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4-1BB signaling activates glucose and fatty acid metabolism to enhance CD8^(+) T cell proliferation

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Cellular & Molecular Immunology 2017年第9期14卷 748-757页

作者： Beom K Choi Do Y Lee Don G Lee Young H Kim seon-Hee Kim Ho s Oh Chungyong Han byoung s kwon Cancer Immunology Branch Division of Cancer BiologyNational Cancer CenterGoyangGyeonggi 10408Korea Department of Internal Medicine Yonsei University College of MedicineSeoul 120-752Korea Immune Cell Production Unit Program for Immunotherapeutic ResearchNational Cancer CenterGyeonggi 10408Korea Eutilex Catholic University School of MedicineSeoul 06591Korea Department of Medicine Tulane University Health Sciences CenterNew OrleansLA 70112USA

4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T *** these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activated glucose and fatty acid *** found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8^(+)T cells in vitro,increasing their size and *** with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8^(+)T cell proliferation required both glucose and fatty acid ***-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1(LKB1)-AMP-activated protein kinase(AMPK)-acetyl-CoA carboxylase(ACC)signaling pathway,which may be responsible for activating the metabolism of glucose and fatty *** also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB *** increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8^(+)T cells with the fatty acid oxidation inhibitor,etomoxir,but not with the glycolysis inhibitor,*** conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass,and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8^(+)T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.

关键词： AMPK CD8^(+)T cells 4-1BB(CD137) LKB1 metabolism

Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8^(+)T cell responses

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Cellular & Molecular Immunology 2021年第8期18卷 1956-1968页

作者： seon-Hee Kim Rohit singh Chungyong Han Eunjung Cho Yu I.Kim Don G.Lee Young H.Kim sang soo Kim Dong Hoon shin Hye Jin You Hyeon-Woo Lee byoung s.kwon Beom K.Choi Division of Tumor Immunology National Cancer CenterGoyang10408Republic of Korea Graduate school of Cancer science and Policy National Cancer CenterGoyang10408Republic of Korea Biomedicine Production Branch Program for Immunotherapy ResearchGoyang10408Republic of Korea Eutilex Institute for Biomedical Research EutilexCo.Ltd.Seoul08594Republic of Korea Division of Convergence Technology National Cancer CenterGoyang10408Republic of Korea Division of Translational science National Cancer CenterGoyang10408Republic of Korea Institute of Oral Biology School of DentistryGraduate SchoolKyung Hee UniversitySeoul02447Republic of Korea Department of Medicine Tulane University Health Sciences CenterNew OrleansLA70112USA

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor ***,the adverse side effects associated with agonist antibodies have hindered their clinical ***,we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB *** show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1^(+)CD8^(+)T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8^(+)T cells,which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB ***,repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes(TDLNs)of mice due to recruitment and accumulation of macrophages via the CD8^(+)T cell-IFN-γ*** was accompanied by excessive lymph node swelling,which impaired the sequential activation of CD8^(+)T *** data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing,which should be considered during the clinical development of immunomodulating therapy.

关键词： 4-1BB Costimulation Granuloma CD8 lymphocyte Macrophage

4-1BB-4-1BBL cis-interaction contributes to the survival of selfreactive CD8^(+)T cell

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Cellular & Molecular Immunology 2023年第9期20卷 1077-1080页

作者： Eunjung Cho Rohit singh Chungyong Han seon-Hee Kim Kwang H.Kim Bo-Mi Park Dong Hoon shin seongeun Han Young H.Kim byoung s.kwon Ki Taek Nam Beom K.Choi Immuno-oncology Branch Division of Rare and Refractory CancerNational Cancer CenterGoyang 10408Republic of Korea severance Biomedical science Institute Brain Korea 21 Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea Department of Cancer Biomedical science Graduate School of Cancer Science and PolicyNational Cancer CenterGoyang 10408Republic of Korea Department of Biomedical Laboratory science Catholic Kwandong UniversityGangneung 25601Republic of Korea Biomedicine Production Branch Research InstituteNational Cancer CenterGoyang 10408Republic of Korea Anticancer Resistance Branch Division of Rare and Refractory CancerResearch InstituteNational Cancer CenterGoyang 10408Republic of Korea Eutilex Co. Ltd.Geumcheon-guSeoul 08594Republic of Korea Department of Medicine Tulane University Health Sciences CenterNew OrleansLA 70112USA Innobationbio Co. Ltd.Mapo-guSeoul 03929Republic of Korea

