64 results on '"Avolio R."'
Search Results
2. Seasonal variability of trace elements bioaccumulation in Pacific Oysters (Crassostrea gigas) from an experimental pilot farm in the Calich Lagoon (Sardinia, Italy).
- Author
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Meloni D, Mudadu AG, Abete MC, Bazzoni AM, Griglione A, Avolio R, Serra S, Fois N, Esposito G, Melillo R, and Squadrone S
- Subjects
- Animals, Italy, Bioaccumulation, Farms, Water Pollutants, Chemical analysis, Water Pollutants, Chemical metabolism, Environmental Monitoring, Pilot Projects, Trace Elements analysis, Trace Elements metabolism, Seasons, Crassostrea metabolism, Crassostrea chemistry
- Abstract
Background: Metals pollution is a worldwide environmental issue due to their persistence in the ecosystems, non-degradability, and bioaccumulation in marine biota. Pacific Oysters (Crassostrea gigas) are highly nutritious bivalve representing an important dietary constituent but may accumulate metals through feeding on suspended sediments from surrounding water, then represent a suitable tool for biomonitoring., Materials and Methods: The occurrence of trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Rb, Se, Sn, V, Zn) was investigated in Pacific Oysters (Cassostrea gigas) collected from Calich Lagoon in each season of 2019. Samples were homogenized and subjected to microwave acid digestion before being analyzed by inductively coupled plasma-mass spectrometer (ICP-MS)., Results: The results showed a significant seasonal variation for temperature, dissolved oxygen, chlorophyll, and pH. Moreover, high significant seasonal variation in concentrations of Cd, Mn, Ni, and V was recorded. The highest values were found for Fe (128 mg kg
⁻1 w.w.), and Al (112 mg kg⁻1 w.w.) in October, for Zn (113 mg kg⁻1 w.w.) in March and May., Conclusions: Pacific Oysters were confirmed as suitable bioindicators of the health status of coastal lagoons; trace elements concentrations were highly affected by season of collection, and according to literature the highest values were recorded in autumn and summer. The EU legal limits for Cd and Pb were not exceeded, then the farmed oysters were safe to consumers., Competing Interests: Declaration of Competing Interest Declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)- Published
- 2024
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3. Design of innovative and low-cost dopamine-biotin conjugate sensor for the efficient detection of protein and cancer cells.
- Author
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Notarbartolo M, Alfieri ML, Avolio R, Ball V, Errico ME, Massaro M, Puglisi R, Sànchez-Espejo R, Viseras C, and Riela S
- Subjects
- Humans, Indoles chemistry, Polymers chemistry, HL-60 Cells, MCF-7 Cells, Molecular Structure, Surface Properties, Avidin chemistry, Particle Size, Biotin chemistry, Dopamine analysis, Biosensing Techniques
- Abstract
The rapid, precise identification and quantification of specific biomarkers, toxins, or pathogens is currently a key strategy for achieving more efficient diagnoses. Herein a dopamine-biotin monomer was synthetized and oxidized in the presence of hexamethylenediamine, to obtain adhesive coatings based on polydopamine-biotin (PDA-BT) on different materials to be used in targeted molecular therapy. Insight into the structure of the PDA-BT coating was obtained by solid-state
13 C NMR spectroscopy acquired, for the first time, directly onto the coating, deposited on alumina spheres. The receptor binding capacity of the PDA-BT coating toward 4-hydroxyazobenzene-2-carboxylic acid/Avidin complex was verified by means of UV-vis spectroscopy. Different deposition cycles of avidin onto the PDA-BT coating by layer-by-layer assembly showed that the film retains its receptor binding capacity for at least eight consecutive cycles. Finally, the feasibility of PDA-BT coating to recognize cell lines with different grade of overexpression of biotin receptors (BR) was investigated by tumor cell capture experiments by using MCF-7 (BR+) and HL-60 (BR-) cell lines. The results show that the developed system can selectively capture MCF-7 cells indicating that it could represent a first approach for the development of future more sophisticated biosensors easily accessible, low cost and recyclable with the dual and rapid detection of both proteins and cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2025
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4. Exploring the Untapped Potential of Pine Nut Skin By-Products: A Holistic Characterization and Recycling Approach.
- Author
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Nolasco A, Squillante J, Velotto S, D'Auria G, Ferranti P, Mamone G, Errico ME, Avolio R, Castaldo R, De Luca L, Romano R, Esposito F, and Cirillo T
- Abstract
The increasing population, food demand, waste management concerns, and the search for sustainable alternatives to plastic polymers have led researchers to explore the potential of waste materials. This study focused on a waste of pine nut processing referred to in this paper as pine nut skin. For the first time, its nutritional profile, potential bioactive peptide, contaminants, and morphological structure were assessed. Pine nut skin was composed mainly of carbohydrates (56.2%) and fiber (27.5%). The fat (9.8%) was about 45%, 35%, and 20% saturated, monounsaturated, and polyunsaturated fatty acid, respectively, and Omega-9,-6, and -3 were detected. Notably, oleic acid, known for its health benefits, was found in significant quantities, resembling its presence in pine nut oil. The presence of bioactive compounds such as eicosapentaenoic acid (EPA) and phytosterols further adds to its nutritional value. Some essential elements were reported, whereas most of the contaminants such as heavy metals, polycyclic aromatic hydrocarbons, rare earth elements, and pesticides were below the limit of quantification. Furthermore, the in silico analysis showed the occurrence of potential precursor peptides of bioactive compounds, indicating health-promoting attributes. Lastly, the morphological structural characterization of the pine nut skin was followed by Fourier Transform Infrared and solid-state NMR spectroscopy to identify the major components, such as lignin, cellulose, and hemicellulose. The thermostability of the pine nut skin was monitored via thermogravimetric analysis, and the surface of the integument was analyzed via scanning electron microscopy and volumetric nitrogen adsorption. This information provides a more comprehensive view of the potential uses of pine nut skin as a filler material for biocomposite materials. A full characterization of the by-products of the food chain is essential for their more appropriate reuse.
- Published
- 2024
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5. Trace and rare earth elements in phytoplankton from the Tyrrhenian Sea (Italy).
- Author
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Del Buono E, Nurra N, Sartor RM, Battuello M, Favaro L, Berti G, Griglione A, Trossi A, Avolio R, Abete MC, and Squadrone S
- Subjects
- Ecosystem, Phytoplankton, Environmental Monitoring, Italy, Metals, Rare Earth analysis, Trace Elements analysis, Lanthanoid Series Elements analysis
- Abstract
Plankton plays a very crucial role in bioaccumulation and transfer of metals in the marine food web and represents a suitable bioindicator of the occurrence of trace and rare earth elements in the ecosystem. Trace elements and REEs were analyzed by ICP-MS in phytoplankton samples from the northwestern Mediterranean Sea. Metal concentrations in phytoplankton were found strongly influenced by seasons and depth of collection (- 30 m, - 50 m). Principal component analysis (PCA) has shown that Al, As, Cr, Cu, Ga, and Sn concentrations were related to summer and autumn in samples collected at 30 m depth, while Fe, Mn, Ni, V, and Zn levels related strongly with summer and spring at 50 m depth. Fe, Al, and Zn were the most represented elements in all samples (mean values respectively in the ranges 4.2-8.2, 9.6-13, and 1.0-4.4 mg kg
-1 ) according to their widespread presence in the environment and in the earth crust. Principal component analysis (PCA) performed on REEs showed that mostly all lanthanides' concentrations strongly correlate with summer and autumn seasons (- 30 m depth); the highest ∑REE concentration (75 µg kg-1 ) was found in winter. Phytoplankton REE normalized profile was comparable to those of other marine biota collected in the same area according to the suitability of lanthanides as geological tracers., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2024
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6. Thermophilic biocatalysts for one-step conversion of citrus waste into lactic acid.
- Author
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Aulitto M, Alfano A, Maresca E, Avolio R, Errico ME, Gentile G, Cozzolino F, Monti M, Pirozzi A, Donsì F, Cimini D, Schiraldi C, and Contursi P
- Subjects
- Fermentation, Glucose metabolism, Food, Lactic Acid metabolism, Bacillus coagulans metabolism
- Abstract
Agri-food residues offer significant potential as a raw material for the production of L-lactic acid through microbial fermentation. Weizmannia coagulans, previously known as Bacillus coagulans, is a spore-forming, lactic acid-producing, gram-positive, with known probiotic and prebiotic properties. This study aimed to evaluate the feasibility of utilizing untreated citrus waste as a sustainable feedstock for the production of L-lactic acid in a one-step process, by using the strain W. coagulans MA-13. By employing a thermophilic enzymatic cocktail (Cellic CTec2) in conjunction with the hydrolytic capabilities of MA-13, biomass degradation was enhanced by up to 62%. Moreover, batch and fed-batch fermentation experiments demonstrated the complete fermentation of glucose into L-lactic acid, achieving a concentration of up to 44.8 g/L. These results point to MA-13 as a microbial cell factory for one-step production of L-lactic acid, by combining cost-effective saccharification with MA-13 fermentative performance, on agri-food wastes. Moreover, the potential of this approach for sustainable valorization of agricultural waste streams is successfully proven. KEY POINTS: • Valorization of citrus waste, an abundant residue in Mediterranean countries. • Sustainable production of the L-( +)-lactic acid in one-step process. • Enzymatic pretreatment is a valuable alternative to the use of chemical., (© 2024. The Author(s).)
