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Article ; Online: Metformin prevents cell tumorigenesis through autophagy-related cell death

Mauro De Santi / Giulia Baldelli / Aurora Diotallevi / Luca Galluzzi / Giuditta Fiorella Schiavano / Giorgio Brandi

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract Autophagy is a cellular mechanism by which cells degrade intracellular components in lysosomes, maintaining cellular homeostasis. It has been hypothesized that autophagy could have a role in cancer prevention through the elimination of damaged ... ...

Abstract	Abstract Autophagy is a cellular mechanism by which cells degrade intracellular components in lysosomes, maintaining cellular homeostasis. It has been hypothesized that autophagy could have a role in cancer prevention through the elimination of damaged proteins and organelles; this could explain epidemiological evidence showing the chemopreventive properties of the autophagy-inducer metformin. In this study, we analyzed the autophagy-related effect of metformin in both cancer initiation and progression in non-tumorigenic cells. We also analyzed the induction of tumorigenesis in autophagy-deficient cells, and its correlation with the ER stress. Our results showed that metformin induced massive cell death in preneoplastic JB6 Cl 41-5a cells treated with tumor promoter (phorbol) and in NIH/3T3 treated with H2O2. Inhibiting autophagy with wortmannin or ATG7 silencing, the effect of metformin decreased, indicating an autophagy-related cytotoxic activity under stress conditions. We also found an induction of tumorigenesis in ATG7-silenced NIH/3T3 cell clone (3T3-619C3 cells), but not in wild-type and in scrambled transfected cells, and an upregulation of unfolded protein response (UPR) markers in 3T3-619C3 cells treated with H2O2. These findings suggest that autophagic cell death could be considered as a new mechanism by which eliminate damaged cells, representing an attractive strategy to eliminate potential tumorigenic cells.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A dataset on the effect of exercise-conditioned human sera in three-dimensional breast cancer cell culture

Mauro De Santi / Giulia Baldelli / Francesco Lucertini / Valentina Natalucci / Giorgio Brandi / Elena Barbieri

Data in Brief, Vol 27, Iss , Pp - (2019)

2019

Abstract: Epidemiological evidence shows that physical activity lowers the risk of developing breast cancer and decreases the risk of disease recurrence [1,2]. The main hypothesis on the positive effects of exercise-oncology has focused on lowering the basal ... ...

Abstract	Epidemiological evidence shows that physical activity lowers the risk of developing breast cancer and decreases the risk of disease recurrence [1,2]. The main hypothesis on the positive effects of exercise-oncology has focused on lowering the basal systemic levels of cancer risk factors with exercise training. Recently, the effects of cancer progression control by components released after acute exercise bouts have gained attention [3,4]. However, the evaluation of the antiproliferative potential of a single exercise bout needs technical improvement.Here, we present data of a pilot study showing how to evaluate the anti-cancer potential of single exercise bouts with an in vitro three-dimensional cell growth assay, using a triple-negative breast cancer cell line cultured with exercise-conditioned serum. Keywords: Exercise, Triple negative breast cancer, Three-dimensional in vitro culture, Cell proliferation
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
Subject code	610
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole-Genome Sequencing Characterization of Virulence Profiles of Listeria monocytogenes Food and Human Isolates and In Vitro Adhesion/Invasion Assessment

Giuditta Fiorella Schiavano / Collins Njie Ateba / Annalisa Petruzzelli / Veronica Mele / Giulia Amagliani / Fabrizia Guidi / Mauro De Santi / Francesco Pomilio / Giuliana Blasi / Antonietta Gattuso / Stefania Di Lullo / Elena Rocchegiani / Giorgio Brandi

Microorganisms, Vol 10, Iss 62, p

2022 Volume 62

Abstract: Listeria monocytogenes ( Lm ) is the causative agent of human listeriosis. Lm strains have different virulence potential. For this reason, we preliminarily characterised via Whole-Genome Sequencing (WGS) some Lm strains for their key genomic features and ...

