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Iron and liver fibrosis: Mechanistic and clinical aspects

World journal of Gastroenterology 2019年第5期25卷 521-538页

作者： Kosha j Mehta Sebastien je Farnaud paul A Sharp School of Population Health and Environmental Sciences Faculty of Life Sciences and Medicine King’s College London Division of Human Sciences School of Applied Sciences London South Bank University Faculty Research Centre for Sport Exercise and Life Sciences Coventry University Department of Nutritional Sciences School of Life Course Sciences Faculty of Life Sciences and Medicine King's College London

Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis.

关键词： Iron Liver pathologies Liver fibrosis Hepatic stellate cells Cirrhosis

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Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease

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World journal of Gastroenterology 2014年第27期20卷 8751-8763页

作者： Ahmed Tawfik paul K Flanagan Barry j Campbell Department of Gastroenterology Institute of Translational Medicine University of Liverpool

Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn’s disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn’s pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.

关键词： Crohn's disease Inflammatory bowel disease Escherichia coli Intra-macrophage survival and replication Phagolysosome Autophagy

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Sexual/aggressive behavior of wild yak(Bos mutus Prejevalsky1883) during the rut: influence of female choice

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Chinese Science Bulletin 2014年第22期59卷 2756-2763页

作者： paul j. Buzzard Donghua Xu Huan Li China Exploration & Research Society

Wild yaks(Bos mutus)ranged across the Tibetan Plateau in large herds before being forced to remote areas of the ***,little has been published about their behavioral *** present the first extensive study on wild yak behavior during the *** gathered data on activity budgets,aggressive/sexual behaviors,and the behavior of bulls inside and outside mixed groups during 11 days in 2010 and 9 days in *** ate less and were more social during the rut than during *** ate less than females and socialized more during the *** observed yaks for 234.25 h and recorded 2,078 aggressive/sexual *** bulls inspected and tended cows showing off their profiles during lateral displays,the most common type of indirect *** bulls inside mixed sex groups rested less and socialized more than bulls *** initiated intense intra-sexual competition and led at least 25 bulls on *** then incited fight frenzies of numerous bulls from inside and outside the groups before copulations,and fights could be *** discuss female choice selecting for large size and fighting ability in males,the similarity of yak and bison(genus Bison)behavior,and conservation implications.

关键词：攻击行为野牦牛发情期女性战斗能力青藏高原行为生态学社会化

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A Rare Case of Concordant Atrioventricular Connection to L-Looped Ventricles in Situs Solitus:4-Dimensional Magnetic Resonance Imaging and 3D Printing

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Congenital Heart Disease 2022年第4期17卷 387-392页

作者： Gregory Perens Takegawa Yoshida j.paul Finn UCLA Mattel Children’s Hospital Children’s Heart CenterLos AngelesCAUSA Diagnostic Cardiovascular Imaging Laboratory Department of Radiology12222 David Geffen School of Medicine at UCLALos AngelesCAUSA

An infant male presented with the rare anatomy consisting of situs solitus,concordant atrioventricular connections to L-looped ventricles,double outlet right ventricle(DORV),and hypoplastic aortic arch.6 months after neonatal aortic arch repair,the morphologic right ventricle function deteriorated,and surgical evaluation was undertaken to determine if either biventricular repair with a systemic morphologic left ventricle or right ventricular exclusion was *** initial echocardiography,magnetic resonance imaging(MRI)was used to create detailed axial and 4-dimensional(4D)images and 3-dimensional(3D)printed *** detailed anatomy of this rare,complex case and its use in pre-surgical planning is presented.

关键词： Magnetic resonance imaging cardiac segments 3D printing

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Recent Advancements in Optical Harmonic Generation Microscopy: Applications and Perspectives

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Biomedical Engineering Frontiers 2021年第1期2卷 65-88页

作者： Darian S.james paul j.Campagnola Department of Biomedical Engineering University of Wisconsin-Madison1550 Engineering DrMadisonWI 53706USA

Second harmonic generation(SHG)and third harmonic generation(THG)microscopies have emerged as powerful imaging modalities to examine structural properties of a wide range of biological *** SHG and THG arise from very different contrast mechanisms,the two are complimentary and can often be collected simultaneously using a modified multiphoton *** this review,we discuss the needed instrumentation for these modalities as well as the underlying theoretical principles of SHG and THG in tissue and describe how these can be leveraged to extract unique structural *** provide an overview of recent advances showing how SHG microscopy has been used to evaluate collagen alterations in the extracellular matrix and how this has been used to advance our knowledge of cancers,fibroses,and the cornea,as well as in tissue engineering *** examples using polarization-resolved approaches and machine learning algorithms are ***,we review how THG has enabled developmental biology and skin cancer studies due to its sensitivity to changes in refractive index,which are ubiquitous in all cell and tissue ***,we offer perspectives and outlooks on future directions of SHG and THG microscopies and present unresolved questions,especially in terms of overall miniaturization and the development of microendoscopy instrumentation.

