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Article ; Online: The

Taurino, Giuseppe / Chiu, Martina / Bianchi, Massimiliano G / Griffini, Erika / Bussolati, Ovidio

American journal of physiology. Cell physiology

2023 Volume 325, Issue 2, Page(s) C550–C562

Abstract: ... ...

Abstract	SLC38A5
MeSH term(s)	Pregnancy ; Female ; Humans ; Glutamine ; Amino Acid Transport Systems, Neutral/genetics ; Amino Acid Transport Systems, Neutral/metabolism ; Asparagine ; Tumor Microenvironment ; Amino Acid Transport Systems ; Amino Acids ; Serine ; Neoplasms/genetics
Chemical Substances	Glutamine (0RH81L854J) ; Amino Acid Transport Systems, Neutral ; Asparagine (7006-34-0) ; Amino Acid Transport Systems ; Amino Acids ; Serine (452VLY9402) ; SLC38A5 protein, human
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00169.2023
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Article ; Online: Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications.

Bianchi, Massimiliano G / Chiu, Martina / Taurino, Giuseppe / Bergamaschi, Enrico / Turroni, Francesca / Mancabelli, Leonardo / Longhi, Giulia / Ventura, Marco / Bussolati, Ovidio

Journal of nanobiotechnology

2024 Volume 22, Issue 1, Page(s) 45

Abstract: Amorphous silica nanoparticles (ASNP) are among the nanomaterials that are produced in large quantities. ASNP have been present for a long time in several fast-moving consumer products, several of which imply exposure of the gastrointestinal tract, such ... ...

Abstract	Amorphous silica nanoparticles (ASNP) are among the nanomaterials that are produced in large quantities. ASNP have been present for a long time in several fast-moving consumer products, several of which imply exposure of the gastrointestinal tract, such as toothpastes, food additives, drug excipients, and carriers. Consolidated use and experimental evidence have consistently pointed to the very low acute toxicity and limited absorption of ASNP. However, slow absorption implies prolonged exposure of the intestinal epithelium to ASNP, with documented effects on intestinal permeability and immune gut homeostasis. These effects could explain the hepatic toxicity observed after oral administration of ASNP in animals. More recently, the role of microbiota in these and other ASNP effects has attracted increasing interest in parallel with the recognition of the role of microbiota in a variety of conditions. Although evidence for nanomaterial effects on microbiota is particularly abundant for materials endowed with bactericidal activities, a growing body of recent experimental data indicates that ASNPs also modify microbiota. The implications of these effects are recounted in this contribution, along with a discussion of the more important open issues and recommendations for future research.
MeSH term(s)	Animals ; Humans ; Silicon Dioxide/toxicity ; Gastrointestinal Microbiome ; Nanoparticles/toxicity ; Intestinal Mucosa
Chemical Substances	Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-024-02305-x
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Article: The Role of Amino Acids in the Crosstalk Between Mesenchymal Stromal Cells and Neoplastic Cells in the Hematopoietic Niche.

Chiu, Martina / Taurino, Giuseppe / Bianchi, Massimiliano G / Bussolati, Ovidio

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 714755

Abstract: Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, ...

Abstract	Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, and changes in nutrient pools and fluxes are important components of the bidirectional communication between MSCs and hematological cancer cells. Among nutrients, amino acids play a significant role in cancer progression and chemo-resistance. Moreover, selected types of cancer cells are extremely greedy for glutamine, and significantly deplete the extracellular pool of the amino acid. As a consequence, this influences the behavior of MSCs in terms of either cytokine/chemokine secretion or differentiation potential. Additionally, a direct nutritional interaction exists between MSCs and immune cells. In particular, selected subpopulations of lymphocytes are dependent upon selected amino acids, such as arginine and tryptophan, for full differentiation and competence. This review describes and discusses the nutritional interactions existing in the neoplastic bone marrow niche between MSCs and other cell types, with a particular emphasis on cancer cells and immune cells. These relationships are discussed in the perspective of potential novel therapeutic strategies based on the interference on amino acid metabolism or intercellular fluxes.
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.714755
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Article: The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles.

Bianchi, Massimiliano G / Chiu, Martina / Taurino, Giuseppe / Bergamaschi, Enrico / Cubadda, Francesco / Macaluso, Guido M / Bussolati, Ovidio

Nanomaterials (Basel, Switzerland)

2022 Volume 12, Issue 13

Abstract: Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the ... ...

