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Macrophage-specific inhibition of the histone demethylase JMJd3 decreases STING and pathologic inflammation in diabetic wound repair

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Cellular & Molecular Immunology 2022年第11期19卷 1251-1262页

作者： Christopher O.Audu William J.Melvin Amrita d.Joshi Sonya J.Wolf Jadie Y.Moon Frank M.davis Emily C.barrett Kevin d.Mangum hongping deng Xianying Xing Rachel Wasikowski Lam C.Tsoi Sriganesh B.Sharma Tyler M.Bauer James Shadiow Matthew A.Corriere Andrea TObi Steven LKunkel Benjamin Levi Bethany BMoore Johann EGudjonsson Andrew MSmith Katherine A.Gallagher department of Surgery Section of Vascular SurgeryUniversity of MichiganAnn ArborMIUSA department of Microbiology and Immunology University of MichiganAnn ArborMIUSA department of Medicinal Chemistry University of MichiganAnn ArborMIUSA department of Surgery Section of General SurgeryUniversity of MichiganAnn ArborMIUSA department of Bioengineering University of IllinoisUrbana-ChampaignChampaignILUSA department of dermatology University of MichiganAnn ArborMIUSA department of Pathology University of MichiganAnn ArborMIUSA department of Surgery University of Texas Southwestern Medical CenterDallasTXUSA

Macrophage plasticity is critical for normal tissue repair following injury.In pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are unknown.here,using single-cell RNA sequencing of human diabetic wounds,we identified increased JMJd3 in diabetic wound macrophages,resulting in increased inflammatory gene expression.Mechanistically,we report that in wound healing,JMJd3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling.however,in the diabetic state,we found that IL-6,a cytokine increased in diabetic wound tissue at later time points post-injury,regulates JMJd3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJd3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an h3K27me3 mechanism.Interestingly,RNA sequencing of wound macrophages isolated from mice with JMJd3-deficient myeloid cells(Jmjd3f/fLyz2Cre+)identified that the STING gene(Tmem173)is regulated by JMJd3 in wound macrophages.STING limits inflammatory cytokine production by wound macrophages during healing.however,in diabetic mice,its role changes to limit wound repair and enhance inflammation.This finding is important since STING is associated with chronic inflammation,and we found STING to be elevated in human and murine diabetic wound macrophages at late time points.Finally,we demonstrate that macrophage-specific,nanoparticle inhibition of JMJd3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING.Taken together,this work highlights the central role of JMJd3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

关键词： wound healing epigenetics diabetes JMJd3 STING

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World Journal of Critical Care Medicine 2022年第4期11卷 236-245页

作者： Vincent Issac Lau Jeffrey A Johnson Sean M Bagshaw Oleksa G Rewa John Basmaji Kimberley A Lewis M Elizabeth Wilcox Kali barrett Francois Lamontagne Francois Lauzier Niall d Ferguson Simon J W Oczkowski Kirsten M Fiest daniel J Niven henry T Stelfox Waleed Alhazzani Margaret herridge Robert Fowler deborah J Cook Bram Rochwerg Feng Xie department of Critical Care Medicine University of AlbertaEdmonton T6G 2B7ABCanada School of Public health Inst Hlth EconUniversity of AlbertaEdmonton T6G 2B7ABCanada department of Medicine Division of Critical CareWestern UniversityLondon N6A 5W9Canada division of Critical Care McMaster UniversityHamilton L8N 4A6Canada Interdepartmental division of Critical Care University of TorontoToronto M5T 2S8Canada department of Medicine University SherbrookeSherbrooke J1H 5N4Canada departments of Medicine and Anesthesiology University LavalLaval G1V 4G2Canada department Critical Care Medicine University of TorontoToronto M5G 2C4Canada department of Medicine McMaster ClinHamilton Gen HospMcMaster UniversityHamilton L8N 4A6Canada department of Community health Sciences&Institute for Public health University of CalgaryCalgary T2N 2T9Canada department of Critical Care Medicine University CalgaryCalgary T2N 2T9Canada department of Community health Sciences University of CalgaryCalgary T2N 2T9Canada department of Medicine McMaster UniversityHamilton L8N 4A6Canada Indepartmental division of Critical Care University Health NetworkToronto M5G 2C4Canada departments of Medicine and Critical Care Medicine Sunnybrook Health Sciences CenterInstitute of Health Policy Management and EvaluationUniversity of TorontoToronto M4N 3M5Canada health Research Methods Evidence and ImpactMcMaster UniversityHamilton L8N 3Z5Canada

Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a common end-impact on a patient’s functional capacity and health-related quality-of-life(hRQoL).Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences.hence,as mortality decreases within critical care,it becomes increasingly important to measure intensive care unit(ICU)survivor hRQoL.hRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0(representing death)and 1(representing full health).They can be combined with survival to calculate quality-adjusted life-years(QALY),which are one of the most widely used methods of combining morbidity and mortality into a composite outcome.Although QALYs have been use for health-technology assessment decision-making,an emerging and novel role would be to inform clinical decision-making for patients,families and healthcare providers about what expected hRQoL may be during and after ICU care.Critical care randomized control trials(RCTs)have not routinely measured or reported hRQoL(until more recently),likely due to incapacity of some patients to participate in patient-reported outcome measures.Further differences in hRQoL measurement tools can lead to non-comparable values.To this end,we propose the validation of a gold-standard hRQoL tool in critical care,specifically the EQ-5d-5L.Both combined health-utility and mortality(disaggregated)and QALYs(aggregated)can be reported,with disaggregation allowing for determination of which components are the main drivers of the QALY outcome.Increased use of hRQoL,health-utility,and QALYs in critical care RCTs has the potential to:(1)Increase the likelihood of finding important effects if they exist;(2)improve research efficiency;and(3)help inform optimal management of critically ill patients allowing fo

关键词： Critical care health-related quality of life Quality-adjusted life-years health-utility Mortality Morbidity Kaplan-Meier curves

human Milk Oligosaccharides Enhance Innate Immunity to Respiratory Syncytial Virus and Influenza <i>in Vitro</i>

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Food and Nutrition Sciences 2014年第14期5卷 1387-1398页

作者： Geralyn duska-McEwen Albert P. Senft Teah L. Ruetschilling Edward G. barrett Rachael h. Buck discovery R & d Abbott Nutrition Columbus USA Lovelace Respiratory Research Institute Albuquerque USA

human milk oligosaccharides (hMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. hMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.

关键词： human Milk Oligosaccharides Respiratory Syncytial Virus Influenza Virus Inflammation Innate Immunity

Creation of Molecular Vortex

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量子光学学报 2006年第B8期12卷 62-63页

作者： Weiping Zhang h. Y. Ling S. Yi h. Pu d. Grochowski Key Laboratory of Optical and Magnetic Resonance Spectroscopy （Ministry of Education） Department of Physics East China Normal University Shanghai 200062 P. R. China department of Physics and Astronomy and Rice Quantum Institute Rice University Houston TX 77251-1892 USA department of Physics and Astronomy Rowan University Glassboro New Jersey 08028-1700 USA

肿瘤干细胞分析及CA125检测用于卵巢癌之处理

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癌症 1988年第1期 27-30页

作者：谭道彩,C.Welander,h.d.homesley,M.Berens,R.barrett 中山医科大学肿瘤医院美国Wake Forest大学医学院妇产科美国Wake Forest大学医学院妇产科美国Wake Forest大学医学院妇产科美国Wake Forest大学医学院妇产科

1984年1月至1985年7月,103例卵巢癌进行治疗。属Ⅰ期者11例,Ⅱ期15例,Ⅲ期45例,Ⅳ期7例,复发癌25名;浆液性腺癌70例。患者先行腹式全宫附件及大网切除术,并切除盆、腹腔之肿瘤。残余癌体积的直径超2厘米,是henckhoff管于腹腔。103患者... 详细信息

