Minipig skin: the potent model for dermal toxicology

Hanna Suh,Goo-Hwa Kang,Hyung-Sun Kim 한국실험동물학회 2019 한국실험동물학회 학술발표대회 논문집 Vol.2019 No.7

Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms

Hanna Lee,Ok-Yi Jeong,Hee Jin Park,Sung-Lim Lee,Eun-yeong Bok,Mingyo Kim,Young Sun Suh,Yun-Hong Cheon,Hyun-Ok Kim,Suhee Kim,Sung Hak Chun,Jung Min Park,Young Jin Lee,Sang-Il Lee 대한면역학회 2023 Immune Network Vol.23 No.6

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease- ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

국내 수종별 BVOCs 방출량 (1)

장한나 ( Hanna Chang ),손정아 ( Jounga Son ),제선미 ( Sun Mi Je ),오창영 ( Chang-young Oh ),조민석 ( Minseok Cho ),김주완 ( Juwan Kim ),김재현 ( Jaehyeon Kim ),최원실 ( Won-sil Choi ),이영규 ( Young-kyu Lee ) 한국산림과학회 2021 한국산림과학회지 Vol.110 No.4

피톤치드는 식물체에서 방출되는 생물유래 휘발성유기화합물(BVOCs)에 포함되어있는 isoprene, monoterpene, sesquiterpene과 같은 화합물들 형태로 존재한다. 또한 피톤치드는 중요한 산림치유 인자인 동시에 질소화합물과 광학반응을 하여 오존 및 이차 유기에어로졸 생성에 영향을 미치는 물질로 보고되고 있다. 본 연구에서는 우리나라 도시숲 주요 30 수종을 선정하여 표준환경조건(온도: 30℃, 광도: 1,000 μmol/㎡/sec)에서 400 L Tedlar bag의 순환형 챔버를 이용하여 시료를 포집하여 열탈착-GC/MS로 분석하였고, 해당 수종의 잎을 건조시켜 건중량 당 수종별 isoprene 및 terpene류의 방출량을 분석하였다. Isoprene 방출량은 전체 수종 중에서 왕대에서 가장 높았으며 졸참나무, 굴거리나무, 회양목이 주요 isoprnen 방출 수종으로 나타났다. Monoterpene 방출량은 리기다소나무에서 가장 높았으며 고로쇠, 일본잎갈나무, 백목련, 메타세쿼이아, 잣나무, 소나무, 전나무가 주요 monpterpene 방출 수종으로 나타났다. Monotrerpene 주요 물질은 α-pinene, myrcene, limonene, β-pinen, sabinene이였으며, sesquiterpene의 주요 물질은 caryophyllene, farnesene으로 나타났다. Oxygenated monoterpene의 주요 물질은 pulegone, borneol, menthol, eucalyptol, nerol이였고 oxygenated sesquiterpene에서는 carypphyllene oxide가 주요 물질로 검출되었지만 30개 수종에서 sesquiterpene과 oxygenated sesquiterpene의 방출량은 상대적으로 낮았다. This research focused on the investigation of isoprene and terpene emissions from 30 major urban tree species. We conducted sampling using a specific dynamic enclosure system between August and September 2020. Seedlings less than three years old were enclosed in a chamber consisting of a 400 L transparent Tedlar bag. The air-flows from the chamber’s outlet were sampled using Tenax-filled sorbent tubes in the presence of standard conditions (temperature: 30℃, PAR: 1,000 μmol/㎡/sec). A thermal desorption GC/MS system was used to analyze 38 BVOC compounds (isoprene, monoterpene, sesquiterpene, oxygenated monoterpene, and sesquiterpene). Isoprene emitters included Phyllostachys bambusoides, Quercus serrata, Daphniphyllum macropodum, and Buxus Koreana. Monoterpene emitters included Pinus rigida, Acer pictum subsp. mono, Larix kaempfer, Magnolia denudata, Metasequoia glyptostroboides, Pinus koraiensis, Pinus densiflora, and Abies holophylla. The monoterpene emission profiles were dominated by α-pinene, myrcene, limonene, β-pinen, and sabinene, while caryophyllene and farnesene were the prominent sesquiterpenes. Predominant oxygenated monoterpene compounds were also discovered as pulegone, borneol, menthol, eucalyptol, and nerol, while caryophyllene oxide were the prominent oxygenated sesquiterpenes. Sesquiterpenes and oxygenated sesquiterpenes had relatively lower contributions for all species.

