31 results on '"Taurino, Giuseppe"'
Search Results
2. ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment
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Chiu, Martina, Taurino, Giuseppe, Dander, Erica, Bardelli, Donatella, Fallati, Alessandra, Andreoli, Roberta, Bianchi, Massimiliano G., Carubbi, Cecilia, Pozzi, Giulia, Galuppo, Laura, Mirandola, Prisco, Rizzari, Carmelo, Tardito, Saverio, Biondi, Andrea, D'Amico, Giovanna, and Bussolati, Ovidio
- Published
- 2021
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3. Asparagine transport through SLC1A5/ASCT2 and SLC38A5/SNAT5 is essential for BCP‐ALL cell survival and a potential therapeutic target.
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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, and Bussolati, Ovidio
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CELL survival , *ASPARAGINE , *LYMPHOBLASTIC leukemia , *ACUTE leukemia , *STROMAL cells , *BLAST injuries - Abstract
Summary: 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. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Colon-available mango (poly)phenols exhibit mitigating effects on the intestinal barrier function in human intestinal cell monolayers under inflammatory conditions.
- Author
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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, and Bianchi, Massimiliano G.
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- 2024
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5. Genomic and ecological approaches to identify the Bifidobacterium breve prototype of the healthy human gut microbiota.
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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, and Ventura, Marco
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HUMAN microbiota ,GUT microbiome ,COMMENSALISM ,BIFIDOBACTERIUM ,GASTROINTESTINAL system ,PROTOTYPES - Abstract
Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guided by ecology- and phylogenome-based analyses, was employed to identify a representative strain of B. breve to be exploited as a novel health-promoting candidate. The selected strain, i.e., B. breve PRL2012, was found to well represent the genetic content and functional genomic features of the B. breve taxon. We evaluated the ability of PRL2012 to survive in the gastrointestinal tract and to interact with other human gut commensal microbes. When co-cultivated with various human gut commensals, B. breve PRL2012 revealed an enhancement of its metabolic activity coupled with the activation of cellular defense mechanisms to apparently improve its survivability in a simulated ecosystem resembling the human microbiome. [ABSTRACT FROM AUTHOR]
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- 2024
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6. GH136‐encoding gene (perB) is involved in gut colonization and persistence by Bifidobacterium bifidumPRL2010.
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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, and Ventura, Marco
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BIFIDOBACTERIUM ,BIFIDOBACTERIUM bifidum ,COMPARATIVE genomics ,COLONIZATION (Ecology) ,BIFIDOBACTERIUM longum ,GENOMICS ,HUMAN ecology - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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7. Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications.
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Bianchi, Massimiliano G., Chiu, Martina, Taurino, Giuseppe, Bergamaschi, Enrico, Turroni, Francesca, Mancabelli, Leonardo, Longhi, Giulia, Ventura, Marco, and Bussolati, Ovidio
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SILICA nanoparticles ,SILICA ,GUT microbiome ,HUMAN microbiota ,FOOD additives ,INTESTINAL barrier function - 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. [ABSTRACT FROM AUTHOR]
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- 2024
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8. The SLC38A5/SNAT5 amino acid transporter: from pathophysiology to procancer roles in the tumor microenvironment.
