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Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

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Nano Research 2017年第8期10卷 2743-2760页

作者： Dong-Wan kang Chi kyung Kim Han-Gil Jeong Min Soh Taeho Kim In-Young Choi SeuI-Ki Ki Do Yeon Kim Wookjin Yang Taeghwan Hyeon Seung-Hoon Lee Laboratory of Innovative Nanobiotechnology Biomedical Research Institute Seoul National University Hospital Seoul 03080 Republic of Korea Department of Neurology Seoul National University Hospital Seou103080 Republic of Korea Department of Neurology Korea University Guro Hospital and Korea University College of Medicine Seou108308 Republic of Korea Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 151-742 Republic of Korea School of Chemical and Biological Engineering and Institute of Chemical Processes Seoul National University Seoul 151-742 Republic of Korea

Intracerebral hemorrhage （ICH） is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles （CeNPs） are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol （PEG） to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood-brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.

关键词： ceria nanoparticles intracerebral hemorrhage free radical injury anti-inflammation neuroprotective agents biomedical application

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Enhancement of liposomal stability and cellular drug uptake by incorporating tributyrin into celecoxib-loaded liposomes

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Asian Journal of Pharmaceutical Sciences 2013年第2期8卷 128-133页

作者： Sung Nam kang Soon-Seok Hong Soo-Yeon Kim Heungchan Oh Mi-kyung Lee Soo-Jeong Lim Department of Bioscience and Biotechnology Sejong University98 Kunja-dongKwangjin-guSeoul 143-747Republic of Korea Hanil High School GongjuChungchungnam-Do 314-714Republic of Korea College of Pharmacy Woosuk UniversityWanju-gunJeollabuk-Do 565-701Republic of Korea

Tributyrin,a triglyceride analog of short chain fatty acid butyrate,can act as a prodrug of an anticancer agent *** view of other reports that demonstrated the improved characteristics of conventional liposomes by incorporating small amount of nonphospholipids such as Tween 80,herein we sought to investigate whether the incorporation of tributyrin into the liposomal layers may provide additional advantages for liposomes as an anticancer drug *** were prepared with dimyristoylphosphatidylcholine as a main phospholipid with or without addition of *** was loaded in liposomes as a model anticancer *** 80-incorporated liposomes were also prepared for ***-incorporated liposomes were ineffective in enhancing the skin permeation of celecoxib compared to Tween 80-incorporated ***,tributyrin-incorporated liposomes enhanced the entrapped celecoxib concentration to an extent comparable to Tween 80-incorporated ***,tributyrin-incorporated liposomes exhibited much higher stability compared to Tween 80-incorporated ***,the cellular uptake of celecoxib loaded in tributyrin-incorporated liposomes into mouse melanoma cells were more than 10-fold higher compared to that loaded in conventional-and Tween 80-incorporated *** together,the incorporation of tributyrin into conventional liposomes loaded with anticancer drugs may provide an advanced anticancer drug carrier delivering both drug and tributyrin.

关键词： Tributyrin Liposomes Celecoxib Cancer Formulation

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Changes of tear film lipid layer thickness by 3% diquafosol ophthalmic solutions in patients with dry eye syndrome

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International Journal of Ophthalmology(English edition) 2019年第10期12卷 1555-1560页

作者： Dong-Hyun kang Yong-Woo Lee Kyu-Yeon Hwang kyung-Min Koh Young-A Kwon Byung-Yeop Kim Sang-Wroul Song Kook-Young Kim Myung-Gok Eye Research Institute Department of Ophthalmology Kim’s Eye Hospital Konyang University College of Medicine

AIM: To evaluate the quantitatively changes in lipid layer thickness(LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants(32 males, 92 females;mean age, 28.9 y) diagnosed with dry eye disease(DED) received topical instillation of 4 ophthalmic solutions in one eye: diquafosol, normal saline, 0.1% sodium hyaluronate and 0.3% gatifloxacin, in a masked manner. LLT was measured using an interferometer at baseline and 20 min after the instillation of each ophthalmic ***: Changes of LLT after instillation(nm, mean± standard error) were as follows: 12.6±2.0 for diquafosol(P<0.001), 1.2±2.2 for normal saline(P=0.301), 1.5±2.0 for hyaluronate(P=0.495), and 0.5±3.2 for gatifloxacin(P=0.884).CONCLUSION: Topical instillation of diquafosol increases tear film LLT in DED patients. Diquafosol 3% eye drop might be effective treatment option of evaporative DED with meibomian gland dysfunction.

