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Evaluation of the Mrp2-mediated flavonoid-drug interaction potential of quercetin in rats and in vitro models

Asian Journal of Pharmaceutical Sciences 2019年第6期14卷 621-630页

作者： Ju-Hee Oh joo hyun lee Young-joo lee Division of Biopharmaceutics College of PharmacyKyung Hee UniversitySeoul 02447Republic of Korea Department of Life and Nanopharmaceutical Sciences College of PharmacyKyung Hee UniversitySeoul 02447Republic of Korea

Quercetin is a biologically active flavonoid that has been used as a popular health *** is reported that quercetin may cause flavonoid-drug interaction mediated by P-glycoprotein,the most predominant efflux *** this study,we comprehensively evaluated the potential of the pharmacokinetic interaction of quercetin mediated by multidrug resistance-associated protein 2(MRP2),another major efflux ***2-transfected MDCKII cells and LS174T cells were used to evaluate the potential inhibition and induction of MRP2 by quercetin in *** evaluate the induction effect of quercetin on Mrp2 in vivo,Mrp2 mRNA expression in rat liver,kidney,and small intestinal tissues was determined after the oral administration of quercetin(50,100,or 250 mg/kg)for seven ***2-mediated interaction potential was also evaluated by the pharmacokinetic study of phenolsulfonphthalein in rats after single or multiple doses of ***,the effect of quercetin on absorption of docetaxel,a P-glycoprotein and CYP3A4 substrate,was also *** inhibited the function of MRP2 at 10μM and induced the mRNA expression of MRP2 at 50μM in ***,at 100 mg/kg,quercetin markedly increased Mrp2 expression in the small intestine of ***,there was no significant change in phenolsulfonphthalein pharmacokinetics due to single-(50,100,or 250 mg/kg)or multiple-dose(50,100,or 250 mg/kg for seven days)quercetin *** contrast,a significant interaction caused by quercetin(100 mg/kg)was observed in the absorption of *** results suggested that although quercetin modulates the function and expression of MRP2 in vitro,it may have a low potential of Mrp2-mediated interaction and present negligible safety concerns related to the interaction.

关键词： Quercetin P-glycoprotein Multidrug resistance-associated protein 2 Pharmacokinetics Flavonoid-drug interaction

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Jacobsen syndrome with bilateral periventricular white matter lesions

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World Journal of Pediatrics 2022年第2期18卷 142-143页

作者： hyun-joo lee Hae-ln lee Ji-Hoon Na Young-Mock lee Department of Pediatrics Yonsei University College of MedicineSeoulKorea Department of Pediatrics Gangnam Severance HospitalYonsei University College of Medicine21Eonju-roGangnam-guSeoul 06273Korea

A 2-month-old girl presented facial dimorphism,including frontal bossing,hypertelorism,a broad nasal bridge,low-set ears,hypotonia with mild spasticity,and mild *** head circumference was 40.8 cm(75-90 percentile).The... 详细信息

关键词： white ism Jacobsen

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Occult infection related hepatitis B surface antigen variants showing lowered secretion capacity

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World Journal of Gastroenterology 2015年第6期21卷 1794-1803页

作者： Hong Kim Seoung-Ae lee You-Sub Won hyun joo lee Bum-joon Kim Department of Biomedical Sciences Microbiology and Immunology and Liver Research Institute Seoul National University College of Medicine

AIM:To elucidate the molecular mechanisms underlying hepatitis B virus(HBV)occult infection of genotype ***:A total of 10 types of hepatitis B surface antigen(HBs Ag)variants from a Korean occult cohort were *** a complete HBV genome plasmid mutated such that it does not express HBs Ag and plasmid encoding,each HBs Ag variant was transiently co-transfected into Hu H-7 *** secretion capacity and intracellular expression of the HBV virions and HBs Ags in their respective variants were analyzed using real-time quantitative polymerase chain reaction assays and commercial HBs Ag enzyme-linked immunosorbent assays,***:All variants exhibited lower levels of HBs Ag secretion into the medium compared with the wild *** particular,in eight of the ten variants,very low levels of HBs Ag secretion that were similar to the negative control were *** contrast,most variants(9/10)exhibited normal virion secretion capacities comparable with,or even higher than,the wild *** provided new insight into the intrinsic nature of occult HBV infection,which leads to HBs Ag sero-negativeness but has horizontal ***,most variants generated higher reactive oxidative species production than the wild *** finding provides potential links between occult HBV infection and liver disease ***:The presently obtained data indicate that deficiency in the secretion capacity of HBs Ag variants may have a pivotal function in the occult infections of HBV genotype C.

