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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

11C-Labeled Capsaicin and Its in VivoMolecular imaging in Rats by Positron Emission Tomography

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Food and Nutrition Sciences 2015年第2期6卷 216-220页

作者： Miki Goto Hiroshi Mizuma Yasuhiro Wada Masaaki Suzuki Yasuyoshi Watanabe Hirotaka Onoe Hisashi Doi division of bio-function dynamics imaging RIKEN Center for Life Science Technologies (CLST) Kobe Japan National Center for Geriatrics and Gerontology Obu Japan

Synthesis of 11C-labeled capsaicin ([11C]-2) was accomplished by O-[11C]methylation with [11C]-methyl iodide to a corresponding catechol precursor (1). In Vivo whole-body distribution of [11C]-2 in rats was investigated by positron emission tomography after intravenous injection. The results showed that [11C]-2 accumulated in the brain and body surface, which was closely associated with the expression of transient receptor potential vanilloid 1.

关键词： PET Capsaicin 11C-Labeling TRPV1 Blood-Brain Barrier

biomolecular condensates and disease pathogenesis

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Science China(Life Sciences) 2024年第9期67卷 1792-1832页

作者： Ke Ruan Ge Bai Yanshan Fang Dan Li Tingting Li Xingguo Liu Boxun Lu Qing Lu Zhou Songyang Shuguo Sun Zheng Wang Xin Zhang Wen Zhou Hong Zhang The First Affiliated Hospital&School of Life Sciences Ministry of Education Key Laboratory for Membrane-less Organelles&Cellular DynamicsHefei National Research Center for Interdisciplinary Sciences at the MicroscaleCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Nanhu Brain-computer Interface Institute Hangzhou 311100China Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of MedicineHangzhou 310058China Interdisciplinary Research Center on biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China Department of biomedical Informatics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China CAS Key Laboratory of Regenerative biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Neurology Department at Huashan Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceSchool of Life SciencesFudan UniversityShanghai 200433 China Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of EducationBio-X InstitutesShanghai Jiao Tong UniversityShanghai 200030China State Key Laboratory of biocontrol MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging ResearchSchool of Life SciencesSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510275China Department of Human Anatomy Hist

biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific *** of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological ***,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase *** then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological ***,we describe the emerging discovery of chemical modulators of phase separation.

关键词： liquid-liquid phase separation biomolecular condensate membraneless organelle

Evaluation of TlOH Effect for Pd0-Mediated Cross-Coupling of Methyl Iodide and Excess Boronic Acid Ester toward Fabrication of [11C]CH3-Incorporated PET Tracer

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International Journal of Organic Chemistry 2013年第3期3卷 220-223页

作者： Hiroko Koyama Hisashi Doi Masaaki Suzuki Department of Clinical and Experimental Neuroimaging Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology Obu-shi Japan division of bio-function dynamics imaging Riken Center for Life Science Technologies (CLST) 6-7-3 Minatojima Minamimachi Kobe Japan division of Regeneration and Advanced Medical Science Gifu University Graduated School of Medicine Gifu University Gifu Japan

The use of thallium(I) hydroxide (TlOH) as a base is known to extremely accelerate the Suzuki-Miyaura cross-coupling reaction using organoboronic acid or organoboronic acid ester as a substrate. Here, we investigated the effects of TlOH by comparing with other conventional bases such as KOH, K2CO3, and CsF for Pd0-mediated rapid cross-coupling reactions between CH3I and organoborane reagents, such as phenyl-, (Z)-4-benzyloxy-2-butenyl-, and benzylboronic acid pinacol esters under the conditions CH3I/borane/Pd0/base (1:40:1:3) in THF/H2O or DMF/H2O for 5 min with an aim to fabricate a PET tracer efficiently. Consequently, however, the use of TlOH was much less efficient than the other bases for the acceleration of cross-coupling reactions. Thus, it was reconfirmed that the milder and non-toxic conditions using K2CO3 or CsF so far developed by our group were most appropriate for the rapid C-methylations.

关键词： Synthesis of Short-Lived Positron Emission Tomography Probes Suzuki-Miyaura-Type Rapid Cross-Coupling Rapid C-Methylation TlOH

Dual Oxidase Mutant Retards Mauthner-Cell Axon Regeneration at an Early Stage via Modulating Mitochondrial dynamics in Zebrafish

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Neuroscience Bulletin 2020年第12期36卷 1500-1512页

作者： Lei-Qing Yang Min Chen Da-Long Ren Bing Hu Eye Center The First Affiliated Hospital of USTCHefei National Laboratory for Physical Sciences at the MicroscaleChinese Academy of Sciences Key Laboratory of Brain Function and DiseaseSchool of Life SciencesDivision of Biomedical SciencesUniversity of Science and Technology of ChinaHefei 230026China Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and bio-breeding College of Animal Science and TechnologyAnhui Agricultural UniversityHefei 230036China

Dual oxidase(duox)-deriyed reactive oxygen species(ROS)have been correlated with neuronal polarity,cerebellar development,and ***,there have not been many comprehensive studies of the effect of individual duox isoforms on central-axon regenerationin ***,we explored this question in zebrafish,an excellent model organism for central-axon regeneration *** our research,mutation of the duox gene with CRISPR/Cas9 significantly retarded the singleaxon regeneration of the zebrafish Mauthner cell in *** deep transcriptome sequencing,we found that the expression levels of related functional enzymes in mitochondria were down-regulated in duox mutant *** vivo imaging showed that duox mutants had significantly disrupted mitochondrial transport and redox state in single Mauthner-cell *** research data provide insights into how duox is involved in central-axon regeneration by changing mitochondrial transport.