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Taurino, Giuseppe, Chiu, Martina, Bianchi, Massimiliano G., Griffini, Erika, and Bussolati, Ovidio
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AMINO acids , *TUMOR microenvironment , *GLUTAMINE , *PATHOLOGICAL physiology , *STROMAL cells , *ASPARAGINE - Abstract
SLC38A5/SNAT5 is a system N transporter that can mediate net inward or outward transmembrane fluxes of neutral amino acids coupled with Na+ (symport) and H+ (antiport). Its preferential substrates are not only amino acids with side chains containing amide (glutamine and asparagine) or imidazole (histidine) groups, but also serine, glycine, and alanine are transported by the carrier. Expressed in the pancreas, intestinal tract, brain, liver, bone marrow, and placenta, it is regulated at mRNA and protein levels by mTORC1 and WNT/b-catenin pathways, and it is sensitive to pH, nutritional stress, inflammation, and hypoxia. SNAT5 expression has been found to be altered in pathological conditions such as chronic inflammatory diseases, gestational complications, chronic metabolic acidosis, and malnutrition. Growing experimental evidence shows that SNAT5 is overexpressed in several types of cancer cells. Moreover, recently published results indicate that SNAT5 expression in stromal cells can support the metabolic exchanges occurring in the tumor microenvironment of asparagine-auxotroph tumors. We review the functional role of the SNAT5 transporter in pathophysiology and propose that, due to its peculiar operational and regulatory features, SNAT5 may play important pro-cancer roles when expressed either in neoplastic or in stromal cells of glutamine-auxotroph tumors. NEW & NOTEWORTHY The transporter SLC38A5/SNAT5 provides net influx or efflux of glutamine, asparagine, and serine. These amino acids are of particular metabolic relevance in several conditions. Changes in transporter expression or activity have been described in selected types of human cancers, where SNAT5 can mediate amino acid exchanges between tumor and stromal cells, thus providing a potential therapeutic target. This is the first review that recapitulates the characteristics and roles of the transporter in physiology and pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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9. GPNA inhibits the sodium-independent transport system l for neutral amino acids
- Author
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Chiu, Martina, Sabino, Cosimo, Taurino, Giuseppe, Bianchi, Massimiliano G., Andreoli, Roberta, Giuliani, Nicola, and Bussolati, Ovidio
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- 2017
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10. Nanoemulsions Embedded in Alginate Beads as Bioadhesive Nanocomposites for Intestinal Delivery of the Anti-Inflammatory Drug Tofacitinib.
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Andretto, Valentina, Taurino, Giuseppe, Guerriero, Giulia, Guérin, Hanäé, Lainé, Emmanuelle, Bianchi, Massimiliano G., Agusti, Géraldine, Briançon, Stéphanie, Bussolati, Ovidio, Clayer-Montembault, Alexandra, and Lollo, Giovanna
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- 2023
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11. Epidemiology, Patients' Journey and Healthcare Costs in Early-Stage Non-Small-Cell Lung Carcinoma: A Real-World Evidence Analysis in Italy.
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Cortinovis, Diego Luigi, Perrone, Valentina, Giacomini, Elisa, Sangiorgi, Diego, Andretta, Margherita, Bartolini, Fausto, Taurino, Giuseppe, Belfiore, Marco, Sicari, Emilia, and Degli Esposti, Luca
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NON-small-cell lung carcinoma ,LUNGS ,MEDICAL care costs ,PATHOLOGICAL anatomy ,DIRECT costing ,DISEASE relapse - Abstract
This real-world analysis aims to estimate the epidemiology and economic burden related to early-stage non-small-cell lung carcinoma (eNSCLC) in the clinical practice Italian setting. An observational analysis was performed using administrative databases linked to pathological anatomy data, covering around 2.5 mln health-assisted individuals. From 2015 to mid-2021, eNSCLC patients staged II–IIIA treated with chemotherapy after surgery were included. Patients were stratified into those presenting loco-regional or metastatic recurrence during follow-up and annualized healthcare direct costs covered by the Italian National Health System (INHS) were estimated. In 2019–2020, the prevalence of eNSCLC was 104.3–117.1/million health-assisted subjects, and the annual incidence was 38.6–30.3/million. Data projected to the Italian population estimated 6206 (2019) and 6967 (2020) prevalent and 2297 (2019) and 1803 (2020) incident cases. Overall, 458 eNSCLC patients were included. Of them, 52.4% of patients had a recurrence (5% loco-regional-recurrence, 47.4% metastatic-recurrence). Healthcare total direct costs/patient averaged EUR 23,607, in particular, in the first year after recurrence, costs averaged EUR 22,493 and EUR 29,337 in loco-regional and metastatic-recurrence patients, respectively. This analysis showed that about one-half of eNSCLC patients stage II–IIIA experience a recurrence, and in recurrence patients, total direct costs were almost two-fold those of no-recurrence patients. These data highlighted an unmet clinical need, as the therapeutic optimization of patients at early stages. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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12. Identification of a prototype human gut Bifidobacterium longum subsp. longum strain based on comparative and functional genomic approaches.
