71 results on '"G. Cerrato"'
Search Results
2. Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome.
- Author
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Pan H, Tian AL, Chen H, Xia Y, Sauvat A, Moriceau S, Lambertucci F, Motiño O, Zhao L, Liu P, Mao M, Li S, Zhang S, Joseph A, Durand S, Aprahamian F, Luo Z, Ou Y, Shen Z, Xue E, Pan Y, Carbonnier V, Stoll G, Forveille S, Leduc M, Cerrato G, Cerone A, Maiuri MC, Castinetti F, Brue T, Wang H, Ma Y, Martins I, Kepp O, and Kroemer G
- Abstract
Cushing's syndrome is caused by an elevation of endogenous or pharmacologically administered glucocorticoids. Acyl coenzyme A binding protein (ACBP, encoded by the gene diazepam binding inhibitor, Dbi) stimulates food intake and lipo-anabolic reactions. Here we found that plasma ACBP/DBI concentrations were elevated in patients and mice with Cushing's syndrome. We used several methods for ACBP/DBI inhibition in mice, namely, (1) induction of ACBP/DBI autoantibodies, (2) injection of a neutralizing monoclonal antibody, (3) body-wide or hepatocyte-specific knockout of the Dbi gene, (4) mutation of the ACBP/DBI receptor Gabrg2 and (5) injections of triiodothyronine or (6) the thyroid hormone receptor-β agonist resmetirom to block Dbi transcription. These six approaches abolished manifestations of Cushing's syndrome such as increased food intake, weight gain, excessive adiposity, liver damage, hypertriglyceridaemia and type 2 diabetes. In conclusion, it appears that ACBP/DBI constitutes an actionable target that is causally involved in the development of Cushing's syndrome., Competing Interests: Competing interests: O.K. is a scientific co-founder of Samsara Therapeutics. I.M. consults for Osasuna Therapeutics. G.K. has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys and Vascage. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio; is in the scientific advisory boards of Hevolution, Institut Servier, Longevity Vision Funds and Rejuveron Life Sciences; and is the inventor of patents covering therapeutic targeting of ageing, cancer, cystic fibrosis and metabolic disorders. Among these patents, one, ‘Methods for weight reduction’ (US11905330B1), is relevant to this study. G.K.’s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. G.K.’s wife, Laurence Zitvogel, has held research contracts with GSK, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a co-founder of everImmune and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. The funders had no role in the design of the study, in the writing of the manuscript or in the decision to publish the results. The other authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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3. Investigating the Synergistic Effect of Decoration and Doping in Silver/Strontium Titanate for Air Remediation.
- Author
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Frías Ordóñez M, Sacco E, Scavini M, Cerrato G, Giordana A, Falletta E, and Bianchi CL
- Abstract
Strontium titanate (STO) and its variants have emerged as leading materials in photocatalysis, particularly for degrading nitrogen oxides (NOx), due to their non-toxic nature, structural adaptability, and exceptional thermal stability. Although the one-pot sol-gel method leads to high-quality photocatalysts, areas remain for improvement. This study examines the impact of ethanol as a cosolvent in STO synthesis, focusing on optimizing the water-to-ethanol volume ratio. The findings reveal that a 1:3 ratio significantly enhances macropore formation and photocatalytic efficiency, achieving 42% NOx degradation under LED within three hours. Furthermore, incorporating 8.0 wt.% Ag into STO substantially improves visible light absorption and enables complete NOx elimination, thanks to enhanced charge separation and localized surface plasmon resonance. Even at high temperatures (1100 °C), the Ag-STO photocatalyst maintains partial activity, despite exceeding silver's melting point. These results highlight the potential of STO-based materials for industrial applications, positioning them as a promising solution for effective NOx mitigation.
- Published
- 2024
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4. Novel eco-friendly and easily recoverable bismuth-based materials for capturing and removing polyphenols from water.
- Author
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Galloni MG, Nikonova V, Cerrato G, Giordana A, Pleva P, Humpolicek P, Falletta E, and Bianchi CL
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- Water Pollutants, Chemical chemistry, Water chemistry, Adsorption, Polyphenols chemistry, Polyphenols analysis, Bismuth chemistry, Wastewater chemistry
- Abstract
Olive oil production is one of the most developed Europe's sectors, producing olive oil and undesirable by-products, such as olive mill wastewater (OMWW) and organic waste. OMWW, containing large amounts of compounds (mainly polyphenols, phenols, and tannins), represents a problem. In fact, polyphenols have dual nature: i) antioxidant beneficial properties, useful in many industrial fields, ii) biorefractory character making them harmful in high concentrations. If not properly treated, polyphenols can harm biodiversity, disrupt ecological balance, and degrade water quality, posing risks to both environment and human health. From a circular economy viewpoint, capturing large quantities of polyphenols to reuse and removing their residuals from water is an open challenge. This study proposes, for the first time, a new path beyond the state-of-the-art, combining adsorption and degradation technologies by novel, eco-friendly and easily recoverable bismuth-based materials to capture large amounts of two model polyphenols (gallic acid and 3,4,5-trimethoxybenzoic acid), which are difficult to remove by traditional processes, and photodegrade them under solar light. The coupled process gave rise to collect 98% polyphenols, and to rapidly and effectively photodegrade the remaining portion from water., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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5. Ultrasonic Disintegration of Municipal Sludge: Fundamental Mechanisms, Process Intensification and Industrial Sono-Reactors.
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Djellabi R, Su P, Ambaye TG, Cerrato G, and Bianchi CL
- Subjects
- Bioreactors, Sonication, Anaerobiosis, Waste Disposal, Fluid methods, Sewage
- Abstract
Sludge disintegration is an environmental and industrial challenge that requires intensive research and technological development. Sludge has a complex structure with a high yield of various chemical and biological compounds. Anaerobic digestion is the most commonly used process for sludge disintegration to produce biogas, detoxify sludge, and generate biosolids that can be used in agriculture . Biological cell lysis is the rate-limiting cell lysis. This review discusses the application of sonolysis as a sludge pretreatment for enhanced anaerobic digestion via three combined processes: thermal destruction, hydrochemical shear forces, and radical oxidation. The mechanistic pathways of sono-pretreatment to enhance biogas, sludge-enhanced dewatering, activation of filamentous bacteria, oxidation of organic pollutants, release of heavy metals, reduction of bulking and foaming sludge, and boosting ammonia-oxidizing bacterial activity are discussed in this review. This article also discusses the use of ultrasound in sludge disintegration, highlighting its potential in conjunction with Fenton and cation-binding agents, and reviews common large-scale sonoreactors available on the market.., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)
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- 2024
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6. Spermidine is essential for fasting-mediated autophagy and longevity.
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Hofer SJ, Daskalaki I, Bergmann M, Friščić J, Zimmermann A, Mueller MI, Abdellatif M, Nicastro R, Masser S, Durand S, Nartey A, Waltenstorfer M, Enzenhofer S, Faimann I, Gschiel V, Bajaj T, Niemeyer C, Gkikas I, Pein L, Cerrato G, Pan H, Liang Y, Tadic J, Jerkovic A, Aprahamian F, Robbins CE, Nirmalathasan N, Habisch H, Annerer E, Dethloff F, Stumpe M, Grundler F, Wilhelmi de Toledo F, Heinz DE, Koppold DA, Rajput Khokhar A, Michalsen A, Tripolt NJ, Sourij H, Pieber TR, de Cabo R, McCormick MA, Magnes C, Kepp O, Dengjel J, Sigrist SJ, Gassen NC, Sedej S, Madl T, De Virgilio C, Stelzl U, Hoffmann MH, Eisenberg T, Tavernarakis N, Kroemer G, and Madeo F
- Subjects
- Animals, Humans, Peptide Initiation Factors metabolism, Peptide Initiation Factors genetics, Eukaryotic Translation Initiation Factor 5A, Drosophila melanogaster metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae genetics, Mice, Male, Mice, Inbred C57BL, Autophagy drug effects, Longevity drug effects, Spermidine metabolism, Spermidine pharmacology, Fasting, Caenorhabditis elegans metabolism, Caloric Restriction
- Abstract
Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity., (© 2024. The Author(s).)
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- 2024
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7. High-throughput assessment of cellular senescence.
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Cerrato G, Sauvat A, Peyre F, Kepp O, and Kroemer G
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- Cell Cycle, Cell Division, Cellular Senescence physiology
- Abstract
Cellular senescence is a molecular process that is activated in response to a large variety of distinct stress signals. Mechanistically, cellular senescence is characterized by an arrest in cell cycle accompanied by phenotypic adaptations and physiological alterations including changes in the secretory profile of senescent cells termed the senescence-associated secretory phenotype (SASP). Here we describe a detailed, automation- compatible method for the detection of senescence-associated beta galactosidase (SA-β-gal) activity as a hallmark of cellular senescence using a conventional fluorescent microscope equipped with a transmitted light module. Moreover, we outline a protocol for the automated analysis of cellular senescence using convolutional neural networks (CNNs) and mathematical morphology. In sum, we provide a toolset for the high throughput assessment of cellular senescence based on light microscopy and automated image analysis., Competing Interests: Conflicts of interest OK is a cofounder of Samsara Therapeutics. GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys, and Vascage. GK has been consulting for Reithera. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. GK's wife, Laurence Zitvogel, has held research contracts with 9 Meters Biopharma, Daiichi Sankyo, Pilege, was on the on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. GK's brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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8. 3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis.