Abstract	Listeria monocytogenes ( Lm ) is the causative agent of human listeriosis. Lm strains have different virulence potential. For this reason, we preliminarily characterised via Whole-Genome Sequencing (WGS) some Lm strains for their key genomic features and virulence-associated determinants, assigning the clonal complex (CC). Moreover, the ability of the same strains to adhere to and invade human colon carcinoma cell line Caco-2, evaluating the possible correspondence with their genetic virulence profile, was also assessed. The clinical strains typed belonged to clonal complex (CC)1, CC31, and CC101 and showed a very low invasiveness. The Lm strains isolated from food were assigned to CC1, CC7, CC9, and CC121. All CC1 carried the hypervirulence pathogenicity island LIPI-3 in addition to LIPI-1. Premature stop codons in the inlA gene were found only in Lm of food origin belonging to CC9 and CC121. The presence of LIPI2_inlII was observed in all the CCs except CC1. The CC7 strain, belonging to an epidemic cluster, also carried the internalin genes inlG and inlL and showed the highest level of invasion. In contrast, the human CC31 strain lacked the lapB and vip genes and presented the lowest level of invasiveness. In Lm , the genetic determinants of hypo- or hypervirulence are not necessarily predictive of a cell adhesion and/or invasion ability in vitro. Moreover, since listeriosis results from the interplay between host and virulence features of the pathogen, even hypovirulent clones are able to cause infection in immunocompromised people.
Keywords	Listeria monocytogenes ; Whole-Genome Sequencing (WGS) ; premature stop codon (PMSC) ; virulence genes ; pork-meat products ; adhesion and invasion capacity ; Biology (General) ; QH301-705.5
Subject code	630
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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Article ; Online: Listeriosis Outbreak in South Africa

Christ-Donald Kaptchouang Tchatchouang / Justine Fri / Mauro De Santi / Giorgio Brandi / Giuditta Fiorella Schiavano / Giulia Amagliani / Collins Njie Ateba

Microorganisms, Vol 8, Iss 1, p

A Comparative Analysis with Previously Reported Cases Worldwide

2020 Volume 135

Abstract: Listeria species are Gram-positive, rod-shaped, facultative anaerobic bacteria, which do not produce endospores. The genus, Listeria , currently comprises 17 characterised species of which only two ( L. monocytogenes and L. ivanovii ) are known to be ... ...

Abstract	Listeria species are Gram-positive, rod-shaped, facultative anaerobic bacteria, which do not produce endospores. The genus, Listeria , currently comprises 17 characterised species of which only two ( L. monocytogenes and L. ivanovii ) are known to be pathogenic to humans. Food products and related processing environments are commonly contaminated with pathogenic species. Outbreaks and sporadic cases of human infections resulted in considerable economic loss. South Africa witnessed the world’s largest listeriosis outbreak, characterised by a progressive increase in cases of the disease from January 2017 to July 2018. Of the 1060 laboratory-confirmed cases of listeriosis reported by the National Institute of Communicable Diseases (NICD), 216 deaths were recorded. Epidemiological investigations indicated that ready-to-eat processed meat products from a food production facility contaminated with L. monocytogenes was responsible for the outbreak. Multilocus sequence typing (MLST) revealed that a large proportion (91%) of the isolates from patients were sequence type 6 (ST6). Recent studies revealed a recurrent occurrence of small outbreaks of listeriosis with more severe side-effects in humans. This review provides a comparative analysis of a recently reported and most severe outbreak of listeriosis in South Africa, with those previously encountered in other countries worldwide. The review focuses on the transmission of the pathogen, clinical symptoms of the disease and its pathogenicity. The review also focuses on the major outbreaks of listeriosis reported in different parts of the world, sources of contamination, morbidity, and mortality rates as well as cost implications. Based on data generated during the outbreak of the disease in South Africa, listeriosis was added to the South African list of mandatory notifiable medical conditions. Surveillance systems were strengthened in the South African food chain in order to assist in preventing and facilitating early detection of both sporadic cases and outbreaks of ...
Keywords	food chain ; foodborne disease ; listeria monocytogenes ; listeriosis ; south african outbreak ; sequence type 6 ; Biology (General) ; QH301-705.5
Subject code	590
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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Article: Disinfection of Mycobacterium avium subspecies hominissuis in drinking tap water using ultraviolet germicidal irradiation

