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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 ***3 is a transcription factor that plays a crucial role in regulating various cellular processes,including cancer *** 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 ***4 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 ***: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 ***,adhesion,invasion,and lung metastasis assays were employed to determine whether the ELK3-ID4 axis regulates the metastatic features of ***:We found that ELK3 binds directly to a binding motif close to the ID4 promoter to repress promoter *** expression of E-cadherin in TNBC was regulated by the ELK3-ID4 *** vitro and in vivo analyses showed that inhibiting ID4 expression in ELK3-knockdown MDA-MB-231(ELK3KD)cells restored the ability to extravasate and ***:The results indicate that the ELK3 regulates ID4 promoter activity,and that the ELK3-ID4 axis regulates the metastatic characteristics of TNBC ***,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

M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3169-3183页

作者： Ha eun Shin Jun-Hyeok Han Seungyong Shin Ga-Hyun Bae Boram Son Tae-Hyung Kim Hee Ho Park Chun Gwon Park Wooram Park Department of Integrative Biotechnology Sungkyunkwan University(SKKU)SuwonGyeonggi 16419Republic of Korea Deparment of Inteligent Precision Healthcare Convergence SKKUSuwonGyeonggi 16419Republic of Korea Department of MetaBioHealth SKKU Institute for ConvergenceSKKUSuwonGyeonggi 16419Republic of Korea Department of Bioengineering Hanyang UniversitySeoul 04763Republic of Korea Department of Integrative Engineering Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biomedical Engineering SKKUSuwonGyeonggi 16419Republic of Korea Korea Institute of Science and Technology(KIST) Seoul 02792Republic of Korea

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene *** nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 *** study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid *** dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor *** retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth *** findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

关键词： Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)

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 *** is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of ***: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 ***:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal *** 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 ***4SF5 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-*** mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver ***: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

Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

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Oncology Research 2024年第4期32卷 615-624页

作者： HYUNG SUN KIM YUN SUN LEE SeunG MYUNG DONG HYO JUNG KIM DA eun LEE HYEON WOONG KANG MYEONG JIN KIM JOON SEONG PARK Department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea Department of Surgery Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulKorea Gibiome Co. Ltd.Gyeonggi-doKorea

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been *** this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of *** found that N-WASP is markedly expressed in clinical patients with *** analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile *** of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and *** also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were *** N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic *** results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer *** findings may aid in the development of therapeutic strategies against pancreatic cancer.

关键词： Pancreatic cancer Neural Wiskott-Aldrich syndrome protein(N-WASP)signaling Metastasis Epithelial-mesenchymal transition(EMT) Lysyl oxidase-like 2(LOXL2)

Differential diagnosis and treatment of foot drop caused by an extraneural ganglion cyst above the knee:A case report

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World Journal of Clinical Cases 2022年第21期10卷 7539-7544页

作者： Ki Hong won eun Young Kang Department of Rehabilitation Medicine Kwangju Christian HospitalGwangju 61661South Korea

BACKGROUND One of the causes of foot drop is compression of the common peroneal nerve caused by space-occupying lesions such as a synovial cyst or a ganglion *** previous reports have involved compressive common peroneal neuropathy by intraneural ganglion cysts and synovial *** of the peroneal nerve by extraneural ganglion cysts is *** report a rare case of compressive common peroneal neuropathy by an extraneural ganglion *** SUMMARY A 46-year-old man was hospitalized after he reported a right foot drop for 1 *** muscle testing revealed scores of 1/5 on dorsiflexion of the right *** and paresthesia on the right lateral leg and foot dorsum were *** was diagnosed with a popliteal cyst by using electrophysiologic study and popliteal ultrasound(US).To facilitate common peroneal nerve(CPN)decompression,2 cc of sticky gelatinous material was aspirated from the cyst under US *** stimulation and passive and assisted active ROM exercises of the right ankle and strengthening exercises for weak muscles using elastic band were prescribed based on the change of muscle power.A posterior leaf spring ankle-foot orthosis was prescribed to assist the weak dorsiflexion of the ***-up US revealed that the cystic lesion was growing and magnetic resonance imaging demonstrated compression of the CPN by the cystic *** cyst was resected to prevent impending compression of the *** Precise diagnosis and immediate treatment are important in cases of compressive common peroneal neuropathy caused by an extraneural cyst.