关键词： Occult infection Hepatitis B virus Hepatitis B sur

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The Phytophthora nucleolar effector Pi23226 targets host ribosome biogenesis to induce necrotrophic cell death

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Plant Communications 2023年第5期4卷 263-276页

作者： Soeui lee Jaehwan Kim Myung-Shin Kim Cheol Woo Min Sun Tae Kim Sang-Bong Choi joo hyun lee Doil Choi Plant Immunity Research Center Seoul National UniversitySeoul 08826Republic of Korea Plant Genomics and Breeding Institute Department of AgricultureForestry and BioresourcesCollege of Agriculture and Life ScienceSeoul National UniversitySeoul 08826Republic of Korea Interdisciplinary Programs in Agricultural Genomics College of Agriculture and Life ScienceSeoul National UniversitySeoul 08826Republic of Korea Department of Plant Bioscience Life and Industry Convergence Research InstitutePusan National UniversityMiryang 50463Republic of Korea Division of Bioscience and Bioinformatics Myongji UniversityYongin 449-728Republic of Korea

Pathogen effectors target diverse subcellular organelles to manipulate the plant immune *** the nucleolus has emerged as a stress marker and several effectors are localized in the nucleolus,the roles of nucleolar-targeted effectors remain *** this study,we showed that Phytophthora infestans infection of Nicotiana benthamiana results in nucleolar inflation during the transition from the biotrophic to the necrotrophic *** *** effectors were localized in the nucleolus:Pi23226 induced cell death in *** and nucleolar inflation similar to that observed in the necrotrophic stage of infection,whereas its homolog Pi23015 and a deletion mutant(Pi23226DC)did not induce cell death or affect nucleolar *** immunoprecipitation and individual-nucleotide-resolution UV crosslinking and immunoprecipitation sequencing analysis indicated that Pi23226 bound to the 30 end of 25S rRNA precursors,resulting in accumulation of unprocessed 27S *** nucleolar stress marker NAC082 was strongly upregulated under Pi23226-expressing ***23226 subsequently inhibited global protein translation in host cells by interacting with ***23226 enhanced *** pathogenicity,indicating that Pi23226-induced ribosome malfunction and cell death were beneficial for pathogenesis in the *** results provide evidence for the molecular mechanism underlying RNA-binding effector activity in host ribosome biogenesis and lead to new insights into the nucleolar action of effectors in pathogenesis.

关键词： Phytophthora infestans hemibiotroph nucleolar effector cell death ribosome biogenesis translation inhibition

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Vertical graphene on flexible substrate,overcoming limits of crack-based resistive strain sensors

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npj Flexible Electronics 2022年第1期6卷 28-35页

作者： Hong Ryeol Na hyun joo lee Jae Ho Jeon Han-Jin Kim Sahng-Kyoon Jerng Sanjib Baran Roy Seung-hyun Chun Sunghun lee Yong Ju Yun Department of Physics and Astronomy Sejong UniversitySeoul 05006Korea Graduate School of Energy and Environment(KU-KIST Green School) Korea UniversitySeoul 02841Korea Center for Energy Materials Research Korea Institute of Science and TechnologySeoul 02792Korea Graphene Research Institute Sejong UniversitySeoul 05006Korea

Resistive strain sensors(RSS)with ultrasensitivity have attracted much attention as multifunctional ***,since most ultrasensitive RSS are designed by cracked conductive metals,the sensing performance is severely degraded due to accumulated structural deformation with consecutive *** overcome such limitation,newly designed structures have been suggested,but the development of mechanosensors exhibiting superior stability and ultrasensitivity still remains a ***,we demonstrate that vertical graphene(VG)RSS with high sensitivity(gauge factor greater than 5000),remarkable durability(>10,000 cycles),and extraordinary resilience can serve multifunctional *** find that well-defined cracks on tufted network structure result in highly reversible resistance variation,especially revivable status even after broken current path,confirmed by microscopic in situ *** VG integrated with a wireless sensing system exhibits excellent timbre recognition *** findings provide inspirable insights for mechanosensing system,making VG a promising component for future practicable flexible sensor technologies.

关键词： strain durability Vertical

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Expression of protein S100A4 is a predictor of recurrence in colorectal cancer

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World Journal of Gastroenterology 2010年第31期16卷 3897-3904页

作者： Jung Myun Kwak hyun joo lee Seon Hahn Kim Han Kyeom Kim Young Jae Mok Young Tae Park Jong Sang Choi Hong Young Moon Department of Surgery Korea University Anam Hospital Department of Pathology Korea University Guro Hospital Department of Surgery Korea University Guro Hospital Department of Gastroenterology Korea Uni-versity Guro Hospital

