检索结果-南通市图书馆

MEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS

在线全文

学校读者我要写书评

暂无评论

Bone Research 2021年第1期9卷 50-62页

作者： Takayuki Fujii Koichi Murata Se-Hwan Mun Seyeon Bae Ye Ji Lee Tannia Pannellini Kyuho Kang David Oliver kyung-hyun park-min Lionel B.Ivashkiv Arthritis and Tissue Degeneration Program and David Z.Rosensweig Genomics Research Center Hospital for Special SurgeryNew YorkNY 10021USA Department of Orthopaedic Surgery Kyoto University Graduate School of MedicineSakyoKyoto 606-8507Japan Department of Advanced Medicine for Rheumatic Diseases Kyoto University Graduate School of MedicineSakyoKyoto 606-8507Japan Department of Biology Chungbuk National UniversityCheongju 28644Republic of Korea BCMB Allied Program Weill Cornell Graduate School of Medical ScienceNew YorkNY 10021USA Immunology and Microbial Pathogenesis Program Weill Cornell Graduate School of Medical ScienceNew YorkNY 10021USA

Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation,which results in decreased bone mineral *** MEF2C locus,which encodes the transcription factor MADS box transcription enhancer factor 2,polypeptide C(MEF2C),is strongly associated with adult osteoporosis and osteoporotic *** the role of MEF2C in bone and cartilage formation by osteoblasts,osteocytes,and chondrocytes has been studied,the role of MEF2C in osteoclasts,which mediate bone resorption,remains *** this study,we identified MEF2C as a positive regulator of human and mouse osteoclast *** decreased MEF2C expression resulted in diminished osteoclastogenesis,ectopic expression of MEF2C enhanced osteoclast *** transcriptomic and bioinformatic approaches,we found that MEF2C promotes the RANKL-mediated induction of the transcription factors c-FOS and NFATc1,which play a key role in ***,MEF2C binds to FOS regulatory regions to induce c-FOS expression,leading to the activation of NFATC1 and downstream *** deletion of Mef2c in mice resulted in increased bone mass under physiological conditions and protected mice from bone erosion by diminishing osteoclast formation in K/BxN serum induced arthritis,a murine model of inflammatory *** findings reveal direct regulation of osteoclasts by MEF2C,thus adding osteoclasts as a cell type in which altered MEF2C expression or function can contribute to pathological bone remodeling.

关键词： osteoclast MEF2C pathologic

RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae Kibyeong Kim Keunsoo Kang Haemin Kim minjoon Lee Brian Oh Kaichi Kaneko Sungkook Ma Jae Hoon Choi Hojoong Kwak Eun Young Lee Sung Ho park kyung-hyun park-min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA Department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA Department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea Department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea Department of Microbiology Dankook UniversityCheonan3116Republic of Korea Department of Molecular Biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BCMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to t

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Bone Research 2021年第4期9卷 571-581页

作者： Se Hwan Mun Seyeon Bae Steven Zeng Brian Oh Carmen Chai Matthew Jundong Kim Haemin Kim George Kalliolias Chitra Lekha Dahia Younseo Oh Tae-Hwan Kim Jong Dae Ji kyung-hyun park-min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterNew YorkNYUSA Tissue Engineering Regeneration and RepairHospital for Special SurgeryNew YorkNYUSA Department of Cell and Developmental Biology Weill Cornell Medical CollegeNew YorkNYUSA BCMB allied program Weill Cornell Graduate School of Medical SciencesNew YorkNYUSA Hanyang University Institute for Rheumatology Research SeoulKorea Department of Rheumatology Hanyang University Hospital for Rheumatic DiseasesSeoulKorea Rheumatology College of MedicineKorea UniversitySeoulKorea Department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA

Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone *** colony stimulating factor(M-CSF)is abundant in rheumatoid arthritis(RA).However,the role of M-CSF in arthritic bone erosion is not completely ***,we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS,a receptor for M-CSF,leading to the generation of FMS intracellular domain(FICD)*** levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory ***,myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis *** FICD formed a complex with DAP5,and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATcl protein ***,targeting the MNK1/2 pathway diminished arthritic bone *** results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion.

