39 results on '"Vadalà R"'
Search Results
2. The sophisticated transcriptional response governed by transposable elements in human health and disease
- Author
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Marasca, F, Gasparotto, E, Polimeni, B, Vadalà, R, Ranzani, V, Bodega, B, Marasca F., Gasparotto E., Polimeni B., Vadalà R., Ranzani V., Bodega B., Marasca, F, Gasparotto, E, Polimeni, B, Vadalà, R, Ranzani, V, Bodega, B, Marasca F., Gasparotto E., Polimeni B., Vadalà R., Ranzani V., and Bodega B.
- Abstract
Transposable elements (TEs), which cover ~45% of the human genome, although firstly considered as “selfish” DNA, are nowadays recognized as driving forces in eukaryotic genome evolution. This capability resides in generating a plethora of sophisticated RNA regulatory networks that influence the cell type specific transcriptome in health and disease. Indeed, TEs are transcribed and their RNAs mediate multi-layered transcriptional regulatory functions in cellular identity establishment, but also in the regulation of cellular plasticity and adaptability to environmental cues, as occurs in the immune response. Moreover, TEs transcriptional deregulation also evolved to promote pathogenesis, as in autoimmune and inflammatory diseases and cancers. Importantly, many of these findings have been achieved through the employment of Next Generation Sequencing (NGS) technologies and bioinformatic tools that are in continuous improvement to overcome the limitations of analyzing TEs sequences. However, they are highly homologous, and their annotation is still ambiguous. Here, we will review some of the most recent findings, questions and improvements to study at high resolution this intriguing portion of the human genome in health and diseases, opening the scenario to novel therapeutic opportunities.
- Published
- 2020
3. Epigenetic role of transposable elements in human T lymphocytes identity and plasticity
- Author
-
Vadalà, R, VADALÀ, REBECCA, Vadalà, R, and VADALÀ, REBECCA
- Abstract
I linfociti infiltranti il tumore (TIL) sono i componenti principali del microambiente tumorale e svolgono un ruolo centrale nell'immunità antitumorale. Durante l'immunoediting del cancro, i TIL diventano disfunzionali, un fenotipo associato alla compromissione delle funzioni effettrici, alla ridotta crescita cellulare e alla ridotta capacità di uccisione. Infatti, i trattamenti di immunoterapie contro il cancro cercano di ripristinare lo stato disfunzionale dei TIL al fine di promuovere la clearance del tumore. Le immunoterapie rappresentano oggigiorno la nuova frontiera nella lotta contro il cancro, ma ancora poco si sa per quanto riguarda i modulatori epigenetici responsabili delle proprietà dei TIL; la scoperta di nuove molecole e meccanismi di azione possibili potrebbe migliorare sostanzialmente le conoscenze relative alle immunoterapie e alla reattività del paziente ad esse. Per questo motivo, stiamo applicando nuovi approcci e tecnologie in questo campo, vale a dire lo studio delle funzioni degli elementi trasponibili (TE) come nuovi attori epigenetici nell'identità, nella plasticità e nell'adattabilità dei TIL all'ambiente tumorale. I TE sono sequenze di DNA ripetute che coprono il 40-45% del genoma umano e diversi studi suggeriscono che i TE esercitano una funzione cruciale nella regolazione epigenetica sia in cis che in trans, essendo una fonte di RNA regolatori non codificanti e partecipando al ripiegamento della cromatina. Tra i TE, siamo interessati alle possibili funzioni epigenetiche degli elementi LINE1, che rappresentano il 18% del genoma umano, considerati come nuove molecole chiave coinvolte nella regolazione epigenetica dell'identità cellulare. Fino ad oggi il ruolo e la dinamica degli RNA derivati dai TEs sono stati studiati solo nelle cellule staminali embrionali o durante lo sviluppo dell'organismo, mentre non c'era evidenza delle loro possibili funzioni in cellule completamente differenziate derivate da tessuti adulti, come i linfocit, Tumor infiltrating lymphocytes (TILs) are the principal components of the tumor microenvironment, and play a central role in antitumor immunity. During cancer immunoediting, TILs became dysfunctional, a phenotype associated to effector functions impairment, reduced cell growth and decreased killing capability. Indeed, cancer immunotherapies treatments try to revert TILs dysfunctional state in order to promote tumor clearance. Immunotherapies nowadays represent the novel frontier in fighting cancer but still little is known regarding the epigenetic modulators responsible for TILs properties; the discovery of novel, possible targetable molecules and mechanisms could substantially improve knowledges regarding immunotherapies and patient responsiveness to them. For this reason, we are applying novel approaches and technologies in this filed, namely the investigation of transposable elements (TEs) functions as novel epigenetic players in TILs identity, plasticity and adaptability to the environmental cancer driven milieu. TEs are interspersed repetitive DNA sequences that cover 40 - 45% of the human genome and growing evidence suggests that TEs exert a crucial function in epigenetic regulation both in cis and in trans, being a source of non-coding regulatory RNAs and participating to chromatin folding. Among TEs, we are interested in the possible epigenetic functions of LINE1 elements, that represents 18% of the human genome, considered as novel key molecules involved in epigenetic regulation of cell identity. Until today the role and the dynamics of TEs-derived RNAs were investigated only in embryonic stem cells or during organism development, while there was no evidence of their possible functions in fully differentiated cells derived from adult tissues, as human Naïve T lymphocytes, that are plastic cells able to adapt and differentiate to diverse effector cells based on the cytokine milieu. We demonstrate that, among T cells subsets, there is a specific enrichment f
- Published
- 2022
4. LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion
- Author
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Marasca, F, Sinha, S, Vadalà, R, Polimeni, B, Ranzani, V, Paraboschi, E, Burattin, F, Ghilotti, M, Crosti, M, Negri, M, Campagnoli, S, Notarbartolo, S, Sartore-Bianchi, A, Siena, S, Prati, D, Montini, G, Viale, G, Torre, O, Harari, S, Grifantini, R, Soldà, G, Biffo, S, Abrignani, S, Bodega, B, Marasca, Federica, Sinha, Shruti, Vadalà, Rebecca, Polimeni, Benedetto, Ranzani, Valeria, Paraboschi, Elvezia Maria, Burattin, Filippo Vittorio, Ghilotti, Marco, Crosti, Mariacristina, Negri, Maria Luce, Campagnoli, Susanna, Notarbartolo, Samuele, Sartore-Bianchi, Andrea, Siena, Salvatore, Prati, Daniele, Montini, Giovanni, Viale, Giuseppe, Torre, Olga, Harari, Sergio, Grifantini, Renata, Soldà, Giulia, Biffo, Stefano, Abrignani, Sergio, Bodega, Beatrice, Marasca, F, Sinha, S, Vadalà, R, Polimeni, B, Ranzani, V, Paraboschi, E, Burattin, F, Ghilotti, M, Crosti, M, Negri, M, Campagnoli, S, Notarbartolo, S, Sartore-Bianchi, A, Siena, S, Prati, D, Montini, G, Viale, G, Torre, O, Harari, S, Grifantini, R, Soldà, G, Biffo, S, Abrignani, S, Bodega, B, Marasca, Federica, Sinha, Shruti, Vadalà, Rebecca, Polimeni, Benedetto, Ranzani, Valeria, Paraboschi, Elvezia Maria, Burattin, Filippo Vittorio, Ghilotti, Marco, Crosti, Mariacristina, Negri, Maria Luce, Campagnoli, Susanna, Notarbartolo, Samuele, Sartore-Bianchi, Andrea, Siena, Salvatore, Prati, Daniele, Montini, Giovanni, Viale, Giuseppe, Torre, Olga, Harari, Sergio, Grifantini, Renata, Soldà, Giulia, Biffo, Stefano, Abrignani, Sergio, and Bodega, Beatrice
- Abstract
How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion.
- Published
- 2022
5. Stereotactic body radiotherapy in non-operable lung cancer patients
- Author
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Vadalà, R. E., Santacaterina, A., Sindoni, A., Platania, A., Arcudi, A., Ferini, G., Mazzei, M. M., Marletta, D., Rifatto, C., Risoleti, E. V. I., Severo, C., Pontoriero, A., Iatì, G., and Pergolizzi, S.
