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Macrophage secretory products induce an inflammatory phenotype in hepatocytes

World Journal of Gastroenterology 2012年第15期18卷 1732-1744页

作者： Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson elizabeth e Powell Centre for Liver Disease Research School of MedicineThe University of QueenslandPrincess Alexandra HospitalBrisbane 4102QueenslandAustralia Department of Gastroenterology and Hepatology Princess Alexandra HospitalBrisbane 4102QueenslandAustralia Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre The University of QueenslandBrisbane 4072QueenslandAustralia Diamantina Institute The University of QueenslandBrisbane 4102QueenslandAustralia

AIM:To investigate the influence of macrophages on hepatocyte phenotype and ***:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression *** in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)***:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,Pegulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA *** analysis revealed significant upregulation of lipocalin-2(17-fold,P ed with inflammation,and substantial downregulation of pathways related to hepatocyte *** patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver *** performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,Pe-conditioned media treated HepG2 *** patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of ***:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participat

关键词： Macrophages Hepatic fibrosis Lipocalin-2 Transforming growth factor-β1 Matrix metalloproteinase-9

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Molecular Characterization of the Calvin Cycle enzyme Phosphoribulokinase in the Stramenopile Alga Vaucheria litorea and the Plastid Hosting Mollusc elysia chlorotica

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Molecular Plant 2009年第6期2卷 1384-1396页

作者： Mary e. Rumpho Sirisha Pochareddy Jared M. Worful elizabeth J. Summer Debashish Bhattacharya Karen N. Pelletreau Mary S. Tyler Jungho Lee James R. Manhart Kara M. Soule Department of Biochemistry Microbiology and Molecular Biology 5735 Hitchner Halt University of Maine Orono ME 04469 USA Department of Biology Texas A&M University College Station TX 77843 USA Department of ecology Evolution and Natural Resources Institute of Marine and Coastal Sciences Rutgers University New Brunswick NJ 08901 USA School of Biology and ecology University of Maine Orono ME 04469 USA Green Plant Institute #2-202 Bio Valley Seoul National University 103-2 Seodun Gwonseon Suwon Gyeonggi 441-853 Korea Department of Biochemistry and Biophysics Texas A&M University College Station TX 77843 USA

Phosphoribulokinase （PRK）, a nuclear-encoded plastid-localized enzyme unique to the photosynthetic carbon reduction （Calvin） cycle, was cloned and characterized from the stramenopile alga Vaucheria litorea. This alga is the source of plastids for the mollusc （sea slug） elysia chlorotica which enable the animal to survive for months solely by photoautotrophic CO2 fixation. The 1633-bp V. litorea prk gene was cloned and the coding region, found to be interrupted by four introns, encodes a 405-amino acid protein. This protein contains the typical bipartite target sequence expected of nuclearencoded proteins that are directed to complex （i.e. four membrane-bound） algal plastids. De novo synthesis of PRK and enzyme activity were detected in e. chlorotica in spite of having been starved of V. litorea for several months. Unlike the algal enzyme, PRK in the sea slug did not exhibit redox regulation. Two copies of partial PRK-encoding genes were isolated from both sea slug and aposymbiotic sea slug egg DNA using PCR. each copy contains the nucleotide region spanning exon 1 and part of exon 2 of V litorea prk, including the bipartite targeting peptide. However, the larger prk fragment also includes intron 1. The exon and intron sequences of prk in e. chlorotica and V/itorea are nearly identical. These data suggest that PRK is differentially regulated in V. litorea and e. chlorotica and at least a portion of the V. litorea nuclear PRK gene is present in sea slugs that have been starved for several months.

关键词： Alga Calvin cycle elysia chlorotica kleptoplast mollusc phosphoribulokinase photosynthesis plastid redox regulation stramenopile symbiosis Vaucheria litorea.

