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  1. Article ; Online: Repurposing Amphotericin B and Its Liposomal Formulation for the Treatment of Human Mpox.

    Peruzzu, Daniela / Fecchi, Katia / Venturi, Giulietta / Gagliardi, Maria Cristina

    International journal of molecular sciences

    2023  Volume 24, Issue 10

    Abstract: Mpox (monkeypox) is a zoonotic viral disease caused by the mpox virus (MPXV). Recently in 2022, a multi-country Mpox outbreak has determined great concern as the disease rapidly spreads. The majority of cases are being noticed in European regions and are ...

    Abstract Mpox (monkeypox) is a zoonotic viral disease caused by the mpox virus (MPXV). Recently in 2022, a multi-country Mpox outbreak has determined great concern as the disease rapidly spreads. The majority of cases are being noticed in European regions and are unrelated to endemic travel or known contact with infected individuals. In this outbreak, close sexual contact appears to be important for MPXV transmission, and an increasing prevalence in people with multiple sexual partners and in men who have sex with men has been observed. Although
    MeSH term(s) Male ; Animals ; Humans ; Amphotericin B/pharmacology ; Amphotericin B/therapeutic use ; Drug Repositioning ; Homosexuality, Male ; Mpox (monkeypox) ; Sexual and Gender Minorities ; Zoonoses ; Liposomes
    Chemical Substances Amphotericin B (7XU7A7DROE) ; 2-aminomethyl-4-(4-chlorophenyl)-4-hydroxybutyric acid (129238-76-2) ; Liposomes
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24108896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Intraluminal vesicle trafficking is involved in the secretion of base excision repair protein APE1.

    Parolini, Isabella / Degrassi, Monica / Spadaro, Francesca / Caponnetto, Federica / Fecchi, Katia / Mastantuono, Serena / Zhouyiyuan, Xue / Demple, Bruce / Cesselli, Daniela / Tell, Gianluca

    The FEBS journal

    2024  

    Abstract: The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an essential enzyme of the base excision repair pathway of non-distorting DNA lesions. In response to genotoxic treatments, APE1 is highly secreted (sAPE1) in association with small- ... ...

    Abstract The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an essential enzyme of the base excision repair pathway of non-distorting DNA lesions. In response to genotoxic treatments, APE1 is highly secreted (sAPE1) in association with small-extracellular vesicles (EVs). Interestingly, its presence in the serum of patients with hepatocellular or non-small-cell-lung cancers may represent a prognostic biomarker. The mechanism driving APE1 to associate with EVs is unknown, but is of paramount importance in better understanding the biological roles of sAPE1. Because APE1 lacks an endoplasmic reticulum-targeting signal peptide, it can be secreted through an unconventional protein secretion endoplasmic reticulum-Golgi-independent pathway, which includes an endosome-based secretion of intraluminal vesicles, mediated by multivesicular bodies (MVBs). Using HeLa and A549 cell lines, we investigated the role of endosomal sorting complex required for transport protein pathways (either-dependent or -independent) in the constitutive or trichostatin A-induced secretion of sAPE1, by means of manumycin A and GW 4869 treatments. Through an in-depth biochemical analysis of late-endosomes (LEs) and early-endosomes (EEs), we observed that the distribution of APE1 on density gradient corresponded to that of LE-CD63, LE-Rab7, EE-EEA1 and EE-Rab 5. Interestingly, the secretion of sAPE1, induced by cisplatin genotoxic stress, involved an autophagy-based unconventional secretion requiring MVBs. The present study enlightens the central role played by MVBs in the secretion of sAPE1 under various stimuli, and offers new perspectives in understanding the biological relevance of sAPE1 in cancer cells.
    Language English
    Publishing date 2024-02-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.17088
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Human Monocyte-Derived Dendritic Cells Are the Pharmacological Target of the Immunosuppressant Flavonoid Silibinin.

    Pagano, Maria Teresa / Fecchi, Katia / Pierdominici, Marina / Ortona, Elena / Peruzzu, Daniela

    International journal of molecular sciences

    2022  Volume 23, Issue 18

    Abstract: Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) ...

    Abstract Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) remain to be elucidated. In this study, we have attempted to ascertain whether Silibinin influences the maturation, cytokine production, and antigen-presenting capacity of human monocyte-derived DC. We show that Silibinin significantly suppresses the upregulation of costimulatory and MHC molecules in LPS-stimulated mature DC and inhibits lipopolysaccharide (LPS)-induced interleukin (IL)-12, IL-23, and TNF-α production. Furthermore, Silibinin impairs the proliferation response of the allogenic memory CD4 T lymphocytes elicited by LPS-matured DC and their Th1/Th17 profile. These findings demonstrate that Silibinin displays immunosuppressive activity by inhibiting the maturation and activation of human DC and support its potential application of adjuvant therapy in the treatment of autoimmune diseases.
    MeSH term(s) Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Cell Differentiation ; Cells, Cultured ; Cytokines/pharmacology ; Dendritic Cells ; Flavonoids/pharmacology ; Humans ; Immunosuppressive Agents/pharmacology ; Interleukin-12 ; Interleukin-23 ; Lipopolysaccharides/pharmacology ; Monocytes ; Silybin/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology
    Chemical Substances Anti-Inflammatory Agents ; Antioxidants ; Cytokines ; Flavonoids ; Immunosuppressive Agents ; Interleukin-23 ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; Interleukin-12 (187348-17-0) ; Silybin (4RKY41TBTF)
    Language English
    Publishing date 2022-09-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms231810417
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Zika Virus Exploits Lipid Rafts to Infect Host Cells.