4-1BB is an inducible receptor expressed on activated T cells,while its ligand,4-1BBL,is mainly expressed in antigen-presenting cells and macrophages[1,2].To the best of our knowledge,ligandmediated transactivation of... 详细信息

关键词： interaction activation knowledge

Laser‑Induced and MOF‑Derived Metal Oxide/Carbon Composite for synergistically Improved Ethanol sensing at Room temperature

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Nano-Micro Letters 2024年第6期16卷 210-220页

作者： Hyeongtae Lim Hyeokjin kwon Hongki Kang Jae Eun Jang Hyuk‑Jun kwon Department of Electrical Engineering and Computer science DGISTDaegu 42988South Korea Convergence Research Advanced Centre for Olfaction DGISTDaegu 42988South Korea

Advancements in sensor technology have significantly enhanced atmospheric ***,metal oxide and carbon(MO_(x)/C)hybrids have gained attention for their exceptional sensitivity and room-temperature sensing ***,previous methods of synthesizing MO_(x)/C composites suffer from problems,including inhomogeneity,aggregation,and challenges in ***,we introduce a refined method that employs a metal–organic framework(MOF)as a precursor combined with direct laser *** inherent structure of MOFs ensures a uniform distribution of metal ions and organic linkers,yielding homogeneous MO_(x)/C *** laser processing facilitates precise micropatterning(sensor rapidly detected ethanol gas even at room temperature(105 and 18 s for response and recovery,respectively),with a broad range of sensing performance from 170 to 3,400 ppm and a high response value of up to 3,500%.Additionally,this sensor exhibited enhanced stability and thermal resilience compared to previous MOF-based *** research opens up promising avenues for practical applications in MOF-derived sensing devices.

关键词： Metal-organic frameworks Metal oxide Carbon composite Laser Gas sensor

Enhancing Identity Protection in Metaverse-Based Psychological Counseling system

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Computers, Materials & Continua 2024年第1期78卷 617-632页

作者： Jun Lee Hanna Lee seong Chan Lee Hyun kwon Department of Game software Hoseo UniversityAsan-si31499Korea Yatav Enter Seoul04799Korea Department of Artificial Intelligence and Data science Korea Military AcademySeoul01805Korea

Non-face-to-face psychological counseling systems rely on network technologies to anonymize information regard-ing client ***,these systems often face challenges concerning voice data leaks and the suboptimal communication of the client’s non-verbal expressions,such as facial cues,to the *** study proposes a metaverse-based psychological counseling system designed to enhance client identity protection while ensuring efficient information delivery to counselors during non-face-to-face *** proposed systemincorporates a voicemodulation function that instantlymodifies/masks the client’s voice to safeguard their ***,it employs real-time client facial expression recognition using an ensemble of decision trees to mirror the client’s non-verbal expressions through their avatar in the metaverse *** system is adaptable for use on personal computers and smartphones,offering users the flexibility to access metaverse-based psychological counseling across diverse *** performance evaluation of the proposed system confirmed that the voice modulation and real-time facial expression replication consistently achieve an average speed of 48.32 frames per second or higher,even when tested on the least powerful smartphone ***,a total of 550 actual psychological counseling sessions were conducted,and the average satisfaction rating reached 4.46 on a 5-point *** indicates that clients experienced improved identity protection compared to conventional non-face-to-face metaverse counseling ***,the counselor successfully addressed the challenge of conveying non-verbal cues from clients who typically struggled with non-face-to-face psychological *** proposed systemholds significant potential for applications in interactive discussions and educational activities in the metaverse.