关键词： diquafosol ophthalmic solutions dry eye syndrome tear film lipid layer thickness

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Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis:Cross-sectional imaging evaluation

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World Journal of Gastroenterology 2011年第43期17卷 4757-4771页

作者： Nam kyung Lee Suk Kim Hyun Sung Kim Tae Yong Jeon Gwang Ha Kim Dong Uk Kim Do Youn Park Tae Un Kim Dae Hwan kang Department of Radiology Pusan National University Hospital Medical Research Institute Pusan National University School of Medicine Pusan National University Department of Surgery Pusan National University Hospital Department of Internal Medicine Pusan National University Hospital Department of Pathology Pusan National University Hospital Department of Radiology Yangsan Pusan National University Hospital Medical Research Institute Pusan National University School of Medicine Department of Internal Medicine Yangsan Pusan National University Hospital

Various mucin-producing neoplasms originate in different abdominal and pelvic *** neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging *** carcinoma,in which at least 50%of the tumor is composed of large pools of extracellular mucin and columns of malignant cells,is associated with a worse *** ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the *** prognosis is also generally *** contrast,intraductal papillary mucinous neoplasm of the bile duct and pancreas,which is characterized by proliferation of ductal epithelium and variable mucin production,has a better prognosis than other malignancies in the pancreaticobiliary *** modalities play a critical role in differentiating mucinous from non-mucinous *** to high water content,mucin has a similar appearance to water on ultrasound(US) ,computed tomography(CT) ,and magnetic resonance imaging,except when thick and proteinaceous,and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US,hyperdense on CT,and hyperintense on T1and hypointense on T2-weighted images,compared to ***,knowledge of characteristic mucin imaging features is helpful to diagnose various mucinproducing neoplastic conditions and to facilitate appropriate treatment.

关键词：恶性肿瘤生产条件黏液性影像学腹部横断面计算机断层扫描评价

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A simple, flexible and high-throughput cloning system for plant genome editing via CRISPR-Cas system

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Journal of Integrative Plant Biology 2016年第8期58卷 705-712页

作者： Hyeran Kim Sang-Tae Kim Jahee Ryu Min kyung Choi Jiyeon Kweon Beum-Chang kang Hyo-Min Ahn Suji Bae Jungeun Kim Jin-Soo Kim Sang-Gyu Kim Center for Genome Engineering Institute for Basic Science Department of Chemistry Seoul National University

CRISPR-Cas9 system is now widely used to edit a target genome in animals and plants. Cas9 protein derived from Streptococcus pyogenes（Sp Cas9） cleaves double-stranded DNA targeted by a chimeric single-guide RNA（sg RNA）. For plant genome editing, Agrobacterium-mediated T-DNA transformation has been broadly used to express Cas9 proteins and sg RNAs under the control of Ca MV 35 S and U6/U3 promoter, respectively. We here developed a simple and high-throughput binary vector system to clone a 19 20 bp of sg RNA, which binds to the reverse complement of a target locus, in a large T-DNA binary vector containing an Sp Cas9 expressing cassette. Twostep cloning procedures：（1） annealing two target-specific oligonucleotides with overhangs specific to the Aar I restriction enzyme site of the binary vector; and（2） ligating the annealed oligonucleotides into the two Aar I sites of the vector, facilitate the high-throughput production of the positive clones. In addition, Cas9-coding sequence and U6/U3 promoter can be easily exchanged via the GatewayTMsystem and unique Eco RI/Xho I sites on the vector, respectively. We examined the mutation ratio and patterns when we transformed these constructs into Arabidopsis thaliana and a wild tobacco, Nicotiana attenuata. Our vector system will be useful to generate targeted large-scale knock-out lines of model as well as non-model plant.

关键词： Aar I-mediated sg RNA cloning CRISPR-Cas9 T-DNA binary vector Exchangeable U6/U3 promoter Gateway compatible Cas9 cloning

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Anti-angiogenic effects of the water extract of HangAmDan(WEHAD),a Korean traditional medicine

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Science China(Life Sciences) 2011年第3期54卷 248-254页

作者： BANG Ji-Young KIM kyung-Soon KIM Eung-Yoon YOO Hwa-Seung LEE Yeon-Weol CHO Chong-Kwan CHOI YoungJin JEONG Hyun-Ja kang In-Cheol InnoPharmasceen Inc. Hoseo UniversityAsan 336-795Republic of Korea East-West Cancer Center Dunsan Oriental Medical Hospital of Daejeon UniversityDaejeon 302-122Republic of Korea BioChip Research Center Hoseo UniversityAsan 336-795Republic of Korea Department of Biological Science College of Natural ScienceHoseo UniversityAsan 336-795Republic of Korea

We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD),which is a crude extract of nine Korean medicinal substances of animal and plant *** human umbilical vein endothelial cells,WEHAD significantly inhibited bFGF-induced proliferation,adhesion,migration,and capillary tube *** used an antibody array to perform an analysis of signaling proteins,which showed up-regulated expression of various proteins including RAD51,RAD52,and p73,and down-regulated expression of *** vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD was markedly reduced in length compared with a PBS-treated control *** results suggest that inhibition of angiogenesis by WEHAD may be the mechanism of action for the anti-cancer effects of HAD.

