신경섬유종증 제 1형에 동반한 소뇌 모양세포 성상세포종 1례

전인상,김정선,김지혜,김나래 대한소아과학회 2004 小兒科 Vol.47 No.4

Depletion of adipocyte Becn1 leads to lipodystrophy and metabolic dysregulation

Yaechan Song,Young Jin,Yul Ji,Sung Sik Choe,Yong Geun Jeon,Heeju Na,Tae Wook Nam,Hye Jeong Kim,Hahn Nahmgoong,Sung Min Kim,Jae-woo Kim,Ki Taek Nam,Je Kyung Seong,Daehee Hwang,Chan Bae Park,In Hye Lee 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Macroautophagy is a catabolic process that delivers damaged and unnecessary cytosolic contents to lysosomes for removal of defective subcellular organelles and proteins. Becn1 is a key regulator of autophagy, forming a complex with class III phosphatidylinositol 3-kinase (PI3K-III) to initiate autophagosome formation. Although Becn1 has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, its function in mature adipocytes remains elusive. In this study, we implemented Adipoq-Cre to generate adipocyte-specific Becn1 KO (BaKO) mice to identify the function of autophagy in adipose tissue homeostasis. BaKO mice naturally developed severe lipodystrophy and metabolic dysregulation, which were exacerbated upon high dietary fat intake. These mice also acquired adipose tissue inflammation, hepatic steatosis, and insulin resistance which advanced to early mortality. Immortalized stromal vascular cells (imSVCs) were established in-vitro to conditionally knock-out Becn1 upon tamoxifen treatment. Ablation of Becn1 in adipocytes led to programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Furthermore, we observed that Becn1 depletion sensitized mature adipocytes to ER stress through activation of protein kinase R-like ER kinase (PERK) – eukaryotic initiation factor 2α (eiF2α) axis. This led to excessive unfolded protein response (UPR) and accelerated cell death through notable induction of C/EBP homologous protein (CHOP) and Bax expression. Taken together, these data suggest that adipocyte-Becn1 would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.

Seasonal Fluctuation of Chlorophyll a Concentration in the Size Fractionation of Phytoplankton in Daechung Reservoir

Mun, Jong-Jeon,Lee, Sang-Wook,Hwang, Soon-Jin,Oh, In-Hye 한국육수학회 2001 생태와 환경 Vol.34 No.4

여러 지역의 호소환경에서 picoplankton이 중요한 일차 생산자로 보고되고 있는데 대청호에서 이를 조사하기 위하여 1998년 9월부터 1999년 9월까지 식물 플랑크톤 크기에 따른 엽록소 농도의 계절적 변화를 조사하였다. 200㎛ 이하의 식물플랑크톤은 대전취수탑에서 0.7∼36.9㎍/ℓ, 만입부에서 0.5∼23.5㎍/ℓ 회남대교에서 1.9∼20.1㎍/ℓ, 대청댐에서 0.5∼17.4㎍/ℓ이었는데, 조사지점 4곳에서 모두 9월에 최대치를 나타내었으며 그 이후는 서서히 감소되어 4∼6월에 최소값을 보이는 경향을 나타내었다. 계절에 따른 엽록소 농도의 크기별 조성비율을 보면, 연중 microplankton과 nanoplankton 조성비율은 큰 변이를 보였는데, 회남 대교를 제외한 조사지역 3 곳에서 6∼10월에는 microplankton의 비율이 높았으나 3월에는 조성비율이 매우 낮은 경향을 보였다. 그러나 조사지역 4곳 모두에서 picoplankton은 연중 2.0∼24.3%로 거의 일정하였다. Since a substantial part of the total planktonic primary production is due to the activity of the picoplankton, seasonal change of chlorophyll a in the picoplankton, nanoplankton and microplankton was determined at four locations in Daechung Reservoir from September in 1998 to September in 1999. Chlorophyll a concentration(<200㎛) was 0.7∼36.9㎍/ℓin TAE(Taejeon site), 0.5∼23.5㎍/ℓin MAN(Man site), 1.9∼20.1㎍/ℓ in HOE(Hoenam site), and 0.5∼17.4㎍/ℓin DAM(Dam site). Generally it was observed the the highest concentration of chlorophyll a was in September and the lowest in April to June. The relative contribution of chlorophyll a of each fraction was changed dramatically through the year. Relative contribution of chlorophyll a of microplankton was high from June to October, and low in March in all locations except HOE. However chlorophyll a concentration of picoplankton fraction was 2.0∼24.3% of total chlorophyll a (<200㎛) through the year and did not show any dramatic changes at all locations.