关键词： harmonic resolved directions

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Impulsive perturbation and bifurcation of solutions for a model of chemostat with variable yield

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Applied Mathematics and Mechanics(English Edition) 2009年第7期30卷 933-944页

作者：张弘 paul Georgescu juan j.Nieto 陈兰荪 Department of Mathematics Jiangsu University Department of Mathematics and Mathematical Statistics Ume University Department of Mathematics "Gh.Asachi" Technical University of Iasi Departamento de Análisis Matemático Facultad de Matemáticas Universidadde Santiago de Compostela Institute of Mathematics Chinese Academy of Sciences

In this paper, we consider a variable yield model of a single-species growth in a well-stirred tank containing fresh medium, assuming the instances of time as triggering factors in which the nutrient refilling process and the removal of microorganisms by the uptake of lethal external antibiotic are initiated. It is also assumed that the periodic nutrient refilling and the periodic antibiotic injection occur with the same periodicity, but not simultaneously. The model is then formulated in terms of autonomous differential equations subject to impulsive perturbations. It is observed that either the population of microorganisms essentially washes out, or more favorably, the system is permanent. To describe this dichotomy, some biologically significant integral conditions are introduced. Further, it is shown that in a certain critical situation, a nontriviai periodic solution emerges via a bifurcation phenomenon. Finally, the dynamics of the model is illustrated with numerical experiments and computer simulations.

关键词： chemostat impulsive differential equation permanence extinction fixedpoint approach bifurcation

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An Investigation of Freezing of Supercooled Water on Anti-Freeze Protein Modified Surfaces

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journal of Bionic Engineering 2013年第2期10卷 139-147页

作者： Thibaut V j Charpentier Anne Neville paul Millner Rob Hewson Ardian Morina Institute of Engineering Thermofluids Surfaces and Interfaces (iETSI) Mechanical Engineering University of Leeds LS2 9JT Leeds UK

This work investigates how functionalization of aluminium surfaces with natural type III Anti-Freeze Protein （AFP） affects the mechanism of heterogeneous ice nucleation. First the bulk ice nucleation properties of distilled water and aqueous solution of AFP were evaluated by differential scanning calorimetry. Then the modified surface was characterized by Secondary Ions Mass Spectroscopy （SIMS）, Fourier Transform InfraRed （FTIR） spectroscopy and contact angle measurement. Freezing experiments were then conducted in which water droplets underwent a slow controlled cooling. This study shows that compared to uncoated aluminium, the anti-freeze proteins functionalized surfaces exhibit a higher and narrower range of freezing temperature. It was found that these proteins that keep living organisms from freezing in cold environment act in the opposite way once immobilized on surfaces by promoting ice nucleation. Some suggestions regarding the mechanism of action of the observed phenomena were proposed based on the Classical Nucleation Theory （CNT）.

关键词： anti-freeze protein surface functionalization ice nucleation temperature ice-like monolayer

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Comparison of esophageal capsule endoscopy and esophagogastroduodenoscopy for diagnosis of esophageal varices

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World journal of Gastroenterology 2008年第28期14卷 4480-4485页

作者： Catherine T Frenette john G Kuldau Donald j Hillebrand jill Lane paul j Pockros Division of Gastroenterology and Hepatology Scripps ClinicLa JollaCaliforniaSan Francisco 94115United States

AIM： To investigate the utility of esophageal capsule endoscopy in the diagnosis and grading of esophageal varices. METHODS： Cirrhotic patients who were undergoing esophagogastroduodenoscopy （EGD） for variceal screening or surveillance underwent capsule endoscopy. Two separate blinded investigators read each capsule endoscopy for the following results： variceal grade, need for treatment with variceal banding or prophylaxis with beta-blocker therapy, degree of portal hypertensive gastropathy, and gastric varices. RESULTS： Fifty patients underwent both capsule and EGD. Forty-eight patients had both procedures on the same day, and 2 patients had capsule endoscopy within 72 h of EGD. The accuracy of capsule endoscopy to decide on the need for prophylaxis was 74%, with sensitivity of 63% and specificity of 82%. Interrater agreement was moderate （kappa = 0.56）. Agreement between EGD and capsule endoscopy on grade of varices was 0.53 （moderate）. Inter-rater reliability was good （kappa = 0.77）. In diagnosis of portal hypertensive gastropathy, accuracy was 57%, with sensitivity of 96% and specificity of 17%. Two patients had gastric varices seen on EGD, one of which was seen on capsule endoscopy. There were no complications from capsule endoscopy.CONCLUSION： We conclude that capsule endoscopy has a limited role in deciding which patients would benefit from EGD with banding or beta-blocker therapy. More data is needed to assess accuracy for staging esophageal varices, PHG, and the detection of gastric varices.