Schiavano, Giuditta Fiorella / Mauro De Santi / Maurizio Sisti / Giulia Amagliani / Giorgio Brandi

Environmental technology. 2018 Dec. 17, v. 39, no. 24

2018

Abstract: Nontuberculous mycobacteria are resistant to conventional water treatments, and are opportunistic human pathogen, particularly in hospitalized patients. The aim of this investigation was to assess the effectiveness of an ultraviolet UV-C lamp treatment ... ...

Abstract	Nontuberculous mycobacteria are resistant to conventional water treatments, and are opportunistic human pathogen, particularly in hospitalized patients. The aim of this investigation was to assess the effectiveness of an ultraviolet UV-C lamp treatment against Mycobacterium avium subspecies hominissuis in drinking tap water. Ultraviolet treatments (0–192 mJ/cm²) were performed using UV lamp immerged onto cylindrical glass tubes containing artificially contaminated water. The results showed that susceptibility to UV varied considerably according to the strains and the diameter of the tube. With a dose of 32 mJ/cm², a significant inactivation (p < .05) of 3 log (99.9%) or more was obtained in only 5 of the 14 strains. To obtain a complete inactivation of all strains an irradiation of 192 mJ/cm² was needed, a dose that is much higher than the limits recommended by the international standards for UV disinfection of drinking water. In conclusion, it may be difficult to standardize a UV dose for the elimination of waterborne mycobacteria.
Keywords	Mycobacterium avium ; animal pathogens ; disinfection ; environmental technology ; glass ; irradiation ; patients ; tap water ; ultraviolet radiation ; water pollution
Language	English
Dates of publication	2018-1217
Size	p. 3221-3227.
Publishing place	Taylor & Francis
Document type	Article
ISSN	1479-487X
DOI	10.1080/09593330.2017.1375028
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Phenotype Screening of an Azole-bisindole Chemical Library Identifies URB1483 as a New Antileishmanial Agent Devoid of Toxicity on Human Cells

Aurora Diotallevi / Laura Scalvini / Gloria Buffi / Yolanda Pérez-Pertejo / Mauro De Santi / Michele Verboni / Gianfranco Favi / Mauro Magnani / Alessio Lodola / Simone Lucarini / Luca Galluzzi

ACS Omega, Vol 6, Iss 51, Pp 35699-

2021 Volume 35710

Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	American Chemical Society
Document type	Article ; Online
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Article ; Online: Differentiation of Leishmania ( L .) infantum , Leishmania ( L .) amazonensis and Leishmania ( L .) mexicana Using Sequential qPCR Assays and High-Resolution Melt Analysis

Marcello Ceccarelli / Aurora Diotallevi / Gloria Buffi / Mauro De Santi / Edith A. Fernández-Figueroa / Claudia Rangel-Escareño / Said A. Muñoz-Montero / Ingeborg Becker / Mauro Magnani / Luca Galluzzi

Microorganisms, Vol 8, Iss 818, p

2020 Volume 818

Abstract: Leishmania protozoa are the etiological agents of visceral, cutaneous and mucocutaneous leishmaniasis. In specific geographical regions, such as Latin America, several Leishmania species are endemic and simultaneously present; therefore, a diagnostic ... ...