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Cerrato G, Alvarez-Lucena C, Sauvat A, Hu Y, Forveille S, Chen G, Durand S, Aprahamian F, Leduc M, Motiño O, Boscá L, Xu Q, Kepp O, and Kroemer G
- Subjects
- Mice, Animals, Hyperplasia pathology, Aorta pathology, Disease Models, Animal, Autophagy, Mice, Inbred C57BL, Neointima drug therapy, Neointima pathology, Atherosclerosis pathology
- Abstract
Autophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux. In this respect, 3,4-DC showed a broader autophagy-inducing activity than another chalcone (4,4- dimethoxychalcone), spermidine and triethylene tetramine. Thus, we characterized the potential antiatherogenic activity of 3,4-DC in two different mouse models, namely, (i) neointima formation with smooth muscle expansion of vein segments grafted to the carotid artery and (ii) genetically predisposed ApoE
-/- mice fed an atherogenic diet. In the vein graft model, local application of 3,4-DC was able to maintain the lumen of vessels and to reduce neointima lesions. In the diet-induced model, intraperitoneal injections of 3,4-DC significantly reduced the number of atherosclerotic lesions in the aorta. In conclusion, 3,4-DC stands out as an autophagy inducer with potent antiatherogenic activity., (© 2023. The Author(s).)- Published
- 2023
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9. Effect of the Synthetic Parameters over ZnO in the CO 2 Photoreduction.
- Author
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Zanardo D, Forghieri G, Ghedini E, Menegazzo F, Giordana A, Cerrato G, Cattaruzza E, Di Michele A, Cruciani G, and Signoretto M
- Abstract
Zinc oxide (ZnO) is an attractive semiconductor material for photocatalytic applications, owing to its opto-electronic properties. Its performances are, however, strongly affected by the surface and opto-electronic properties (i.e., surface composition, facets and defects), in turn related to the synthesis conditions. The knowledge on how these properties can be tuned and how they are reflected on the photocatalytic performances (activity and stability) is thus essential to achieve an active and stable material. In this work, we studied how the annealing temperature (400 °C vs. 600 °C) and the addition of a promoter (titanium dioxide, TiO
2 ) can affect the physico-chemical properties of ZnO materials, in particular surface and opto-electronic ones, prepared through a wet-chemistry method. Then, we explored the application of ZnO as a photocatalyst in CO2 photoreduction, an appealing light-to-fuel conversion process, with the aim to understand how the above-mentioned properties can affect the photocatalytic activity and selectivity. We eventually assessed the capability of ZnO to act as both photocatalyst and CO2 adsorber, thus allowing the exploitation of diluted CO2 sources as a carbon source.- Published
- 2023
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10. Biostimulants derived from organic urban wastes and biomasses: An innovative approach.
- Author
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Giordana A, Malandrino M, Zambon A, Lusvardi G, Operti L, and Cerrato G
- Abstract
We used humic and fulvic acids extracted from digestate to formulate nanohybrids with potential applications in agronomy. In order to obtain a synergic co-release of plant-beneficial agents, we functionalized with humic substances two inorganic matrixes: hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂, HP) and silica (SiO₂) nanoparticles (NPs). The former is a potential controlled-release fertilizer of P, and the latter has a beneficial effect on soil and plants. SiO
2 NPs are obtained from rice husks by a reproducible and fast procedure, but their ability to absorb humic substances is very limited. HP NPs coated with fulvic acid are instead a very promising candidate, based on desorption and dilution studies. The different dissolutions observed for HP NPs coated with fulvic and humic acids could be related to the different interaction mechanisms, as suggested by the FT-IR study., 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 © 2023 Giordana, Malandrino, Zambon, Lusvardi, Operti and Cerrato.)- Published
- 2023
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11. Efficient Day-and-Night NO 2 Abatement by Polyaniline/TiO 2 Nanocomposites.
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Meroni D, Galloni MG, Cionti C, Cerrato G, Falletta E, and Bianchi CL
- Abstract
Finding innovative and highly performing approaches for NOx degradation represents a key challenge to enhance the air quality of our environment. In this study, the high efficiency of PANI/TiO
2 nanostructures in the NO2 abatement both in the dark and under light irradiation is demonstrated for the first time. Heterostructures were synthesized by a "green" method and their composition, structure, morphology and oxidation state were investigated by a combination of characterization techniques. The results show that the unique PANI structure promotes two mechanisms for the NO2 abatement in the dark (adsorption on the polymeric chains and chemical reduction to NO), whereas the photocatalytic behavior prevails under light irradiation, leading to the complete NOx degradation. The best-performing materials were subjected to recycling tests, thereby showing high stability without any significant activity loss. Overall, the presented material can represent an innovative and efficient night-and-day solution for NOx abatement.- Published
- 2023
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12. Parent, child, and environmental predictors of vegetable consumption in Italian, Polish, and British preschoolers.
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Masento NA, Dulay KM, Harvey K, Bulgarelli D, Caputi M, Cerrato G, Molina P, Wojtkowska K, Pruszczak D, Barlińska J, Messer D, and Houston-Price C
- Abstract
This study compared the vegetable intake of preschool children from three European countries [Italy, Poland, and the United Kingdom (UK)] and explored the parent, child, and environmental factors that predicted intake in each country. A total of 408 parents of preschoolers (Italy: N = 61, Poland: N = 124, and UK: N = 225; child mean age = 32.2 months, SD = 9.47) completed an online survey comprising a set of standardised questionnaires. For all three countries, the questionnaires included measures of children's vegetable intake (VegFFQ), child eating behaviour (CEBQ-FF), parents' mealtime goals (FMGs), and sociodemographic questions about family background and environment. In the UK and Italy, additional questionnaires were used to assess child temperament (EAS-T) and parents' feeding practices (CFPQ). The results showed that the number of child-sized portions of vegetables consumed per day varied significantly across countries; Polish children consumed the most (∼3 portions) and Italian children the least (∼1.5 portions). Between-country differences were seen in parents' goals for family mealtimes; compared to Italian parents, Polish and UK parents were more motivated to minimise mealtime stress, increase family involvement in meal preparation, and share the same foods with family members. British and Italian parents also adopted different feeding practices; parents in the UK reported more use of healthy modelling behaviours and more use of foods to support their child's emotion regulation. In terms of child factors, Italian children were reported to be more emotional and more sociable than British children. Analyses of the relationships between the parent, child, and environmental factors and children's vegetable intake revealed both similarities and differences between countries. Negative predictors of vegetable intake included child food fussiness in the UK and Poland, child temperament (especially, shyness) in Italy, and the use of food as a reward and child emotionality in the UK. Positive predictors included the parental mealtime goal of 'family involvement' in the UK. These results highlight differences in the extent to which European preschoolers achieve recommended levels of vegetable intake, and in the factors that influence whether they do. The results suggest a need to develop healthy eating interventions that are adopted to meet the specific needs of the countries in which they are implemented., 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 © 2022 Masento, Dulay, Harvey, Bulgarelli, Caputi, Cerrato, Molina, Wojtkowska, Pruszczak, Barlińska, Messer and Houston-Price.)
- Published
- 2022
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13. Nanoparticles releasing immunogenic cell death inducers upon near-infrared light exposure.
- Author
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Kepp O, Cerrato G, Sauvat A, and Kroemer G
- Subjects
- Immunogenic Cell Death, Infrared Rays, Antineoplastic Agents, Nanoparticles adverse effects
- Abstract
Competing Interests: OK is a cofounder of Samsara Therapeutics. GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sotio, Tollys, Vascage and Vasculox/Tioma. GK has been consulting for Reithera. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders.
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- 2022
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14. Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.