- Published
- 2016
- Full Text
- View/download PDF
6. Psychological issues and sleep deprivation: are there gender differences?
- Author
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Bhatted, D., Ranganathan, L., Vadala, R., and Ramakrishnan, N.
- Published
- 2017
- Full Text
- View/download PDF
7. Appropriate bmi criteria for Indian population: does it help stratify obstructive sleep apnea (OSA) patients better?
- Author
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Vadala, R., Deenadayalan, H., Ranganathan, L., and Ramakrishnan, N.
- Published
- 2017
- Full Text
- View/download PDF
8. LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion
- Author
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Federica Marasca, Shruti Sinha, Rebecca Vadalà, Benedetto Polimeni, Valeria Ranzani, Elvezia Maria Paraboschi, Filippo Vittorio Burattin, Marco Ghilotti, Mariacristina Crosti, Maria Luce Negri, Susanna Campagnoli, Samuele Notarbartolo, Andrea Sartore-Bianchi, Salvatore Siena, Daniele Prati, Giovanni Montini, Giuseppe Viale, Olga Torre, Sergio Harari, Renata Grifantini, Giulia Soldà, Stefano Biffo, Sergio Abrignani, Beatrice Bodega, Marasca, F, Sinha, S, Vadalà, R, Polimeni, B, Ranzani, V, Paraboschi, E, Burattin, F, Ghilotti, M, Crosti, M, Negri, M, Campagnoli, S, Notarbartolo, S, Sartore-Bianchi, A, Siena, S, Prati, D, Montini, G, Viale, G, Torre, O, Harari, S, Grifantini, R, Soldà, G, Biffo, S, Abrignani, S, and Bodega, B
- Subjects
CD4-Positive T-Lymphocytes ,Transcription, Genetic ,RNA Splicing ,RNA-Binding Proteins ,TIL ,LINE1 ,Mechanistic Target of Rapamycin Complex 1 ,Lymphocyte Activation ,Phosphoproteins ,Chromatin ,Heterogeneous-Nuclear Ribonucleoproteins ,Histones ,Transcription Factors, TFII ,Long Interspersed Nucleotide Elements ,Lymphocytes, Tumor-Infiltrating ,Gene Expression Regulation ,Interferon Regulatory Factors ,Genetics ,Humans ,RNA ,Polypyrimidine Tract-Binding Protein ,Signal Transduction - Abstract
How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion.
- Published
- 2022
- Full Text
- View/download PDF
9. Epigenetic role of transposable elements in human T lymphocytes identity and plasticity
- Author
-
VADALÀ, REBECCA and Vadalà, R
- Subjects
Trasposoni ,linfociti T ,tumore ,T lymphocyte ,cancer ,immunoterapia ,LINE1 ,BIO/11 - BIOLOGIA MOLECOLARE ,TE - Abstract
I linfociti infiltranti il tumore (TIL) sono i componenti principali del microambiente tumorale e svolgono un ruolo centrale nell'immunità antitumorale. Durante l'immunoediting del cancro, i TIL diventano disfunzionali, un fenotipo associato alla compromissione delle funzioni effettrici, alla ridotta crescita cellulare e alla ridotta capacità di uccisione. Infatti, i trattamenti di immunoterapie contro il cancro cercano di ripristinare lo stato disfunzionale dei TIL al fine di promuovere la clearance del tumore. Le immunoterapie rappresentano oggigiorno la nuova frontiera nella lotta contro il cancro, ma ancora poco si sa per quanto riguarda i modulatori epigenetici responsabili delle proprietà dei TIL; la scoperta di nuove molecole e meccanismi di azione possibili potrebbe migliorare sostanzialmente le conoscenze relative alle immunoterapie e alla reattività del paziente ad esse. Per questo motivo, stiamo applicando nuovi approcci e tecnologie in questo campo, vale a dire lo studio delle funzioni degli elementi trasponibili (TE) come nuovi attori epigenetici nell'identità, nella plasticità e nell'adattabilità dei TIL all'ambiente tumorale. I TE sono sequenze di DNA ripetute che coprono il 40-45% del genoma umano e diversi studi suggeriscono che i TE esercitano una funzione cruciale nella regolazione epigenetica sia in cis che in trans, essendo una fonte di RNA regolatori non codificanti e partecipando al ripiegamento della cromatina. Tra i TE, siamo interessati alle possibili funzioni epigenetiche degli elementi LINE1, che rappresentano il 18% del genoma umano, considerati come nuove molecole chiave coinvolte nella regolazione epigenetica dell'identità cellulare. Fino ad oggi il ruolo e la dinamica degli RNA derivati dai TEs sono stati studiati solo nelle cellule staminali embrionali o durante lo sviluppo dell'organismo, mentre non c'era evidenza delle loro possibili funzioni in cellule completamente differenziate derivate da tessuti adulti, come i linfociti T umani, che sono cellule plastiche in grado di adattarsi e differenziarsi in base all'ambiente circostante. Abbiamo dimostrato che, tra i sottotipi di cellule T, esiste un arricchimento specifico per gli RNA associati alla cromatina LINE1 nelle cellule T CD4 + naïve. Inoltre, gli RNA LINE1 mostrano una dinamica specifica e tempestiva, essendo rapidamente downregolati dopo l'attivazione del TCR. In particolare, esperimenti funzionali hanno suggerito che questi RNA potrebbero regolare le funzioni effettrici dei linfociti T. A seguito di queste evidenze, lo scopo di questa tesi è stato quello di valutare il coinvolgimento di LINE1 nella regolazione epigenetica dell'identità cellulare e delle funzioni nei TIL. Abbiamo generato un modello in vitro per studiare la dinamica di LINE1 in cellule T esauste e disfunzionali, inoltre, abbiamo avuto la possibilità di isolare da pazienti con tumore al colon e al polmone i TIL dai tessuti tumorali e dalla loro controparte normale per eseguire esperimenti funzionali e valutare le funzioni di LINE1 in un contesto patologico. Abbiamo dimostrato che le TIL mostrano un riaccumulo aberrante degli RNA di LINE1 che è associato al fenotipo disfunzionale e che il silenziamento di questi RNA è sufficiente per riattivare le loro funzioni effettrici e di uccisione permettendo una reversione del fenotipo. Infine, miriamo a definire gli RNA di LINE1 come nuove molecole regolatrici di TIL per trovare nuove molecole di RNA che potrebbero essere utilizzate come adiuvanti nella terapia per rafforzare la risposta immunitaria del paziente. Tumor infiltrating lymphocytes (TILs) are the principal components of the tumor microenvironment, and play a central role in antitumor immunity. During cancer immunoediting, TILs became dysfunctional, a phenotype associated to effector functions impairment, reduced cell growth and decreased killing capability. Indeed, cancer immunotherapies treatments try to revert TILs dysfunctional state in order to promote tumor clearance. Immunotherapies nowadays represent the novel frontier in fighting cancer but still little is known regarding the epigenetic modulators responsible for TILs properties; the discovery of novel, possible targetable molecules and mechanisms could substantially improve knowledges regarding immunotherapies and patient responsiveness to them. For this reason, we are applying novel approaches and technologies in this filed, namely the investigation of transposable elements (TEs) functions as novel epigenetic players in TILs identity, plasticity and adaptability to the environmental cancer driven milieu. TEs are interspersed repetitive DNA sequences that cover 40 - 45% of the human genome and growing evidence suggests that TEs exert a crucial function in epigenetic regulation both in cis and in trans, being a source of non-coding regulatory RNAs and participating to chromatin folding. Among TEs, we are interested in the possible epigenetic functions of LINE1 elements, that represents 18% of the human genome, considered as novel key molecules involved in epigenetic regulation of cell identity. Until today the role and the dynamics of TEs-derived RNAs were investigated only in embryonic stem cells or during organism development, while there was no evidence of their possible functions in fully differentiated cells derived from adult tissues, as human Naïve T lymphocytes, that are plastic cells able to adapt and differentiate to diverse effector cells based on the cytokine milieu. We demonstrate that, among T cells subsets, there is a specific enrichment for LINE1 chromatin associated RNAs in naïve CD4+ T cells. Moreover, LINE1 RNAs show a peculiar and timely specific dynamic, being rapidly depleted from the nuclei after TCR activation. Notably, functional experiments suggested that these transcripts could regulate T cells effector functions. Since these data, the aim of this thesis is to evaluate LINE1 involvement in the epigenetic regulation of cell identity and functions in TILs. We generated an in vitro model to study LINE1 dynamics in exhausted and dysfunctional T cells, moreover, we had the possibility to isolate ex vivo TILs from NSCL cancer, CRC and their normal counterpart derived from patients to perform functional experiments and assess LINE1 functions in a real pathological context. We have demonstrated that TILs show aberrant re-accumulation of LINE1 RNAs which is associated with the dysfunctional phenotype and that the silencing of these RNAs is sufficient to reactivate their effector and killing functions allowing a reversion of the phenotype. Finally, we aim to define LINE1 RNAs as novel TILs regulatory molecules to find novel targetable RNA molecules that could be used as adjuvants in therapy to reinforce patient’s immune response.
