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Diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1245-1246页

作者： Christian Herder Michael Roden Nicolas Venteclef Institute for Clinical Diabetology German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf40225DüsseldorfGermany German center for Diabetes research(DZD) Partner Düsseldorf85764München-NeuherbergGermany Department of Endocrinology and Diabetology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University Düsseldorf40225DüsseldorfGermany Institut Necker-Enfants Malades(INEM) UniversitéParis CitéINSERM UMR-S1151CNRS UMR-S8253ParisFrance

In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory *** analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

关键词： impaired lung respiratory

The germline genetics of mild-to-moderate penetrance:An intriguing role of PRAME in multiple carcinogenesis

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Genes & Diseases 2024年第3期11卷 7-10页

作者： Diaddin Hamdan Van Tai Nguyen Justine Paris Christophe Leboeuf Morad El Bouchtaoui Marc Espie Anne Janin Geraldine Falgarone Melanie Di Benedetto Guithem Bousquet Universite de Paris Cite INSERMUMR_S942MASCOTParis F-75006France Hopital La Porte Verte Versailles F-78004France National cancer Hospital Cancer Research and Clinical Trials CenterHaNoi100000VietNam AP-HP-Hopital Saint Louis Centre de Maladies du SeinParisF-75010France Universite Sorbonne Paris Nord Bobigny F-93000France AP-HP-Hopital Avicenne Unite de Medecine AmbulatoireBobigny F-93000France

Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10%of *** assume that most cancers are the result of germline mutations of low to moderate penetrance,combined with acquired mutations due to external carcinogenic *** their accumulation over time,aging is associated with an increased risk of multiple cancer development in a given *** decades,germline genetics have been based on familial linkage studies enabling most high-penetrance genes to be *** recently,population-wide studies have led to the identification of considerable numbers of polymorphisms associated with cancer ***,most of them are of unknown functional value,thus limiting their translational application.

关键词： carcinogenesis BRCA linkage

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

What lessons can be learned from y T cell-based cancer immunotherapy trials？

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Cellular & Molecular Immunology 2013年第1期10卷 35-41页

作者： Jean-Jacques Fournie Helene Sicard Mary Poupot Christine Bezombes Amandine Blanc Franqois-Romagne Loic Ysebaert Guy Laurent inserm umr1037-cancer researchcenter of toulouse Toulouse France University of toulouse Toulouse France ERL 5294 CNRS BP3028 Hospital Purpan ToulouseFrAnce lnnate Pharma Marseilles France and Department of Hematology Hospital Purpan Toulouse France

During the last several years, research has produced a significant amount of knowledge concerning the characteristics of human 76 T lymphocytes. Findings regarding the immune functions of these cells, particularly their natural killer cell-like lyric activity against tumor cells, have raised expectations for the therapeutic applications of these cells for cancer. Pharmaceutical companies have produced selective agonists for these lymphocytes, and several teams have launched clinical trials of y8 T cell-based cancer therapies. The findings from these studies include hematological malignancies （follicular lymphoma, multiple myeloma, acute and chronic myeloid leukemia）, as well as solid tumors （renal cell, breast and prostate carcinomas）, consisting of samples from more than 250 patients from Europe, Japan and the United States. The results of these pioneering studies are now available, and this short review summarizes the lessons learned and the role of y6 T cell-based strategies in the current landscape of cancer immunotherapies.

关键词： cancer cell therapy gamma-delta lymphocytes immunotherapy lymphoma trials

Perspectives in human brain plasticity sparked by glioma invasion:from intraoperative(re)mappings to neural reconfigurations

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Neural Regeneration research 2024年第5期19卷 947-948页

作者： Sam Ng Hugues Duffau Guillaume Herbet Department of Neurosurgery Gui de Chauliac HospitalMontpellier University Medical CenterMontpellierFrance Institute of Functional Genomics University of MontpellierCNRSINSERMMontpellierFrance Praxiling Laboratory UMR5267CNRSPaul Valéry-Montpellier 3 UniversityMontpellierFrance

Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative *** term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical ***,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.