关键词： osteoclast stimulating 1/2

Dibutyl phthalate disrupts[Ca^(2+)]_(i),reactive oxygen species,[pH]_(i),protein kinases and mitochondrial activity,impairing sperm function

在线全文

学校读者我要写书评

暂无评论

Journal of Environmental Sciences 2025年第5期151卷 68-78页

作者： Seung hyun park Myung Chan Gye Department of Life Science and Institute for Natural Sciences Hanyang UniversitySeoul 04763Republic of Korea

To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse *** 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]***,DBP showed biphasic effects on[pH]*** at 10–100μg/mL significantly decreased sperm ***,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm *** significantly increased ROS and *** at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by *** as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm *** at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm ***,DBP showed a biphasic effect on intracellular signaling in *** concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm *** at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.

关键词： Dibutyl phthalate Reactive oxygen species(ROS) [Ca^(2+)]_(i) [pH]_(i) Mitochondria Protein kinases Sperm

Gut–brain axis and environmental factors in parkinson's disease:bidirectional link between disease onset and progression

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第12期20卷 3416-3429页

作者： Soo Jung park kyung Won Kim Eun Jeong Lee Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Life Science and Multidisciplinary Genome Institute Hallym UniversityChuncheonSouth Korea

parkinson's disease has long been considered a disorder that primarily affects the brain,as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containingα-synuclein *** recent decades,however,accumulating research has revealed that parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut,called the“gut–brain axis.”Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in parkinson's disease patients,with findings including impaired intestinal permeability,heightened inflammation,and distinct gut microbiome profiles and ***,α-synuclein deposition has been consistently observed in the gut of parkinson's disease patients,suggesting a potential role in disease ***,individuals with vagotomy have a reduced parkinson's disease *** these observations,researchers have hypothesized thatα-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut–brain axis,leading to parkinson's *** review comprehensively examines the gut's involvement in parkinson's disease,focusing on the concept of a gut-origin for the *** also examine the interplay between altered gut-related factors and the accumulation of pathologicalα-synuclein in the gut of parkinson's disease *** the accessibility of the gut to both dietary and pharmacological interventions,targeting gut-localizedα-synuclein represents a promising avenue for developing effective parkinson's disease therapies.

关键词： gut inflammation gut microbiome gut-brain axis micro/nano-plastics parkinson’s disease α-synuclein

Effect of preprocessing on performances of machine learning-based mineral composition analysis on gas hydrate sediments, Ulleung Basin, East Sea

在线全文

学校读者我要写书评

暂无评论

Petroleum Science 2025年第1期22卷 151-162页

作者： Hongkeun Jin Ju Young park Sun Young park Byeong-Kook Son Baehyun min kyungbook Lee Department of Geoenvironmental Sciences Kongju National University Tunnel & Underground Facility Division ESCO Consultant & Engineers Company Yellow Sea Institute of Geoenvironmental Sciences Petroleum and Marine Research Division Korea Institute of Geoscience and Mineral Resources Department of Climate and Energy Systems Engineering Ewha Womans University Center for Climate/Environment Change Prediction Research Ewha Womans University

Gas hydrate(GH) is an unconventional resource estimated at 1000-120,000 trillion *** on GH is ongoing to determine its geological and flow characteristics for commercial production. After two large-scale drilling expeditions to study the GH-bearing zone in the Ulleung Basin, the mineral composition of 488 sediment samples was analyzed using X-ray diffraction(XRD). Because the analysis is costly and dependent on experts, a machine learning model was developed to predict the mineral composition using XRD intensity profiles as input data. However, the model's performance was limited because of improper preprocessing of the intensity profile. Because preprocessing was applied to each feature, the intensity trend was not preserved even though this factor is the most important when analyzing mineral composition. In this study, the profile was preprocessed for each sample using minmax scaling because relative intensity is critical for mineral analysis. For 49 test data among the 488data, the convolutional neural network(CNN) model improved the average absolute error and coefficient of determination by 41% and 46%, respectively, than those of CNN model with feature-based preprocessing. This study confirms that combining preprocessing for each sample with CNN is the most efficient approach for analyzing XRD data. The developed model can be used for the compositional analysis of sediment samples from the Ulleung Basin and the Korea Plateau. In addition, the overall procedure can be applied to any XRD data of sediments worldwide.