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Abdellatif M, Trummer-Herbst V, Heberle AM, Humnig A, Pendl T, Durand S, Cerrato G, Hofer SJ, Islam M, Voglhuber J, Ramos Pittol JM, Kepp O, Hoefler G, Schmidt A, Rainer PP, Scherr D, von Lewinski D, Bisping E, McMullen JR, Diwan A, Eisenberg T, Madeo F, Thedieck K, Kroemer G, and Sedej S
- Subjects
- Aged, Animals, Health Promotion, Humans, Male, Mice, Myocytes, Cardiac metabolism, Phosphatidylinositol 3-Kinases metabolism, Receptor, IGF Type 1 genetics, Receptor, IGF Type 1 metabolism, Insulin-Like Growth Factor I metabolism, Longevity
- Abstract
Background: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial., Methods: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic flux, and targeted metabolome profiling, and immunoblots of key IGF1R downstream targets in mouse and human explanted failing and nonfailing hearts, as well., Results: Young mice with increased IGF1R signaling exhibited superior cardiac function that progressively declined with aging in an accelerated fashion compared with wild-type animals, resulting in heart failure and a reduced lifespan. In contrast, mice with low cardiac IGF1R signaling exhibited inferior cardiac function early in life, but superior cardiac performance during aging, and increased maximum lifespan, as well. Mechanistically, the late-life detrimental effects of IGF1R activation correlated with suppressed autophagic flux and impaired oxidative phosphorylation in the heart. Low IGF1R activity consistently improved myocardial bioenergetics and function of the aging heart in an autophagy-dependent manner. In humans, failing hearts, but not those with compensated hypertrophy, displayed exaggerated IGF1R expression and signaling activity., Conclusions: Our findings indicate that the relationship between IGF1R signaling and cardiac health is not linear, but rather biphasic. Hence, pharmacological inhibitors of the IGF1 pathway, albeit unsuitable for young individuals, might be worth considering in older adults.
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- 2022
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15. Cancer cell-autonomous overactivation of PARP1 compromises immunosurveillance in non-small cell lung cancer.
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Juncheng P, Joseph A, Lafarge A, Martins I, Obrist F, Pol J, Saavedra E, Li S, Sauvat A, Cerrato G, Lévesque S, Leduc M, Kepp O, Durand S, Aprahamian F, Nirmalathansan N, Michels J, Kroemer G, and Castedo M
- Subjects
- Animals, Cisplatin pharmacology, Cisplatin therapeutic use, Mice, Monitoring, Immunologic, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Tumor Microenvironment, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms metabolism
- Abstract
Background: High activity of poly(ADP-ribose) polymerase-1 (PARP1) in non-small cell lung cancer (NSCLC) cells leads to an increase in immunohistochemically detectable PAR, correlating with poor prognosis in patients with NSCLC, as well as reduced tumor infiltration by cytotoxic T lymphocytes (CTLs). Intrigued by this observation, we decided to determine whether PARP1 activity in NSCLC cells may cause an alteration of anticancer immunosurveillance., Methods: Continuous culture of mouse NSCLC cells in the presence of cisplatin led to the generation of cisplatin-resistant PAR
high clones. As compared with their parental controls, such PARhigh cells formed tumors that were less infiltrated by CTLs when they were injected into immunocompetent mice, suggesting a causative link between high PARP1 activity and compromised immunosurveillance. To confirm this cause-and-effect relationship, we used CRISPR/Cas9 technology to knock out PARP1 in two PARhigh NSCLC mouse cell lines (Lewis lung cancer [LLC] and tissue culture number one [TC1]), showing that the removal of PARP1 indeed restored cisplatin-induced cell death responses., Results: PARP1 knockout (PARP1KO ) cells became largely resistant to the PARP inhibitor niraparib, meaning that they exhibited less cell death induction, reduced DNA damage response, attenuated metabolic shifts and no induction of PD-L1 and MHC class-I molecules that may affect their immunogenicity. PARhigh tumors implanted in mice responded to niraparib irrespective of the presence or absence of T lymphocytes, suggesting that cancer cell-autonomous effects of niraparib dominate over its possible immunomodulatory action. While PARhigh NSCLC mouse cell lines proliferated similarly in immunocompetent and T cell-deficient mice, PARP1KO cells were strongly affected by the presence of T cells. PARP1KO LLC tumors grew more quickly in immunodeficient than in immunocompetent mice, and PARP1KO TC1 cells could only form tumors in T cell-deficient mice, not in immunocompetent controls. Importantly, as compared with PARhigh controls, the PARP1KO LLC tumors exhibited signs of T cell activation in the immune infiltrate such as higher inducible costimulator (ICOS) expression and lower PD-1 expression on CTLs., Conclusions: These results prove at the genetic level that PARP1 activity within malignant cells modulates the tumor microenvironment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2022
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16. Local anesthetics elicit immune-dependent anticancer effects.
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Bezu L, Wu Chuang A, Sauvat A, Humeau J, Xie W, Cerrato G, Liu P, Zhao L, Zhang S, Le Naour J, Pol J, van Endert P, Kepp O, Barlesi F, and Kroemer G
- Subjects
- Activating Transcription Factor 4 genetics, Activating Transcription Factor 4 metabolism, Animals, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum pathology, Eukaryotic Initiation Factor-2 genetics, Eukaryotic Initiation Factor-2 metabolism, Humans, Mice, Retrospective Studies, Anesthetics, Local metabolism, Neoplasms pathology
- Abstract
Background: Retrospective clinical trials reported a reduced local relapse rate, as well as improved overall survival after injection of local anesthetics during cancer surgery. Here, we investigated the anticancer effects of six local anesthetics used in clinical practice., Results: In vitro , local anesthetics induced signs of cancer cell stress including inhibition of oxidative phosphorylation, and induction of autophagy as well as endoplasmic reticulum (ER) stress characterized by the splicing of X-box binding protein 1 (XBP1s) mRNA, cleavage of activating transcription factor 6 (ATF6), phosphorylation of eIF2α and subsequent upregulation of activating transcription factor 4 (ATF4). Both eIF2α phosphorylation and autophagy required the ER stress-relevant eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, best known as PERK). Local anesthetics also activated two hallmarks of immunogenic cell death, namely, the release of ATP and high-mobility group box 1 protein (HMGB1), yet failed to cause the translocation of calreticulin (CALR) from the ER to the plasma membrane. In vivo , locally injected anesthetics decreased tumor growth and improved survival in several models of tumors established in immunocompetent mice. Systemic immunotherapy with PD-1 blockade or intratumoral injection of recombinant CALR protein, increased the antitumor effects of local anesthetics. Local anesthetics failed to induce antitumor effects in immunodeficient mice or against cancers unable to activate ER stress or autophagy due to the knockout of EIF2AK3/PERK or ATG5, respectively. Uncoupling agents that inhibit oxidative phosphorylation and induce autophagy and ER stress mimicked the immune-dependent antitumor effects of local anesthetics., Conclusion: Altogether, these results indicate that local anesthetics induce a therapeutically relevant pattern of immunogenic stress responses in cancer cells., Competing Interests: Competing interests: GK and OK are cofounders of Samsara Therapeutics. JP is the inventor of patents for cancer vaccination licensed to Turnstone Biologics., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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17. Biological Investigation of a Water-Soluble Isoginkgetin-Phosphate Analogue, Targeting the Spliceosome with In Vivo Antitumor Activity.
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Letribot B, Nascimento M, Cerrato G, Darrigrand R, Salgues V, Renko D, Pruvost A, Alami M, Messaoudi S, and Apcher S
- Subjects
- Phosphates, Water, Biflavonoids pharmacology, Spliceosomes
- Abstract
The first total synthesis of the natural product Isoginkgetin as well as four water-soluble Isoginkgetin-phosphate analogues is reported herein. Moreover, the full study of the IP2 phosphate analogue with respect to pharmacological properties (metabolic and plasmatic stabilities, pharmacokinetic, off-target, etc.) as well as in vitro and in vivo biological activities are disclosed herein.
- Published
- 2022
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18. Assessment of transcription inhibition as a characteristic of immunogenic cell death.
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Cerrato G, Humeau J, Sauvat A, Kepp O, and Kroemer G
- Subjects
- Click Chemistry, Immunogenic Cell Death, RNA genetics
- Abstract
Anticancer drugs that suppress DNA-to-RNA transcription are particularly efficient in stimulating immunogenic cell death and hence eradicate malignant cells in a way that they will ignite an antitumor immune response. This is therapeutically relevant as it allows treatment response to last beyond drug discontinuation. For this reason, it is important to measure transcription inhibition in a precise fashion. Here, we detail two complementary assays for the assessment of transcription inhibition, one that detects the physical separation of fibrillarin and nucleolin by two-color immunofluorescence and another that measures the diminution of incorporated 5-ethynyl uridine (EU) into RNA, as revealed by click chemistry and the per-cell-intensity of a fluorescent signal., Competing Interests: Conflict of interest G.K. and O.K. are cofounders of Samsara Therapeutics. G.K. is a founder of everImmune and Therafast Bio., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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19. Solar Light Photoactive Floating Polyaniline/TiO 2 Composites for Water Remediation.