- Published
- 2022
10. Channel Tracking Guidewire and Technique for Retrograde Approach
- Author
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Davide Diana, Rocco Giunta, Giuseppe Vadalà, Alfredo R. Galassi, Giuseppina Novo, and A. Galassi, G. Vadalà, R. Giunta, D. Diana, G. Novo
- Subjects
Change over time ,medicine.medical_specialty ,Collateral ,Computer science ,Radiation dose ,medicine ,Retrograde approach ,Radiology ,Collateral circulation ,Angiography, Chronic Total Occlusion, Intravascular Ultrasound, Percutaneous Coronary Intervention ,Communication channel - Abstract
Evaluation of the collateral circulation is critical for determining the feasibility of the retrograde approach. When assessing collateral channels it is of paramount importance to take time and review the previous angiogram carefully, for multiple potential collateral pathways, as the predominant collateral may change over time prior to the procedure. Careful review of collaterals prior to the procedure can reduce contrast and radiation dose as well as the duration of the procedure.Retrograde access to the distal vessel can be achieved via septal collaterals, epicardial collaterals (atrial channel), or (patent or occluded) coronary bypass grafts. Generally septals are used more often 65–70% of cases, epicardial 15–20% of cases, atrial 8–10% of cases, and graft 5–8% of cases. In order to identify the best collateral collateral size, tortuosity, bifurcations angle of entry to and exit from the collateral, and distance from the collateral exit to the distal cap should be taken into consideration. Among these parameters the most important predictor of successful guidewire tracking and device crossing is lack of tortuosity, followed by size [1, 2]. The size of the collaterals is often assessed using the Werner classification (CC0: no continuous connection; CC1: threadlike connection; CC2: side branch-like connection) [3].
- Published
- 2020
11. The Sophisticated Transcriptional Response Governed by Transposable Elements in Human Health and Disease
- Author
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Beatrice Bodega, Valeria Ranzani, Benedetto Polimeni, Rebecca Vadalà, Federica Marasca, Erica Gasparotto, Marasca, F, Gasparotto, E, Polimeni, B, Vadalà, R, Ranzani, V, and Bodega, B
- Subjects
Transposable element ,co-option ,Review ,Computational biology ,Disease ,Biology ,genome plasticity ,Catalysis ,DNA sequencing ,Evolution, Molecular ,Inorganic Chemistry ,Transcriptome ,lcsh:Chemistry ,chemistry.chemical_compound ,Humans ,Physical and Theoretical Chemistry ,next generation sequencing approaches ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Genome, Human ,Organic Chemistry ,High-Throughput Nucleotide Sequencing ,RNA ,General Medicine ,cancer progression ,Computer Science Applications ,Next generation sequencing approache ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,immune system response ,DNA Transposable Elements ,Transcriptional response ,Human genome ,transposable elements ,DNA - Abstract
Transposable elements (TEs), which cover ~45% of the human genome, although firstly considered as “selfish” DNA, are nowadays recognized as driving forces in eukaryotic genome evolution. This capability resides in generating a plethora of sophisticated RNA regulatory networks that influence the cell type specific transcriptome in health and disease. Indeed, TEs are transcribed and their RNAs mediate multi-layered transcriptional regulatory functions in cellular identity establishment, but also in the regulation of cellular plasticity and adaptability to environmental cues, as occurs in the immune response. Moreover, TEs transcriptional deregulation also evolved to promote pathogenesis, as in autoimmune and inflammatory diseases and cancers. Importantly, many of these findings have been achieved through the employment of Next Generation Sequencing (NGS) technologies and bioinformatic tools that are in continuous improvement to overcome the limitations of analyzing TEs sequences. However, they are highly homologous, and their annotation is still ambiguous. Here, we will review some of the most recent findings, questions and improvements to study at high resolution this intriguing portion of the human genome in health and diseases, opening the scenario to novel therapeutic opportunities.
- Published
- 2020
12. LINE1 modulate human T cell function by regulating protein synthesis during the life span.
- Author
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Burattin FV, Vadalà R, Panepuccia M, Ranzani V, Crosti M, Colombo FA, Ruberti C, Erba E, Prati D, Nittoli T, Montini G, Ronchi A, Pugni L, Mosca F, Ricciardi S, Abrignani S, Pietrasanta C, Marasca F, and Bodega B
- Subjects
- Humans, Heterogeneous-Nuclear Ribonucleoproteins metabolism, Heterogeneous-Nuclear Ribonucleoproteins genetics, Signal Transduction, Adult, T-Lymphocytes metabolism, T-Lymphocytes immunology, Receptors, Antigen, T-Cell metabolism, Lymphocyte Activation, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes immunology, Aging metabolism, Gene Expression Regulation, Child, Protein Biosynthesis, Mechanistic Target of Rapamycin Complex 1 metabolism, Long Interspersed Nucleotide Elements, Polypyrimidine Tract-Binding Protein metabolism, Polypyrimidine Tract-Binding Protein genetics
- Abstract
The molecular mechanisms responsible for the heightened reactivity of quiescent T cells in human early life remain largely elusive. Our previous research identified that quiescent adult naïve CD4
+ T cells express LINE1 (long interspersed nuclear elements 1) spliced in previously unknown isoforms, and their down-regulation marks the transition to activation. Here, we unveil that neonatal naïve T cell quiescence is characterized by enhanced energy production and protein synthesis. This phenotype is associated with the absence of LINE1 expression attributed to tonic T cell receptor/mTOR complex 1 (mTORC1) signaling and (polypyrimidine tract-binding protein 1 (PTBP1)-mediated LINE1 splicing suppression. The absence of LINE1 expression primes these cells for rapid execution of the activation program by directly regulating protein synthesis. LINE1 expression progressively increases in childhood and adults, peaking in elderly individuals, and, by decreasing protein synthesis, contributes to immune senescence in aging. Our study proposes LINE1 as a critical player of human T cell function across the human life span.- Published
- 2024
- Full Text
- View/download PDF
13. Toxicological analysis of metals content in agro-food wastes as possible supplement in animal feed.
- Author
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Naccari C, Cicero N, Vadalà R, Bartolomeo G, and Palma E
- Subjects
- Animals, Agriculture, Metals, Heavy analysis, Animal Feed analysis, Metals analysis, Dietary Supplements analysis
- Abstract
The agro-food surplus is considered the most abundant renewable resource, interesting for the economic and environmental impact, with a possible employment in different productive fields such as supplement in animal feed. For a safe and effective enhancement of agro-food wastes it is needed a toxicological analysis before of their employment, to avoid potential risks to animals, humans and environment. The purpose of this study was to evaluate the metals content (Cu, Fe, Zn, Mg, Na, K, Ca, Mn, Se, Zn, Co, Ni, V, Sb, Mo, Cr and Pb, Cd, As, Ba), in agro-food wastes through ICP-MS analysis. The results obtained showed the presence of metals analysed with a significant content of essential micro and macro-elements; with regard to toxic metals, only strawberries and fennel samples showed Pb levels above the MRL. These data confirm, from the toxicological point of view, a possible and safe reuse of the most of all agro-food wastes, as raw material at low cost and rich of essential nutrients and particularly as supplement in animal feed.
