Antonio Noto - Academia.edu (original) (raw)
Papers by Antonio Noto
ABSTRACT Recently it has been hypothesized that a reactivation of the epithelial-mesenchymal trop... more ABSTRACT Recently it has been hypothesized that a reactivation of the epithelial-mesenchymal trophic unit (EMTU) of the respiratory mucosa, caused by extensive epithelial damage, may be responsible for the pathogenesis of asthma. However, most research on this subject so far has been limited by the unavailability of in vitro models correctly mimicking the three-dimensional architecture of the properly differentiated human bronchial mucosa. For this reason, we have developed a novel 3D outgrowth model, obtained from bronchial biopsies and composed of both human bronchial epithelial cells (goblet and columnar cells) and fibroblasts with their basement membrane. Here we present the preliminary data obtained by both SEM and TEM on the characterization of these bronchial outgrowths showing that cells and matrices within the 3D structures are well differentiated, presenting all the normal features of human bronchial mucosa such as microvilli, cilia, mucus, tight junctions, collagens etc. We also show the effects of medium-term treatment with cigarette smoke extracts in terms of cell survival and remodeling.
The Open Tissue Engineering and Regenerative Medicine Journal, 2009
Several acute and chronic inflammatory pathologies of the lung are accompanied by structural modi... more Several acute and chronic inflammatory pathologies of the lung are accompanied by structural modifications of airway mucosa that vary depending on the severity, duration and type of the disease. These morphological changes, that determine organ dysfunction, are not always reversible. Indeed, the cycle of injury and repair, influencing airway wall regeneration, may sometimes break off and an exacerbation of the pathology may occur. The mechanisms at the base of airway remodelling during inflammation have been widely studied and numerous evidences indicate that the molecular dialogue among the cells of the mucosa has an essential role in orchestrating cell differentiation and tissue repair. In this review, we revise old notions on pulmonary morphology at the light of some of the most recent discoveries concerning stem cell differentiation, tissue homeostasis and organ regeneration of the lung.
Thorax, 2010
scaffold protein involved in the proteasomal processing of p105 into the p50 subunit. Inhibition ... more scaffold protein involved in the proteasomal processing of p105 into the p50 subunit. Inhibition of this process impairs the nuclear translocation of NF-kB and the consequent p65/p50 regulated gene transcription. Hence, TRUSS may be a novel target for modulating the inflammatory functions of TNFa-TNF-R1 signalling.
Journal of Allergy and Clinical Immunology, 2010
RATIONALE: Non-invasive techniques may assist in the management of children with asthma by detect... more RATIONALE: Non-invasive techniques may assist in the management of children with asthma by detecting chronic airway inflammation documented by low exhaled breath condensate (EBC) pH and an increased expired nitric oxide (eNO) as compared to healthy-matched control children. METHODS: Sixty children age 5-17 years with mild intermittent to moderate persistent asthma and 30 age-matched controls were evaluated for 12 months using spirometry, eNO and EBC. The children with asthma were stratified into steroid-treated (ST) and steroid-naive (SN) groups.
Keywords aluminium atherosclerosis cardiac stem cells cyclosporine dorsal root ganglia dynamic os... more Keywords aluminium atherosclerosis cardiac stem cells cyclosporine dorsal root ganglia dynamic osteogenesis endothelium epicardiallyderived cells epicardium epithelialmesenchymal transition intramembranous ossification kidney mammals mercury ...
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 23, 2016
Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorde... more Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorders. We introduce the different classification systems of aggression and related disorders as a basis for discussing biochemical biomarkers and then present an overview of studies in humans (published between 1990 and 2015) that reported statistically significant associations of biochemical biomarkers with aggression, DSM-IV disorders involving aggression, and their subtypes. The markers are of different types, including inflammation markers, neurotransmitters, lipoproteins, and hormones from various classes. Most studies focused on only a limited portfolio of biomarkers, frequently a specific class only. When integrating the data, it is clear that compounds from several biological pathways have been found to be associated with aggressive behavior, indicating complexity and the need for a broad approach. In the second part of the paper, using examples from the aggression literature and ps...
Journal of Maternal Fetal and Neonatal Medicine, Oct 1, 2014
Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in... more Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in neonatology. They are characterized by a large amount of data that reflect the complexity of all biological systems more accurately than traditional methods utilized in clinical chemistry. In this review paper we present the modifications of the salivary proteome, which represents an easy and non-invasive method that offers the opportunity to investigate changes in the metabolism of preterm infants and in pediatric patients. Moreover, we present the metabolomics-histologic correlations in newborn piglets at baseline and following normocapnic hypoxia and reoxygenation. A new method of data analysis, here summarized as the "triple-I" approach will be finally discussed: interdisciplinary, intersectorial, interactive.