- Author
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Falletta E, Bruni A, Sartirana M, Boffito DC, Cerrato G, Giordana A, Djellabi R, Khatibi ES, and Bianchi CL
- Abstract
In the present study, the development of innovative polyurethane-polyaniline/TiO
2 modified floating materials applied in the sorption and photodegradation of rhodamine B from water matrix under solar light irradiation is reported. All the materials were fabricated with inexpensive and easy approaches and were properly characterized. The effect of the kind of polyaniline (PANI) dopant on the materials' behavior was investigated, as well as the role of the conducting polymer in the pollutant abatement on the basis of its physico-chemical characteristics. Rhodamine B is removed by adsorption and/or photodegradation processes depending on the type of doping agent used for PANI protonation. The best materials were subjected to recycle tests in order to demonstrate their stability under the reaction conditions. The main transformation products formed during the photodegradation process were identified by ultraperformance liquid chromatography-mass spectrometry (UPLC/MS). The results demonstrated that photoactive floating PANI/TiO2 composites are useful alternatives to common powder photocatalysts for the degradation of cationic dyes.- Published
- 2021
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20. Corrigendum: See & Eat! Using E-books to Promote Vegetable Eating Among Preschoolers: Findings From an Italian Sample.
- Author
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Caputi M, Dulay KM, Bulgarelli D, Houston-Price C, Cerrato G, Fanelli M, Masento NA, and Molina P
- Abstract
[This corrects the article DOI: 10.3389/fpsyg.2021.712416.]., (Copyright © 2021 Caputi, Dulay, Bulgarelli, Houston-Price, Cerrato, Fanelli, Masento and Molina.)
- Published
- 2021
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21. See & Eat! Using E-books to Promote Vegetable Eating Among Preschoolers: Findings From an Italian Sample.
- Author
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Caputi M, Dulay KM, Bulgarelli D, Houston-Price C, Cerrato G, Fanelli M, Masento NA, and Molina P
- Abstract
Different strategies have been developed to help parents with introducing new or disliked vegetables. Nonetheless, many parents of preschoolers struggle against children's refusal to eat vegetables. In this study, we aimed to evaluate the effectiveness of e-books in promoting positive attitudes toward vegetables through repeated visual exposures. A total of 61 families with preschoolers joined the See & Eat study and received an e-book about one of two vegetables chosen from a list of 24. Parents provided ratings of children's willingness to taste, intake, and liking of the chosen vegetables before and after reading the e-book; parents also evaluated their children's food fussiness and their agreement with respect to three mealtime goals of the family. Using a 2 (vegetable: target or non-target) × 2 (time: pre-test or post-test) within-subjects analysis, results from 53 families revealed a significant increase in children's willingness to taste, intake, and liking at post-test of both target and non-target vegetables. Following a two-week parent-child e-book reading intervention, children's food fussiness and parents' endorsement of positive mealtime goals slightly but significantly increased. Results suggest that e-books are effective in encouraging healthy eating among preschoolers and that the positive effect of e-book reading can generalize to other vegetables., 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 Caputi, Dulay, Bulgarelli, Houston-Price, Cerrato, Fanelli, Masento and Molina.)
- Published
- 2021
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22. Oxidative Inactivation of SARS-CoV-2 on Photoactive AgNPs@TiO 2 Ceramic Tiles.
- Author
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Djellabi R, Basilico N, Delbue S, D'Alessandro S, Parapini S, Cerrato G, Laurenti E, Falletta E, and Bianchi CL
- Subjects
- Antiviral Agents pharmacology, COVID-19 virology, Humans, Light, Oxidative Stress drug effects, Oxidative Stress radiation effects, Pandemics, Particle Size, SARS-CoV-2 metabolism, Surface Properties, Virus Inactivation drug effects, Virus Inactivation radiation effects, Ceramics chemistry, Metal Nanoparticles chemistry, SARS-CoV-2 drug effects, SARS-CoV-2 radiation effects, Titanium chemistry
- Abstract
The current SARS-CoV-2 pandemic causes serious public health, social, and economic issues all over the globe. Surface transmission has been claimed as a possible SARS-CoV-2 infection route, especially in heavy contaminated environmental surfaces, including hospitals and crowded public places. Herein, we studied the deactivation of SARS-CoV-2 on photoactive AgNPs@TiO
2 coated on industrial ceramic tiles under dark, UVA, and LED light irradiations. SARS-CoV-2 inactivation is effective under any light/dark conditions. The presence of AgNPs has an important key to limit the survival of SARS-CoV-2 in the dark; moreover, there is a synergistic action when TiO2 is decorated with Ag to enhance the virus photocatalytic inactivation even under LED. The radical oxidation was confirmed as the the central mechanism behind SARS-CoV-2 damage/inactivation by ESR analysis under LED light. Therefore, photoactive AgNPs@TiO2 ceramic tiles could be exploited to fight surface infections, especially during viral severe pandemics.- Published
- 2021
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23. Piezo-enhanced photocatalytic diclofenac mineralization over ZnO.
- Author
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Meroni D, Bianchi CL, Boffito DC, Cerrato G, Bruni A, Sartirana M, and Falletta E
- Abstract
The degradation of diclofenac has been realized for the first time by a piezo-enhanced sonophotocatalytic approach based on ZnO. The sonophotocatalytic degradation showed a slight enhancement in the degradation of the parent compound, whereas strong synergistic effects were observed for the mineralization process when suitable ZnO morphologies are used, reaching 70% of complete degradation of 25 ppm diclofenac using 0.1 g/L ZnO in 360 min. Tests in a complex water matrix show enhanced diclofenac removal, outperforming a TiO
2 benchmark photocatalyst. These promising experimental results promote this process as a good alternative to traditional degradation approaches for remediation of real water matrices., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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24. High-throughput label-free detection of DNA-to-RNA transcription inhibition using brightfield microscopy and deep neural networks.
- Author
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Sauvat A, Cerrato G, Humeau J, Leduc M, Kepp O, and Kroemer G
- Subjects
- Cell Nucleus, DNA, Image Processing, Computer-Assisted, RNA genetics, Microscopy, Neural Networks, Computer
- Abstract
Drug discovery is in constant evolution and major advances have led to the development of in vitro high-throughput technologies, facilitating the rapid assessment of cellular phenotypes. One such phenotype is immunogenic cell death, which occurs partly as a consequence of inhibited RNA synthesis. Automated cell-imaging offers the possibility of combining high-throughput with high-content data acquisition through the simultaneous computation of a multitude of cellular features. Usually, such features are extracted from fluorescence images, hence requiring labeling of the cells using dyes with possible cytotoxic and phototoxic side effects. Recently, deep learning approaches have allowed the analysis of images obtained by brightfield microscopy, a technique that was for long underexploited, with the great advantage of avoiding any major interference with cellular physiology or stimulatory compounds. Here, we describe a label-free image-based high-throughput workflow that accurately detects the inhibition of DNA-to-RNA transcription. This is achieved by combining two successive deep convolutional neural networks, allowing (1) to automatically detect cellular nuclei (thus enabling monitoring of cell death) and (2) to classify the extracted nuclear images in a binary fashion. This analytical pipeline is R-based and can be easily applied to any microscopic platform., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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25. TiO₂-Chitosan Hybrid Materials for Drug Delivery Applications: Conjugation Reaction with a Model Drug and Evaluation of the Functional Properties.
- Author
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Cerrato G, Martra G, Viscardi G, and Signoretto M
- Subjects
- Drug Delivery Systems, Hydrogen-Ion Concentration, Titanium, Chitosan, Pharmaceutical Preparations
- Abstract
The combination of TiO₂ and chitosan is known to allow the achievement of implantable devices which combines the mechanical properties of TiO₂, with the presence of chitosan, which ensures antibacterial properties combined with an in-situ drug-delivery of biomolecules physisorbed and/or covalently linked to chitosan. In this study, 5-aminofluorescein (5-AF), a derivative of fluorescein containing a primary amino group, has been used as model molecule to simulate a drug. This dye is characterized by low cost and low toxicity, and due to its high molar absorptivity it can easily be detected by means of absorption and emission spectroscopies. The combination of 5-AF and maleic anhydride (MA) with TiO₂-chitosan materials has generated a range of novel hybrid materials tailored to applications in localized stimuli-responsive drug delivery systems. Maleic anhydride has been used as pH sensitive spacer for the covalent functionalization of the TiO₂-chitosan hybrid with MA as linker molecule. This functionalization allowed to obtain a pH-sensitive hybrid material. The efficiency of the functionalization has been verified by means of different physico-chemical characterization techniques. The behaviour of the functionalized materials is related to different parameters, among which the ratio between physisorbed/coordinated and chemisorbed 5-AF and the matrix degradation. Moreover, delivery tests in simulated body solutions at different pH have been performed showing a pH-sensitive drug delivery behaviour and indicating that the release of 5-AF is favoured at basic pH.
- Published
- 2021
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26. Oleate-induced aggregation of LC3 at the trans-Golgi network is linked to a protein trafficking blockade.