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Survey to Inform the Development of an Online Support System for Higher education Students <br>—Higher education and Online Support

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Health 2018年第3期10卷 351-364页

作者： Rhianna Goozée Marietta Papadatou-Pastou elizabeth Barley Mark Haddad Patapia Tzotzoli Independent Scholar London UK School of education National and Kapodistrian University of Athens Athens Greece Florence Nightingale Faculty of Nursing and Midwifery King’s College London London UK Interim Head of School Human and Social Sciences and Professor of Health and Wellbeing University of West London London UK Private Practice at Bank and Harley Street London UK iConcipio Ltd. London UK

An increasing number of higher education students face mental health difficulties, but the universities’ student support services (SSS) struggle to meet demand with limited resources. Web-based alternatives hold promise as a novel medium through which students could access support. Online interventions appear to be effective and may therefore provide a cost-effective alternative, relieving some of the burden on struggling SSS. This paper presents results from an explorative survey of 61 students questioned about their opinion of online support systems. The majority of students indicated that they would use such a system and that it should be interactive and personalized, focusing on time and money management, relaxation exercises, and building social skills. Future directions towards the development of such a system are discussed.

关键词： Online Intervention Mental Health Study Skills Students Well-Being Higher education

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Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer

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World Journal of Gastrointestinal Surgery 2017年第4期9卷 103-108页

作者： Kathryn e Hitchcock R Charles Nichols Christopher G Morris Debashish Bose Steven J Hughes John A Stauffer Scott A Celinski elizabeth A Johnson Robert A Zaiden Nancy P Mendenhall Michael S Rutenberg Department of Radiation Oncology University of Florida Department of Surgical Oncology UF Health Cancer Center-Orlando Health Department of Surgery University of Florida Department of Surgery Mayo Clinic Department of Surgery Baylor University Medical Center at Dallas Department of Hematology/Oncology Mayo Clinic Department of Hematology/Oncology Baptist Health

AIM To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic *** From April 2010 to September 2013,15 patients with initially unresectable pancreatic cancer were treated withproton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy(RBe) to the gross disease and 1 patient received 50.40 Gy(RBe) to high-risk nodal targets. There were no treatment interruptions and no chemotherapy dose reductions. Six patients achieved a radiographic response sufficient to justify surgical exploration,of whom 1 was identified as having intraperitoneal dissemination at the time of surgery and the planned pancreatectomy was aborted. Five patients underwent resection. Procedures included:Laparoscopic standard pancreaticoduodenectomy(n = 3),open pyloris-sparing pancreaticoduodenectomy(n = 1),and open distal pancreatectomy with irreversible electroporation(IRe) of a pancreatic head mass(n = 1). ReSULTS The median patient age was 60 years(range,51-67). The median duration of surgery was 419 min(range,290-484),with a median estimated blood loss of 850 cm^3(range,300-2000),median ICU stay of 1 d(range,0-2),and median hospital stay of 10 d(range,5-14). Three patients were re-admitted to a hospital within 30 d after discharge for wound infection(n = 1),delayed gastric emptying(n = 1),and ischemic gastritis(n = 1). Two patients underwent R0 resections and demonstrated minimal residual disease in the final pathology specimen. One patient,after negative pancreatic head biopsies,underwent IRe followed by distal pancreatectomy with no tumor seen in the specimen. Two patients underwent R2 resections. Only 1 patient demonstrated ultimate local progression at the primary site. Median survival for the 5 resected patients was 24 mo(range,10-30).CONCLUSION Pancreatic resection for patients with initially unresectable cancers is feasible after

关键词： Pancreatic cancer Pancreatectomy Pancreas Proton therapy Radiotherapy

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Surveillance of Australian Hajj pilgrims for carriage of potentially pathogenic bacteria:Data from two pilot studies

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World Journal of Clinical Cases 2017年第3期5卷 102-111页

