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Exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer

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Bioactive Materials 2023年第7期25卷 527-540页

作者： Hyosuk Kim Hyun-Ju Park Hyo Won chang ji Hyun Back Su jin Lee Yae eun Park eun Hye Kim Yeonsun Hong Gijung Kwak Ick chan Kwon ji eun Lee Yoon Se Lee Sang Yoon Kim Yoosoo Yang Sun Hwa Kim Medicinal Materials Research center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea Department of Functional Genomics KRIBB School of BioscienceKorea University of Science and Technology(UST)Daejeon34141Republic of Korea Department of Otolaryngology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul05505Republic of Korea chemical&Biological Integrative Research center Biomedical Research InstituteKorea Institute of Science and TechnologySeoul02792Republic of Korea Department of Biotechnology College of Life Sciences and BiotechnologyKorea UniversitySeoul02841Republic of Korea Department of Life Sciences Korea UniversitySeoul02841Republic of Korea

Highly immunosuppressive tumor microenvironment containing various protumoral immune cells accelerates malignant transformation and treatment *** particular,tumor-associated macrophages(TAMs),as the predominant infiltrated immune cells in a tumor,play a pivotal role in regulating the immunosuppressive tumor *** a potential therapeutic strategy to counteract TAMs,here we explore an exosome-guided in situ direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type *** derived from M1-type macrophages(M1-Exo)promote a phenotypic switch from anti-inflammatory M2-like TAMs toward pro-inflammatory M1-type macrophages with high conversion *** M1 macrophages possessing protein-expression profiles similar to those of classically activated M1 macrophages display significantly increased phagocytic function and robust cross-presentation ability,potentiating antitumor immunity surrounding the ***,these M1-Exo also lead to the conversion of human patient-derived TAMs into M1-like macrophages that highly express MHc class II,offering the clinical potential of autologous and allogeneic exosome-guided direct TAM reprogramming for arming macrophages to join the fight against cancer.

关键词： Exosome cancer therapy Tumor microenvironment Tumor-associated macrophage Direct conversion

Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

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Nano Research 2018年第10期11卷 5584-5595页

作者： Jonathan Wang christopher Poon Deborah chin Sarah Milkowski Vivian Lu Kenneth R. Hallows eun ji c.ung Department of Biomedical Engineering University of Southern California Los Angeles CA 90089 USA Division of Nephrology and Hypertension Department of Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA USc/UKRO Kidney Research center Keck School of Medicine University of Southern California Los Angeles CA 90033 USA Norris comprehensive cancer center University of Southern California Los Angeles CA 90033 USA Department of Stem cell Biology and Regenerative Medicine University of Southern California Los Angeles CA 90033 USA Mork Family Department of chemical Engineering and Materials Science University of Southern California Los Angeles CA 90089 USA

One in three Americans is at risk for developing chronic kidney disease （cKD） and end-stage renal disease （ESRD）, leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel kidney-targeting multimodal micelle （KM） system for drug delivery applications. SpecificaU~ we incorporated the kidney-targeting peptide （Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid）3-Lysine）（（KKEEE）3K） into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted （NT） control upon intravenous injection in wild-type c57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen （BUN） and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of （KKEEE）BK in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in cKD.

关键词： micelle kidney disease renal targeting biodistribution nanoparticle

cT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1231-1237页

作者： Roh-Eul Yoo Sun-Won Park Jung Hyo Rhim ji eun Kim Soo chin Kim ji-Young choe Ho-Kyung choung Sang In Khwarg ji-hoon Kim Jeong Hyun Lee Bo eun Lee Yeonah Kang Department of Radiology Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Radiology Seoul National University HospitalSeoul 03080Republic of Korea Department of Radiology Seoul Metropolitan Government Seoul National University Boramae Medical CenterSeoul 07061Republic of Korea Department of Pathology Seoul Metropolitan Government Seoul National University Boramae Medical CenterSeoul 07061Republic of Korea Department of Pathology Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Radiology Asan Medical CenterSeoul 05505Republic of Korea Department of Pathology Hallym University Sacred Heart HospitalAnyang14068Republic of Korea Department of Ophthalmology Seoul Metropolitan Government Seoul National University Boramae Medical CenterSeoul 07061Republic of Korea Department of Ophthalmology Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Radiology Ulsan University College of MedicineSeoul 05505Republic of Korea Department of Radiology Inje University Haeundae Paik HospitalBusan 47392Republic of Korea