- Author
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Cerrato G, Leduc M, Müller K, Liu P, Zhao L, Humeau J, Xie W, Zhang S, Kepp O, Sauvat A, and Kroemer G
- Subjects
- Animals, Autophagy, Humans, Mice, Lactosylceramides metabolism, Oleic Acid metabolism, Protein Transport genetics, trans-Golgi Network metabolism
- Abstract
Oleate, the most abundant endogenous and dietary cis-unsaturated fatty acid, has the atypical property to cause the redistribution of microtubule-associated proteins 1A/1B light chain 3B (referred to as LC3) to the trans-Golgi network (TGN), as shown here. A genome-wide screen identified multiple, mostly Golgi transport-related genes specifically involved in the oleate-induced relocation of LC3 to the Golgi apparatus. Follow-up analyses revealed that oleate also caused the retention of secreted proteins in the TGN, as determined in two assays in which the secretion of proteins was synchronized, (i) an assay involving a thermosensitive vesicular stomatitis virus G (VSVG) protein that is retained in the endoplasmic reticulum (ER) until the temperature is lowered, and (ii) an isothermic assay involving the reversible retention of the protein of interest in the ER lumen and that was used both in vitro and in vivo. A pharmacological screen searching for agents that induce LC3 aggregation at the Golgi apparatus led to the identification of "oleate mimetics" that share the capacity to block conventional protein secretion. In conclusion, oleate represents a class of molecules that act on the Golgi apparatus to cause the recruitment of LC3 and to stall protein secretion.
- Published
- 2021
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27. A genome-wide RNA interference screen disentangles the Golgi tropism of LC3.
- Author
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Cerrato G, Kepp O, Sauvat A, and Kroemer G
- Subjects
- Golgi Apparatus, Protein Transport, RNA Interference, Tropism, trans-Golgi Network, Autophagy, Oleic Acid
- Abstract
Oleate, the most abundantly occurring cis -unsaturated fatty acid, has the particularity to induce the accumulation of MAP1LC3B/LC3 (microtubule associated protein 1 light chain 3 beta) at the trans -Golgi apparatus. A genome-wide RNA interference screen designed to identify the mechanisms of this LC3 redistribution led to the identification of a BECN1-PIK3C3-independent pathway that, however, requires the ATG12-ATG5 and ATG7-dependent conjugation system, and several genes/proteins involved in endoplasmic reticulum (ER)-to-Golgi anterograde protein transport, as well as the unfolded protein response, including the integrated stress response that results in the phosphorylation of EIF2A/eIF2α (eukaryotic translation initiation factor 2A). Functional experiments revealed that oleate blocks conventional protein secretion, stalling the process at the level of the trans -Golgi network. Oleate-induced blockade of protein secretion occurred even after depletion of ATG5, suggesting that it does not rely on the recruitment of LC3 to the Golgi apparatus (which does require ATG5). Rather, it appears that oleate and other pharmacological inhibitors of protein secretion with a similar mode of action provoke a perturbation of the trans -Golgi compartment that secondarily results in the local enrichment of LC3.
- Published
- 2021
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28. A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency.
- Author
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Le Naour J, Liu P, Zhao L, Adjemian S, Sztupinszki Z, Taieb J, Mulot C, Silvin A, Dutertre CA, Ginhoux F, Sauvat A, Cerrato G, Castoldi F, Martins I, Stoll G, Paillet J, Mangane K, Richter C, Kepp O, Maiuri MC, Pietrocola F, Vandenabeele P, André F, Delaloge S, Szallasi Z, Laurent-Puig P, Zucman-Rossi J, Zitvogel L, Pol JG, Vacchelli E, and Kroemer G
- Subjects
- Animals, Colorectal Neoplasms genetics, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Poly I-C pharmacology, Receptors, Formyl Peptide genetics, Cell Transformation, Neoplastic drug effects, Colorectal Neoplasms drug therapy, Ligands, Poly I-C therapeutic use, Toll-Like Receptor 3
- Abstract
For anthracycline-based chemotherapy to be immunogenic, dying cancer cells must release annexin A1 (ANXA1) that subsequently interacts with the pattern recognition receptor, formyl peptide receptor 1 (FPR1), on the surface of dendritic cells (DC). Approximately 30% of individuals bear loss-of-function alleles of FPR1 , calling for strategies to ameliorate their anticancer immune response. Here, we show that immunotherapy with a ligand of Toll-like receptor-3, polyinosinic:polycytidylic acid (pIC), restores the deficient response to chemotherapy of tumors lacking ANXA1 developing in immunocompetent mice or those of normal cancers growing in FPR1-deficient mice. This effect was accompanied by improved DC- and T-lymphocyte-mediated anticancer immunity. Of note, carcinogen-induced breast cancers precociously developed in FPR1-deficient mice as compared with wild-type controls. A similar tendency for earlier cancer development was found in patients carrying the loss-of-function allele of FPR1 . These findings have potential implications for the clinical management of FPR1-deficient patients. SIGNIFICANCE: The loss-of-function variant rs867228 in FPR1 , harbored by approximately 30% of the world population, is associated with the precocious manifestation of breast, colorectal, esophageal, and head and neck carcinomas. pIC restores deficient chemotherapeutic responses in mice lacking Fpr1 , suggesting a personalized strategy for compensating for the FPR1 defect. This article is highlighted in the In This Issue feature, p. 211 ., (©2020 American Association for Cancer Research.)
- Published
- 2021
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29. High throughput screening for autophagy.
- Author
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Forveille S, Leduc M, Sauvat A, Cerrato G, Kroemer G, and Kepp O
- Subjects
- Drug Discovery, Drug Evaluation, Preclinical, Green Fluorescent Proteins genetics, Microtubule-Associated Proteins, Autophagy, High-Throughput Screening Assays
- Abstract
Robotized high throughput screening allows for the assessment of autophagy in a large number of samples. Here, we describe a drug discovery platform for the phenotypic identification of novel autophagy inducers by means of automated cell biology workflows employing robotized cell culture, sample preparation and data acquisition. In this setting, fluorescent biosensor cells that express microtubule-associated proteins 1A/1B light chain 3B (best known as LC3) conjugated to green fluorescent protein (GFP), are utilized together with automated high content microscopy for the image-based assessment of autophagy. In sum, we detail a drug discovery screening workflow from high throughput sample preparation and processing to data acquisition and analysis., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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30. Live cell imaging of LC3 dynamics.
- Author
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Cerrato G, Sauvat A, Kepp O, and Kroemer G
- Subjects
- Autophagy, Cell Nucleus, Cytoplasm, Green Fluorescent Proteins genetics, Autophagosomes, Microtubule-Associated Proteins
- Abstract
Macroautophagy (hereafter referred to as autophagy) serves the liberation of energy resources through the degradation of cellular components and is characterized by the formation of double-membraned vesicles, commonly referred to as autophagosomes. Microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) plays a crucial role during autophagosome formation, as cleavage of its immature form and subsequent conjugation to phosphatidylethanolamine facilitates autophagosomal membrane biogenesis. Indeed, the redistribution of green fluorescent protein (GFP)-conjugated LC3 from a diffuse cytosolic pattern into forming autophagosomes constitutes a morphological phenotype (commonly referred to as LC3 puncta) applicable to phenotypic analysis. The quantification of LC3 puncta in end-point assays has extensively been used in the past, allowing for the identification of autophagy modulators. Here, we describe a robust method employing automated confocal live cell imaging for the study of time-resolved LC3 dynamics. Furthermore, this method can be used to differentiate between phenotypes such as the homogeneous distribution of LC3 puncta in the cytoplasm, and the aggregation of LC3 clusters juxtaposed to the nucleus thus allowing for functional predictions., Competing Interests: Conflict of interest G.K. and O.K. are cofounders of Samsara Therapeutics. G.K. is a founder of everImmune and Therafast Bio., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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31. Morphology, Surface Structure and Water Adsorption Properties of TiO 2 Nanoparticles: A Comparison of Different Commercial Samples.
- Author
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Mino L, Negri C, Santalucia R, Cerrato G, Spoto G, and Martra G
- Subjects
- Adsorption, Spectroscopy, Fourier Transform Infrared, Spectroscopy, Near-Infrared, Nanoparticles chemistry, Titanium chemistry, Water chemistry
- Abstract
Water is a molecule always present in the reaction environment in photocatalytic and biomedical applications of TiO
2 and a better understanding of its interaction with the surface of TiO2 nanoparticles is crucial to develop materials with improved performance. In this contribution, we first studied the nature and the surface structure of the exposed facets of three commercial TiO2 samples (i.e., TiO2 P25, SX001, and PC105) by electron microscopy and IR spectroscopy of adsorbed CO. The morphological information was then correlated with the water adsorption properties, investigated at the molecular level, moving from multilayers of adsorbed H2 O to the monolayer, combining medium- and near-IR spectroscopies. Finally, we assessed in a quantitative way the surface hydration state at different water equilibrium pressures by microgravimetric measurements.- Published
- 2020
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32. ORR in Non-Aqueous Solvent for Li-Air Batteries: The Influence of Doped MnO 2 -Nanoelectrocatalyst.