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Alessandri, Giulia, Fontana, Federico, Tarracchini, Chiara, Rizzo, Sonia Mirjam, Bianchi, Massimiliano G., Taurino, Giuseppe, Chiu, Martina, Lugli, Gabriele Andrea, Mancabelli, Leonardo, Argentini, Chiara, Longhi, Giulia, Anzalone, Rosaria, Viappiani, Alice, Milani, Christian, Turroni, Francesca, Bussolati, Ovidio, van Sinderen, Douwe, and Ventura, Marco
- Abstract
Bifidobacteria are extensively exploited for the formulation of probiotic food supplements due to their claimed ability to exert health-beneficial effects upon their host. However, most commercialized probiotics are tested and selected for their safety features rather than for their effective abilities to interact with the host and/or other intestinal microbial players. In this study, we applied an ecological and phylogenomic-driven selection to identify novel B. longum subsp. longum strains with a presumed high fitness in the human gut. Such analyses allowed the identification of a prototype microorganism to investigate the genetic traits encompassed by the autochthonous bifidobacterial human gut communities. B. longum subsp. longum PRL2022 was selected due to its close genomic relationship with the calculated model representative of the adult human-gut associated B. longum subsp. longum taxon. The interactomic features of PRL2022 with the human host as well as with key representative intestinal microbial members were assayed using in vitro models, revealing how this bifidobacterial gut strain is able to establish extensive cross-talk with both the host and other microbial residents of the human intestine. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Designation of optimal reference strains representing the infant gut bifidobacterial species through a comprehensive multi‐omics approach.
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Fontana, Federico, Alessandri, Giulia, Tarracchini, Chiara, Bianchi, Massimiliano Giovanni, Rizzo, Sonia Mirjam, Mancabelli, Leonardo, Lugli, Gabriele Andrea, Argentini, Chiara, Vergna, Laura Maria, Anzalone, Rosaria, Longhi, Giulia, Viappiani, Alice, Taurino, Giuseppe, Chiu, Martina, Turroni, Francesca, Bussolati, Ovidio, van Sinderen, Douwe, Milani, Christian, and Ventura, Marco
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SPECIES ,BACTERIAL diversity ,METAGENOMICS ,REPRODUCIBLE research ,INFANTS ,BIFIDOBACTERIUM - Abstract
The genomic era has resulted in the generation of a massive amount of genetic data concerning the genomic diversity of bacterial taxa. As a result, the microbiological community is increasingly looking for ways to define reference bacterial strains to perform experiments that are representative of the entire bacterial species. Despite this, there is currently no established approach allowing a reliable identification of reference strains based on a comprehensive genomic, ecological, and functional context. In the current study, we developed a comprehensive multi‐omics approach that will allow the identification of the optimal reference strains using the Bifidobacterium genus as test case. Strain tracking analysis based on 1664 shotgun metagenomics datasets of healthy infant faecal samples were employed to identify bifidobacterial strains suitable for in silico and in vitro analyses. Subsequently, an ad hoc bioinformatic tool was developed to screen local strain collections for the most suitable species‐representative strain alternative. The here presented approach was validated using in vitro trials followed by metagenomics and metatranscriptomics analyses. Altogether, these results demonstrated the validity of the proposed model for reference strain selection, thus allowing improved in silico and in vitro investigations both in terms of cross‐laboratory reproducibility and relevance of research findings. [ABSTRACT FROM AUTHOR]
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- 2022
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14. The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles.
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Bianchi, Massimiliano G., Chiu, Martina, Taurino, Giuseppe, Bergamaschi, Enrico, Cubadda, Francesco, Macaluso, Guido M., and Bussolati, Ovidio
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SILICA nanoparticles ,SILICA ,INFLAMMATION ,GLUTAMINE synthetase ,NATURAL immunity - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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15. [18F](2 S ,4 R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma.