关键词： Sample-based preprocessing X-ray diffraction (XRD) Machine learning mineral composition Gas hydrate (GH) Ulleung basin

Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO kyung park minSUK KWON minAE AN JUNG YONG HONG JOON OH park SUNG HEE LIM SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2025年第6期31卷 44-61页

作者： Han-Ning Xuan Yuan hyun Sung Kim Gye Ryeol park Jae Eun Ryu Ji Eun Kim In Young Kang Hye Young Kim Seung min Lee Ju Hee Oh Eileen L Yoon Dae Won Jun Department of Internal Medicine Hanyang University School of MedicineSeoul 04763South Korea Department of Pathology Hanyang University School of MedicineSeoul 04763South Korea Department of Translational Medicine Graduate School of Biomedical Science and EngineeringHanyang UniversitySeoul 04763South Korea Department of Obstetrics and Gynecology Institute of Women’s Medical Life ScienceYonsei Cancer CenterSeverance HospitalYonsei University College of MedicineSeoul 04763South Korea Department of Internal Medicine Sanggye Paik HospitalInje University College of MedicineSeoul 01757South Korea

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver *** study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease *** focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related *** To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver *** Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various *** human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate ***,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver *** While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and ***,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid *** MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease *** MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

关键词： RAW 264.7 cell Cell death Necroptosis Mixed lineage kinase domain-like protein Non-alcoholic fatty liver disease Mixed lineage kinase domain-like protein adenosine triphosphate binding inhibitor Alcoholic liver disease

Immortalization of epidural fat-derived mesenchymal stem cells: In vitro characterization and adipocyte differentiation potential

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Stem Cells 2025年第1期17卷 40-52页

作者： Seoung-Woo Lee Young-Ju Lim Hee-Yeon Kim Wansoo Kim Wook-Tae park min-Jung Ma Junho Lee min-Soo Seo Young In Kim Sangbum park Seong-Kyoon Choi Gun Woo Lee Core Protein Resources Center Daegu-Gyeongbuk Institute of Science and TechnologyDaegu 42988South Korea Department of Orthopedic Surgery Yeungnam University Medical CenterYeungnam University College of MedicineDaegu 42415South Korea Department of Veterinary Pathology College of Veterinary MedicineKyungpook National UniversityDaegu 41566South Korea School of Life Science BK21 FOUR KNU Creative BioResearch GroupKyungpook National UniversityDaegu 41566South Korea Laboratory of Veterinary Tissue Engineering College of Veterinary MedicineKyungpook National UniversityDaegu 41566South Korea College of Veterinary Medicine Kyungpook National UniversityDaegu 41566South Korea Department of Veterinary Tissue Engineering Kyungpook National UniversityDaegu 41566South Korea Cellexobio. Ltd.Daegu 42415South Korea Michigan State University Institute for Quantitative Health Science&EngineeringEast LansingMI 48824United States Department of Orthopedic Surgery Yeungnam University College of MedicineDaegu 42415South Korea

BACKGROUND Mesenchymal stem cells(MSCs)are promising candidates for regenerative therapy due to their self-renewal capability,multilineage differentiation potential,and immunomodulatory *** molecular characteristics of MSCs are influenced by their ***,epidural fat(EF)and EF-derived MSCs(EF-MSCs)have garnered attention due to their potential benefits to the spinal microenvironment and their high expression of neural SC ***,their clinical applications are limited due to cell senescence and limited accessibility of *** many studies have attempted to establish an immortalized,stable SC line,the characteristics of immortalized EF-MSCs remain to be *** To establish and analyze stable immortalized *** The phenotypes of EF-MSCs were analyzed using optical *** immortalization was performed using lentiviral *** biomolecular characteristics of the cells were analyzed by immunoblotting,quantitative PCR,and *** The immortalized EF-MSCs demonstrated a significantly extended lifespan compared to the control group,with well-preserved adipogenic potential and SC surface marker *** of human telomerase reverse transcriptase genes markedly increased the lifespan of *** analysis revealed substantial increase in the expression of DNA replication pathway components in immortalized *** Immortalized EF-MSCs exhibited significantly enhanced proliferative capacity,retained adipogenic potential,and upregulated the expression of DNA replication pathway components.

关键词： Immortalization Transfection Stem cell Epidural fat Proteomics