- Author
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Pargoletti E, Salvi A, Giordana A, Cerrato G, Longhi M, Minguzzi A, Cappelletti G, and Vertova A
- Abstract
One of the major drawbacks in Lithium-air batteries is the sluggish kinetics of the oxygen reduction reaction (ORR). In this context, better performances can be achieved by adopting a suitable electrocatalyst, such as MnO
2 . Herein, we tried to design nano-MnO2 tuning the final ORR electroactivity by tailoring the doping agent (Co or Fe) and its content (2% or 5% molar ratios). Staircase-linear sweep voltammetries (S-LSV) were performed to investigate the nanopowders electrocatalytic behavior in organic solvent (propylene carbonate, PC and 0.15 M LiNO3 as electrolyte). Two percent Co-doped MnO2 revealed to be the best-performing sample in terms of ORR onset shift (of ~130 mV with respect to bare glassy carbon electrode), due to its great lattice defectivity and presence of the highly electroactive γ polymorph (by X-ray diffraction analyses, XRPD and infrared spectroscopy, FTIR). 5% Co together with 2% Fe could also be promising, since they exhibited fewer diffusive limitations, mainly due to their peculiar pore distribution (by Brunauer-Emmett-Teller, BET) that disfavored the cathode clogging. Particularly, a too-high Fe content led to iron segregation (by energy dispersive X-ray spectroscopy, EDX, X-ray photoelectron spectroscopy, XPS and FTIR) provoking a decrease of the electroactive sites, with negative consequences for the ORR.- Published
- 2020
- Full Text
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33. Understanding Solid-Gas Reaction Mechanisms by Operando Soft X-Ray Absorption Spectroscopy at Ambient Pressure.
- Author
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Braglia L, Fracchia M, Ghigna P, Minguzzi A, Meroni D, Edla R, Vandichel M, Ahlberg E, Cerrato G, and Torelli P
- Abstract
Ambient-pressure operando soft X-ray absorption spectroscopy (soft-XAS) was applied to study the reactivity of hydroxylated SnO
2 nanoparticles toward reducing gases. H2 was first used as a test case, showing that the gas phase and surface states can be simultaneously probed: Soft-XAS at the O K-edge gains sensitivity toward the gas phase, while at the Sn M4,5 -edges, tin surface states are explicitly probed. Results obtained by flowing hydrocarbons (CH4 and CH3 CHCH2 ) unequivocally show that these gases react with surface hydroxyl groups to produce water without producing carbon oxides and release electrons that localize on Sn to eventually form SnO. The partially reduced SnO2 - x layer at the surface of SnO2 is readily reoxidized to SnO2 by treating the sample with O2 at mild temperatures (>200 °C), revealing the nature of "electron sponge" of tin oxide. The experiments, combined with DFT calculations, allowed devising of a mechanism for dissociative hydrocarbon adsorption on SnO2 , involving direct reduction of Sn sites at the surface via cleavage of C-H bonds and the formation of methoxy- and/or methyl-tin species at the surface., Competing Interests: The authors declare no competing financial interest.- Published
- 2020
- Full Text
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34. Role of Synthetic Parameters on the Structural and Optical Properties of N,Sn-Copromoted Nanostructured TiO 2 : A Combined Ti K-Edge and Sn L 2,3 -Edges X-ray Absorption Investigation.
- Author
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Fracchia M, Ghigna P, Minguzzi A, Vertova A, Turco F, Cerrato G, and Meroni D
- Abstract
Sn-modification of TiO
2 photocatalysts has been recently proposed as a suitable strategy to improve pollutant degradation as well as hydrogen production. In particular, visible light activity could be promoted by doping with Sn2+ species, which are, however, thermally unstable. Co-promotion with N and Sn has been shown to lead to synergistic effects in terms of visible light activity, but the underlying mechanism has, so far, been poorly understood due to the system complexity. Here, the structural, optical, and electronic properties of N,Sn-copromoted, nanostructured TiO2 from sol-gel synthesis were investigated: the Sn/Ti molar content was varied in the 0-20% range and different post-treatments (calcination and low temperature hydrothermal treatment) were adopted in order to promote the sample crystallinity. Depending on the adopted post-treatment, the optical properties present notable differences, which supports a combined role of Sn dopants and N-induced defects in visible light absorption. X-ray absorption spectroscopy at the Ti K-edge and Sn L2,3 -edges shed light onto the electronic properties and structure of both Ti and Sn species, evidencing a marked difference at the Sn L2,3 -edges between the samples with 20% and 5% Sn/Ti ratio, showing, in the latter case, the presence of tin in a partially reduced state.- Published
- 2020
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35. Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy.
- Author
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Humeau J, Leduc M, Cerrato G, Loos F, Kepp O, and Kroemer G
- Subjects
- Animals, Autophagy physiology, Cell Line, Tumor, Humans, Mice, Phosphoric Monoester Hydrolases antagonists & inhibitors, Phosphoric Monoester Hydrolases metabolism, Phosphorylation drug effects, eIF-2 Kinase antagonists & inhibitors, eIF-2 Kinase metabolism, Eukaryotic Initiation Factor-2 metabolism
- Abstract
The integrated stress response is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) on serine 51 by one out of four specific kinases (EIF2AK1 to 4). Here we provide three series of evidence suggesting that macroautophagy (to which we refer to as autophagy) induced by a variety of distinct pharmacological agents generally requires this phosphorylation event. First, the induction of autophagic puncta by various distinct compounds was accompanied by eIF2α phosphorylation on serine 51. Second, the modulation of autophagy by >30 chemically unrelated agents was partially inhibited in cells expressing a non-phosphorylable (S51A) mutant of eIF2α or lacking all four eIF2α kinases, although distinct kinases were involved in the response to different autophagy inducers. Third, inhibition of eIF2α phosphatases was sufficient to stimulate autophagy. In synthesis, it appears that eIF2α phosphorylation is a central event for the stimulation of autophagy.
- Published
- 2020
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36. Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress.
- Author
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Humeau J, Sauvat A, Cerrato G, Xie W, Loos F, Iannantuoni F, Bezu L, Lévesque S, Paillet J, Pol J, Leduc M, Zitvogel L, de Thé H, Kepp O, and Kroemer G
- Subjects
- Artificial Intelligence, Dactinomycin pharmacology, Dactinomycin therapeutic use, Humans, Immunogenic Cell Death, Antineoplastic Agents therapeutic use, Neoplasms drug therapy
- Abstract
Chemotherapy still constitutes the standard of care for the treatment of most neoplastic diseases. Certain chemotherapeutics from the oncological armamentarium are able to trigger pre-mortem stress signals that lead to immunogenic cell death (ICD), thus inducing an antitumor immune response and mediating long-term tumor growth reduction. Here, we used an established model, built on artificial intelligence to identify, among a library of 50,000 compounds, anticancer agents that, based on their molecular descriptors, were predicted to induce ICD. This algorithm led us to the identification of dactinomycin (DACT, best known as actinomycin D), a highly potent cytotoxicant and ICD inducer that mediates immune-dependent anticancer effects in vivo. Since DACT is commonly used as an inhibitor of DNA to RNA transcription, we investigated whether other experimentally established or algorithm-selected, clinically employed ICD inducers would share this characteristic. As a common leitmotif, a panel of pharmacological ICD stimulators inhibited transcription and secondarily translation. These results establish the inhibition of RNA synthesis as an initial event for ICD induction., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2020
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37. Exploring Sn x Ti 1-x O 2 Solid Solutions Grown onto Graphene Oxide (GO) as Selective Toluene Gas Sensors.
- Author
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Pargoletti E, Verga S, Chiarello GL, Longhi M, Cerrato G, Giordana A, and Cappelletti G
- Abstract
The major drawback of oxide-based sensors is the lack of selectivity. In this context, Sn
x Ti1-x O2 /graphene oxide (GO)-based materials were synthesized via a simple hydrothermal route, varying the titanium content in the tin dioxide matrix. Then, toluene and acetone gas sensing performances of the as-prepared sensors were systematically investigated. Specifically, by using 32:1 SnO2 /GO and 32:1 TiO2 /GO, a greater selectivity towards acetone analyte, also at room temperature, was obtained even at ppb level. However, solid solutions possessing a higher content of tin relative to titanium (as 32:1 Sn0.55 Ti0.45 O2 /GO) exhibited higher selectivity towards bigger and non-polar molecules (such as toluene) at 350 °C, rather than acetone. A deep experimental investigation of structural (XRPD and Raman), morphological (SEM, TEM, BET surface area and pores volume) and surface (XPS analyses) properties allowed us to give a feasible explanation of the different selectivity. Moreover, by exploiting the UV light, the lowest operating temperature to obtain a significant and reliable signal was 250 °C, keeping the greater selectivity to the toluene analyte. Hence, the feasibility of tuning the chemical selectivity by engineering the relative amount of SnO2 and TiO2 is a promising feature that may guide the future development of miniaturized chemoresistors.- Published