Abstract	Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we study the effects of pyrogenic ASNP on the LPS-dependent activation of human macrophages differentiated from peripheral blood monocytes. In macrophages, 24 h of pre-exposure to non-cytotoxic doses of ASNP markedly inhibited the LPS-dependent induction of pro-inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NFκB activation and the increased intracellular sequestration of the TLR4 receptor. The late induction of glutamine synthetase (GS) by LPS was also prevented by pre-exposure to ASNP, while GS silencing did not interfere with cytokine secretion. It is concluded that (i) macrophages exposed to ASNP are less sensitive to LPS-dependent activation and (ii) GS induction by LPS is likely secondary to the stimulation of cytokine secretion. The observed interference with LPS effects may point to a dampening of the acute inflammatory response after exposure to ASNP in humans.
Language	English
Publishing date	2022-07-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662255-5
ISSN	2079-4991
ISSN	2079-4991
DOI	10.3390/nano12132307
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Article: Genomic and ecological approaches to identify the

Argentini, Chiara / Lugli, Gabriele Andrea / Tarracchini, Chiara / Fontana, Federico / Mancabelli, Leonardo / Viappiani, Alice / Anzalone, Rosaria / Angelini, Leonora / Alessandri, Giulia / Longhi, Giulia / Bianchi, Massimiliano G / Taurino, Giuseppe / Bussolati, Ovidio / Milani, Christian / van Sinderen, Douwe / Turroni, Francesca / Ventura, Marco

Frontiers in microbiology

2024 Volume 15, Page(s) 1349391

Abstract: Members of the ... ...

Abstract	Members of the genus
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1349391
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Article ; Online: GH136-encoding gene (perB) is involved in gut colonization and persistence by Bifidobacterium bifidum PRL2010.

Rizzo, Sonia Mirjam / Vergna, Laura Maria / Alessandri, Giulia / Lee, Ciaran / Fontana, Federico / Lugli, Gabriele Andrea / Carnevali, Luca / Bianchi, Massimiliano G / Barbetti, Margherita / Taurino, Giuseppe / Sgoifo, Andrea / Bussolati, Ovidio / Turroni, Francesca / van Sinderen, Douwe / Ventura, Marco

Microbial biotechnology

2024 Volume 17, Issue 2, Page(s) e14406

Abstract: Bifidobacteria are commensal microorganisms that typically inhabit the mammalian gut, including that of humans. As they may be vertically transmitted, they commonly colonize the human intestine from the very first day following birth and may persist ... ...

Abstract	Bifidobacteria are commensal microorganisms that typically inhabit the mammalian gut, including that of humans. As they may be vertically transmitted, they commonly colonize the human intestine from the very first day following birth and may persist until adulthood and old age, although generally at a reduced relative abundance and prevalence compared to infancy. The ability of bifidobacteria to persist in the human intestinal environment has been attributed to genes involved in adhesion to epithelial cells and the encoding of complex carbohydrate-degrading enzymes. Recently, a putative mucin-degrading glycosyl hydrolase belonging to the GH136 family and encoded by the perB gene has been implicated in gut persistence of certain bifidobacterial strains. In the current study, to better characterize the function of this gene, a comparative genomic analysis was performed, revealing the presence of perB homologues in just eight bifidobacterial species known to colonize the human gut, including Bifidobacterium bifidum and Bifidobacterium longum subsp. longum strains, or in non-human primates. Mucin-mediated growth and adhesion to human intestinal cells, in addition to a rodent model colonization assay, were performed using B. bifidum PRL2010 as a perB prototype and its isogenic perB-insertion mutant. These results demonstrate that perB inactivation reduces the ability of B. bifidum PRL2010 to grow on and adhere to mucin, as well as to persist in the rodent gut niche. These results corroborate the notion that the perB gene is one of the genetic determinants involved in the persistence of B. bifidum PRL2010 in the human gut.
MeSH term(s)	Animals ; Bifidobacterium bifidum/genetics ; Bifidobacterium/genetics ; Epithelial Cells/microbiology ; Mucins ; Mammals
Chemical Substances	Mucins
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14406
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Article ; Online: Colon-available mango (poly)phenols exhibit mitigating effects on the intestinal barrier function in human intestinal cell monolayers under inflammatory conditions.

Pereira-Caro, Gema / Cáceres-Jiménez, Salud / Moreno-Ortega, Alicia / Dobani, Sara / Pourshahidi, Kirsty / Gill, Chris I R / Mena, Pedro / Del Rio, Daniele / Moreno-Rojas, José Manuel / Taurino, Giuseppe / Bussolati, Ovidio / Almutairi, Tahani M / Crozier, Alan / Bianchi, Massimiliano G

Food & function

2024 Volume 15, Issue 9, Page(s) 5118–5131

Abstract: This study investigated the impact ... ...

Abstract	This study investigated the impact of
MeSH term(s)	Humans ; Mangifera/chemistry ; Caco-2 Cells ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Interleukin-8/metabolism ; Mucin-2/metabolism ; HT29 Cells ; Polyphenols/pharmacology ; Colon/drug effects ; Colon/metabolism ; Nitric Oxide/metabolism ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Inflammation/drug therapy ; Intestinal Barrier Function
Chemical Substances	Interleukin-8 ; Mucin-2 ; Polyphenols ; Nitric Oxide (31C4KY9ESH) ; Plant Extracts ; MUC2 protein, human
Language	English
Publishing date	2024-05-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d4fo00451e
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Article ; Online: Asparagine transport through SLC1A5/ASCT2 and SLC38A5/SNAT5 is essential for BCP-ALL cell survival and a potential therapeutic target.

