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Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats

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Bioactive materials 2022年第12期7卷 339-353页

作者： Justin C.Burrell Suradip Das Franco A.Laimo Kritika S.Katiyar Kevin D.Browne Robert B.Shultz Vishal J.Tien Phuong T.Vu Dmitriy Petrov Zarina SAli Joseph m.Rosen D.Kacy Cullen Center for Brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Department of Bioengineering School of Engineering&Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA19104USA Axonova medical LLCPhiladelphiaPAUSA Dartmouth-Hitchcock medical Center Division of Plastic SurgeryDartmouth CollegeLebanonNHUSA

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NmIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NmIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NmI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NmIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NmIs provide the potential to improve functional recovery following delayed nerve repair.

关键词： Nerve regeneration Neuromuscular injury muscle preservation Tissue engineering microtissue Axon fusion

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Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome

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World Journal of Clinical Oncology 2021年第11期12卷 1023-1036页

作者： Jeshua DeJesse Ravy K Vajravelu Christina Dudzik Gillain Constantino Jessica m Long Kirk J Wangensteen Kathleen D Valverde Bryson W Katona Department of Genetics University of PennsylvaniaPhiladelphiaPA 19104United States Division of Gastroenterology and Hepatology University of Pennsylvania Perelman School of MedicinePhiladelphiaPA 19104United States Division of Hematology and Oncology University of PennsylvaniaPhiladelphiaPA 19104United States

BACKGROUND Lynch syndrome(LS)is a hereditary cancer predisposition syndrome associated with increased risk of multiple *** colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines,there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS,including small intestinal cancer(SIC)and urinary tract cancer(UTC).Given the limited evidence,guidelines do not consistently recommend surveillance for SIC and UTC,and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance *** To study factors associated with SIC and UTC surveillance uptake and outcomes in *** This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral *** individuals had a pathogenic or likely pathogenic variant in mLH1,mSH2,mSH6,PmS2,or EPCAm,or were a confirmed obligate carrier,and had at least one documented visit to our *** regarding SIC and UTC surveillance was captured for each individual,and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center’s dedicated high-risk LS clinic between January 1,2017 and October 29,*** these initial management visits,all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC *** analysis using Pearson’s chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance,and a P value below 0.05 was deemed statistically *** Of 317 individuals with LS,86(27%)underwent a total of 105 SIC surveillance examinations,with 5 leading to additional work-up and no SICs ***,99(31%)patients underwent a total of 3

关键词： Lynch syndrome Urinary tract cancer Intestinal neoplasms Early diagnosis of cancer Patient preference Gastrointestinal surgical procedure

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Diet-Induced Alteration of the murine Intestinal microbiome Following Antibiotic Ablation

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Advances in microbiology 2017年第7期7卷 545-564页

作者： Adam Irvin Andrew Cockburn Donald A. Primerano Jim Denvir Goran Boskovic Aniello m. Infante Gary D. Wu Christopher F. Cuff Department of microbiology Immunology and Cell Biology Robert C. Byrd Health Sciences Center West Virginia University Morgantown WV USA Department of Biomedical Sciences Robert C. Byrd Biotechnology Science Center Joan C. Edwards School of Medicine Marshall University Huntington WV USA Department of Biostatistics Robert C. Byrd Health Sciences Center West Virginia University Morgantown WV USA Division of Gastroenterology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

mouse models of antibiotic-induced ablation of the intestinal microbiome have been used to study the microbiome in health and disease. The fecal microbiomes of mice treated with broad-spectrum antibiotics while being fed different laboratory chows were analyzed by Gram stain, quantitative flow cytometry, bacterial cell culture, next generation sequencing of the V3 regions of the 16S ribosomal RNA (rRNA) gene, microscopy, and sequence analysis of the tuf gene. Noncultivatable gram-positive cocci and cultivatable yeast were the microorganisms most readily detected in feces of antibiotic-treated mice fed a defined diet that utilizes casein as a protein source, maltodextrin 10 and sucrose as sources of carbohydrates, and lard as the major source of fat. High-throughput sequencing of the variable regions of the 16S rRNA gene and tuf gene sequencing identified the major bacterial phylotype as Lactococcus. The mouse chow was heavily laden with noncultivatable Lactococcus, which dominated the intestinal flora after consumption. The microbiome of antibiotic-treated mice fed a grain-based diet (mainly wheat, corn and alfalfa) consisted predominantly of a member of the Enterobacteriaceae identified as Escherichia coli, and yeast was not detected by culture or Gram stain. Appearance of intestinal yeast by culture and Gram stain was dependent on the specific chow, although yeast was not detected by culture or Gram stain in the chow. We conclude that bacteria found in food sources can influence qualitative and quantitative assessments of the fecal microbiome, at least in the context of antibiotic therapy, and potentially confound molecular studies that assess the effects of diet on the intestinal ecology. Not surprisingly, different food sources can influence the microbiome, particularly in the context of antibiotic-mediated ablation of the intestinal microbiome. Whether and how the food-derived dead bacteria alter intestinal physiology needs to be determined.