关键词： Foot drop Extranueral ganglion cyst Common peroneal neuropathy Popliteal ultrasound Electrodiagnostic study Cystectomy Case report

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 51-60页

作者： Ga Hee Kim Yeong Chan Lee Tae Jun Kim Sung Noh Hong Dong Kyung Chang Young-Ho Kim Dong-Hoon Yang Chang Mo Moon Kyunga Kim Hyun Gun Kim eun-Ran Kim Division of Gastroenterology Department of Internal MedicineAsan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Digital Health Samsung Advanced Institute for Health Science and TechnologySungkyunkwan University School of MedicineSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineEwha Womans UniversitySeoul 07985South Korea Biomedical Statistics Center Samsung Medical CenterSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineSoonchunhyang University College of MedicineSeoul 04401South Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several *** To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in *** This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic ***-related complications by age group were also *** The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age *** the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of *** 2009,the increase has been rapid,showing a pattern similar to the increase in *** rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after *** rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of *** The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies *** the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

关键词： Colorectal cancer Preinvasive colorectal cancer Colorectal polypectomy Colonoscopy

Mechanical strength and corrosion resistance of Al-additive friction stir welded AZ31B joints

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Journal of Magnesium and Alloys 2023年第5期11卷 1519-1535页

作者： Jae-Yeon Kim eun-Woo Kim Dong-O Kim eun-Kyo Ju Ji-eun Lee Jaeheon Lee Jai-won Byeon Mining Engineering Department Colorado School of MinesGoldenCO 80401USA Department of Materials Science and Engineering Seoul National University of Science and TechnologySeoul 01811Republic of Korea

Compared to other structural alloys,magnesium alloys have a relatively poor corrosion resistance and low mechanical strength,which can be further deteriorated when these alloys are subjected to joining processes using the existing joining ***,we propose for the first time an additive friction stir-welding(AFSW)using fine Al powder as an additive to improve the mechanical strength as well as corrosion resistance of AZ31B weld *** is a solid-state welding method of forming a high-Al AZ31B joint via an in-situ reaction between pure Al powders filled in a machined groove and the AZ31B *** optimize the process parameters,AFSW was performed under different rotational and transverse speeds,and number of passes,using tools with a square or screw *** particular,to fabricate a weld zone,where the Al was homogenously dispersed,the effects of the groove shape were investigated using three types of grooves:surface one-line groove,surface-symmetric grooves,and inserted symmetric *** homogenous and defect-less AFS-welded AZ31B joint was successfully fabricated with the following optimal parameters:1400 rpm,25 mm/min,four passes,inserted symmetric grooves,and the tool with a square *** AFSW fully dissolved the additive Al intoα-Mg and in-situ precipitated Mg_(17)Al_(12)particles,which was confirmed via scanning electron microscopy,transmission electron microscope,and X-ray diffraction *** microhardness,joint efficiency,and elongation at the fracture point of the AFS-welded AZ31B joint were 80 HV,101%,and 8.9%,*** values are higher than those obtained for the FS-welded AZ31 joint in previous *** corrosion resistance of the AFS-welded AZ31B joint,evaluated via hydrogen evolution measurements and potentiodynamic polarization tests,was enhanced to 55%relative to the FS-welded AZ31B joint.