Expert Review of Molecular Diagnostics, 2016
Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the place... more Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus's urine. Since AF reflects the mother's and the fetus's health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.
Advances in Clinical Chemistry, 2016
The American Journal of Emergency Medicine, 2015
Cytochrome c, an electron carrier that normally resides in the mitochondrial intermembrane space,... more Cytochrome c, an electron carrier that normally resides in the mitochondrial intermembrane space, may translocate to the cytosol under ischemic and hypoxic conditions and contribute to mitochondrial permeability transition pore opening. In addition, reperfusion of brain tissue following ischemia initiates a cell death cascade that includes cytochrome c-mediated induction of apoptosis. Further studies are needed to determine the contribution of cytochrome c in the regulation of cell death, as well as its value as an in vivo prognostic marker after cardiac arrest and resuscitation.
Molecules (Basel, Switzerland), 2015
Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and ... more Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last ye...
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2014
Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in... more Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in neonatology. They are characterized by a large amount of data that reflect the complexity of all biological systems more accurately than traditional methods utilized in clinical chemistry. In this review paper we present the modifications of the salivary proteome, which represents an easy and non-invasive method that offers the opportunity to investigate changes in the metabolism of preterm infants and in pediatric patients. Moreover, we present the metabolomics-histologic correlations in newborn piglets at baseline and following normocapnic hypoxia and reoxygenation. A new method of data analysis, here summarized as the "triple-I" approach will be finally discussed: interdisciplinary, intersectorial, interactive.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2014
In the present review article we have summarized the use of the metabolomics approach to study th... more In the present review article we have summarized the use of the metabolomics approach to study the metabolic modifications occurring in several bio-fluids due to viral infections. The aim is to highlight the ability of metabolomics to find early fingerprints, which are related to the infections. The (1)H-NMR, UHPLC/MS/MS(2), UPLC/ESI-SYNAPT-HDMS, UPLC-Q-TOF-HDMS analyses were used for the determination of several metabolites representative of the viral infections. The data were analyzed by Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA) and by regression techniques. The major changes were related to nucleotide, carbohydrates, lipids and amino acid metabolisms. The metabolomics approach could be considered a viable option for characterization of the viral infection and for detecting on going differences in the bio-fluids composition.
BioMed research international, 2014
Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers h... more Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called "omics" allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in...
ABSTRACT Recently it has been hypothesized that a reactivation of the epithelial-mesenchymal trop... more ABSTRACT Recently it has been hypothesized that a reactivation of the epithelial-mesenchymal trophic unit (EMTU) of the respiratory mucosa, caused by extensive epithelial damage, may be responsible for the pathogenesis of asthma. However, most research on this subject so far has been limited by the unavailability of in vitro models correctly mimicking the three-dimensional architecture of the properly differentiated human bronchial mucosa. For this reason, we have developed a novel 3D outgrowth model, obtained from bronchial biopsies and composed of both human bronchial epithelial cells (goblet and columnar cells) and fibroblasts with their basement membrane. Here we present the preliminary data obtained by both SEM and TEM on the characterization of these bronchial outgrowths showing that cells and matrices within the 3D structures are well differentiated, presenting all the normal features of human bronchial mucosa such as microvilli, cilia, mucus, tight junctions, collagens etc. We also show the effects of medium-term treatment with cigarette smoke extracts in terms of cell survival and remodeling.
The Open Tissue Engineering and Regenerative Medicine Journal, 2009
Several acute and chronic inflammatory pathologies of the lung are accompanied by structural modi... more Several acute and chronic inflammatory pathologies of the lung are accompanied by structural modifications of airway mucosa that vary depending on the severity, duration and type of the disease. These morphological changes, that determine organ dysfunction, are not always reversible. Indeed, the cycle of injury and repair, influencing airway wall regeneration, may sometimes break off and an exacerbation of the pathology may occur. The mechanisms at the base of airway remodelling during inflammation have been widely studied and numerous evidences indicate that the molecular dialogue among the cells of the mucosa has an essential role in orchestrating cell differentiation and tissue repair. In this review, we revise old notions on pulmonary morphology at the light of some of the most recent discoveries concerning stem cell differentiation, tissue homeostasis and organ regeneration of the lung.
Thorax, 2010
scaffold protein involved in the proteasomal processing of p105 into the p50 subunit. Inhibition ... more scaffold protein involved in the proteasomal processing of p105 into the p50 subunit. Inhibition of this process impairs the nuclear translocation of NF-kB and the consequent p65/p50 regulated gene transcription. Hence, TRUSS may be a novel target for modulating the inflammatory functions of TNFa-TNF-R1 signalling.