- Published
- 2024
- Full Text
- View/download PDF
14. Blue Bounty: Italy's Dual-Use Solution for Crab Invasion, Nutritional Value, Safety, and Valorization.
- Author
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Di Salvo E, Virga AN, Forgia S, Nalbone L, Genovese C, Nava V, Giorgianni CM, Vadalà R, and Cicero N
- Abstract
In the past few years, non-native blue crab has been expanding its range in the Adriatic and Mediterranean Seas. However, when non-indigenous species establish a lasting presence in a novel ecosystem and actively expand into other regions, posing potential risks to local biodiversity and economic harm, they are classified as invasive species. For this study, two different batches of blue crabs were collected: one from the Mediterranean Sea and the other from the Adriatic coast area. Considering the negative ecological impact that blue crab has had and continues to have on the Italian coasts, this work was aimed to evaluate the characteristics of the Adriatic Sea "variant"; another goal was to propose the potential use of blue crab as a commercially profitable source due to its organoleptic characteristics. Data obtained revealed a high protein content, a good lipid profile, a low number of plastic particles, and the absence of toxic metals and pathogenic microorganisms. A deep statistical analysis was conducted to compare different portions of blue crab from the Adriatic and Mediterranean Seas. The results suggest that Callinectes sapidus is beneficial for human consumption and represents a valuable seafood, and its carapace could be used as compliant feed for aquaculture due to its metal composition and microbiological content.
- Published
- 2024
- Full Text
- View/download PDF
15. Supplementation of date palm (Phoenix dactylifera L.) residue for growth and lactic acid production of probiotic bacterial Lactobacillus spp.
- Author
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Di Salvo E, Vadalà R, De Maria L, Genovese C, and Cicero N
- Abstract
Date palm is an age-old cultivated plant that thrives in tropical and subtropical regions. The date palm is a bountiful source of carbohydrates, encompassing sucrose, glucose, and fructose and proteins. The date industry generates a significant volume of unused by-products. Dates offer a diverse range of by-products beyond the agri-food sector. LAB have garnered extensive utilisation across diverse food sectors, spanning meat, vegetables, beverages, dairy products, and other fermented foods. In the quest for establishing a new large-scale fermentation process for lactic acid there has been a concerted effort to utilise more cost-effective medium components. In the present work, date palm residue (DPR) derived from date palm fruit, after sugar extraction, was incorporated into MRS. The fermentation process was executed through two distinct fermentation systems. Initially, experiments were conducted in flasks. Afterward, the optimal conditions for bacterial growth were determined, and the experiment was carried out using a bioreactor. DPR supported the probiotic Lactobacillus spp. growth especially after 48 h incubation. The prebiotic effect of DPR on Lactobacillus spp. was reported. An increase in the total number of bacterial populations was observed in response to the addition the DPR until 48 h. Specifically, the supplementing DPR at a concentration of 1.5% in batch fermentation enhanced the growth and lactic acid production of Lactobacillus casei . This study suggests that DPR could potentially function as an economical prebiotic source and could be seamlessly incorporated as a functional food ingredient, thereby transforming a waste product into an economically sustainable food substrate.
- Published
- 2024
- Full Text
- View/download PDF
16. A Versatile Pipeline for Analyzing Dynamic Changes in Nuclear Bodies in a Variety of Cell Types.
- Author
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Di Gioia V, Zamporlini J, Vadalà R, Parmigiani E, Bodega B, and Marasca F
- Subjects
- Humans, Cell Nucleus chemistry, Cell Nucleus metabolism, T-Lymphocytes cytology, T-Lymphocytes metabolism, T-Lymphocytes chemistry, Image Processing, Computer-Assisted methods, Fluorescent Antibody Technique methods
- Abstract
Various nuclear processes, such as transcriptional control, occur within discrete structures known as foci that are discernable through the immunofluorescence technique. Investigating the dynamics of these foci under diverse cellular conditions via microscopy yields valuable insights into the molecular mechanisms governing cellular identity and functions. However, performing immunofluorescence assays across different cell types and assessing alterations in the assembly, diffusion, and distribution of these foci present numerous challenges. These challenges encompass complexities in sample preparation, determination of parameters for analyzing imaging data, and management of substantial data volumes. Moreover, existing imaging workflows are often tailored for proficient users, thereby limiting accessibility to a broader audience. In this study, we introduce an optimized immunofluorescence protocol tailored for investigating nuclear proteins in different human primary T cell types that can be customized for any protein of interest and cell type. Furthermore, we present a method for unbiasedly quantifying protein staining, whether they form distinct foci or exhibit a diffuse nuclear distribution. Our proposed method offers a comprehensive guide, from cellular staining to analysis, leveraging a semi-automated pipeline developed in Jython and executable in Fiji. Furthermore, we provide a user-friendly Python script to streamline data management, publicly accessible on a Google Colab notebook. Our approach has demonstrated efficacy in yielding highly informative immunofluorescence analyses for proteins with diverse patterns of nuclear organization across different contexts.
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- 2024
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17. Development of a Chitosan-Based Film from Shellfish Waste for the Preservation of Various Cheese Types during Storage.
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Vadalà R, De Maria L, De Pasquale R, Di Salvo E, Lo Vecchio G, Di Bella G, Costa R, and Cicero N
- Abstract
The global concern about the use of disposable plastics has fed the research on sustainable packaging for food products. Among the virtuous materials, chitosan emerges as a valid alternative to conventional polyethylene films because of its abundance in nature. In this work, a novel film for food wrapping was developed by exploiting shellfish waste according to a vision of circular economy. Compared to previous studies, here, novel ingredients, such as polyvinyl alcohol (PVA), fibroin, and essential oils, were used in a synergistic combination to functionally postpone cheese deterioration. The fermentative procedure applied for the obtainment of chitin contributes to filling the existing gap in the literature, since the majority of studies are based on the chemical pathways that dramatically impact the environment. After pretreatment, the shrimp shell waste (SSW) was fermented through two bacterial strains, namely Lactobacillus plantarum and Bacillus subtilis . A deacetylation step in an alkaline environment transformed chitin into chitosan, yielding 78.88 g/kg SWW. Four different film formulations were prepared, all containing chitosan with other ingredients added in order of decreasing complexity from the A to D groups. The novel films were tested with regard to their physico-mechanical and antioxidant properties, including the tensile strength (12.10-23.25 MPa), the elongation at break (27.91-46.12%), the hardness (52-71 Shore A), the film thickness (308-309 μm), and the radical scavenging activity (16.11-76.56%). The performance as a cling film was tested on two groups of cheese samples: the control (CTR), wrapped in conventional polyethylene (PE) film; treated (TRT), wrapped in the chitofilm formulation deemed best for its mechanical properties. The volatiles entrapped into the headspace were investigated by means of the SPME-GC technique. The results varied across soft, Camembert, and semi-hard cheeses, indicating a growing abundance of volatiles during the conservation of cheese. The bacterial growth trends for mesophilic, enterobacteriaceae, and lactic acid bacteria were expressed as the mean colony forming units (CFU)/mL for each type of cheese at different sampling times (day 2, day 8, and day 22): the highest load was quantified as 8.2 × 10
6 CFU/mL at day 22 in the CTR Camembert cheese. The TRT samples generally exhibited inhibitory activity comparable to or lower than that observed in the CTR samples. The sensory analysis revealed distinctions in cheese taste between the TRT and CTR groups., 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.- Published
- 2024
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18. Evaluating the inhibition effect of a novel bio-packaging on histamine content in mackerel ( Scomber scombrus ): a new strategy with environment respect.
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La Torre GL, Vadalà R, Cicero N, Lo Cascio G, Cicero A, Calabrese V, Ferrantelli V, Ingallina C, and Salvo A
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- Animals, Chromatography, High Pressure Liquid methods, Biofilms drug effects, Histamine analysis, Perciformes, Food Packaging methods
- Abstract
This is the first study in which the impact of a new bio-packaging on histamine formation in mackerel was investigated. To monitor the preservation of fresh fish samples a treatment with innovative polymeric film and a soaking procedure in liquid new biomaterial was adopted. Ultra HPLC diode array detection (UHPLC-DAD) analyses for histamine monitoring were performed on fresh, packaged, and soaked mackerel samples at different time. The histamine content threshold value was up to 7 days, and after this period the results showed that histamine levels were affected by application of biomaterial. Significant increase was detected in sample that was not treated with biofilm. The new biofilm extended the shelf-life and reveals a promising packaging system to prevent histamine biosynthesis.
