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  1. Article ; Online: Diethylnitrosamine Induction of Hepatocarcinogenesis in Mice.

    Sotty, Jules / Bablon, Pierre / Weiss, Paul-Henry / Soussan, Patrick

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2769, Page(s) 15–25

    Abstract: Diethylnitrosamine (DEN) is a chemical hepatocarcinogenic agent that triggers a large array of oncogenic mutations after a single injection. Initiated hepatocytes subsequently undergo clonal expansion within a proliferative environment, rendering the DEN ...

    Abstract Diethylnitrosamine (DEN) is a chemical hepatocarcinogenic agent that triggers a large array of oncogenic mutations after a single injection. Initiated hepatocytes subsequently undergo clonal expansion within a proliferative environment, rendering the DEN model a comprehensive carcinogen. In rodent studies, DEN finds extensive utility in experimental liver cancer research, mimicking several aspects of human hepatocellular carcinoma (HCC), including angiogenesis, metabolic reprogramming, immune exhaustion, and the ability to metastasize. Beyond the wealth of scientific insights gleaned from this model, the objective of this chapter is to review morphological, genomic, and immunological characteristics associated to DEN-induced HCC. Furthermore, this chapter provides a detailed procedural guide to effectively induce hepatocarcinogenesis in mice through a single intraperitoneal injection of DEN.
    MeSH term(s) Mice ; Humans ; Animals ; Carcinoma, Hepatocellular/chemically induced ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Diethylnitrosamine/toxicity ; Liver Neoplasms/chemically induced ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Carcinogenesis/chemically induced ; Carcinogenesis/genetics ; Hepatocytes/pathology ; Mice, Inbred C57BL
    Chemical Substances Diethylnitrosamine (3IQ78TTX1A)
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3694-7_2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hepatitis B Virus spliced 1 RNA, a key factor for viral expression.

    Bablon, Pierre / Goy, Céline / Dang, Hoan Nguyen / Sotty, Jules / Soussan, Patrick

    Journal of hepatology

    2024  

    Language English
    Publishing date 2024-05-09
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2024.04.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Flow Cytometry Assessment of Lymphocyte Populations Infiltrating Liver Tumors.

    Pérez-Lanzón, Maria / Plantureux, Céleste / Paillet, Juliette / Sotty, Jules / Soussan, Patrick / Kroemer, Guido / Maiuri, Maria Chiara / Pol, Jonathan

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2769, Page(s) 129–141

    Abstract: Tissue-resident and recruited immune cells are essential mediators of natural and therapy-induced immunosurveillance of liver neoplasia. This idea has been recently reinforced by the clinical approval of immune checkpoint inhibitors for the immunotherapy ...

    Abstract Tissue-resident and recruited immune cells are essential mediators of natural and therapy-induced immunosurveillance of liver neoplasia. This idea has been recently reinforced by the clinical approval of immune checkpoint inhibitors for the immunotherapy of hepatocellular carcinoma and cholangiocarcinoma. Such research progress relies on the in-depth characterization of the immune populations that are present in pre-neoplastic and neoplastic hepatic lesions. A convenient technology for advancing along this path is high-dimensional cytometry.In this chapter, we present a protocol to assess the subtype and differentiation state of hepatic lymphocyte populations by multicolor immunofluorescence staining and flow cytometry. We detail the steps required for viability assessment and immune cell phenotyping of single-cell suspensions of liver cells by means of surface and intracellular staining of more than a dozen markers of interest. This protocol does not require prior removal of debris and dead cells and allows to process multiple samples in parallel. The procedure includes the use of a fixative-resistant viability dye that allows cell fixation and permeabilization after cell surface staining and before intracellular staining and data acquisition on a flow cytometer. Moreover, we provide a panel of fluorochrome-labeled antibodies designed for the characterization of lymphocytic subsets that can be adapted to distinct experimental settings. Finally, we present an overview of the post-staining pipeline, including data acquisition on a flow cytometer and tools for post-acquisition analyses.
    MeSH term(s) Humans ; Flow Cytometry/methods ; Lymphocyte Subsets ; Liver Neoplasms ; Bile Duct Neoplasms ; Bile Ducts, Intrahepatic
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Review ; Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3694-7_10
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Alternative splicing of viral transcripts: the dark side of HBV.

    Kremsdorf, Dina / Lekbaby, Bouchra / Bablon, Pierre / Sotty, Jules / Augustin, Jérémy / Schnuriger, Aurélie / Pol, Jonathan / Soussan, Patrick

    Gut

    2021  Volume 70, Issue 12, Page(s) 2373–2382

    Abstract: Regulation of alternative splicing is one of the most efficient mechanisms to enlarge the proteomic diversity in eukaryotic organisms. Many viruses hijack the splicing machinery following infection to accomplish their replication cycle. Regarding the HBV, ...

    Abstract Regulation of alternative splicing is one of the most efficient mechanisms to enlarge the proteomic diversity in eukaryotic organisms. Many viruses hijack the splicing machinery following infection to accomplish their replication cycle. Regarding the HBV, numerous reports have described alternative splicing events of the long viral transcript (pregenomic RNA), which also acts as a template for viral genome replication. Alternative splicing of HBV pregenomic RNAs allows the synthesis of at least 20 spliced variants. In addition, almost all these spliced forms give rise to defective particles, detected in the blood of infected patients. HBV-spliced RNAs have long been unconsidered, probably due to their uneasy detection in comparison to unspliced forms as well as for their dispensable role during viral replication. However, recent data highlighted the relevance of these HBV-spliced variants through (1) the trans-regulation of the alternative splicing of viral transcripts along the course of liver disease; (2) the ability to generate defective particle formation, putative biomarker of the liver disease progression; (3) modulation of viral replication; and (4) their intrinsic propensity to encode for novel viral proteins involved in liver pathogenesis and immune response. Altogether, tricky regulation of HBV alternative splicing may contribute to modulate multiple viral and cellular processes all along the course of HBV-related liver disease.
    MeSH term(s) Alternative Splicing ; Genome, Viral ; Hepatitis B virus/genetics ; Humans ; Proteomics ; RNA Splicing
    Language English
    Publishing date 2021-09-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80128-8
    ISSN 1468-3288 ; 0017-5749
    ISSN (online) 1468-3288
    ISSN 0017-5749
    DOI 10.1136/gutjnl-2021-324554
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Diversity of the nucleic acid forms of circulating HBV in chronically infected patients and its impact on viral cycle.

    Sotty, Jules / Bablon, Pierre / Lekbaby, Bouchra / Augustin, Jérémy / Girier-Dufournier, Morgane / Langlois, Lucas / Dorival, Céline / Carrat, Fabrice / Pol, Stanislas / Fontaine, Hélène / Sarica, Nazim / Neuveut, Christine / Housset, Chantal / Kremdsorf, Dina / Schnuriger, Aurélie / Soussan, Patrick

    Hepatology international

    2022  Volume 16, Issue 6, Page(s) 1259–1272

    Abstract: Background: Besides the prototypical hepatitis B virus (HBV) infectious particle, which contains a full-length double-stranded DNA (flDNA), additional circulating virus-like particles, which carry pregenomic RNA (pgRNA), spliced1RNA (sp1RNA) or spliced- ... ...

    Abstract Background: Besides the prototypical hepatitis B virus (HBV) infectious particle, which contains a full-length double-stranded DNA (flDNA), additional circulating virus-like particles, which carry pregenomic RNA (pgRNA), spliced1RNA (sp1RNA) or spliced-derived DNA (defDNA) forms have been described. We aimed to determine the level of these four circulating forms in patients and to evaluate their impact on viral lifecycle.
    Methods: Chronic HBV untreated patients (n = 162), included in the HEPATHER cohort, were investigated. Pangenomic qPCRs were set up to quantify the four circulating forms of HBV nucleic acids (HBV
    Results: Hierarchical clustering individualized two clusters of HBV
    Conclusion: Besides the critical role of HBV replication in circulating HBV
    Clinical trial registration: Patients were included from a prospective multicenter French national cohort (ANRS CO22 HEPATHER, NCT01953458).
    MeSH term(s) Humans ; Hepatitis B virus/genetics ; Nucleic Acids/therapeutic use ; Prospective Studies ; DNA, Viral/genetics ; Hepatitis B, Chronic/drug therapy ; Virus Replication ; Hepatitis B ; RNA ; RNA, Viral/analysis
    Chemical Substances Nucleic Acids ; DNA, Viral ; RNA (63231-63-0) ; RNA, Viral
    Language English
    Publishing date 2022-08-04
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2270316-0
    ISSN 1936-0541 ; 1936-0533
    ISSN (online) 1936-0541
    ISSN 1936-0533
    DOI 10.1007/s12072-022-10389-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Exposure to Atmospheric Ultrafine Particles Induces Severe Lung Inflammatory Response and Tissue Remodeling in Mice.

    Saleh, Yara / Antherieu, Sébastien / Dusautoir, Romain / Y Alleman, Laurent / Sotty, Jules / De Sousa, Corentin / Platel, Anne / Perdrix, Esperanza / Riffault, Véronique / Fronval, Isabelle / Nesslany, Fabrice / Canivet, Ludivine / Garçon, Guillaume / Lo-Guidice, Jean-Marc

    International journal of environmental research and public health

    2019  Volume 16, Issue 7

    Abstract: Exposure to particulate matter (PM) is leading to various respiratory health outcomes. Compared to coarse and fine particles, less is known about the effects of chronic exposure to ultrafine particles, despite their higher number and reactivity. In the ... ...

    Abstract Exposure to particulate matter (PM) is leading to various respiratory health outcomes. Compared to coarse and fine particles, less is known about the effects of chronic exposure to ultrafine particles, despite their higher number and reactivity. In the present study, we performed a time-course experiment in mice to better analyze the lung impact of atmospheric ultrafine particles, with regard to the effects induced by fine particles collected on the same site. Trace element and PAH analysis demonstrated the almost similar chemical composition of both particle fractions. Mice were exposed intranasally to FF or UFP according to acute (10, 50 or 100 µg of PM) and repeated (10 µg of PM 3 times a week during 1 or 3 months) exposure protocols. More particle-laden macrophages and even greater chronic inflammation were observed in the UFP-exposed mice lungs. Histological analyses revealed that about 50% of lung tissues were damaged in mice exposed to UFP for three months versus only 35% in FF-exposed mice. These injuries were characterized by alveolar wall thickening, macrophage infiltrations, and cystic lesions. Taken together, these results strongly motivate the update of current regulations regarding ambient PM concentrations to include UFP and limit their emission.
    MeSH term(s) Air Pollutants/adverse effects ; Air Pollutants/analysis ; Animals ; Disease Models, Animal ; Environmental Exposure/adverse effects ; Environmental Exposure/analysis ; Lung/drug effects ; Lung/immunology ; Lung/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Particle Size ; Particulate Matter/administration & dosage ; Particulate Matter/adverse effects ; Systemic Inflammatory Response Syndrome/chemically induced ; Systemic Inflammatory Response Syndrome/pathology ; Time Factors
    Chemical Substances Air Pollutants ; Particulate Matter
    Language English
    Publishing date 2019-04-04
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1660-4601
    ISSN (online) 1660-4601
    DOI 10.3390/ijerph16071210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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