关键词： Esophageal varices Capsule endoscopy Portal hypertension

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Artificial lights improve the catchability of snow crab (Chionoecetes opilio) traps

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Aquaculture and Fisheries 2017年第3期2卷 124-133页

作者： Khanh Q.Nguyen paul D.Winger Corey Morris scott M.Grant Fisheries and Marine Institute Memorial University of NewfoundlandSt.John'sNL A1C 5R3Canada Fisheries and Oceans Canada St John'sNL A1C 5X1Canada Nha Trang University 2 Nguyen Dinh ChieuNha Trang 57000Viet Nam

This study investigated the behaviour and commercial catchability of snow crab(Chionoecetes opilio)in response to different low-powered LED lights under laboratory and field *** created a novel choice-experiment in a laboratory setting in which we investigated the behaviour of snow crab in response to coloured LED *** results showed that snow crab movement was dependent on light colour,with animals choosing to move toward blue and white lights,away from purple lights,and no detectable effect for green and red *** then conducted two field experiments to investigate the effect of the same LED lights on the catch rates of commercial traps during the 2016 snow crab fishery on the east coast of Newfoundland and *** from the first field experiment showed that adding white and purple LED lights into baited traps significantly improved Catch Per Unit Effort(CPUE)by 77% and 47% *** from the second field experiment showed that unbaited traps equipped with only LED lights(no bait),could also catch snow crab in comparable amounts to traditional baited traps,with soak time and depth explaining some of the variation in *** together,these experiments suggest that fishing enterprises can improve their catching performance and profitability by adding LED lights to their traps,or by using LED lights as a bait replacement.

关键词： Chionoecetes opilio Snow crab LED light Catchability Crab behaviour

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Modified EASL-CLIF criteria that is easier to use and perform better to prognosticate acute-on-chronic liver failure

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World journal of Hepatology 2022年第2期14卷 420-428页

作者： paul j Thuluvath Feng Li Institute of Digestive Health and Liver Diseases Mercy Medical CenterBaltimoreMD 21202United States Department of Medicine University of Maryland School of MedicineBaltimoreMD 21202United States

BACKGROUND We have recently shown that the European Association for the Study of the Liver-Chronic Liver Failure Consortium(EASL-CLIF)criteria showed a better sensitivity to detect acute-on-chronic liver failure(ACLF)with a better prognostic capability than the North American Consortium for the Study of End-Stage Liver Disease *** To simplify EASL-CLIF criteria for ease of use without sacrificing its sensitivity and prognostic *** Using the United Network for Organ Sharing data(january 11,2016,to August 31,2020),we modified EASL-CLIF(mEACLF)criteria;the modified mEACLF criteria included six organ failures(OF)as in the original EASL-CLIF,but renal failure was defined as creatinine≥2.35 mg/dL and coagulation failure was defined as international normalized ratio(INR)≥*** mEACLF grades(0,1,2,and≥3)directly reflected the number of *** Of the 40357 patients,14044 had one or more OF,and 9644 had ACLF grades 1-3 by EASL-CLIF *** the mEACLF criteria,15574 patients had one or more *** area under the receiver operating characteristic(AUROC)for 30-d allcause mortality by OF was 0.842(95%CI:0.831-0.853)for mEACLF and 0.835(95%CI:0.824-0.846)for EASL-CLIF(P=0.006),and AUROC for 30-d transplantfree mortality by OF was 0.859(95%CI:0.849-0.869)for mEACLF and 0.851(95%CI:0.840-0.861)for EASL-CLIF(P=0.001).The AUROC of 30-d all-cause mortality by ACLF grades was 0.842(95%CI:0.831-0.853)for mEACLF and 0.793(95%CI:0.781-0.806)for EASL-CLIF(P<0.0001).The AUROC of 30-d transplant-free mortality by ACLF was 0.859(95%CI:0.848-0.869)for mEACLF and 0.805(95%CI:0.793-0.817)for EASL-CLIF(P<0.0001).CONCLUSION Our study showed that EASL-CLIF criteria for ACLF grades could be simplified for ease of use without losing its prognostication capability and sensitivity.

关键词： Acute on chronic liver failure Organ failure 30-d transplant-free mortality Liver transplantation EASL-CLIF criteria

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