- Published
- 2024
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7. Layer-by-Layer-Coated Cellulose Fibers Enable the Production of Porous, Flame-Retardant, and Lightweight Materials.
- Author
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Marcioni M, Zhao M, Maddalena L, Pettersson T, Avolio R, Castaldo R, Wågberg L, and Carosio F
- Abstract
New sustainable materials produced by green processing routes are required in order to meet the concepts of circular economy. The replacement of insulating materials comprising flammable synthetic polymers by bio-based materials represents a potential opportunity to achieve this task. In this paper, low-density and flame-retardant (FR) porous fiber networks are prepared by assembling Layer-by-Layer (LbL)-functionalized cellulose fibers by means of freeze-drying. The LbL coating, encompassing chitosan and sodium hexametaphosphate, enables the formation of a self-sustained porous structure by enhancing fiber-fiber interactions during the freeze-drying process. Fiber networks prepared from 3 Bi-Layer (BL)-coated fibers contain 80% wt of cellulose and can easily self-extinguish the flame during flammability tests in vertical configuration while displaying extremely low combustion rates in forced combustion tests. Smoke release is 1 order of magnitude lower than that of commercially available polyurethane foams. Such high FR efficiency is ascribed to the homogeneity of the deposited assembly, which produces a protective exoskeleton at the air/cellulose interface. The results reported in this paper represent an excellent opportunity for the development of fire-safe materials, encompassing natural components where sustainability and performance are maximized.
- Published
- 2023
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8. Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins.
- Author
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Avolio R, Agliarulo I, Criscuolo D, Sarnataro D, Auriemma M, De Lella S, Pennacchio S, Calice G, Ng MY, Giorgi C, Pinton P, Cooperman BS, Landriscina M, Esposito F, and Matassa DS
- Subjects
- Humans, HSP90 Heat-Shock Proteins genetics, HSP90 Heat-Shock Proteins metabolism, Ribosomes genetics, Ribosomes metabolism, Peptide Chain Elongation, Translational genetics, Peptide Chain Elongation, Translational physiology, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Molecular Chaperones genetics, Molecular Chaperones metabolism, Neoplasms genetics, Neoplasms metabolism, Neoplasms pathology, Protein Biosynthesis genetics, Protein Biosynthesis physiology, Mitochondria genetics, Mitochondria metabolism
- Abstract
A complex interplay between mRNA translation and cellular respiration has been recently unveiled, but its regulation in humans is poorly characterized in either health or disease. Cancer cells radically reshape both biosynthetic and bioenergetic pathways to sustain their aberrant growth rates. In this regard, we have shown that the molecular chaperone TRAP1 not only regulates the activity of respiratory complexes, behaving alternatively as an oncogene or a tumor suppressor, but also plays a concomitant moonlighting function in mRNA translation regulation. Herein, we identify the molecular mechanisms involved, showing that TRAP1 (1) binds both mitochondrial and cytosolic ribosomes, as well as translation elongation factors; (2) slows down translation elongation rate; and (3) favors localized translation in the proximity of mitochondria. We also provide evidence that TRAP1 is coexpressed in human tissues with the mitochondrial translational machinery, which is responsible for the synthesis of respiratory complex proteins. Altogether, our results show an unprecedented level of complexity in the regulation of cancer cell metabolism, strongly suggesting the existence of a tight feedback loop between protein synthesis and energy metabolism, based on the demonstration that a single molecular chaperone plays a role in both mitochondrial and cytosolic translation, as well as in mitochondrial respiration., (© 2023 Avolio et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2023
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9. Preliminary Data on Essential and Non-essential Element Occurrence in Processed Animal Proteins from Insects.
- Author
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Pederiva S, Avolio R, Marchis D, Abete MC, and Squadrone S
- Subjects
- Animals, Preliminary Data, Insecta, Larva, Animal Feed analysis, Arsenic metabolism
- Abstract
Insects represent a valuable and environmentally friendly protein alternative in food and feed. The Farm to Fork strategy encouraged the reintroduction of animal by-products in feed production to optimise recycling and to valorise under-used resources. In order to grant safe and valuable feed products, this study investigated the black soldier fly (BSF) (Hermetia illucens) chemical risk. Samples collected in different steps of production (8 samples of substrate for culturing, 7 samples of larvae, 15 samples of protein meal, 18 samples of spent substrate) were analysed for microessential elements (chromium, copper, iron, nickel, selenium and zinc) and inorganic contaminants (aluminium, arsenic, cadmium, lead, tin and vanadium) by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). Microessential elements were found in the following order: Fe > Zn > Cu > Ni > Se > Cr (mg kg
-1 ). Non-essential element concentrations were found lower than the set limits according to the European Union Regulations. The growing demand for alternative protein sources for feed production could be partially compensated by black soldier fly (BSF) (Hermetia illucens) meal, as it appears a good source for high-quality proteins and microessential elements which play a pivotal role in animal growth. In the foreseeable future the current legislation and the official monitoring plans may be implemented and broaden, to focus and assess limits for upcoming matrices, and to ensure feed and food safety., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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10. Poly(lactic acid)/Plasticizer/Nano-Silica Ternary Systems: Properties Evolution and Effects on Degradation Rate.
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Capuano R, Avolio R, Castaldo R, Cocca M, Dal Poggetto G, Gentile G, and Errico ME
- Abstract
Plasticized nanocomposites based on poly(lactic acid) have been prepared by melt mixing following a two-step approach, adding two different oligomeric esters of lactic acid (OLAs) as plasticizers and fumed silica nanoparticles. The nanocomposites maintained a remarkable elongation at break in the presence of the nanoparticles, with no strong effects on modulus and strength. Measuring thermo-mechanical properties as a function of aging time revealed a progressive deterioration of properties, with the buildup of phase separation, related to the nature of the plasticizer. Materials containing hydroxyl-terminated OLA showed a higher stability of properties upon aging. On the contrary, a synergistic effect of the acid-terminated plasticizer and silica nanoparticles was pointed out, inducing an accelerated hydrolytic degradation of PLA: materials at high silica content exhibited a marked brittleness and a dramatic decrease of molecular weight after 16 weeks of aging.
- Published
- 2023
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11. Sustainable and Green Production of Nanostructured Cellulose by a 2-Step Mechano-Enzymatic Process.
- Author
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Aulitto M, Castaldo R, Avolio R, Errico ME, Xu YQ, Gentile G, and Contursi P
- Abstract
Nanostructured cellulose (NC) represents an emerging sustainable biomaterial for diverse biotechnological applications; however, its production requires hazardous chemicals that render the process ecologically unfriendly. Using commercial plant-derived cellulose, an innovative strategy for NC production based on the combination of mechanical and enzymatic approaches was proposed as a sustainable alternative to conventional chemical procedures. After ball milling, the average length of the fibers was reduced by one order of magnitude (down to 10-20 μm) and the crystallinity index decreased from 0.54 to 0.07-0.18. Moreover, a 60 min ball milling pre-treatment followed by 3 h Cellic Ctec2 enzymatic hydrolysis led to NC production (15% yield). Analysis of the structural features of NC obtained by the mechano-enzymatic process revealed that the diameters of the obtained cellulose fibrils and particles were in the range of 200-500 nm and approximately 50 nm, respectively. Interestingly, the film-forming property on polyethylene (coating ≅ 2 μm thickness) was successfully demonstrated and a significant reduction (18%) of the oxygen transmission rate was obtained. Altogether, these findings demonstrated that nanostructured cellulose could be successfully produced using a novel, cheap, and rapid 2-step physico-enzymatic process that provides a potential green and sustainable route that could be exploitable in future biorefineries.
- Published
- 2023
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12. Optimization and validation of a quick and responsive LC-ESI-MS/MS method to evaluate tetracycline residues in processed animal proteins (PAPs).
- Author
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Morello S, Pederiva S, Avolio R, Squadrone S, Abete MC, and Marchis D
- Subjects
- Animals, Cattle, Chromatography, Liquid methods, Proteins, Anti-Bacterial Agents, Tetracyclines analysis, Chromatography, High Pressure Liquid, Tandem Mass Spectrometry methods, Tetracycline
- Abstract
Following the bovine spongiform encephalopathy (BSE) in 2001, processed animal proteins (PAPs) reintroduction is envisaged in non-ruminant feed thanks to their high protein content, easy availability and cost-effective characteristics. PAPs must be submitted to rendering practices, providing sterilization of products, under standardized conditions of temperature and pressure, according to Regulation (EC) No 142/2011. However, the chemical risk associated to these raw materials has been never evaluated. The aim of this study was to develop and validate a reliable liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of tetracycline residues in PAPs at µg kg
-1 level. The LC-MS/MS method performances were evaluated in terms of specificity, linearity (25-500 µg kg-1 ), limit of quantitation (LOQ) (25 µg kg-1 ), accuracy and precision (CV% < 25%), uncertainty, recovery (80-120%) and ruggedness. All the evaluated parameters fulfilled the analytical performance criteria, and the validated LC-MS/MS method fits for purpose as confirmatory method on the occurrence of residues (µg kg-1 ) of tetracyclines in PAPs. PAPs are a powerful product which could be used both as raw materials in feed and in organic fertilizer production in a circular economy context. Therefore, the lack of regulation and control over antibiotic occurrence should be implemented to avoid a misuse and an increment of antibiotic resistance pressure over the environment and to ensure safety of the feed and food chain., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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13. Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins.
