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Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice

World Journal of Gastroenterology 2022年第48期28卷 6935-6949页

作者： Karim Atmani Fabien Wuestenberghs Maximilien Baron Illona Bouleté Charlène Guérin Wafa Bahlouli David Vaudry Jean Claude do Rego Jean-Nicolas Cornu Anne-Marie Leroi Moïse Coëffier Mathieu Meleine Guillaume Gourcerol Nutrition Gut and Brain Unit(Inserm U1073)Institute for Research and Innovation in BiomedicineUniversitéde Rouen NormandieRouen 76000France Department of Gastroenterology and Hepatology UniversitéCatholique de LouvainCHU UCL NamurYvoir 5530Belgium Department of Physiology CHU RouenUniversitéde Rouen NormandieRouen 76031France Department of urology CHU RouenUniversitéde Rouen NormandieRouen 76000France inserm UMR 1245Team Epigenetics and Pathophysiology of Neurodevelopmental DisordersUniversitéde Rouen NormandieRouen 76000France Behavioural Analysis Platform(SCAC) HeRacLeS Inserm US51-CNRS UAR2026Institute for Research and Innovation in BiomedicineUniversitéde Rouen NormandieRouen 76000France Department of Nutrition CHU RouenUniversitéde Rouen NormandieRouen 76000France inserm u1107 NeuroDolClermont Auvergne UniversityClermont-Ferrand 63000France

BACKGROuND Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral *** pelvic organs share common sensory pathways,it is likely that those syndromes involve a cross-sensitization of the bladder and the *** precise pathophysiology remains poorly *** To develop a model of chronic bladder-colon cross-sensitization and to investigate the mechanisms *** Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane *** sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal ***,used as a marker of colorectal inflammation,was measured in the colon,and colorectal permeability was measured using chambers.c-Fos protein expression,used as a marker of neuronal activation,was assessed in the spinal cord(L6-S1 level)using *** fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal *** expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western *** Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid vs saline(Pup to 7 d *** increased permeability or inflammation was shown in the bladder or colon 7 d *** hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord(Puorescent protein on the fractalkine receptor-positive mice,intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord(Pup to 7 d after

关键词： Cross-organ sensitization MAPK-p38 Microglia NK1 receptor Pain Visceral hypersensitivity

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Transient micro-elastography:A novel non-invasive approach to measure liver stiffness in mice

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World Journal of Gastroenterology 2011年第8期17卷 968-975页

作者： Cécile Bastard Matteo R Bosisio Michèle Chabert Athina D Kalopissis Meriem Mahrouf-Yorgov Hélène Gilgenkrantz Sebastian Mueller Laurent Sandrin Laurent Sandrin Echo-sens Research and Development Department inserm U930 CNRS ERL3106 univ Franois Rabelais uPMC univ Paris 06 UMR 7623 LIP CNRS UMR 7623 Laboratoire d'Imagerie Paramétrique inserm U872 Centre de Recherche des Cordeliers Equipe 4 uPMC univ Paris 06 UMR S 872 Equipe 4 univ Paris Descartes UMR S 872 Equipe 4 EPHE Laboratoire de Pharmacologie Cellulaire Et Moléculaire inserm U1016 Institut Cochin CNRS UMR8104 univ Paris Descartes Department of Medicine and Center for Alcohol Research Liver Disease and Nutrition Salem Medical Center University of Heidelberg

AIM:To develop and validate a transient micro-elastography device to measure liver stiffness(LS) in ***:A novel transient micro-elastography(TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm *** novel probe was validated in a classical fibrosis model(CCl4) and in a transgenic murine model of systemic ***:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement(0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls(18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover,fibrosis stage was highly correlated with LS(Spearman coefficient = 0.88,P uch higher LS values were obtained,reaching maximum values of > 150 *** significantly correlated with the amyloidosis index(0.93,P utant hapoA-□(0.62,P uSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS.