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- 2024
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19. The Role of Nutraceuticals and Functional Foods in Skin Cancer: Mechanisms and Therapeutic Potential.
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Peterle L, Sanfilippo S, Borgia F, Li Pomi F, Vadalà R, Costa R, Cicero N, and Gangemi S
- Abstract
Skin cancer is a prevalent type of cancer worldwide and has a high growth rate compared to other diseases. Although modern targeted therapies have improved the management of cutaneous neoplasms, there is an urgent requirement for a safer, more affordable, and effective chemoprevention and treatment strategy for skin cancer. Nutraceuticals, which are natural substances derived from food, have emerged as a potential alternative or adjunctive treatment option. In this review, we explore the current evidence on the use of omega-3 fatty acids and polyphenols (curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein) for the treatment of melanoma and non-melanoma skin cancer (NMSC), as well as in their prevention. We discuss the mechanisms of action of the aforementioned nutraceuticals and their probable therapeutic benefits in skin cancer. Omega-3 fatty acids, curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein have several properties, among which are anti-inflammatory and anti-tumor, which can help to prevent and treat skin cancer. However, their effectiveness is limited due to poor bioavailability. Nanoparticles and other delivery systems can improve their absorption and targeting. More research is needed to evaluate their safety and effectiveness as a natural approach to skin cancer prevention and treatment. These compounds should not replace conventional cancer treatments, but may be used as complementary therapy under the guidance of a healthcare professional.
- Published
- 2023
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20. Natural Pigments Production and Their Application in Food, Health and Other Industries.
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Di Salvo E, Lo Vecchio G, De Pasquale R, De Maria L, Tardugno R, Vadalà R, and Cicero N
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- Cost-Benefit Analysis, Pigments, Biological pharmacology, Food Industry
- Abstract
In addition to fulfilling their function of giving color, many natural pigments are known as interesting bioactive compounds with potential health benefits. These compounds have various applications. In recent times, in the food industry, there has been a spread of natural pigment application in many fields, such as pharmacology and toxicology, in the textile and printing industry and in the dairy and fish industry, with almost all major natural pigment classes being used in at least one sector of the food industry. In this scenario, the cost-effective benefits for the industry will be welcome, but they will be obscured by the benefits for people. Obtaining easily usable, non-toxic, eco-sustainable, cheap and biodegradable pigments represents the future in which researchers should invest.
- Published
- 2023
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21. Potential benefits of using an energy-dense, high-protein formula enriched with β-hydroxy-β-methylbutyrate, fructo-oligosaccharide, and vitamin D for enteral feeding in the ICU: A pilot case-control study in COVID-19 patients.
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Cereda E, Guzzardella A, Tamayo L, Piano M, Alquati O, Vadalà R, Resta MV, Balzarini A, Tavola M, Ripamonti C, Cerri M, Pennacchio N, Cozzi S, Crotti S, Masi S, Grasselli G, and Caccialanza R
- Subjects
- Humans, Vitamin D, Case-Control Studies, Intensive Care Units, Proteins, Energy Intake, Oligosaccharides, Critical Illness therapy, Respiration, Artificial, Enteral Nutrition methods, COVID-19 therapy
- Abstract
Objectives: The aim of this study was to investigate the potential benefits of using an energy-dense, high-protein (HP) formula enriched with β-hydroxy-β-methylbutyrate (HMB), fructo-oligosaccharide (FOS), and vitamin D (VitD) for enteral feeding in the intensive care unit (ICU)., Methods: This was a nested case-control multicenter study. Mechanically ventilated patients with COVID-19 in whom enteral nutrition was not contraindicated and receiving an energy-dense, HP-HMB-FOS-VitD formula (1.5 kcal/mL; 21.5% of calories from protein; n = 53) were matched (1:1) by age (±1 y), sex, body mass index (±1 kg/m
2 ) and Sequential Organ Failure Assessment score (±1 point) and compared with patients fed with a standard HP, fiber-free formula (1.25-1.3 kcal/mL; 20% of calories from protein; n = 53). The primary end point was daily protein intake (g/kg) on day 4. Protein-calorie intake on day 7, gastrointestinal intolerance, and clinical outcomes were addressed as secondary end points., Results: The use of a HP-HMB-FOS-VitD formula resulted in higher protein intake on days 4 and 7 (P = 0.006 and P = 0.013, respectively), with similar energy intake but higher provision of calories from enteral nutrition at both times (P <0 .001 and P = 0.017, respectively). Gastrointestinal tolerance was superior, with fewer patients fed with a HP-HMB-FOS-VitD formula reporting at least one symptom of intolerance (55 versus 74%; odds ratio [OR], 0.43; 95% confidence interval [CI], 0.18-0.99; P = 0.046) and constipation (38 versus 66%; OR, 0.27; 95% CI, 0.12-0.61; P = 0.002). A lower rate of ICU-acquired infections was also observed (42 versus 72%; OR, 0.29; 95% CI, 0.13-0.65; P = 0.003), although no difference was found in mortality, ICU length of stay, and ventilation-free survival., Conclusions: An energy-dense, HP-HMB-FOS-VitD formula provided a more satisfactory protein intake and a higher provision of caloric intake from enteral nutrition than a standard HP formula in mechanically ventilated patients with COVID-19. Lower rates of gastrointestinal intolerance and ICU-acquired infections were also observed., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2023
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22. From by-product to functional food: the survival of L. casei shirota , L. casei immunitas and L. acidophilus johnsonii , during spray drying in orange juice using a maltodextrin/pectin mixture as carrier.
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Gervasi C, Pellizzeri V, Vecchio GL, Vadalà R, Foti F, Tardugno R, Cicero N, and Gervasi T
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- Lactobacillus acidophilus, Pectins, Spray Drying, Powders, Functional Food, Citrus sinensis, Probiotics
- Abstract
The study reports the production of an innovative functional orange powder supplemented with probiotics and prebiotics, by implementing new ecofriendly and sustainable technologies, such as spray drying. The survival of Lactobacillus casei shirota, Lactobacillus casei immunitas and Lactobacillus acidophilus johnsonii , during spray drying in orange juice was proven and the stability of the powder obtained at room temperature and at 4 °C was investigated. Furthermore, the study highlighted the possibility to enhance the pectin obtained from the food agroindustry as a carrier for the spray-drying process. Combining maltodextrins and pectins at a 10:1 weight ratio. The study showed the efficiency of the maltodextrin/pectin mixture as carriers for the spray-drying process and the viability of the tested microorganisms during both the storage at room temperature and at 4 °C, showing that the latter represents the best storing condition for a longer viability of the microorganisms.
- Published
- 2022
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23. Effect of Dietary Enrichment with Flaxseed, Vitamin E and Selenium, and of Market Class on the Broiler Breast Meat-Part 2: Technological and Sensorial Traits.
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Albergamo A, Vadalà R, Metro D, Giuffrida D, Monaco F, Pergolizzi S, Leonardi M, Bartolomeo G, Petracci M, and Cicero N
- Abstract
The influence of diet enrichment with flaxseed, selenium and vitamin E, and market class on breast meat was investigated in terms of technological and sensorial quality of breast meat. A randomized complete block design with an experimental unit of n = 6000 broilers receiving a standard or enriched diet, and slaughtered at 37 (light class), 47 (medium class), or 57 (heavy class) days of life, was developed. Then, enriched and standard breast muscles from every market class were studied for their technological and sensorial traits—both at 24 h post-mortem and after one month of frozen storage—by a statistical multiple linear model. Redness and yellowness of muscles significantly (p < 0.05) increased and decreased with increasing market age. Moreover, the yellowness significantly (p < 0.05) raised after frozen storage. However, obtained data were always indicative of a normal meat color. The water holding capacity improved following fed enrichment and significantly (p < 0.05) worsened after frozen storage. For the sensory analysis, juiciness and chewing rest of meat resulted significantly (p < 0.05) improved with increasing slaughtering age and diet enrichment, as well as their mutual interaction, while they deteriorated after frozen storage. Overall, fresh and enriched muscles from heavy broilers had the best technological and sensorial traits, thus, confirming that market size and diet should be highly considered to obtain breast meat with greater consumer acceptance.
