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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 *** 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

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Defining and tracing subtypes of patient-derived xenograft models in pancreatic ductal adenocarcinoma

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Cancer Communications 2024年第8期44卷 915-920页

作者： Sangyeop hyun Youngmin Han Jae Yun Moon Young-Ah Suh Won-Gun Yun Wooil Kwon Jong-Eun Lee Daeun kim Ja-Lok Ku Jin-Young Jang Daechan Park Department of Molecular Science and Technology Ajou UniversitySuwonRepublic of Korea Department of Surgery and Cancer Research Institute Seoul National University College of MedicineSeoulRepublic of Korea Molecular Science and Technology Research Center Ajou UniversitySuwonRepublic of Korea DNA Link Inc. SeoulRepublic of Korea Korean Cell Line Bank Laboratory of Cell BiologyCancer Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea

Patient-derived xenograft(PDX)models have been used to explore therapeutic opportunities for pancreatic ductal adenocarcinoma(PDAC)[1].Although original tumor characteristics are altered by cancer-stromal interactions... 详细信息

关键词： adenocarcinoma ductal xenograft

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan kim Donghyun kim Wan-Uk kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of il-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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Galectin 3-binding protein(LGALS3BP)depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1(TGF-β1)availability and inhibits hepatocarcinogenesis

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Cancer Communications 2024年第10期44卷 1106-1129页

作者： Dae-Hwan kim Minjeong Sung Myong-Suk Park Eun-Gene Sun Sumin Yoon Kyung hyun Yoo Kamalakannan Radhakrishnan Sung Yun Jung Woo-Kyun Bae Sang-Hee Cho Ik-Joo Chung Department of Internal Medicine Division of Hematology and OncologyChonnam National University Medical SchoolHwasunSouth Korea Department of Internal Medicine Division of Hematology and OncologyChonnam National University Hwasun HospitalHwasunSouth Korea Combinatorial Tumor Immunotherapy MRC Center Chonnam National University Medical SchoolHwasunSouth Korea National Immunotherapy Innovation Center HwasunSouth Korea BioMedical Sciences Graduate Program Chonnam National UniversityHwasunSouth Korea Department of Biological Science SookmyungWomen’s UniversitySeoulSouth Korea Clinical Vaccine R&D Center Chonnam National UniversityHwasunSouth Korea Department of Biochemistry and Molecular Pharmacology Baylor College of MedicineHoustonTexasUSA

Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling ***:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and *** omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 *** effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout ***:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive *** of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of *** fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 ***3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin *** released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback ***3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced ***,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β***:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.

关键词： F-actin FAK hepatic carcinogenesis IntegrinαV Interferonα JunB LGALS3BP metabolic dysfuntion-associated steatohepatitis tensile force TGF-β1

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Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice

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Journal of Integrative Medicine 2024年第5期22卷 600-613页

作者： Mijung Yeom Sora Ahn Dae-hyun Hahm Sun-Young Jang Se Hoon Jang Su-Yang Park Jae-Hwan Jang Jihan Park Ju-Young Oh In-Seon Lee Kyuseok kim Soon-Kyeong Kwon Hi-Joon Park Acupuncture and Meridian Science Research Center College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Department of Physiology School of MedicineKyung Hee UniversitySeoul 02447Republic of Korea BioNanocomposite Research Center Kyung Hee UniversitySeoul 02447Republic of Korea Department of Science in Korean Medicine College of Korean MedicineGraduate SchoolKyung Hee UniversitySeoul 02447Republic of Korea College of Korean Medicine Kyung Hee UniversitySeoul 02447Republic of Korea Department of Ophthalmology Otorhinolaryngology and Dermatology of Korean MedicineCollege of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Division of Applied Life Science(BK21) Gyeongsang National UniversityJinju 52828Republic of Korea Department of Anatomy&Information Sciences College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea

Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut *** has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely *** purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut *** AD-like skin lesions were induced by applying MC903 topically to the cheek of the *** was done at the Gok-Ji(LI11)***-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and *** microbiota was profiled using 16S rRNA gene sequencing from fecal *** Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of *** beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated ***,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the *** attenuated these abnormalities,which was gut *** Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for

关键词： Atopic dermatitis Acupuncture Gut microbiota Intestinal barrier function

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Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

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Asian Journal of Urology 2024年第3期11卷 450-459页

作者： Jung Ki Jo Seong il Seo MinYong Kang Jinsoo Chung Cheol Kwak Sung-Hoo Hong Cheryn Song Jae Young Park Chang Wook Jeong Seok Hwan Choi Sung Han kim Eu Chang Hwang Chan Ho Lee Hakmin Lee Department of Urology Medical and Digital EngineeringCollege of MedicineHanyang UniversitySeoulRepublic of Korea Department of Urology Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Department of Urology National Cancer CenterGoyangRepublic of Korea Department of Urology Seoul National University HospitalSeoulRepublic of Korea Department of Urology Kangnam St Mary’s HospitalSeoulRepublic of Korea Department of Urology Asan Medical CenterSeoulRepublic of Korea Department of Urology Korea University Ansan HospitalAnsanRepublic of Korea Department of Urology Kyungpook National University HospitalDaeguRepublic of Korea Department of Urology Chonnam National University Hwasun HospitalHwasunRepublic of Korea Department of Urology Inje University Busan Paik HospitalBusanRepublic of Korea Department of Urology Seoul National University Bundang HospitalSeongnamRepublic of Korea

Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment ***:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December *** focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study *** generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as *** addition,frequencies of discontinuation and adverse events were compared among the therapy ***:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in *** that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.