关键词：抗血管生成粗提取物传统医学韩国脐静脉内皮细胞鸡胚绒毛尿囊膜血管生成抑制水

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Actinomycosis of the appendix mimicking appendiceal tumor:A case report

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World Journal of Gastroenterology 2010年第3期16卷 395-397页

作者： Sang-Yun Lee Hee-Jin Kwon Jin-Han Cho Jong-Young Oh kyung-Jin Nam Jin-Hwa Lee Seong-Kuk Yoon Myong-Jin kang Jin-Sook Jeong Department of Radiology Dong-A University Hospital Department of Pathology Dong-A University Hospital

Actinomycosis is an uncommon chronic infectious disease. Common sites of involvement include the cervicofacial, thoracic and abdominopelvic regions. In abdominopelvic actinomycosis, the ileocecal region, including the appendix, is the most commonly involved site. In some reports, limited appendiceal actinomycosis has revealed a thickened appendiceal wall with peri-appendiceal inflammation as acute appendicitis or perforated appendicitis. We experienced pathologically confirmed intraluminal limited appendiceal actinomycosis without peri-appendiceal infiltration. Here, we report the computed tomography and ultrasound findings.

关键词： Actinomyces Actinomycosis Appendiceal neoplasms Appendicitis

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Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B

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World Journal of Gastroenterology 2023年第24期29卷 3843-3854页

作者： Yewan Park Danbee kang Dong Hyun Sinn Hyunsoo Kim Yun Soo Hong Juhee Cho Geum-Youn Gwak Department of Internal Medicine Kyung Hee University HospitalSeoul 02447South Korea Department of Digital Health SAIHSTSungkyunkwan UniversitySeoul 06355South Korea Department of Clinical Research Design and Evaluation SAIHSTSungkyunkwan UniversitySeoul 06355South Korea Center for Clinical Epidemiology Samsung Medical CenterSungkyunkwan UniversitySeoul 06351South Korea Department of Medicine Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Departments of Epidemiology and Medicine and Welch Center for PreventionEpidemiology and Clinical ResearchJohns Hopkins Medical InstitutionsBaltimoreMD 21287United States

BACKGROUND Research exploring the influence of healthier lifestyle modification(LSM)on the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB)is *** To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational *** Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1,2009,and December 31,2017,those aged≥20 years who drank alcohol,smoked cigarettes,and were sedentary were *** included at least one LSM,including alcohol abstinence,smoking cessation,and regular *** primary outcome was HCC development,and the secondary outcome was liver-related *** used 2:1 propensity score matching to account for *** With 48766 patients in the LSM group and 103560 in the control group,the adjusted hazard ratio(HR)for incident HCC and liver-related mortality was 0.92[95%confidence interval(CI):0.87-0.96]and 0.92(95%CI:0.86-0.99)in the LSM group,respectively,compared with the control *** the LSM group,the adjusted HR(95%CI)for incident HCC was 0.84(0.76-0.94),0.87(0.81-0.94),and 1.08(1.00-1.16)for alcohol abstinence,smoking cessation,and regular exercise,*** adjusted HR(95%CI)for liver-related mortality was 0.92(0.80-1.06),0.81(0.72-0.91),and 1.15(1.04-1.27)for alcohol abstinence,smoking cessation,and regular exercise,*** LSM lowered the risk of HCC and mortality in patients with ***,active LSM,particularly alcohol abstinence and smoking cessation,should be encouraged in patients with CHB.

