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Role of the receptor for advanced glycation end products in hepatic fibrosis

World Journal of Gastroenterology 2009年第46期15卷 5789-5798页

作者： christina Lohwasser Daniel Neureiter Yury Popov Michael Bauer Detlef Schuppan Department of Medicine Ⅰ University of Erlangen-NurembergErlangen-Nürnberg Institute of Pathology Paracelsus Private Medicine UniversitySalzburg Division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBoston

AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells （HSC） were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin （AGE- BSA） and N＇-（carboxymethyl） lysine （CML）-BSA, or with tumor necrosis factor-α （TNF-α）. In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS： In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1（ I ） mRNA by AGE-BSA. CONCLUSION： Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.

关键词： Advanced glycation end product Extracellularmatrix Hepatic stellate cell Matrix metalloproteinase Myofibroblast Receptor for advanced glycation endproducts Transforming growth factor β Tissue inhibitorof metalloproteinase Tumor necrosis factor α

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Wetland Economic Valuation Approaches and Prospects in China

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Chinese Geographical Science 2016年第2期26卷 143-154页

作者： JIANG Bo christina P.WONG CUI Lijuan OUYANG Zhiyun State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China Changjiang Water Resources Protection Institute Wuhan 430051 China School of Sustainability Arizona State University Tempe AZ 85287 US.A Institute of Wetland Research Chinese Academy of Forestry Beijing 100091China

Ecosystem services valuation seeks to increase the social relevance of ecosystem characteristics, the underlying biological mechanisms that support services, by making the contribution of ecosystems to human well-being explicit. Economic valuation can help management by clarifying the full range of benefits and costs of proposed management actions. In the past two decades, economic valuation of wetland ecosystem services has become one of the most significant scientific priorities for wetland protection. In this paper, we provide an overview of ecosystem services, and summarize the main interdisciplinary approaches to measure and value wetland ecosystem services. We identified four main methodological gaps preventing progress on wetland valuation of ecosystem services in China, which are: 1) confusion on terminology like intermediate and final ecosystem services, 2) lack of ecological production functions to link ecosystem characteristics to final ecosystem services, 3) static valuation making it difficult to evaluate the trade-offs and synergies among ecosystem services, and 4) lack of clear guidance on relating ecological compensation programs to conservation targets. Overcoming these gaps is important to inform wetland compensation mechanisms and conservation policies. We propose future research on wetland ecosystem services in China should be focused on: 1) defining final ecosystem services based on beneficiary preferences and underlying biophysical mechanisms, 2) establishing wetland monitoring programs at specific sites to collect data on final ecosystem service indicators and ecosystem characteristic metrics to create ecological production functions for economic valuation and rescaling techniques, and 3) incorporating wetland ecosystem service values into decision-making processes to inform wetland management.

关键词： ecosystem services wetlands economic valuation methodological gaps China

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Modifier-concept of colorectal carcinogenesis: Lipidomics as a technical tool in pathway analysis

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World Journal of Gastroenterology 2010年第15期16卷 1820-1827页

作者： Nikolaus Gassler christina Klaus Elke Kaemmerer Andrea Reinartz Institute of Pathology RWTH Aachen University Department of Pediatrics RWTH Aachen University School of Biology Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology

In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discussion to modify the development of colorectal carcinoma in humans. Saturated long-chain fatty acids, in particular, are assumed to promote carcinogenesis, whereas poly-unsaturated forms are likely to act in the opposite way. At present, the molecular mechanisms behind these effects are not well understood. Recently, it has been demonstrated by lipidomics and associated molecular techniques, that activation and metabolic channeling of long-chain fatty acids are important mechanisms to modify colorectal carcinogenesis. In this Editorial, an overview about the present concept of long-chain fatty acids and its derivatives in colorectal carcinogenesis as well as technical algorithms in lipid analysis is given.

