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  1. Article ; Online: Molecular Mechanisms and Function of the p53 Protein Family Member - p73.

    Melino, G

    Biochemistry. Biokhimiia

    2020  Volume 85, Issue 10, Page(s) 1202–1209

    Abstract: Over 20 years after identification of p53 and its crucial function in cancer progression, two members of the same protein family were identified, namely p63 and p73. Since then, a body of information has been accumulated on each of these genes and their ... ...

    Abstract Over 20 years after identification of p53 and its crucial function in cancer progression, two members of the same protein family were identified, namely p63 and p73. Since then, a body of information has been accumulated on each of these genes and their interrelations. Biological role of p73 has been elucidated thanks to four distinct knockout mice models: (i) with deletion of the entire TP73 gene, (ii) with deletion of exons encoding the full length TAp73 isoforms, (iii) with deletions of exons encoding the shorter DNp73 isoform, and (iv) with deletion of exons encoding C-terminal of the alpha isoform. This work, as well as expression studies in cancer and overwhelming body of molecular studies, allowed establishing major role of TP73 both in cancer and in neuro-development, as well as ciliogenesis, and metabolism. Here, we recapitulate the major milestones of this endeavor.
    MeSH term(s) Animals ; Carcinogenesis ; Humans ; Mice ; Mice, Knockout ; Neurogenesis ; Signal Transduction ; Tumor Protein p73/physiology
    Chemical Substances TP73 protein, human ; Trp73 protein, mouse ; Tumor Protein p73
    Language English
    Publishing date 2020-12-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297920100089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 220: Show issues Location:
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  2. Article: Tissue transglutaminase (TG2) acting as G protein protects hepatocytes against Fas-mediated cell death in mice.

    Sarang, Zsolt / Molnár, Péter / Németh, Tamás / Gomba, Szabolcs / Kardon, Tamás / Melino, Gerry / Cotecchia, Susanna / Fésüs, László / Szondy, Zsuzsa

    Hepatology (Baltimore, Md.)

    2005  Volume 42, Issue 3, Page(s) 578–587

    Abstract: ... by hepatocytes and to be induced during the in vivo hepatic apoptosis program. TG2 is also a G protein ...

    Abstract Tissue transglutaminase (TG2) is a protein cross-linking enzyme known to be expressed by hepatocytes and to be induced during the in vivo hepatic apoptosis program. TG2 is also a G protein that mediates intracellular signaling by the alpha-1b-adrenergic receptor (AR) in liver cells. Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti-Fas antibodies to mice causes both disseminated endothelial cell apoptosis and fulminant hepatic failure. Here we report that an intraperitoneal dose of anti-Fas antibodies, which is sublethal for wild-type mice, kills all the TG2 knock-out mice within 20 hours. Although TG2-/- thymocytes exposed to anti-Fas antibodies die at the same rate as wild-type mice, TG2-/- hepatocytes show increased sensitivity toward anti-Fas treatment both in vivo and in vitro, with no change in their cell surface expression of Fas, levels of FLIP(L) (FLICE-inhibitory protein), or the rate of I-kappaBalpha degradation, but a decrease in the Bcl-xL expression. We provide evidence that this is the consequence of the impaired AR signaling that normally regulates the levels of Bcl-xL in the liver. In conclusion, our data suggest the involvement of adrenergic signaling pathways in the hepatic regeneration program, in which Fas ligand-induced hepatocyte proliferation with a simultaneous inhibition of the Fas-death pathway plays a determinant role.
    MeSH term(s) Animals ; Antibodies/pharmacology ; Apoptosis/physiology ; Cell Death ; Cell Division ; Cell Survival/drug effects ; Cells, Cultured ; GTP-Binding Proteins/deficiency ; GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Hepatocytes/cytology ; Hepatocytes/drug effects ; Hepatocytes/enzymology ; Hepatocytes/pathology ; Liver Regeneration/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Knockout ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/physiology ; Transglutaminases/deficiency ; Transglutaminases/genetics ; Transglutaminases/metabolism ; fas Receptor/genetics ; fas Receptor/immunology ; fas Receptor/pharmacology ; fas Receptor/physiology
    Chemical Substances Antibodies ; fas Receptor ; transglutaminase 2 (EC 2.3.2.-) ; Transglutaminases (EC 2.3.2.13) ; GTP-Binding Proteins (EC 3.6.1.-)
    Language English
    Publishing date 2005-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.20812
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    Zs.A 1660: Show issues Location:
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  3. Article ; Online: Gian Maria Fimia (1967-2024), an outstanding scientist with immense human qualities.

