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Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressionsin Pancreas and Liver Tissues

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Chinese Journal of Integrative Medicine 2024年第2期30卷 125-134页

作者： Piao Wang Yi Liu Seok Yong Kang Chenzi Lyu Xiang Han Tianjun Ho kyung jae Lee Xianglong Meng Yong-Ki Park Hyo Won jung Department of Herbology College of Korean MedicineDongguk UniversityGyeongju 38066Korea College of Pharmacy&Graduate School of Pharmaceutical Sciences Ewha Womans UniversitySeoul 03760Korea Korean Medicine R&D Center Dongguk UniversityGyeongju 38066Korea Shanxi Key Laboratory of Traditional Herbal Medicines Processing Shanxi University of Chinese MedicineJinzhong(030619)ShanxiProvinceChina

Objective:To investigate the effects of Clean-DM1(C-DM1),a polyherbal formulation of Radix Scrophulariae,Radix Astragali,Rhizoma Atractylodis,and Radix Salviae Miltiorrhizae,on high-fat diet(HFD)-induced diabetes mice.Methods:The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis.Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry(HPLC-MS)analysis were conducted for quality control.For in vivo study,mice were induced diabetes by HFD for 12 weeks.The mice in the normal group(Nor)were maintained with a regular diet and treated with saline by gavage.The HFD model mice were randomly divided into 3 groups,including a HFD diabetic model group,a C-DM1 extract-administered group(C-DM1,500 mg/kg),and metformin-administered groups(Met,500 mg/kg),8 mice in each group.Food intake,body weight(BW),and fasting blood glucose(FBG)levels were recorded weekly for 4 weeks.After 4 weeks of treatment,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood glucose,low-density lipoprotein cholesterol(LDL-C)were determined using an automated clinical chemistry analyzer,and homeostatic model for assessing insulin resistance(HOMA-IR)levels and oral glucose tolerance test(OGTT)were detected.The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining.Insulin receptor substrate(IRS)/phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)and adenosine 5'-monophosphate-activated protein kinase(AMPK)expressions in liver and pancreas tissues were detected by Western blot analysis.Results:HPLC-MS identified dihydroisotanshinone,dihydroisotanshinone I,cryptotanshinone,harpagoside,and atractyloside A in C-DM1 extract.The administration of C-DM1 extract significantly decreased body weight,calorie intake,and the levels of blood glucose and insulin in the diabetic mice(P<0.05 or P<0.01).The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance

关键词： high-fat diet type 2 diabetes mellitus herbal formulation insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B adenosine 5'-monophosphate-activated protein kinase network pharmacology high performance liquid chromatography-mass spectrometry analysis

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Comparison of macular changes according to the etiology of optic neuritis:a cross-sectional study

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 686-692页

作者： Yeji Moon Sung-Min Kim jae Ho jung Department of Ophthalmology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Department of Neurology Seoul National University HospitalSeoul 03080Republic of Korea Department of Ophthalmology Seoul National University HospitalSeoul 03080Republic of Korea Department of Ophthalmology Seoul National University College of MedicineSeoul 03080Republic of Korea

AIM:To compare the macular structure including foveal thickness among patients with optic neuritis(ON)according to the etiology and to investigate the possible correlation between structural and visual outcomes METHODS:In this retrospective cross-sectional study,the clinical data of patients with aquaporin-4 immunoglobulin G-related ON(AQP4 group,40 eyes),myelin oligodendrocyte glycoprotein IgG-related ON(MOG group,31 eyes),and multiple sclerosis-related ON(MS group,24 eyes)were obtained.The retinal thickness of the foveal,parafoveal and perifoveal regions were measured.Visual acuity(VA),visual field index and mean deviation were measured as visual outcomes.RESULTS:The AQP4 group showed a significantly thinner fovea(226.4±13.4μm)relative to the MOG(236.8±14.0μm,P=0.015)and MS(238.9±14.3μm,P=0.007)groups.The thickness in the parafoveal area also was thinner in the AQP4 group,though the difference in perifoveal retinal thickness was not significant.Foveal thickness was correlated with VA in the AQP4 group(coefficientρ=-0.418,P=0.014),but not in the MOG and MS groups(P=0.218 and P=0.138,respectively).There was no significant correlation between foveal thickness and visual field test in all three groups.CONCLUSION:The significant thinning in the fovea and parafoveal areas in the AQP4 group compared to the MOG and MS groups are found.Additionally,macular changes in AQP4-ON show a significant correlation with VA.The results provide the possibility that retinal structural damage could reflect functional damage in AQP4-ON,distinct from MOGON and MS-ON.

