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Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

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World Journal of Gastroenterology 2013年第42期19卷 7327-7340页

作者： María Rojas-feria manuel Castro Emilio Suárez Javier Ampuero manuel Romero-Gómez Unit for Medical and Surgical Management of Digestive Diseases and CIBERehd Valme University HospitalUniversity of SevilleE-41014 SevillaSpain

Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic *** and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal *** sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in *** 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these *** common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver *** B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with *** prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral *** negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load *** the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history *** of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is *** in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically *** hepatotoxicity has been describ

关键词： Inflammatory bowel disease Hepatobiliary disorders Extraintestinal manifestations Primary sclerosing cholangitis Drug-induced liver injury Hepatotoxicity Hepatitis B Hepatitis C

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

New approach to assess sperm DNA fragmentation dynamics： Fine-tuning mathematical models

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Journal of Animal Science and Biotechnology 2017年第3期8卷 592-600页

作者： Isabel ortiz Jesus Dorado Jane Morrell Jaime Gosalvez Francisco Crespo Juan M.Jimenez manuel Hidalgo Veterinary Reproduction Group Department of Animal Medicine and Surgery Faculty of Veterinary Medicine University of Cordoba 14071 Cordoba Spain Department of Clinical Sciences Division of Reproduction Swedish University of Agricultural Sciences Box 7054 SE-75007 Uppsala Sweden Department of Biology Universidad Aut6noma de Madrid 28049 Madrid Spain Department of Reproduction Centro Militar de Cria Caballar (FESCCR-Ministry of Defense) 05005 Avila Spain Department of Chemistry and Physics of Materials University of Salzburg Hellbrunner StraBe 34/111 A-5020 Salzburg Austria

Background： Sperm DNA fragmentation（sDF） has been proved to be an important parameter in order to predict in vitro the potential fertility of a semen sample. Colloid centrifugation could be a suitable technique to select those donkey sperm more resistant to DNA fragmentation after thawing. Previous studies have shown that to elucidate the latent damage of the DNA molecule, sDF should be assessed dynamically, where the rate of fragmentation between treatments indicates how resistant the DNA is to iatrogenic damage. The rate of fragmentation is calculated using the slope of a linear regression equation. However, it has not been studied if s DF dynamics fit this model. The objectives of this study were to evaluate the effect of different after-thawing centrifugation protocols on sperm DNA fragmentation and elucidate the most accurate mathematical model（linear regression, exponential or polynomial） for DNA fragmentation over time in frozen-thawed donkey ***： After submitting post-thaw semen samples to no centrifugation（UDC）, sperm washing（SW） or single layer centrifugation（SLC） protocols, sD F values after 6 h of incubation were significantly lower in SLC samples than in SW or *** of determination（R-2） values were significantly higher for a second order polynomial model than for linear or exponential. The highest values for acceleration of fragmentation（aSDF） were obtained for SW, fol owed by SLC and ***： SLC after thawing seems to preserve longer DNA longevity in comparison to UDC and SW. Moreover,the fine-tuning of models has shown that sDF dynamics in frozen-thawed donkey semen fit a second order polynomial model, which implies that fragmentation rate is not constant and fragmentation acceleration must be taken into account to elucidate hidden damage in the DNA molecule.

关键词： Colloid centrifugation Dynamics Fine-tuning Mathematical models Sperm DNA fragmentation

Repellent and Insecticidal Activity of Naphthoquinones from the Heartwood of Tectona grandis on Incisitermes marginipennis(Latreille)

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Phyton-International Journal of Experimental Botany 2023年第7期92卷 2165-2181页

作者： Crisanto Velázquez-Becerra Gu Yen Ambriz-ortiz Rafael Torres-Martínez Mauro manuel Martínez-Pacheco Facultad de Ingeniería en Tecnología de la Madera Universidad Michoacana de San Nicolás de HidalgoMoreliaMéxico Escuela Nacional de Estudios Superiores Unidad MoreliaMoreliaMéxico Instituto de Investigaciones Químico-Biológicas Universidad Michoacana de San Nicolás de HidalgoMoreliaMéxico