1984年1月至1985年7月,103例卵巢癌进行治疗。属Ⅰ期者11例,Ⅱ期15例,Ⅲ期45例,Ⅳ期7例,复发癌25名;浆液性腺癌70例。患者先行腹式全宫附件及大网切除术,并切除盆、腹腔之肿瘤。残余癌体积的直径超2厘米,是henckhoff管于腹腔。103患者中49例作肿瘤干细胞分析及CA 125检测,54名为对照组。据肿瘤干细胞分析以选择抗癌药,研究组采用15种不同化疗方案;对照患者用12种。患者经手术及化疗达完全缓解或部分缓解伴有顽固难消的癌块则行再剖腹手术。本文103例患者中72人生存12至30个月,生存率为69.90％;研究组49例有43例生存,生存率为87.76％,对照组生存29例,占53.70％,二组之生存率比较,P值≤0.113,有差异。对照组25例死亡,平均生存5.5个月,6例研究组死亡者,平均生13.2月。

关键词：卵巢癌 CA125 患者卵巢恶性肿瘤肿瘤干细胞生存期

前列腺T1加权MRI所见的出血除外征对前列腺癌检出的价值

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国际医学放射学杂志 2012年第4期 384-385页

作者： T. barrett h.A. Vargas O. Akin d.A. Goldman h. hricak 唐光健 department of Radiology Memorial Sloan -Kettering Cancer Center1275 York Ave New York NY 10065 USA

摘要目的回顾性确定T1加权MRI上所见的出血除外征结合T2加权影像表现在前列腺癌检出中的出现率与阳性预期值(PPV),采用前列腺切除全量逐层切片病理标本作为参考标准。材料与方法此项回顾性研究由学院审查委员会批准,免除知情同意通知。... 详细信息

摘要目的回顾性确定T1加权MRI上所见的出血除外征结合T2加权影像表现在前列腺癌检出中的出现率与阳性预期值(PPV),采用前列腺切除全量逐层切片病理标本作为参考标准。材料与方法此项回顾性研究由学院审查委员会批准,免除知情同意通知。292例活检证实为前列腺癌的病人接受了直肠

关键词：前列腺癌 T1 检出 MRI

Characterization of gut microbiome and metabolome in helicobacter pylori patients in an underprivileged community in the United States

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World Journal of Gastroenterology 2021年第33期27卷 5575-5594页

作者： Brian White John d Sterrett Zoya Grigoryan Lauren Lally Jared d heinze hyder Alikhan Christopher A Lowry Lark J Perez Joshua deSipio Sangita Phadtare department of Biomedical Sciences Cooper Medical School of Rowan UniversityCamdenNJ 08103United States department of Integrative Physiology University of Colorado BoulderBoulderCO 80309United States department of Internal Medicine Lenox Hill HospitalNYCNY 10075United States department of Internal Medicine Thomas Jefferson University HospitalPhiladelphiaPA 19107United States department of Biological Sciences Rowan UniversityGlassboroNJ 08028United States department of Chemistry and Biochemistry Rowan UniversityGlassboroNJ 08028United States department of Gastroenterology Cooper University HospitalCamdenNJ 08103United States