关键词： Transient elastography Micro-elastography Liver stiffness Liver Mice Amyloidosis Fibrosis ultrasound

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αV integrin:A new gastrin target in human pancreatic cancer cells

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World Journal of Gastroenterology 2011年第40期17卷 4488-4495页

作者： Celine Cayrol Claudine Bertrand Aline Kowalski-Chauvel Laurence Daulhac Elizabeth Cohen-Jonathan-Moyal Audrey Ferrand Catherine Seva inserm umr1037-Cancer Research Center of Toulouse Paul Sabatier university Toulouse Ⅲ 31432 Toulouse cedex 4 France inserm u766 Department of pharma-cology Clermont 1 university of Pharmacy 63001 Clermont-Ferrand France

AIM： To analyse αv integrin expression induced by gas- trin in pancreatic cancer ***： αv integrin mRNA expression in human pan- creatic cancer cells was analysed using a ＂cancer genes＂ array and confirmed by real-time reverse transcription- polymerase chain reaction （PCR）. Western blotting and semi-quantitative immunohistochemistry were used to examine protein levels in human pancreatic cancer cell lines and pancreatic tissues, respectively, The role of αv integrin on gastrin-induced cell adhesion was examined using blocking anti-αv integrin monoclonal antibodies. Adherent cells were quantified by staining with crystal ***： using a ＂cancer genes＂ array we identi- fied c^v integrin as a new gastrin target gene in human pancreatic cancer cells. A quantitative real-time PCR approach was used to confirm αv integrin gene expression. We also demonstrate that Src family kinases and the PI 3-kinase, two signalling pathways specifically activated by the CCK-2 receptor （CCK2R）, are involved in gastrin-mediated αv integrin expression. In contrast, inhibition of the ERK pathway was without any effect on αv integrin expression induced by gastrin. Our results also show that gastrin modulates cell adhesion via αv integrins. Indeed, in vitro adhesion assays performed on fibronectin show that gastrin significantly increases adhesion of pancreatic cancer cells. The use of blocking anti-αv integrin monoclonal antibodies completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we showed in vivo that the targeted CCK2R expression in the pancreas of Elas-CCK2 mice, leads to the overexpression of αv integrin. This process may contribute to pancreatic turnout development observed in these transgenic ***： αv integrin is a new gastrin target in pancreatic cancer models and contributes to gastrin effects on cell adhesion.

关键词： v integrin Cell adhesion CCK-2 receptor Gastrin Pancreatic cancer

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Class switch recombination junctions are not affected by the absence of the immunoglobulin heavy chain E_(μ) enhancer

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Cellular & Molecular Immunology 2019年第7期16卷 671-673页

作者： Hussein Issaoui Nour Ghazzaui Mélissa Ferrad François Boyer Yves Denizot umr CNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

After encountering antigen,B-cells undergo class switch recombination(CSR)that substitutes the constant(C)μgene with Cγ,Cε,or Cα,thereby generating IgG,IgE,and IgA antibodies with new effector functions but the same antigenic specificity.1 The DNA-editing enzyme activation-induced deaminase(AID)is required for CSR by targeting specific DNA switch(S)regions preceding the C region,except Cδ.2 Sμis the donor region,while Sγ,ε,αare the acceptor *** is controlled in cis by the immunoglobulin heavy chain(IgH)3’regulatory region(3’RR).3 The 3’RR is essential to poise AID on the S acceptor *** CSR IgH,intrachromosomal interactions(schematized in Fig.1a)are found between the 3’RR and the intronic Eμenhancer.1,4 Looping allows transcriptional binding activators to enhancers to facilitate ***,CSR is only modestly influenced by Eμdeletion.5–7 During CSR,two different DNA repair pathways take place:the classical nonhomologous end joining(c-NHEJ)and the alternative end joining(A-EJ)pathways.