关键词： Tyrosinekinase inhibitor Metastaticrenalcell carcinoma Overall survival Progression-free survival

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Chronic Hepatitis B in Indian Americans: Lack of Screening and Poor Linkage to Care

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International Journal of Clinical Medicine 2024年第4期15卷 197-209页

作者： Chul hyun Soonsik kim Emily Li Minhee Lee Mitchell K. Spinnell Joseph McMenamin Dohyun Cho The Center for Viral Hepatitis Englewood Cliffs NJ USA Korean Community Services of Metropolitan New York New York City NY USA Englewood Hospital Medical Center Englewood NJ USA Christian & Barton LLP Richmond VA USA

Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence

关键词： Hepatitis B Virus Chronic Hepatitis B Indian Americans Health Disparity Community-Based Screening Linkage-to-Care

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ROS-induced metabolic reprogramming to one-carbon metabolism and S-adenosylmethionine-mediated epigenetic modification in il-10-producing B cells for the resolution of pneumonia

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Cellular & Molecular Immunology 2024年第2期21卷 203-204页

作者： Sujin Lee Tae Jin kim Department of Immunology Sungkyunkwan University School of MedicineSuwon16419Republic of Korea

B cells have an essential immunoregulatory function,which is mediated by the secretion of il-10 and TGFβand interaction with activated CD4^(+)T *** antibody-independent function of B cells contributes to ameliorating autoimmune diseases or infection-induced tissue *** this Cellular and Molecular Immunology issue,Fu et *** that regulatory B(Breg)cells play a critical role in resolving Pseudomonas aeruginosa-induced pneumonia[1].

关键词： metabolism pneumonia Immunology

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Aging Behavior of Mg-Y-Zr and Mg-Nd-Zr Cast Alloys

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Journal of Materials Science & Technology 2008年第1期24卷 80-84页

作者： Yang-Do kim Nam-hyun Kang il-Guk Jo Kyung-hyun kim In-Bae kim School of Materials Science and Engineering Pusan National University 30 Jangjun-dongGeumjeong-guBusan 609-735Korea Deptartment of Materials Engineering Korea Institute of Machinery & Materials 66 Sangnam-dongChangwonGyeongsangnam-do 641-010Korea

Aging behavior of Mg-3.6Y-0.5Zr and ***-0.5Zr alloys was investigated by microhardness measurement and transmission electron *** the case of Mg-Y-Zr alloy,the presence ofβ″phase,a major strength- ener,having base centered orthorhombic structure with its lattice constants of a-（β″）=0.64 nm,b-（β″）=2.22 nm, and c-（β″）=0.52 nm was *** the case of Mg-Nd-Zr alloy aged at 250℃,the presence ofβ″andβ′phases was *** crystal structure ofβ″phase was found to be DO-（19） and its orientation relationships with Mg matrix were [0001]-（β″）//[0001]-（Mg） and [01（？）0]-（β″）//[01（？）0]-（Mg）.Theβ′phase had face centered cubic structure and its orientation relationships with Mg matrix were [011]-（β′）//[0001]-（Mg） and [（？）1（？）]β′//[（？）110]）-（Mg）. The ***-0.5Zr alloy showed higher hardness compared with Mg-3.6Y-0.5Zr alloy.

关键词： Mg-Y-Zr alloy Mg-Nd-Zr alloy Precipitation sequence

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TonEBP expression is essential in the il-1β–induced migration and invasion of human A549 lung cancer cells

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Oncology Research 2024年第1期32卷 151-161页

作者： HEE JU SONG TAEHEE kim HAN NA CHOI SOO JIN kim SANG DO LEE Department of Physiology School of MedicineChungnam National UniversityDaejeon35015Korea

Lung cancer has the highest mortality rate among all cancers,in part because it readily *** tumor microenvironment,comprising blood vessels,fibroblasts,immune cells,and macrophages[including tumor-associated macrophages(TAMs)],is closely related to cancer cell growth,migration,and *** secrete several cytokines,including interleukin(il)-1β,which participate in cancer migration and invasion.p21-activated kinase 1(PAK1),an important signaling molecule,induces cell migration and invasion in several ***responsive enhancer-binding protein(TonEBP)is also known to participate in cancer cell growth,migration,and ***,the mechanisms by which it increases lung cancer migration remain ***,in this study,we aimed to elucidate the mechanisms by which il-1βand TonEBP affect lung cancer cell migration and *** found that A549 cocultured-MΦ-secreted il-1βinduced A549 cell migration and invasion via the PAK1 *** deficiency reduced A549 cell migration and invasion and increased responsiveness to il-1β–induced migration and ***1 phosphorylation,which was promoted by il-1β,was reduced when TonEBP was *** results suggest that TonEBP plays an important role in il-1βinduction and invasiveness of A549 cells via the PAK1 *** findings could be valuable in identifying potential targets for lung cancer treatment.

关键词： Lung cancer TonEBP Tumor microenvironment Tumor-associated macrophage il-1β

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