Wood is a lignocellulosic material that,because of its organic nature,is a source of nutrients for bacteria,fungi,and *** marginipennis(Latreille)is an interesting dry wood-boring *** it is an extremely destructive pest,difficult to control due to its cryptic lifestyle,and for its role in the biogeochemical cycle of carbon and other elements;it is a fundamental *** use of less toxic and eco-friendly substances is important for protecting domestic,cultural,and historical heritage made of wood or lignocellulosic *** aim of this study was to evaluate the biological activity of various naphthoquinones extracted from the heartwood of *** on ***,heartwood flour was used for Soxhlet-type extractions to isolate and characterize the heartwood compounds by thin-layer *** identify the heartwood compounds,nuclear magnetic resonance and gas chromatography coupled to a mass spectrometer were *** information obtained was supported using the Interactive Spectroscopy *** identified heartwood compounds were lapachol,tectoquinone,deoxylapachol,dehydro-α-lapachone,tectol and *** nymphal termites of *** as a biological model,the isolated and identified molecules were under three different tests(repellent,insecticide and protective)and their biological activity was individually *** results showed that the molecules obtained have a repellent-protective effect against ***,although not in all cases,these molecules have high percentages of mortality and decreased the weight loss of the treated material exposed to ***.

关键词： Naphthoquinones dry wood termite Incisitermes marginipennis wood preservatives

Modulation of faecal metagenome in Crohn's disease:Role of microRNAs as biomarkers

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World Journal of Gastroenterology 2018年第46期24卷 5223-5233页

作者： María Rojas-feria Teresa Romero-García Jose Angel Fernández Caballero-Rico Helena Pastor Ramírez Marta Avilés-Recio manuel Castro-Fernandez Natalia Chueca Porcuna manuel Romero-Gomez Federico García Lourdes Grande JoséA Del Campo Department of Digestive Diseases Valme University HospitalUGC Digestive Disease and CIBERehdServicio Andaluz de SaludSeville E-41014Spain Complejo Hospitalario Universitario de Granada MicrobiologyGranada E-18016Spain Institute of Biomedicine of Seville Digestive DiseasesHospital Universitario Virgen del Rocío and CIBERehdSeville E-41013Spain Facultad de ciencias de la salud.Universidad Europea Miguel de Cervantes Madrid E-28280Spain

BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro RNAs(miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut *** To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut *** Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16 S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGRAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative *** Microbial community was characterized using 16 S rRNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showe

关键词： Crohn’s disease Dysbiosis microRNAs Firmicutes Bacteroidetes

The uPA/uPAR system in astrocytic wound healing

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Neural Regeneration Research 2022年第11期17卷 2404-2406页

作者： manuel Yepes Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research CenterAtlantaGAUSA Department of Neurology Emory University School of MedicineAtlantaGAUSA Department of Neurology Veterans Affairs Medical CenterAtlantaGAUSA

The repair of injured tissue is a highly complex process that involves cell prolife ration,differentiation,and *** migration requires the dismantling of intercellular contacts in the injured zone and their subsequent reconstitution in the wounded ***-type plasminogen activator(u PA)is a serine proteinase found in multiple cell types including endothelial cells,smooth muscle cells,monocytes,and macrophages.A substantial body of experimental evidence with different cell types outside the central nervous system indicates that the binding of uPA to its receptor(uPAR)on the cell surface prompts cell migration by inducing plasmin-mediated degradation of the extracellular *** contrast,although uPA and uPAR are abundantly found in astrocytes and u PA binding to uPAR triggers astrocytic activation,it is unknown if uPA also plays a role in astrocytic *** cadherin is a member of cell adhesion proteins pivotal for the formation of cell-cell conta cts between *** specifically,while the extracellular domain of neuronal cadherin interacts with the extracellular domain of neuronal cadherin in neighboring cells,its intracellular domain binds toβ-catenin,which in turn links the complex to the actin cytos *** synthase kinase 3βis a serine-threonine kinase that prevents the cytoplasmic accumulation ofβ-catenin by inducing its phosphorylation at Ser33,Ser37,and Ser41,thus activating a sequence of events that lead to its proteasomal *** data discussed in this perspective indicate that astrocytes release u PA following a mechanical injury,and that binding of this u PA to uPAR on the cell membrane induces the detachment ofβ-catenin from the intracellular domain of neuronal cadherin by triggering its extracellular signal-regulated kinase 1/2-mediated phosphorylation at ***,this is followed by the cytoplasmic accumulation ofβ-catenin because uPA-induced extracellular signalregulated kinase 1/2 activ

