at K381. This coded p53 shows increased DNA binding to p53 response elements in the promoters of <I>CDKN1A</I> (cyclin-dependent kinase inhibitor 1) and apoptosis genes, subsequently inducing cell cycle arrest and potent apoptosis. KAISO is a critical regulator of DNA damage responses in multiple cell types and carries out this function by regulating p53-mediated cell cycle arrest and apoptosis.</P><P>An unresolved issue in genotoxic stress response is identification of induced regulatory proteins and how these activate tumor suppressor p53 to determine appropriate cell responses. Transcription factor KAISO was previously described to repress transcription following binding to methylated DNA. In this study, we show that <I>KAISO</I> is induced by DNA damage in p53-expressing cells and then interacts with the p53–p300 complex to increase acetylation of p53 K320 and K382 residues, although decreasing K381 acetylation. Moreover, the p53 with this particular acetylation pattern shows increased DNA binding and potently induces cell cycle arrest and apoptosis by activating transcription of <I>CDKN1A</I> (cyclin-dependent kinase inhibitor 1) and various apoptotic genes. Analogously, in <I>Kaiso</I> KO mouse embryonic fibroblast cells, p53-to-promoter binding and up-regulation of <I>p21</I> and apoptosis gene expression is significantly compromised. KAISO may therefore be a critical regulator of p53-mediated cell cycle arrest and apoptosis in response to various genotoxic stresses in mammalian cells.</P>

Outcome of Endodontic Micro-resurgery: A Retrospective Study Based on Propensity Score–matched Survival Analysis

Kim, Dohyun,Kim, Sunil,Song, Minju,Kang, Dae Ryong,Kohli, Meetu R.,Kim, Euiseong Elsevier 2018 JOURNAL OF ENDODONTICS - Vol.44 No.11

<P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>The purpose of this retrospective study was to evaluate and compare the outcome of endodontic micro-resurgery with that of primary endodontic microsurgery and determine prognostic factors affecting the outcome of micro-resurgery.</P> <P><B>Methods</B></P> <P>A clinical database was searched for endodontic microsurgery cases between 2001 and 2016. Nearest neighbor 2:1 propensity score matching for the following 5 variables was performed for cases of primary microsurgery and those of micro-resurgery: age, sex, tooth type, lesion type, and postoperative restoration. For the matched cases, the outcome was categorized as success or failure according to clinical and radiographic evaluations performed at least 1 year after surgery. Kaplan-Meier survival analysis and log-rank tests were performed to compare the outcome of primary microsurgery with that of micro-resurgery over time. For the micro-resurgery group, multivariate Cox proportional hazard regression analysis was performed to identify prognostic factors and estimate their effects.</P> <P><B>Results</B></P> <P>In total, 571 cases of endodontic microsurgery (498 primary microsurgery and 73 micro-resurgery cases) were identified, and 146 cases of primary microsurgery were matched to 73 cases of micro-resurgery through 2:1 propensity score matching. After matching, all covariates demonstrated an absolute standardized difference of <0.1. The estimated 5-year success rates were 91.6% and 87.6% for primary microsurgery and micro-resurgery, respectively (<I>P</I> = .594). The tooth type was found to be the only contributing factor for the outcome of micro-resurgery, with molars showing a higher probability of failure than anterior teeth (hazard ratio, 8.53; <I>P</I> = .002).</P> <P><B>Conclusions</B></P> <P>Within the limitations, the findings of this study suggest that the outcome of endodontic micro-resurgery is comparable with that of primary endodontic microsurgery.</P>

구미 불산 누출사고로 인한 주변지역 환경영향권 설정에 관한 연구

고도현,김정수,최경호,Koh, Dohyun,Kim, Jeongsoo,Choi, Kyungho 한국환경보건학회 2014 한국환경보건학회지 Vol.40 No.1

Objectives: On September 27, 2012, leakage of anhydrous hydrofluoric acid occurred in a chemical plant in the Gumi National Industrial Complex. Following the accident, local factory workers and residents complained of abnormal health conditions. In addition, visual discolorations were widely observed in crops and trees in surrounding areas. The main objectives of the present study were to identify the area that was affected by the spill using data obtained from plants, soil, and water samples after the accident. Methods: Fluoride concentrations were analyzed in pine tree needles, soil, nearby streams, ponds and reservoirs collected from an area within a radius of three kilometers from the plant where the leak occurred. Fluoride concentrations in the air at the time of leakage were then estimated from fluoride concentrations that were measured in the pine tree needles. A Kriged map was developed to describe the spatial distribution of hydrofluoric acid at the time of the leakage and was compared with the area designated as a Special Disaster Zone by the government. Results: The Special Disaster Zone did not include all the affected area that was estimated by the Kriged map. Analytical results of the environmental samples also supported this discrepancy. Conclusion: Using plants, atmospheric concentrations of fluoride at the time of the leakage could be estimated. For the area that was identified as affected, further public health risk assessment and environmental risk assessment should be considered. Also, in the absence of air monitoring at the time of leakage, studies employing plants may be conducted in order to better understand the spatial extent and severity of the contamination.