- Published
- 2022
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24. Exploring Lignans, a Class of Health Promoting Compounds, in a Variety of Edible Oils from Brazil.
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Tardugno R, Cicero N, Costa R, Nava V, and Vadalà R
- Abstract
Lignans, a group of polyphenols, have been identified in eight cold pressed oils from fruits, nuts, and seeds, retrieved from the Brazilian market. The oils under investigation were avocado, Brazilian nut, canola, coconut, grapeseed, macadamia, palm, and pequi. Olive oil was selected as a reference oil, since numerous data on its lignan content are available in literature. The qualitative and quantitative profiles were obtained, after extraction, by means of UFLC-ESI-MS/MS analyses. The total lignan content showed a high variability, ranging from 0.69 mg·Kg
-1 (pequi) to 7.12 mg·Kg-1 (grapeseed), with the highest content registered for olive oil. Seven lignans were quantified, matairesinol and pinoresinol being the most abundant. The LC-MS/MS method was validated, showing linearity in the range of 12.5-212.5 mg·Kg-1 , LOD in the range of 0.18-11.37 mg·Kg-1 , and LOQ in the range of 0.53-34.45 mg·Kg-1 . Additionally, part of the study was focused on the evaluation of the flavor profile, this being a key element in consumers' evaluations, by means of HS-SPME-GC. In total, 150 volatile compounds were determined in the eight oils, with identified fractions ranging from 91.85% (avocado) to 96.31% (canola), with an average value of 94.1%. Groups of components contributed characteristically to the flavour of each oil.- Published
- 2022
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25. Effect of Dietary Enrichment with Flaxseed, Vitamin E and Selenium, and of Market Class on the Broiler Breast Meat-Part 1: Nutritional and Functional Traits.
- Author
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Albergamo A, Vadalà R, Nava V, Bartolomeo G, Rando R, Colombo N, Gualtieri R, Petracci M, Di Bella G, Costa R, and Cicero N
- Subjects
- Animal Feed analysis, Animals, Chickens metabolism, Diet veterinary, Dietary Supplements, Lipids, Meat analysis, Vitamin E metabolism, Vitamin E pharmacology, Flax metabolism, Selenium metabolism
- Abstract
The effect of dietary enrichment with flaxseed, selenium and vitamin E, and market class on the nutritional and functional value of breast meat was evaluated. A completely randomized block design was set up, where the experimental unit (n = 6000 birds) received conventional or enriched diet and was slaughtered at 37 (light class), 47 (medium class), or 57 (heavy class) days of life. Hence, functional and standard Pectoralis major muscles from every market class were analyzed for FA composition, inorganic elements and vitamin E. Lipid metabolism indices and health lipid indicators were assessed along with the nutritional value. A multiple linear model revealed that in breasts, the dietary treatment significantly influenced (p < 0.05) the FA profile, lipid metabolism and health lipid indices, while the slaughtering weight was related (p < 0.05) to most of elements (e.g., Na, Mg, K, Mn, and Se) and vitamin E. The interdependence of the two factors had strong relations (p < 0.05) with total PUFAs, including linolenic acid, desaturase activities, health lipid indices, trace essential elements and vitamin E. Consequently, enriched meat from heavy chickens showed the best functional and nutritional traits. Overall, the study pointed out that both market class and dietary manipulation are two relevant factors to consider for producing breast meat with higher nutritional and functional value.
- Published
- 2022
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26. Mineral and Microbiological Analysis of Spices and Aromatic Herbs.
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Cicero N, Gervasi T, Durazzo A, Lucarini M, Macrì A, Nava V, Giarratana F, Tardugno R, Vadalà R, and Santini A
- Abstract
Spices and aromatic herbs have always had great historical importance in human nutrition. Their use has been documented for centuries as a rich source of bioactive compounds; they have been used for their health benefits and also for flavoring or coloring food. However, despite the many health properties linked to the use of spices and aromatic herbs, these can represent biological hazards and can contain chemical substances of concern. Certainly, monitoring potential health hazards in spices and aromatic herbs includes microbiological safety and also the content of inorganic substances: both represent a key step. This research aims at monitoring the compliance of various spices and aromatic herbs from a non-European country market (namely: black cumin seeds, Iranian Tokhme Sharbati, clove buds, Shahjeera, Abbaszadeh saffron, organic fenugreek, whole black pepper, cinnamon, Abthul Ahmar (Asario), Ajwan seeds, whole coriander seeds, black sesame seeds, Sabja seeds) with the current European Union (EU) and WHO regulations, when available, regarding mineral and microbiological parameters. In particular, microbiological assays using rapid and conventional methods, and trace mineral determination by inductively coupled plasma mass spectrometry (ICP-MS) were performed. Results show the safety of the tested spices, given that the microbiological parameters were within the legal microbiological criteria set by the European Commission Regulation (EC) No. 2073/2005 and its amendment Regulation (EC) No. 1441/2007. With reference to potentially toxic Cd, Pb, As, Hg, these were within the limits set by the European Commission Regulation (EC) No. 1881/2006 and its amendments, Regulation (EU) No. 1317/2021 and Regulation (EU) No. 1323/2021, and WHO. According to EU regulations, for Pb content, 2 samples out of 16 showed values different from the set limits.
- Published
- 2022
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27. Left egocentric neglect in early subacute right-stroke patients is related to damage of the superior longitudinal fasciculus.
- Author
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Spanò B, Nardo D, Giulietti G, Matano A, Salsano I, Briani C, Vadalà R, Marzi C, De Luca M, Caltagirone C, and Santangelo V
- Subjects
- Functional Laterality, Humans, Magnetic Resonance Imaging, Neuropsychological Tests, Space Perception, Perceptual Disorders diagnostic imaging, Perceptual Disorders etiology, Stroke diagnostic imaging, White Matter diagnostic imaging
- Abstract
A typical consequence of stroke in the right hemisphere is unilateral spatial neglect. Distinct forms of neglect have been described, such as space-based (egocentric) and object-based (allocentric) neglect. However, the relationship between these two forms of neglect is still far from being understood, as well as their neural substrates. Here, we further explore this issue by using voxel lesion symptoms mapping (VLSM) analyses on a large sample of early subacute right-stroke patients assessed with the Apples Cancellation Test. This is a sensitive test that simultaneously measures both egocentric and allocentric neglect. Behaviourally, we found no correlation between egocentric and allocentric performance, indicating independent mechanisms supporting the two forms of neglect. This was confirmed by the VLSM analysis that pointed out a link between a damage in the superior longitudinal fasciculus and left egocentric neglect. By contrast, no association was found between brain damage and left allocentric neglect. These results indicate a higher probability to observe egocentric neglect as a consequence of white matter damages in the superior longitudinal fasciculus, while allocentric neglect appears more "globally" related to the whole lesion map. Overall, these findings on early subacute right-stroke patients highlight the role played by white matter integrity in sustaining attention-related operations within an egocentric frame of reference., (© 2021. The Author(s).)
- Published
- 2022
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28. LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion.