Abstract	Leishmania protozoa are the etiological agents of visceral, cutaneous and mucocutaneous leishmaniasis. In specific geographical regions, such as Latin America, several Leishmania species are endemic and simultaneously present; therefore, a diagnostic method for species discrimination is warranted. In this attempt, many qPCR-based assays have been developed. Recently, we have shown that L. (L.) infantum and L. (L.) amazonensis can be distinguished through the comparison of the Cq values from two qPCR assays (qPCR-ML and qPCR-ama), designed to amplify kDNA minicircle subclasses more represented in L. (L.) infantum and L. (L.) amazonensis , respectively. This paper describes the application of this approach to L. (L.) mexicana and introduces a new qPCR-ITS1 assay followed by high-resolution melt (HRM) analysis to differentiate this species from L. (L.) amazonensis . We show that L. (L.) mexicana can be distinguished from L. (L.) infantum using the same approach we had previously validated for L. (L.) amazonensis . Moreover, it was also possible to reliably discriminate L. (L.) mexicana from L. (L .) amazonensis by using qPCR-ITS1 followed by an HRM analysis. Therefore, a diagnostic algorithm based on sequential qPCR assays coupled with HRM analysis was established to identify/differentiate L. (L.) infantum , L. (L.) amazonensis , L. (L.) mexicana and Viannia subgenus. These findings update and extend previous data published by our research group, providing an additional diagnostic tool in endemic areas with co-existing species.
Keywords	leishmania infantum ; leishmania amazonensis ; leishmania mexicana ; qPCR ; high resolution melting ; kDNA ; Biology (General) ; QH301-705.5
Subject code	630
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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Article ; Online: Leishmania infantum Induces Mild Unfolded Protein Response in Infected Macrophages.

Luca Galluzzi / Aurora Diotallevi / Mauro De Santi / Marcello Ceccarelli / Fabrizio Vitale / Giorgio Brandi / Mauro Magnani

PLoS ONE, Vol 11, Iss 12, p e

2016 Volume 0168339

Abstract: The Leishmaniases are a group of parasitic diseases caused by protozoa of the Leishmania genus affecting both humans and other vertebrates. Leishmania is an intracellular pathogen able to confer resistance to apoptosis in the early phase of macrophages ... ...

Abstract	The Leishmaniases are a group of parasitic diseases caused by protozoa of the Leishmania genus affecting both humans and other vertebrates. Leishmania is an intracellular pathogen able to confer resistance to apoptosis in the early phase of macrophages infection by activation of host PI3K/Akt pathway and inhibition of caspase-3 activation. Intracellular pathogens hijack organelles such as ER to facilitate survival and replication, thus eliciting ER stress and activating/modulating the unfolded protein response (UPR) in the host cell. The UPR is aimed to mitigate ER stress, thereby promoting cell survival. However, prolonged ER stress will activate the apoptotic pathway. The aim of this study was to investigate the ER stress response in Leishmania-infected macrophages to gain insights about the mechanisms underlying the apoptosis resistance in parasitized cells. Macrophages differentiated from human monocytic cell lines (U937 and THP-1) and murine primary macrophages were infected with Leishmania infantum MHOM/TN/80/IPT1 (WHO international reference strain). Several ER stress/autophagy expression markers, as well as cell survival/apoptosis markers (phospho-Akt and cleaved caspase-3) were evaluated by qPCR and/or by western blotting. As ER stress positive control, cells were treated with tunicamycin or dithiothreitol (DTT). The gene expression analyses showed a mild but significant induction of the ER stress/autophagy markers. The western blot analyses revealed that the Leishmania infection induced Akt phosphorylation and significantly inhibited the induction of caspase-3 cleavage, eIF2α phosphorylation and DDIT3/CHOP expression in tunicamycin and DTT treated cells. The mild but significant increase in ER stress expression markers and the delay/attenuation of the effects of ER stress inducers in infected cells support the hypothesis that L. infantum could promote survival of host cells by inducing a mild ER stress response. The host ER stress response could be not only a common pathogenic mechanism among Leishmania species but also a target for development of new drugs.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Leishmania infantum Induces Mild Unfolded Protein Response in Infected Macrophages.

