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Role of ion channels in gastrointestinal cancer

World journal of Gastroenterology 2019年第38期25卷 5732-5772页

作者： Kyle j Anderson robert T Cormier Patricia M Scott Department of Biomedical Sciences University of Minnesota Medical School

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer *** functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of *** this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and *** members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon ***-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle *** VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC *** have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer ***2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal *** distinct types of K+channels are found dysregulated in the GI *** are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CR

关键词： Ion channels Gastrointestinal cancer Colorectal cancer Gastric cancer Pancreatic cancer Esophageal cancer Hepatocellular carcinoma Prognostic biomarker Novel therapies Clinical targets

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Trait plasticity, not values, best corresponds with woodland plant success in novel and manipulated habitats

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journal of Plant Ecology 2013年第3期6卷 201-210页

作者： robert j.Warren II jeffrey K.Lake Department of Biology SUNY Buffalo State1300 Elmwood AvenueBuffaloNY 14222USA Department of Biology Adrian CollegeAdrianMI49221USA

Aims The clustering of plants with similar leaf traits along environmental gradients may arise from adaptation as well as acclimation to het-erogeneous habitat *** the forces that shape plant leaf traits requires both linking variation in trait morphology with abiotic gradients and linking that trait variation with plant per-formance under varying abiotic *** the spectrum of plant types,shade-tolerant evergreen herbs are relatively low in trait plasticity,compared to deciduous and sun-adapted *** plants employ stress-tolerant strategies for survival,which coincide with relatively static trait morphologies,slow growth and hence a lower ability to adjust to changing environmental *** We investigate how the survival of two ecologically similar under-story evergreen species,Asarum arifolium and Hepatica nobilis,cor-responds with variation in six commonly measured functional traits(leaf area,specific leaf area,plant height,leaf number,leaf length and shoot mass)along natural and experimental abiotic *** examine temporal(the period 2007-9)and spatial(100 km)variations in these traits after(i)translocating 576 plants across a span from the southerm Appalachian Mountains in NC,USA,to the Piedmont,GA,USA,which includes north-and south-facing slope habitats and(ii)the experimental manipulation of diffuse light and soil *** findings We find that when translocated into a novel habitats,with novel environmental conditions that often are more extreme than the source habitat,both species appear capable of considerable mor-phological acclimation and generally converge to similar trait *** nobilis does not exhibit mean trait values particu-larly different from those of ***,but it demonstrates much greater phenotypic *** results indicate that relatively conservative plant species nonetheless acclimate and survive across heterogeneous environmental conditions.

关键词： Functional traits Asarum arifolium Hepatica nobilis niche specific leaf area understory

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Diagnosis and management of splanchnic ischemia

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World journal of Gastroenterology 2008年第48期14卷 7309-7320页

作者： jeroen j Kolkman Marloes Bargeman Ad B Huisman robert H Geelkerken Department of Gastro-enterology Medisch Spectrum Twente Department of Interventional Radiology Medisch Spectrum Twente Department of Vascular Surgery Medisch Spectrum Twente

Splanchnic or gastrointestinal ischemia is rare and randomized studies are absent. This review focuses on new developments in clinical presentation, diagnostic approaches, and treatments. Splanchnic ischemia can be caused by occlusions of arteries or veins and by physiological vasoconstriction during low-flow states. The prevalence of significant splanchnic arterial stenoses is high, but it remains mostly asymptomatic due to abundant collateral circulation. This is known as chronic splanchnic disease (CSD). Chronic splanchnic syndrome (CSS) occurs when ischemic symptoms develop. Ischemic symptoms are characterized by postprandial pain, fear of eating and weight loss. CSS is diagnosed by a test for actual ischemia. Recently, gastro-intestinal tonometry has been validated as a diagnostic test to detect splanchnic ischemia and to guide treatment. In single- vessel CSD, the complication rate is very low, but some patients have ischemic complaints, and can be treated successfully. In multi-vessel stenoses, the complication rate is considerable, while most have CSS and treatment should be strongly considered. CT and MR-based angiographic reconstruction techniques have emerged as alternatives for digital subtraction angiography for imaging of splanchnic vessels. Duplex ultrasound is still the first choice for screening purposes. The strengths and weaknesses of each modality will be discussed. CSS may be treated by minimally invasive endoscopic treatment of the celiac axis compression syndrome, endovascular antegrade stenting, or laparotomy-assisted retrograde endovascular recanalization and *** treatment plan is highly individualized and is mainly based on precise vessel anatomy, body weight, co- morbidity and severity of ischemia.