AIM:To report cT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease(IgG4-MALT lymphoma),a rare but clinically important complication of ocular adnexal IgG4-related ***:We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three ter tiary and one secondary referral centers,between February 2003 and December *** cases of histopathologically diagnosed IgG4-MALT lymphoma were *** and MR images were analyzed by consensus of two experienced head and neck ***:Lacrimal glands were the main site of involvement in all seven *** lesions typically showed well-demarcated margins,iso-to hyperattenuation on precontrast cT,T2 hypo-to isointensity,T1 isointensity,and homogenous internal architecture with homogenous enhancement *** were mostly hyperdense and isointense to normal extraocular muscles on postcontrast cT and MR images,***:Unlike in typical ocular adnexal IgG4-related disease,T2 isointensity and hyperattenuation on precontrast cT images were noted in some IgG4-MALT lymphoma *** the findings may be nonspecific,the possibility of accompanying MALT lymphoma may need to be considered,when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast cT for the optimal management of the ***,this is a case series of a very rare complication of ocular adnexal IgG4-related disease,and thus caution is warranted to generalize the conclusion.

关键词： cT IgG4-related disease MR ocular adnexal mucosa-associated lymphoid tissue lymphoma

Long-term, in vivo therapeutic effects of a single dose of miR-145 micelles for atherosclerosis

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Bioactive Materials 2023年第9期27卷 327-336页

作者： Deborah D.chin Neil Patel Woori Lee Sonali Kanaya Jackson cook eun ji c.ung Department of Biomedical Engineering University of Southern CaliforniaLos AngelesCA90089United States Division of Vascular Surgery and Endovascular Therapy Department of SurgeryKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Mork Family Department of chemical Engineering and Materials Science University of Southern CaliforniaLos AngelesCA90089United States Eli and Edythe Broad center for Regenerative Medicine and Stem cell Research Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Division of Nephrology and Hypertension Department of MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Norris comprehensive cancer center Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90089United States

Atherosclerosis is a chronic inflammatory disease that is characterized by the build-up of lipid-rich plaques in the arterial walls. The standard treatment for patients with atherosclerosis is statin therapy aimed to lower serum lipid levels. Despite its widespread use, many patients taking statins continue to experience acute events. Thus, to develop improved and alternative therapies, we previously reported on microRNA-145 (miR-145 micelles) and its ability to inhibit atherosclerosis by targeting vascular smooth muscle cells (VSMcs). Importantly, one dose of miR-145 micelles significantly abrogated disease progression when evaluated two weeks post-administration. Thus, in this study, to evaluate how long the sustained effects of miR-145 micelles can be maintained and towards identifying a dosing regimen that is practical for patients with chronic disease, the therapeutic effects of a single dose of miR-145 micelles were evaluated for up to two months in vivo. After one and two months post-treatment, miR-145 micelles were found to reduce plaque size and overall lesion area compared to all other controls including statins without causing adverse effects. Furthermore, a single dose of miR-145 micelle treatment inhibited VSMc transdifferentiation into pathogenic macrophage-like and osteogenic cells in plaques. Together, our data shows the long-term efficacy and sustained effects of miR-145 micelles that is amenable using a dosing frequency relevant to chronic disease patients.