- Author
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Avolio R, Agliarulo I, Criscuolo D, Sarnataro D, Auriemma M, Pennacchio S, Calice G, Ng MY, Giorgi C, Pinton P, Cooperman B, Landriscina M, Esposito F, and Matassa DS
- Abstract
A complex interplay between mRNA translation and cellular respiration has been recently unveiled, but its regulation in humans is poorly characterized in either health or disease. Cancer cells radically reshape both biosynthetic and bioenergetic pathways to sustain their aberrant growth rates. In this regard, we have shown that the molecular chaperone TRAP1 not only regulates the activity of respiratory complexes, behaving alternatively as an oncogene or a tumor suppressor, but also plays a concomitant moonlighting function in mRNA translation regulation. Herein we identify the molecular mechanisms involved, demonstrating that TRAP1: i) binds both mitochondrial and cytosolic ribosomes as well as translation elongation factors, ii) slows down translation elongation rate, and iii) favors localized translation in the proximity of mitochondria. We also provide evidence that TRAP1 is coexpressed in human tissues with the mitochondrial translational machinery, which is responsible for the synthesis of respiratory complex proteins. Altogether, our results show an unprecedented level of complexity in the regulation of cancer cell metabolism, strongly suggesting the existence of a tight feedback loop between protein synthesis and energy metabolism, based on the demonstration that a single molecular chaperone plays a role in both mitochondrial and cytosolic translation, as well as in mitochondrial respiration.
- Published
- 2023
- Full Text
- View/download PDF
14. A versatile approach to evaluate the occurrence of microfibers in mussels Mytilus galloprovincialis.
- Author
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Volgare M, Santonicola S, Cocca M, Avolio R, Castaldo R, Errico ME, Gentile G, Raimo G, Gasperi M, and Colavita G
- Subjects
- Animals, Humans, Plastics analysis, Environmental Monitoring, Seafood analysis, Mytilus, Water Pollutants, Chemical analysis
- Abstract
Microplastics of fibrous shape are esteemed to be the most abundant micro-debris form present in the environment. Despite the occurrence of microfibers in fish may pose a risk to human health, the literature is scarce regarding studies on the contamination in commercial marine fish mostly due to methodological issues. In this study, a versatile approach, able to discriminate among natural and synthetic microfibers according to the evaluation of specific morphological features, is proposed in farmed mussels (Mytilus galloprovincialis). The approach was useful to determine that microfibers were present in 74% of mussel samples, with a mean number of 14.57 microfibers/individual, corresponding to 3.13 microfibers/g w.w. A negative correlation between the size of analysed mussels and the amount of microfibers/g w.w. was detected, showing that smaller specimens contained more microfibers than the larger ones. This work paves the way to further studies aimed to adequately assess the risk that microfibers may pose to marine biota, also considering the commercial value as seafood items of many species of the Mytilus genus and the potential implication for human exposure., (© 2022. The Author(s).)
- Published
- 2022
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15. Regulation of mitochondrial complex III activity and assembly by TRAP1 in cancer cells.
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Matassa DS, Criscuolo D, Avolio R, Agliarulo I, Sarnataro D, Pacelli C, Scrima R, Colamatteo A, Matarese G, Capitanio N, Landriscina M, and Esposito F
- Abstract
Background: Metabolic reprogramming is an important issue in tumor biology. A recently-identified actor in this regard is the molecular chaperone TRAP1, that is considered an oncogene in several cancers for its high expression but an oncosuppressor in others with predominant oxidative metabolism. TRAP1 is mainly localized in mitochondria, where it interacts with respiratory complexes, although alternative localizations have been described, particularly on the endoplasmic reticulum, where it interacts with the translational machinery with relevant roles in protein synthesis regulation., Results: Herein we show that, inside mitochondria, TRAP1 binds the complex III core component UQCRC2 and regulates complex III activity. This decreases respiration rate during basal conditions but allows sustained oxidative phosphorylation when glucose is limiting, a condition in which the direct TRAP1-UQCRC2 binding is disrupted, but not TRAP1-complex III binding. Interestingly, several complex III components and assembly factors show an inverse correlation with survival and response to platinum-based therapy in high grade serous ovarian cancers, where TRAP1 inversely correlates with stage and grade and directly correlates with survival. Accordingly, drug-resistant ovarian cancer cells show high levels of complex III components and high sensitivity to complex III inhibitory drug antimycin A., Conclusions: These results shed new light on the molecular mechanisms involved in TRAP1-dependent regulation of cancer cell metabolism and point out a potential novel target for metabolic therapy in ovarian cancer., (© 2022. The Author(s).)
- Published
- 2022
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16. Polystyrene nanoplastics affect the human ubiquitin structure and ubiquitination in cells: a high-resolution study.
- Author
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Della Valle M, D'Abrosca G, Gentile MT, Russo L, Isernia C, Di Gaetano S, Avolio R, Castaldo R, Cocca M, Gentile G, Malgieri G, Errico ME, and Fattorusso R
- Abstract
Humans are estimated to consume several grams per week of nanoplastics (NPs) through exposure to a variety of contamination sources. Nonetheless, the effects of these polymeric particles on living systems are still mostly unknown. Here, by means of CD, NMR and TEM analyses, we describe at an atomic resolution the interaction of ubiquitin with polystyrene NPs (PS-NPs), showing how a hard protein corona is formed. Moreover, we report that in human HeLa cells exposure to PS-NPs leads to a sensible reduction of ubiquitination. Our study overall indicates that PS-NPs cause significant structural effects on ubiquitin, thereby influencing one of the key metabolic processes at the base of cell viability., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2022
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17. Decreased Levels of GSH Are Associated with Platinum Resistance in High-Grade Serous Ovarian Cancer.
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Criscuolo D, Avolio R, Parri M, Romano S, Chiarugi P, Matassa DS, and Esposito F
- Abstract
High-grade serous ovarian cancer (HGSOC) is the most common and aggressive OC histotype. Although initially sensitive to standard platinum-based chemotherapy, most HGSOC patients relapse and become chemoresistant. We have previously demonstrated that platinum resistance is driven by a metabolic shift toward oxidative phosphorylation via activation of an inflammatory response, accompanied by reduced cholesterol biosynthesis and increased uptake of exogenous cholesterol. To better understand metabolic remodeling in OC, herein we performed an untargeted metabolomic analysis, which surprisingly showed decreased reduced glutathione (GSH) levels in resistant cells. Accordingly, we found reduced levels of enzymes involved in GSH synthesis and recycling, and compensatory increased expression of thioredoxin reductase. Cisplatin treatment caused an increase of reduced GSH, possibly due to direct binding hindering its oxidation, and consequent accumulation of reactive oxygen species. Notably, expression of the cysteine-glutamate antiporter xCT, which is crucial for GSH synthesis, directly correlates with post-progression survival of HGSOC patients, and is significantly reduced in patients not responding to platinum-based therapy. Overall, our data suggest that cisplatin treatment could positively select cancer cells which are independent from GSH for the maintenance of redox balance, and thus less sensitive to cisplatin-induced oxidative stress, opening new scenarios for the GSH pathway as a therapeutic target in HGSOC.
- Published
- 2022
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18. Glyceroltriheptanoate (GTH) occurrence in animal by-products: a monitoring study to minimise safety-related risk of misuse.
- Author
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Pederiva S, Avolio R, Morello S, Abete MC, and Marchis D
- Subjects
- Animal Feed analysis, Animals, Cattle, Meat analysis, Minerals, Triglycerides analysis, Biological Products, Encephalopathy, Bovine Spongiform epidemiology
- Abstract
Early in this century, the crisis connected to the spread of bovine spongiform encephalopathy caused a great concern related to the use of animal by-products (ABPs). According to the Commission Regulation (EU) No 1069/2009, these materials are classified in three categories according to their related risk. In 2011 Commission Regulation (EU) No 142/2011 established that meat and bone meal (MBM) and fat deriving from ABPs not intended for human consumption (category 1 and 2) are required to be permanently marked with glyceroltriheptanoate (GTH), at a minimum concentration of 250 mg kg
-1 of fat, while category 3 processed animal proteins (PAPs) must not contain this compound. PAPs are bio resources, which could be used in a renewable and regenerative way in a circular economy model for a conscious usage of raw materials. The aim of this study was to provide information on GTH occurrence in MBM and, if any, in PAPs. Samples were collected from 2017 to 2021 and analysed by GC-MS. Detected non-compliant samples were exclusively of MBM category 1 and 2, probably due to the addition of an inadequate amount of GTH during the manufacturing processes. These results highlighted the importance of National Monitoring Programs as a useful tool to minimise safety related risk due to the misuse of GTH. Thus, investigating the critical points in feed supply-chain and sharing the information on its occurrence may help to improve animal and human wellness and safety.- Published
- 2022
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19. Sustainable Cellulose-Aluminum-Plastic Composites from Beverage Cartons Scraps and Recycled Polyethylene.
