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The hidden switches undertying RORα-mediated circuits that critically regulate uncontrolled cell proliferation

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Journal of Molecular Cell Biology 2014年第4期8卷 338-348页

作者： Dongkwan shin Ik Soo Kim Ji Min Lee Sung-Young shin Jong-Hoon Lee Sung Hee Baek Kwang-hyun Cho Department of Bio and Brain Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon 305-701 Republic of Korea Department of Biological Sciences Creative Research Initiative Center for Chromatin Dynamics Seoul National University Seou1151-742 Republic of Korea

Prostaglandin E2 （PGE2） is known to have a key role in the development of colorectal cancer, but previous experiments showed its contrasting （i.e. tumor-promoting or tu mor-suppressive） roles depending on experimental conditions. To elucidate the mechanisms underlying such contrasting roles of PG E2 in tumorigenesis, we investigated all the previous experiments and found a new signal transduction pathway mediated by retinoic acid receptor-related orphan receptor （ROR）α, in which PGE2/PKCα-dependent phosphorylation of RORα attenuates Wnt target gene expression in colon cancer ceils. From mathematical simulations combined with biochemical experimentation, we revealed that RORα induces a biphasic response of Wnt target genes to PGE2 stimulation through a regulatory switch formed by an incoherent feedforward loop, which provides a mechanistic explanation on the contrasting roles of PGE2 observed in previous experiments. More interestingly, we found that RORα constitutes another regulatory switch formed by coupled positive and negative feedback loops, which regulates the hysteretic response of Wnt signaling and eventually converts a proliferative cellular state into an anti-proliferative state in a very delicate way. Our results indicate that RORα is the key regulator at the center of these hidden switches that critically regulate cancer celt proliferation and thereby being a promising anti-cancer therapeutic target.

关键词： colorectal cancer Wnt signaling RORα mathematical modeling biphasic response hysteresis systems biology

Free radical scavenger effect of rebamipide in sperm processing and cryopreservation

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Asian Journal of Andrology 2003年第3期5卷 195-201页

作者： Nam Cheol Park hyun Jun Park Kyeong Mi Lee Dong Gil shin Department of Urology College of Medicine Pusan National University Busan 602 739 KoreaDepartment of Urology College of Medicine Pusan National University Busan 602 739 KoreaDepartment of Urology College of Medicine Pusan National University Busan 602 739 KoreaDepartment of Urology College of Medicine Pusan National University Busan 602 739 Korea

Aim: To study the effect of rebamipide added to semen samples and cryoprotectant on reactive oxygen species (ROS) production. Methods: Semen samples from 30 fertile and healthy volunteers were collected by masturbation after 2 days - 3 days of abstinence. After liquefaction, the specimens were diluted with sperm wash media to a uniform density of 20×106/mL. Rebamipide was added to semen samples and cryoprotectant to a final concentration of 10 μmol/L, 30 μmol/L, 100 μmol/L or 300 μmol/L. Specimens were incubated at 37 ℃ in a 0.5 % CO2 incubator for 1 h or cryopreserved at -196 ℃ LN2 for 3 days. The sperm motility and viability and the levels of ROS and lipid peroxidation of sperm membrance were assessed before and after incubation and cryopreservation by means of computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence and thiobarbituric acid assay, respectively. Results: The sperm motility was significantly increased after incubation with 100 μmol/L and 300 μmol/L rebamipide (P0.05). The levels of ROS and lipid peroxidation in semen were significantly decreased in proportion to the concentrations of rebamipide both after incubation and cryopreservation (P<0.05). Conclusion: Rebamipide is an effective free radical scavenger in semen in vitro.

关键词： male infertility reactive oxygen species rebamipide

Plasma skincare device based on floating electrode dielectric barrier discharge

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Plasma Science and Technology 2019年第12期21卷 33-39页

作者： kyu-Hang LEE Sichan KIM hyun JO Byung-Koo SON Myung-Sun shin Guangsup CHO Department of Electrical and Biological Physics Kwangwoon University20 Kwangwoon-RoNowon-GuSeoul 01897Republic of Korea Division of Plasma Convergence R&BD Cheorwon Plasma Research InstituteCheorwon 24047Republic of Korea

A portable skincare plasma-device with a rechargeable battery is presented here. The device comprises two pads made of thin polyimide film as the dielectric layer, namely, the dielectric barrier discharge pad(DBD-pad) for skin-touch and a capacitive ground-pad(G-pad) for hand holding. High AC voltage of approximately 1 kV with frequency of 40 kHz is induced in the DBD-pad that contacts the skin, which serves as the floating electrode, while low voltage is induced on the G-pad. Considering the requirement for impedance matching between the DBDpad capacitance and the inverter along with the need for low skin current less than approximately 5 mA for electrical safety, the electrode area of the DBD-pad is minimized to be smaller than that of the G-pad.

