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  1. Article ; Online: Hemopexin and Cancer

    Veronica Fiorito / Emanuela Tolosano

    International Journal of Molecular Sciences, Vol 23, Iss 997, p

    2022  Volume 997

    Abstract: Hemopexin is the plasma protein with the highest affinity for heme. Seminal studies have highlighted its role in different kinds of heme-associated disorders, but its implication in cancer has been neglected for a long time. Considering the emerging ... ...

    Abstract Hemopexin is the plasma protein with the highest affinity for heme. Seminal studies have highlighted its role in different kinds of heme-associated disorders, but its implication in cancer has been neglected for a long time. Considering the emerging importance of heme in tumors, the present review proposes an update of the works investigating hemopexin involvement in cancer, with the attempt to stimulate further future studies on this topic.
    Keywords hemopexin ; cancer ; heme ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Heme in pathophysiology

    EmanuelaTolosano

    Frontiers in Pharmacology, Vol

    a matter of scavenging, metabolism and trafficking across cell membranes

    2014  Volume 5

    Abstract: Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is ... ...

    Abstract Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is highly toxic due to its ability to promote oxidative stress and lipid peroxidation, thus leading to membrane injury and, ultimately, apoptosis. Thus, heme metabolism needs to be finely regulated. Intracellular heme amount is controlled at multiple levels: synthesis, utilization by hemoproteins, degradation and both intracellular and intercellular trafficking. This review focuses on recent findings highlighting the importance of controlling intracellular heme levels to counteract heme-induced oxidative stress. The contributions of heme scavenging from the extracellular environment, heme synthesis and incorporation into hemoproteins, heme catabolism and heme transport in maintaining adequate intracellular heme content are discussed. Particular attention is put on the recently described mechanisms of heme trafficking through the plasma membrane mediated by specific heme importers and exporters. Finally, the involvement of genes orchestrating heme metabolism in several pathological conditions is illustrated and new therapeutic approaches aimed at controlling heme metabolism are discussed.
    Keywords Hemopexin ; ABCG2 ; HO-1 ; FLVCR1 ; FLVCR2 ; HCP1/PCFT ; heme exporter ; heme importer ; heme synthesis ; heme catabolism ; Therapeutics. Pharmacology ; RM1-950 ; Medicine ; R
    Subject code 612
    Language English
    Publishing date 2014-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Hereditary Ataxia

    Deborah Chiabrando / Francesca Bertino / Emanuela Tolosano

    International Journal of Molecular Sciences, Vol 21, Iss 3760, p

    A Focus on Heme Metabolism and Fe-S Cluster Biogenesis

    2020  Volume 3760

    Abstract: Heme and Fe-S clusters regulate a plethora of essential biological processes ranging from cellular respiration and cell metabolism to the maintenance of genome integrity. Mutations in genes involved in heme metabolism and Fe-S cluster biogenesis cause ... ...

    Abstract Heme and Fe-S clusters regulate a plethora of essential biological processes ranging from cellular respiration and cell metabolism to the maintenance of genome integrity. Mutations in genes involved in heme metabolism and Fe-S cluster biogenesis cause different forms of ataxia, like posterior column ataxia and retinitis pigmentosa (PCARP), Friedreich’s ataxia (FRDA) and X-linked sideroblastic anemia with ataxia (XLSA/A). Despite great efforts in the elucidation of the molecular pathogenesis of these disorders several important questions still remain to be addressed. Starting with an overview of the biology of heme metabolism and Fe-S cluster biogenesis, the review discusses recent progress in the understanding of the molecular pathogenesis of PCARP, FRDA and XLSA/A, and highlights future line of research in the field. A better comprehension of the mechanisms leading to the degeneration of neural circuity responsible for balance and coordinated movement will be crucial for the therapeutic management of these patients.
    Keywords ataxia ; FLVCR1 ; FRATAXIN ; ABCB7 ; PCARP ; FRDA and XLSA/A ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Mitochondrial Targeting in Neurodegeneration

    Veronica Fiorito / Deborah Chiabrando / Emanuela Tolosano

    Pharmaceuticals, Vol 11, Iss 3, p

    A Heme Perspective

    2018  Volume 87

    Abstract: Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the ... ...

