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A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1093-1109页

作者： Sae-Bom Yoon Hyowon Hong hee-Jong lim Ji Hye Choi Yoon Pyo Choi Seong Wook Seo Hyuk Woo Lee Chong Hak Chae Woo-Kyu Park Hyun Young Kim Daeyoung Jeong Tran Quang De Chang-Seon Myung heeyeong Cho Therapeutics&Biotechnology Division Korea Research Institute of Chemical TechnologyYuseong-guDaejeon 34114Republic of Korea Department of Pharmacology Chungnam National University College of PharmacyYuseong-guDaejeon 34134Republic of Korea Future Medicine Co. Ltd.Rm616 LH-Business Growth CenterSeongnamGyeonggido 13449Republic of Korea Department of Chemistry College of Natural SciencesCan Tho UniversityCan Tho city 9000Viet Nam

Interleukin-1 receptor-associated kinase 4(IRAK4)is a pivotal enzyme in the Toll-like receptor(TLR)/MYD88 dependent signaling pathway,which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL).Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of ***,proviral integration site for Moloney murine leukemia virus 1(PIM1)functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib *** developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in *** rheumatoid arthritis mouse models,treatment with KIC-0101 significantly ameliorated cartilage damage and ***-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in *** addition,KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 *** results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

关键词： Drug discovery IRAK4 PIM1 NF-κB pathway Rheumatoid arthritis ABC-DLBCL Ibrutinib resistance Dual inhibitor

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Environmental Benefit to Enhance the Dust Filtration in a Subway Ventilation Chamber

Environmental Benefit to Enhance the Dust Filtration in a Su...

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第七届亚洲气溶胶会议

作者： Hyun hee lim Ju Yeol Lee Young Min Jo Department.of Environmental Engineering Kyung Hee University South Korea 446-701

Air quality of underground railway is of critical interests in Seoul, Korea. National government has emphasized the stringent management of IAQ of metro-subway. In order to satisfy the legislative standard and public needs, air purification must be much more enhanced with the addition of high quality control facilities. Thus, this work focused on the review of cost effectiveness for replacing fine dust filters. The inflow amount of PM10 and PM2.5 into the test ventilation chamber in which deals with the air, 900 CMM, was 19.4 kg/yr and 8.9 kg/yr respectively. It corresponds to US $ 5,857 for PM 10 and US $ 6,608 for PM2.5 based on the environmental cost evaluation. The current filtration system collects approximately 55% of the inlet PM10 and 35% of PM2.5. Even if it obeys the National IAQ regulation for platforms and ticket rooms, civic groups strongly insist better quality of air inside. Thus, additional facilities to improve the air filtration up to 80% of PM10 and 55% of PM2.5 would cost US$ 8,756 per year. However, the increase of environmental benefit on the atmospheric dust will in part compensate the cost.

关键词： Air ventilation Subway IAQ Filtration Electret filter Environmental benefit

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Critical factors to inhibit water-splitting side reaction in carbon-based electrode materials for zinc metal anodes

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Carbon Energy 2022年第6期4卷 1080-1092页

作者： Dong Hyuk Kang Eunji Lee Beom Sik Youn Son Ha Jong Chan Hyun Juhee Yoon Dawon Jang Kyoung Sun Kim Hyungsub Kim Sang Moon Lee Sungho Lee Hyoung-Joon Jin Hyung-Kyu lim Young Soo yun KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoulSeongbuk-guSouth Korea Division of Chemical Engineering and Bioengineering Kangwon National UniversityChuncheonGangwon-doSouth Korea Department of Eco-Polymer Science and Engineering Inha UniversityIncheonMichuhol-guSouth Korea Carbon Composite Materials Research Center Institute of Advanced Composite MaterialsKorea Institute of Science and Technology(KIST)Jeollabuk-doSouth Korea Department of Chemical and Biological Engineering Korea UniversitySeoulSeongbuk-guSouth Korea Neutron Science Division Korea Atomic Energy Research Institute(KAERI)DaejeonYuseong-guSouth Korea Research Center for Materials Analysis Korea Basic Science Institute(KBSI)DaejeonYuseong-guSouth Korea Department of Integrative Energy Engineering Korea UniversitySeoulSeongbuk-guSouth Korea