关键词： foveal thickness optic neuritis aquaporin-4 immunoglobulin myelin oligodendrocyte glycoprotein multiple sclerosis

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Varifocal occlusion in an optical see-through near-eye display with a single phase-only liquid crystal on silicon

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Photonics Research 2024年第4期12卷 833-853页

作者： WOONGSEOB HAN jae-WON LEE jung-YEOP SHIN MYEONG-HO CHOI HAK-RIN KIM jae-HYEUNG PARK Department of Electrical and Computer Engineering Inha University100 Inha-roMichuhol-guIncheon 22212Republic of Korea School of Electronic and Electrical Engineering Kyungpook National University80 Daehak-roBuk-guDaegu 41566Republic of Korea School of Electronics Engineering Kyungpook National University80 Daehak-roBuk-guDaegu 41566Republic of Korea Department of Information and Communication Engineering Inha University100 Inha-roMichuhol-guIncheon 22212Republic of Korea

We propose a near-eye display optics system that supports three-dimensional mutual occlusion.By exploiting the polarization-control properties of a phase-only liquid crystal on silicon (LCoS),we achieve real see-through scene masking as well as virtual digital scene imaging using a single LCoS.Dynamic depth control of the real scene mask and virtual digital image is also achieved by using a focus tunable lens (FTL) pair of opposite curvatures.The proposed configuration using a single LCoS and opposite curvature FTL pair enables the self-alignment of the mask and image at an arbitrary depth without distorting the see-through view of the real scene.We verified the feasibility of the proposed optics using two optical benchtop setups:one with two off-the-shelf FTLs for continuous depth control,and the other with a single Pancharatnam–Berry phase-type FTL for the improved form factor.

关键词： optics crystal phase

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Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le jung Hoon Lee Min jae Lee Department of Biochemistry and Molecular Biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the neurons.Tau has unique biophysical properties that make it both highly water-soluble and positively charged.Although tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

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Intracellular zinc signaling via Kruppel-like transcription factor 6 promotes HuD expression in pancreaticβcell

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Genes & Diseases 2024年第4期11卷 24-27页

作者： Seongho Cha Chongtae Kim Myeongwoo jung Seungyeon Ryu Sukyoung Han Wook Kim Eun kyung Lee Department of Biochemistry Department of Biomedicine&Health SciencesCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea Catholic Institute for Visual Science College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Molecular Science&Technology Ajou UniversitySuwon 16499South Korea

Dysfunction of pancreaticβcells caused by zinc deficiency is related to the pathogenesis of diabetes.1 Impaired zinc homeostasis in diabetes is associated with reduced zinc transporters.2 Down-regulation of HuD,an es... 详细信息

关键词： βcell homeostasis zinc

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Utilization of biomarkers for the prognostic prediction of cardiac arrest survivors using a multi-modal approach

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World Journal of Emergency Medicine 2024年第2期15卷 131-134页

作者： Changshin Kang Yeonho You jung Soo Park Byeong Kwon Park jae Kwang Lee Byung Kook Lee Department of Emergency Medicine College of MedicineChungnam National UniversityDaejeon 35015Republic of Korea Department of Emergency Medicine Chungnam National University HospitalDaejoen 35015Republic of Korea Department of Emergency Medicine Konyang University HospitalCollege of MedicineDaejeon 35015Republic of Korea Department of Emergency Medicine Chonnam National University Medical SchoolChonnam National University HospitalGwangju 61469Republic of Korea

International guidelines for post-cardiac arrest care recommend using multi-modal strategies to avoid the withdrawal of life-sustaining therapy(WLST)in patients with the potential for neurological recovery.[1]However,a clear methodology for multi-modal approaches has yet to be developed.Neuron-specific enolase(NSE)is currently the only recommended biomarker,and the European Resuscitation Council(ERC)and the European SocietyofIntensiveCareMedicine(ESICM)have proposed a cutoff value of 60μg/L at 48 and/or 72 h after the return of spontaneous circulation(ROSC)as a multimodal prognostic tool for predicting poor neurological outcomes.