- Author
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Bonadies I, Capuano R, Avolio R, Castaldo R, Cocca M, Gentile G, and Errico ME
- Abstract
The sustainable management of multilayer paper/plastic waste is a technological challenge due to its composite nature. In this paper, a mechanical recycling approach for multilayer cartons (MC) is reported, illustrating the realization of thermoplastic composites based on recycled polyethylene and an amount of milled MC ranging from 20 to 90 wt%. The effect of composition of the composites on the morphology and on thermal, mechanical, and water absorption behavior was investigated and rationalized, demonstrating that above 80 wt% of MC, the fibrous nature of the filler dominates the overall properties of the materials. A maleated polyethylene was also used as a coupling agent and its effectiveness in improving mechanical parameters of composites up to 60 wt% of MC was highlighted.
- Published
- 2022
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20. Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1.
- Author
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Avolio R, Inglés-Ferrándiz M, Ciocia A, Coll O, Bonnin S, Guitart T, Ribó A, and Gebauer F
- Subjects
- Animals, Cell Cycle Checkpoints genetics, Cell Cycle Checkpoints physiology, Cell Line, Cell Proliferation physiology, Cellular Senescence genetics, DNA-Binding Proteins physiology, Female, Gene Expression genetics, Gene Expression Regulation genetics, Humans, Keratinocytes metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Nude, Oncogenes genetics, Primary Cell Culture, RNA Processing, Post-Transcriptional physiology, RNA-Binding Proteins physiology, Senescence-Associated Secretory Phenotype genetics, Senescence-Associated Secretory Phenotype physiology, Signal Transduction physiology, Y-Box-Binding Protein 1 metabolism, Cellular Senescence physiology, DNA-Binding Proteins metabolism, RNA-Binding Proteins metabolism
- Abstract
Oncogene-induced senescence (OIS) is a form of stable cell-cycle arrest arising in response to oncogenic stimulation. OIS must be bypassed for transformation, but the mechanisms of OIS establishment and bypass remain poorly understood, especially at the post-transcriptional level. Here, we show that the RNA-binding protein UNR/CSDE1 enables OIS in primary mouse keratinocytes. Depletion of CSDE1 leads to senescence bypass, cell immortalization, and tumor formation, indicating that CSDE1 behaves as a tumor suppressor. Unbiased high-throughput analyses uncovered that CSDE1 promotes OIS by two independent molecular mechanisms: enhancement of the stability of senescence-associated secretory phenotype (SASP) factor mRNAs and repression of Ybx1 mRNA translation. Importantly, depletion of YBX1 from immortal keratinocytes rescues senescence and uncouples proliferation arrest from the SASP, revealing multilayered mechanisms exerted by CSDE1 to coordinate senescence. Our data highlight the relevance of post-transcriptional control in the regulation of senescence., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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21. Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy.
- Author
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Criscuolo D, Avolio R, Matassa DS, and Esposito F
- Abstract
Extensive metabolic remodeling is a fundamental feature of cancer cells. Although early reports attributed such remodeling to a loss of mitochondrial functions, it is now clear that mitochondria play central roles in cancer development and progression, from energy production to synthesis of macromolecules, from redox modulation to regulation of cell death. Biosynthetic pathways are also heavily affected by the metabolic rewiring, with protein synthesis dysregulation at the hearth of cellular transformation. Accumulating evidence in multiple organisms shows that the metabolic functions of mitochondria are tightly connected to protein synthesis, being assembly and activity of respiratory complexes highly dependent on de novo synthesis of their components. In turn, protein synthesis within the organelle is tightly connected with the cytosolic process. This implies an entire network of interactions and fine-tuned regulations that build up a completely under-estimated level of complexity. We are now only preliminarily beginning to reconstitute such regulatory level in human cells, and to perceive its role in diseases. Indeed, disruption or alterations of these connections trigger conditions of proteotoxic and energetic stress that could be potentially exploited for therapeutic purposes. In this review, we summarize the available literature on the coordinated regulation of mitochondrial and cytosolic mRNA translation, and their effects on the integrity of the mitochondrial proteome and functions. Finally, we highlight the potential held by this topic for future research directions and for the development of innovative therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Criscuolo, Avolio, Matassa and Esposito.)
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- 2021
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22. Washing load influences the microplastic release from polyester fabrics by affecting wettability and mechanical stress.
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Volgare M, De Falco F, Avolio R, Castaldo R, Errico ME, Gentile G, Ambrogi V, and Cocca M
- Abstract
Microplastics released from textiles during the washing process represent the most prevalent type of microparticles found in different environmental compartments and ecosystems around the world. Release of microfibres during the washing process of synthetic textiles is due to the mechanical and chemical stresses that clothes undergo in washing machines. Several washing process parameters, conditions, formulations of laundering additives have been correlated to microfibre release and some of them have been identified to affect microfibre release during washing process, while no correlation has been evaluated between microfibre release and washing load. In the present study, microfibre release was evaluated as function of the washing load in a real washing process, indicating a progressive decrease of microfibre release with increasing washing load. The quantity of released microfibres increased by around 5 times by decreasing the washing load due to a synergistic effect between water-volume to fabric ratio and mechanical stress during washing. Moreover, the higher mechanical stress to which the fabric is subjected in the case of a low washing load, hinders the discrimination of the effect on the release of other washing parameters like the type of detergent and laundry additives used., (© 2021. The Author(s).)
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- 2021
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23. Valorization and Mechanical Recycling of Heterogeneous Post-Consumer Polymer Waste through a Mechano-Chemical Process.
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Capuano R, Bonadies I, Castaldo R, Cocca M, Gentile G, Protopapa A, Avolio R, and Errico ME
- Abstract
In this paper, a sustainable strategy to valorize and recycle heterogeneous polymer-based post-consumer waste is proposed. This strategy is based on a high-energy mechano-chemical treatment and has been applied to a polyolefin-rich fraction, coded as FIL/S, deriving from household plastic waste collection. This processing, performed in a planetary ball mill, allowed us to obtain fine grinding and, consequently, to induce an intimate mixing of the different polymer fractions and contaminants composing the FIL/S, as demonstrated by SEM analysis. As a result, an improvement in the deformability of the treated material was obtained, recording values for elongation at the break which were two and half times higher than the neat FIL/S. Finally, the addition of small amounts of organic peroxide during mechano-chemical treatment was tested, determining a more homogeneous morphology and a further improvement in mechanical parameters.
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- 2021
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24. O/W Pickering Emulsions Stabilized with Cellulose Nanofibrils Produced through Different Mechanical Treatments.
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Pirozzi A, Capuano R, Avolio R, Gentile G, Ferrari G, and Donsì F
- Abstract
This work aimed at studying the stabilization of O/W Pickering emulsions using nanosized cellulosic material, produced from raw cellulose or tomato pomace through different mechanical treatments, such as ball milling (BM) and high-pressure homogenization (HPH). The cellulose nanofibrils obtained via HPH, which exhibited longer fibers with higher flexibility than those obtained via ball milling, are characterized by lower interfacial tension values and higher viscosity, as well as better emulsion stabilization capability. Emulsion stability tests, carried out at 4 °C for 28 d or under centrifugation at different pH values (2.0, 7.0, and 12.0), revealed that HPH-treated cellulose limited the occurrence of coalescence phenomena and significantly slowed down gravitational separation in comparison with BM-treated cellulose. HPH-treated cellulose was responsible for the formation of a 3D network structure in the continuous phase, entrapping the oil droplets also due to the affinity with the cellulose nanofibrils, whereas BM-treated cellulose produced fibers with a more compact structure, which did adequately cover the oil droplets. HPH-treated tomato pomace gave similar results in terms of particle morphology and interfacial tension, and slightly lower emulsion stabilization capability than HPH-treated cellulose, suggesting that the used mechanical disruption process does not require cellulose isolation for its efficient defibrillation.
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- 2021
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25. Comparison of biodegradable polyesters degradation behavior in sand.
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De Falco F, Avolio R, Errico ME, Di Pace E, Avella M, Cocca M, and Gentile G
- Subjects
- Kinetics, Polymers, Polyesters, Sand
- Abstract
Sandy beaches represent environmental compartments particularly vulnerable to litter pollution, and they reflect the magnitude of pollution of adjacent compartments: water and coastal areas. The substitution of conventional polymers by biodegradable materials is generally considered as an alternative for reducing environmental accumulation of plastic debris. The present study is aimed to investigate the degradation of poly(lactic acid), poly(ε-caprolactone), poly(butylenesuccinate adipate) and poly(3-hydroxybutyrate) buried in sand for 267 days, simulating them as beach litter. The analysed polyesters showed different degradation mechanisms and kinetics. PLA is mainly subjected to weathering by physical aging; after an initial faster degradation of the amorphous phase, PCL showed a decrease of its degradation rate; similarly to PCL, the degradation of PBSA started from the amorphous phase; PHB is clearly subjected to biological degradation. The degradation trend of the investigated materials in sand decreased in the order PHB > PBSA > PCL > PLA. PLA, PCL and PBSA did not undergo complete degradation in sand during the testing time., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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26. Ecology of oxidative stress in the Danube barbel (Barbus balcanicus) from a winegrowing district: Effects of water parameters, trace and rare earth elements on biochemical biomarkers.