Zinc metal anodes(ZMA)have high theoretical capacities(820 mAh g−1 and 5855 mAh cm−3)and redox potential(−0.76 V *** hydrogen electrode),similar to the electrochemical voltage window of the hydrogen evolution reaction(HER)in a mild acidic electrolyte system,facilitating aqueous zinc batteries competitive in next-generation energy storage ***,the HER and byproduct formation effectuated by water-splitting deteriorate the electrochemical performance of ZMA,limiting their *** this study,a key factor in promoting the HER in carbon-based electrode materials(CEMs),which can provide a larger active surface area and guide uniform zinc metal deposition,was investigated using a series of threedimensional structured templating carbon electrodes(3D-TCEs)with different local graphitic orderings,pore structures,and surface *** ultramicropores of CEMs are the determining critical factors in initiating HER and clogging active surfaces by Zn(OH)2 byproduct formation,through a systematic comparative study based on the 3D-TCE series *** the 3D-TCEs had a proper graphitic structure with few ultramicropores,they showed highly stable cycling performances over 2000 cycles with average Coulombic efficiencies of≥99%.These results suggest that a well-designed CEM can lead to high-performance ZMA in aqueous zinc batteries.

关键词： aqueous batteries carbon electrode hydrogen evolution reaction multivalent ion zinc metal anode

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Anti-Helicobacter pylori effect of CaG-NANA, a new sialic acid derivative

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World Journal of Gastrointestinal Pathophysiology 2016年第4期7卷 300-306页

作者： yun-hee Rhee Hyun-Jeong Ku Hye-Ji Noh Hyang-Hyun Cho hee-Kyong Kim Jin-Chul Ahn Beckman Laser Institute Korea Dankook University Chungnam 31116South Korea MEDINUTROL Co. Jeonnam 57024 South Korea Department of Biomedical Science College of Medicine Dankook University Chungnam 31116 South Korea Medical Laser Research Center Dankook University Chungnam 31116 South Korea

AIM To investigate the bactericidal effects of calcium chelated N-acetylneuraminic acid-glycomacropeptide(CaG-NANA) against Helicobacter pylori(***).METHODS For manufacture of Ca G-NANA,calcium(Ca) was combined with glycomacropeptide(GMP) by chelating,and N-acetylneuraminic acid(NANA) was produced with Ca-GMP substrate by an enzymatic *** final concentration of each component was 5% Ca,7% NANA,85% GMP,and 3% *** in vitro study,various concentrations of CaG-NANA were investigated under the minimal inhibitory concentration(MIC).For in vivo study,Ca G-NANA was administered orally for 3 wk after *** *** levels of inflamma-tory cytokines in blood were analyzed by enzyme-linked immunosorbent assay and eradication of *** was assessed by histological *** The time-kill curves showed a persistent decrease in cellnumbers,which depended on the dose of CaG-NANA,and MIC of Ca G-NANA against *** was 0.5% in *** observation revealed no obvious inflammation or pathologic changes in the gastric mucosa in the CaG-NANA treatment group in *** colonization of *** was reduced after CaG-NANA *** levels of interleukin(IL)-6,IL-1β,tumor necrosis factor-α,and IL-10 were also decreased by *** Ca G-NANA demonstrates effective anti-bactericidal activity against *** both in vitro and in vivo.

关键词： Helicobacter pylori Calcium chealated N-acetylneuraminic acid-glycomacropeptide

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基于全自动免疫磁珠净化技术快速测定中药材中4种黄曲霉毒素

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分析测试学报 2024年第4期43卷 622-629页

作者：黄晓静陈素云周恒王江果旗王雄胡青季申上海市食品药品检验研究院国家药品监督管理局中药质量控制重点实验室上海201203 北京中检维康生物技术有限公司北京100044

基于全自动免疫磁珠净化前处理技术,建立了适用于多种中药材基质中4种黄曲霉毒素的快速测定方法。中药材中的黄曲霉毒素经乙腈-水(9∶1)提取后,采用免疫磁珠自动富集净化后,由0.5%乙酸甲醇洗脱后定容;经Inertsil ODS-3 C18柱(250 mm×4.... 详细信息