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Valtorta, Silvia, Toscani, Denise, Chiu, Martina, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Taurino, Giuseppe, Grioni, Matteo, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, Bussolati, Ovidio, and Giuliani, Nicola
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BORTEZOMIB ,POSITRON emission tomography ,MULTIPLE myeloma ,LABORATORY mice ,EXTRAMEDULLARY diseases ,PROTEASOME inhibitors - Abstract
The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with
18 F-fluorodeoxyglucose ([18 F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18 F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2 S ,4 R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of3 H-labelled Gln. We then radiosynthesized [18 F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18 F]4-FGln and [18 F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18 F]4-FGln and [18 F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18 F](2 S ,4 R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients. [ABSTRACT FROM AUTHOR]- Published
- 2021
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16. Length-dependent toxicity of TiO2 nanofibers: mitigation via shortening.
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Bianchi, Massimiliano G., Campagnolo, Luisa, Allegri, Manfredi, Ortelli, Simona, Blosi, Magda, Chiu, Martina, Taurino, Giuseppe, Lacconi, Valentina, Pietroiusti, Antonio, Costa, Anna L., Poland, Craig A., Baird, Daniel, Duffin, Rodger, Bussolati, Ovidio, and Bergamaschi, Enrico
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NANOFIBERS ,PHAGOCYTOSIS ,MACROPHAGE activation ,TIGHT junctions ,PERITONEUM ,CELL survival ,EPITHELIAL cells - Abstract
Length and aspect ratio represent important toxicity determinants of fibrous nanomaterials. We have previously shown that anatase TiO
2 nanofibers (TiO2 NF) cause a dose-dependent decrease of cell viability as well as the loss of epithelial barrier integrity in polarized airway cell monolayers. Herein we have investigated the impact of fiber shortening, obtained by ball-milling, on the biological effects of TiO2 NF of industrial origin. Long TiO2 NF (L-TiO2 NF) were more cytotoxic than their shortened counterparts (S-TiO2 NF) toward alveolar A549 cells and bronchial 16HBE cells. Moreover, L-TiO2 NF increased the permeability of 16HBE monolayers and perturbed the distribution of tight-junction proteins, an effect also mitigated by fiber shortening. Raw264.7 macrophages efficiently internalized shortened but not long NF, which caused cell stretching and deformation. Compared with L-TiO2 NF, S-TiO2 NF triggered a more evident macrophage activation, an effect suppressed by the phagocytosis inhibitor cytochalasin B. Conversely, a significant increase of inflammatory markers was detected in either the lungs or the peritoneal cavity of mice exposed to L-TiO2 NF but not to S-TiO2 NF, suggesting that short-term macrophage activation in vitro may not be always a reliable indicator of persistent inflammation in vivo. It is concluded that fiber shortening mitigates NF detrimental effects on cell viability and epithelial barrier competence in vitro as well as inflammation development in vivo. These data suggest that fiber shortening may represent an effective safe-by-design strategy for mitigating TiO2 NF toxic effects. [ABSTRACT FROM AUTHOR]- Published
- 2020
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17. Asparagine Synthetase in Cancer: Beyond Acute Lymphoblastic Leukemia.
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Chiu, Martina, Taurino, Giuseppe, Bianchi, Massimiliano G., Kilberg, Michael S., and Bussolati, Ovidio
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LYMPHOBLASTIC leukemia ,ACUTE leukemia ,ASPARAGINE ,AMINO acid synthesis ,CANCER - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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18. γ-Glutamyltransferase enzyme activity of cancer cells modulates L-γ-glutamyl-p-nitroanilide (GPNA) cytotoxicity.
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Corti, Alessandro, Dominici, Silvia, Piaggi, Simona, Belcastro, Eugenia, Chiu, Martina, Taurino, Giuseppe, Pacini, Simone, Bussolati, Ovidio, and Pompella, Alfonso
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- 2019
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19. Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth.
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Chiu, Martina, Taurino, Giuseppe, Bianchi, Massimiliano G., Ottaviani, Laura, Andreoli, Roberta, Ciociola, Tecla, Lagrasta, Costanza A. M., Tardito, Saverio, and Bussolati, Ovidio
- Subjects
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GLUTAMINE , *METABOLISM , *GENE expression , *ANTINEOPLASTIC agents , *CANCER cells - Abstract
In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC50 of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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20. Mesenchymal stromal cells cultured in physiological conditions sustain citrate secretion with glutamate anaplerosis.