AIM: To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. METHODS: A cohort of archival formalin-fixed paraff inembedded specimens was selected from 127 patients with colorectal cancer who underwent surgical resection between April 2000 and March 2004 at the Department of Surgery, Korea University Guro Hospital. The expression of protein S100A4 was evaluated according to the proportion of positively stained cancer cells. In each case, three core biopsies with a diameter of 2 mm were punched out and positioned in a recipient paraff in array block. Four-μm sections of these tissue array blocks were used for immunohistochemical analysis of protein S100A4, E-cadherin, and p53. Clinicopathological data were based on the original histopathologic reports and clinical records of patients. RESULTS: In normal colorectal mucosa, protein S100A4 immunoreactivity was clearly absent in both cytoplasm and nucleus. However, positive immunoreactivity of protein S100A4 was detected in 45 (35.4%) of the tumor cases. There was no significant association between positive immunoreactivity of protein S100A4 and clinicopathological parameters such as tumor differentiation or TNM stage, and also no correlation between the reactivity and E-cadherin or p53 expression. However, positive immunoreactivity of protein S100A4 was found to be associated with tumor recurrence (P = 0.004), and was also associated with significantly worse overall survival in the Kaplan-Meyer survival analysis (P = 0.044). After adjustment for tumor differentiation, tumor depth and nodal status, however, it failed to achieve statistical significance (P = 0.067). CONCLUSION: The expression of protein S100A4 is associated with tumor recurrence and poor overall survival in patients with colorectal cancer.

关键词： S100A4 E-cadherin p53 Prognostic factor Colorectal cancer

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Small but big leaps towards neuroglycomics:exploring N-glycome in the brain to advance the understanding of brain development and function

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Neural Regeneration Research 2024年第3期19卷 489-490页

作者： Boyoung lee hyun joo An Center for Cognition and Sociality Institute for Basic Science(IBS)DaejeonSouth Korea Asia-Pacific Glycomics Reference Site DaejeonSouth Korea Graduate School of Analytical Science&Technology Chungnam National UniversityDaejeonSouth Korea

Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic *** these,protein glycosylation is one of the most prevalent forms of post-translational modification,playing a crucial role in biological *** more than ten monosaccharides identified within mammalian brain cells and more than 1×1012 possible combinations,the heterogeneity of glycosylation is extensive(Conroy et al.,2021).The diversity of glycans and the complexity of their structures allow for a wide range of protein functions.N-glycans are one of the most abundant forms of glycans and are involved in various cellular functions.N-glycans can be added to proteins at specific sequons,Asn-X-Ser/Thr,and are classified into three main types in mature glycoproteins:high mannose,complex,and *** mannose N-glycans consist of 5-9 mannose residues linked to a chitobiose core and undergo processing into complex or hybrid forms in the Golgi apparatus(Varki et al.,2017).Complex N-glycans are more diverse and contain various branched structures such as antennae with fucose,galactose,and sialic acid *** N-glycans contain one or more complex branches in conjunction with an oligomannose branch(Fisher and Ungar,2016).Understanding the specific functions of these different types of N-glycans in protein regulation,folding,and function is an active area of research in the life sciences,including glycobiology.

关键词： functions function apparatus

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Evolution of nonmetallic inclusions in 80-t 9CrMoCoB large-scale ingots during electroslag remelting process

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International Journal of Minerals,Metallurgy and Materials 2024年第7期31卷 1525-1539页

作者： Shengchao Duan Min joo lee Yao Su Wangzhong Mu Dong Soo Kim joo hyun Park School of Mechanical and Materials Engineering North China University of TechnologyBeijing 100144China Department of Materials Science and Chemical Engineering Hanyang UniversityAnsan 15588Rep.of Korea Department of Materials Science and Engineering KTH Royal Institute of TechnologyBrinellvägen 23Stockholm 10044Sweden Department of Engineering Science and Mathematics Division of Materials ScienceLuleåUniversity of Technology97187 LuleåSweden Casting&Forging Business Unit Nuclear Business GroupDoosan EnerbilityChangwon 51711Rep.of Korea

In combination with theoretical calculations,experiments were conducted to investigate the evolution behavior of nonmetallic inclusions(NMIs)during the manufacture of large-scale heat-resistant steel ingots using 9CrMoCoB heat-resistant steel and CaF_(2)–CaO–Al_(2)O_(3)–SiO_(2)–B_(2)O_(3)electroslag remelting(ESR)-type slag in an 80-t industrial ESR *** main types of NMI in the consumable electrode comprised pure alumina,a multiphase oxide consisting of an Al_(2)O_(3)core and liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO shell,and M_(23)C_(6)carbides with an MnS *** Al_(2)O_(3)and MnS inclusions had higher precipitation temperatures than the M_(23)C_(6)-type carbide under equilibrium and nonequilibrium solidification ***,inclusions can act as nucleation sites for carbide layer *** ESR process completely removed the liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO oxide and MnS inclusion with a carbide shell,and only the Al_(2)O_(3)inclusions and Al_(2)O_(3)core with a carbide shell occupied the remelted *** M_(23)C_(6)-type carbides in steel were determined as Cr_(23)C_(6)based on the analysis of transmission electron microscopy *** substitution of Cr with W,Fe,or/and Mo in the Cr_(23)C_(6)lattice caused slight changes in the lattice parameter of the Cr_(23)C_(6)***,Cr_(21.34)Fe_(1.66)C_(6),(Cr_(19)W_(4)C_(6),Cr_(18.4)Mo_(4.6)C_(6),and Cr_(16)Fe_(5)Mo_(2)C_(6)can match the fraction pattern of Cr_(23)C_(6)*** Al_(2)O_(3)inclusions in the remelted ingot formed due to the reduction of CaO,SiO_(2),and MnO components in the liquid *** increased Al content in liquid steel or the higher supersaturation degree of Al_(2)O_(3)precipitation in the remelted ingot than that in the electrode can be attributed to the evaporation of CaF_(2)and the increase in CaO content in the ESR-type slag.