基于全自动免疫磁珠净化前处理技术,建立了适用于多种中药材基质中4种黄曲霉毒素的快速测定方法。中药材中的黄曲霉毒素经乙腈-水(9∶1)提取后,采用免疫磁珠自动富集净化后,由0.5%乙酸甲醇洗脱后定容;经Inertsil ODS-3 C18柱(250 mm×4.6 mm,5µm)分离,以乙腈-甲醇-水为流动相等度洗脱,采用高效液相色谱-荧光检测器(HPLC-FLD)测定。以5种易污染黄曲霉毒素的中药材基质进行方法学验证。结果表明该方法的线性关系良好,相关系数(r^(2))均达到0.9999;检出限为0.06~0.2µg·kg^(-1),定量下限为0.12~0.40µg·kg^(-1);不同基质中的平均回收率为71.9%~116%,相对标准偏差为0.10%~6.9%;在18 min内可完成24批样品的净化,比免疫亲和柱法的检测效率提高近85%。该方法快速、准确,通用性强,可用于多种中药材中4种黄曲霉毒素的批量快速测定。

关键词：全自动免疫磁珠快速测定中药材黄曲霉毒素高效液相色谱

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Improvement of oxidation resistance in graphite for MgO-C refractory through surface modification

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Transactions of Nonferrous Metals Society of China 2014年第S1期24卷 119-124页

作者： Geun-Ho CHO Eun-hee KIM Jing LI Je-Hyun LEE Yeon-Gil JUNG yun-Ki BYEUN Chang-Yong JO School of Materials Engineering Changwon National University Technical Research Laboratories Pohang Research Laboratory Steelmaking Research Group POSCOPhohang Gyeongbuk 790-300 Korea High Temperature Materials Research Group Korea Institute of Materials Science Changwon Gyeongnam 641-831 Korea

Graphite, used as a carbon source in a conventional magnesia-carbon(MgO-C) refractory, was modified with an acid reagent, resulting in a negative charge on the surface of graphite, to enhance the coating efficiency of aluminum(Al) phase, which was compared to the pristine graphite through its dispersibity and oxidation behavior. The graphite particles with and without surface modification were added, respecticely, in an Al(NO3)3 suspension used as a coating reagent, and then filtered at room temperature. The modified graphite shows better disperbility than the pristine graphite, indicating that the coating efficiency of Al precursor is enhanced in the modified graphite. With respect to oxidation behavior, the modified graphite without the coating layer is totally reacted with oxygen at heat treatment of 900 °C in air. However, the Al-coated graphite starts to react with oxygen at heat treatment of 900 °C and fully reacted with oxygen at heat treatment of 1000 °C, showing the gray and white colors, respectively. It is verified that the Al layer is individually and uniformly formed on the surface of graphite and the oxidation resistance of graphite is enhanced owing to the increased coating efficiency of Al precursor.

关键词： refractory graphite surface modification aluminum coating

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Effects of primary glaucoma on sleep quality and daytime sleepiness of patients residing at an equatorial latitude

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International Journal of Ophthalmology(English edition) 2020年第9期13卷 1451-1458页

作者： Jacob YH Chin Zhi Hong Toh Ying Tai Lo Hannah TY Wang Elizabeth YW Poh Chun Hau Chua Owen Kim hee Boon Ang lim Vernon KY Yong Augustinus Laude Hon Tym Wong Leonard WL Yip Department of Ophthalmology National Healthcare Group Eye InstituteTan Tock Seng Hospital308433Singapore Monash School of Medicine Monash UniversityVictoria 3800Australia