    Piacentini, Mauro / Tripodi, Marco / Melino, Gerry / Ippolito, Giuseppe

    Cell death & disease

    2024  Volume 15, Issue 3, Page(s) 185

    Language English
    Publishing date 2024-03-04
    Publishing country England
    Document type Editorial
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-024-06532-w
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  4. Article: Carmine Melino and the Institute of Hygiene.

    Melino, G

    Annali di igiene : medicina preventiva e di comunita

    2017  Volume 29, Issue 5, Page(s) 371–379

    Abstract: Throughout his 94 years of life, Carmine Melino brilliantly pursued different professional paths ...

    Abstract Throughout his 94 years of life, Carmine Melino brilliantly pursued different professional paths, his life being a constant stimulus for students, colleagues, friends and the family. Following the early formative years of study, here, we briefly list his scientific achievements in Occupational Medicine and Hygiene as well as his broad literary interests. Carmine was an inspiration to his generation not only because of his professional achievements, but also for his warm personality, exemplary hard-playing life and unbounded enthusiasm. A polymath, post-enlightenment ethos flowed to all his friends and colleagues, creating an ambience where intellectual excellence was highly appreciated and avidly pursued.
    MeSH term(s) Academies and Institutes/history ; History, 20th Century ; History, 21st Century ; Humans ; Hygiene/history ; Italy ; Occupational Medicine/history
    Language English
    Publishing date 2017-09-18
    Publishing country Italy
    Document type Biography ; Historical Article ; Journal Article
    ZDB-ID 1018045-x
    ISSN 1120-9135 ; 0029-6287
    ISSN 1120-9135 ; 0029-6287
    DOI 10.7416/ai.2017.2163
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Order must spring from chaos in Italian research.

    Melino, Gerry

    Nature

    2018  Volume 556, Issue 7702, Page(s) 436

    MeSH term(s) Italy ; Politics ; Research ; Science
    Language English
    Publishing date 2018-04-11
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-018-04896-6
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    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

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  6. Article ; Online: Gene expression in organoids: an expanding horizon.

    Smirnov, Artem / Melino, Gerry / Candi, Eleonora

    Biology direct

    2023  Volume 18, Issue 1, Page(s) 11

    Abstract: Recent development of human three-dimensional organoid cultures has opened new doors and opportunities ranging from modelling human development in vitro to personalised cancer therapies. These new in vitro systems are opening new horizons to the classic ... ...

    Abstract Recent development of human three-dimensional organoid cultures has opened new doors and opportunities ranging from modelling human development in vitro to personalised cancer therapies. These new in vitro systems are opening new horizons to the classic understanding of human development and disease. However, the complexity and heterogeneity of these models requires cutting-edge techniques to capture and trace global changes in gene expression to enable identification of key players and uncover the underlying molecular mechanisms. Rapid development of sequencing approaches made possible global transcriptome analyses and epigenetic profiling. Despite challenges in organoid culture and handling, these techniques are now being adapted to embrace organoids derived from a wide range of human tissues. Here, we review current state-of-the-art multi-omics technologies, such as single-cell transcriptomics and chromatin accessibility assays, employed to study organoids as a model for development and a platform for precision medicine.
    MeSH term(s) Humans ; Gene Expression Profiling ; Organoids/metabolism ; Precision Medicine ; Gene Expression
    Language English
    Publishing date 2023-03-25
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2221028-3
    ISSN 1745-6150 ; 1745-6150
    ISSN (online) 1745-6150
    ISSN 1745-6150
    DOI 10.1186/s13062-023-00360-2
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  7. Article ; Online: The birth of death, 30 years ago.

    Melino, Gerry / Knight, Richard A / Mak, Tak Wah / Piacentini, Mauro / Simon, Hans-Uwe / Shi, Yufang

    Cell death and differentiation

    2024  

    Language English
    Publishing date 2024-04-10
    Publishing country England
    Document type Editorial
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-024-01276-8
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    Zs.A 4230: Show issues Location:
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    Zs.MG 80: Show issues

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  8. Article: Senataxin and R-loops homeostasis: multifaced implications in carcinogenesis.