<i>Orientia tsutsugamushi</i> Subverts Dendritic Cell Functions by Escaping from Autophagy and Impairing Their Migration

Choi, Ji-Hye,Cheong, Taek-Chin,Ha, Na-Young,Ko, Youngho,Cho, Chung-Hyun,Jeon, Ju-Hong,So, Insuk,Kim, In-Kyu,Choi, Myung-Sik,Kim, Ik-Sang,Cho, Nam-Hyuk Public Library of Science 2013 PLoS neglected tropical diseases Vol.7 No.1

<▼1><P><B>Background</B></P><P>Dendritic cells (DCs) are the most potent antigen-presenting cells that link innate and adaptive immune responses, playing a pivotal role in triggering antigen-specific immunity. Antigen uptake by DCs induces maturational changes that include increased surface expression of major histocompatibility complex (MHC) and costimulatory molecules. In addition, DCs actively migrate to regional lymph nodes and activate antigen-specific naive T cells after capturing antigens. We characterize the functional changes of DCs infected with <I>Orientia tsutsugamushi</I>, the causative agent of scrub typhus, since there is limited knowledge of the role played by DCs in <I>O. tsutsugamushi</I> infection.</P><P><B>Methodology/Principal Finding</B></P><P><I>O. tsutsugamushi</I> efficiently infected bone marrow-derived DCs and induced surface expression of MHC II and costimulatory molecules. In addition, <I>O. tsutsugamushi</I> induced autophagy activation, but actively escaped from this innate defense system. Infected DCs also secreted cytokines and chemokines such as IL-6, IL-12, MCP5, MIP-1α, and RANTES. Furthermore, <I>in vitro</I> migration of DCs in the presence of a CCL19 gradient within a 3D collagen matrix was drastically impaired when infected with <I>O. tsutsugamushi</I>. The infected cells migrated much less efficiently into lymphatic vessels of ear dermis <I>ex vivo</I> when compared to LPS-stimulated DCs. <I>In vivo</I> migration of <I>O. tsutsugamushi</I>-infected DCs to regional lymph nodes was significantly impaired and similar to that of immature DCs. Finally, we found that MAP kinases involved in chemotactic signaling were differentially activated in <I>O. tsutsugamushi</I>-infected DCs.</P><P><B>Conclusion/Significance</B></P><P>These results suggest that <I>O. tsutsugamushi</I> can target DCs to exploit these sentinel cells as replication reservoirs and delay or impair the functional maturation of DCs during the bacterial infection in mammals.</P></▼1><▼2><P><B>Author Summary</B></P><P>Scrub typhus is an acute febrile illness caused by <I>Orientia tsutsugamushi</I> infection and is one of the main causes of febrile illness in the Asia-Pacific region. If not properly treated with antibiotics, patients often develop severe vasculitis that affects multiple organs, and the mortality rate of untreated patients reaches up to 30%. To understand the pathogenic mechanisms of the infectious disease, we characterized the functional changes of <I>O. tsutsugamushi</I>–infected dendritic cells (DCs), which play a pivotal role in orchestrating innate and adaptive immune responses. The obligate intracellular bacteria efficiently infected bone marrow-derived DCs and activated the cells as measured by induced surface expression of MHC II and costimulatory molecules, secretion of cytokines and chemokines, and autophagy induction. However, the live bacteria actively escaped from host autophagosomes and the migration of infected cells was severely impaired <I>in vitro</I>, <I>ex vivo</I>, and <I>in vivo</I> infection models. Finally, we found that MAP kinases involved in chemotactic signaling were differentially activated in <I>O. tsutsugamushi</I>-infected DCs. These results suggest that <I>O. tsutsugamushi</I> can target DCs to exploit these sentinel cells as replication reservoirs and delay or impair the functional maturation of DCs during the bacterial infection in mammals.</P></▼2>

Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages.