AIM:To investigate the impact of primary glaucoma on sleep quality and daytime sleepiness of ***:Prospective cross-sectional study with consecutive sampling in South-East Asian population was *** questionnaires:the Pittsburg Sleep Quality Index(PSQI)and Epworth Sleepiness Scale(ESS)were administered *** with nonglaucomatous optic neuropathy or concomitant retinal pathology were *** severity was based on HVF 24-2 *** single vision was represented based on the better *** of and predictive factors for poor sleep quality and excessive daytime sleepiness were ***:A total of 79 primary open angle glaucoma(POAG),27 primary angle-closure glaucoma(PACG)patients,and 89 controls were *** patients had higher median PSQI scores(P=0.004)and poorer sleep quality(P<0.001).Compared to controls,PACG patients were 3.34 times more likely to have poor sleep quality(P=0.008),which remained significant after adjustment for demographics(P=0.016)and predictive variables(P=0.013).PACG patients have poorer sleep quality when visual acuity(VA)was 6/15 or worse(P=0.009).Univariate and multivariate analysis of predictive variables for poor sleep quality and daytime sleepiness did not find statistical ***:PACG patients have poorer sleep quality but not daytime *** is important in South-East Asian population with heavy disease *** on sleep disturbances can be considered to provide more ho istic care.

关键词： sleep disturbances primary glaucoma intrinsically photosensitive retinal ganglion cells daytime sleepiness sleep quality South-East Asia

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Flow cytometric investigation on degradation of macro-DNA by common laboratory manipulations

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Journal of Biophysical Chemistry 2011年第2期2卷 102-111页

作者： hee-Bong Yoo Hyuk-Min lim Inchul Yang Sook-Kyung Kim Sang-Ryoul Park Center for Bioanalysis Korea Research Institute of Standards and Science Daejeon 305-340 Korea

The degree and characteristics of physical degradation of macro-DNA molecules by common laboratory manipulations are reported. With linearized lambda-phage viral DNA as the model DNA, fragmentation of macro-DNA by various indispensable laboratory manipulations were investigated using a high sensitivity flow cytometric setup. Investigated manipulations included pipetting, vortexing, rocking, freeze-thawing, ultrasonication and ultrafiltration. “Exhaustive counting” of the intact lambda DNA molecules following such manipulations enabled a quantitative assessment of the resulting fragmentation, which also revealed the type of degradation reflected in the fragmentation patterns. The use of high sensitivity flow cytometry was especially suited to investigate the degradation of dilute DNA solutions that may not be suitable for analysis using traditional methods. Notable findings of this study included: the boarderline-size of DNA chains in terms of susceptibility to shear stresses by such manipulations;discernable instability of nicked DNAs;shattering-fragmentation of DNAs by freeze-thawing or ultrasonication;effectiveness of some protection media;marked “self-protection effect” of concentrated DNA solutions. These findings support and refine our traditional knowledge on how to maintain the physical integrity of macro-DNA molecules against inevitable laboratory manipulations.

关键词： Physical Degradation Of DNA Laboratory Manipulations Flow Cytometry Exhaustive Counting Self-Protection Effect

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Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal neurons through maintaining calbindin D28k immunoreactivity following subsequent transient cerebral ischemia

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Neural Regeneration Research 2017年第6期12卷 918-924页

作者： In Hye Kim Yong Hwan Jeon Tae-Kyeong Lee Jeong Hwi Cho Jae-Chul Lee Joon Ha Park Ji Hyeon Ahn Bich-Na Shin Yang hee Kim Seongkweon Hong Bing Chun Yan Moo-Ho Won yun Lyul Lee Department of Neurobiology School of Medicine Kangwon National University Department of Radiology School of Medicine Kangwon National University Department of Biomedical Science Research Institute of Bioscience and Biotechnology Hallym University Department of Physiology College of Medicine Hallym University Department of Surgery School of Medicine Kangwon National University Institute of Integrative Traditional & Western Medicine Medical College Yangzhou University

Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning（2-minute transient cerebral ischemia） on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult（5-minute transient cerebral ischemia）. A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.

关键词： hippocampal subsequent minute pyramidal maintaining attenuated hippocampus neuronal occlusion fatal

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Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence

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World Journal of Gastroenterology 2012年第39期18卷 5581-5588页

作者： Jae yun lim Sun Och Yoo Soon Won Hong Jong Won Kim Seung Ho Choi Jae Yong Cho Department of Medical Oncology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Pathology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Surgery Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea

AIM:To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS:TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real- time reverse transcription polymerase chain reaction in 68 independent stage Ⅲ gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein. RESULTS:TXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage Ⅲ patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simulta-neously high TXN and low TXNIP expression group ex- perienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors

关键词： Gastric cancer Thioredoxin Thioredoxin-interacting protein Biomarker Prognosis

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