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Taurino, Giuseppe, Deshmukh, Ruhi, Villar, Victor H., Chiu, Martina, Shaw, Robin, Hedley, Ann, Shokry, Engy, Sumpton, David, Dander, Erica, D'Amico, Giovanna, Bussolati, Ovidio, and Tardito, Saverio
- Abstract
Bone marrow mesenchymal stromal cells (MSCs) have immunomodulatory and regenerative potential. However, culture conditions govern their metabolic processes and therapeutic efficacy. Here we show that culturing donor-derived MSCs in Plasmax™, a physiological medium with the concentrations of nutrients found in human plasma, supports their proliferation and stemness, and prevents the nutritional stress induced by the conventional medium DMEM. The quantification of the exchange rates of metabolites between cells and medium, untargeted metabolomics, stable isotope tracing and transcriptomic analysis, performed at physiologically relevant oxygen concentrations (1%O 2), reveal that MSCs rely on a high rate of glucose to lactate conversion, coupled with parallel anaplerotic fluxes from glutamine and glutamate to support citrate synthesis and secretion. These distinctive traits of MSCs shape the metabolic microenvironment of the bone marrow niche and can influence nutrient cross-talks under physiological and pathological conditions. [Display omitted] • Physiological nutrient concentrations support MSCs proliferation and stemness in vitro. • ATF4 levels are higher in primary MSCs cultured in DMEM than in Plasmax. • MSCs are highly glycolytic and use glutamine and glutamate for anaplerosis. • The high affinity glutamate uptake of MSCs supports citrate synthesis and secretion. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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21. P-016: The role [18F]-(2S,4R)-4-Fluoroglutamine as a new positron emission tomography tracer in Myeloma in vivo models.
- Author
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Toscani, Denise, Valtorta, Silvia, Chiu, Martina, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Taurino, Giuseppe, Grioni, Matteo, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, Bussolati, Ovidio, and Giuliani, Nicola
- Published
- 2021
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22. In an Un-deconstructed Way.
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Taurino, Giuseppe
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AUTHORS ,LETTERS ,AUTHORSHIP - Abstract
Presents an interview with writer John Weir. He gives information on his books "The Irreversible Decline of Eddie Socket," and "What I Did Wrong." When asked about his developments as a writer, he refers to the letters that he wrote to his grandmother in his childhood. He believes that the constant narration is not distracting.
- Published
- 2006
23. Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability.
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Chiu, Martina, Toscani, Denise, Marchica, Valentina, Taurino, Giuseppe, Costa, Federica, Bianchi, Massimiliano G., Andreoli, Roberta, Franceschi, Valentina, Storti, Paola, Burroughs-Garcia, Jessica, Eufemiese, Rosa Alba, Dalla Palma, Benedetta, Campanini, Nicoletta, Martella, Eugenia, Mancini, Cristina, Shan, Jixiu, Kilberg, Michael S., D'Amico, Giovanna, Dander, Erica, and Agnelli, Luca
- Subjects
GLUTAMINE metabolism ,ASPARAGINE ,BONE marrow ,CELL differentiation ,CELL lines ,ENZYMES ,MULTIPLE myeloma ,STEM cells ,OSTEOBLASTS ,IN vitro studies ,IN vivo studies - Abstract