Taurino, Giuseppe / Dander, Erica / Chiu, Martina / Pozzi, Giulia / Maccari, Chiara / Starace, Rita / Silvestri, Daniela / Griffini, Erika / Bianchi, Massimiliano G / Carubbi, Cecilia / Andreoli, Roberta / Mirandola, Prisco / Valsecchi, Maria Grazia / Rizzari, Carmelo / D'Amico, Giovanna / Bussolati, Ovidio

British journal of haematology

2024

Abstract: B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) blasts strictly depend on the transport of extra-cellular asparagine (Asn), yielding a rationale for L-asparaginase (ASNase) therapy. However, the carriers used by ALL blasts for Asn transport have ...

Abstract	B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) blasts strictly depend on the transport of extra-cellular asparagine (Asn), yielding a rationale for L-asparaginase (ASNase) therapy. However, the carriers used by ALL blasts for Asn transport have not been identified yet. Exploiting RS4;11 cells as BCP-ALL model, we have found that cell Asn is lowered by either silencing or inhibition of the transporters ASCT2 or SNAT5. The inhibitors V-9302 (for ASCT2) and GluγHA (for SNAT5) markedly lower cell proliferation and, when used together, suppress mTOR activity, induce autophagy and cause a severe nutritional stress, leading to a proliferative arrest and a massive cell death in both the ASNase-sensitive RS4;11 cells and the relatively ASNase-insensitive NALM-6 cells. The cytotoxic effect is not prevented by coculturing leukaemic cells with primary mesenchymal stromal cells. Leukaemic blasts of paediatric ALL patients express ASCT2 and SNAT5 at diagnosis and undergo marked cytotoxicity when exposed to the inhibitors. ASCT2 expression is positively correlated with the minimal residual disease at the end of the induction therapy. In conclusion, ASCT2 and SNAT5 are the carriers exploited by ALL cells to transport Asn, and ASCT2 expression is associated with a lower therapeutic response. ASCT2 may thus represent a novel therapeutic target in BCP-ALL.
Language	English
Publishing date	2024-05-13
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19516
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Article ; Online: Ecology- and genome-based identification of the

Argentini, Chiara / Lugli, Gabriele Andrea / Tarracchini, Chiara / Fontana, Federico / Mancabelli, Leonardo / Viappiani, Alice / Anzalone, Rosaria / Angelini, Leonora / Alessandri, Giulia / Bianchi, Massimiliano G / Taurino, Giuseppe / Bussolati, Ovidio / Milani, Christian / van Sinderen, Douwe / Turroni, Francesca / Ventura, Marco

Applied and environmental microbiology

2024 Volume 90, Issue 2, Page(s) e0201423

Abstract: Bifidobacteria are among the first microbial colonizers of the human gut, being frequently associated with human health-promoting activities. In the current study, ... ...

Abstract	Bifidobacteria are among the first microbial colonizers of the human gut, being frequently associated with human health-promoting activities. In the current study, an
MeSH term(s)	Adult ; Humans ; Bifidobacterium adolescentis/genetics ; Bifidobacterium adolescentis/metabolism ; Gastrointestinal Microbiome/genetics ; Bifidobacterium/genetics ; Bifidobacterium/metabolism ; Probiotics ; Phylogeny
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/aem.02014-23
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Article: Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia.

Chiu, Martina / Taurino, Giuseppe / Bianchi, Massimiliano G / Kilberg, Michael S / Bussolati, Ovidio

Frontiers in oncology

2020 Volume 9, Page(s) 1480

Abstract: Asparagine Synthetase (ASNS) catalyzes the synthesis of the non-essential amino acid asparagine (Asn) from aspartate (Asp) and glutamine (Gln). ASNS expression is highly regulated at the transcriptional level, being induced by both the Amino Acid ... ...

Abstract	Asparagine Synthetase (ASNS) catalyzes the synthesis of the non-essential amino acid asparagine (Asn) from aspartate (Asp) and glutamine (Gln). ASNS expression is highly regulated at the transcriptional level, being induced by both the Amino Acid Response (AAR) and the Unfolded Protein Response (UPR) pathways. Lack of ASNS protein expression is a hallmark of Acute Lymphoblastic Leukemia (ALL) blasts, which, therefore, are auxotrophic for Asn. This peculiarity is the rationale for the use of bacterial L-Asparaginase (ASNase) for ALL therapy, the first example of anti-cancer treatment targeting a tumor-specific metabolic feature. Other hematological and solid cancers express low levels of ASNS and, therefore, should also be Asn auxotrophs and ASNase sensitive. Conversely, in the last few years, several reports indicate that in some cancer types ASNS is overexpressed, promoting cell proliferation, chemoresistance, and a metastatic behavior. However, enhanced ASNS activity may constitute a metabolic vulnerability in selected cancer models, suggesting a variable and tumor-specific role of the enzyme in cancer. Recent evidence indicates that, beyond its canonical role in protein synthesis, Asn may have additional regulatory functions. These observations prompt a re-appreciation of ASNS activity in the biology of normal and cancer tissues, with particular attention to the fueling of Asn exchange between cancer cells and the tumor microenvironment.
Language	English
Publishing date	2020-01-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.01480
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