关键词： cardiac modal return

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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of Animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin jung Dae-Hyun Kim Jun-Koo Yi jae-jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea Comparative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising cost.Furthermore,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in cattle.In this point of view,electroporation in embryos has been risen as an alternative.Results First,editing efficiency of our electroporation methods were tested for embryos.Presence of mutation on embryo was confirmed by T7E1 assay.With first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,respectively.In case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for BLG.Afterwards,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing.Thirteen recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double KO.Ten surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both genes.Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied.Finally,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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ELK3-ID4 axis governs the metastatic features of triple negative breast cancer

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Oncology Research 2024年第1期32卷 127-138页

作者： JIN-HO CHOI JOO DONG PARK SEUNG HEE CHOI EUN-SU KO HYE jung JANG kyung-SOON PARK Department of Biomedical Science CHA UniversitySeongnamKorea

Purpose:Cancer cell metastasis is a multistep process,and the mechanism underlying extravasation remains unclear.ELK3 is a transcription factor that plays a crucial role in regulating various cellular processes,including cancer metastasis.Based on the finding that ELK3 promotes the metastasis of triple-negative breast cancer(TNBC),we investigated whether ELK3 regulates the extravasation of TNBC by forming the ELK3-ID4 axis.ID4 functions as a transcriptional regulator that interacts with other transcription factors,inhibiting their activity and subsequently influencing various biological processes associated with cell differentiation,survival,growth,and metastasis.Methods:We assessed the correlation between the expression of ELK3 and that of ID4 in TNBCs using bioinformatics analyses,QRT-PCR,western blot analysis,luciferase reporter assays,and chromatin immunoprecipitation.Migration,adhesion,invasion,and lung metastasis assays were employed to determine whether the ELK3-ID4 axis regulates the metastatic features of TNBC.Results:We found that ELK3 binds directly to a binding motif close to the ID4 promoter to repress promoter activity.The expression of E-cadherin in TNBC was regulated by the ELK3-ID4 axis.In vitro and in vivo analyses showed that inhibiting ID4 expression in ELK3-knockdown MDA-MB-231(ELK3KD)cells restored the ability to extravasate and metastasize.Conclusion:The results indicate that the ELK3 regulates ID4 promoter activity,and that the ELK3-ID4 axis regulates the metastatic characteristics of TNBC cells.Additionally,the data suggest that the ELK3-ID4 axis regulates metastasis of TNBCs by modulating expression of E-cadherin.

关键词： E-cadherin Extravasation Colonization

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Oxygen vacancy engineering for tuning the catalytic activity of LaCoO_(3) perovskite

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Journal of Rare Earths 2024年第3期42卷 506-514,I0003页

作者： Jeong Hyun Cho Minjae Kim Inchan Yang kyung Tae Park Chang Houn Rhee Hai Woong Park Ji Chul jung Department of Chemical Engineering Myongji UniversityYongin 17058Republic of Korea Institute of Advanced Composite Materials Korea Institute of Science and TechnologyWanju-gunJeollabuk-do 55324Republic of Korea Iron&Steel Process Engineering Research Group POSCOPohang 37859Republic of Korea Hydrogen Research Center Research Institute of Industrial Science&Technology(RIST)Pohang 37673Republic of Korea

Herein, we attempted to engineer oxygen vacancies on the surface of LaCoO_(3) perovskite through simple post-treatments(acid or reductive thermal treatments). Acid treatment induces oxygen vacancies through the selective etching of the La cations, whereas thermal treatment in a reducing atmosphere generates oxygen vacancies by directly removing lattice oxygen. The characterization results confirm that the number of surface oxygen vacancies, which are crucial in various catalytic oxidation reactions,considerably increases in the LaCoO_(3) catalysts treated with acid or reducing gas. Acid treatment enriches the oxygen vacancies while maintaining the structure of the LaCoO_(3) catalysts, which can not be achieved through reductive thermal treatment. Therefore, the acid treatment is considered a promising technique for oxygen vacancy engineering of perovskite catalysts for tuning their catalytic activities. Furthermore,the catalytic activities of the posttreated LaCoO_(3) catalysts for CO oxidation were evaluated and are noted to be considerably better than those of the pristine LaCoO_(3) catalyst due to their abundant oxygen vacancies. Consequently, we conclude that the oxygen vacancies of perovskite catalysts can be effectively engineered via two simple methods and play a significant role in CO oxidation.

关键词： LaCoO_(3)perovskite Acid treatment Reductive thermal treatment Oxygen vacancy CO oxidation Rare earths

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Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon Kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song jae Woo jung Haesong Lee Eun-Ae Shin Yangie Pinanga kyung-hee Pyo Eun Hae Lee Wonsik Kim Soyeon Kim Chang-Duck Jun Jeanho Yun Sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic contexts.It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms.Methods:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution etc.Results:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal TM4SF5.Proximity labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and autophagy.TM4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-oxidation.In mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver malignancy.Conclusions:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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