Simple Summary: Osteolytic bone lesions represent an important clinical feature of multiple myeloma (MM). MM cells metabolize very high amounts of glutamine (Gln) and significantly lower Gln in the bone marrow. In this contribution we demonstrate that MM-dependent Gln depletion impairs the differentiation of bone marrow mesenchymal stromal cells into osteoblasts, the cells that form new bone tissue. We also found that osteoblast differentiation is associated with increased expression of glutaminase, the main enzyme that metabolizes Gln, SNAT2, a transporter able to accumulate Gln into the cells, and asparagine synthetase, the enzyme that uses Gln to obtain asparagine (Asn). Asn rescued osteoblast differentiation of Gln-starved mesenchymal stromal cells. These results demonstrate that MM cells impair osteoblast differentiation, hindering mesenchymal Asn synthesis through Gln depletion. Besides providing a metabolic mechanism underlying osteolytic lesions in MM, these results suggest that Asn supplementation may prevent bone disease in MM patients. Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-culturing human mesenchymal stromal cells (MSCs) with MM cells. Moreover, glutamine depletion hinders osteoblast differentiation of MSCs, which is also severely blunted by the spent, low-glutamine medium of MM cells, and rescued by glutamine restitution. Glutaminase and the concentrative glutamine transporter SNAT2 are induced during osteoblastogenesis in vivo and in vitro, and both needed for MSCs differentiation, pointing to enhanced the requirement for the amino acid. Osteoblastogenesis also triggers the induction of glutamine-dependent asparagine synthetase (ASNS), and, among non-essential amino acids, asparagine rescues differentiation of glutamine-starved MSCs, by restoring the transcriptional profiles of differentiating MSCs altered by glutamine starvation. Thus, reduced asparagine availability provides a mechanistic link between MM-dependent Gln depletion in BM and impairment of osteoblast differentiation. Inhibition of Gln metabolism in MM cells and supplementation of asparagine to stromal cells may, therefore, constitute novel approaches to prevent osteolytic lesions in MM. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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24. Pyrogenic and Precipitated Amorphous Silica Nanoparticles Differentially Affect Cell Responses to LPS in Human Macrophages.
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G. Bianchi, Massimiliano, Chiu, Martina, Taurino, Giuseppe, Ruotolo, Roberta, Marmiroli, Nelson, Bergamaschi, Enrico, Cubadda, Francesco, and Bussolati, Ovidio
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SILICA nanoparticles ,SILICA ,GLUTAMINE synthetase ,CELLS ,MACROPHAGE activation ,MACROPHAGES - Abstract
Previous work has demonstrated that precipitated (NM-200) and pyrogenic (NM-203) Amorphous Silica Nanoparticles (ASNPs) elicit the inflammatory activation of murine macrophages, with more pronounced effects observed with NM-203. Here, we compare the effects of low doses of NM-200 and NM-203 on human macrophage-like THP-1 cells, assessing how the pre-exposure to these nanomaterials affects the cell response to lipopolysaccharide (LPS). Cell viability was affected by NM-203, but not by NM-200, and only in the presence of LPS. While NM-203 stimulated mTORC1, neither ASNPs activated NFκB or the transcription of its target genes PTGS2 and IL1B. NM-200 and NM-203 caused a block of the autophagic flux and inhibited the LPS-dependent increase of Glutamine Synthetase (GS) expression. Both ASNPs suppressed the activation of caspase-1, delaying the LPS-dependent secretion of IL-1β. Thus, ASNPs modulate several important pathways in human macrophages, altering their response to LPS. NM-203 had larger effects on autophagy, mTORC1 activity and GS expression than NM-200, confirming the higher biological activity of pyrogenic ASNPs when compared with precipitated ASNPs. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
25. Functional Consequences of Low Activity of Transport System A for Neutral Amino Acids in Human Bone Marrow Mesenchymal Stem Cells.