    Abstract Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the same disease. The central role of mitochondria in neurodegenerative disorders has stimulated studies intended to implement therapeutic protocols based on the targeting of the distinct mitochondrial processes. The review summarizes the most relevant mechanisms by which mitochondria contribute to neurodegeneration, encompassing therapeutic approaches. Moreover, a new perspective is proposed based on the heme impact on neurodegeneration. The heme metabolism plays a central role in mitochondrial functions, and several evidences indicate that alterations of the heme metabolism are associated with neurodegenerative disorders. By reporting the body of knowledge on this topic, the review intends to stimulate future studies on the role of heme metabolism in neurodegeneration, envisioning innovative strategies in the struggle against neurodegenerative diseases.
    Keywords neurodegeneration ; mitochondria ; therapy ; heme ; haem ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 610
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Promote Corneal Wound Repair by Regulating Inflammation and Angiogenesis

    Gabriele Saccu / Valeria Menchise / Chiara Gai / Marina Bertolin / Stefano Ferrari / Cristina Giordano / Marta Manco / Walter Dastrù / Emanuela Tolosano / Benedetta Bussolati / Enzo Calautti / Giovanni Camussi / Fiorella Altruda / Sharmila Fagoonee

    Cells, Vol 11, Iss 3892, p

    2022  Volume 3892

    Abstract: Severe corneal damage leads to complete vision loss, thereby affecting life quality and impinging heavily on the healthcare system. Current clinical approaches to manage corneal wounds suffer from severe drawbacks, thus requiring the development of ... ...

    Abstract Severe corneal damage leads to complete vision loss, thereby affecting life quality and impinging heavily on the healthcare system. Current clinical approaches to manage corneal wounds suffer from severe drawbacks, thus requiring the development of alternative strategies. Of late, mesenchymal stromal/stem cell (MSC)-derived extracellular vesicles (EVs) have become a promising tool in the ophthalmic field. In the present study, we topically delivered bone-marrow-derived MSC-EVs (BMSC-EVs), embedded in methylcellulose, in a murine model of alkali-burn-induced corneal damage in order to evaluate their role in corneal repair through histological and molecular analyses, with the support of magnetic resonance imaging. Our data show that BMSC-EVs, used for the first time in this specific formulation on the damaged cornea, modulate cell death, inflammation and angiogenetic programs in the injured tissue, thus leading to a faster recovery of corneal damage. These results were confirmed on cadaveric donor-derived human corneal epithelial cells in vitro. Thus, BMSC-EVs modulate corneal repair dynamics and are promising as a new cell-free approach for intervening on burn wounds, especially in the avascularized region of the eye.
    Keywords extracellular vesicles ; cornea ; MRI ; Gd-AAZTA-MADEC ; methylcellulose ; mesenchymal stromal/stem cells ; Biology (General) ; QH301-705.5
    Subject code 500 ; 570
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Endothelial Cells Promote Osteogenesis by Establishing a Functional and Metabolic Coupling With Human Mesenchymal Stem Cells

    Sara Petrillo / Tullio Genova / Giorgia Chinigò / Ilaria Roato / Giorgia Scarpellino / Joanna Kopecka / Fiorella Altruda / Emanuela Tolosano / Chiara Riganti / Federico Mussano / Luca Munaron

    Frontiers in Physiology, Vol

    2022  Volume 12

    Abstract: Bone formation involves a complex crosstalk between endothelial cells (EC) and osteodifferentiating stem cells. This functional interplay is greatly mediated by the paracrine and autocrine action of soluble factors released at the vasculature-bone ... ...

    Abstract Bone formation involves a complex crosstalk between endothelial cells (EC) and osteodifferentiating stem cells. This functional interplay is greatly mediated by the paracrine and autocrine action of soluble factors released at the vasculature-bone interface. This study elucidates the molecular and functional responses triggered by this intimate interaction. In this study, we showed that human dermal microvascular endothelial cells (HMEC) induced the expression of pro-angiogenic factors in stem cells from human exfoliated deciduous teeth (SHED) and sustain their osteo-differentiation at the same time. In contrast, osteodifferentiating SHED increased EC recruitment and promoted the formation of complex vascular networks. Moreover, HMEC enhanced anaerobic glycolysis in proliferating SHED without compromising their ability to undergo the oxidative metabolic shift required for adequate osteo-differentiation. Taken together, these findings provide novel insights into the molecular mechanism underlying the synergistic cooperation between EC and stem cells during bone tissue renewal.
    Keywords HMEC ; endothelial cell (EC) ; osteogenesis ; bone regeneration ; bone biology ; metabolism ; Physiology ; QP1-981
    Subject code 571
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Proteomics-Based Evidence for a Pro-Oncogenic Role of ESRP1 in Human Colorectal Cancer Cells