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Marasca F, Sinha S, Vadalà R, Polimeni B, Ranzani V, Paraboschi EM, Burattin FV, Ghilotti M, Crosti M, Negri ML, Campagnoli S, Notarbartolo S, Sartore-Bianchi A, Siena S, Prati D, Montini G, Viale G, Torre O, Harari S, Grifantini R, Soldà G, Biffo S, Abrignani S, and Bodega B
- Subjects
- CD4-Positive T-Lymphocytes immunology, Chromatin genetics, Heterogeneous-Nuclear Ribonucleoproteins metabolism, Histones metabolism, Humans, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating immunology, Mechanistic Target of Rapamycin Complex 1 metabolism, Phosphoproteins metabolism, Polypyrimidine Tract-Binding Protein metabolism, RNA genetics, RNA metabolism, RNA-Binding Proteins metabolism, Signal Transduction, Transcription Factors, TFII metabolism, Transcription, Genetic, Nucleolin, CD4-Positive T-Lymphocytes physiology, Chromatin metabolism, Gene Expression Regulation, Long Interspersed Nucleotide Elements, RNA Splicing
- Abstract
How gene expression is controlled to preserve human T cell quiescence is poorly understood. Here we show that non-canonical splicing variants containing long interspersed nuclear element 1 (LINE1) enforce naive CD4
+ T cell quiescence. LINE1-containing transcripts are derived from CD4+ T cell-specific genes upregulated during T cell activation. In naive CD4+ T cells, LINE1-containing transcripts are regulated by the transcription factor IRF4 and kept at chromatin by nucleolin; these transcripts act in cis, hampering levels of histone 3 (H3) lysine 36 trimethyl (H3K36me3) and stalling gene expression. T cell activation induces LINE1-containing transcript downregulation by the splicing suppressor PTBP1 and promotes expression of the corresponding protein-coding genes by the elongating factor GTF2F1 through mTORC1. Dysfunctional T cells, exhausted in vitro or tumor-infiltrating lymphocytes (TILs), accumulate LINE1-containing transcripts at chromatin. Remarkably, depletion of LINE1-containing transcripts restores TIL effector function. Our study identifies a role for LINE1 elements in maintaining T cell quiescence and suggests that an abundance of LINE1-containing transcripts is critical for T cell effector function and exhaustion., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2022
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29. Physicochemical, Nutritional, Microbiological, and Sensory Qualities of Chicken Burgers Reformulated with Mediterranean Plant Ingredients and Health-Promoting Compounds.
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Albergamo A, Vadalà R, Metro D, Nava V, Bartolomeo G, Rando R, Macrì A, Messina L, Gualtieri R, Colombo N, Sallemi S, Leonardi M, Lo Turco V, Dugo G, and Cicero N
- Abstract
The quality of chicken burgers reformulated by the partial replacement of meat by Mediterranean plant ingredients and enriched with peculiar amounts of n-3 PUFAs, Mg, Fe, Se, and folic acid, was evaluated in comparison to conventional chicken burgers. Specifically, two types of burger were developed, namely the "Sicilian burger"-based on cherry tomato and rosemary-and the "Mediterranean burger"-with basil leaves and thyme essential oil-every recipe being differentially functionalized according to the nutritional requirements of consumers, such as children, pregnant women and elderly. Mediterranean ingredients were responsible for different pH, color, and cooking loss between conventional and functional burgers. Except for n-3 PUFAs resulting poorly fortified, the functionalization with Mg, Fe, Se, and vitamin B9 was successful in all products. Considering the target consumer categories, the daily consumption of the functional burger may assure an intake of Mg, Fe, and Se equal, respectively, to 37.31-59.90%, 17.76-46.81%, and 27.20-50.05%, and a cover of vitamin B9 of 31.98-48.31% of the relative population reference intakes. Fortified products kept a good microbiological quality during 5 days of refrigerated storage, and, according to the sensorial descriptive analysis and the hedonic test, they showed a higher acceptability than conventional burgers.
- Published
- 2021
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30. Properties of a New Food Supplement Containing Actinia equina Extract.
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Lanza M, Casili G, Torre GL, Giuffrida D, Rotondo A, Esposito E, Ardizzone A, Rando R, Bartolomeo G, Albergamo A, Vadalà R, and Salvo A
- Abstract
Marine species represent a great source of biologically active substances; Actinia equina (AE), an Anthozoa Cnidaria belonging to the Actinidiae family, have been proposed as original food and have already been included in several cooking recipes in local Mediterranean shores, and endowed with excellent nutraceutical potential. The aim of this study was to investigate some unexplored features of AE, through analytical screening and an in-vitro and in-vivo model. An in-vitro study, made on RAW 264.7 stimulated with H
2 O2 , showed that the pre-treatment with AE exerted an antioxidant action, reducing lipid peroxidation and up-regulating antioxidant enzymes. On the other hand, the in-vivo study over murine model demonstrated that the administration of AE extracts is able to reduce the carrageenan (CAR)-induced paw edema. Furthermore, the histological damage due to the neutrophil infiltration is prevented, and this highlights precious anti-inflammatory features of the interesting food-stuff. Moreover, it was assessed that AE extract modulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and The nuclear factor erythroid 2-related factor 2 (Nrf-2) pathways. In conclusion, our data demonstrated that thanks to the antioxidant and anti-inflammatory properties, AE extract could be used as a new food supplement for inflammatory pathology prevention.- Published
- 2020
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31. Assessment and Monitoring of Fish Quality from a Coastal Ecosystem under High Anthropic Pressure: A Case Study in Southern Italy.
- Author
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La Torre GL, Cicero N, Bartolomeo G, Rando R, Vadalà R, Santini A, Durazzo A, Lucarini M, Dugo G, and Salvo A
- Subjects
- Animals, Ecosystem, Fishes, Humans, Italy, Risk Assessment, Arsenic analysis, Dietary Exposure analysis, Food Contamination analysis, Metals, Heavy analysis, Seafood analysis
- Abstract
Fish is a nutrient-rich food but, at the same time, consumption of fish is a possible source of exposure to heavy metals. Since many coastal Mediterranean areas suffer from great anthropomorphic pressure, the aim of this study was to assess the level of potentially toxic inorganic elements in different fish samples from the coastal zone of Southern Italy (Gela) where there is a high mortality rate linked to cancer disease and congenital malformations. The presence of mercury, cadmium, lead, nickel, arsenic, vanadium, and chromium was measured by inductively coupled plasma-mass spectrometry (ICP-MS). The risk assessment was evaluated in terms of estimated daily intake by calculating the amount of potentially toxic elements that an average individual adult weighing 60 kg would ingest. Moreover the non-carcinogenic risk was estimated by target hazard quotient (THQ). The study evidenced significant contamination by inorganic elements, especially cadmium, which can be linked to industrial pollution. The THQ indexes, as indicators of human health, suggest that the consumption of fish from the study area is not free of risk.
- Published
- 2020
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32. Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice.
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Iatì G, Parisi S, Santacaterina A, Pontoriero A, Cacciola A, Brogna A, Platania A, Palazzolo C, Cambareri D, Davì V, Napoli I, Lillo S, Severo C, Tamburella C, Vadalà R, Delia P, and Pergolizzi S
- Abstract
Aim: To evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice., Background: Despite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies., Material and Methods: We reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated., Results: 37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months., Conclusion: SIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies., (© 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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33. Grape water: reclaim and valorization of a by-product from the industrial cryoconcentration of grape (Vitis vinifera) must.
- Author
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Albergamo A, Costa R, Bartolomeo G, Rando R, Vadalà R, Nava V, Gervasi T, Toscano G, Germanò MP, DʼAngelo V, Ditta F, and Dugo G
- Subjects
- Dietary Supplements, Food Handling methods, Recycling, Wine, Industrial Waste analysis, Vitis chemistry, Waste Disposal, Fluid methods, Wastewater chemistry
- Abstract
Background: The term 'grape (Vitis vinifera) water' refers to a by-product from the cryoconcentration of must that, if not reclaimed, would be considered as wastewater. In this study, the nutraceutical potential of waters reclaimed from the cryoconcentration of Grillo and Moscato musts was evaluated., Results: Both waters showed physicochemical parameters in agreement with Italian regulation for drinking water, and interesting levels of F
- (3.02-8.02 mg L-1 ) and SO4 - (52.85-49.34 mg L-1 ). Inorganic elements, including Mg (5.54-7.78 mg L-1 ), K (47.12-59.87 mg L-1 ), Fe (219.09-205.32 μg L-1 ), and Zn (189.65-127.30 μg L-1 ), and phenolic contents <35 mg GAE L-1 contributed to determine moderate antioxidant activities. Considering fatty acid composition, oleic and linoleic acids predominated, being higher in Moscato than Grillo samples (64.42% versus 58.22%, and 5.42% versus 6.07%). Grape waters displayed also rich aroma profiles, including mainly esters, alcohols and terpenoids. The latter components (i.e. linalool and α-terpineol) were more abundant in Moscato than in Grillo (13% versus 8%). Interestingly, some minor volatiles, characterized the vine of provenance (e.g. benzaldehyde and 3-methylbutylacetate in Moscato). All grape waters showed also a considerable fraction of ethyl lactate, six-carbon compounds and acetates, reflecting the proximity of samples to the grapes of origin., Conclusion: In a growing scenario of environmental decay and resource depletion, results from this study support an innovative and profitable waste recycling strategy for the wine industry. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)- Published
- 2020
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34. The Sophisticated Transcriptional Response Governed by Transposable Elements in Human Health and Disease.