关键词： plasticity figuration consequences

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

Machine learning approach to assess the association between anthropometric,metabolic,and nutritional status and semen parameters

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Asian Journal of Andrology 2024年第4期26卷 349-355页

作者： Guillaume Bachelot Antonin Lamaziere Sebastien Czernichow Celine Faure Chrystelle Racine Rachel Levy Charlotte Dupont Nutrition and Fertility(ALIFERT)Group Author Information Sorbonne University School of Medicine Saint-Antoine Research CenterINSERM UMR 93827 rue ChalignyParis 75012France Reproductive Biology Department-CECOS Tenon HospitalAP-HP.Sorbonne UniversityParis 75020France Clinical Metabolomics Department Saint-Antoine HospitalAP-HP27 rue ChalignyParis 75012France Nutrition Department Obesity Specialist CentreGeorges Pompidou European HospitalAP-HPParis 75015France 不详

Many lifestyle factors,such as nutritional imbalance leading to obesity,metabolic disorders,and nutritional deficiency,have been identified as potential risk factors for male *** aim of this study was to evaluate the relationship between semen parameters and anthropometric,metabolic and nutritional *** was first assessed individually,then after the application of a previously constructed and validated machine learning score that allows their ***,metabolic,antioxidant,micronutrient,and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France(Jean-Verdier ART center Hospital,Bondy;North Hospital ART center,Saint-Étienne;Navarre Polyclinic ART center,Pau;and Cochin Hospital ART center,Paris)between September 2009 and December 2013 were *** assessing standard correlation analysis,a previously built machine learning model,providing a score ranging from 0(the poorest)to 1(the most favorable),was calculated for each man in the study *** machine learning model,which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature,provides a more holistic evaluation of the influence of the considered markers(anthropometric,metabolic,and oxidative status).We observed a significant correlation of some anthropometric,metabolic,and nutritional disorders with some sperm ***,an unfavorable machine learning score was associated with a high level of sperm DNA *** anthropometric,metabolic,and oxidative patterns,which may reflect an appropriate lifestyle,appear to positively impact overall health,in particular reproductive *** study,consistent with previous publications,suggests that beyond semen quality parameters,in an essential assessment of male fertility,other key factors should be taken into *** this regard,the application of emerging artificial intelligence t

关键词： lifestyle machine learning metabolism nutrition sperm DNA fragmentation

Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

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Journal of Molecular Cell Biology 2020年第3期12卷 202-215页

作者： Augustin Le Naour Melissa Prat Benolt Thibault Renaud Mével Léa Lemaitre Helene Leray Marie-Veronique Joubert Kimberley Coulson Muriel Golzio Lise Lefevre Eliane Mery Alejandra Martinez Gwénael Ferron Jean-Pierre Delord Agnès Coste Bettina Couderc Institut Claudius Regaud-IUCT Oncopole Universite de ToulouseToulouseFrance inserm umr 1037 Cancer Research Center of Toulouse(CRCT)ToulouseFrance umr 152 Pharma Dev Universite de ToulouseIRDUPSToulouseFrance umr CNRS 5089 Institut de Pharmacologie et de Biologie Structurale(IPBS)ToulouseFrance

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells(CA-MSCs)are involved in tumor progression and *** this study,we characterize the mechanisms by which naYve mesenchymal stromal cells(MSCs)can acquire a CA-MSCs *** tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells,resulting in the secretion of high levels of CXC chemokine receptors 1 and 2(CXCR1/2)ligands such as chemokine(C-X-C motif)ligand 1(CXCL1),CXCL2,and interleukin 8(IL-8).CXCR1/2 ligands can also inhibit the immune response against ovarian tumor ***,through their released factors,CA-MSCs promote the differentiation of monocytes towards M2 macrophages,which favors tumor *** CXCR1/2 receptors are inhibited,these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral *** ex vivo and in vivo,we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of *** high concentrations of CXCR1/2 ligands in patients*blood are associated with chemoresistance,CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.

关键词： chemoresistance macrophages mesenchymal stromal cells ovarian adenocarcinoma chemokines

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia cancer research cancer Lyon Universitéde LyonLyonFrance inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS umr5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8