关键词： mouse Intestinal microbiome Antibiotics Diet Lactococcus

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识别乳腺癌固有成像表型:与基因表达谱相关的初步研究

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国际医学放射学杂志 2014年第5期 480-481页

作者： A.B.Ashraf D.Daye S.Gavenonis C.mies m.Feldman m.Rosen 左影 Department of Radiology University of Pennsylvania Perelman School of Medicine

摘要目的采用一种识别乳腺癌肿瘤固有成像表型的方法并研究其与预测基因表达谱的相关性。材料与方法回顾性分析2005—2010年期间,56例患有雌激素受体阳性乳

关键词：乳腺癌乳腺肿瘤基因表达谱表型

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mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep m. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

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颅内血管壁mRI：原理和美国神经放射学学会专家共识

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国际脑血管病杂志 2018年第9期26卷 641-653页

作者： D.m.mandell m.mossa—Basha Y.Qiao C.P.Hess F.Hui C.matouk m.H.Johnson m.J.A.P.Daemen A Vossough m.Edjlali D.Saloner S.A.Ansari B.A.Wasserman D.J.mikulis代表美国神经放射学学会血管壁成像研究组曹旭(译) 田秀秀(译) 闫福岭(译) From the Division of Neuroradiology Department of Medical Imaging University Health Network and the University of Toronto Toronto Ontario Canada Department of Radiology University of Washington Seattle Washington The Russell H. morgan Department of Radiology and Radiological Sciences Johns Hopkins Hospital Baltimore Maryland Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco California Departments of Neurosurgery Radiology and Biomedical Imaging Surgery Yale University School of medicine New Haven Connecticut Departnlent of Pathology Academic Medical Center Amsterdam the Netherlands Departments of Surgery Radiology Children's Hospital of Philadelphia and Perelman School of Medicine at the University ofPennsylvania Philadelphia Pennsylvania Department of Radiology Universite Paris Descartes Sorbonne Paris Cite Institut National de la Sante et de la Recherche Medicale S894 Centre Hospitafier Sainte-AnneParis France Departments of Radiology Neurology Neurological Surgery Northwestern UniversityFeinberg School of Medicine Chicago Illinois. 不详东南大学附属中大医院神经内科南京210009

颅内血管壁磁共振成像是对常规血管造影方法（CT血管造影、磁共振血管造影或数字减影血管造影）的一种补充.该技术在缺血性卒中和颅内出血情况下有诸多潜在用途.尽管对颅内血管壁磁共振成像结果的理解还存在歧异,相关研究也还正在进行之... 详细信息

颅内血管壁磁共振成像是对常规血管造影方法（CT血管造影、磁共振血管造影或数字减影血管造影）的一种补充.该技术在缺血性卒中和颅内出血情况下有诸多潜在用途.尽管对颅内血管壁磁共振成像结果的理解还存在歧异,相关研究也还正在进行之中,但该技术已在许多中心应用于临床.本文代表美国神经放射学学会血管壁成像研究组为当前临床实践提供了专家共识推荐意见.