- Author
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Marasca F, Gasparotto E, Polimeni B, Vadalà R, Ranzani V, and Bodega B
- Subjects
- Evolution, Molecular, High-Throughput Nucleotide Sequencing, Humans, DNA Transposable Elements genetics, Genome, Human genetics
- Abstract
: Transposable elements (TEs), which cover ~45% of the human genome, although firstly considered as "selfish" DNA, are nowadays recognized as driving forces in eukaryotic genome evolution. This capability resides in generating a plethora of sophisticated RNA regulatory networks that influence the cell type specific transcriptome in health and disease. Indeed, TEs are transcribed and their RNAs mediate multi-layered transcriptional regulatory functions in cellular identity establishment, but also in the regulation of cellular plasticity and adaptability to environmental cues, as occurs in the immune response. Moreover, TEs transcriptional deregulation also evolved to promote pathogenesis, as in autoimmune and inflammatory diseases and cancers. Importantly, many of these findings have been achieved through the employment of Next Generation Sequencing (NGS) technologies and bioinformatic tools that are in continuous improvement to overcome the limitations of analyzing TEs sequences. However, they are highly homologous, and their annotation is still ambiguous. Here, we will review some of the most recent findings, questions and improvements to study at high resolution this intriguing portion of the human genome in health and diseases, opening the scenario to novel therapeutic opportunities., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
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35. Accumulation of PCBs, PAHs, plasticizers and inorganic elements in Hexanchus griseus from the strait of Messina (Central Mediterranean sea).
- Author
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Salvo A, La Torre GL, Rotondo A, Mangano V, Gervasi T, Gervasi C, Vadalà R, Bartolomeo G, Iaria C, Lanteri G, Capparucci F, and Dugo G
- Subjects
- Animals, Environmental Pollutants analysis, Liver chemistry, Liver metabolism, Mass Spectrometry, Mediterranean Sea, Pesticides analysis, Tandem Mass Spectrometry, Metals, Heavy analysis, Plasticizers analysis, Polychlorinated Biphenyls analysis, Polycyclic Aromatic Hydrocarbons analysis, Sharks metabolism
- Abstract
This study investigates the inorganic elements and the persistent organic pollutants (POPs) accumulated in liver of a sexually mature Hexanchus griseus living in the Mediterranean Sea. The casual finding of a specimen in the Strait of Messina (April 2018) allowed us to carefully analyse its liver which can be considered a very important biological indicator. The determination of inorganic elements was carried out by ICP-MS technique. Quantitative determination of polycyclic aromatic hydrocarbons (PAH) and poly-chloro-biphenyl compounds (PCB), distinguished in dioxine-like (DL) and not-dioxine-like (NDL) derivates, has been carried out by HRGC/MS and HRGC-MS/MS respectively. Worrying levels of PCB-DL (TEQ = Σ(PCB-DL)*TEF = 5.96 ng g
-1 ), PCB-NDL (Σ(PCB-NDL) = 1390.4 ng g-1 ) together with the presence of pesticides and plasticizers were found in the shark liver oil. The levels of heavy metals were below the legal limits.- Published
- 2020
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36. Traceability of Opuntia ficus-indica L. Miller by ICP-MS multi-element profile and chemometric approach.
- Author
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Mottese AF, Naccari C, Vadalà R, Bua GD, Bartolomeo G, Rando R, Cicero N, and Dugo G
- Subjects
- Fruit chemistry, Mass Spectrometry, Minerals chemistry, Sicily, Opuntia chemistry, Plant Extracts chemistry
- Abstract
Background: Opuntia ficus-indica L. Miller fruits, particularly 'Ficodindia dell'Etna' of Biancavilla (POD), 'Fico d'india tradizionale di Roccapalumba' with protected brand and samples from an experimental field in Pezzolo (Sicily) were analyzed by inductively coupled plasma mass spectrometry in order to determine the multi-element profile. A multivariate chemometric approach, specifically principal component analysis (PCA), was applied to individuate how mineral elements may represent a marker of geographic origin, which would be useful for traceability., Results: PCA has allowed us to verify that the geographical origin of prickly pear fruits is significantly influenced by trace element content, and the results found in Biancavilla PDO samples were linked to the geological composition of this volcanic areas. It was observed that two principal components accounted for 72.03% of the total variance in the data and, in more detail, PC1 explains 45.51% and PC2 26.52%, respectively., Conclusion: This study demonstrated that PCA is an integrated tool for the traceability of food products and, at the same time, a useful method of authentication of typical local fruits such as prickly pear. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)
- Published
- 2018
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37. Interdonato lemon from Nizza di Sicilia (Italy): chemical composition of hexane extract of lemon peel and histochemical investigation.
- Author
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Salvo A, Bruno M, La Torre GL, Vadalà R, Mottese AF, Saija E, Mangano V, Casale KE, Cicero N, and Dugo G
- Subjects
- Histocytochemistry, Citrus chemistry, Plant Extracts analysis
- Abstract
Considering that the determination of authenticity and of the geographical origin of food is a very challenging issue, in this study we studied by means of histological and histochemical analyses the famous Sicilian lemon known as 'Interdonato Lemon of Messina PGI'. Since the protected geographical indication Interdonato lemon of Messina possesses high organoleptic properties, the composition of the hexane extract of lemon peel was determined by HRGC and HRGC-MS analyses and compared with that of lemon of different cultivars. The results obtained are informative of the oil's quality and explain the variation of the lemon essential oil composition. Given the fundamental economic implications of any fraud, the aim of this study was to determine a fingerprint able to evaluate the authentication of the geographic origin in such way to prevent frauds in national and international markets.
- Published
- 2016
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38. Statistical Analysis of Mineral Concentration for the Geographic Identification of Garlic Samples from Sicily (Italy), Tunisia and Spain.
- Author
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Vadalà R, Mottese AF, Bua GD, Salvo A, Mallamace D, Corsaro C, Vasi S, Giofrè SV, Alfa M, Cicero N, and Dugo G
- Abstract
We performed a statistical analysis of the concentration of mineral elements, by means of inductively coupled plasma mass spectrometry (ICP-MS), in different varieties of garlic from Spain, Tunisia, and Italy. Nubia Red Garlic (Sicily) is one of the most known Italian varieties that belongs to traditional Italian food products (P.A.T.) of the Ministry of Agriculture, Food, and Forestry. The obtained results suggest that the concentrations of the considered elements may serve as geographical indicators for the discrimination of the origin of the different samples. In particular, we found a relatively high content of Selenium in the garlic variety known as Nubia red garlic, and, indeed, it could be used as an anticarcinogenic agent.
- Published
- 2016
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39. Toxic and essential metals determination in commercial seafood: Paracentrotus lividus by ICP-MS.
- Author
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Salvo A, Cicero N, Vadalà R, Mottese AF, Bua D, Mallamace D, Giannetto C, and Dugo G
- Subjects
- Animals, Gonads chemistry, Mediterranean Sea, Pacific Ocean, Spectrum Analysis, Food Contamination analysis, Metals, Heavy analysis, Paracentrotus chemistry, Seafood analysis
- Abstract
Toxic and essential metals content was determined by inductively coupled plasma mass spectrometry in commercial sea urchins samples from the Mediterranean Sea and Pacific Ocean. Results show that Chilean samples have the highest values of Cd, As, Ni, Cr and V; Spanish samples have the maximum Hg content while Sicilian samples have the lowest content of toxic metals. The toxic metal traces were compared with the limits of European Community (EC) No. 1881/2006 for bivalve molluscs. All samples exceed Pb and Cd limit levels; regarding Hg levels, only Sicilian and Sardinian samples have Hg content below the EC limits. The dietary intake of toxic and essential elements was evaluated for an adult. Furthermore, our study highlights a correlation between the toxic elements content and the marine environmental conditions of the places of origin even though only the generic FAO fishing area is specified.
- Published
- 2016
- Full Text
- View/download PDF
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