关键词： Splanchnic ischemia Mesenteric ischemia Tonometry Blood flow Chronic splanchnic syndrome Chronic splanchnic disease Chronic mesenteric isch-emia Celiac artery compression syndrome Ischemiccolitis

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Geochronological constraints on the metamorphic sole of the Semail ophiolite in the United Arab Emirates

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Geoscience Frontiers 2016年第4期7卷 609-619页

作者： Nick M.W.roberts robert j.Thomas joachim jacobs NERC Isotope Geosciences Laboratory British Geological SurveyKeyworthNG12 5GGUK Council for Geoscience P.O.Box 572Bellville 7535South Africa University of Bergen.Department of Earth Science PB 78035020 BergenNorway Norwegian Polar Institute Fram Centre9296 TromsoNorway

The Semail ophiolite of Oman and the United Arab Emirates （UAE） provides the best preserved large slice of oceanic lithosphere exposed on the continental crust, and offers unique opportunities to study processes of ocean crust formation, subduction initiation and obduction. Metamorphic rocks exposed in the eastern UAE have traditionally been interpreted as a metamorphic sole to the Semail ophiolite. However, there has been some debate over the possibility that the exposures contain components of older Arabian continental crust. To help answer this question, presented here are new zircon and futile U-Pb geochronological data from various units of the metamorphic rocks. Zircon was absent in most samples. Those that yielded zircon and futile provide dominant single age populations that are 95-93 Ma, partially overlapping with the known age of oceanic crust formation （96.5-94.5 Ma）, and partially overlapping with cooling ages of the metamorphic rocks （95 90 Ma）. The data are interpreted as dating high-grade metamorphism during subduction burial of the sediments into hot mantle lithosphere, and rapid cooling during their subsequent exhumation. A few discordant zircon ages, interpreted as late Neoproterozoic and younger, represent minor detrital input from the continent. No evidence is found in favour of the existence of older Arabian continental crust within the metamorphic rocks of the UAE.

关键词： Semail ophiolite United Arab Emirates Metamorphic sole U-Pb geochronology Zircon Rutile

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Gastrointestinal manifestations of systemic mastocytosis

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World journal of Gastroenterology 2008年第45期14卷 7005-7008页

作者： jason K Lee Scott j Whittaker robert A Enns Peter Zetler Internal Medicine University of British Columbia St. Paul's Hospital Division of Gastroenterology University of British Columbia St. Paul's Hospital Division of Pathology University of British Columbia

Systemic mastocytosis (SM) is a rare disease with abnormal proliferation and infiltration of mast cells in the skin, bone marrow, and viscera including the mucosal surfaces of the digestive tract. Gastrointestinal (GI) symptoms occur in 14%-85% of patients with systemic mastocytosis. The GI symptoms may be as frequent as the better known pruritis, urticaria pigmentosa, and flushing. In fact most recent studies show that the GI symptoms are especially important clinically due to the severity and chronicity of the effects that they produce. GI symptoms may include abdominal pain, diarrhea, nausea, vomiting, and bloating. A case of predominantly GI systemic mastocytosis with unique endoscopic images and pathologic confirmation is herein presented, as well as a current review of the GI manifestations of this disease including endoscopic appearances. Issues such as treatment and prognosis will not be discussed for the purposes of this paper.