Kim, Jung-Hee,Jeong, Ji-Hye,Jeon, Sung-Tak,Kim, Ho,Ock, Jiyeon,Suk, Kyoungho,Kim, Sang-In,Song, Kyung-Sik,Lee, Won-Ha American Society for Pharmacology and Experimental 2006 Molecular pharmacology Vol.69 No.6

<P>In the course of screening inhibitors of matrix metalloproteinase (MMP)-9 induction in macrophages, we isolated decursin, a coumarin compound, from the roots of Angelicae gigas. As a marker for the screening and isolation, we tested expression of MMP-9 in RAW264.7 cells and THP-1 cells after treatment with bacterial lipopolysaccharide (LPS), the TLR-4 ligand. Decursin suppressed MMP-9 expression in cells stimulated by LPS in a dose-dependent manner at concentrations below 60 microM with no sign of cytotoxicity. The suppressive effect of decursin was observed not only in cells stimulated with ligands for TLR4, TLR2, TLR3, and TLR9 but also in cells stimulated with interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha, indicating that the molecular target of decursin is common signaling molecules induced by these stimulants. In addition to the suppression of MMP-9 expression, decursin blocked nitric oxide production and cytokine (IL-8, MCP-1, IL-1beta, and TNF-alpha) secretion induced by LPS. To find out the molecular mechanism responsible for the suppressive effect of decursin, we analyzed signaling molecules involved in the TLR-mediated activation of MMP-9 and cytokines. Decursin blocked phosphorylation of IkappaB and nuclear translocation of NF-kappaB in THP-1 cells activated with LPS. Furthermore, expression of a luciferase reporter gene under the promoter containing NF-kappaB binding sites was blocked by decursin. These data indicate that decursin is a novel inhibitor of NF-kappaB activation in signaling induced by TLR ligands and cytokines.</P>

A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses

Sun, Dawei,Lee, Gina,Lee, Jun Hee,Kim, Hye-Yeon,Rhee, Hyun-Woo,Park, Seung-Yeol,Kim, Kyung-Jin,Kim, Yongsung,Kim, Bo Yeon,Hong, Jong-In,Park, Chankyu,Choy, Hyon E,Kim, Jung Hoe,Jeon, Young Ho,Chung, J Nature Publishing Group, a division of Macmillan P 2010 Nature Structural and Molecular Biology Vol.17 No.10

In nutrient-starved bacteria, RelA and SpoT proteins have key roles in reducing cell growth and overcoming stresses. Here we identify functional SpoT orthologs in metazoa (named Mesh1, encoded by HDDC3 in human and Q9VAM9 in Drosophila melanogaster) and reveal their structures and functions. Like the bacterial enzyme, Mesh1 proteins contain an active site for ppGpp hydrolysis and a conserved His-Asp??box motif for Mn<SUP>2+</SUP> binding. Consistent with these structural data, Mesh1 efficiently catalyzes hydrolysis of guanosine 3??5??diphosphate (ppGpp) both in vitro and in vivo. Mesh1 also suppresses SpoT-deficient lethality and RelA-induced delayed cell growth in bacteria. Notably, deletion of Mesh1 (Q9VAM9) in Drosophila induces retarded body growth and impaired starvation resistance. Microarray analyses reveal that the amino acid??starved Mesh1 null mutant has highly downregulated DNA and protein synthesis??related genes and upregulated stress-responsible genes. These data suggest that metazoan SpoT orthologs have an evolutionarily conserved function in starvation responses.

Evaluation on Four Volatile Organic Compounds (VOCs) Contents in the Groundwater and Their Human Risk Level

Dahee Song,Sunhwa Park,Sang-Ho Jeon,Jong Yeon Hwang,Moonsu Kim,Hun-Je Jo,Deok-Hyun Kim,Gyeong-Mi Lee,Ki-In Kim,Hye-Jin Kim,Tae-Seung Kim,Hyen Mi Chung,Hyun-Koo Kim 한국토양비료학회 2017 한국토양비료학회지 Vol.50 No.4