关键词： joining thereby generating

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Molecular analysis of γ1, γ3, and α class switch recombination junctions in APOBEC3-deficient mice using high-throughput sequencing

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Cellular & Molecular Immunology 2020年第4期17卷 418-420页

作者： Hussein Issaoui Mélissa Ferrad Nour Ghazzaui Sandrine Lecardeur Jeanne Cook-Moreau François Boyer Yves Denizot umr CNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

Activation-induced deaminase(AID)is required for immunoglobulin(Ig)class switch recombination(CSR),in which the constant(C)μgene of IgM is substituted with C_(γ),C_(ε),or C_(α),thereby generating IgG,IgE,and IgA antibodies,respectively,with new effector functions but the same antigenic specificity.1 AID targets specific DNA switch(S)regions preceding C regions except for Cδ.2 Sμis usually the donor region,while Sγ,ε,αare the acceptor *** deaminates C into u on single-stranded DNA by targeting the WRCY(W=A/T,R=A/G,and Y=C/T)hot motif and,to a lesser extent,the SYC(S=G/C,Y=C/T)cold motif.3,4 AID is a member of the apolipoprotein B editing complex(APOBEC)*** APOBEC genes,a family of evolutionarily conserved cytidine deaminases,APOBEC3 is implicated in diverse cell functions including innate immunity against retroviruses.4 The DNA-editing APOBEC3 enzymes have recently attracted attention due to their involvement in cancer and potential applications in gene editing.5–7 While a single copy of each APOBEC3 gene is present in rodents,seven copies of each APOBEC3 gene are found in humans.

关键词： immunity involvement thereby

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Ferritin surplus in mouse spleen 14 months after intravenous injection of iron oxide nanoparticles at clinical dose

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Nano Research 2016年第8期9卷 2398-2410页

作者： Alexandre Tamion Matthias Hillenkamp Arnaud Hillion Valentin A. Maraloiu Ioana D. Vlaicu Mariana Stefan Daniela Ghica Hugo Rositi Fabien Chauveau Marie-Genevieve Blanchin Marlene Wiart Veronique Dupuis Institut Lumiere Matiere UMR5306 Universite Lyon 1- CNRS Universite de Lyon 69622 Villeurbanne cedex France National Institute of Materials Physics 105bis AtomistilorSt. R-077125 Bucharest-Magurele Romania CNRS UMR 5220 INSERM U1044 INSA de Lyon Universite de Lyon Lyon 1 CREATIS 69003 Lyon France CRNL-BIORAN CNRS UMR5292 INSERM U 1028 Universite Lyon 1 59 BD PINEL 69677 Bron France

In this study, we followed the biodegradation of ultra-small superparamagnetic iron oxide nanoparticles injected intravenously at clinical doses in mice. An advanced fitting procedure for magnetic susceptibility curves and low- temperature hysteresis loops was used to fully characterize the magnetic size distribution as well as the magnetic anisotropy energy of the injected P904 nano- particles （Guerbet Laboratory）. Additional magnetometry measurements and transmission electronic microscopy observations were systematically performed to examine dehydrated samples from the spleen and liver of healthy C57B16 mice after nanoparticle injection, with sacrifice of the mice for up to 14 months. At 3 months after injection, the magnetic properties of the spleen and liver were dramatically different. While the liver showed no magnetic signals other than those also present in the reference species, the spleen showed an increased magnetic signal attributed to ferritin. This surplus of ferritin remained constant up to 14 months after injection.

关键词： nanoparticles biodegradation iron oxide nanomagnetism contrast agent

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Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

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World Journal of Gastroenterology 2022年第36期28卷 5324-5337页

作者： Gael Roth Yann Teyssier Maxime Benhamou Mélodie Abousalihac Stefano Caruso Christian Sengel Olivier Seror Julien Ghelfi Arnaud Seigneurin Nathalie Ganne-Carrie Elia Gigante Lorraine Blaise Olivier Sutter Thomas Decaens Jean-Charles Nault univ.Grenoble-Alpes Grenoble 38058France Department of Hepatology Gastroenterology and Digestive OncologyCHU Grenoble AlpesGrenoble 38043France Institute for Advanced Biosciences INSERM U1209/CNRS UMR 5309Grenoble 38043France Department of Radiology CHU Grenoble AlpesGrenoble 38043France Department of Radiology CHU Avicenne-APHPBobigny 93000France Functional Genomics of Solid Tumors Laboratory Centre de Recherche des Cordeliers-INSERM UMR 1138InsermUniversitéParisParis 75006France unitéde Formation et de Recherche SantéMédecine et Biologie Humaine UniversitéParis NordParis 93430France Service d'Epidémiologie et Evaluation Médicale CHU Grenoble AlpesGrenoble 38043France Department of Hepatology CHU Avicenne-APHPBobigny 93000France