PPARδ Inhibits UVB-Induced Secretion of MMP-1 through MKP-7-Mediated Suppression of JNK Signaling

Ham, Sun A,Kang, Eun S,Lee, Hanna,Hwang, Jung S,Yoo, Taesik,Paek, Kyung S,Park, Chankyu,Kim, Jin-Hoi,Lim, Dae-Seog,Seo, Han G The Society for Investigative Dermatology, Inc 2013 The Journal of investigative dermatology Vol.133 No.11

In the present study, we investigated the role of peroxisome proliferator–activated receptor (PPAR) δ in modulating matrix-degrading metalloproteinases and other mechanisms underlying photoaging processes in the skin. In human dermal fibroblasts (HDFs), activation of PPARδ by its specific ligand GW501516 markedly attenuated UVB-induced secretion of matrix metalloproteinase (MMP)-1, concomitant with decreased generation of reactive oxygen species. These effects were significantly reduced in the presence of PPARδ small interfering RNA and GSK0660. Furthermore, c-Jun N-terminal kinase (JNK), but not p38 or extracellular signal–regulated kinase, mediated PPARδ-dependent inhibition of MMP-1 secretion in HDFs exposed to UVB. PPARδ-mediated messenger RNA stabilization of mitogen-activated protein kinase phosphatase (MKP)-7 was responsible for the GW501516-mediated inhibition of JNK signaling. Inhibition of UVB-induced secretion of MMP-1 by PPARδ was associated with the restoration of types I and III collagen to levels approaching those in cells not exposed to UVB. Finally, in HR-1 hairless mice exposed to UVB, administration of GW501516 significantly reduced wrinkle formation and skin thickness, downregulated MMP-1 and JNK phosphorylation, and restored the levels of MKP-7, types I and III collagen. These results suggest that PPARδ-mediated inhibition of MMP-1 secretion prevents some effects of photoaging and maintains the integrity of skin by inhibiting the degradation of the collagenous extracellular matrix.

Predominant subcortical accumulation of ¹⁸F-flortaucipir binding in behavioral variant frontotemporal dementia

Cho, Hanna,Seo, Sang Won,Choi, Jae Yong,Lee, Hye Sun,Ryu, Young Hoon,Lee, Myung Sik,Na, Duk L.,Kim, Hee Jin,Lyoo, Chul Hyoung PERGAMON PRESS LTD 2018 NEUROBIOLOGY OF AGING Vol. No.

<P><B>Abstract</B></P> <P>Behavioral variant frontotemporal dementia (bvFTD) is the most common form of frontotemporal dementia, and tau pathology can be found in 40%–50% of bvFTD patients. In this study, we sought to investigate <SUP>18</SUP>F-flortaucipir-binding patterns and their correlates in clinically diagnosed bvFTD patients by comparing with results for Alzheimer's disease (AD) patients. We enrolled 20 bvFTD, 20 AD, and 20 age-matched healthy subjects who underwent neuropsychological tests, magnetic resonance imaging, and tau positron emission tomography scans with <SUP>18</SUP>F-flortaucipir. Regional standardized uptake value ratios for the cerebral cortex and underlying white matter were compared between the 2 groups. The bvFTD patients showed increased <SUP>18</SUP>F-flortaucipir binding in the putamen and globus pallidus when compared to the healthy controls. In addition, bvFTD was associated with increased binding in the white matter regions underlying the frontal, anterior cingulate, and insula cortices. The bvFTD patients may exhibit predominantly subcortical <SUP>18</SUP>F-flortaucipir-binding pattern that is distinct from the patterns seen in AD patients. We hypothesize that the clinical characteristics of bvFTD patients may be attributable to the dysfunctional frontal-subcortical networks. However, concerns remain regarding unknown “off-target” binding in the white matter and the basal ganglia.</P>