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Chiu, Martina, Taurino, Giuseppe, Bianchi, Massimiliano G., Dander, Erica, Fallati, Alessandra, Giuliani, Nicola, D'Amico, Giovanna, and Bussolati, Ovidio
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MESENCHYMAL stem cells , *AMINO acids , *BONE marrow , *AMINO acid transport , *AMINO acid metabolism , *CELL size - Abstract
In cultured human fibroblasts, SNAT transporters (System A) account for the accumulation of non-essential neutral amino acids, are adaptively up-regulated upon amino acid deprivation and play a major role in cell volume recovery upon hypertonic stress. No information is instead available on the expression and activity of SNAT transporters in human bone marrow mesenchymal stromal cells (MSC), although they are increasingly investigated for their staminal and immunomodulatory properties and used for several therapeutic applications. The uptake of glutamine and proline, two substrates of SNAT1 and SNAT2 transporters, was measured in primary human MSC and an MSC line. The amino acid analogue MeAIB, a specific substrate of these carriers, has been used to selectively inhibit SNAT-dependent transport of glutamine and, through its sodium-dependent transport, as an indicator of SNAT1/2 activity. SNAT1/2 expression and localization were assessed with RT-PCR and confocal microscopy, respectively. Cell volume was assessed from urea distribution space. In all these experiments, primary human fibroblasts were used as the positive control for SNAT expression and activity. Compared with fibroblasts, MSC have a lower SNAT1 expression and hardly detectable membrane localization of both SNAT1 and SNAT2. Moreover, they exhibit no sodium-dependent MeAIB uptake or MeAIB-inhibitable glutamine transport, and exhibit a lower ability to accumulate glutamine and proline than fibroblasts. MSC exhibited an only marginal increase in MeAIB transport upon amino acid starvation and did not recover cell volume after hypertonic stress. In conclusion, the activity of SNAT transporters is low in human MSC. MSC adaptation to amino acid shortage is expected to rely on intracellular synthesis, given the absence of an effective up-regulation of the SNAT transporters. [ABSTRACT FROM AUTHOR]
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- 2020
- Full Text
- View/download PDF
26. Glutamine addiction of myeloma cells shapes the metabolic features of the bone microenvironment and impairs osteoblast differentiation.
- Author
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Toscani, Denise, Chiu, Martina, Vicario, Emanuela, Taurino, Giuseppe, Accardi, Fabrizio, Bussolati, Ovidio, and Giuliani, Nicola
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- 2019
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27. Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers.
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Bianchi, Massimiliano G., Chiu, Martina, Taurino, Giuseppe, Brighenti, Furio, Del Rio, Daniele, Mena, Pedro, and Bussolati, Ovidio
- Abstract
The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B
2 (PB2 ), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
28. Comparative in Vitro Cytotoxicity of Realistic Doses of Benchmark Multi-Walled Carbon Nanotubes towards Macrophages and Airway Epithelial Cells.
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Di Cristo, Luisana, Bianchi, Massimiliano G., Chiu, Martina, Taurino, Giuseppe, Donato, Francesca, Garzaro, Giacomo, Bussolati, Ovidio, and Bergamaschi, Enrico
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PERITONEAL macrophages ,MULTIWALLED carbon nanotubes ,EPITHELIAL cells ,CARBON nanotubes ,MACROPHAGES - Abstract
Multi-walled carbon nanotubes (MWCNT) have many outstanding physical and chemical properties that make them useful in many applications in nanotechnology. However, these properties are reported to be potentially harmful for the human body. The effects of low and realistic doses of three well-characterized preparations of MWCNT, obtained from the Joint Research Centre (JRC) (NM-400, NM-401, and NM-402), were assessed in two murine macrophage lines, Raw264.7, of peritoneal origin, and MH-S, derived from alveolar macrophages. Macrophage viability, evaluated with two distinct methods, was significantly lowered by NM-401 (needle-like, average length 4 μm, diameter 67 nm) with IC
50 values of 10 μg/cm2 , whereas NM-400 and NM-402 (tangled, average lengths 846–1372 nm, diameter 11 nm) had much smaller effects. In contrast, at 10 μg/cm2 , NM-400 and NM-402 induced the M1 marker Nos2 and, consistently, a sizable accumulation of nitrites in the medium, whereas NM-401 had no significant effect. None of the MWCNT preparations induced the M2 marker Arg1. Phagocytic activity, assessed in Raw264.7 macrophages, was significantly reduced in cells exposed to NM-401, but not to NM-400 or NM-402. When tested on Calu-3 bronchial epithelial cell monolayers, the three MWCNT preparations did not affect cell viability, but decreased the trans-epithelial electrical resistance at the maximal dose tested (80 μg/cm2 ), with the most evident effect detected for NM-401, even at 10 μg/cm2 . In conclusion, among the possible structural determinants of the toxic effects exerted by MWCNT towards macrophages and airway epithelial cells, shape and length appear the most relevant at low, realistic doses. [ABSTRACT FROM AUTHOR]- Published
- 2019
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29. Ecology- and genome-based identification of the Bifidobacterium adolescentis prototype of the healthy human gut microbiota.