关键词： plasma discharge atmospheric pressure nonthermal plasma skincare device

Liver stiffness and perfusion changes for hepatic sinusoidal obstruction syndrome in rabbit model

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World Journal of Gastroenterology 2020年第7期26卷 706-716页

作者： Jaeseung shin Haesung Yoon Yoon Jin Cha kyunghwa Han Mi-Jung Lee Myung-Joon Kim hyun Joo shin Department of Radiology Severance HospitalResearch Institute of Radiological ScienceYonsei University College of MedicineSeoul 03722South Korea Department of Pathology Gangnam Severance HospitalYonsei University College of MedicineSeoul 06273South Korea Department of Radiology Severance HospitalResearch Institute of Radiological ScienceCenter for Clinical Imaging Data ScienceSeoul 03722South Korea

BACKGROUND Hepatic sinusoidal obstruction syndrome(SOS)is caused by damage to hepatic sinusoidal endothelial cells that results in fibrous obliteration of intrahepatic venules and necrosis of *** the diagnosis is primarily based on nonspecific clinical features and invasive liver ***,noninvasive imaging methods are required for the early diagnosis and severity assessment of hepatic *** To determine the effectiveness of supersonic shear wave imaging(SSI)and dual energy computed tomography(DECT)for diagnosing hepatic SOS using a rabbit *** Among nine New Zealand white rabbits(3-4 kg,male),three in control group ingested normal saline for 20 d and six in the SOS group ingested 6-thioguanine(5 mg/kg/d)for 20 *** stiffness was measured using SSI on days 0,3,10,and *** the same days,liver perfusion was evaluated from virtual monochromatic images of 55 keV and iodine map using *** changes in the liver were assessed using *** pathology scores were compared between the two *** stiffness and perfusion parameters were compared according to the groups,days,and pathology *** Final pathology scores were significantly higher in the SOS than the control group(median 22 vs 2,P=0.024).No gross morphologic changes were seen in *** stiffness,Hounsfield Unit values,and iodine concentrations were higher in the SOS compared to the control group on days 10 and 20(all,P≤0.007).Compared to day 0,liver stiffness and perfusion parameters were higher on day 20 in the SOS group(all,P≤0.001).Correlation coefficients for liver stiffness(r=0.635),Hounsfield Unit values(r=0.587),and iodine concentration(r=0.611)with final pathology scores were positive without significance(all,P>0.05).CONCLUSION Liver stiffness and perfusion parameters were significantly increased in the livers of a rabbit SOS *** and DECT might aid in early diagnosis of hepatic SOS.

关键词： Hepatic sinusoidal obstruction syndrome Elasticity imaging techniques Iodine Computed tomography Liver Animals

Anti-scarring effects of butaprost on human subconjunctival Tenon's fibroblasts

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International Journal of Ophthalmology(English edition) 2017年第7期10卷 1028-1033页

作者： Jong Hoon shin Je hyun Seo Jae Ho Jung Tae Woo Kim Department of Ophthalmology Pusan National University Hospital Department of Ophthalmology Pusan National University Yangsan Hospital Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan Hospital Department of Ophthalmology Seoul National University College of MedicineSeoul National University Bundang Hospital

AIM： To investigate the toxicity of the E-prostanoid 2（EP2） receptor agonist, butaprost against human subconjunctival（Tenon＇s capsule） fibroblasts, and to determine the underlying mechanism. METHODS： We isolated Tenon＇s fibroblasts from the subconjunctival area of healthy subjects and evaluated the types of EP receptors expressed using quantitative realtime reverse transcription polymerase chain reaction（RTPCR）. The toxicity of butaprost against the fibroblasts was evaluated using methyl thiazolyl tetrazolium and lactic dehydrogenase assays. The inhibition of conjunctival fibroblast proliferation by butaprost was assessed by measuring α-actin levels. The underlying mechanism was assessed by measuring intracellular cyclic adenosine monophosphate（c AMP） levels. Intergroup differences were statistically analyzed using an independent t-test. Densitometry of the Western blot bands was performed using the Image J software. RESULTS： Quantitative real-time RT-PCR revealed that the fibroblast EP2 receptor levels were higher than those of the other EP receptors. Butaprost did not show toxicity against Tenon＇s tissue, but inhibited conjunctival fibroblast proliferation by reducing collagen synthesis. EP2 receptor activation enhanced the c AMP cascade, which might be an important mechanism underlying this ***： Butaprost effectively reduces the subconjunctival scarring response. Given the significanceof wound healing modulation in blebs, butaprost＇s inhibitory effect on subconjunctival Tenon＇s fibroblasts may be beneficial in managing postoperative scarring in glaucoma surgery.

关键词： butaprost Tenon's capsule trabeculectomy fibroblasts

Why are children less affected than adults by severe acute respiratory syndrome coronavirus 2 infection?