텍스트마이닝 방법론을 활용한 미래교육 키워드 분석

권선아(Sun Kyun),김한나(Hanna Kim),이수영(Soo Young Lee) 인문사회과학기술융합학회 2019 예술인문사회융합멀티미디어논문지 Vol.9 No.5

본 연구는 ‘미래비전 수립 워크숍(이하 미래워크숍)’과 ‘신문기사’로부터 수집한 미래교육 관련 텍스트를 대상으로 텍스트마이닝을 수행하여 그 결과를 비교 분석하였다. 미래워크숍에는 창의‧융합 교육에 관심과 경험을 지닌 전‧현직 초중등 교사 및 교육전문가 그리고 대학생 25명이 참여하였다. 25명의 참여자는 6개의 집단으로 나뉘어 미래교육과 관련된 자유토론을 수행하였고, 토론의 내용을 담은 녹취록을 텍스트 자료로 활용하였다. 신문기사는 데이터베이스 시스템인 빅카인즈으로부터 2017년 1월 1일부터 2018년 2월 28일까지 보도된 자료를 수집하였다. 1)텍스트마이닝을 통하여 수집된 텍스트로부터 키워드를 추출하였고, 2)키워드 빈도분석을 거쳐 워드 클라우드를 생성하였으며, 3)미래교육과 관련된 주요 키워드 두 개를 추출하여 미래사회 시나리오 별로 상관분석을 수행하였다. 분석결과, 미래워크숍에서는 미래사회와 미래교육에 대한 다양한 전망이 논의된 반면, 신문기사에서는 교육정책 수행 및 그 이해관계자들에 대한 내용이 주를 이루었다. This study compared/analyzed the results of text-mining of Future Education related text collected from ‘Future Vision Workshop (hereafter, Future Workshop)’and ‘newspaper articles’. 25 elementary & middle school teachers, education experts, and college students, who were interested in and experienced in STEAM education, attended the Future workshop. 25 participants were divided into six groups, conducted discussion related to future education, and the recoding of the discussion was used as text material. The newspaper articles were collected from BIGKINDS (i.e., newspaper database system), which were published from Jan 1 2017 to Feb 28 2018. 1)Keywords were extracted from collected text through text-mining, 2)Wordcloud was created through Keyword frequency analysis. 3) Two keywords related to future education were extracted and a correlation analysis was performed for each future scenario. Results indicated that various prospects for future society and education were discussed in the future workshop, compared to the newspaper articles featuring the implementation of education policy and stakeholders.

Activation of PPARδ counteracts angiotensin II-induced ROS generation by inhibiting rac1 translocation in vascular smooth muscle cells

Lee, Hanna,Ham, Sun Ah,Kim, Min Young,Kim, Jae-Hwan,Paek, Kyung Shin,Kang, Eun Sil,Kim, Hyo Jung,Hwang, Jung Seok,Yoo, Taesik,Park, Chankyu,Kim, Jin-Hoi,Lim, Dae-Seog,Han, Chang Woo,Seo, Han Geuk Informa Healthcare 2012 Free radical research Vol.46 No.7

<P>Angiotensin II (Ang II)-mediated modification of the redox milieu of vascular smooth muscle cells (VSMCs) has been implicated in several pathophysiological processes, including cell proliferation, migration and differentiation. In this study, we demonstrate that the peroxisome proliferator-activated receptor (PPAR) δ counteracts Ang II-induced production of reactive oxygen species (ROS) in VSMCs. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly reduced Ang II-induced ROS generation in VSMCs. This effect was, however, reversed in the presence of small interfering (si)RNA against PPARδ. The marked increase in ROS levels induced by Ang II was also eliminated by the inhibition of phosphatidylinositol 3-kinase (PI3K) but not of protein kinase C, suggesting the involvement of the PI3K/Akt signalling pathway in this process. Accordingly, ablation of Akt with siRNA further enhanced the inhibitory effects of GW501516 in Ang II-induced superoxide production. Ligand-activated PPARδ also blocked Ang II-induced translocation of Rac1 to the cell membrane, inhibiting the activation of NADPH oxidases and consequently ROS generation. These results indicate that ligand-activated PPARδ plays an important role in the cellular response to oxidative stress by decreasing ROS generated by Ang II in vascular cells.</P>