- Author
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Pastorino P, Pizzul E, Barceló D, Abete MC, Magara G, Brizio P, Avolio R, Bertoli M, Dondo A, Prearo M, and Elia AC
- Subjects
- Animals, Biomarkers metabolism, Catalase metabolism, Ecosystem, Gills metabolism, Glutathione Transferase metabolism, Italy, Oxidative Stress, Superoxide Dismutase metabolism, Water, Cyprinidae metabolism, Water Pollutants, Chemical analysis, Water Pollutants, Chemical toxicity
- Abstract
Fish can be highly vulnerable to environmental pressures because they are exposed to oxidative stressors in the aquatic environment. Such stressors can affect the levels of antioxidant biomarkers against reactive oxygen species (ROS). With this study we investigated the oxidative stress ecology in Danube barbel (Barbus balcanicus) from the Barbucina creek (northeast Italy), a watercourse in the Collio winegrowing district. To do this, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) activity was measured in gills, liver, and muscle, while metallothioneins (MT) and trace and rare earth elements (REEs) levels were determined in muscle. The effect of environmental factors (physicochemical parameters of water, trace elements and REEs) on oxidative stress biomarkers was thus assessed. High concentrations were determined for cerium (Ce), scandium (Sc), neodymium (Nd), lanthanum (La), yttrium (Y), and praseodymium (Pr) among the REEs. Among the trace elements, arsenic (As), copper (Cu), and mercury (Hg) levels were higher compared to published data, suggesting their role as stressors. The multiple linear regression (MLR) model showed a statistically significant association (R
2 = 0.858; F = 10.07; p = 0.015) between As, Cu, Hg, and Pr and SOD activity in the gills, indicating a functional relationship between them. Differently, CAT activity was significantly higher in the liver, probably in response to long-term Cu contamination of the watercourse. This was confirmed by the MLR model that showed a significant association (R2 = 0.638; F = 8.152; p = 0.02) between the concentration of MT and of Cu. Our data show a biochemical defensive response by Danube barbel to the disturbances in the aquatic ecosystem of the Barbucina creek. These insights advance our understanding of the role and the effects of environmental factors as trace elements and REEs on oxidative stress in fish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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27. Retrospective data analysis of animal poisoning events in Liguria.
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Avolio R, Andreoli T, Ercolini C, Mignone W, Beltrame R, Razzuoli E, Modesto P, Zoppi S, Crescio MI, Ostorero F, Gili M, Abete MC, Meloni D, and Dellepiane M
- Abstract
Intentional poisoning represents a serious risk to domestic and wild animals, and it can be an environmental and human health issue as well . This paper is a retrospective study, which covers a decade, based on animal poisoning cases and poisoned baits that were submitted for diagnostic examinations to the Veterinary Medical Research Institute for Piedmont, Liguria and the Aosta Valley (IZS-PLVA) in Liguria region. All data were collected through a passive surveillance system introduced in Italy by a decree of the Ministry of Health in January 2009. 43.2% of the animal poisoning cases were confirmed by toxicological analysis, whereas toxic agents were detected in 31.1% of the baits. The most affected animal species were dogs and cats, followed by synanthropic birds,. Only 4% of the total poisoning events analysed involved wild animals and cases of livestock poisoning were minimal. An increased number of cases in January, March, April and August was noticed, but no seasonal trend was detected. The most affected areas were the ones with the highest level of urbanization and population density. The major cause of the poisonings and the most common substances detected in the examined baits were anticoagulants whereas cholinesterase inhibitors, organochlorine pesticides and carbamates were detected in a minor number of cases. This study raises concerns about deliberate animal poisoning in ligurian region and highlights the necessity to fight this phenomenon as it endangers animals, humans and environment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)
- Published
- 2021
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28. The quest for long non-coding RNAs involved in aging.
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Avolio R, Bechara E, and Tartaglia GG
- Subjects
- Signal Transduction, NF-kappa B, RNA, Long Noncoding genetics, MicroRNAs
- Published
- 2021
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29. Tetracyclines in Processed Animal Proteins: A Monitoring Study on Their Occurrence and Antimicrobial Activity.
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Morello S, Pederiva S, Avolio R, Amato G, Zoppi S, Di Blasio A, Abete MC, Casalone C, Desiato R, Ru G, and Marchis D
- Abstract
In 2013, the European Union (EU) lifted the feed ban restriction, authorizing the use of non-ruminant (NR) processed animal proteins (PAPs) as ingredient in aquafeed. A further relaxation is soon expected, and NR PAPs will be allowed in next future in poultry and pig feed, avoiding cannibalism. Other potential hazards linked to PAPs as raw material should be evaluated. Antibiotics administered along the lifecycle of animals may leave residue in tissues and bones and still be present in PAPs. This monitoring study aimed to determine tetracyclines (TCLs), known to cumulate in bones, in PAPs and their possible residual antibiotic activity (RAC). A sensitive Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) method for the quantification of TCLs in PAPs was developed and applied to 55 PAPs from EU manufactures. Most PAP samples ( n = 40) contained TCLs (concentrations 25.59 ÷ 456.84 µg kg
-1 ). Among samples containing more than 25 µg kg-1 for at least three TCLs, three PAPs were chosen for RAC test before and after TCLs extraction procedure applying an in vitro acidic digestion: in two out of those three samples, RAC was observed after in vitro digestion. TCLs were determined in the digested PAPs (concentrations 26.07 ÷ 64.55 µg kg-1 ). The detection of TCLs in PAPs should promptly target the risk assessments of this unconsidered way of exposure to antibiotic residues.- Published
- 2021
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30. Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression.
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Parisi S, Castaldo D, Piscitelli S, D'Ambrosio C, Divisato G, Passaro F, Avolio R, Castellucci A, Gianfico P, Masullo M, Scaloni A, and Russo T
- Subjects
- 3' Untranslated Regions genetics, 3' Untranslated Regions physiology, Blotting, Western, Chromatography, Gel, DNA (Cytosine-5-)-Methyltransferases genetics, DNA Methyltransferase 3A, Humans, Immunoprecipitation, RNA-Binding Proteins genetics, DNA (Cytosine-5-)-Methyltransferases metabolism, Proteomics methods, RNA-Binding Proteins metabolism
- Abstract
Lin28 is an evolutionary conserved RNA-binding protein that plays important roles during embryonic development and tumorigenesis. It regulates gene expression through two different post-transcriptional mechanisms. The first one is based on the regulation of miRNA biogenesis, in particular that of the let-7 family, whose expression is suppressed by Lin28. Thus, loss of Lin28 leads to the upregulation of mRNAs that are targets of let-7 species. The second mechanism is based on the direct interaction of Lin28 with a large number of mRNAs, which results in the regulation of their translation. This second mechanism remains poorly understood. To address this issue, we purified high molecular weight complexes containing Lin28a in mouse embryonic stem cells (ESCs). Numerous proteins, co-purified with Lin28a, were identified by proteomic procedures and tested for their possible role in Lin28a-dependent regulation of the mRNA encoding DNA methyltransferase 3a (Dnmt3a). The results show that Lin28a activity is dependent on many proteins, including three helicases and four RNA-binding proteins. The suppression of four of these proteins, namely Ddx3x, Hnrnph1, Hnrnpu or Syncrip, interferes with the binding of Lin28a to the Dnmt3a mRNA, thus suggesting that they are part of an oligomeric ribonucleoprotein complex that is necessary for Lin28a activity.
- Published
- 2021
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31. Environmental life cycle assessment of the recycling processes of waste plastics recovered by landfill mining.
- Author
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Cappucci GM, Avolio R, Carfagna C, Cocca M, Gentile G, Scarpellini S, Spina F, Tealdo G, Errico ME, and Ferrari AM
- Subjects
- Mining, Plastics, Recycling, Waste Disposal Facilities, Petroleum, Waste Management
- Abstract
Enhanced Landfill Mining (ELFM) is a powerful tool for the sustainable management of landfill sites, aiming at both land reclamation and material recovery/reuse. To enhance the recovery and recycling rate of excavated plastic fractions, in most cases destined to energy recovery, new convenient, effective and sustainable strategies are needed. In this study, a recovery and valorization process of ELFM excavated plastics has been validated through an integrated experimental and Life Cycle Assessment (LCA) approach, demonstrating the environmental sustainability of the secondary raw material generated, in terms of use of resources and emissions generated. In particular, the secondary granulate from ELFM was compared with a virgin product and the last one resulted to have a higher impact (more than 4.46 times greater than the first one), in particular for the use of the resource crude oil as raw material in the production of primary LDPE. The valorization process of the excavated plastic made the mechanical properties of the secondary raw material comparable to that of a primary material., Competing Interests: Declaration of Competing Interest Patent of one of the authors (Gianluigi Tealdo). Tealdo, G., 2018. Procedimento per la bonifica di discariche. patent nr. 102015000089311 of italian Ministry of Economic Development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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32. Hyper-Crosslinked Polymer Nanocomposites Containing Mesoporous Silica Nanoparticles with Enhanced Adsorption Towards Polar Dyes.
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Guerritore M, Castaldo R, Silvestri B, Avolio R, Cocca M, Errico ME, Avella M, Gentile G, and Ambrogi V
- Abstract
The development of new styrene-based hyper-crosslinked nanocomposites (HCLN) containing mesoporous silica nanoparticles (MSN) is reported here as a new strategy to obtain functional high surface area materials with an enhanced hydrophilic character. The HCLN composition, morphology and porous structure were analyzed using a multi-technique approach. The HCLN displayed a high surface area (above 1600 m
2 /g) and higher microporosity than the corresponding hyper-crosslinked neat resin. The enhanced adsorption properties of the HCLN towards polar organic dyes was demonstrated through the adsorption of a reactive dye, Remazol Brilliant Blue R (RB). In particular, the HCLN containing 5phr MSN showed the highest adsorption capacity of RB.- Published
- 2020
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33. Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer.