关键词： Lifestyle modification Chronic hepatitis B Hepatocellular carcinoma Cancer Mortality

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Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage

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Nano Research 2018年第7期11卷 3582-3592页

作者： Bong Geun Cha Han-Gil Jeong Dong-Wan kang Myong-Joo Nam Chi kyung Kim Do Yeon Kim In-Young Choi Seul Ki Ki Song I Kim Ju hee Han Jaeyun Kim Seung-Hoon Lee School of Chemical Engineering Sungkyunkwan University Suwon 16419 Republic of Korea Department of Laboratory of Innovative Nanobiotechnology Biomedical Research Institute Seoul National University Hospital 101 Daehak-ra Jongno-gu Seou103080 Republic of Korea Department of Neurology Seoul National University Hospital 101 Daehak-ro Jongno-gu Seou103080 Republic of Korea Department of Neurology Korea University Guro Hospital and Korea University College of Medicine Seoul 08308 Republic of Korea Department of Health Sdences and Technology Samsung Advanced Institute for Health Science & Technology (SAIHST) Sungkyunkwan University Suwon 16419 Republic of Korea Biomedical Institute for Convergence at SKKU (BICS) Sungkyunkwan University Suwon 16419 Republic of Korea

Intracerebral hemorrhage （ICH）, caused by the sudden rupture of an artery within the brain, is a devastating subtype of stroke, which currently has no effective treatment. Intense inflammatory reactions that occur in the peri-hematomal area after ICH are more deleterious than the hematoma itself, resulting in subsequent brain edema and neurologic deterioration. Thus, we developed lipid-coated magnetic mesoporous silica nanoparticles doped with ceria nanoparticles （CeNPs）, abbreviated as LMCs, which have both potent anti-inflammatory therapeutic effects via scavenging reactive oxygen species and help in increasing the efficacy of magnetic resonance imaging enhancement in the peri-hematomal area. LMCs consist of mesoporous silica nanopartide-supported lipid bilayers, which are loaded with large amounts of CeNPs for scavenging of reactive oxygen species, and iron oxide nanoparticles for magnetic resonance imaging contrast. LMCs loaded with CeNPs exhibited strong anti-oxidative and anti-inflammatory activities in vitro. In the rodent ICH model, intracerebraUy injected LMCs reached the peri-hematomal area and were engulfed by macrophages, which were clearly visualized by magnetic resonance imaging of the brain. Moreover, LMCs reduced inflammatory macrophage infiltration, and thus significantly reduced brain edema. Finally, LMC treatment markedly improved neurologic outcomes of the animals with ICH. Thus, LMC is the first nanobiomaterial that successfully showed theragnostic effects in ICH.

关键词： magnetic mesoporous silica nanoparticle ceria nanoparticles intracerebral hemorrhage reactive oxygen species therapeutics imaging

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Handheld endomicroscope using a fiber-optic harmonograph enables real-time and in vivo confocal imaging of living cell morphology and capillary perfusion

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Microsystems & Nanoengineering 2020年第1期6卷 449-459页

作者： kyungmin Hwang Yeong-Hyeon Seo Daniel YKim Jinhyo Ahn Soyoung Lee kyung Hee Han Koun-Hee Lee Sangyong Jon Pilhan Kim Kate EYu Hyungsin Kim Shin-Hyuk kang Ki-Hun Jeong Department of Bio and Brain Engineering KAIST and KAIST Institute of Health Science and TechnologyDaejeon 34141Republic of Korea Graduate School of Nanoscience and Technology KAIST and KAIST Institute of Health Science and TechnologyDaejeon 34141Republic of Korea Department of Biological Sciences KAIST and KAIST Institute for the BioCenturyDaejeon 34141Republic of Korea Hyunjoo In-Tech Seoul 08390Republic of Korea VPIX Medical IncDeajeon 34141Republic of Korea Graduate School of Medical Science and Engineering Daejeon 34141Republic of Korea Department of Neurosurgery Korea University Anam HospitalKorea University MedicineSeoul 02842Korea

Confocal laser endomicroscopy provides high potential for noninvasive and in vivo optical biopsy at the cellular ***,we report a fully packaged handheld confocal endomicroscopic system for real-time,high-resolution,and in vivo cellular imaging using a Lissajous scanning fiber-optic *** endomicroscopic system features an endomicroscopic probe with a fiber-optic harmonograph,a confocal microscope unit,and an image signal *** fiber-optic harmonograph contains a single mode fiber coupled with a quadrupole piezoelectric tube,which resonantly scans both axes at~1 kHz to obtain a Lissajous *** fiber-optic harmonograph was fully packaged into an endomicroscopic probe with an objective *** endomicroscopic probe was hygienically packaged for waterproofing and disinfection of medical instruments within a 2.6-mm outer diameter stainless tube capable of being inserted through the working channel of a clinical *** probe was further combined with the confocal microscope unit for indocyanine green imaging and the image signal processor for high frame rate and high density Lissajous *** signal processing unit delivers driving signals for probe actuation and reconstructs confocal images using the auto phase matching process of Lissajous fiber *** confocal endomicroscopic system was used to successfully obtain human in vitro fluorescent images and real-time ex vivo and in vivo fluorescent images of the living cell morphology and capillary perfusion inside a single mouse.

关键词： fiber processor confocal

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