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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)

Comparative efficacy and optimal duration of first-line antibiotic regimens for acute otitis media in children and adolescents:a systematic review and network meta-analysis of 89 randomized clinicaltrials

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World Journal of Pediatrics 2024年第3期20卷 219-229页

作者： Min Seo Kim Jae Han Kim Seohyun Ryu Seung Won Lee Dong Keon Yon Eunyoung Kim Ai Koyanagi Elena Dragioti Jae Il shin Lee Smith Samsung Advanced Institute forHealth Sciences&Technology(SAIHST) Samsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea Yonsei University Collegeof Medicine SeoulRepublicof Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Center for Digital Health Medical Science Research InstituteKyung Hee University College of MedicineSeoulRepublic of Korea Evidence-Based Research Laboratory Department of Clinical Pharmacy and Pharmaceutical CareCollege of PharmacyChung-Ang UniversitySeoulRepublic of Korea Parc Sanitari Sant Joan de Deu/CIBERSAM/ISCIII Universitat de BarcelonaFundacio Sant Joan de Déu.Sant Boi de LlobregatBarcelonaSpain ICREA Pg.Lluis Companys 23BarcelonaSpain Pain and Rehabilitation Centre and Department of Medical and Health SciencesLinkoping University58185 LinkopingSweden Department of Pediatrics Yonsei University College of MedicineYonsei-ro 50Seodaemun-gu8044Seoul 03722Republic of Korea Centre for Health Performanceand WellbeingAnglia Ruskin UniversityCambridge CB11PTUK Research Laboratory Psychology of Patients Families&Health ProfessionalsDepartment of NursingSchool of Health SciencesUniversity of IoanninaIoannina 45500Greece

Introduction Antibiotic use for acute otitis media(AOM)is one of the major sources of antimicrobial ***,the effective minimal antibiotic duration for AOM remains ***,guidelines often recommend broad ranges(5-10 days)of antibiotic use,yet the clinical impact of such a wide window has not been *** We systematically searched PubMed/MEDLINE,Embase,Scopus,Web of Science,and Cochrane Library from database inception to 6 October *** meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children(PROSPERO CRD42020196107).Results For amoxicillin and amoxicillin-clavulanate,7-day regimens were noninferior to 10-day regimens in clinical responses[amoxicillin:risk ratio(RR)0.919(95%CI 0.820-1.031),amoxicillin-clavulanate:RR 1.108(0.957-1.282)],except for≤2 *** the third-generation cephalosporins,7-day and 10-day regimens had similar clinical responses compared to placebo[7-day:RR 1.420(1.190-1.694),10-day:RR 1.238(1.125-1.362)compared to placebo].However,5-day regimens of amoxicillin-clavulanate and third-generation cephalosporins were inferior to 10-day *** to amoxicillin,a shorter treatment duration was tolerable with *** Our findings indicated that 1O days of antibiotic use may be unnecessarily long,while the treatment duration should be longer than 5 ***,5-day regimens would be sufficient for a modest treatment *** findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM,and a narrower antibiotic duration window should be re-established.

关键词： Amoxicillin-potassium Amoxicillin Antibacterial agents Cephalosporins Duration of therapy

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

三维石墨烯-碳纳米管磁性气凝胶的制备及其染料吸附性能

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新型炭材料 2022年第2期37卷 424-434页

作者： Zu Rong ang Ing Kong Rachel shin Yie Lee Cin Kong Akesh Babu Kakarla Ai Bao Chai Wei Kong Department of Mechanical Materials and Manufacturing EngineeringUniversity of Nottingham MalaysiaJalan Broga43500 SemenyihSelangorMalaysia School of Computing Engineering and Mathematical SciencesLa Trobe UniversityBendigoVictoria 3552Australia School of Pharmacy University of Nottingham MalaysiaJalan Broga43500 SemenyihSelangorMalaysia Faculty of Engineering Science and TechnologyInfrastructure University Kuala LumpurCorporate BlockUnipark SuriaJalan Ikram-Uniten43000 KajangSelangorMalaysia

将ZnCl_(2)、NiCl_(2)·6H_(2)O、FeCl_(2)·4H_(2)O和FeCl_(3)·6H_(2)O分别加入氧化石墨烯和碳纳米管的悬浮液中,在碱性条件下共沉淀和水中与聚乙烯醇交联后,冷冻干燥制备气凝胶。制备的气凝胶由磁性Ni_(0.5)Zn_(0.5)Fe_(2)O_(4)纳米... 详细信息

将ZnCl_(2)、NiCl_(2)·6H_(2)O、FeCl_(2)·4H_(2)O和FeCl_(3)·6H_(2)O分别加入氧化石墨烯和碳纳米管的悬浮液中,在碱性条件下共沉淀和水中与聚乙烯醇交联后,冷冻干燥制备气凝胶。制备的气凝胶由磁性Ni_(0.5)Zn_(0.5)Fe_(2)O_(4)纳米粒子、氧化石墨烯、碳纳米管和聚乙烯醇组成,不仅具有吸附染料分子的活性位点,而且可通过外加磁场从水中分离。在最佳质量比下,制备的气凝胶对亚甲基蓝具有高的吸附容量(q_(e)=71.03 mg g^(-1))和中等磁性强度(M_(S)=3.519 emu g^(-1))。在染料浓度为0.025 mg mL^(-1)的条件下,气凝胶对亚甲基蓝、甲基橙、结晶紫及其相等质量的混合物的去除效率分别为70.1%、4.2%、8.9%和11.1%。该气凝胶重复使用3次后,再生效率仍超过82%。此外,它对生物体无毒,有望用作处理工业废水的吸附剂。

关键词：磁性气凝胶染料去除石墨烯碳纳米管秀丽隐杆线虫