- Author
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Criscuolo D, Avolio R, Calice G, Laezza C, Paladino S, Navarra G, Maddalena F, Crispo F, Pagano C, Bifulco M, Landriscina M, Matassa DS, and Esposito F
- Subjects
- Cell Line, Tumor, Cisplatin pharmacology, Drug Resistance, Neoplasm drug effects, Female, HSP90 Heat-Shock Proteins metabolism, Humans, Inflammation metabolism, Inflammation pathology, Lipase metabolism, Lipid Metabolism drug effects, Models, Biological, Oxidative Stress drug effects, Cholesterol metabolism, Cisplatin therapeutic use, Homeostasis, Ovarian Neoplasms drug therapy, Ovarian Neoplasms metabolism
- Abstract
Despite initial chemotherapy response, ovarian cancer is the deadliest gynecologic cancer, due to frequent relapse and onset of drug resistance. To date, there is no affordable diagnostic/prognostic biomarker for early detection of the disease. However, it has been recently shown that high grade serous ovarian cancers show peculiar oxidative metabolism, which is in turn responsible for inflammatory response and drug resistance. The molecular chaperone TRAP1 plays pivotal roles in such metabolic adaptations, due to the involvement in the regulation of mitochondrial respiration. Here, we show that platinum-resistant ovarian cancer cells also show reduced cholesterol biosynthesis, and mostly rely on the uptake of exogenous cholesterol for their needs. Expression of FDPS and OSC, enzymes involved in cholesterol synthesis, are decreased both in drug-resistant cells and upon TRAP1 silencing, whereas the expression of LDL receptor, the main mediator of extracellular cholesterol uptake, is increased. Strikingly, treatment with statins to inhibit cholesterol synthesis reduces cisplatin-induced apoptosis, whereas silencing of LIPG, an enzyme involved in lipid metabolism, or withdrawal of lipids from the culture medium, increases sensitivity to the drug. These results suggest caveats for the use of statins in ovarian cancer patients and highlights the importance of lipid metabolism in ovarian cancer treatment.
- Published
- 2020
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34. Local context and environment as risk factors for acute poisoning in animals in northwest Italy.
- Author
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Di Blasio A, Bertolini S, Gili M, Avolio R, Leogrande M, Ostorero F, Ru G, Dondo A, and Zoppi S
- Subjects
- Agriculture, Animals, Italy, Poisons, Risk Factors, Insecticides analysis
- Abstract
Animal and bait poisoning data for northwest Italy collected between 2012 and 2017 were described and analyzed to estimate the risk of exposure to hazardous substances by animals. In about 4% of animals necropsied (n = 356/9512), the cause of death was poisoning and domestic pets (9.5%) and synanthropic animals (12.2%) appear to be the most involved. Furthermore, 294 out of 728 baits (40.4%) were positive for toxic substances and/or inert hazardous material. Application of a mixed-effects Poisson regression model and local cluster analysis evidenced increased risk of exposure to poisoning with altimetry (>600 m.a.s.l.) and municipality (PR = 1.6, 95%CI 1.2-2.1 for poisoning, PR = 2.2, 95%CI 1.2-4.2 for poisoning by insecticides and PR = 2.9, 95%CI 1.4-6.2 for poisoning by metaldehyde). Since the mountainous areas in the region are mostly devoted to pasture and extensive farming, the high frequency of animal and bait poisoning events may be related to farmers' need to protect their livestock and crops against foxes, wolves, rodents or wild boars. Summarizing, the type of land use and context may influence the frequency and type of toxin chosen to kill animals considered a nuisance for hunting, farming, agriculture and apiculture. Despite bans and limitations, the use of harmful substances is not perceived as an environmental threat but rather as routine pest control. Animal and bait poisoning constitute a public health concern because it is potentially harmful to humans and the environment. Our findings may inform risk communication strategies, as well as prevention and control measures for the reduction of illegal and non-targeted species poisoning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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35. Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer.
- Author
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Avolio R, Matassa DS, Criscuolo D, Landriscina M, and Esposito F
- Subjects
- Animals, Antineoplastic Agents therapeutic use, Energy Metabolism drug effects, HSP90 Heat-Shock Proteins metabolism, Humans, Metabolic Networks and Pathways drug effects, Mitochondria metabolism, Molecular Targeted Therapy, Neoplasms metabolism, Antineoplastic Agents pharmacology, Drug Resistance, Neoplasm drug effects, Mitochondria drug effects, Neoplasms drug therapy, Oxidative Stress drug effects
- Abstract
Metabolic reprogramming, carried out by cancer cells to rapidly adapt to stress such as hypoxia and limited nutrient conditions, is an emerging concepts in tumor biology, and is now recognized as one of the hallmarks of cancer. In contrast with conventional views, based on the classical Warburg effect, these metabolic alterations require fully functional mitochondria and finely-tuned regulations of their activity. In turn, the reciprocal regulation of the metabolic adaptations of cancer cells and the microenvironment critically influence disease progression and response to therapy. This is also realized through the function of specific stress-adaptive proteins, which are able to relieve oxidative stress, inhibit apoptosis, and facilitate the switch between metabolic pathways. Among these, the molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1), the most abundant heat shock protein 90 (HSP90) family member in mitochondria, is particularly relevant because of its role as an oncogene or a tumor suppressor, depending on the metabolic features of the specific tumor. This review highlights the interplay between metabolic reprogramming and cancer progression, and the role of mitochondrial activity and oxidative stress in this setting, examining the possibility of targeting pathways of energy metabolism as a therapeutic strategy to overcome drug resistance, with particular emphasis on natural compounds and inhibitors of mitochondrial HSP90s., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
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36. Critical Factors for the Recycling of Different End-of-Life Materials: Wood Wastes, Automotive Shredded Residues, and Dismantled Wind Turbine Blades.
- Author
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Castaldo R, De Falco F, Avolio R, Bossanne E, Cicaroni Fernandes F, Cocca M, Di Pace E, Errico ME, Gentile G, Jasiński D, Spinelli D, Albein Urios S, Vilkki M, and Avella M
- Abstract
Different classes of wastes, namely wooden wastes, plastic fractions from automotive shredded residues, and glass fiber reinforced composite wastes obtained from dismantled wind turbines blades were analyzed in view of their possible recycling. Wooden wastes included municipal bulky wastes, construction and demolition wastes, and furniture wastes. The applied characterization protocol, based on Fourier transform infrared (FTIR) spectroscopy in attenuated total reflection (ATR) mode, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDX), and thermogravimetric analysis (TG) coupled with FTIR spectrometry for the investigation of the evolved gases, revealed that the selected classes of wastes are very complex and heterogeneous materials, containing different impurities that can represent serious obstacles toward their reuse/recycling. Critical parameters were analyzed and discussed, and recommendations were reported for a safe and sustainable recycling of these classes of materials., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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37. Hexamethylenediamine-Mediated Polydopamine Film Deposition: Inhibition by Resorcinol as a Strategy for Mapping Quinone Targeting Mechanisms.
- Author
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Alfieri ML, Panzella L, Oscurato SL, Salvatore M, Avolio R, Errico ME, Maddalena P, Napolitano A, Ball V, and d'Ischia M
- Abstract
Hexamethylenediamine (HMDA) and other long chain aliphatic diamines can induce substrate-independent polymer film deposition from dopamine and several other catechols substrates at relatively low concentrations, however the mechanism of the diamine-promoted effect has remained little understood. Herein, we report data indicating that: (a) film deposition from 1 mM HMDA and dopamine is not affected by chemical oxidation with periodate but is markedly inhibited by resorcinol, which also prevents PDA film formation at 10 mM monomer concentration in the absence of HMDA; (b) N-acetylation of HMDA completely inhibits the effect on PDA film formation; (c) HMDA enables surface functionalization with 1 mM 5,6-dihydroxyindole (DHI) polymerization at pH 9.0 in a resorcinol-inhibitable manner. Structural investigation of the polymers produced from dopamine and DHI in the presence of HMDA using solid state
13 C and15 N NMR and MALDI-MS suggested formation of covalent cross linked structures. It is concluded that HMDA enhances polydopamine adhesion by acting both on dopamine quinone and downstream, e.g., via covalent coupling with DHI. These results provide new insights into the mechanisms of PDA adhesion and disclose resorcinol as a new potent tool for targeting/mapping quinone intermediates and for controlling polymer growth.- Published
- 2019
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38. System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection.