High-throughput platform for 3D in vitro tumor vasculature model for real-time monitoring of Immune Cell Cytotoxicity

Jiyoung Song,Hyeri Choi,Seung Kwon Koh,Dohyun Park,Youngtaek Kim,Duck Cho,Noo Li Jeon 한국당과학회 2022 한국당과학회 학술대회 Vol.2022 No.07

Several advances in anticancer therapy have demonstrated significant improvements in clinical outcomes, and adoptive cell therapy has emerged as a type of immunotherapy that can modulate immune responses by transferring engineered immune cells. However, it remains a challenge because only a small percentage of respondents have responded. Three-dimensional (3D) in vitro models of the tumor microenvironment (TME) have the potential to provide a platform for assessing and predicting responses to therapy. Here, we propose an in vitro 3D tumor model with clusters of colorectal cancer (CRC) cells around perfusable vascular networks to evaluate immune cell-mediated cytotoxicity against cancer cells. A 3D injection-molded co-culture model consists of 28 microwells where identical vascularized cancer models can be formed in separate wells. It allows robust hydrogel patterning, resulting in high-throughput experiments. Compared to the polydimethylsiloxane (PDMS)-based microfluidic devices, our devices allowed a greater number of experiments to be conducted. A permeability test was also conducted to confirm the characteristics of the tumor vasculature. Primary natural killer (NK) cells were introduced into a tumor vascularized network and monitored using live-cell imaging. The extravasation, migration, and cytotoxic activity of six types of CRC cell lines were examined. Based on the consensus molecular subtypes (CMS) of CRC with distinct immune responses, CMS1 cancer cells were most susceptible to NK cell cytotoxicity. This study indicates the potential of our vascularized tumor model in assessing the responses to adoptive cell therapy by understanding the various steps involved in the immune response.

초음파진단에 의한 단순 신낭종의 유병율, 그리고 연령 및 고혈압과의 연관성에 관한 연구

박종욱,최기철,이성철,고영일,강영준,조인종,남미영,류도현,강호철 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.6

Simple renal cyst is the most common space- occupying lesion of kidney in adults. However, there were a few systematic Korean reports for the prevalence of simple renal cysts. Our purpose was to estimate the prevalence of simple renal cysts using ultrasonography, and to determine the relations to age and hypertension. The subjects were 504 volunteers(aged over 29 years) of the persons who were enrolled a health check-up program of Naju Hospital, Naju, Korea. Number of male in 504 persons was 334(66.3%) and female 170(33.7%). Mean age was 55 years(range; 30-86). The results were as follows: 1) One or more renal cysts were found in 50 individuals of 504 persons aged over 29 years(9.9%). In 331 persons aged over 49 years, the prevalence of simple renal cysts was 12.1%. The prevalence was significantly increased with age(P<0.001), but the difference between male(9.6%) and female(10.6%) was insignificant. 2) Mean value of cyst diameter was 23mm(5-69 mm) and was not correlated with age. However, the cyst diameter was significantly higher in female than in male, 32.4mm vs 18.0mm(P<0.001). Total number of cysts per person tended to increase with age(P<0.001). 3) The correlation between prevalence of simple renal cysts and blood pressure was statistically insignificant. However, the prevalence of hypertension in persons with cysts was higher than in persons with no cyst(27.9% vs 15.3%, P<0.05). Cyst diameter was not correlated with blood pressure. 4)Urinalysis in persons with cysts, showed microscopic hematuria in 47.4% and proteinuria in 26.3 %, however, grade of microscopic hematuria and proteinuria were not correlated with cyst diameter. The concentrations of blood urea nitrogen, serum creatinine, hemoglobin and hematocrit were not affected by presence or absence of simple renal cysts. By comparison with the recent foreign reports, the prevalence of simple renal cysts in Korean was similar to those in foreigners. Our study ascertained that simple renal cysts are age-dependent and total number of cysts per person also increases with age. In most of persons with simple renal cysts, the renal function is not affected and the related symptoms are trivial. However, we suggested that simple renal cysts may cause hypertension. To elucidate the correlation between simple renal cyst and hypertension, further studies are needed.