Luca Galluzzi / Aurora Diotallevi / Mauro De Santi / Marcello Ceccarelli / Fabrizio Vitale / Giorgio Brandi / Mauro Magnani

PLoS ONE, Vol 11, Iss 12, p e

2016 Volume 0168339

Abstract	The Leishmaniases are a group of parasitic diseases caused by protozoa of the Leishmania genus affecting both humans and other vertebrates. Leishmania is an intracellular pathogen able to confer resistance to apoptosis in the early phase of macrophages infection by activation of host PI3K/Akt pathway and inhibition of caspase-3 activation. Intracellular pathogens hijack organelles such as ER to facilitate survival and replication, thus eliciting ER stress and activating/modulating the unfolded protein response (UPR) in the host cell. The UPR is aimed to mitigate ER stress, thereby promoting cell survival. However, prolonged ER stress will activate the apoptotic pathway. The aim of this study was to investigate the ER stress response in Leishmania-infected macrophages to gain insights about the mechanisms underlying the apoptosis resistance in parasitized cells. Macrophages differentiated from human monocytic cell lines (U937 and THP-1) and murine primary macrophages were infected with Leishmania infantum MHOM/TN/80/IPT1 (WHO international reference strain). Several ER stress/autophagy expression markers, as well as cell survival/apoptosis markers (phospho-Akt and cleaved caspase-3) were evaluated by qPCR and/or by western blotting. As ER stress positive control, cells were treated with tunicamycin or dithiothreitol (DTT). The gene expression analyses showed a mild but significant induction of the ER stress/autophagy markers. The western blot analyses revealed that the Leishmania infection induced Akt phosphorylation and significantly inhibited the induction of caspase-3 cleavage, eIF2α phosphorylation and DDIT3/CHOP expression in tunicamycin and DTT treated cells. The mild but significant increase in ER stress expression markers and the delay/attenuation of the effects of ER stress inducers in infected cells support the hypothesis that L. infantum could promote survival of host cells by inducing a mild ER stress response. The host ER stress response could be not only a common pathogenic mechanism among ...
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The intrinsically disordered E-domains regulate the IGF-1 prohormones stability, subcellular localisation and secretion

Giosuè Annibalini / Serena Contarelli / Mauro De Santi / Roberta Saltarelli / Laura Di Patria / Michele Guescini / Anna Villarini / Giorgio Brandi / Vilberto Stocchi / Elena Barbieri

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 13

Abstract: Abstract Insulin-like growth factor-1 (IGF-1) is synthesised as a prohormone (proIGF-1) requiring enzymatic activity to yield the mature IGF-1. Three proIGF-1s are encoded by alternatively spliced IGF-1 mRNAs: proIGF-1Ea, proIGF-1Eb and proIGF-1Ec. These ...

Abstract	Abstract Insulin-like growth factor-1 (IGF-1) is synthesised as a prohormone (proIGF-1) requiring enzymatic activity to yield the mature IGF-1. Three proIGF-1s are encoded by alternatively spliced IGF-1 mRNAs: proIGF-1Ea, proIGF-1Eb and proIGF-1Ec. These proIGF-1s have a common IGF-1 mature sequence but different E-domains. The structure of the E-domains has not been resolved, and their molecular functions are still unclear. Here, we show that E-domains are Intrinsically Disordered Regions that have distinct regulatory functions on proIGF-1s production. In particular, we identified a highly conserved N-glycosylation site in the Ea-domain, which regulated intracellular proIGF-1Ea level preventing its proteasome-mediated degradation. The inhibition of N-glycosylation by tunicamycin or glucose starvation markedly reduced proIGF-1Ea and mature IGF-1 production. Interestingly, 2-deoxyglucose, a glucose and mannose analogue, increased proIGF-1Ea and mature IGF-1 levels, probably leading to an accumulation of an under-glycosylated proIGF-1Ea that was still stable and efficiently secreted. The proIGF-1Eb and proIGF-1Ec were devoid of N-glycosylation sites, and hence their production was unaffected by N-glycosylation inhibitors. Moreover, we demonstrated that alternative Eb- and Ec-domains controlled the subcellular localisation of proIGF-1s, leading to the nuclear accumulation of both proIGF-1Eb and proIGF-1Ec. Our results demonstrated that E-domains are regulatory elements that control IGF-1 production and secretion.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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