- Author
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Garcia-Moreno M, Noerenberg M, Ni S, Järvelin AI, González-Almela E, Lenz CE, Bach-Pages M, Cox V, Avolio R, Davis T, Hester S, Sohier TJM, Li B, Heikel G, Michlewski G, Sanz MA, Carrasco L, Ricci EP, Pelechano V, Davis I, Fischer B, Mohammed S, and Castello A
- Subjects
- 5' Untranslated Regions, Binding Sites, Epithelial Cells metabolism, Exoribonucleases genetics, Exoribonucleases metabolism, Female, Gene Expression Regulation, Viral, HEK293 Cells, HeLa Cells, Host-Pathogen Interactions, Humans, Microtubule-Associated Proteins genetics, Microtubule-Associated Proteins metabolism, Protein Binding, RNA, Viral metabolism, RNA-Binding Proteins metabolism, Ribonucleoproteins, Small Nuclear genetics, Ribonucleoproteins, Small Nuclear metabolism, SMN Complex Proteins, Sindbis Virus growth & development, Sindbis Virus metabolism, Sindbis Virus pathogenicity, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms metabolism, Virus Replication, Epithelial Cells virology, Gene Expression Profiling methods, RNA, Viral genetics, RNA-Binding Proteins genetics, Sindbis Virus genetics, Transcriptome, Uterine Cervical Neoplasms virology
- Abstract
The compendium of RNA-binding proteins (RBPs) has been greatly expanded by the development of RNA-interactome capture (RIC). However, it remained unknown if the complement of RBPs changes in response to environmental perturbations and whether these rearrangements are important. To answer these questions, we developed "comparative RIC" and applied it to cells challenged with an RNA virus called sindbis (SINV). Over 200 RBPs display differential interaction with RNA upon SINV infection. These alterations are mainly driven by the loss of cellular mRNAs and the emergence of viral RNA. RBPs stimulated by the infection redistribute to viral replication factories and regulate the capacity of the virus to infect. For example, ablation of XRN1 causes cells to be refractory to SINV, while GEMIN5 moonlights as a regulator of SINV gene expression. In summary, RNA availability controls RBP localization and function in SINV-infected cells., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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39. Recycling Polyethylene-Rich Plastic Waste from Landfill Reclamation: Toward an Enhanced Landfill-Mining Approach.
- Author
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Avolio R, Spina F, Gentile G, Cocca M, Avella M, Carfagna C, Tealdo G, and Errico ME
- Abstract
In the frame of a circular economy, the maximization of secondary raw-material recovery is necessary to increase the economic and environmental sustainability of landfill mining and reclamation activities. In this paper, the polyethylene-rich plastic fraction recovered from the reclamation of an abandoned industrial landfill (landfill-recovered plastic, LRP) has been characterized through spectroscopic, thermal, morphological, and mechanical analyses. Then, an economically viable valorization and recycling strategy was set up. The effectiveness of this strategy in the enhancement of LRP properties has been demonstrated through morphological and mechanical characterizations.
- Published
- 2019
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40. Protein Syndesmos is a novel RNA-binding protein that regulates primary cilia formation.
- Author
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Avolio R, Järvelin AI, Mohammed S, Agliarulo I, Condelli V, Zoppoli P, Calice G, Sarnataro D, Bechara E, Tartaglia GG, Landriscina M, Castello A, Esposito F, and Matassa DS
- Subjects
- Cilia metabolism, Ciliopathies genetics, HCT116 Cells, HSP90 Heat-Shock Proteins metabolism, HeLa Cells, Humans, Neoplasms genetics, Polyribosomes metabolism, Protein Binding genetics, Protein Biosynthesis genetics, Protein Interaction Domains and Motifs genetics, Protein Structure, Tertiary, RNA-Binding Proteins chemistry, RNA-Binding Proteins genetics, Cilia genetics, RNA-Binding Proteins physiology
- Abstract
Syndesmos (SDOS) is a functionally poorly characterized protein that directly interacts with p53 binding protein 1 (53BP1) and regulates its recruitment to chromatin. We show here that SDOS interacts with another important cancer-linked protein, the chaperone TRAP1, associates with actively translating polyribosomes and represses translation. Moreover, we demonstrate that SDOS directly binds RNA in living cells. Combining individual gene expression profiling, nucleotide crosslinking and immunoprecipitation (iCLIP), and ribosome profiling, we discover several crucial pathways regulated post-transcriptionally by SDOS. Among them, we identify a small subset of mRNAs responsible for the biogenesis of primary cilium that have been linked to developmental and degenerative diseases, known as ciliopathies, and cancer. We discover that SDOS binds and regulates the translation of several of these mRNAs, controlling cilia development.
- Published
- 2018
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41. Pectin based finishing to mitigate the impact of microplastics released by polyamide fabrics.
- Author
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De Falco F, Gentile G, Avolio R, Errico ME, Di Pace E, Ambrogi V, Avella M, and Cocca M
- Abstract
Washing processes of synthetic clothes have been identified as the main source of microplastic pollution in marine ecosystems. Textile microfibres have been found in marine sediments and organisms, posing a real threat for the environment. The development of mitigation approaches is strongly needed to prevent the impact of microplastics. In this work, an innovative finishing treatment of polyamide fabrics is proposed to mitigate the microplastic impact, by preventing the damage of fabrics during washings. The treatment is based on the use of pectin, a natural polysaccharide present in the cell walls of plants. To functionalize the fabric, pectin was firstly modified with glycidyl methacrylate (GMA) and then grafted on polyamide. Washing tests of treated fabrics showed the effectiveness of the treatment in reducing of about 90% the amount of microfibres released by untreated fabrics. Post-wash analysis of the treated fabrics revealed a promising resistance to the washing process., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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42. The Chemistry of Polydopamine Film Formation: The Amine-Quinone Interplay.
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Alfieri ML, Panzella L, Oscurato SL, Salvatore M, Avolio R, Errico ME, Maddalena P, Napolitano A, and D'Ischia M
- Abstract
Despite extensive investigations over the past decade, the chemical basis of the extraordinary underwater adhesion properties of polydopamine (PDA) has remained not entirely understood. The bulk of evidence points to PDA wet adhesion as a complex process based on film deposition, and growth in which primary amine groups, besides catechol moieties, play a central role. However, the detailed interplay of chemical interactions underlying the dynamics of film formation has not yet been elucidated. Herein, we report the results of a series of experiments showing that coating formation from dopamine at pH 9.0 in carbonate buffer: (a) Requires high dopamine concentrations (>1 mM); (b) is due to species produced in the early stages of dopamine autoxidation; (c) is accelerated by equimolar amounts of periodate causing fast conversion to the o -quinone; and (d) is enhanced by the addition of hexamethylenediamine (HMDA) and other long chain aliphatic amines even at low dopamine concentrations (<1 mM). It is proposed that concentration-dependent PDA film formation reflects the competition between intermolecular amine-quinone condensation processes, leading to adhesive cross-linked oligomer structures, and the intramolecular cyclization route forming little adhesive 5,6-dihydroxyindole (DHI) units. Film growth would then be sustained by dopamine and other soluble species that can be adsorbed on the surface.
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- 2018
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43. Effect of Microfibrillated Cellulose on Microstructure and Properties of Poly(vinyl alcohol) Foams.
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Gentile G, Cocca M, Avolio R, Errico ME, and Avella M
- Abstract
Poly(vinyl alcohol) foams, containing different amounts of microfibrillated cellulose, were prepared through an eco-friendly procedure based on high-speed mixing and freeze-drying. The effect of filler amount on cell shape and regularity was studied by scanning electron microscopy (SEM) and the evolution of the microstructure was assessed through dynamic cryo-SEM. Fourier Transformed Infrared Analysis and Differential Scanning Calorimetry measurements revealed the presence of hydrogen bond interaction among cellulosic filler and the matrix. The modulus and compression deflection of neat PVA were significantly improved by increasing the amount of microfibrillated cellulose content with respect to foams realised with pulp cellulose fibers.
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- 2018
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44. TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor.
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Matassa DS, Agliarulo I, Avolio R, Landriscina M, and Esposito F
- Abstract
Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance. TRAP1 is the only mitochondrial member of the Heat Shock Protein 90 (HSP90) family that directly interacts with respiratory complexes, contributing to their stability and activity but it is still unclear if such interactions lead to reduced or increased respiratory capacity. The role of TRAP1 is to enhance or suppress oxidative phosphorylation; the effects of such regulation on tumor development and progression are controversial. These observations encourage the study of the mechanisms responsible for the dualist role of TRAP1 as an oncogene or oncosuppressor in specific tumor types. In this review, TRAP1 puzzling functions were recapitulated with a special focus on the correlation between metabolic reprogramming and tumor outcome. We wanted to investigate whether metabolism-targeting drugs can efficiently interfere with tumor progression and whether they might be combined with chemotherapeutics or molecular-targeted agents to counteract drug resistance and reduce therapeutic failure.
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- 2018
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45. Green and Facile Esterification Procedure Leading to Crystalline-Functionalized Graphite Oxide.
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Acocella MR, D'Urso L, Maggio M, Avolio R, Errico ME, and Guerra G
- Abstract
A simple and eco-friendly procedure of esterification of graphite oxide (GO), which uses acetic anhydride as a model reagent and ethyl acetate as a green solvent, is reported. The procedure leads to high functionalization degrees (at least up to 4.5 mol % of acetyl groups, referred to as graphitic C atoms) and it is much more effective than the literature method based on pure acetic anhydride. Surprisingly, our acetylation procedure does not destroy or reduce GO crystallinity but, irrespective of a substantial increase of distance between GO layers (from 0.84 nm up to 0.95 nm), leads to an increased order in the direction perpendicular to the graphitic planes. This phenomenon indicates that acetyl groups of acetylated GO (AcGO) are easily accommodated between graphitic layers, even improving interlayer order. The esterification procedure is generally applicable with various anhydrides providing differently functionalized graphite oxide. Dispersion of crystalline functionalized GO in volatile organic solvents followed by solvent fast removal, can easily lead to complete exfoliation.