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Cellular & Molecular Immunology 2022年第5期19卷 555-557页

作者： Chang kyung Kang hyun Mu shin Wan Beom Park Hang-Rae Kim Department of Internal Medicine Seoul National University College of MedicineSeoul03080Republic of Korea Department of Biomedical Sciences Seoul National University College of MedicineSeoul03080Republic of Korea BK21 FOUR Biomedical Science Project Seoul National University College of MedicineSeoul03080Republic of Korea Medical Research Institute Seoul National University College of MedicineSeoul03080Republic of Korea WideRiver Institute of Immunology Seoul National UniversityHongcheon25159Republic of Korea Department of Anatomy&Cell Biology Seoul National University College of MedicineSeoul03080Republic of Korea

An adequate immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial to not only clear the virus but also prevent tissue *** children generally experience a milder course of coronavirus... 详细信息

关键词： respiratory acute infection

In vivo analysis of post-joint-preserving surgery fracture of 3D-printed Ti-6Al-4V implant to treat bone cancer

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Bio-Design and Manufacturing 2021年第4期4卷 879-888页

作者： Jong Woong Park Ye Chan shin hyun Guy Kang Sangeun Park Eunhyeok Seo Hyokyung Sung Im Doo Jung Division of Convergence Technology National Cancer CenterGoyang 10408Republic of Korea Orthopaedic Oncology Clinic National Cancer CenterGoyang 10408Republic of Korea Department of Materials Engineering and Convergence Technology Gyeongsang National UniversityJin-Ju 52828Republic of Korea Department of Mechanical Engineering Ulsan National Institute of Science and TechnologyUNIST-Gil 50Ulsan 44919Republic of Korea

Cancer growth in the bone due to its random shape disables bone strength and thus changes its capacity to support body weight or muscles,which can crucially affect the quality of human life in terms of normal walking or daily *** successful patient recovery,it is necessary to remove the cancer-affected minimal bone area and quickly replace it with a biocompatible metal implant within less than 2 *** electron beam-melted Ti-6Al-4V implant was designed and applied in a patient to preserve the natural knee joint close to the bone *** developed implant fits the bone defect well,and the independent ambulatory function of the natural knee joint was restored in the patient within six weeks after surgery.A delayed fracture occurred six months after the successful replacement of cancer-affected bone with Ti-6Al-4V implant at the proximal meshed junction of the implant because of a minor downward ***,mechanical,and computational analyses were conducted for the fractured area to find the main reason for the delayed *** findings pertaining to the mechanical and material investigation can help realize the safe implantation of the three-dimensionally printed titanium implant to preserve the natural joints of patients with massive bone defects of the extremities.

关键词： 3D printing Bone cancer Titanium alloy implant Electron beam melting Fracture analysis

Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population

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Asian Journal of Andrology 2015年第2期17卷 285-291,I0010页

作者： Jun hyun Han Yong Seong Lee Hae Jong Kim shin Young Lee Soon Chul Myung Department of Urology Hallym University Dongtan Sacred Heart Hospital Hwaseong-si 445-170 Korea Department of Urology Hallym University Kangnam Sacred Heart Hospital Seoul 150-950 Korea Advanced Urogenital Disease Research Center Chung-Ang University College of Medicine Seoul 156-756 Korea Research Institute for Translational System Biomics Chung-Ang University College of Medicine Seoul 156-756 Korea Department of Urology Seoul Medical Center Seoul 131-865 Korea Department of Urology Chung-Ang University Hospital Seou1156-756 Korea.

In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer （PCa） in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 singie-nucleotide polymorphism （SNP） database variants detected, 129 were reported in two Asian groups （Han Chinese and Japanese） in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians （d = 1）, locations （SNPs in exons were preferred）, and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 （Ht-2）（odds ratio [OR], 1.51; 95% confidence interval [Cl], 1.04-2,18） was associated with PCa susceptibility. CYP3A4 Ht-2 （OR. 1.87; 95% CI. 1.02-3.43） was associated with PCa metastatic potential according to tumor stage, rs17115149 （OR： 1.96; 95% Ch 1.04-3.68） and CYP17A1 Ht-4 （OR： 2.01; 95% Ch 1.07-4.11） showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.

关键词： androgens CYP17A1 CYP3A4 CYP3A43 genetics prostatic neoplasms

Memory-centric neuromorphic computing for unstructured data processing

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Nano Research 2021年第9期14卷 3126-3142页

作者： Sang hyun Sung Tae Jin Kim Hera shin Hoon Namkung Tae Hong Im Hee Seung Wang Keon Jae Lee Department of Materials Science and Engineering Korea Advanced Institute of Science and Technology(KAIST)291 Daehak-roYuseong-guDaejeon 34141Republic of Korea

The unstructured data such as visual information,natural language,and human behaviors opens up a wide array of opportunities in the field of artificial intelligence(Al).The memory-centric neuromorphic computing(MNC)has been proposed for the efficient processing of unstructured data,bypassing the von Neumann bottleneck of current computing *** development of MNC would provide massively parallel processing of unstructured data,realizing the cognitive Al in edge and wearable *** this review,recent advances in memory-centric neuromorphic devices are discussed in terms of emerging nonvolatile memories,volatile switches,synaptic plasticity,neuronal models,and memristive neural network.

关键词： neuromorphic computing memory-centric memristor artificial synapses artificial neurons memristive neural network