- 2020
- Full Text
- View/download PDF
38. Quantitative determination of phagocytosis by bone marrow-derived dendritic cells via imaging flow cytometry.
- Author
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Cerrato G, Liu P, Martins I, Kepp O, and Kroemer G
- Subjects
- Animals, Bone Marrow Cells cytology, Bone Marrow Cells immunology, Cell Line, Tumor, Cells, Cultured, Dendritic Cells cytology, Female, Mice, Inbred C57BL, Dendritic Cells immunology, Flow Cytometry methods, Neoplasms immunology, Phagocytosis
- Abstract
Immunogenic cell death (ICD), induced by certain anticancer chemotherapeutics, leads to the emission of danger associated molecular patterns (DAMP) by cancer cells, which facilitates the attraction, activation and maturation of dendritic cells (DC) as well as the subsequent priming of effector T cells. In this context calreticulin (CALR) exposed at an early stage of ICD at the surface of the cancer cells serves as phagocytic signal and triggers the formation of immunological synapses between malignant cells and DC. Subsequent phagocytosis facilitates the transfer of tumor associated antigen and thus depicts a fundamental step in the generation of anticancer immunity. Here we provide an imaging flowcytometric protocol for the quantification of ICD-associated DC phagocytosis of cancer cells. As compared to the traditional flowcytometry-based analysis, the presented method offers additional means of differentiation between the transient formation of immunological synapses and the final DC-mediated phagocytosis of cancer cells., (© 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
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39. Photocatalytic porcelain grés large slabs digitally coated with AgNPs-TiO 2 .
- Author
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Bianchi CL, Cerrato G, Pirola C, Galli F, and Capucci V
- Subjects
- Air Pollutants analysis, Air Pollutants radiation effects, Catalysis, Nitrogen Oxides analysis, Nitrogen Oxides radiation effects, Printing, Three-Dimensional, Surface Properties, Air Pollution, Indoor prevention & control, Construction Materials, Nanoparticles chemistry, Silver chemistry, Titanium chemistry, Ultraviolet Rays
- Abstract
TiO
2 is employed as both photocatalytic and structural materials, leading to its applications in external coatings or in interior furnishing devices, including cement mortar, tiles, floorings, and glass supports. The authors have already demonstrated the efficiency of photoactive micro-sized TiO2 and here its industrial use is reported using the digital printing to coat porcelain grés slabs. Many advantages are immediately evident, namely rapid and precise deposition, no waste of raw materials, thus positively affecting the economy of the process. Data for the thin films deposited by digital printing were compared with those obtained for the conventional spray method. The use of metal-doped TiO2 is also reported so that the photoactivity of these materials can be exploited even under LED light. The digital inkjet printed coatings exhibited superior photocatalytic performance owing to both higher exposed surface area and greater volume of deposited anatase, as well as the greater areal distribution density of thinly and thickly coated regions. Moreover, the presence of TiO2 doped silver increased the efficiency of the materials in NOx degradation both under UVA and LED lights.- Published
- 2019
- Full Text
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40. Ultrasound to improve both synthesis and pollutants degradation based on metal nanoparticles supported on TiO 2 .
- Author
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Stucchi M, Cerrato G, and Bianchi CL
- Abstract
Sonochemistry is based on acoustic cavitation, which consist in the formation, growth, and implosive collapse of bubbles within a liquid. Collapsing bubbles generate localized hot spots, characterized by temperatures up to 5000 K and pressures up to 1800 atm. These extreme conditions allow producing a variety of nanostructured and amorphous materials, as well as they are advantageous for chemical processes. Ultrasound requires inexpensive equipment and fewer steps than conventional methods. Combining ultrasound and photocatalysis enhances the performance of the processes, reduces reaction time, avoids the use of extreme physical conditions and improves the photocatalytic materials properties increasing their activity. Here, we reported the positive effect of US in synthesizing Me-modified TiO
2 (Me = Ag, Cu, Mn) for pollutants degradation in gas-phase; also, we proved the advantageous application of ultrasound for the photocatalytic removal of organic compounds in water. Ultrasound produced more efficient Me-doped TiO2 , which showed higher activity in visible light. When combined with photocatalytic water treatment, the organic compounds degradation and mineralization increases., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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41. Micro-TiO 2 coated glass surfaces safely abate drugs in surface water.
- Author
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Cerrato G, Bianchi CL, Galli F, Pirola C, Morandi S, and Capucci V
- Subjects
- Glass, Ibuprofen chemistry, Ultraviolet Rays, Water Pollutants, Chemical chemistry, Ibuprofen radiation effects, Photolysis, Titanium chemistry, Water Pollutants, Chemical radiation effects
- Abstract
The ingredients of Pharmaceuticals and Personal Care Products (PPCPs) persist in water and conventional treatment plants are not able to remove them efficiently. Sonochemical treatment is insufficient to mineralize organics such as ibuprofen into CO
2 and H2 O. TiO2 degrades ibuprofen (IBP) under UV light; however, it does not reach a high grade of conversion. Here, we investigated the mineralization of ibuprofen to CO2 by TiO2 UV-C photocatalysis. We replaced nano-sized P25 (the standard catalyst) with a micro-sized commercial sample of TiO2 to preclude the use of nanoparticles which are dangerous for human health and because typical filtration systems are expensive and inefficient. We deposited micro-TiO2 on glass Raschig rings to ensure an easy recovery and reuse of the photocatalyst and we studied its performance both with a batch and a continuous reactor. Micro-TiO2 mineralized 100% of IBP in 24 h. TiO2 -coated glass Raschig rings degraded 87% of IBP in 6 h of UV-C irradiation in a continuous reactor, with a mineralization of 25%. Electronspray ionization mass spectrometer (ESI-MS, positive mode) analyses identified 13 different byproducts and we hypothised a degradration pathway for IBP degradation., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
42. Trial watch: Peptide-based vaccines in anticancer therapy.
- Author
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Bezu L, Kepp O, Cerrato G, Pol J, Fucikova J, Spisek R, Zitvogel L, Kroemer G, and Galluzzi L
- Abstract
Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics. Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen.
- Published
- 2018
- Full Text
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43. Nano-MnO₂ Decoration of TiO₂ Microparticles to Promote Gaseous Ethanol Visible Photoremoval.
- Author
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Stucchi M, Boffito DC, Pargoletti E, Cerrato G, Bianchi CL, and Cappelletti G
- Abstract
TiO₂-based photocatalysis under visible light is an attractive way to abate air pollutants. Moreover, developing photocatalytic materials on a large-scale requires safe and low-cost precursors. Both high-performance TiO₂ nanopowders and visible-light active noble metals do not match these requirements. Here, we report the design of novel Mn-decorated micrometric TiO₂ particles. Pigmentary TiO₂ replaced unsafe nano-TiO₂ and firmly supported MnO
x particles. Mn replaced noble metals such as Au or Ag, opening the way for the development of lower cost catalysts. Varying Mn loading or pH during the impregnation affected the final activity, thus giving important information to optimize the synthesis. Photocatalytic activity screening occurred on the gas-phase degradation of ethanol as a reference molecule, both under ultraviolet (UV) (6 h) and Light Emitting Diode (LED) (24 h) irradiation. Mn-doped TiO₂ reached a maximum ethanol degradation of 35% under visible light after 24 h for the sample containing 20% of Mn. Also, we found that an acidic pH increased both ethanol degradation and mineralization to CO₂, while an alkaline pH drastically slowed down the reaction. A strict correlation between photocatalytic results and physico-chemical characterizations of the synthesized powders were drawn.- Published
- 2018
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44. Micro-sized TiO 2 as photoactive catalyst coated on industrial porcelain grès tiles to photodegrade drugs in water.
- Author
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Bianchi CL, Sacchi B, Capelli S, Pirola C, Cerrato G, Morandi S, and Capucci V
- Subjects
- Catalysis, Clay, Drinking Water chemistry, Manufactured Materials, Particle Size, Water chemistry, Water Pollutants, Chemical chemistry, Acetaminophen chemistry, Aspirin chemistry, Pharmaceutical Preparations chemistry, Photolysis, Titanium chemistry, Wastewater chemistry, Water Purification methods
- Abstract
Pharmaceutical compounds and their metabolites raise worrying questions because of their continuous release and lack of efficient removal by conventional wastewater treatments; therefore, they are being detected in groundwater, surface water and drinking water in increasing concentrations. Paracetamol and aspirin are two of the most commonly used drugs employed as fever reducer, analgesic and anti-inflammatory. They and their metabolites are very often found in river water, so their degradation is necessary in order to render water suitable for human consumption. The present work is focused on the comparison of the photocatalytic performance of industrial active grés porcelain tiles covered with a commercial micro-sized TiO
2 by industrial process using either conventional spray deposition or innovative digital printing methods. The photodegradation of two commonly used drugs, namely aspirin and paracetamol, was investigated both individually and as a mixture, in both deionized and tap water. The results reveal the full conversion of the drugs and the significant role of the photocatalytic tiles in the mineralization processes leading to harmless inorganic species. In particular, the digitally printed tiles exhibited better photodegradation performance for both drugs compared to the spray deposited tiles. No deactivation was observed on both photocatalytic tiles.- Published
- 2018
- Full Text
- View/download PDF
45. Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids.