关键词： MicroRNA-145 Atherosclerosis Vascular smooth muscle cell Nanoparticle Gene therapy

Effect of Asiasari radix on osteoblastic differentiation of stem cells derived from gingiva

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Journal of Traditional chinese Medicine 2016年第6期36卷 756-759页

作者： Su-Hyeon Jeong ji-eun Lee Seong-Ho jin Youngkyung Ko Jun-Beom Park Department of Rehabilitation Medicine of Korean Medicine Chungju Hospital of Korean MedicineCollege of Korean Medicine Semyung University Development of Periodontics College of MedicineThe Catholic University of Korea

OBJEcTIVE: To examine the dose-dependent impact of Asiasari Radix(A. radix) on the cell viability,differentiation and mineralization of stem cells derived from ***: Stem cells that were derived from gingiva were grown in the presence of A. radix at final concentrations that ranged from 0.001 to 10 μg/m L. The morphology of the cells was viewed under an inverted microscope and the analysis of cell proliferation was performed by using cell counting Kit-8(ccK-8) on day 1. The alkaline phosphatase activity test was used to assess differentiation and Alizarin red S staining was used to assess mineralization of treated ***: The control group showed spindleshaped, fibroblast-like morphology and the shapesof the cells in 0.001, 0.01, 0.1, 1 and 10 μg/mL of *** were similar to that of the control group at day 1. The cultures growing in the presence of0.001 μg/m L of A. radix at day 1 showed an increase in the ccK-8 value(P cultures growing in the presence of 0.001 μg/m L of A. radix presented the highest value for alkaline phosphatase activity(P > 0.05). Mineralized extracellular deposits were observed after Alizarin Red S staining and the cultures grown in the presence of 0.001 μg/m L of A. radix showed the highest value for quantitative results for bound dye(P cONcLUSION: Within the limits of this study, A. radix influenced the proliferation of stem cells derived from the gingiva and low concentrations of *** might enhance osteogenic differentiation of the stem cells.

关键词： cell differentiation Plant roots Plant extracts Stem cells Drugs,chinese herbal

Evaluation of anatomical considerations in the posterior maxillae for sinus augmentation

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World Journal of clinical cases 2014年第11期2卷 683-688页

作者： ji-eun Lee Seong-Ho jin Youngkyung Ko Jun-Beom Park Department of Periodontics Seoul St. Mary’s Hospital College of Medicine The Catholic University of Korea Seoul 137-701South Korea

The edentulous posterior maxilla is considered a clinical challenge during dental implant treatment for many dental practitioners. This is because its insufficient bone quality, deficient alveolar ridge, spiny ridges, undercuts, and sinus pneumatization are often encountered after tooth loss. To overcome these problems, several approaches have been developed and are currently used, including sinus augmentation and bone augmentation. Today, two main procedures of sinus floor elevation for dental implant placement are in use: a two-stage technique using the lateral window approach, and a onestage technique using a lateral or a crestal approach. In this study, we deal with the anatomic relations ofthe structures of the maxillary sinus during sinus augmentation. These anatomical findings can help in complications and potential injuries of the maxillary sinus procedures. It can be suggested that pre-operative evaluation is helpful for diagnosis and treatment planning and minimizing complication during the surgery.

关键词： Anatomy Intraoperative complications Sinus floor augmentation

An Effective Threat Detection Framework for Advanced Persistent cyberattacks

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computers, Materials & continua 2023年第5期75卷 4231-4253页

作者： So-eun Jeon Sun-jin Lee eun-Young Lee Yeon-ji Lee Jung-Hwa Ryu Jung-Hyun Moon Sun-Min Yi Il-Gu Lee Department of Future convergence Technology Engineering Sungshin Women’s UniversitySeoul02844Korea Department of convergence Security Engineering Sungshin Women’s UniversitySeoul02844Korea