关键词： Systemic mastocytosis Idiopathic diarrhea Gastrointestinal manifestations

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Ultrastructure of the gastro intestinal tract of healthy japanese quail(Coturnix japonica) using light and scanning electron microscopy

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Animal Nutrition 2018年第4期4卷 378-387页

作者： Ngare Wilkinson Ivan Dinev William j.Aspden robert j.Hughes Ingrid Christiansen james Chapman Sheeana Gangadoo robert j.Moore Dragana Stanley Central Queensland University Institute for Future Farming Systems Poultry Cooperative Research Centre University of New England Armidale Faculty of Veterinary Medicine Trakia University South Australian Research and Development Institute Pig and Poultry Production Institute School of Animal and Veterinary Sciences University of Adelaide School of Science RMIT University Department of Microbiology Monash University

The japanese quail(Coturnix japonica) are popular both as an alternative protein source and as a model of choice for scientific research in several disciplines. There is limited published information on the histological features of the intestinal tract of japanese quail. The only comprehensive reference is a book published in 1969. This study aims to fill that niche by providing a reference of general histological features of the japanese quail, covering all the main sections of the intestinal tract. Both light and scanning electron microscope(SEM) images are presented. Results showed that the japanese quail intestinal tract is very similar to that of the chicken with the exception of the luminal koilin membrane of the gizzard. Scanning electron microscopic photomicrographs show that in the japanese quail koilin vertical rods are tightly packed together in a uniform manner making a carpet-like appearance. This differs in chicken where the conformations of vertical rods are arranged in clusters.

关键词： japanese quail Coturnix japonica Histology Microscopy Scanning electron microscopy Gastrointestinal tract

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Magnetic Flux Controllers for Induction Heating Applications

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材料热处理学报 2004年第5期25卷 567-572页

作者： Valentin Nemkov robert Goldstein robert Ruffini FluxtroUCentre for Induction Technology USAFluxtroUCentre for Induction Technology USAFluxtroUCentre for Induction Technology USA

Application of magnetic flux controllers/concentrators to induction heating coils can drastically improve the process efficiency and heat pattern control. Presentation includes: benefits provided by flux controllers, materials available for controllers, application techniques, computer assisted design of induction coils with concentrators, examples of applications. Depending on induction system design, magnetic flux controllers can concentrate heating in a specified area, change heat source distribution and shield a particular part zone or external area preventing unintended eddy current heating. Besides of the coil efficiency improvement and optimal power distribution, magnetic flux controllers reduce the coil current demand from a supplying circuitry thus strongly reducing losses in busswork, cables, transformers and inverter components. Improvement that can be achieved due to magnetic flux controllers is case dependable. 2D and 3D computer simulation allows the designer to predict accurately effect of controllers on the coil parameters and temperature distribution and optimize the whole electromagnetic system. Special attention in presentation is paid to new magnetodielectric materials optimized for induction heating conditions. These materials have high magnetic permeability and saturation flux density, excellent machinability, good chemical and temperature resistance. Concentrators from these materials can work in a wide range of frequencies and specific powers. Examples of magnetic flux controller application include surface hardening of shafts and gears, induction surface hardfacing and brazing.

关键词：热处理感应器磁通量计算机模拟

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Agenesis of the dorsal pancreas

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World journal of Gastroenterology 2009年第3期15卷 376-377页

作者： Wolfgang j Schnedl Claudia Piswanger-Soelkner Sandra j Wallner robert Krause Rainer W Lipp Practice for General Internal Medicine Hauptstrasse 5A-8940 LiezenAustria Department of Internal Medicine Medical UniversityAuenbruggerplatz 15A-8036 GrazAustria Institute of Pathophysiology Center for Molecular MedicineHeinrichstrasse 31aA-8010 GrazAustria

During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World j Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas in *** of the dorsal pancreas,a rare congenital pancreatic malformation,is associated with some other medical conditions such as hyperglycemia,abdominal pain,pancreatitis and a few other *** approximately 50% of reported patients with this congenital malformation,hyperglycemia was *** of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose,oral glucose tolerance test,glycated hemoglobin and medical treatment would be a future *** autosomal dominant transmission has been suggested in single families,more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this *** this letter to the editor,we aim to increase available information for the better understanding of this rare disease.