BACKGROUNd helicobacter pylori(h.pylori),a bacterium that infects approximately half of the world’s population,is associated with various gastrointestinal diseases,including peptic ulcers,non-ulcer dyspepsia,gastric adenocarcinoma,and gastric lymphoma.As the burden of antibiotic resistance increases,the need for new adjunct therapies designed to facilitate h.pylori eradication and reduce negative distal outcomes associated with infection has become more pressing.Characterization of the interactions between h.pylori,the fecal microbiome,and fecal fatty acid metabolism,as well as the mechanisms underlying these interactions,may offer new therapeutic approaches.AIM To characterize the gut microbiome and metabolome in h.pylori patients in a socioeconomically challenged and underprivileged inner-city community.METhOdS Stool samples from 19 h.pylori patients and 16 control subjects were analyzed.16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2.Alpha and beta diversity analyses were performed in QIIME 2.Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry,which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters.Multi-dimensional scaling(MdS)was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MdS coordinates.RESULTS Fecal microbiome analysis showed that alpha diversity was lowest in h.pylori patients over 40 years of age compared to control subjects of similar age group.Beta diversity analysis of the samples revealed significant differences in microbial community structure between h.pylori patients and control subjects across all ages.Thirty-eight and six taxa had lower and higher relative abundance in h.pylori patients,respectively.Taxa that were enriched in h.pylori patients included Atopobium,

关键词： Gut microbiome Metabolome helicobacter pylori Antibiotic resistance dysbiosis Eradication

验证PI-RAdS 2.0版本中的主要序列和动态对比增强成像的作用

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国际医学放射学杂志 2018年第1期 102-102页

作者： M.d.Greer J.h.Shih N.Lay T.barrett L.K.Bittencourt S.Borofsky 周波 Molecular Imaging National Cancer InstituteNational Institutes of Health

摘要目的采用多阅片者间研究数据验证前列腺成像报告和数据系统(PI-RAdS)2.0版中主要脉冲序列和动态对比增强(dCE)MRI的有限作用。材料与方法本回顾性研究

关键词：动态对比增强 dCE 检出率 PI-RAdS 2.0 dWI

Measurement of the integrated luminosity of the Phase 2 data of the Belle Ⅱ experiment

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Chinese Physics C 2020年第2期44卷 1-12页