关键词：神经放射学血管壁颅内专家学会美国 mRI 数字减影血管造影

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Nature：大规模研究揭示生命所必需的基因

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现代生物医学进展 2016年第31期16卷 I0002-I0003页

作者： Dickinson, mary E. Flenniken, Ann m. Ji, Xiao Teboul, Lydia Wong, michael D. White, Jacqueline K. meehan, Terrence F. Weninger, Wolfgang J. Westerberg, Henrik Adissu, Hibret Baker, Candice N. Bower, Lynette Brown, James m. Caddle, L. Brianna Chiani, Francesco Clary, Dave Cleak, James Daly, mark J. Denegre, James m. Doe, Brendan Dolan, mary E. Edie, Sarah m. Fuchs, Helmut Gailus-Durner, Valerie Galli, Antonella Gambadoro, Alessia Gallegos, Juan Guo, Shiying Horner, Neil R. Hsu, Chih-Wei Johnson, Sara J. Kalaga, Sowmya Keith, Lance C. Lanoue, Louise Lawson, Thomas N. Lek, monkol mark, manuel Arschall, Susan m. mason, Jeremy mcElwee, melissa L. Newbigging, Susan Nutter, Lauryl m. J. Peterson, Kevin A. Ramirez-Solis, Ramiro Rowland, Douglas J. Ryder, Edward Samocha, Kaitlin E. Seavitt, John R. Selloum, mohammed Szoke-Kovacs, Zsombor Tamura, masaru Trainor, Amanda G. Tudose, Ilinca Wakana, Shigeharu Warren, Jonathan Wendling, Olivia West, David B. Wong, Leeyean Yoshiki, Atsushi macArthur, Daniel G. Tocchini-Valentini, Glauco P. Gao, Xiang Flicek, Paul Bradley, Allan Skarnes, William C. Justice, monica J. Parkinson, Helen E. moore, mark Wells, Sara Braun, Robert E. Svenson, Karen L. de Angelis, martin Hrabe Herault, Yann mohun, Tim mallon, Ann-marie Henkelman, R. mark Brown, Steve D. m. Adams, David J. Lloyd, K. C. Kent mcKerlie, Colin Beaudet, Arthur L. Bucan, maja murray, Stephen A. Dept mol Physiol & Biophys Houston TX 77030 USA Toronto Ctr Phenogen Toronto ON M5T 3H7 Canada mt Sinai Hosp Toronto ON M5G 1X5 Canada Univ Penn Perelman Sch Med Genom & Computat Biol Program Philadelphia PA 19104 USA med Res Council Harwell Mammalian Genet Unit Harwell OX11 0RD Oxon England mary Lyon Ctr Harwell OX11 0RD Oxon England Hosp Sick Children Mouse Imaging Ctr Toronto ON M5T 3H7 Canada Wellcome Trust Sanger Inst Wellcome Trust Genome Campus Cambridge CB10 1SA England European Bioinformat Inst European Mol Biol Lab Wellcome Trust Genome Campus Cambridge CB10 1SD England med Univ Vienna Ctr Anat & Cell Biol A-1090 Vienna Austria Hosp Sick Children 555 Univ Ave Toronto ON M5G 1X8 Canada Jackson Lab 600 Main St Bar Harbor ME 04609 USA Univ Calif Davis Mouse Biol Program Davis CA 95618 USA Italian Natl Res Council CNR Inst Cell Biol & Neurobiol Monterotondo Mouse Clin I-00015 Monterotondo Italy massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA Broad Inst mIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA German Res Ctr Environm Hlth Helmholtz Zentrum Munchen Inst Expt Genet D-85764 Neuherberg Germany German mouse Clin D-85764 Neuherberg Germany Baylor Coll med Dept Mol & Human Genet Houston TX 77030 USA Nanjing Univ Nanjing Biomed Res Inst Collaborat Innovat Ctr Genet & Dev SKL Pharmaceut Biotechnol & Model Anim Res Ctr Nanjing 210061 Jiangsu Peoples R China Univ Strasbourg ICS Infrastruct Natl PHENOMIN F-67404 Illkirch Graffenstaden France Univ Strasbourg INSERM CNRS IGBMC F-67404 Illkirch Graffenstaden France RIKEN BioResource Ctr Tsukuba Ibaraki 3050074 Japan Childrens Hosp Oakland Res Inst Oakland CA 94609 USA ImPC San Anselmo CA 94960 USA Tech Univ munich Sch Life Sci Weihenstephan Chair Expt Genet D-81675 Freising Weihenstephan Germany German Ctr Diabet Res DZD D-85764 Neuherberg Germany Francis Crick Inst Mill Hill Lab Mill Hill London NW1 1AT England Univ Penn Perlman