Tuning of chain chirality by interchain stacking forces and the structure–property relationship in coordination systems constructed by meridional Fe^III cyanide and Mn^III Schiff bases

Sohn, Ah Ram,Lim, Kwang Soo,Kang, Dong Won,Song, Jeong Hwa,Koh, Eui Kwan,Moon, Dohyun,Hong, Chang Seop The Royal Society of Chemistry 2016 Dalton Transactions Vol.45 No.48

<▼1><P>Cyanide-bridged Fe(iii)Mn(iii) coordination polymers with racemic arrangements show a correlation between the coupling constant and Mn–NC angle.</P></▼1><▼2><P>We synthesized six Fe(iii)–Mn(iii) bimetallic compounds by self-assembling the newly developed <I>mer</I>-Fe cyanide PPh4[Fe(Clqpa)(CN)3]·H2O (1) and PPh4[Fe(Brqpa)(CN)3]·H2O (2) with Mn Schiff base Mn(5-Xsalen)<SUP>+</SUP> cations. These compounds include [Fe(Xqpa)(CN)3][Mn(5-Ysalen)]·<I>p</I>MeOH·<I>q</I>H2O [qpaH2 = <I>N</I>-(quinolin-8-yl)picolinamide; salen = <I>N</I>,<I>N</I>′-ethylenebis(salicylideneiminato) dianion; X = Cl, Y = H (3); X = Cl, Y = Br (4); X = Br, Y = H (5); X = Br, Y = F (6); X = Br, Y = Cl (7); X = Br, Y = Br (8)]. When precursor 1 was used, compounds 3 and 4 were isolated to give a dinuclear entity and a linear chain structure, respectively. The reaction of precursor 2 with the Schiff bases afforded four linear Fe(iii)–Mn(iii) chain complexes. Chain chirality with <I>P</I>- and <I>M</I>-helicity emerges in 4, 7, and 8, while 5 exhibits chain helicity opposite to the previous chain complexes and 6 presents no chain helicity. Such a structural feature is heavily dependent on the interchain π–π contacts and the Fe precursor bridging unit. Chiral induction from a local ethylenediamine link of Y-salen is propagated over the chain <I>via</I> noncovalent π–π interactions. All the bimetallic compounds show antiferromagnetic interactions transmitted by the cyanide linkage. A field-induced metamagnetic transition is involved in 4, 7, and 8, while a field-induced two-step transition is evident in 6. From a magnetostructural viewpoint, the coupling constant is primarily governed by the Mn–Nax–Cax angle (ax = axial) in the bimetallic chain complexes composed of <I>mer</I>-Fe(iii) tricyanides, although the torsion angle plays a role.</P></▼2>

Urinary phthalate metabolites among elementary school children of Korea

Sunmi Kim,Sungkyoon Kim,Sungeun Kang,Gowoon Lee,Saeram Lee,Areum Jo,Kyunghee Kwak,Dohyung Kim,Dohyun Koh,Young Lim Kho,Kyungho Choi 환경독성보건학회 2013 한국독성학회 심포지움 및 학술발표회 Vol.2013 No.10

비료제조공장 인근 지역의 담배특이니트로사민 환경 노출

하재나(Jae-Na Ha),윤미라(Mi-Ra Yoon),장준영(Jun Young Chang),고도현(Dohyun Koh),신호상(Ho-Sang Shin),김수향(Suhyang Kim),이철우(Chul-Woo Lee),이보은(Bo-Eun Lee),김정수(Jeong-Soo Kim) 한국환경보건학회 2020 한국환경보건학회지 Vol.46 No.4

Objectives: This study aimed to evaluate environmental exposure to tobacco-specific nitrosamines (TSNAs) by conducting an analysis of the concentration of TSNAs in deposited dust collected from a fertilizer plant and the surrounding village, a simulation of high-temperature drying of tobacco waste, and CALPUFF modeling. Methods: The raw materials of the products, deposited dust (inside and outside the plant and residential area), soil, and wastewater were sampled and the TSNA concentrations were analyzed by LC-MS/MS. As the plant was closed down before the investigation, simulation tests were conducted to confirm the substances discharged during high-temperature (300o C) drying of tobacco waste. CALPUFF modeling was performed to identify the area of influence due to exposure to TSNAs. Results: TSNAs were detected in organic fertilizers estimated to contain tobacco waste, deposited dust, and soil collected from inside and outside the plant. N -nitrosonornicotine (NNN), 4-(methylnitrosoamino)-1-(3-pyridyl)- 1-butanone (NNK), and N -nitrosoanatabine (NAT) components were detected in five of 15 deposited dust samples collected from the residential area around the plant, while TSNAs were not detected in the five sampling points in the control area. Also, the simulation test for the high temperature drying of tobacco waste found emissions of TSNAs. The CALPUFF modeling results showed that the survey area was likely to be included in the area of influence of TSNA emissions from the plant. Conclusions: It is estimated that harmful tobacco ingredients such as TSNAs were dispersed in nearby areas due to the illegal use of tobacco waste as a raw material to produce organic fertilizers at the plant. These findings assume that the residents have been exposed to TSNAs and suggest that the need for the establishment of measures to manage environmental health.