Recently,with the normalization of non-face-to-face online environments in response to the cOVID-19 pandemic,the possibility of cyberattacks through endpoints has *** endpoint devices are managed meticulously to prevent cyberattacks and ensure timely responses to potential security *** particular,because telecommuting,telemedicine,and teleeducation are implemented in uncontrolled environments,attackers typically target vulnerable endpoints to acquire administrator rights or steal authentication information,and reports of endpoint attacks have been increasing *** persistent threats(APTs)using various novel variant malicious codes are a form of a sophisticated ***,conventional commercial antivirus and anti-malware systems that use signature-based attack detectionmethods cannot satisfactorily respond to such *** this paper,we propose a method that expands the detection coverage inAPT attack *** this model,an open-source threat detector and log collector are used synergistically to improve threat detection *** the scope of attack log collection through interworking between highly accessible open-source tools can efficiently increase the detection coverage of tactics and techniques used to deal with APT attacks,as defined by MITRE Adversarial Tactics,Techniques,and common Knowledge(ATT&cK).We implemented an attack environment using an APT attack scenario emulator called carbanak and analyzed the detection coverage of Google Rapid Response(GRR),an open-source threat detection tool,and Graylog,an open-source log *** proposed method expanded the detection coverage against MITRE ATT&cK by approximately 11%compared with that conventional methods.

关键词： Advanced persistent threat cybersecurity endpoint security MITRE ATT&cK open-source threat detector threat log collector

Molecular Dynamics Simulation of Behaviours of Non-Polar Droplets Merging and Interactions with Hydrophobic Surfaces

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Journal of Bionic Engineering 2008年第4期5卷 271-281页

作者： Y.Y. Yan c.Y. ji School of the Built Environment University of Nottingham Nottingham NG7 2RD UK

This paper presents a molecular dynamics simulation of the behaviours of non-polar droplets merging and also the fluid molecules interacting with a hydrophobic surface. Such behaviours and transport phenomena are popular in general microchannel flow boiling and two-phase flow. The droplets are assumed to be composed of Lennards-Jones type molecules. Periodic boundary conditions are applied in three coordinate directions of a 3-D system, where there exist two liquid droplets and their vapour. The two droplets merge when they come within the prescribed small distance. The merging of two droplets apart from each other at different initial distances is tested and the possible larger （or critical） non-dimensional distance, in which droplets merging can occur, is discussed. The evolution of the merging process is simulated numerically by employing the Molecular Dynamics （MD） method. For interactions with hydrophobic solid wall, a system with fluid confined between two walls is used to study the wetting phenomena of fluid and solid wall. The results are compared with those of hydrophilic wall to show the unique characteristics of hydrophobic interactions by microscopic methods.

关键词： molecular dynamics simulation mist flow droplets merging hydrophobic wetting

Ascaris-mimicking common bile duct stone: A case report

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World Journal of clinical cases 2020年第19期8卷 4499-4504页

作者： Seo-Youn choi Ha eun Jo Yun Nah Lee ji eun Lee Min Hee Lee San ghyeok Lim Boem Ha Yi Radiology Soonchunhyang University HospitalBucheonBucheon 14584South Korea Digestive disease center and research institute Soonchunhyang University HospitalBucheonBucheon 14584South Korea

BAcKGROUND In most cases,it is not difficult to differentiate common bile duct(cBD)stone from Ascaris infection because they are different disease entities and have different imaging *** two diseases usually demonstrate unique characteristic findings on computed tomography or magnetic resonance ***,we report a rare case from our experience in which a cBD stone mimicked and was misdiagnosed as *** SUMMARY A 72-year-old male presented with elevated serum liver *** tomography showed a hyper-attenuated,elongated lesion in the cBD lumen and associated biliary *** resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography revealed a linear filling defect in the bile ***,elongated echogenic material with a central hypoechogenic area was seen on endoscopic *** the imaging findings caused us to suspect infection with the nematode Ascaris,the lesion was revealed to be a dark-brown-colored cBD stone through endoscopic *** We report a rare case of a cBD stone that mimicked *** also review the literature for side-by-side comparisons of the imaging features of cBD stones and ascariasis.

关键词： case report common bile duct Gallstones Ascaris Ascariasis Multidetector computed tomography Magnetic resonance cholangiopancreatography