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COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm

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Signal Transduction and Targeted Therapy 2020年第1期5卷 910-920页

作者： Wonhwa Lee june hong ahn Hee Ho Park hong Nam Kim Hyelim Kim Youngbum Yoo Hyosoo Shin Kyung Soo hong Jong Geol Jang Chun Gwon Park Eun Young Choi Jong-Sup Bae Young-Kyo Seo Aging Research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 34141Republic of Korea Division of Pulmonology and Allergy Department of Internal MedicineCollege of MedicineYeungnam University and Regional Center for Respiratory DiseasesYeungnam University Medical CenterDaegu 42415Republic of Korea Department of Biotechnology and Bioengineering Kangwon National UniversityChuncheonGangwon-do 24341Republic of Korea Center for BioMicrosystems Brain Science InstituteKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Division of Bio-Medical Science and Technology KIST SchoolKorea University of Science and TechnologySeoul 02792Republic of Korea College of Pharmacy Chungnam National UniversityDaejeon 34134Republic of Korea Department of Biomedical Engineering SKKU Institute for ConvergenceSungkyunkwan University(SKKU)SuwonRepublic of Korea Biomedical Institute for Convergence at SKKU(BICS) Sungkyunkwan University2066 Seobu-roJangan-guSuwon 16419Republic of Korea College of Pharmacy CMRIResearch Institute of Pharmaceutical SciencesBK21 Plus KNU Multi-Omics based Creative Drug Research TeamKyungpook National UniversityDaegu 41566Republic of Korea

Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is ***,we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in ***,we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’blood and propose SREBP-2 C-terminal fragment as an indicator for determining *** confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression,while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU *** an infectious disease mouse model,inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary *** results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

关键词： cytokine diagnosis damage

Biphasic Nano-Domains of Planar Lipid Bilayer Complexed with Fluorogenic Polymer Reporter Tailored for Antimicrobial Detection

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CCS Chemistry 2022年第11期4卷 3637-3647页

作者： Jimin Hwang Woo Hyuk Jung Yeol Kyo Choi Dong june ahn Department of Chemical and Biological Engineering Korea UniversitySeoul 02841 Department of Biological Sciences Lehigh UniversityBethlehemPennsylvania 18015 KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841

We have fabricated an unexpected type of supported planar bilayer composed of receptor phospholipids and single-chained diacetylenes as fluorogenic reporters using protruded anchor moieties with a positive terminal *** topographical and surface thermodynamic analyses,as well as molecular dynamics simulations,revealed the coexistence of well-dispersed liquid-condensed(L_(c))domains forming nano-islands and liquid-expanded(L_(e))region in the planar bilayer,enhancing sensitivity against a prototype of ubiquitous membrane-associated antimicrobial peptides,*** L_(e)regions,acting as target receptors,enabled sensitive detection as the melittin adsorbed and inserted into these regions due to strong hydrophobic interactions between phospholipids and *** L_(c)domains,serving as signal reporters,enabled diacetylenes to assemble,polymerize,and fluoresce in response to the insertion of melittin into the L_(e)***,biphasic nanodomains of the planar lipid bilayer finally endowed this sensor system with a detection range of 100μMto 50 nM and a limit of detection(LOD)of∼37 nM for *** exceeded the operational performance of the colorimetric polydiacetylene vesicle solution 45 times,which reportedly ranged from 100 to 4μM with an LOD of∼1.7μM.

关键词： biphasic nano-domain supported lipid bilayer fluorogenic polymer reporter liquid-expanded region liquid-condensed domain

Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

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World Journal of Stem Cells 2020年第1期12卷 70-86页

作者： Ok-Hee Kim Ha-Eun hong Haeyeon Seo Bong Jun Kwak Ho Joong Choi Kee-Hwan Kim Joseph ahn Sang Chul Lee Say-june Kim Catholic Central Laboratory of Surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Department of Surgery Division of Hepato-biliary Pancreatic SurgerySeoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Department of Surgery Uijeongbu St.Mary's HospitalCollege of Medicinethe Catholic University of KoreaSeoul 11765South Korea Department of Surgery Daejeon St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 34943South Korea

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its *** To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing *** We collected the secretory materials(named as inducers)released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA)and generated the TAA-induced secretome(TAA-isecretome)after stimulating adipose-derived stem cells with the *** TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial *** TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2)inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase)compared to the naïve secretome infusion in mice with TAA-induced hepatic ***,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized *** analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the *** addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic *** Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant *** results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting agains

关键词： Adipose-derived stem cells Disease-specificity Mesenchymal stem cells Secretome Peroxiredoxin-1 Thioacetamide Toxic hepatic failure

Ameliorating liver fibrosis in an animal model using the secretome released from miR-122-transfected adipose-derived stem cells

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World Journal of Stem Cells 2019年第11期11卷 990-1004页