作者： Mohammad Irfan Azeem Mohamed Tashani Al-Mamoon Badahdah Leon Heron Kristen Pedersen Neisha Jeoffreys Jen Kok elizabeth Haworth Dominic e Dwyer Grant Hill-Cawthorne Harunor Rashid Robert Booy National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases Kids Research Institutethe Children’s Hospital at Westmead the Discipline of Child and Adolescent Health Sydney Medical Schoolthe University of Sydney Marie Bashir Institute for Infectious Diseases and Biosecurity the University of Sydney Department of Family and Community Medicine Faculty of Medicine in RabighKing Abdulaziz Uni-versity Centre for Infectious Diseases and Microbiology Laboratory Services Institute of Clinical Pathology and Medical ResearchPathology WestWestmead Hospital Menzies Research Institute Tasmania School of Public Health the University of Sydney World Health Organization Collaborating Centre for Mass Gatherings and High Consequence/High Visibility events Flinders University

AIM To estimate the pharyngeal carriage rate of Neisseria meningitidis(N. meningitidis), Streptococcus pneumoniae(S. pneumoniae) and Staphylococcus aureus(S. aureus) among Australian Hajj *** In 2014, surveillance was conducted in two phases among Australian Hajj pilgrims: The first phase during Hajj in Mina, and the second phase soon after returning home to Australia. Nasopharyngeal or oropharyngeal swabs were taken from participants then tested, firstly by nucleic acid testing, and also by standard *** Of 183 participants recruited in the first phase, 26(14.2%) tested positive for S. pneumoniae; 4 had received pneumococcal conjugate vaccine(PCV13). Only one tested positive for N. meningitidis(W). Of 93 2^(nd) phase samples cultured, 17(18.3%) grew S. aureus, all methicillin sensitive, 2(2.2%) grew N. meningitidis(on subculture; one serotype B, one negative), and 1(1%), from an unvaccinated pilgrim, grew S. *** Relatively high carriage of S. pneumoniae and little meningococcal carriage was found. This indicates the importance of a larger study for improved infection surveillance and possible vaccine evaluation.

关键词： Carriage Conjugate vaccine Staphylococcus aureus Neisseria meningitidis Streptococcus pneumoniae Hajj

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B cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2022年第11期28卷 1088-1101页

作者： Francesca Romana Delvecchio Michelle R Goulart Rachel elizabeth Ann Fincham Michele Bombadieri Hemant M Kocher William Harvey Research Institute Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts Cancer Institute Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre Barts Health NHS TrustLondon E11BBUnited Kingdom

Pancreatic cancer is a disease with high unmet clinical *** cancer is also characterised by an intense fibrotic stroma,which harbours many immune *** in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and *** human pancreatic ductal adenocarcinoma,high B-cell infiltration correlates with better patient ***,B cells have received recent interest in pancreatic cancer as potential therapeutic ***,the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to ***,it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells(DCs),surrounded by T cells and DCs to form tertiary lymphoid structures(TLS).TLS are increasingly recognised as sites for antigen presentation,T-cell activation,Bcell maturation and differentiation in plasma *** this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.

关键词： B cells Pancreatic cancer Cancer immunology Tertiary lymphoid structures Anti-tumour immunoglobulins Plasma cells

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T cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第46期27卷 7956-7968页

作者： Michelle R Goulart Konstantinos Stasinos Rachel elizabeth Ann Fincham Francesca R Delvecchio Hemant M Kocher Centre for Tumour Biology Barts Cancer Institute-A CRUK Centre of excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre The Royal London HospitalBarts Health NHS TrustLondon E11BBUnited Kingdom Centre for experimental Medicine and Rheumatology William Harvey Research InstituteQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival *** has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T *** cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant *** tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted ***,we review the role of T cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.