关键词： Metaverse counseling system face tracking identity protection

Learning Improves Peripheral Vision Via Enhanced Cortico-Cortical Communications

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Neuroscience Bulletin 2024年第7期40卷 1007-1011页

作者： Yuwei Cui Xincheng Lu MiYoung kwon Nihong Chen Department of Psychological and Cognitive sciences Tsinghua UniversityBeijing 100084China IDG/McGovern Institute for Brain Research at Tsinghua University Beijing 100084China Department of Psychology Northeastern UniversityBostonMA 02115USA

Dear Editor,The adult human visual system is capable of reshaping its oculomotor control and sensory coding to adapt to impoverished visual *** one's central vision is deprived,a spared part of the peripheral retina acts as a pseudo fovea termed as preferred retinal locus(PRL).In people with normal vision,a PRL can be induced via oculomotor training with simulated central vision loss[1,2].

关键词： visual shaping capable

Primary Ewing sarcoma of the kidney mimicking cystic papillary renal cell carcinoma in an older patient:A case repor

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World Journal of Clinical Cases 2024年第15期12卷 2606-2613页

作者： suhong Kim Jongsoo Park Young Hwii Ko Hee Jung kwon Department of Radiology Yeungnam UniversityDaegu 42415South Korea Department of Urology Yeungnam UniversityDaegu 42415South Korea Department of Pathology Yeungnam UniversityDaegu 42415South Korea

BACKGROUND Ewing’s sarcoma(Es)is a neuroectodermal tumor that typically occurs in the bones and soft tissues of children and young *** renal Es is rare;only a few cases and a small case series have been documented,and only four cases involved primary renal Es in older people(>65 years old).CAsE sUMMARY Herein,we describe the radiological and pathological features of primary renal Es in an older person.A 76-year-old man complained of poor oral intake and was found to have a large cystic renal mass with indistinct margins on computed ***-guided biopsy revealed that the tumor contained small round blue *** patient underwent a right radical *** tumor cells showed diffuse membranous CD99,and nuclear friend leukemia integration 1 transcription factor and NK2 Homeobox *** in situ hybridization revealed EWsR1 ***,18F-fluorodeoxyglucose positron emission tomography revealed no evidence of *** patient was diagnosed with primary renal *** months following the surgery,local recurrence and distant metastasis were *** renal Es is rare and often lethal in older *** specific imaging findings are unknown,and treatment protocols have not been *** This case report describes the radiological and pathological features of primary renal Es in an older person.

关键词： Ewing sarcoma Elder Renal Kidney Neuroectodermal Case report

Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun kwon Taeyeon Kim Jin Woo Lee Min-Kyoo shin sang Hee shim Natural Products Research Institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea College of Pharmacy and Research Institute of Pharmaceutical sciences Seoul National UniversitySeoul 08826Republic of Korea College of Pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** structures were elucidated using 1D,2D NMR,and *** configurations were established on the basis of 1H coupling constants,ROEsY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,sH-sY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

Lactose-free milk powder can effectively relieve diarrhea symptoms in weaning sD rats and children

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Food science and Human Wellness 2024年第3期13卷 1494-1502页

作者： Manman Liu shiwen Han Boya Li Cheng Chen Lu Yao Jung-il kwon Juan Jin Huilian Che Beijing Advanced Innovation Center for Food Nutrition and Human Health College of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijing 100083China Maeil Innovation Center Maeil Dairies Co.Ltd.Seoul 03142South Korea

Diarrhea has become the leading cause of illness and death among infants and young children in developing ***,patients with diarrhea showed damaged intestinal epithelial villi,usually accompanied by lactase *** this study,we evaluated the therapeutic effects of lactose-free milk powder on rats and children with ***-associated diarrhea(AAD)model was established by gavage with antibiotic mixture in sD rats,followed by administration of milk powder containing lactose or *** results showed that lactose-free milk powder ameliorated A AD-related diarrhea symptoms,and accelerated the recovery from *** 16s sequencing results indicated lactose-free milk powder contributed to increase theα-andβ-diversity of intestinal flora,and restore the intestinal microbiota *** conclusion,our data demonstrate that lactose-free milk powder could alleviate diarrhea by restoring gut microbiota and intestinal barrier function.

关键词： Diarrhea Lactose-free Milk powder Intestinal barrier Gut microbiota