关键词： Colorectal neoplasms Carcinogenesis Long-chain fatty acids Acyl-CoA Lipidomics

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Insights into erlotinib action in pancreatic cancer cells using a combined experimental and mathematical approach

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World Journal of Gastroenterology 2012年第43期18卷 6226-6234页

作者： Falko Lange Katja Rateitschak christina Kossow Olaf Wolkenhauer Robert Jaster Department of Systems Biology and Bioinformatics University of Rostock 18057 Rostock Germany Department of Medicine Ⅱ Division of Gastroenterology University Medicine Rostock 18057 Rostock Germany Stellenbosch Institute for Advanced Study Wallenberg Research Centre at Stellenbosch University Stellenbosch 7600 South Africa

AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells. METHODS:Two PC cell lines, BxPC-3 and Capan-1, were treated with various concentrations of erlotinib, the specific mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and protein kinase B (AKT) inhibitor XIV. DNA synthesis was measured by 5-bromo-2'-deoxyuridine (BrdU) assays. Expression and phosphorylation of the epidermal growth factor receptor (EGFR) and downstream signaling molecules were quantified by Western blot analysis. The data were processed to calibrate a mathematical model, based on ordinary differential equations, describing the EGFRmediated signal transduction. RESULTS:Erlotinib significantly inhibited BrdU incorporation in BxPC-3 cells at a concentration of 1 mol/L, whereas Capan-1 cells were much more resistant. In both cell lines, MEK inhibitor U0126 and erlotinib attenuated DNA synthesis in a cumulative manner, whereas the AKT pathway-specific inhibitor did not enhance the effects of erlotinib. While basal phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) did not differ much between the two cell lines, BxPC-3 cells displayed a more than five-times higher basal phospho-AKT level than Capan-1 cells. Epidermal growth factor (EGF) at 10 ng/mL induced the phosphorylation of EGFR, AKT and ERK in both cell lines with similar kinetics. In BxPC-3 cells, higher levels of phospho-AKT and phospho-ERK (normalized to the total protein levels) were observed. Independent of the cell line, erlotinib efficiently inhibited phosphorylation of EGFR, AKT and ERK. The mathematical model successfully simulated the experimental findings and provided predictions regarding phosphoprotein levels that could be verified experimentally. CONCLUSION:Our data suggest basal AKT phosphorylation and the degree of EGF-induced activation of AKT and ERK as molecular determinants of erlotinib efficiency in PC cells.

关键词： Erlotinib Pancreatic cancer Epidermal growth factor receptor Signal transduction Mathematical modeling

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Determination of selected semi-volatile organic compounds in water using automated online solid-phase extraction with large-volume injection/gas chromatography/mass spectrometry

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Frontiers of Environmental Science & Engineering 2011年第3期5卷 417-425页

作者： Yongtao LI christina L.MCCARTY Ed J.GEORGE Drinking Water Quality Laboratory Underwriters Laboratories Inc.South BendIN 46617USA Chemical Analysis Bruker DaltonicsFremontCA 94538USA

A rapid,sensitive,and cost-effective analyticalmethod was developed for the analysis of selected semivolatileorganic compounds in *** method used anautomated online solid-phase extraction technique coupledwith programmed-temperature vaporization large-volumeinjection gas chromatography/mass *** samples were extracted by using a fully automatedmobile rack system based on x-y-z robotic techniquesusing syringes and disposable 96-well extraction *** method was validated for the analysis of 30 semivolatileanalytes in drinking water,groundwater,andsurface *** a sample volume of 10 mL,the linearcalibrations ranged from 0.01 or 0.05 to 2.5μg·L^(-1),and themethod detection limits were less than 0.1μg·L^(-1).For thereagent water samples fortified at 1.0μg·L^(-1)and2.0μg·L^(-1),the obtained mean absolute recoveries were70%-130%with relative standard deviations of less than20%for most *** the drinking water,groundwater,and surface water samples fortified at 1.0μg·L^(-1),theobtained mean absolute recoveries were 50%-130%withrelative standard deviations of less than 20%for *** new method demonstrated three advantages:1)no manipulation except the fortification of surrogatestandards prior to extraction;2)significant cost reductionassociated with sample collection,shipping,storage,andpreparation;and 3)reduced exposure to hazardous solventsand other *** a result,this new automatedmethod can be used as an effective approach for screeningand/or compliance monitoring of selected semi-volatileorganic compounds in water.