- Author
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Sauvat A, Chen G, Müller K, Tong M, Aprahamian F, Durand S, Cerrato G, Bezu L, Leduc M, Franz J, Rockenfeller P, Sadoshima J, Madeo F, Kepp O, and Kroemer G
- Subjects
- Animals, Cell Line, Tumor, Drosophila melanogaster drug effects, Drosophila melanogaster physiology, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress drug effects, Female, Golgi Apparatus drug effects, Golgi Apparatus metabolism, Humans, Kinetics, Longevity drug effects, Mice, Inbred C57BL, Oleic Acid pharmacology, Oleic Acids, Saccharomyces cerevisiae drug effects, Signal Transduction drug effects, Autophagy drug effects, Fatty Acids pharmacology, Trans Fatty Acids pharmacology
- Abstract
Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids., (Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
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46. Ultrasound assisted synthesis of Ag-decorated TiO 2 active in visible light.
- Author
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Stucchi M, Bianchi CL, Argirusis C, Pifferi V, Neppolian B, Cerrato G, and Boffito DC
- Abstract
Titanium dioxide is the most popular photocatalyst to degrade organic pollutants in air, as well as in water. The principal drawback preventing its commercial application lies in its limited absorption of the visible light (400-700nm), while it is active under UV irradiation (≤387nm). Supporting noble metals in the form of nanoparticles on TiO
2 increases its activity in the visible range. However, both the synthesis of noble metal nanoparticles and their deposition on TiO2 are multi-step processes that often require organic solvents. Here, we deposit Ag nanoparticles from AgNO3 on the surface of micrometric TiO2 with H2 O as a solvent and under ultrasound irradiation at 30Wcm-2 . Ultrasound increases the surface amount of Ag on TiO2 with heterogeneous size distribution of Ag nanoparticles, which are bigger and overlaid (1-20nm vs. 0.5-3nm) compared to the sample obtained in traditional conditions (TEM images). While this change in morphology had no effect on acetone photodegradation under UV light, the 5%, 10%, and 20% Ag-TiO2 degraded 17%, 20% and 24% acetone under visible light, respectively. The 10% by weight Ag-TiO2 sample obtained in absence of ultrasound only degraded 14% acetone in 6h, while the bare TiO2 was not active., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
47. Aspirin and paracetamol removal using a commercial micro-sized TiO 2 catalyst in deionized and tap water.
- Author
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Bianchi CL, Sacchi B, Pirola C, Demartin F, Cerrato G, Morandi S, and Capucci V
- Subjects
- Catalysis, Titanium, Water Pollutants, Chemical, Acetaminophen, Aspirin
- Abstract
Micro-sized TiO
2 catalyst was employed to degrade pharmaceutical compounds, i.e. aspirin and paracetamol, two of the most widely used drugs, purchasable without prescription. Their active agents, acetylsalicylic acid and acetaminophen, are characterized by different substituent groups, linked to the aromatic ring, which affect both the photodegradation and mineralization processes. The experimental conditions highlight the relationship between the nature of the pristine molecules, their degradation mechanisms, their mutual interference and the water's role. The research started from model systems with a single pollutant to the mixture of them and finally by moving from deionized water to tap water.- Published
- 2017
- Full Text
- View/download PDF
48. Copper NPs decorated titania: A novel synthesis by high energy US with a study of the photocatalytic activity under visible light.
- Author
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Stucchi M, Bianchi CL, Pirola C, Cerrato G, Morandi S, Argirusis C, Sourkouni G, Naldoni A, and Capucci V
- Abstract
The most important drawback of the use of TiO2 as photocatalyst is its lack of activity under visible light. To overcome this problem, the surface modification of commercial micro-sized TiO2 by means of high-energy ultrasound (US), employing CuCl2 as precursor molecule to obtain both metallic copper as well as copper oxides species at the TiO2 surface, is here. We have prepared samples with different copper content, in order to evaluate its impact on the photocatalytic performances of the semiconductor, and studied in particular the photodegradation in the gas phase of some volatile organic molecules (VOCs), namely acetone and acetaldehyde. We used a LED lamp in order to have only the contribution of the visible wavelengths to the TiO2 activation (typical LED lights have no emission in the UV region). We employed several techniques (i.e., HR-TEM, XRD, FT-IR and UV-Vis) in order to characterize the prepared samples, thus evidencing different sample morphologies as a function of the various copper content, with a coherent correlation between them and the photocatalytic results. Firstly, we demonstrated the possibility to use US to modify the TiO2, even when it is commercial and micro-sized as well; secondly, by avoiding completely the UV irradiation, we confirmed that pure TiO2 is not activated by visible light. On the other hand, we showed that copper metal and metal oxides nanoparticles strongly and positively affect its photocatalytic activity., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
49. Conjugation of amino-bioactive glasses with 5-aminofluorescein as probe molecule for the development of pH sensitive stimuli-responsive biomaterials.
- Author
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Aina V, Malavasi G, Magistris C, Cerrato G, Martra G, Viscardi G, Menabue L, and Lusvardi G
- Subjects
- Biocompatible Materials chemistry, Drug Carriers chemistry, Drug Delivery Systems, Hydrogen-Ion Concentration, Maleates chemistry, Maleic Anhydrides chemistry, Molecular Probes chemistry, Propylamines, Silanes chemistry, Stimulation, Chemical, Biocompatible Materials chemical synthesis, Drug Carriers chemical synthesis, Fluoresceins chemistry, Glass chemistry, Molecular Probes chemical synthesis
- Abstract
Bioceramics, such as silica-based glasses, are widely used in bone and teeth restoration. Nowadays, the association between nanotechnology and pharmacology is one of the most promising research fields in cancer therapy. The advanced processing methods and new chemical strategies allow the incorporation of drugs within them or on their functionalized surfaces. Bioceramics can act as local drug delivery systems to treat bone and teeth diseases. The present paper reports data related to the development of a pH-stimuli responsive bioactive glass. The glass conjugation with 5-aminofluorescein (5-AF), through a pH-sensitive organic spacer, allows to produce a pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favour the release of 5-AF directly at the target site. 5-AF has been chosen as a simple, low cost, non toxic model to simulate doxorubicin, an anticancer drug. As doxorubicin, 5-AF contains an amino group in its structure in order to form an amide bond with the carboxylic functionalities of the glass. Raman spectroscopy and thermal analysis confirm the glass conjugation of 5-AF by means of an amide bond; the amount of 5-AF loaded was very high (≈ 65 and 44 wt%). The release tests at two different pH (4.2 and 7.4) show that the amount of released 5-AF is higher at acid pH with respect to physiological one. This preliminary datum evidenced that a pH-sensitive drug delivery system has been developed. The low amount of 5-AF released (<1 wt% of the total 5-AF) is due to the very low solubility of 5-AF in aqueous medium. This disadvantage, may be overcome in a dynamic environment (physiological conditions), where it is possible to obtain a drug release system ensuring an effective therapeutic dose for long times and, at the same time, avoiding the drug toxicity.
- Published
- 2014
- Full Text
- View/download PDF
50. New formulation of functionalized bioactive glasses to be used as carriers for the development of pH-stimuli responsive biomaterials for bone diseases.
- Author
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Aina V, Magistris C, Cerrato G, Martra G, Viscardi G, Lusvardi G, Malavasi G, and Menabue L
- Subjects
- Animals, Bone Diseases drug therapy, Cysteamine chemistry, Fluoresceins chemistry, Humans, Hydrogen-Ion Concentration, Biocompatible Materials chemistry, Drug Delivery Systems methods, Glass chemistry
- Abstract
The aim of the present contribution is to prepare a functionalized bioactive glass potentially useful as prosthetic material, but also able to release organic molecules in response to a change of the pH environment. By this approach it is possible to develop devices which can be used for a triggered drug release in response to specific stimuli; this is an attractive research field, in order to avoid either systemic and/or local toxic effects of drugs. In particular, in the present paper we report data related to the development of a new formulation of bioactive glasses, their functionalization with organic molecules to obtain a pH-sensitive bond, their physicochemical characterization and in vitro bioactivity in simulated biological fluids (SBF), and organic molecule delivery tests at different pH. The glass functionalization, by means of a covalent reaction, allows us to produce a model of pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favor the release of the organic molecules directly at the target site. Cysteamine and 5-aminofluorescein are used as model molecules to simulate a drug. The materials, before and after the different functionalization steps and in vitro release tests at different pH, have been characterized by means of different experimental techniques such as X-ray powder diffraction (XRPD), Raman, FTIR and fluorescence spectroscopies, N2 adsorption, thermogravimetric (TGA) and elemental analysis.
- Published
- 2014
- Full Text
- View/download PDF
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