In this study, we monitored 4 volatile organic compounds (VOCs) such as chloroform, dichloromethane, 1,2-dichloroethane, and tetrachloromethane in groundwater samples to determine the detection frequency and their concentrations and evaluated the health risk level considering ingestion, inhalation, and skin contact. 75 groundwater wells were selected. 24 wells were from monitoring background groundwater quality level and 51 wells were from monitoring groundwater quality level in industrial or contamination source area. In the results, the detection frequency for chloroform, dichloromethane, 1,2-dichloroethane, and tetrachloromethane was 42.3%, 8.1%, 6.0%, and 3.4%, respectively. The average concentrations of VOCs were high in the order of chloroform (1.7 μg L<SUP>-1</SUP>), dichloromethane (0.08 μg L<SUP>-1</SUP>), tetrachloromethane (0.05 μg L<SUP>-1</SUP>), and 1,2-dichloroethane (0.05 μg L<SUP>-1</SUP>). Chloroform had the highest detection frequency and average detection concentration. In the contaminated groundwater, the detection frequency of VOCs was high in the order of chloroform, dichloromethane, 1,2-dchloroethane, and tetrachloromethane. The average concentrations for chloroform, dichloromethane, 1,2-dichloroethane, and tetrachloromethane were 2.23 μg L<SUP>-1</SUP>, 0.08 μg L<SUP>-1</SUP>, 0.07 μg L<SUP>-1</SUP>, and 0.06 μg L<SUP>-1</SUP>, respectively. All the 4 compounds were detected at industrial complex and storage tank area. The maximum concentration of chloroform, dichloromethane, and 1,2-dichloroethane was detected at industrial complex area. Especially, the maximum concentration of chloroform and dichloromethane was detected at a chemical factory area. In the uncontaminated groundwater, the detection frequency of VOCs was high in the order of chloroform, dichloromethane, and 1,2-dchloroethane and tetrachloromethane was not detected. The average concentrations for chloroform, dichloromethane, and 1,2-dichloroethane were 0.57 μg L<SUP>-1</SUP>, 0.07 μg L<SUP>-1</SUP>, and 0.03 μg L<SUP>-1</SUP>, respectively. Although chloroform in the uncontaminated groundwater was detected the most, the concentration of chloroform was not exceeding water quality standards. By land use, the maximum detection frequency of 1,2-dichloroethane was found near a traffic area. For human risk assessment, the cancer risk for the 4 VOCs was 1<SUP>0-6</SUP>~10<SUP>-9</SUP>, while the non-cancer risk (HQ value) for the 4 VOCs is 10<SUP>-2</SUP>~10<SUP>-3</SUP>.

Electro-hyperthermia up-regulates tumour suppressor Septin 4 to induce apoptotic cell death in hepatocellular carcinoma

Jeon, Tae-Won,Yang, Heebum,Lee, Chang Geol,Oh, Sang Taek,Seo, Daekwan,Baik, In Hye,Lee, Eun Hye,Yun, Ina,Park, Kyung Ran,Lee, Yun-Han Informa UK (TaylorFrancis) 2016 International journal of hyperthermia Vol.32 No.6

<P>Purpose: Modulated electro-hyperthermia (mEHT) has been shown to be effective against various types of human tumours, including hepatocellular carcinoma (HCC). Here we aimed to investigate the molecular mechanism underlying the cytotoxic effects of mEHT to HCC cells. Materials and methods: Human liver cancer cell lines, Huh7 and HepG2, were treated with mEHT (42 degrees C/60 min) three times at 2-day intervals. Growth inhibition and apoptotic induction were evaluated using MTS, microscopic analysis, a clonogenic assay, annexin V/PI staining and a ccK18 ELISA. Global changes in gene expression were examined using RNA sequencing to obtain insights into molecular changes in response to mEHT. For in vivo evaluation of mEHT we used HepG2 HCC xenografts grown in nude mice. Results: mEHT suppressed HCC cell proliferation and long-term colony formation through induction of apoptosis. The growth inhibitory effects are induced through a subset of molecular changes. Notably the expression level of septin 4 (SEPT4) (involved in pro-apoptotic activity and growth suppression) was up-regulated, whereas a key regulator of invasiveness G-Protein coupled receptor 64 (GPR64) was repressed. Subsequent Western blotting confirmed that the common increase in tumour suppressor SEPT4 in both Huh7 and HepG2 cells is accompanied by the restoration of cyclin-dependent kinase (CDK) inhibitor p21 and decrease in pro-caspase 7 and pro-caspase 3, thereby accelerating apoptotic signalling in HCC cells. Additionally, mEHT significantly inhibited the growth of human HCC xenografts in nude mice. Conclusions: These findings suggest that apoptotic cell death induced by mEHT is mediated by the up-regulation of tumour suppressor SEPT4 in human HCC cells.</P>