    Gatti, Veronica / De Domenico, Sara / Melino, Gerry / Peschiaroli, Angelo

    Cell death discovery

    2023  Volume 9, Issue 1, Page(s) 145

    Abstract: R-loops are inherent byproducts of transcription consisting of an RNA:DNA hybrid and a displaced single-stranded DNA. These structures are of key importance in controlling numerous physiological processes and their homeostasis is tightly controlled by ... ...

    Abstract R-loops are inherent byproducts of transcription consisting of an RNA:DNA hybrid and a displaced single-stranded DNA. These structures are of key importance in controlling numerous physiological processes and their homeostasis is tightly controlled by the activities of several enzymes deputed to process R-loops and prevent their unproper accumulation. Senataxin (SETX) is an RNA/DNA helicase which catalyzes the unwinding of RNA:DNA hybrid portion of the R-loops, promoting thus their resolution. The key importance of SETX in R-loops homeostasis and its relevance with pathophysiological events is highlighted by the evidence that gain or loss of function SETX mutations underlie the pathogenesis of two distinct neurological disorders. Here, we aim to describe the potential impact of SETX on tumor onset and progression, trying to emphasize how dysregulation of this enzyme observed in human tumors might impact tumorigenesis. To this aim, we will describe the functional relevance of SETX in regulating gene expression, genome integrity, and inflammation response and discuss how cancer-associated SETX mutations might affect these pathways, contributing thus to tumor development.
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-023-01441-x
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  9. Article ; Online: Orchestration of Mesenchymal Stem/Stromal Cells and Inflammation During Wound Healing.

    Zhu, Mengting / Cao, Lijuan / Melino, Sonia / Candi, Eleonora / Wang, Ying / Shao, Changshun / Melino, Gerry / Shi, Yufang / Chen, Xiaodong

    Stem cells translational medicine

    2023  Volume 12, Issue 9, Page(s) 576–587

    Abstract: Wound healing is a complex process and encompasses a number of overlapping phases, during which coordinated inflammatory responses following tissue injury play dominant roles in triggering evolutionarily highly conserved principals governing tissue ... ...

    Abstract Wound healing is a complex process and encompasses a number of overlapping phases, during which coordinated inflammatory responses following tissue injury play dominant roles in triggering evolutionarily highly conserved principals governing tissue repair and regeneration. Among all nonimmune cells involved in the process, mesenchymal stem/stromal cells (MSCs) are most intensely investigated and have been shown to play fundamental roles in orchestrating wound healing and regeneration through interaction with the ordered inflammatory processes. Despite recent progress and encouraging results, an informed view of the scope of this evolutionarily conserved biological process requires a clear understanding of the dynamic interplay between MSCs and the immune systems in the process of wound healing. In this review, we outline current insights into the ways in which MSCs sense and modulate inflammation undergoing the process of wound healing, highlighting the central role of neutrophils, macrophages, and T cells during the interaction. We also draw attention to the specific effects of MSC-based therapy on different pathological wound healing. Finally, we discuss how ongoing scientific advances in MSCs could be efficiently translated into clinical strategies, focusing on the current limitations and gaps that remain to be overcome for achieving preferred functional tissue regeneration.
    MeSH term(s) Humans ; Mesenchymal Stem Cell Transplantation/methods ; Wound Healing/physiology ; Mesenchymal Stem Cells/physiology ; Macrophages ; Inflammation
    Language English
    Publishing date 2023-07-23
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6580
    ISSN (online) 2157-6580
    ISSN 2157-6580
    DOI 10.1093/stcltm/szad043
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  10. Article ; Online: Antidepressants synergize with chemotherapy against cancer stem cells.

    Melino, Gerry

    Aging

    2015  Volume 7, Issue 12, Page(s) 1024–1025

    MeSH term(s) Adenocarcinoma/pathology ; Antineoplastic Agents/pharmacology ; Clomipramine/analogs & derivatives ; Humans ; Lung Neoplasms/pathology ; Neoplastic Stem Cells/drug effects ; Repressor Proteins/genetics ; Ubiquitin-Protein Ligases/genetics
    Chemical Substances Antineoplastic Agents ; Repressor Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Clomipramine (NUV44L116D)
    Language English
    Publishing date 2015-12-08
    Publishing country United States
    Document type Editorial ; Comment
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.100848
    Database MEDical Literature Analysis and Retrieval System OnLINE

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