    Peruzzu, Daniela / Amendola, Antonello / Venturi, Giulietta / de Turris, Valeria / Marsili, Giulia / Fortuna, Claudia / Fecchi, Katia / Gagliardi, Maria Cristina

    Viruses

    2022  Volume 14, Issue 9

    Abstract: Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus-host cell interaction has not yet been ... ...

    Abstract Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus-host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by
    MeSH term(s) Amphotericin B/metabolism ; Amphotericin B/therapeutic use ; Animals ; Antifungal Agents/metabolism ; Antifungal Agents/therapeutic use ; Antiviral Agents/pharmacology ; Chlorocebus aethiops ; Female ; Flavivirus ; Humans ; Membrane Lipids/metabolism ; Membrane Microdomains ; Pregnancy ; Vero Cells ; Zika Virus ; Zika Virus Infection
    Chemical Substances Antifungal Agents ; Antiviral Agents ; Membrane Lipids ; Amphotericin B (7XU7A7DROE)
    Language English
    Publishing date 2022-09-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14092059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Anti-Inflammatory Effects of 1,25(OH)2D/Calcitriol in T Cell Immunity: Does Sex Make a Difference?

    Peruzzu, Daniela / Dupuis, Maria Luisa / Pierdominici, Marina / Fecchi, Katia / Gagliardi, Maria Cristina / Ortona, Elena / Pagano, Maria Teresa

    International journal of molecular sciences

    2022  Volume 23, Issue 16

    Abstract: Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an ... ...

    Abstract Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about the mechanisms underlying this anti-inflammatory effect and the potential sex differences of calcitriol immune regulation. Hence, the aim of this study was to investigate whether calcitriol could act differently in modulating T cell immunity of age-matched male and female healthy donors. We analyzed the effects of calcitriol in T lymphocytes from healthy women and men on the expression levels of the vitamin D receptor (VDR) and pro- and anti-inflammatory cytokine production. We showed that a treatment with calcitriol induced a significant increase in the VDR expression levels of activated T lymphocytes from male and female healthy subjects. Moreover, we found that calcitriol significantly reduced the expression level of pro-inflammatory cytokines IL-17, INF-γ and TNF-α in the T lymphocytes of both sexes. Notably, we observed that calcitriol induced a significant increase in the expression level of anti-inflammatory cytokine IL-10 only in the T lymphocytes from female healthy donors. In conclusion, our study provides new insights regarding the sex-specific anti-inflammatory role of calcitriol in T cell immunity.
    MeSH term(s) Calcitriol/pharmacology ; Cytokines/metabolism ; Female ; Humans ; Male ; Receptors, Calcitriol/metabolism ; Sex Factors ; T-Lymphocytes/metabolism ; Vitamin D/metabolism ; Vitamins/metabolism
    Chemical Substances Cytokines ; Receptors, Calcitriol ; Vitamins ; Vitamin D (1406-16-2) ; Calcitriol (FXC9231JVH)
    Language English
    Publishing date 2022-08-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23169164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Sex differences in antiviral immunity in SARS-CoV-2 infection: Mitochondria and mitomiR come into view.

    Iessi, Elisabetta / Cittadini, Camilla / Anticoli, Simona / Fecchi, Katia / Matarrese, Paola / Ruggieri, Anna

    Acta physiologica (Oxford, England)

    2020  Volume 231, Issue 2, Page(s) e13571

    MeSH term(s) Animals ; Antibodies, Viral/genetics ; Antibodies, Viral/immunology ; COVID-19/genetics ; COVID-19/immunology ; Female ; Immunity, Innate ; Male ; MicroRNAs/genetics ; Mitochondria/genetics ; Mitochondria/immunology ; Oxidative Stress ; SARS-CoV-2/immunology ; Sex Characteristics
    Chemical Substances Antibodies, Viral ; MicroRNAs
    Keywords covid19
    Language English
    Publishing date 2020-11-05
    Publishing country England
    Document type Editorial
    ZDB-ID 2218636-0
    ISSN 1748-1716 ; 1748-1708
    ISSN (online) 1748-1716
    ISSN 1748-1708
    DOI 10.1111/apha.13571
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Zika Virus Exploits Lipid Rafts to Infect Host Cells

    Peruzzu, Daniela / Amendola, Antonello / Venturi, Giulietta / de Turris, Valeria / Marsili, Giulia / Fortuna, Claudia / Fecchi, Katia / Gagliardi, Maria Cristina

    Viruses. 2022 Sept. 16, v. 14, no. 9

    2022  

    Abstract: Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus–host cell interaction has not yet been ... ...