Journal of Allergy and Clinical Immunology, 2010
RATIONALE: Non-invasive techniques may assist in the management of children with asthma by detect... more RATIONALE: Non-invasive techniques may assist in the management of children with asthma by detecting chronic airway inflammation documented by low exhaled breath condensate (EBC) pH and an increased expired nitric oxide (eNO) as compared to healthy-matched control children. METHODS: Sixty children age 5-17 years with mild intermittent to moderate persistent asthma and 30 age-matched controls were evaluated for 12 months using spirometry, eNO and EBC. The children with asthma were stratified into steroid-treated (ST) and steroid-naive (SN) groups.
Keywords aluminium atherosclerosis cardiac stem cells cyclosporine dorsal root ganglia dynamic os... more Keywords aluminium atherosclerosis cardiac stem cells cyclosporine dorsal root ganglia dynamic osteogenesis endothelium epicardiallyderived cells epicardium epithelialmesenchymal transition intramembranous ossification kidney mammals mercury ...
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 23, 2016
Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorde... more Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorders. We introduce the different classification systems of aggression and related disorders as a basis for discussing biochemical biomarkers and then present an overview of studies in humans (published between 1990 and 2015) that reported statistically significant associations of biochemical biomarkers with aggression, DSM-IV disorders involving aggression, and their subtypes. The markers are of different types, including inflammation markers, neurotransmitters, lipoproteins, and hormones from various classes. Most studies focused on only a limited portfolio of biomarkers, frequently a specific class only. When integrating the data, it is clear that compounds from several biological pathways have been found to be associated with aggressive behavior, indicating complexity and the need for a broad approach. In the second part of the paper, using examples from the aggression literature and ps...
Journal of Maternal Fetal and Neonatal Medicine, Oct 1, 2014
Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in... more Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in neonatology. They are characterized by a large amount of data that reflect the complexity of all biological systems more accurately than traditional methods utilized in clinical chemistry. In this review paper we present the modifications of the salivary proteome, which represents an easy and non-invasive method that offers the opportunity to investigate changes in the metabolism of preterm infants and in pediatric patients. Moreover, we present the metabolomics-histologic correlations in newborn piglets at baseline and following normocapnic hypoxia and reoxygenation. A new method of data analysis, here summarized as the "triple-I" approach will be finally discussed: interdisciplinary, intersectorial, interactive.
Expert Review of Molecular Diagnostics, 2016
Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the place... more Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus's urine. Since AF reflects the mother's and the fetus's health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.
Advances in Clinical Chemistry, 2016
The American Journal of Emergency Medicine, 2015
Cytochrome c, an electron carrier that normally resides in the mitochondrial intermembrane space,... more Cytochrome c, an electron carrier that normally resides in the mitochondrial intermembrane space, may translocate to the cytosol under ischemic and hypoxic conditions and contribute to mitochondrial permeability transition pore opening. In addition, reperfusion of brain tissue following ischemia initiates a cell death cascade that includes cytochrome c-mediated induction of apoptosis. Further studies are needed to determine the contribution of cytochrome c in the regulation of cell death, as well as its value as an in vivo prognostic marker after cardiac arrest and resuscitation.
Molecules (Basel, Switzerland), 2015
Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and ... more Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last ye...
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2014
Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in... more Proteomics and metabolomics are emerging in recent years as one of the most challenging topics in neonatology. They are characterized by a large amount of data that reflect the complexity of all biological systems more accurately than traditional methods utilized in clinical chemistry. In this review paper we present the modifications of the salivary proteome, which represents an easy and non-invasive method that offers the opportunity to investigate changes in the metabolism of preterm infants and in pediatric patients. Moreover, we present the metabolomics-histologic correlations in newborn piglets at baseline and following normocapnic hypoxia and reoxygenation. A new method of data analysis, here summarized as the "triple-I" approach will be finally discussed: interdisciplinary, intersectorial, interactive.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2014
In the present review article we have summarized the use of the metabolomics approach to study th... more In the present review article we have summarized the use of the metabolomics approach to study the metabolic modifications occurring in several bio-fluids due to viral infections. The aim is to highlight the ability of metabolomics to find early fingerprints, which are related to the infections. The (1)H-NMR, UHPLC/MS/MS(2), UPLC/ESI-SYNAPT-HDMS, UPLC-Q-TOF-HDMS analyses were used for the determination of several metabolites representative of the viral infections. The data were analyzed by Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA) and by regression techniques. The major changes were related to nucleotide, carbohydrates, lipids and amino acid metabolisms. The metabolomics approach could be considered a viable option for characterization of the viral infection and for detecting on going differences in the bio-fluids composition.
BioMed research international, 2014
Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers h... more Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called "omics" allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in...