作者： F.Abudinén I.Adachi P.Ahlburg h.Aihara N.Akopov A.Aloisio F.Ameli L.Andricek N.Anh Ky d.M.Asner h.Atmacan T.Aushev V.Aushev T.Aziz K.Azmi V.Babu S.Baehr S.Bahinipati A.M.Bakich P.Bambade Sw.Banerjee S.Bansal V.Bansal M.barrett J.Baudot A.Beaulieu J.Becker P.K.Behera J.V.Bennett E.Bernieri F.U.Bernlochner M.Bertemes M.Bessner S.Bettarini V.Bhardwaj F.Bianchi T.Bilka S.Bilokin d.Biswas G.Bonvicini A.Bozek M.Bračko P.Branchini N.Braun T.E.Browder A.Budano S.Bussino M.Campajola L.Cao G.Casarosa C.Cecchi d.Červenkov M.-C.Chang P.Chang R.Cheaib V.Chekelian Y.Q.Chen Y.-T.Chen B.G.Cheon K.Chilikin h.-E.Cho K.Cho S.Cho S.-K.Choi S.Choudhury d.Cinabro L.Corona L.M.Cremaldi S.Cunliffe T.Czank F.dattola E.de La Cruz-Burelo G.de Nardo M.de Nuccio G.de Pietro R.de Sangro M.destefanis S.dey A.de Yta-hernandez F.di Capua S.di Carlo J.dingfelder Z.doležal I.domínguez Jiménez T.V.dong K.dort S.dubey S.duell S.Eidelman M.Eliachevitch T.Ferber d.Ferlewicz G.Finocchiaro S.Fiore A.Fodor F.Forti A.Frey B.G.Fulsom M.Gabriel E.Ganiev M.Garcia-hernandez R.Garg A.Garmash V.Gaur A.Gaz U.Gebauer A.Gellrich J.Gemmler T.Geßler R.Giordano A.Giri B.Gobbo R.Godang P.Goldenzweig B.Golob P.Gomis P.Grace W.Gradl E.Graziani d.Greenwald C.hadjivasiliou S.halder K.hara T.hara O.hartbrich K.hayasaka h.hayashii C.hearty M.T.hedges I.heredia de la Cruz M.hernández Villanueva A.hershenhorn T.higuchi E.C.hill h.hirata M.hoek S.hollitt T.hotta C.-L.hsu Y.hu K.huang T.Iijima K.Inami G.Inguglia J.Irakkathil Jabbar A.Ishikawa R.Itoh M.Iwasaki Y.Iwasaki S.Iwata P.Jackson W.W.Jacobs d.E.Jaffe E.-J.Jang h.B.Jeon S.Jia Y.Jin C.Joo J.Kahn h.Kakuno A.B.Kaliyar G.Karyan Y.Kato T.Kawasaki h.Kichimi C.Kiesling B.h.Kim C.-h.Kim d.Y.Kim S.-h.Kim Y.K.Kim Y.Kim T.d.Kimmel K.Kinoshita C.Kleinwort B.Knysh P.Kodyš T.Koga I.Komarov T.Konno S.Korpar d.Kotchetkov N.Kovalchuk T.M.G.Kraetzschmar P.Križan R.Kroeger J.F.Krohn P.Krokovny W.Kuehn T.Kuhr M.Kumar R.Kumar K.Kumara S.Kurz A.Kuzmin Y.-J.Kwon S.Lacaprara Y.-T.Lai C.La Licata K.Lalwani L.Lanceri J.S.Lange K.Lautenbach I.-S.Le Beihang University Beijing 100191 Brookhaven National Laboratory UptonNew York 11973 Budker Institute of Nuclear Physics SB RAS Novosibirsk 630090 Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Mexico City 07360 Faculty of Mathematics and Physics Charles University12116 Prague Chiba University Chiba 263-8522 Consejo Nacional de Ciencia y Tecnología Mexico City 03940 deutsches Elektronen–Synchrotron 22607 Hamburg duke University DurhamNorth Carolina 27708 Earthquake Research Institute University of TokyoTokyo 113-0032 Forschungszentrum Jülich 52425 Jülich department of Physics Fu Jen Catholic UniversityTaipei 24205 Key Laboratory of Nuclear Physics and Ion-beam Application(MOE)and Institute of Modern Physics Fudan UniversityShanghai 200443 II.Physikalisches Institut Georg-August-Universität Göttingen37073 Göttingen Gifu University Gifu 501-1193 The Graduate University for Advanced Studies(SOKENdAI) Hayama 240-0193 Gyeongsang National University Jinju 52828 department of Physics and Institute of Natural Sciences Hanyang UniversitySeoul 04763 high Energy Accelerator Research Organization(KEK) Tsukuba 305-0801 J-PARC Branch KEK Theory CenterHigh Energy Accelerator Research Organization(KEK)Tsukuba 305-0801 Indian Institute of Science Education and Research Mohali SAS Nagar140306 Indian Institute of Technology Bhubaneswar Satya Nagar 751007 Indian Institute of Technology hyderabad Telangana 502285 Indian Institute of Technology Madras Chennai 600036 Indiana University BloomingtonIndiana 47408 Institute for high Energy Physics Protvino 142281 Institute of high Energy Physics Vienna 1050 Institute of high Energy Physics Chinese Academy of SciencesBeijing 100049 Institute of Particle Physics(Canada) VictoriaBritish Columbia V8W 2Y2 Institute of Physics Hanoi Instituto de Fisica Corpuscular Paterna 46980 INFN Laboratori Nazionali di Frascati I-00044 Frascati INFN Sezione di Napoli I-80126 Napoli INFN Sezione di Padova I-35131 Padova INFN Sezione di Perugia I-06123 Perugia

From April to July 2018,a data sample at the peak energy of the T(4 S) resonance was collected with the Belle Ⅱ detector at the SuperKEKB electron-positron collider.This is the first data sample of the Belle Ⅱ experiment.Using Bhabha and digamma events,we measure the integrated luminosity of the data sample to be(496.3±0.3±3.0) pb-1,where the first uncertainty is statistical and the second is systematic.This work provides a basis for future luminosity measurements at Belle Ⅱ.

关键词： luminosity Bhabha digamma Belle II

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