Quality of Life and Economic Burden in Recessive Dystrophic Epidermolysis Bullosa

( In Kyung Jeon ),( Hye Rang On ),( Soo Chan Kim ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.1

Background: Patients with recessive dystrophic epidermolysis bullosa (RDEB) exhibit blisters and erosions since birth, causing pain, pruritus and various complications. RDEB affects quality of life (QoL) in physical, emotional and social aspects. Furthermore, interminable dressing changes and supportive therapies impose a significant economic burden on the patient s family. Objective: We assessed the QoL and economic burden in patients with RDEB. Methods:Sixteen patients with RDEB were surveyed to assess the QoL and economic burden. Patients answered questionnaires consisting of a visual analogue scale (VAS) on pain and pruritus, Skindex-29, Quality of Life in EB questionnaire (QOLEB), and the economic burden due to EB. Results:Thirteen patients with RDEB completed the questionnaire. Female patients presented higher VAS, QOLEB and total Skindex-29 scores than male patients. Patients with RDEB showed severe levels of pruritus, which was more intolerable than pain. Mean VAS score on pain in RDEB was higher than in oral lichen planus and post-herpetic neuralgia. VAS score on pruritus was similar to those in chronic urticaria, atopic dermatitis, and prurigo nodularis. Compared with other dermatologic conditions, patients with RDEB were profoundly affected in all three scales of skindex-29. Mean “medical cost” in a month was $257. 54 (USD) (±169. 39) and mean “dressing cost” was $358. 41 (USD) (±312. 55), which was negatively related to patient age. Conclusion: RDEB had a profound impact on QoL and economic burden. Compared with other dermatologic diseases, RDEB showed severe symptoms and QoL was seriously impaired. Most patients sustained economic burdens, especially on preparing dressing materials. Younger patients experienced more economic burdens.

In Situ Neutron Powder Diffraction and X-ray Photoelectron Spectroscopy Analyses on the Hydrogenation of MOF-5 by Pt-Doped Multiwalled Carbon Nanotubes

Lee, Heeju,Choi, Yong Nam,Choi, Sang Beom,Seo, Jung Hye,Kim, Jaheon,Cho, In Hwa,Gang, Seunggi,Jeon, Cheol Ho American Chemical Society 2014 The Journal of Physical Chemistry Part C Vol.118 No.11

<P>Recent research on hydrogen storage in metal–organic frameworks focuses on how to achieve increased hydrogen binding energies by using doped metal, using unsaturated metal ions, or forming composites comprising Pt-doped carbon materials. In particular, noticeable progress using MOFs and Pt-doped carbons has been achieved to enhance the hydrogen storage capacity near room temperature. A three-component composite material, Pt-MWCNT-MOF5 (PMM5), which is a metal–organic framework (MOF-5) hybridized with Pt nanoparticles on multiwalled carbon nanotubes (MWCNT), stores 0.22 wt % hydrogen at 320 K and 30 bar, which is larger than 0.13 wt % at 300 K and 30 bar. Although the increased quantity is small, it is possible to detect the origin of uptake increase based on various analyses. In situ neutron diffraction experiments of deuterium-sorbed PMM5 with a temperature cycling process (D<SUB>2</SUB> loading at 50 K → 4 K → 320 K, 2 h → 50 K → 4 K) result in a significant background increase owing to both chemisorbed deuterium atoms and a local deformation of the MOF-5 framework. Hydrogen loading in PMM5 induces significant binding energy shifts in C 1s and Zn 2p<SUB>3/2</SUB> electrons in the X-ray photoelectron spectra, suggesting the chemical environment change in Zn<SUB>4</SUB>O(COO)<SUB>6</SUB> coordination sphere in MOF-5. All accumulated experimental data support the fact that the hydrogen receptor is the oxygen atoms of benzene-1,4-dicarboxylates of MOF-5, which is facilitated by the embedded Pt-MWCNT.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2014/jpccck.2014.118.issue-11/jp411955y/production/images/medium/jp-2013-11955y_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp411955y'>ACS Electronic Supporting Info</A></P>