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医学和临床工程学

医学和临床工程学

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

作者： b.·贾可布森(b. jacobson) J.G.·韦勃斯特(J.G. Webster)

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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 *** pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are ***,using single-cell RNA sequencing of human diabetic wounds,we identified increased JMJD3 in diabetic wound macrophages,resulting in increased inflammatory gene ***,we report that in wound healing,JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 ***,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 ***,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 *** limits inflammatory cytokine production by wound macrophages during ***,in diabetic mice,its role changes to limit wound repair and enhance *** 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 ***,we demonstrate that macrophage-specific,nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and *** 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

Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 79-87页

作者： Jeremy P.Tervo Patricia T.jacobson brandon J.Vilarello Tiana M.Saak Francesco F.Caruana Liam W.Gallagher Joseph b.Gary David A.Gudis Paule V.Joseph D.P.Devanand Terry E.Goldberg Jonathan b.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-Head and Neck Surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long *** on the prevalence of persistent OD predominantly rely on self-reported olfactory *** studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute *** anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of *** study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical ***:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time *** had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not ***:baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up *** participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year *** had reliable trends in self-rated versus psychophysically tested olfactory function at both time *** total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at *** in threshold,but not discrimination or identification,most significantly mediate improvement

关键词： long COVID olfaction post-COVID condition smell dysfunction

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新型杀虫剂—二氢吡唑类

农药译丛 1992年第3期14卷 24-27,47页

作者： Richard M.jacobson 周红晞美国罗姆-哈斯公司研究实验室

70年代,荷兰Philips-Duphar b.V.公司披露了一类新型的杀虫剂(以PH60-41和效力更高的PH60-42为例)。也许按合成化学家的看法这些化合物是类似于PH60-40(除虫脲,diflubenzuron)的几丁质合成抑制剂。然而,生物学研究表明,这些新化合物虽... 详细信息

70年代,荷兰Philips-Duphar b.V.公司披露了一类新型的杀虫剂(以PH60-41和效力更高的PH60-42为例)。也许按合成化学家的看法这些化合物是类似于PH60-40(除虫脲,diflubenzuron)的几丁质合成抑制剂。然而,生物学研究表明,这些新化合物虽是效力很高的杀虫剂,但它们是作用方式与任何商品化杀虫剂都完全不同的神经毒剂。

关键词：杀虫剂二氢吡唑

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Development and assessment of a cutaneous tissue stretch device as a novel scar therapy

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Plastic and Aesthetic Research 2016年第1期3卷 351-358页

作者： Jonathan Kanevsky Joshua Vorstenbosch Julian Diaz-Abele tyler Safran Markus Prinz Youssef Tahiri Mirko Gilardino Satya Prakash Division of Plastic and Reconstructive Surgery McGill University Health CentreMontrealQC H3G 1B3Canada Section of Plastic and Reconstructive Surgery University of ManitobaWinnipegMB R3T 2N2Canada McGill Medical School McGill UniversityMontrealQC H3G 2M1Canada Division of General Surgery University of SherbrookeSherbrookeQC J1K 2R1Canada Division of Plastic and Reconstructive Surgery Indiana UniversityIndianapolisIN 46202USA biomedical Engineering Department Artificial Cells and Organs Research CentreMontrealQC H3A 2B4Canada

Aim:Scar prevention and reduction is an area of therapeutic opportunity and unmet medical *** no current effective scar therapy,patients are often disappointed in their appearance post surgery and re-present to surgeons,only to be turned *** purpose of this study was to develop and test a device that produces intermittent parallel stretch on new scars and to analyze its potential to reduce ***:Mice were randomized into 5 scar stretch treatment groups:1 control,1 sham,and 3 stretch models(0.5×,1×,or 2×device strength)and treated for 10 *** were scored using the Vancouver Scar *** tissue samples were compared by histology and transforming growth factor beta 1(TGF-β1)expression between control and treatment ***:Scar scores of 0.5×and 1×groups were significantly lower than the control group(Pbroblasts with more collagen deposition than the 0.5×and 2×***-β1 levels were significantly lower in the 0.5×(342.1±9.2)and 1×(254.1±3.1)groups than in the control group(Pbrosis on a macroscopic,microscopic and biochemical level.

关键词： Mechanotransduction scar therapy hypertrophic scar skin stretch

VLGR1基因突变(USH2C)引起的Usher综合征表达与USH2A表型的比较研究

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世界核心医学期刊文摘（眼科学分册） 2005年第7期1卷 30-31页

作者： Schwartz S.b. Aleman T.S. Cideciyan A.V. S.G. jacobson 刘炜 Scheie Eye Institute University of Pennsylvania51 North 39th Street Philadelphia PA 19104 United States

PURPOSE. To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome. METHODS. Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT). RESULTS. The siblings with VLGR1 mutation showed abnormal photoreceptor- mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change. CONCLUSIONS. USH2C and USH2A manifest photoreceptor disease with rod- and cone- mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross- sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.