    Ugo Ala / Marta Manco / Giorgia Mandili / Emanuela Tolosano / Francesco Novelli / Paolo Provero / Fiorella Altruda / Sharmila Fagoonee

    International Journal of Molecular Sciences, Vol 21, Iss 2, p

    2020  Volume 575

    Abstract: The RNA-binding protein, Epithelial Splicing Regulatory Protein 1 (ESRP1) can promote or suppress tumorigenesis depending on the cell type and disease context. In colorectal cancer, we have previously shown that aberrantly high ESRP1 expression can drive ...

    Abstract The RNA-binding protein, Epithelial Splicing Regulatory Protein 1 (ESRP1) can promote or suppress tumorigenesis depending on the cell type and disease context. In colorectal cancer, we have previously shown that aberrantly high ESRP1 expression can drive tumor progression. In order to unveil the mechanisms by which ESRP1 can modulate cancer traits, we searched for proteins affected by modulation of Esrp1 in two human colorectal cancer cell lines, HCA24 and COLO320DM, by proteomics analysis. Proteins hosted by endogenous ESRP1 ribonucleoprotein complex in HCA24 cells were also analyzed following RNA-immunoprecipitation. Proteomics data were complemented with bioinformatics approach to exploit publicly available data on protein-protein interaction (PPI). Gene Ontology was analysed to identify a common molecular signature possibly explaining the pro-tumorigenic role of ESRP1. Interestingly, proteins identified herein support a role for ESRP1 in response to external stimulus, regulation of cell cycle and hypoxia. Our data provide further insights into factors affected by and entwined with ESRP1 in colorectal cancer.
    Keywords esrp1 ; proteomics ; bioinformatics ; colorectal cancer ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

    Viviana Cernigliaro / Rossella Peluso / Beatrice Zedda / Lorenzo Silengo / Emanuela Tolosano / Rinaldo Pellicano / Fiorella Altruda / Sharmila Fagoonee

    Cells, Vol 9, Iss 2, p

    2020  Volume 386

    Abstract: Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism ... ...

    Abstract Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.
    Keywords liver diseases ; transplantation ; cell therapy ; extracellular vesicles ; organoids ; scaffolds ; organ printing ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Age-dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical Outcomes Following Traumatic Brain Injury

    Alexander V Glushakov / Rodrigo A Arias / Emanuela Tolosano / Sylvain Dore

    Frontiers in Molecular Biosciences, Vol

    2016  Volume 3

    Abstract: Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most ... ...

    Abstract Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most abundant in blood plasma, is involved in the intrinsic molecular defensive mechanism, though its role in TBI is poorly understood. The aim of this study was to investigate the effects of Hp deletion on the anatomical and behavioral outcomes in the controlled cortical impact model using wild type (WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp-/-) in two age cohorts [2–4 mo old (young adult) and 7–8 mo old (older adult)]. The data obtained suggest age-dependent significant effects on the behavioral and anatomical TBI outcomes and recovery from the injury. Moreover, in the adult cohort, neurological deficits of Hp-/- mice at 24 h were significantly improved as compared to WT; whereas there were no significant differences in brain pathology between these genotypes. In contrast, in the older adult cohort, Hp-/- mice had significantly larger lesion volumes compared to WT, but neurological deficits were not significantly different. Immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) revealed significant differences in microglial and astrocytic reactivity between Hp-/- and WT in selected brain regions of the adult but not the older adult age cohort. In conclusion, the data obtained in the study provide clarification on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp that might be involved in complex pathways differentially affecting acute brain trauma outcomes.
    Keywords Gliosis ; Hemorrhage ; Trauma ; Hemoglobin ; GFAP ; controlled cortical impact ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2016-07-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism

    Emanuela Tolosano / Deborah Chiabrando

    Advances in Hematology , Vol

    2010  Volume 2010

    Keywords Diseases of the blood and blood-forming organs ; RC633-647.5 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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