关键词： Agenesis of dorsal pancreas Diabetesmellitus Glucose intolerance Abdominal pain Pancreatitis

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Hyponatraemia and cirrhosis

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Gastroenterology Report 2014年第1期2卷 21-26页

作者： robert j.Gianotti Andres Cardenas Department of Gastroenterology Beth Israel Deaconess Medical CenterBoston MA GI Unit Institut Clinic de Malalties Digestives i MetaboliquesHospital ClinicUniversity of Barcelona

Hyponatraemia is a common complication of advanced cirrhosis related to an impairment in the renal capacity for eliminating solute-free water,causing a retention of water that is disproportionate to the retention of sodium,thus leading to a reduction in serum sodium concentration and *** main pathogenic factor responsible for hyponatraemia is a non-osmotic hypersecretion of arginine vasopressin(AVP)or antidiuretic hormone from the neurohypophysis,related to circulatory *** in cirrhosis is associated with increased morbidity and *** is also associated with increased morbidity and impaired short-term survival after *** current standard of care based on restricting fluids to 1-1.5 L/day is rarely *** approaches,such as albumin infusion and the use of vaptans—which act by specifically antagonizing the effects of AVP on the V2 receptors located in the kidney tubules—have been evaluated for their role in the management of *** short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatraemia;however their use in patients with end-stage liver disease is limited by hepatotoxic effects of some of these *** administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration,but the available information is still limited.

关键词： hyponatraemia cirrhosis end-stage liver disease vaptans

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Acetylsalicylic acid supplementation improves protein utilization efficiency while vitamin E supplementation reduces markers of the inflammatory response in weaned pigs challenged with enterotoxigenic ***

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journal of Animal Science and Biotechnology 2017年第1期8卷 143-153页

作者： jae Cheol Kim Bruce P. Mullan john L. Black robert j. E. Hewitt robert j. van Barneveld john R. Pluske School of Veterinary and Life Sciences Murdoch University Murdoch WA 6150 Australia Department of Agriculture and Food Pork Innovation South Perth WA 6151 Australia john L Black Consulting Warrimoo NSW 2774 Australia SunPork Farms Solutions Loganholme QLD 4129 Australia Barneveld Nutrition Pry Ltd Loganholme QLD 4129 Australia

Background： This experiment was conducted to test the hypothesis that vitamin E（Vit E） and acetylsalicylic acid（ASA）, a cyclooxygenase-2（COX-2） inhibitor, will additively reduce the production of the immunosuppressive molecule prostaglandin E_2（PGE_2） and hence reduce inflammatory responses in weaner pigs experimentally infected with an enterotoxigenic strain of E. ***： The experiment was conducted in a research facility with 192 individually-housed male weaner pigs（Landrace × Large White） weighing 6.6 ± 0.04 kg（mean ± SEM）. The pigs were experimentally infected with an enterotoxigenic strain of E. coli and were allocated to a 2 × 3 factorial design with the respective factors being without and with 125 ppm ASA and three levels of Vit E supplementation（50, 100 or 200 IU/kg diet, dl-α-tocopheryl acetate）.Results： Acetylsalicylic acid supplementation improved average daily gain（P 〈 0.05） and tended to improve feed：gain ratio（P 〈 0.10） during the first 14 d after weaning. Acetylsalicylic acid supplementation also improved（P 〈 0.001） amino acid utilization efficiency（as assessed by plasma urea level） and tended to decrease（P 〈 0.10） PGE2 production in the liver without affecting smal intestinal histology and tight junction protein mR NA expression in the jejunal epithelium. Vitamin E supplementation greater than 100 IU/kg diet sustained both the plasma Vit E concentration（P 〈 0.001） and plasma haptoglobin content（P 〈 0.001） after weaning. However, there was no additive effects of the combined supplementation of ASA and Vit E on performance, intestinal barrier function and inflammatory responses of weaned ***： Although ASA and vitamin E improved amino acid utilization efficiency and reduced acute inflammatory responses, ASA and vitamin E did not additively reduce production of PGE2 and inflammatory responses in weaner pigs experimental y infected with an enterotoxigenic strain of E. coli.

关键词： Acetylsalicylic acid E.coli infection PGE_2 Vitamin E Weaner pigs

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