Alternaria brassicicola SW-3의 항진균 활성

정동선,라여정,변한나,정은영 서울여자대학교 자연과학연구소 2003 자연과학연구논문집 Vol.15 No.-

The fungus Alternaria brassicicola is a causal agent of black leaf spot in. several cruciferous plants. We found A. brassicicola SW-3 produced antifungal metabolite, in addition to depudecin, reported as a histone deacetylase inhibitor. The metabolite produced by A. brassicicola SW-3 exhibited antifungal activity against various filamentous fungi such as Rhizopus, Mucor, Aspergillus, Microsporium, and Trichophyton. The antifungal metabolite was extracted with ethyl acetate from the culture filtrate of A. brassicicola, and purified through silica gel column chromatography. The purified compound exhibited a broad antifungal spectrum, particularly potent activity against Microsporum canis and Trichophyton rubrum which are dermatophytes associated with cutaneous Mycosiscause. The purified metabolite showed very complex spectral data from proton and carbon-13 NMR analysis, indicating the compound contains both lipid and carbohydrate moiety. Although structure of the antifungal metabolite is not elucidated yet, these preliminary results suggest that the antifungal metabolite from A. brassicicola could be used as a lead compound for treatment of skin diseases caused by filamentous fungi.

Intestinibaculum porci gen. nov., sp. nov., a new member of the family Erysipelotrichaceae isolated from the small intestine of a swine

Ji-Sun Kim,Hanna Choe,Yu-Ri Lee,Kyung Mo Kim,DOO-SANG PARK 한국미생물학회 2019 The journal of microbiology Vol.57 No.5

A strictly anaerobic, Gram-stain-positive, catalase-negative, non-motile, rod-shaped bacterium, designated SG0102T, was isolated from the small intestine of a swine. Optimal growth occurred at 37°C and pH 7.0. Furthermore, growth was observed in the presence of up to 3% (w/v) NaCl but not at salinity levels higher than 4%. The comparative analysis of 16S rRNA gene sequences showed that strain SG0102T was most closely related to Kandleria vitulina DSM 20405T (93.3%), followed by Catenibacterium mitsuokai KCTC 5053T (91.1%), Sharpea azabuensis KCTC 15217T (91.0%), and Eggerthia catenaformis DSM 5348T (89.6%). The average nucleotide identity values between strain SG0102T and related species, K. vitulina DSM 20405T, C. mitsuokai KCTC 5053T, S. azabuensis KCTC 15217T, and E. catenaformis DSM 5348T, were 71.0, 69.3, 70.0, and 69.2%, respectively. The phylogenetic analysis based on 16S rRNA gene sequence revealed that strain SG0102T belonged to the family Erysipelotrichaceae in the class Erysipelotrichia. The DNA G+C content of the strain SG0102T was 39.5 mol%. The major cellular fatty acids (> 10%) of strain SG0102T were C16:0, C16:0 dimethyl acetal, and C18:2 ω9/12c. The cell wall peptidoglycan of strain SG0102T contained the meso-diaminopimelic acid. The strain SG0102T produced lactic acid as a major end product of fermentation. These distinct phenotypic and phylogenetic properties suggest that strain SG0102T represents a novel species in a novel genus of the family Erysipelotrichaceae, for which the name Intestinibaculum porci gen. nov. sp. nov. is proposed. The type strain is SG0102T (= KCTC 15725T = NBRC 113396T).

De novo assembly and phasing of a Korean human genome

Seo, Jeong-Sun,Rhie, Arang,Kim, Junsoo,Lee, Sangjin,Sohn, Min-Hwan,Kim, Chang-Uk,Hastie, Alex,Cao, Han,Yun, Ji-Young,Kim, Jihye,Kuk, Junho,Park, Gun Hwa,Kim, Juhyeok,Ryu, Hanna,Kim, Jongbum,Roh, Mira Nature Publishing Group, a division of Macmillan P 2016 Nature Vol.538 No.7624

<P>Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing(2), next-generation mapping(3), microfluidics-based linked reads(4), and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.</P>