作者： Kee-Hwan Kim Jae Im Lee Ok-Hee Kim Ha-Eun hong Bong Jun Kwak Ho Joong Choi Joseph ahn Tae Yun Lee Sang Chul Lee Say-june Kim Department of Surgery Uijeongbu St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 11765South Korea Catholic Central Laboratory of Surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Department of Surgery Seoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Department of Surgery Daejeon St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 34943South Korea

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,called secretome,rather than cells,has been evaluated for overcoming the limitations of cell-based therapy,while maintaining its ***,the use of na?ve secretome may not fully satisfy the specificity of each ***,it appears to be more advantageous to use the functionally reinforced secretome through a series of processes involving physico-chemical adjustments or genetic manipulation rather than to the use na?ve *** To determine the therapeutic potential of the secretome released from miR-122-transfected adipose-derived stromal cells(ASCs).METHODS We collected secretory materials released from ASCs that had been transfected with antifibrotic miR-122(MCM)and compared their antifibrotic effects with those of the na?ve secretome(CM).MCM and CM were intravenously administered to the mouse model of thioacetamide-induced liver fibrosis,and their therapeutic potentials were *** MCM infusion provided higher therapeutic potential in terms of:(A)Reducing collagen content in the liver;(B)Inhibiting proinflammatory cytokines;and(C)Reducing abnormally elevated liver enzymes than the infusion of the na?ve *** proteomic analysis of MCM also indicated that the contents of antifibrotic proteins were significantly elevated compared to those in the na?ve *** We could,thus,conclude that the secretome released from miR-122-transfected ASCs has higher antifibrotic and anti-inflammatory properties than the na?ve *** miR-122 transfection into ASCs provides a specific way of potentiating the antifibrotic properties of ASC secretome,it could be considered as an enhanced method for reinforcing secretome effectiveness.

关键词： Adipose-derived stem cells Liver fibrosis MicroRNAs miR-122 Mesenchymal stem cells Secretome

Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection

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World Journal of Gastroenterology 2022年第15期28卷 1548-1562页

作者： Jiyoung Yoon Seung-Yeon Yoo Young Soo Park Kee Don Choi Beom Su Kim Moon-Won Yoo In Seob Lee Jeong Hwan Yook Ga Hee Kim Hee Kyong Na Ji Yong ahn Jeong Hoon Lee Kee Wook Jung Do Hoon Kim Ho june Song Gin Hyug Lee Hwoon-Yong Jung Department of Gastroenterology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Pathology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Surgery Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea

BACKGROUND Although the criteria for the indication of endoscopic submucosal dissection(ESD)for undifferentiated early gastric cancer(UD-EGC)have been recently proposed,accumulating reports on the non-negligible rate of lymph node metastasis(LNM)after indicated ESD raise questions on the reliability of the current *** To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for *** We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center,a tertiary university hospital in *** identify the risk factors of LNM of UDEGC meeting the expanded criteria for ESD,we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:*** reviewed the clinical,endoscopic,and histologic features of the cases to identify features with a significant difference according to the presence of *** and multivariate logistic regression analyses were performed to estimate the odds ratios(ORs).RESULTS Of the 4780 UD-EGC cases,1240(25.9%)were identified to meet the expanded indication for *** the 1240 cases,14(1.1%)cases had *** the various clinical,endoscopic,and histopathological features that were evaluated,mixed histology(tumors consisting of 10%-90%of signet ring cells)had a marginally significant association(P=0.059)with the risk of ***,diffuse blurring of the muscularis mucosae(MM)underneath the tumorous epithelium,a previously unrecognized histologic feature,had a significant association with the absence of LNM(P=0.028).Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM(OR:0.12,95%CI:0.02-0.95;P=0.045).CONCLUSION The risk of LNM is higher than expected when using the current expanded indication for *** evaluation could provide useful clues for reducing the

关键词： Gastric cancer Undifferentiated carcinoma Endoscopic submucosal dissection Lymph node metastasis

Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether

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World Journal of Gastroenterology 2019年第39期25卷 5936-5952页

作者： Dong Do You Suk Joon Cho Ok-Hee Kim Jin Sook Song Kyu-Seok Hwang Sang Chul Lee Kee-Hwan Kim Ho Joong Choi Ha-Eun hong Haeyeon Seo Tae Ho hong Jung Hyun Park Tae Yoon Lee Joseph ahn Jae-Kyung Jung Kwan-Young Jung Say-june Kim Department of Surgery St.Vincent's HospitalCollege of MedicineThe Catholic University of KoreaSeoul 16247South Korea College of Pharmacy Chungbuk National UniversityCheongju 28644South Korea Department of Surgery Seoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Catholic Central Laboratory of Surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Bio and Drug Discovery Division Korea Research Institute of Chemical TechnologyDaejeon 34114South Korea Department of Surgery Daejeon St.Mary's HospitalCollege of Medicinethe Catholic University of KoreaSeoul 34943South Korea Department of Surgery Uijeongbu St.Mary's HospitalCollege of Medicinethe Catholic University of KoreaSeoul 11765South Korea Department of Biomedicine and Health Science College of Medicinethe Catholic University of KoreaSeoul 06591South Korea Department of Surgery Eunpyeong St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 03312South Korea Department of Medicinal Chemistry and Pharmacology University of Science and TechnologyDaejeon 34113South Korea