关键词： AZ31B magnesium alloy Additive friction stir-welding In-situ reaction Mg_(17)Al_(12)particles Joint efficiency Corrosion resistance

High-efficiency single and tandem fullerene solar cells with asymmetric monofluorinated diketopyrrolopyrrole-based polymer

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Journal of Energy Chemistry 2022年第1期31卷 236-245,I0007页

作者： Shafket Rasool Quoc Viet Hoang Doan Van Vu Chang eun Song Hang Ken Lee Sang Kyu Lee jong-Cheol Lee Sang-Jin Moon won Suk Shin Institute of Chemical Technology(KRICT) 141 Gajeong-roYuseongDaejeon 34114Republic of Korea Advanced Materials and Chemical Engineering University of Science and Technology(UST)217 CajeongroYuseongDaejeon 34113Republic of Korea Vietnam Standards and Quality Institute(VSQI) Directorate for StandardsMetrology and Quality(STAMEQ)No.8.Hoang Quoc VietCau GiayHanoiViet Nam

Design and synthesis of low bandgap(LBG) polymer donors is inevitably challenging and their processability from a non-halogenated solvent system remains a hurdle to overcome in the area of highperformance polymer solar cells(PSCs).Due to a high aggregation tendency of LBG polymers,especially diketopyrrolopyrrole(DPP)-based polymers coupled with bithiophenes in the polymer backbones,their widespread adoption in non-ha logena ted solvent-processed PSCs has been ***,a novel LBG DPP-based polymer,called PDPP4 T-1 F with asymmetric arrangement of fluorine atom,has been successfully synthesized and showed an outstanding power conversion efficiency(PCE) of 10.10% in a singlejunction fullerene-based ***,an impressive PCE of 13.21% has been achieved in a tandem device from a fully non-halogenated solvent system,which integrates a wide bandgap PDTBTBz-2 F polymer in the bottom cell and LBG PDPP4 T-1 F polymer in the top *** achieved efficiency is the highest value reported in the literature to date in fullerene-based tandem *** found that a uniformly distributed interpenetrating fibril network with nano-scale phase separation and anisotropy of the polymer backbone orientation for efficient charge transfer/transport and suppressed charge recombination in PDPP4 T-1 F-based PSCs led to outstanding PCEs in single and tandem-junction PSCs.

关键词： Low bandgap polymers Diketopyrrolopyrrole Tandem polymer solar cells Non-halogenated solvent Monofluoro-bithiophene

Clinical efficacy of 0.05%cyclosporine nano-emulsion in the treatment of dry eye syndrome associated with meibomian gland dysfunction

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International Journal of Ophthalmology(English edition) 2022年第12期15卷 1924-1931页

作者： Yeon Ji Jo Ji eun Lee jong Soo Lee Efficacy of nano-cyclosporine to DES with MGD 1 Department of Ophthalmology Pusan National University School of Medicine&Medical Research InstitutePusan National University HospitalPusan 49241Republic of Korea Department of Ophthalmology Pusan National University School of Medicine&Medical Research CenterYangsan Pusan National University HospitalYangsan 626-770Republic of Korea

AIM:To evaluate the clinical efficacy of topical 0.05%cyclosporine nano-emulsion in the treatment of dry eye syndrome(DES)with meibomian gland dysfunction(MGD).METHODS:This prospective study included 64 patients with DES and MGD who were randomly assigned to three groups:Group 1(n=24,conventional cyclosporine),Group 2(n=21,nano-emulsion cyclosporine),and Group 3(n=19,control).Lid margin telangiectasia(LMT),meibomian gland secretion(MGS),conjunctival injection(CI),corneal staining(CS),tear break-up time(TBUT),Schirmer test I(STI),Ocular Surface Disease Index(OSDI),and lipid layer thickness(LLT)was evaluated at 4,8,and 12wk of ***:In Group 3(control),LMT,CS,and CI improved after 8wk,MGS,TBUT after 12wk of *** Group 1(conventional cyclosporine),LMT,MGS,and TBUT improved significantly after 4wk,whereas CS,CI,STI,and LLT improved significantly after 8wk,and OSDI at *** Group 2(nano-cyclosporine),LMT,MGS,CS,CI,TBUT,and OSDI significantly improved after 4wk,and STI after ***,LLT was significantly higher than other groups after ***:Cyclosporine and nano-cyclosporine shows significant improvement in DES with MGD than the control *** contrast,the nano-cyclosporine group shows more statistically improved CI and CS at 4wk,especially LLT at 4,8,and 12wk compared to the conventional cyclosporine group.

关键词： anti-inflammatory treatment cyclosporine dry eye disease meibomian gland dysfunction