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- 2017
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46. Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo.
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Pepe A, Avolio R, Matassa DS, Esposito F, Nitsch L, Zurzolo C, Paladino S, and Sarnataro D
- Abstract
Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp
0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrPSc ), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrPC to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit "prion-like" properties, such as PK-resistance and aggregation state, also in live cells. We tested this hypothesis, by different approaches in neuronal cells, finding that Sho shows folding properties partially dependent on lipid rafts integrity whose alteration, as well as proteasomal block, regulated generation of intermediate Sho isoforms and exacerbated its misfolding. Moreover, a 18 kDa isoform of Sho, likely bearing the signal peptide, was targeted to mitochondria by interacting with the molecular chaperone TRAP1 which, in turn controlled Sho dual targeting to ER or mitochondria. Our studies contribute to understand the role of molecular chaperones and of PrP-related folding intermediates in "prion-like" conversion.- Published
- 2017
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47. Multifunctional Thin Films and Coatings from Caffeic Acid and a Cross-Linking Diamine.
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Iacomino M, Paez JI, Avolio R, Carpentieri A, Panzella L, Falco G, Pizzo E, Errico ME, Napolitano A, Del Campo A, and d'Ischia M
- Abstract
The exploitation of easily accessible and nontoxic natural catechol compounds for surface functionalization and coating is attracting growing interest for biomedical applications. We report herein the deposition on different substrates of chemically stable thin films by autoxidation of 1 mM caffeic acid (CA) solutions at pH 9 in the presence of equimolar amounts of hexamethylenediamine (HMDA). UV-visible, mass spectrometric, and solid state
13 C and15 N NMR analysis indicated covalent incorporation of the amine during CA polymerization to produce insoluble trioxybenzacridinium scaffolds decorated with carboxyl and amine functionalities. Similar coatings are obtained by replacing CA with 4-methylcatechol (MC) in the presence of HMDA. No significant film deposition was detected in the absence of HMDA nor by replacing it with shorter chain ethylenediamine, or with monoamines. The CA/HMDA-based films resisted oxidative and reductive treatments, displayed efficient Fe(II) and Cu(II) binding capacity and organic dyes adsorption, and provided an excellent cytocompatible platform for growing embryonic stem cells. These results pointed to HMDA as an efficient cross-linking mediator of film deposition from natural catechols for surface functionalization and coatings.- Published
- 2017
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48. Stress-Adaptive Response in Ovarian Cancer Drug Resistance: Role of TRAP1 in Oxidative Metabolism-Driven Inflammation.
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Amoroso MR, Matassa DS, Agliarulo I, Avolio R, Maddalena F, Condelli V, Landriscina M, and Esposito F
- Subjects
- Animals, Antineoplastic Agents pharmacology, Epithelial-Mesenchymal Transition drug effects, Female, HSP90 Heat-Shock Proteins analysis, HSP90 Heat-Shock Proteins immunology, Humans, Inflammation drug therapy, Inflammation immunology, Inflammation pathology, Ovarian Neoplasms immunology, Ovarian Neoplasms pathology, Ovary immunology, Ovary metabolism, Ovary pathology, Drug Resistance, Neoplasm, HSP90 Heat-Shock Proteins metabolism, Inflammation metabolism, Ovarian Neoplasms drug therapy, Ovarian Neoplasms metabolism, Ovary drug effects, Oxidative Phosphorylation drug effects
- Abstract
Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts. In recent years, oxidative phosphorylation has been linked to a remodeling of inflammatory response due to autocrine or paracrine secretion of interleukines that, in turn, induces a regulation of gene expression involving, among others, molecules responsible for the onset of drug resistance. This process is especially relevant in ovarian cancer, characterized by low survival, high frequency of disease relapse and chemoresistance. Recently, the molecular chaperone TRAP1 (tumor necrosis factor-associated protein 1) has been identified as a key junction molecule in these processes in ovarian cancer: in fact, TRAP1 mediates a metabolic switch toward oxidative phosphorylation that, in turn, triggers cytokines secretion, with consequent gene expression remodeling, finally leading to cisplatin resistance and epithelial-to-mesenchymal transition in ovarian cancer models. This review summarizes how metabolism, chemoresistance, inflammation, and epithelial-to-mesenchymal transition are strictly interconnected, and how TRAP1 stays at the crossroads of these processes, thus shedding new lights on molecular networks at the basis of ovarian cancer., (© 2017 Elsevier Inc. All rights reserved.)
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- 2017
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49. TRAP1 downregulation in human ovarian cancer enhances invasion and epithelial-mesenchymal transition.
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Amoroso MR, Matassa DS, Agliarulo I, Avolio R, Lu H, Sisinni L, Lettini G, Gabra H, Landriscina M, and Esposito F
- Subjects
- Carcinoma, Ovarian Epithelial, Cell Line, Tumor, Cell Movement genetics, Female, Gene Deletion, Gene Expression Regulation, Neoplastic, HSP90 Heat-Shock Proteins metabolism, Humans, Kaplan-Meier Estimate, Neoplasm Invasiveness, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Down-Regulation genetics, Epithelial-Mesenchymal Transition genetics, HSP90 Heat-Shock Proteins genetics, Neoplasms, Glandular and Epithelial genetics, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology
- Abstract
Ovarian cancer (OC) is the second leading cause of gynecological cancer death worldwide. Although the list of biomarkers is still growing, molecular mechanisms involved in OC development and progression remain elusive. We recently demonstrated that lower expression of the molecular chaperone TRAP1 in OC patients correlates with higher tumor grade and stage, and platinum resistance. Herein we show that TRAP1 is often deleted in high-grade serous OC patients (N=579), and that TRAP1 expression is correlated with the copy number, suggesting this could be one of the driving mechanisms for the loss of TRAP1 expression in OC. At molecular level, downregulation of TRAP1 associates with higher expression of p70S6K, a kinase frequently active in OC with emerging roles in cell migration and tumor metastasis. Indeed, TRAP1 silencing in different OC cells induces upregulation of p70S6K expression and activity, enhancement of cell motility and epithelial-mesenchymal transition (EMT). Consistently, in a large cohort of OC patients, TRAP1 expression is reduced in tumor metastases and directly correlates with the epithelial marker E-Cadherin, whereas it inversely correlates with the transcription factor Slug and the matrix metallopeptidases 2 and 9. Strikingly, pharmacological inhibition of p70S6K reverts the high motility phenotype of TRAP1 knock-down cells. However, although p70S6K inhibition or silencing reduces the expression of the transcription factors Snail and Slug, thus inducing upregulation of E-Cadherin expression, it is unable to revert EMT induced by TRAP1 silencing; furthermore, p70S6K did not show any significant correlation with EMT genes in patients, nor with overall survival or tumor stage, suggesting an independent and predominant role for TRAP1 in OC progression. Altogether, these results may provide novel approaches in OC with reduced TRAP1 expression, which could be resistant to therapeutic strategies based on the inhibition of the p70S6K pathway, with potential future intervention in OC invasion and metastasis.
- Published
- 2016
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50. Pure titanium particle loaded nanocomposites: study on the polymer/filler interface and hMSC biocompatibility.
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Avolio R, D'Albore M, Guarino V, Gentile G, Cocca MC, Zeppetelli S, Errico ME, Avella M, and Ambrosio L
- Subjects
- Adsorption, Cell Adhesion, Cell Line, Cell Proliferation, Cell Survival, Humans, Image Processing, Computer-Assisted, Materials Testing, Microscopy, Electron, Transmission, Nanoparticles chemistry, Nitrogen chemistry, Oxygen chemistry, Pressure, Solvents chemistry, Stress, Mechanical, Surface Properties, Temperature, Biocompatible Materials chemistry, Mesenchymal Stem Cells cytology, Nanocomposites chemistry, Polymers chemistry, Polymethyl Methacrylate chemistry, Titanium chemistry
- Abstract
The integration of inorganic nanoparticles into polymer matrices allows for the modification of physical properties as well as the implementation of new features for unexplored application fields. Here, we propose the study of a new metal/polymer nanocomposite fabricated by dispersing pure Ti nanoparticles into a poly(methylmetacrilate) matrix via solvent casting process, to investigate its potential use as new biomaterial for biomedical applications. We demonstrated that Ti nanoparticles embedded in the poly(methylmetacrilate) matrix can act as reinforcing agent, not negatively influencing the biological response of human mesenchymal stem cell in terms of cytotoxicity and cell viability. As a function of relative amount and surface treatment, Ti nanoparticles may enhance mechanical strength of the composite-ranging from 31.1 ± 2.5 to 43.7 ± 0.7 MPa-also contributing to biological response in terms of adhesion and proliferation mechanisms. In particular, for 1 wt% Ti, treated Ti nanoparticles improve cell materials recognition, as confirmed by higher cell spreading-quantified in terms of cell area via image analysis-locally promoting stronger interactions at cell matrix interface. At this stage, these preliminary results suggest a promising use of pure Ti nanoparticles as filler in polymer composites for biomedical applications.
- Published
- 2016
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