BACKGROUND The use of methyl-tertiary butyl ether(MTBE)to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic *** adverse effects of MTBE are largely attributed to its low boiling point,resulting in a tendency to ***,if there is a material with a higher boiling point and similar or higher dissolubility than MTBE,it is expected to be an attractive alternative to *** To determine whether tert-amyl ethyl ether(TAEE),an MTBE analogue with a relatively higher boiling point(102°C),could be used as an alternative to MTBE in terms of gallstone dissolubility and *** The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two *** in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control(dimethyl sulfoxide)-treated gallstones,after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented *** The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%,56.5%and 38.75%for cholesterol,mixed,and pigmented gallstones,respectively,which represented a 1.2-,1.4-,and 1.3-fold increase in dissolubility compared to that of *** the in vitro experiment,the 24 h-dissolubility of TAEE was 71.7%and 63.0%for cholesterol and pigmented gallstones,respectively,which represented a 1.4-and 1.9-fold increase in dissolubility compared to that of *** addition,the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than *** We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of *** such,TAEE could present an attractive alternative to MTBE if our findings

关键词： Tert-amyl ethyl ether Gallstones Methyl-tert-butyl ether Contact litholytic agent

Enhancement of Toxic Gas Detecting Ability of Film Type Colorimetric Sensor

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Journal of Materials Science and Chemical Engineering 2016年第1期4卷 40-45页

作者： Sung Yeol Kim Seung Kyun Yoon Jungho ahn Dong june Chung School of Chemical Engineering Sungkyunkwan University Suwon Korea

In this study, we tried to develop the in situ coating methods of hydrophilic polymer solution containing water soluble dye on nonwoven sheet for the colorimetric film sensor. And color change of coated dye according to contact various gas samples (as strong acid and base, chloroform, ammonia and HF) of this dye-coated nonwoven film was examined for the application of chemically toxic materials detecting tools in the actual site of working place without aid of any kinds of detecting devices. By the addition of electron transfer agent (quinone derivatives), quick color change behaviors were observed within 10 seconds under the contact of various toxic gases in general condition(room temperature, 50% humidity).

关键词： Toxic Gas Detection Colorimetric Sensor pH Indicating Dyes Polymer Binder Electron Transfer Reagent

Endoscopic submucosal dissection as alternative to surgery for complicated gastric heterotopic pancreas

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World Journal of Clinical Cases 2020年第20期8卷 4708-4718页

作者： Jin Hee Noh Do Hoon Kim So-Woon Kim Young Soo Park Hee Kyong Na Ji Yong ahn Kee Wook Jung Jeong Hoon Lee Kee Don Choi Ho june Song Gin Hyug Lee Hwoon-Yong Jung Department of Gastroenterology University of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea Department of Pathology University of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND Gastric heterotopic pancreas(GHP)is generally asymptomatic and rarely features complications such as pancreatitis,pseudocysts,gastric outlet obstruction,bleeding,obstructive jaundice,or ***,the treatment of complicated GHP is challenging and often requires surgical *** To investigate the clinical outcomes of endoscopic submucosal dissection(ESD)as alternative to surgical resection for complicated *** This is a single-center,retrospective *** January 2013 and December 2017,a total of 5 patients underwent ESD for complicated GHP at Asan Medical *** who were diagnosed with complicated GHP were treated conservatively as with general practice for acute *** conservative management for resolving the acute phase of pancreatitis,ESD was performed as definitive treatment for complicated *** was performed using the conventional method under conscious *** clinical features of patients and tumors,procedure-related characteristics,and long-term outcomes were *** The age of the 5 patients ranged from 28-43 *** of the patients were *** lesions were located in the greater curvature of the *** endoscopic ultrasonography during the pain episode,all lesions were located across the muscularis mucosa,submucosa,and proper muscle *** median lesion size was 20[interquartile range(IQR),18-35]during the pain episode at the time of the diagnosis of complicated GHP,and 15 mm(IQR,9-33)at the time of ESD after conservative *** procedure time ranged from 15-120 *** were no procedure-related adverse events such as perforation or *** length of hospital stay after the procedure ranged from 2-4 *** patients were symptom free during the median follow-up period of 46.0 mo(IQR,39-60).CONCLUSION ESD appears to be a feasible and effective treatment option for complicated GHP based on the favorable clinical outcomes.

关键词： Endoscopic submucosal dissection Gastric Heterotopic pancreas Pancreatitis

Relationship between Insulin Resistance and Obesity to Serum Prostate-Specific Antigen in Healthy Men

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Relationship between Insulin Resistance and Obesity to Serum...