关键词： Immunosuppression T cell exhaustion Tumour microenvironment Pancreatic ductal adenocarcinoma Pancreatic cancer stroma

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Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis

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Liver Research 2022年第4期6卷 238-250页

作者： Nancy Magee Forkan Ahamed Natalie eppler elizabeth Jones Priyanka Ghosh Lily He Yuxia Zhang Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA Liver Center University of KansasKansas CityKSUSA

Background and aim:Non-alcoholic fatty liver disease(NAFLD)is becoming a leading cause of chronic liver disease *** molecular events that influence disease progression from non-alcoholic fatty liver(NAFL)to aggressive non-alcoholic steatohepatitis(NASH)remain incompletely understood,leading to lack of mechanism-based targeted treatment options for *** study aims to identify early signatures associated with disease progression from NAFL to NASH in mice and *** and methods:Male C57BL/6J mice were fed a high-fat,-cholesterol,and-fructose(HFCF)diet for up to 9 *** extent of steatosis,inflammation,and fibrosis was evaluated in liver *** RNA sequencing(RNA-seq)was conducted to determine liver transcriptomic ***:After being fed the HFCF diet,mice sequentially developed steatosis,early steatohepatitis,steatohepatitis with fibrosis,and eventually spontaneous liver *** RNA-seq revealed that the key signatures during steatosis progression to early steatohepatitis were pathways related to extracel-lular matrix organization and immune responses such as T cell migration,arginine biosynthesis,C-type lectin receptor signaling,and cytokine-cytokine receptor *** regulated by transcription factors forkhead box M1(FOXM1)and negative elongation factor complex member e(NeLFe)were significantly altered during disease *** phenomenon was also observed in patients with NASH.

关键词： Liver Transcriptome Steatosis Inflammation Fibrosis Non-alcoholic steatohepatitis(NASH)

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Compression Therapy to Prevent Recurrent Cellulitis of the Leg

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四川生理科学杂志 2021年第1期43卷 163-163页

作者： elizabeth Webb From the Physiotherapy Department Calvary Public Hospital Bruce Bruce ACT (E.W.) the Biological Data Science Institute the Australian National University Joint Colleges of Science Health and Medicine (T.N.) and the Medical School (F.J.B.) Australian National University the University of Canberra Research Institute for Sport and Exercise (J.G.) and the Discipline of Physiotherapy Faculty of Health University of Canberra (E.W. B.B.) Canberra ACT and the Australian Institute of Health Innovation Macquarie University Sydney (V.M.) — all in Australia.

Background:Chronic edema of the leg is a risk factor for *** use of compression garments on the leg has been recommended to prevent the recurrence of cellulitis,but there is limited evidence from trials regarding its ***:In this single-center,randomized,nonblinded trial,we assigned participants with chronic edema of the leg and recurrent cellulitis,in a 1:1 ratio,to receive leg compression therapy plus education on cellulitis prevention(compression group)or education alone(control group).Follow-up occurred every 6 months for up to 3 years or until 45 episodes of cellulitis had occurred in the *** primary outcome was the recurrence of cellulitis.

关键词： prevention edema education

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A Reexamination of the Legacy of Lt. General James Longstreet, CSA

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History Research 2012年第1期2卷 66-72页

作者： Jimi elizabeth Thomas Virginia Beach Public Schools USA

It is the purpose of this paper to reexamine the systematic process by which James Longstreet became the scapegoat for the defeat of the Battle of Gettysburg and consequently caused the South to lose her chance to become an independent country. James Longstreet played a crucial role in the American Civil War. He was Robert e. Lee＇s hand chosen Senior Lt. General, commanding the 1st Corp of the Army of northern Virginia. At the close of the war, he was a highly respected and accomplished general. However, following the death of Robert e. Lee, Longstreet＇s military reputation came under severe criticism. Without Lee to dispute the controversial allegations, the public accepted them as true. This organized effort of a small group of Confederate officers to destroy Longstreet＇s military accomplishment was also known as The Lost Cause Writers.

关键词： Civil War Confederate States James Longstreet Gettysburg Robert e. Lee Scapegoat

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