关键词： nonmetallic inclusion heat-resistant steel electroslag remelting M_(23)C_(6) carbide MnS inclusion supersaturation degree

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Periportal thickening on magnetic resonance imaging for hepatic fibrosis in infantile cholestasis

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World Journal of Gastroenterology 2020年第21期26卷 2821-2830页

作者： Myung Hwan lee hyun joo Shin Haesung Yoon Seok joo Han Hong Koh Mi-Jung lee Department of Radiology Severance HospitalSeverance Pediatric Liver Disease Research GroupResearch Institute of Radiological ScienceYonsei University College of MedicineSeoul 03722South Korea Department of Surgery Severance HospitalSeverance Pediatric Liver Disease Research GroupYonsei University College of MedicineSeoul 03722South Korea Division of Gastroenterology Hepatology and NutritionDepartment of PediatricsSeverance Children’s HospitalSeverance Pediatric Liver Disease Research GroupYonsei University College of MedicineSeoul 03722South Korea

BACKGROUND Untreated neonatal cholestasis can progress to liver cirrhosis and end stage liver disease in infancy due to prolonged hepatocyte and biliary tree injury and may require liver ***,non-invasive evaluation of hepatic fibrosis is important in infants with *** To investigate the usefulness of periportal thickening(PT)measured on liver magnetic resonance imaging(MRI)for the assessment of hepatic fibrosis in infants with cholestasis including biliary atresia(BA).METHODS This retrospective study included infants less than 6 mo who underwent liver MRI and biopsy for the evaluation of infantile *** and spleen size were measured on *** assessment was based on aspartate transaminase to platelet ratio index(APRI).The grade of histopathologic fibrosis was assessed by the METAVIR grading *** and diagnostic performance of PT,normalized spleen size ratio(SR,using the upper normal size limit),and APRI for diagnosing hepatic fibrosis were obtained by receiveroperating characteristic(ROC)curve *** A total of 155 patients were included,110 of which were diagnosed with *** age at the time of MRI was 57.6±34.4 *** were positive correlations between fibrosis grade and PT and SR,even after adjusting age(all,P<0.001).For the diagnosis of significant fibrosis(METAVIR grade F2-F4),the area under the ROC curve was 0.899(95%CI:0.840–0.941)for PT(cutoff,4.2 mm),which was higher than 0.741(95%CI:0.664–0.808)for SR and 0.712(95%CI:0.634–0.782)for APRI(both,P<0.001).For the diagnosis of cirrhosis(F4),the area under the ROC curve was the highest with SR as 0.790(95%CI:0.718–0.852).CONCLUSION Liver MRI findings of PT and SR are useful to assess clinically significant hepatic fibrosis(F2 and higher)in infants with cholestasis including BA.

关键词： Infants Cholestasis Biliary atresia Liver Fibrosis Magnetic resonance imaging

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Effect of CaF2 content in refining slag on formation behavior of spinel inclusion in Ni-Cr-V-alloyed special steel

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Journal of Iron and Steel Research International 2018年第2期25卷 157-163页

作者： Jae-hong Shin joo-hyun Park Department of Materials Engineering Hanyang UniversityAnsan 426-791 Korea

The influence of CaF2 content on the formation behavior of spinel inclusions in the Ni-Cr-V-alloyed special steel was presented. The spinel was not formed at CaF2 content lower than 10 wt%. However, it was formed at early stage when the CaF2 content was greater than 30 wt%, followed by a modification to the aluminosilicate-type inclusions. Because the slag was saturated by MgO, the activity of MgO was unity irrespective of CaF2 content in the slag. Thus, Mg was transferred from slag to metal phase. Mg transferred to molten steel reacted with Al2O3-rich inclusions to form ***2O3 spinel. However, the spinel inclusion was modified to aluminosilicate-type inclusions by the reaction with Si and Ca transferred from slag to molten steel about 2-3 h later.

关键词： Spinel inclusion Refining slag CaF2 content Ni-Cr-V-alloyed special steel

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