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Argentini, Chiara, Andrea Lugli, Gabriele, 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, and Ventura, Marco
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BIFIDOBACTERIUM , *GUT microbiome , *HUMAN microbiota , *PROTOTYPES , *GASTROINTESTINAL system , *MICROBIAL cells - 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 in silico methodology based on an ecological and phylogenomic-driven approach allowed the selection of a Bifidobacterium adolescentis prototype strain, i.e., B. adolescentis PRL2023, which best represents the overall genetic content and functional features of the B. adolescentis taxon. Such features were confirmed by in vitro experiments aimed at evaluating the ability of this strain to survive in the gastrointestinal tract of the host and its ability to interact with human intestinal cells and other microbial gut commensals. In this context, co-cultivation of B. adolescentis PRL2023 and several gut commensals revealed various microbe-microbe interactions and indicated co-metabolism of particular plant-derived glycans, such as xylan. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
30. Bioinspired hyaluronic acid and polyarginine nanoparticles for DACHPt delivery.
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Matha, Kevin, Lollo, Giovanna, Taurino, Giuseppe, Respaud, Renaud, Marigo, Ilaria, Shariati, Molood, Bussolati, Ovidio, Vermeulen, An, Remaut, Katrien, and Benoit, Jean-Pierre
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BIODEGRADABLE nanoparticles , *HYALURONIC acid , *PLATINUM nanoparticles , *NANOPARTICLES , *INTRAVENOUS injections , *PHARMACOLOGY - Abstract
This work here presented provides insights over a novel biodegradable polymeric nanosystem made of hyaluronic acid and polyarginine for diaminocyclohexane-platinum (DACHPt) encapsulation. Using mild conditions based on ionic gelation technique, monodispersed blank and DACHPt-loaded nanoparticles (NP) with a size of around 200 nm and negative ζ potential (−35 mV) were obtained. The freeze-drying process was optimized to improve the stability and shelf-life of the developed nanoparticles. After reconstitution, nanoparticles maintained their size showing an association efficiency of around 70% and a high drug loading (8%). In vitro cytotoxicity studies revealed that DACHPt-loaded nanoparticles had a superior anticancer activity compared with oxaliplatin solution. The IC50 was reduced by a factor of two in HT-29 cells (IC50 39 µM vs 74 µM, respectively), and resulted almost 1.3 fold lower in B6KPC3 cells (18 µM vs 23 µM respectively). Whereas toxic effects of both drug and DACHPt-loaded nanoparticles were comparable in the A549 cell line (IC50 11 µM vs 12 µM). DACHPt-loaded nanoparticles were also able to modulate immunogenic cell death (ICD) in vitro. After incubation with B6KPC3 cells, an increase in HMGB1 (high-mobility group box 1) production associated with ATP release occurred. Then, in vivo pharmacokinetic studies were performed after intravenous injection (IV) of DACHPt-loaded nanoparticles and oxaliplatin solution in healthy mice (35.9 µg of platinum equivalent/mouse). An AUC six times higher (24 h * mg/L) than the value obtained following the administration of oxaliplatin solution (3.76 h * mg/L) was found. C max was almost five times higher than the control (11.4 mg/L for NP vs 2.48 mg/L). Moreover, the reduction in volume of distribution and clearance clearly indicated a more limited tissue distribution. A simulated repeated IV regimen was performed in silico and showed no accumulation of platinum from the nanoparticles. Overall, the proposed approach discloses a novel nano-oncological treatment based on platinum derivative with improved antitumor activity in vitro and in vivo stability as compared to the free drug. [ABSTRACT FROM AUTHOR]
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- 2020
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- View/download PDF
31. I Think I Should Speak Now.
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Taurino, Giuseppe
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FRIENDSHIP ,FICTION - Abstract
Reviews the book "The Anomalies," by Joey Goebel.
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- 2005
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