关键词： automated solid-phase extraction programmed-temperature vaporization large-volume injection gas chromatography/mass spectrometry semi-volatile organic compounds water analysis

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New technologies to investigate the brain-gut axis

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World Journal of Gastroenterology 2009年第2期15卷 182-191页

作者： Abhishek Sharma Dina Lelic christina Brock Peter Paine Qasim Aziz Department of Gastrointestinal Science University of Manchester Manchester M13 9PL United Kingdom Neurogastro-enterology Group Wingate Institute of Neurogastroenterology Barts and the London School of Medicine and Dentistry London E1 2AJ United Kingdom Mech-Sense Department of Gastroenterology Aalborg Hospital Boulevarden 13 DK-9000 Aalborg Denmark

Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission Tomography, Magnetoencephalography, and Electroencephalography （EEG）. Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways （primary afferents, spinal and supraspinal transmission）, brainimaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal disorders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the phenotypic differences that determine an individual＇s response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual＇s psychological, autonomic, neuroendocrine, neurophysiological, and genetic profile to define phenotypic traits that may be at greater risk of developing sensitised states in response to gut inflammation or injury.

关键词： Brain-gut axis Central processing Neuraxis Neurophysiology

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Informal Caregiving and Disaster Risk Reduction:A Scoping Review

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International Journal of Disaster Risk Science 2021年第2期12卷 169-187页

作者： christina J.Pickering Maya Dancey Karen Paik Tracey O’Sullivan Interdisciplinary School of Health Sciences University of OttawaOttawa KIN 6N5Canada EnRiCH Research Lab University of OttawaOttawa KIN 6N5Canada Telfer School of Management University of OttawaOttawa KIN 6N5Canada

Informal caregivers are a population currently in the shadows of disaster risk reduction(DRR),and yet essential to the provision of healthcare *** scoping review explored the literature to understand issues related to informal caregiving and promising practices to support resilience for *** guidelines for scoping review as outlined by Tricco et al.(2016),relevant publications were identified from five major databases—Medline,Embase,PubMed,Web of Science,and *** studies referenced informal caregiving and disasters for a variety of population groups including children,people with disabilities or chronic illnesses,and older *** were excluded if they discussed formal caregiving services(for example,nursing),lacked relevance to disasters,or had insufficient discussion of informal ***,21 articles met the inclusion criteria and were fully *** themes were identified:(1)the need for education and training in DRR;(2)stressors around medication and supply issues;(3)factors affecting the decision-making process in a disaster;(4)barriers leading to disaster-related problems;and(5)factors promoting *** areas of strategic action and knowledge gaps are *** informal caregivers do not feel adequately prepared for *** the important role of informal caregivers in healthcare provision,preparedness strategies are essential to support community resilience for those requiring personal care *** understanding and mobilizing assets to support the resilience of informal caregivers,we also support the resilience of the greater healthcare system and the community,in disaster contexts.

关键词： Caregiving Disaster resilience Disaster risk reduction Healthcare Informal caregiving

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Simulation of urban microclimate with uhiSolver:software validation using simplifed material data

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Ecological Processes 2021年第1期10卷 921-943页

作者： Florian Teichmann christina Maria Baumgartner Andras Horvath Markus Luisser Azra Korjenic Vienna University of Technology ViennaAustria. Rheologic GmbH ViennaAustria.

Background:Increasing urbanization as well as global warming requires an investigation of the infuence of diferent construction methods and ground surfaces on the urban heat island efect(UHI efect).The extent of the infuence of the urban structure,the building materials used and their surfaces on the UHI efect can be signifcantly reduced already in the planning phase using a designated OpenFOAM-based solver“uhiSolver”.Results:In the frst part of this research work,it is shown that inner building details and components can be neglected while still obtaining sufciently accurate *** this purpose,the building model was divided into two layers:a surface layer without mass,where the interaction with radiation takes place,and a component layer,which contains all relevant components and cavities of the building represented with mass-averaged material *** has become apparent that the three parameters—albedo,heat capacity and thermal resistance—which have a decisive infuence on the interaction,have diferent efects on the component temperatures and the surface *** the second part of this research work,dynamic 3D computational fuid dynamics(CFD)simulations are performed with uhiSolver for a residential block in *** the simulation results with measurement data collected on site,it is shown that the simplifed assumption of homogeneous material data for building bodies provides very good results for the validation case ***,the infuence of the greening measures in the courtyard of the residential block on the air temperature is found to be ***,it was observed that due to locally higher radiation density,lower air velocities and higher air humidity,the apparent temperature in the courtyard is sometimes perceived to be higher than in the adjacent streets,despite the lower air ***:Simplifying the modeling process of the uhiSolver software by reducing the model complexity helps to reduce