关键词： astrocytes lipoprotein receptor-related protein 6 plasmin urokinase receptor urokinase-type plasminogen activator Wnt-β-catenin pathway wound healing β-catenin

The plasminogen activating system in the pathogenesis of Alzheimer’s disease

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Neural Regeneration Research 2021年第10期16卷 1973-1977页

作者： manuel Yepes Department of Neurology Emory University School of MedicineAtlantaGAUSA Department of Neurology Veterans Affairs Medical CenterAtlantaGAUSA Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research CenterAtlantaGAUSA

Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor ***’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated ***,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular *** observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain *** plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of ***,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular *** contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβ*** we discuss the role of the PA system in the pathogenesis of AD and

关键词： Alzheimer’s disease amyloid precursor protein amyloidβ neuroserpin plasmin plasminogen activating system plasminogen activator inhibitor-1 synapse tissue-type plasminogen activator urokinase-type plasminogen activator

Positive curvature, symmetry, and topology

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Frontiers of Mathematics in China 2016年第5期11卷 1099-1122页

作者： manuel AMANN Fakultat fur Mathematik Institut fiir Algebra und Geometrie Karlsruher Institut fiir Technologie Englerstraβe 2 76131 Karlsruhe Germany

We depict recent developments in the field of positive sectional curvature, mainly, but not exclusively, under the assumption of isometric torus actions. After an elaborate introduction to the field, we shall discuss various classification results, before we provide results on the computation of Euler characteristics. This will be the starting point for an examination of more involved invariants and further techniques. In particular, we shall discuss the Hopf conjectures, related decomposition results like the Wilhelm conjecture, results in differential topology and index theory as well as in rational homotopy theory, geometrically formal metrics in positive curvature and much more. The results we present will be discussed for arbitrary dimensions, but also specified to small dimensions. This survey article features mainly depictions of our own work interest in this area and cites results obtained in different collaborations; full statements and proofs can be found in the respective original research articles.

关键词： Positive sectional curvature torus actions Euler characteristic Hopf conjecture index theory Wilhelm conjecture geometric formality

Urokinase-type plasminogen activator is a modulator of synaptic plasticity in the central nervous system:implications for neurorepair in the ischemic brain

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Neural Regeneration Research 2020年第4期15卷 620-624页

作者： manuel Yepes Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research Center Department of Neurology Emory University School of Medicine Department of Neurology Veterans Affairs Medical Center

The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with various degrees of ***,the lack of an effective therapeutic strategy to promote neurological recovery among stroke survivors has led to a rapidly growing population of disabled ***,understanding the mechanisms of neurorepair in the ischemic brain is a priority with wide scientific,social and economic *** ischemia has a harmful effect on synaptic structure associated with the development of functional *** agreement with these observations,experimental evidence indicates that synaptic repair underlies the recovery of neurological function following an ischemic ***,it has become evident that synaptic plasticity is crucial not only during development and learning,but also for synaptic repair after an ischemic *** plasminogen activating system is assembled by a cascade of enzymes and their inhibitors initially thought to be solely involved in the generation of ***,recent work has shown that in the brain this system has an important function regulating the development of synaptic plasticity via mechanisms that not always require plasmin ***-type plasminogen activator(uPA)is a serine proteinase and one of the plasminogen activators,that upon binding to its receptor(uPAR)not only catalyzes the conversion of plasminogen into plasmin on the cell surface,but also activates cell signaling pathways that promote cell migration,proliferation and *** role of uPA is the brain is not fully ***,it has been reported while uPA and uPAR are abundantly found in the developing central nervous system,in the mature brain their expression is restricted to a limited group of ***,following an ischemic injury to the mature brain the expressio

关键词： cerebral ischemia neurorepair plasminogen plasticity stoke synapse urokinase urokinase receptor