    Abstract Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus–host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by Aedes spp. Mosquitoes, although other mechanisms such as blood transfusion, sexual and maternal–fetal transmission have been demonstrated. Symptoms are generally mild, such as fever, rash, joint pain and conjunctivitis, but neurological complications, including Guillain-Barré syndrome, have been associated to this viral infection. During pregnancy, it can cause microcephaly and other congenital abnormalities in the fetus, as well as pregnancy complications, representing a serious health threat. In this study, we show for the first time that Zika virus employs cell membrane lipid rafts as a portal of entry into Vero cells. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) hampers a microbe–host cell interaction through the disruption of lipid raft architecture. Here, we found that Amphotericin B by the same mechanism of action inhibits both Zika virus cell entry and replication. These data encourage further studies on the off-label use of Amphotericin B in Zika virus infections as a new and alternate antiviral therapy.
    Keywords Aedes ; Dengue virus ; Hepatitis C virus ; Japanese encephalitis virus ; West Nile virus ; Zika virus ; amphotericin B ; blood transfusion ; cell membranes ; conjunctivitis ; fetus ; fever ; lipids ; mechanism of action ; pain ; pregnancy
    Language English
    Dates of publication 2022-0916
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14092059
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Inhibition of cholesterol transport impairs Cav-1 trafficking and small extracellular vesicles secretion, promoting amphisome formation in melanoma cells.

    Peruzzu, Daniela / Boussadia, Zaira / Fratini, Federica / Spadaro, Francesca / Bertuccini, Lucia / Sanchez, Massimo / Carollo, Maria / Matarrese, Paola / Falchi, Mario / Iosi, Francesca / Raggi, Carla / Parolini, Isabella / Carè, Alessandra / Sargiacomo, Massimo / Gagliardi, Maria Cristina / Fecchi, Katia

    Traffic (Copenhagen, Denmark)

    2023  Volume 24, Issue 2, Page(s) 76–94

    Abstract: Caveolin-1 (Cav-1) is a fundamental constituent of caveolae, whose functionality and structure are strictly dependent on cholesterol. In this work the U18666A inhibitor was used to study the role of cholesterol transport in the endosomal degradative- ... ...

    Abstract Caveolin-1 (Cav-1) is a fundamental constituent of caveolae, whose functionality and structure are strictly dependent on cholesterol. In this work the U18666A inhibitor was used to study the role of cholesterol transport in the endosomal degradative-secretory system in a metastatic human melanoma cell line (WM266-4). We found that U18666A induces a shift of Cav-1 from the plasma membrane to the endolysosomal compartment, which is involved, through Multi Vesicular Bodies (MVBs), in the formation and release of small extracellular vesicles (sEVs). Moreover, this inhibitor induces an increase in the production of sEVs with chemical-physical characteristics similar to control sEVs but with a different protein composition (lower expression of Cav-1 and increase of LC3II) and reduced transfer capacity on target cells. Furthermore, we determined that U18666A affects mitochondrial function and also cancer cell aggressive features, such as migration and invasion. Taken together, these results indicate that the blockage of cholesterol transport, determining the internalization of Cav-1, may modify sEVs secretory pathways through an increased fusion between autophagosomes and MVBs to form amphisome, which in turn fuses with the plasma membrane releasing a heterogeneous population of sEVs to maintain homeostasis and ensure correct cellular functionality.
    MeSH term(s) Humans ; Caveolin 1/metabolism ; Autophagosomes/metabolism ; Extracellular Vesicles/metabolism ; Melanoma ; Cholesterol/metabolism
    Chemical Substances Caveolin 1 ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2023-01-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 1483852-7
    ISSN 1600-0854 ; 1398-9219
    ISSN (online) 1600-0854
    ISSN 1398-9219
    DOI 10.1111/tra.12878
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Amphotericin B Inhibits Mycobacterium tuberculosis Infection of Human Alveolar Type II Epithelial A549 Cells.

    Mariotti, Sabrina / Teloni, Raffaela / de Turris, Valeria / Pardini, Manuela / Peruzzu, Daniela / Fecchi, Katia / Nisini, Roberto / Gagliardi, Maria Cristina

    Antimicrobial agents and chemotherapy

    2020  Volume 64, Issue 10

    MeSH term(s) A549 Cells ; Alveolar Epithelial Cells ; Amphotericin B/pharmacology ; Epithelial Cells ; Humans ; Mycobacterium tuberculosis ; Tuberculosis
    Chemical Substances Amphotericin B (7XU7A7DROE)
    Language English
    Publishing date 2020-09-21
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.01164-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Sex differences in antiviral immunity in SARS-CoV-2 infection: Mitochondria and mitomiR come into view

    Iessi, Elisabetta / Cittadini, Camilla / Anticoli, Simona / Fecchi, Katia / Matarrese, Paola / Ruggieri, Anna

    Acta Physiol (Oxf)

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #884550
    Database COVID19

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