关键词： duox Zebrafish Mauthner cell Axon regeneration Mitochondrial dynamics

Immunoadsorption therapy reduces oxidative stress in patients with dilated cardiomyopathy

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World Journal of Cardiovascular Diseases 2012年第4期2卷 305-312页

作者： Hiroki Kasai Yuichiro Kashima Atsushi Izawa Takeshi Tomita Yusuke Miyashita Jun Koyama Masafumi Takahashi Taku Yoshio Yoshikazu Yazaki Makoto Higuchi Uichi Ikeda Department of Cardiovascular Medicine Shinshu University School of Medicine Nagano Japan Department of Nephrology Shinshu University School of Medicine Nagano Japan Department of Rheumatology and Clinical Immunology Jichi Medical University Tochigi Japan division of bio-imaging Jichi Medical University Tochigi Japan division of Cardiology Matsumoto Medical Center Nagano Japan

Several literatures have reported that the elimination of autoantibodies by immunoadsorption (IA) therapy induced short- and long-term improvements in cardiac function of patients with dilated cardiomyopathy (DCM). We assessed whether reduction in oxidative stress was related to the mechanism underlying left ventricular functional benefit from IA. We studied 7 patients with DCM (New York Heart Association (NYHA) functional class III/IV). Autoantibodies were removed with IA by passing patients’ plasma over tryptophan columns. The level of anti-β1-adrenoreceptor (AR) autoantibodies was measured by enzyme- linked immunosorbent assay. The level of diacron- reactive oxygen metabolite (d-ROM) was determined as a marker of oxidative stress. During IA, the anti- β1-AR autoantibodies titers of all the patients decreased significantly from 27.8 ± 5.0 to 18.7 ± 5.5 U/ml (p < 0.01). IA induced the following hemodynamic improvements: cardiac index increased from 1.71 ± 0.40 to 1.97 ± 0.41 l/min/m2 and left ventricular ejection fraction (LVEF) increased from 22.8 ± 6.1 to 29.1±9.1% (p < 0.05). d-ROM level decreased significantly from 392.7 ±17.0 to 314.1 ± 22.0 Carratelli units (p < 0.05), and was negatively correlated with LVEF before and after IA therapy (r = -0.601, p < 0.05). The anti-β1-AR autoantibodies, LVEF and d- ROM returned to the baseline levels at 12 months after IA. In conclusion, oxidative stress reduction may be responsible for the beneficial effect of IA therapy in patients with DCM.

关键词： Autoantibody Immunoglobulin Plasmapheresis

Dynamical amplification of electric polarization through nonlinear phononics in 2D SnTe

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npj Computational Materials 2020年第1期6卷 155-162页

作者： Dongbin Shin Shunsuke A.Sato Hannes Hübener Umberto De Giovannini Noejung Park Angel Rubio Max Planck Institute for the Structure and dynamics of Matter and Center for Free-Electron Laser Science Luruper Chaussee 149Hamburg 22761Germany Center for Computational Sciences University of TsukubaTsukuba 305-8577Japan Nano-bio Spectroscopy Group Departamento de Fisica de MaterialesUniversidad del Pas VascoSan Sebastian 20018Spain Department of Physics Ulsan National Institute of Science and TechnologyUNIST-gil 50Ulsan 44919Korea Center for Computational Quantum Physics(CCQ) The Flatiron Institute162 Fifth AvenueNew YorkNY 10010USA

Ultrafast optical control of ferroelectricity using intense terahertz fields has attracted significant *** we show that the nonlinear interactions between two optical phonons in SnTe,a two-dimensional in-plane ferroelectric material,enables a dynamical amplification of the electric polarization within subpicoseconds time *** first-principles time-dependent simulations show that the infrared-active out-of-plane phonon mode,pumped to nonlinear regimes,spontaneously generates in-plane motions,leading to rectified oscillations in the in-plane electric *** suggest that this dynamical control of ferroelectric material,by nonlinear phonon excitation,can be utilized to achieve ultrafast control of the photovoltaic or other nonlinear optical responses.

关键词： nonlinear ferroelectric phonon

Global characterization of modifications to the charge isomers of IgG antibody

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Journal of Pharmaceutical Analysis 2022年第1期12卷 156-163页

作者： Xinling Cui Wei Mi Zhishang Hu Xiaoyu Li Bo Meng Xinyuan Zhao Xiaohong Qian Tao Zhu Wantao Ying State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingChina National Institute of Metrology Center for Advanced Measurement ScienceBeijingChina National Institute of Metrology Chemical Metrology&Analytical Science DivisionBeijingChina CanSino bio Corporation Tianjin Key Laboratory of Recombinant Bacterial Recombination and Bacterial Vaccines TianjinChina

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality *** comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is *** intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge *** CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three ***,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation ***,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were *** mapping showed nonuniform deamidation and glycoform distribution among *** total,10 N-glycoforms were detected by peptide ***,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched *** and quantitative analyses demonstrated the dynamics of 24 *** results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight *** study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

关键词： Antibody Charge isomers Mass spectrometry Posttranslational modification Glycopeptide

Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous