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  1. Article: Oncostatin M: From Intracellular Signaling to Therapeutic Targets in Liver Cancer.

    Caligiuri, Alessandra / Gitto, Stefano / Lori, Giulia / Marra, Fabio / Parola, Maurizio / Cannito, Stefania / Gentilini, Alessandra

    Cancers

    2022  Volume 14, Issue 17

    Abstract: ... Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. Oncostatin M (OSM ...

    Abstract Primary liver cancers represent the third-most-common cause of cancer-related mortality worldwide, with an incidence of 80-90% for hepatocellular carcinoma (HCC) and 10-15% for cholangiocarcinoma (CCA), and an increasing morbidity and mortality rate. Although HCC and CCA originate from independent cell populations (hepatocytes and biliary epithelial cells, respectively), they develop in chronically inflamed livers. Evidence obtained in the last decade has revealed a role for cytokines of the IL-6 family in the development of primary liver cancers. These cytokines operate through the receptor subunit gp130 and the downstream Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. Oncostatin M (OSM), a member of the IL-6 family, plays a significant role in inflammation, autoimmunity, and cancer, including liver tumors. Although, in recent years, therapeutic approaches for the treatment of HCC and CCA have been implemented, limited treatment options with marginal clinical benefits are available. We discuss how OSM-related pathways can be selectively inhibited and therapeutically exploited for the treatment of liver malignancies.
    Language English
    Publishing date 2022-08-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14174211
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Oncostatin M is overexpressed in NASH-related hepatocellular carcinoma and promotes cancer cell invasiveness and angiogenesis.

    Di Maira, Giovanni / Foglia, Beatrice / Napione, Lucia / Turato, Cristian / Maggiora, Marina / Sutti, Salvatore / Novo, Erica / Alvaro, Maria / Autelli, Riccardo / Colombatto, Sebastiano / Bussolino, Federico / Carucci, Patrizia / Gaia, Silvia / Rosso, Chiara / Biasiolo, Alessandra / Pontisso, Patrizia / Bugianesi, Elisabetta / Albano, Emanuele / Marra, Fabio /
    Parola, Maurizio / Cannito, Stefania

    The Journal of pathology

    2022  Volume 257, Issue 1, Page(s) 82–95

    Abstract: Oncostatin M (OSM) is a pleiotropic cytokine of the interleukin (IL)-6 family that contributes ...

    Abstract Oncostatin M (OSM) is a pleiotropic cytokine of the interleukin (IL)-6 family that contributes to the progression of chronic liver disease. Here we investigated the role of OSM in the development and progression of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The role of OSM was investigated in (1) selected cohorts of NAFLD/NASH HCC patients, (2) liver cancer cells exposed to human recombinant OSM or stably transfected to overexpress human OSM, (3) murine HCC xenografts, and (4) a murine NASH-related model of hepatic carcinogenesis. OSM was found to be selectively overexpressed in HCC cells of NAFLD/NASH patients, depending on tumor grade. OSM serum levels, barely detectable in patients with simple steatosis or NASH, were increased in patients with cirrhosis and more evident in those carrying HCC. In this latter group, OSM serum levels were significantly higher in the subjects with intermediate/advanced HCCs and correlated with poor survival. Cell culture experiments indicated that OSM upregulation in hepatic cancer cells contributes to HCC progression by inducing epithelial-to-mesenchymal transition and increased invasiveness of cancer cells as well as by inducing angiogenesis, which is of critical relevance. In murine xenografts, OSM overexpression was associated with slower tumor growth but an increased rate of lung metastases. Overexpression of OSM and its positive correlation with the angiogenic switch were also confirmed in a murine model of NAFLD/NASH-related hepatocarcinogenesis. Consistent with this, analysis of liver specimens from human NASH-related HCCs with vascular invasion showed that OSM was expressed by liver cancer cells invading hepatic vessels. In conclusion, OSM upregulation appears to be a specific feature of HCC arising on a NAFLD/NASH background, and it correlates with clinical parameters and disease outcome. Our data highlight a novel pro-carcinogenic contribution for OSM in NAFLD/NASH, suggesting a role of this factor as a prognostic marker and a putative potential target for therapy. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
    MeSH term(s) Animals ; Carcinogenesis ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Mice ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/pathology ; Oncostatin M
    Chemical Substances Oncostatin M (106956-32-5)
    Language English
    Publishing date 2022-03-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3119-7
    ISSN 1096-9896 ; 0022-3417
    ISSN (online) 1096-9896
    ISSN 0022-3417
    DOI 10.1002/path.5871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Reply to Lebeaux D, Revest M. No evidence of clinical benefits of early treatment of COVID-19 patients with hydroxychloroquine and azithromycin.

    Million, Matthieu / Giraud-Gatineau, Audrey / Lagier, Jean-Christophe / Parola, Philippe / Gautret, Philippe / Raoult, Didier

    Travel medicine and infectious disease

    2020  Volume 39, Page(s) 101954

    MeSH term(s) Azithromycin/therapeutic use ; COVID-19/drug therapy ; Drug Therapy, Combination ; France ; Humans ; Hydroxychloroquine/therapeutic use ; Retrospective Studies ; SARS-CoV-2
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH) ; Azithromycin (83905-01-5)
    Language English
    Publishing date 2020-12-13
    Publishing country Netherlands
    Document type Journal Article ; Comment
    ZDB-ID 2170891-5
    ISSN 1873-0442 ; 1477-8939
    ISSN (online) 1873-0442
    ISSN 1477-8939
    DOI 10.1016/j.tmaid.2020.101954
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6236: Show issues Location:
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  4. Article ; Online: Oncostatin M, A Profibrogenic Mediator Overexpressed in Non-Alcoholic Fatty Liver Disease, Stimulates Migration of Hepatic Myofibroblasts.

    Foglia, Beatrice / Sutti, Salvatore / Pedicini, Dario / Cannito, Stefania / Bocca, Claudia / Maggiora, Marina / Bevacqua, Maria Rosaria / Rosso, Chiara / Bugianesi, Elisabetta / Albano, Emanuele / Novo, Erica / Parola, Maurizio

    Cells

    2019  Volume 9, Issue 1

    Abstract: ... by aligning with nascent and established fibrotic septa in response to several mediators. Oncostatin M (OSM ...

    Abstract Background: Hepatic myofibroblasts (MFs) can originate from hepatic stellate cells, portal fibroblasts, or bone marrow-derived mesenchymal stem cells and can migrate towards the site of injury by aligning with nascent and established fibrotic septa in response to several mediators. Oncostatin M (OSM) is known to orchestrate hypoxia-modulated hepatic processes involving the hypoxia-inducible factor 1 (HIF-1).
    Methods: In vivo and in vitro experiments were performed to analyze the expression of OSM and OSM-receptor (OSMR) in three murine models of non-alcoholic-fatty liver disease (NAFLD) and -steatohepatitis (NASH) and in human NASH patients as well as the action of OSM on phenotypic responses of human MFs.
    Results: Hepatic OSM and OSMR levels were overexpressed in three murine NASH models and in NASH patients. OSM stimulates migration in human MFs by involving early intracellular ROS generation and activation of Ras/Erk, JNK1/2, PI3K/Akt as well as STAT1/STAT3 pathways and HIF-1α. OSM-dependent migration relies on a biphasic mechanism requiring early intracellular generation of reactive oxygen species (ROS) and late HIF1-dependent expression and release of VEGF.
    Conclusion: OSM is overexpressed in experimental and human progressive NAFLD and can act as a profibrogenic factor by directly stimulating migration of hepatic MFs.
    MeSH term(s) Animals ; Cell Line ; Cell Movement/drug effects ; Disease Models, Animal ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Mice ; Myofibroblasts/cytology ; Myofibroblasts/metabolism ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Oncostatin M/genetics ; Oncostatin M/metabolism ; Oncostatin M Receptor beta Subunit/genetics ; Oncostatin M Receptor beta Subunit/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Up-Regulation ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Hypoxia-Inducible Factor 1 ; OSM protein, human ; OSMR protein, human ; Oncostatin M Receptor beta Subunit ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; Oncostatin M (106956-32-5)
    Language English
    Publishing date 2019-12-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9010028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Follistatin-like protein 1 and chronic liver disease progression: a novel pro-inflammatory and pro-fibrogenic mediator?

    Parola, Maurizio

    Annals of translational medicine

    2022  Volume 10, Issue 15, Page(s) 841

    Language English
    Publishing date 2022-08-27
    Publishing country China
    Document type Editorial ; Comment
    ZDB-ID 2893931-1
    ISSN 2305-5847 ; 2305-5839
    ISSN (online) 2305-5847
    ISSN 2305-5839
    DOI 10.21037/atm-22-3561
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Organ Fibrosis: Emerging diagnostic and therapeutic strategies.

    Parola, Maurizio / Pinzani, Massimo

    Molecular aspects of medicine

    2024  Volume 96, Page(s) 101259

    MeSH term(s) Humans ; Fibrosis
    Language English
    Publishing date 2024-02-26
    Publishing country England
    Document type Editorial
    ZDB-ID 197640-0
    ISSN 1872-9452 ; 0098-2997
    ISSN (online) 1872-9452
    ISSN 0098-2997
    DOI 10.1016/j.mam.2024.101259
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    Zs.A 1189: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies.

    Parola, Maurizio / Pinzani, Massimo

    Molecular aspects of medicine

    2023  Volume 95, Page(s) 101231

    Abstract: Liver fibrosis, as an excess deposition of extracellular matrix (ECM) components, results from chronic liver injury as well as persistent activation of inflammatory response and of fibrogenesis. Liver fibrosis is a major determinant for chronic liver ... ...

    Abstract Liver fibrosis, as an excess deposition of extracellular matrix (ECM) components, results from chronic liver injury as well as persistent activation of inflammatory response and of fibrogenesis. Liver fibrosis is a major determinant for chronic liver disease (CLD) progression and in the last two decades our understanding on the major molecular and cellular mechanisms underlying the fibrogenic progression of CLD has dramatically improved, boosting pre-clinical studies and clinical trials designed to find novel therapeutic approaches. From these studies several critical concepts have emerged, starting to reveal the complexity of the pro-fibrotic microenvironment which involves very complex, dynamic and interrelated interactions between different hepatic and extrahepatic cell populations. This review will offer first a recapitulation of established and novel pathophysiological basic principles and concepts by intentionally focus the attention on NAFLD/NASH, a metabolic-related form of CLD with a high impact on the general population and emerging as a leading cause of CLD worldwide. NAFLD/NASH-related pro-inflammatory and profibrogenic mechanisms will be analysed as well as novel information on cells, mediators and signalling pathways which have taken advantage from novel methodological approaches and techniques (single cell genomics, imaging mass cytometry, novel in vitro two- and three-dimensional models, etc.). We will next offer an overview on recent advancement in diagnostic and prognostic tools, including serum biomarkers and polygenic scores, to support the analysis of liver biopsies. Finally, this review will provide an analysis of current and emerging therapies for the treatment of NAFLD/NASH patients.
    MeSH term(s) Humans ; Non-alcoholic Fatty Liver Disease/therapy ; Non-alcoholic Fatty Liver Disease/drug therapy ; Liver Cirrhosis/diagnosis ; Liver Cirrhosis/etiology ; Liver Cirrhosis/metabolism ; Liver/metabolism ; Biomarkers/metabolism ; Myofibroblasts/metabolism
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-12-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 197640-0
    ISSN 1872-9452 ; 0098-2997
    ISSN (online) 1872-9452
    ISSN 0098-2997
    DOI 10.1016/j.mam.2023.101231
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: An eye-tracking investigation of the cognitive processes involved in the comprehension of simple and complex communicative acts.

    Parola, Alberto / Bosco, Francesca M

    Quarterly journal of experimental psychology (2006)

    2022  Volume 75, Issue 10, Page(s) 1976–1995

    Abstract: Indirect speech acts communicate more than their literal meaning, and their comprehension relies on the listener's ability to draw the appropriate inferences in a given context. We used eye tracking to investigate the cognitive processing involved in the ...

    Abstract Indirect speech acts communicate more than their literal meaning, and their comprehension relies on the listener's ability to draw the appropriate inferences in a given context. We used eye tracking to investigate the cognitive processing involved in the comprehension of simple (direct) and complex (unconventional indirect) communicative acts, a more general distinction that applies not only to sincere speech acts, but also to irony and deceit. We recorded the eye movements of 40 participants while they read 60 stories (20 sincere, 20 deceitful, 20 ironic) consisting of a context and a target answer. For each story, we created two different contexts so that the same identical target answer was a simple (direct) and a complex (unconventional indirect) communicative act, respectively. We also assessed the indirectness of simple and complex communicative acts, as well as participants' working memory (WM) and theory of mind (ToM). Eye-pattern analysis showed that complex communicative acts were more difficult to understand than simple acts; differences between simple and complex acts held for all the pragmatic phenomena investigated, though processing differences were greater for sincere acts than for irony and deceit. We found a role of indirectness and ToM in the pragmatic processing of simple and complex acts, whereas the role of WM was modest. The present findings underscore the importance of adopting an encompassing theory that can account for different types of indirect speech acts, such as sincere, deceitful and ironic acts; they also suggest the importance of assessing individual differences in inferential and cognitive abilities.
    MeSH term(s) Communication ; Comprehension ; Eye-Tracking Technology ; Humans ; Speech ; Theory of Mind
    Language English
    Publishing date 2022-03-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 219170-2
    ISSN 1747-0226 ; 0033-555X ; 1747-0218
    ISSN (online) 1747-0226
    ISSN 0033-555X ; 1747-0218
    DOI 10.1177/17470218221079629
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    Zs.B 1109: Show issues Location:
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  9. Article ; Online: Programming crack patterns with light in colloidal plasmonic films.

    Thorimbert, Fanny / Odziomek, Mateusz / Chateau, Denis / Parola, Stéphane / Faustini, Marco

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1156

    Abstract: Crack formation observed across diverse fields like geology, nanotechnology, arts, structural engineering or surface science, is a chaotic and undesirable phenomenon, resulting in random patterns of cracks generally leading to material failure. Limiting ... ...

    Abstract Crack formation observed across diverse fields like geology, nanotechnology, arts, structural engineering or surface science, is a chaotic and undesirable phenomenon, resulting in random patterns of cracks generally leading to material failure. Limiting the formation of cracks or "programming" the path of cracks is a great technological challenge since it holds promise to enhance material durability or even to develop low cost patterning methods. Drawing inspiration from negative phototropism in plants, we demonstrate the capability to organize, guide, replicate, or arrest crack propagation in colloidal films through remote light manipulation. The key consists in using plasmonic photothermal absorbers to generate "virtual" defects enabling controlled deviation of cracks. We engineer a dip-coating process coupled with selective light irradiation enabling simultaneous deposition and light-directed crack patterning. This approach represents a rare example of a robust self-assembly process with long-range order that can be programmed in both space and time.
    Language English
    Publishing date 2024-02-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45365-1
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  10. Article: Editorial: Psychotic experiences, social cognition and pragmatic communication in the psychosis continuum.

    Parola, Alberto / Bosia, Marta / Soto, Guillermo / Garcia, Ricardo

    Frontiers in psychology

    2023  Volume 14, Page(s) 1127477

    Language English
    Publishing date 2023-02-08
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2563826-9
    ISSN 1664-1078
    ISSN 1664-1078
    DOI 10.3389/fpsyg.2023.1127477
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