关键词： Urban heat island efect Urban microclimate CFD simulation Microclimate simulation Apparent temperature

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Change in cap rock porosity triggered by pressure and temperature dependent CO_(2)-water-rock interactions in CO_(2) storage systems

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Petroleum 2017年第1期3卷 96-108页

作者： christina Hemme Wolfgang van Berk TU Clausthal Institute of Disposal ResearchDepartment of HydrogeologyLeibnizstrasse 1038642 Clausthal-ZellerfeldGermany

Carbon capture and storage in deep geological formations is a method to reduce greenhouse gas *** CO_(2) is injected into a reservoir and dissolves in the *** the impact of pressure and temperature(P-T)the aqueous species of the CO_(2)-acidified brine diffuse through the cap rock where they trigger CO_(2)-watererock *** geochemical reactions result in mineral dissolution and precipitation along the CO_(2) migration path and are responsible for a change in porosity and therefore for the sealing capacity of the cap *** study focuses on the diffusive mass transport of CO_(2) along a gradient of decreasing PeT *** process is retraced with a one-dimensional hydrogeochemical reactive mass transport *** semigeneric hydrogeochemical model is based on chemical equilibrium *** on a broad variety of scenarios,including different initial mineralogical,chemical and physical parameters,the hydrogeochemical parameters that are most sensitive for safe long-term CO_(2) storage are *** results demonstrate that PeT conditions have the strongest effect on the change in porosity and the effect of both is stronger at high PeT conditions because the solubility of the mineral phases involved depends on PeT ***,modeling results indicate that the change in porosity depends strongly on the initial mineralogical composition of the reservoir and cap rock as well as on the brine ***,a wide range of conditions for safe CO_(2) storage is identified.

关键词： rock reservoir geochemical

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Integrating insulin-like growth factor 1 and sex hormones into neuroprotection:Implications for diabetes

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World Journal of Diabetes 2017年第2期8卷 45-55页

作者： Jacob Huffman christina Hoffmann George T Taylor Behavioral Neuroscience Program Department of Psychological SciencesUniversity of MissouriSt. Interfakultare Biomedizinische Forschung-seinrichtung der Universitat Heidelberg

Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1(IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sexhormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinasesignaling cascades in animal and cell culture models of neuroprotection. Additionally, there is considerable evidence demonstrating the neuroprotective coupling of IGF1 and estrogen. Androgens have also been implicated in many neuroprotective processes that operate on similar signaling cascades as the estrogen-IGF1 relation. Yet, androgens have not been directly linked to the brain IGF1 system and neuroprotection. Despite the sex-specific variations in brain integrity and hormone levels observed in diabetic patients, the IGF1-sex hormone relation in neuroprotection has yet to be fully substantiated in experimental models of diabetes. Taken together, there is a clear need for the comprehensive analysis of sex differences on brain integrity of diabetic patients and the relationship between IGF1 and sex hormones that may influence brain-health outcomes. As such, this review will briefly outline the basic relation of diabetes and IGF1 and its role in neuroprotection. We will also consider the findings on sex hormones and diabetes as a basis for separately analyzing males and females to identify possible hormone-induced brain abnormalities. Finally, we will introduce the neuroprotective interplay of IGF1 and estrogen and how androgen-derived neuroprotection operates through similar si

关键词： Diabetes Androgens Estrogen Insulin Insulin-like growth factor 1 Neuroprotection Brain integrity Cognition

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