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期... 详细信息

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期刊上，论文标题为“High—throughput discovery of novel developmental phenotypes”。

关键词：动物基因组生命哺乳动物研究人员人类疾病医学院

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Doxorubicin-conjugated siRNA lipid nanoparticles for combination cancer therapy

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1429-1437页

作者： Kamila Butowska Xuexiang Han Ningqiang Gong Rakan El-mayta Rebecca mHaley Lulu Xue Wenqun Zhong Wei Guo Karin Wang michael J.mitchell Department of Bioengineering University of PennsylvaniaPhiladelphiaPA 19104USA Intercollegiate Faculty of Biotechnology University of Gdańsk&Medical University of GdańskGdańsk 80-307Poland Department of Biology University of PennsylvaniaPhiladelphiaPA 19104USA Department of Bioengineering Temple UniversityPhiladelphiaPA 19122USA Abramson Cancer Center Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Immunology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Cardiovascular Institute Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Regenerative medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Evasion of apoptosis is a hallmark of cancer,attributed in part to overexpression of the antiapoptotic protein B-cell lymphoma 2(Bcl-2).In a variety of cancer types,including lymphoma,Bcl-2 is *** targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with ***,the development of co-delivery systems for Bcl-2 targeting agents,such as small interfering RNA(siRNA),and chemotherapeutics,such as doxorubicin(DOX),holds promise for enabling combination cancer *** nanoparticles(LNPs)are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and *** by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs,here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNAloaded *** optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts'lymphoma(Raji)cells,leading to effective inhibition of tumor growth in a mouse model of *** on these results,our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.

关键词： Lipid nanoparticles Doxorubicin Bcl-2 siRNA delivery Chemotherapy Lymphoma

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Effect of drug therapies on self-reported chemosensory outcomes after COVID-19

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 88-96页

作者： marco A.Fornazieri Bruno m.Cunha Samuel P.Nicácio Lucas K.Anzolin JoséL.B.da Silva Aristides Fernandes Neto Deusdedit Brandão Neto Richard L.Voegels Fábio D.R.Pinna Department of Surgery Londrina State UniversityLondrinaBrazil Department of medicine Pontifical Catholic University of ParanáLondrinaBrazil Department of Otorhinolaryngology University of São PauloSao PauloBrazil Department of Otorhinolaryngology:Head and Neck Surgery Perelman School of MedicineSmell and Taste CenterUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objective:The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection on self-reported alterations in taste and/or smell ***:Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019(post-COVID-19)chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the *** dependent measure—self-reported total recovery of chemosensory symptoms—was subjected to stepwise logistic *** predictors included demographic and clinical variables,in addition to specific medications used to mitigate disease symptoms(i.e.,systemic corticosteroids,oseltamivir,vitamin C,ibuprofen,hydroxychloroquine,azithromycin,ivermectin,nitazoxanide,anticoagulants,and zinc).Results:The median time between COVID-19 symptom onset and the interviews was 81 days(interquartile range:60-104).Of the 714 subjects,249(34.9%)reported total recovery of their chemosensory function;437(61.2%)had at least one treatment since the beginning of the *** and those with more comorbidities had undergone more *** recovery rates of the treated and nontreated groups did not differ ***,respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell *** who took oral zinc were less likely to ***:No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal,although nitrazoxide trended in a positive *** zinc had a negative effect on the reported recovery of these senses.

关键词： chemosensory disorder coronavirus infections COVID-19 drug therapy SARS-CoV-2 smell loss taste loss

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乳腺X线摄影筛查方式对乳腺密度评估的影响:乳腺数字X线摄影和乳腺数字体层摄影

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国际医学放射学杂志 2019年第4期 478-478页

作者：殷国良 A.Gastounioti A.m.mcCarthy L.Pantalone m.Synnestvedt D.Kontos E.F.Conant Department of Radiology Perelman School of MedicineUniversity of Pennsylvania

摘要放射科医生判定的乳腺成像报告和数据系统(BIRADS)乳腺密度类别,经常会影响对乳腺癌补充筛查的决策和风险评估。乳腺X线摄影技术的不断演变,以及不同的乳

关键词：乳腺密度摄影检查数字乳腺摄影体层摄影

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