• ASD

Artificial Intelligence: the “Trait D’Union” in Different Analysis Approaches of Autism Spectrum Disorder Studies

Febbraio 22nd, 2021|

Abstract Autistic Spectrum Disorder (ASD) is a neurodevelopmental condition affecting approximately 1 out of 70 (range 1:59 - 1:89) children worldwide. It is characterized by a delay in cognitive capabilities, repetitive and restricted behaviors and deficit in communication and social interaction. Several factors seem to be associated with ASD development; its heterogeneous nature makes the diagnosis difficult and slow since it is essentially based on screening tools focused on stereotypical and repetitive behaviors, gait, facial emotion expression and speech assessments. Recently, artificial intelligence (AI) has been widely used to investigate ASD with the overall goal of simplifying and speeding up [...]

  • Humoral signatures of protective and pathological SARS-CoV-2 infection in children

Humoral signatures of protective and pathological SARS-CoV-2 infection in children

Febbraio 20th, 2021|

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses [...]

  • SARS-CoV-2 infection in children

Humoral signatures of protective and pathological SARS-CoV-2 infection in children

Febbraio 12th, 2021|

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil [...]

  • The therapeutic use of the zonulin inhibitor AT-1001 (Larazotide)

In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate

Gennaio 15th, 2021|

Abstract The most severe outcome of COVID-19 infection is the development of interstitial pneumonia causing acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), both responsible for the infected patients' mortality. ALI and ARDS are characterized by a leakage of plasma components into the lungs, compromising their ability to expand and optimally engage in gas exchange with blood, resulting in respiratory failure. We have previously reported that zonulin, a protein dictating epithelial and endothelial permeability in several districts, including the airways, is involved in ALI pathogenesis in mouse models, and that its peptide inhibitor Larazotide acetate (also called AT1001) [...]

  • In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negative.

Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients

Ottobre 22nd, 2020|

Abstract Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negative. We found that circulating caspase-4 was correlated to LDH. However, this effect was not observed in caspase-4 positive tumor tissues, where instead, fatty acid [...]

  • Gemma Autism

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach

Ottobre 21st, 2020|

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation [...]

  • Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

Ottobre 9th, 2020|

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.   Methods We sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography–tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children. Results [...]

  • Endometrial Cancer Screening in Postmenopausal Women

Development and Validation of a Serum Metabolomic Signature for Endometrial Cancer Screening in Postmenopausal Women

Settembre 28th, 2020|

Key Points Question  Is combining the blood metabolomic signature of endometrial carcinoma with an ensemble machine learning algorithm a useful system for building a screening test for endometrial cancer? Findings  In this diagnostic study that included 1550 postmenopausal women, the proposed screening test correctly identified all 16 women with endometrial cancer, with 2 false-positive results and 0 false-negative results. Meaning  The results of this study suggest that the metabolomic profile of a blood sample could provide a noninvasive and accurate screening test with high sensitivity and specificity for endometrial cancer. Abstract Importance  Endometrial carcinoma (EC) is the most commonly diagnosed gynecologic cancer. Its early [...]

Development and Validation of a Serum Metabolomic Signature for Endometrial Cancer Screening in Postmenopausal Women

Settembre 28th, 2020|

Abstract Importance  Endometrial carcinoma (EC) is the most commonly diagnosed gynecologic cancer. Its early detection is advisable because 20% of women have advanced disease at the time of diagnosis. Objective  To clinically validate a metabolomics-based classification algorithm as a screening test for EC. Design, Setting, and Participants  This diagnostic study enrolled 2 cohorts. A multicenter prospective cohort, with 50 cases (postmenopausal women with EC; International Federation of Gynecology and Obstetrics stage I-III and grade G1-G3) and 70 controls (no EC but matched on age, years from menopause, tobacco use, and comorbidities), was used to train multiple classification models. The accuracy of each trained [...]

Altered lung tissue lipidomic profile in caspase-4 positive non-small cell lung cancer (NSCLC) patients

Settembre 22nd, 2020|

Lung cancer is by far the leading cause of cancer death. Metabolomic studies have highlighted that both tumor progression and limited curative treatment options are partly due to dysregulated glucose metabolism and its associated signaling pathways. In our previous studies, we identified caspase-4 as a novel diagnostic tool for non-small cell lung cancer (NSCLC). Here, we analyzed the metabolomic profile of both plasma and tumor tissues of NSCLC patients stratified as caspase-4 positive or negative. We found that circulating caspase-4 was correlated to LDH. However, this effect was not observed in caspase-4 positive tumor tissues, where instead, fatty acid biosynthesis [...]

Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis

Luglio 19th, 2020|

Abstract Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 [...]

  • Lactobacillus paracasei CBA L74-fermented

Analysis of immune, microbiota and metabolome maturation in infants in a clinical trial of Lactobacillus paracasei CBA L74-fermented formula

Giugno 1st, 2020|

Abstract Mother’s milk is the best choice for infants nutrition, however when it is not available or insufficient to satisfy the needs of the infant, formula is proposed as an effective substitute. Here, we report the results of a randomized controlled clinical trial (NCT03637894) designed to evaluate the effects of two different dietary regimens (standard formula and Lactobacillus paracasei CBA L74-fermented formula) versus breastfeeding (reference group) on immune defense mechanisms (primary endpoint: secretory IgA, antimicrobial peptides), the microbiota and its metabolome (secondary outcomes), in healthy full term infants according to the type of delivery (n = 13/group). We show that the fermented [...]

  • Citrus sinensis and Vitis vinifera Protect Cardiomyocytes

Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies

Maggio 2nd, 2020|

Abstract The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ability to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells (H9c2), and human breast adenocarcinoma cell line [...]

  • Clues to Autism’s Origins

Clues to Autism’s Origins

Febbraio 25th, 2020|

Abnormally low levels of a key protein observed in brains of young men with autism spectrum disorder. A neuroimaging study by Harvard Medical School researchers based at Massachusetts General Hospital has shown that the brains of young men with autism spectrum disorder (ASD) have low levels of a protein that appears to play a role in inflammation and metabolism. This surprising discovery, published online in Molecular Psychiatry, provides an important new insight into the possible origins of ASD, which affects one in 59 children. ASD is a developmental disorder that emerges in early childhood and is characterized by difficulty communicating and interacting [...]

Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCIIlowCD11c+CD11b+F4/80+ Cells

Febbraio 17th, 2020|

Abstract Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, [...]