关键词：基因突变 USH2A USH2C Usher VLGR1 视网膜疾病动态视野计视网膜区域光感受器视锥细胞

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《病人既是受害者又是传播者:伦理学与传染病》

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《病人既是受害者又是传播者:伦理学与传染病》

Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

作者： Margaret P.battin Leslie P.Francis J.A.jacobson Charles b.Smith

bioethical Inquiry(2009)6:249-250.2009New York:Oxford University Press,ISbN 019533583X这本新书是哲学家和医生的集体努力,既作为生命伦理学领域的声明,又是给医学、公共卫生和生命伦理学学生的有价值的课文。它写得很亲切,优美,...

bioethical Inquiry(2009)6:249-250.2009New York:Oxford University Press,ISbN 019533583X这本新书是哲学家和医生的集体努力,既作为生命伦理学领域的声明,又是给医学、公共卫生和生命伦理学学生的有价值的课文。它写得很亲切,优美,令人折服,又具有刺激性。battin和她的同事从既是生物学的,又是社会文化的深刻见解开始:人全都一起生活在潜在的和实际的疾病网络之中。即使当他们眼下没有生病,也没有意识到传播的可能的时候,不

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World Journal of Gastroenterology 2016年第12期22卷 3418-3431页

作者： Ira jacobson Stefan Zeuzem Robert Flisiak brygida Knysz Stefan Lueth Dorota Zarebska-Michaluk Ewa Janczewska Peter Ferenci Moises Diago Anna Linda Zignego Rifaat Safadi Yaacov baruch Dzhamal Abdurakhmanov Stephen Shafran Dominique Thabut Rafael bruck Adrian Gadano Alexander James Thompson Justin Kopit Fiona Mc Phee Tracy Michener Eric A Hughes Philip D Yin Stephanie Noviello Weill Cornell Medical College New YorkNY 10029United States Icahn School of Medicine at Mount Sinai New YorkNY 10029United States JW Goethe University Hospital 60323 FrankfurtGermany Uniwersytet Medyczny w bialymstoku 15-089 BialystokPoland EMC and Medical University 50-220 WroclawPoland Universitatsklinikum Hamburg-Eppendorf 20246 HamburgGermany Wojewodzki Szpital Zespolony w Kielcach 25-736 KielcePoland ID Clinic 41-400 MyslowicePoland Medizinische Universitat Wien 1090 ViennaAustria Clinica Quiron 46010 ValenciaSpain Universita degli Studi di Firenze 50121 FlorenceItaly Holy Family Hospital Nazareth 6004Israel Rambam Medical Center Haifa 31096Israel 1st Moscow State Medical University N.A.I.M.Sechenov 119991 MoscowRussia University of Alberta Hospital EdmontonAlberta T6G 2B7Canada Groupe Hospitalier Pitie-Salpetriere 75013 ParisFrance Tel Aviv Sourasky Medical Center and Tel Aviv University Tel Aviv 64239Israel Hospital Italiano de buenos Aires Buenos Aires C1181ACHArgentina St.Vincents Hospital and the University of Melbourne Melbourne 3065Australia Fiona McPhee Bristol-Myers Squibb Research and DevelopmentWallingfordCT 06492United States bristol-Myers Squibb Research and Development PrincetonNJ 08450United States

AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin(peg IFN/RbV), in treatment-naive hepatitis C virus(HCV) genotype(GT) 1-infected ***: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned(2:1) to daclatasvir vs telaprevir, stratified by IL28 b rs12979860 host genotype(CC vs non-CC), cirrhosis status(compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype(GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus peg IFN/RbV. Daclatasvir recipients received 24 wk of daclatasvir plus peg IFN/RbV; those without an extended rapid virologic response(e RVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of peg IFN/RbV. Telaprevir-treated patients received 12 wk of telaprevir plus peg IFN/RbV followed by 12(with e RVR) or 36(no e RVR) wk of peg IFN/RbV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12(SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia(hemoglobin bV than with telaprevir + peg IFN/RbV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5 A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/m L, to investigate any link between NS5 A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups(6.0% and 8.2% in the GT1 b and GT1 a groups, respectively) than in the telaprevi

关键词： Direct-acting antiviral Chronic hepatitis C Daclatasvir Genotype 1b NS5A inhibitor Liver disease

大豆疫霉RXLR效应蛋白Avh238的功能研究

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大豆疫霉RXLR效应蛋白Avh238的功能研究