BACKGROuND At the diagnosis of hepatocellular carcinoma(HCC),more than 90%of HCC patients present cirrhosis,a clinical condition often associated to *** is an indirect marker of malnutrition assessable on computed tomography(CT).AIM To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial(chemo)-*** Patients with HCC treated by a first session of trans-arterial(chemo)embolization and an available CT scan before treatment were *** was assessed using skeletal muscle index at baseline and at the first radiological *** response was recorded after the first session of treatment using *** Of 225 patients treated by trans-arterial bland embolization(n=71)or trans-arterial chemoembolization(n=154)for HCC between 2007 and 2013,Barcelona Clinic of Liver Cancer stage was A,B,and C in 27.5%,55%,and 16.8%of cases,*** was present in 57.7%of the *** with sarcopenia presented a higher rate of progressive disease(19%vs 8%,P=0.0236),a shorter progression-free survival(8.3 vs 13.2 mo,P=0.0035),and a shorter median overall survival(19.4 mo vs 35.5 mo,P=0.0149)compared with non-sarcopenic ***,patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis(P=0.0004).CONCLuSION Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial(chemo)-embolization for HCC.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Bland embolization Sarcopenia Skeletal muscle index

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SNAP23-Kif5 complex controls mGlu1 receptor trafficking

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Journal of Molecular Cell Biology 2018年第5期10卷 423-436页

作者： Fabrice Raynaud Vincent Homburger Martial Seveno Oana Vigy Enora Moutina Laurent Fagni Julie Perroy IGF CNRS INSERM Univ. Montpel[ier F-34094 Montpellier France BioCampus Montpellier CNRS INSERM Univ. Montpellier F-34094 Montpellier France Present address: inserm u1046 PhyMedExp CNRS UMR9214 Univ. Montpellier F-34094 Montpellier France

Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.

关键词： mGlu1 SNARE kinesin neuron traffic

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High doses of catecholamines activate glucose transport in human adipocytes independently from adrenoceptor stimulation or vanadium addition

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World Journal of Diabetes 2022年第1期13卷 37-53页

作者： Christian Carpéné Nathalie Boulet Jean-Louis Grolleau Nathalie Morin Institut des Maladies Métaboliques et Cardiovasculaires INSERM UMR1297Toulouse 31432France Team Dinamix Institute of Metabolic and Cardiovascular Diseases(I2MC)Paul Sabatier UniversityToulouse 31432France Department of Plastic Surgery CHU RangueilToulouse 31059France Facultéde Pharmacie de Paris Universitéde ParisINSERM UMR-S 11393PHMParis 75006France

BACKGROuND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse *** To test whether catecholamines activate glucose transport in human *** The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive *** approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESuLTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to *** stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation *** various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG *** effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine *** peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by *** and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG *** High doses of catecholamines exert insulin-like actions on glucose transport in human *** submillimolar doses,vanadium did not enhance this catecholamine activation of glucose ***,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.

关键词： Human adipocytes Amine oxidases Insulin Diabetes Vanadium Obesity

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MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer

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World Journal of Gastroenterology 2014年第32期20卷 11199-11209页

作者： Marion Gayral Sébastien Jo Naima Hanoun Alix Vignolle-Vidoni Hubert Lulka Yannick Delpu Aline Meulle Marlène Dufresne Marine Humeau Maёl Chalret du Rieu Barbara Bournet Janick Sèlves Rosine Guimbaud Nicolas Carrère Louis Buscail Jérome Torrisani Pierre Cordelier Cancer Research Center of Toulouse Team 10 UMR INSERM U1037Université Paul Sabatier P?le Digestif Centre Hospitalier Universitaire Toulouse

Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.

关键词： MicroRNAs Biomarkers Pancreatic cancer Therapeutic targets Precancerous lesions

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