• 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) [...]

  • 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 [...]

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

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

Luglio 3rd, 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 [...]

  • Zonulin-Dependent Intestinal Permeability in Children

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

Luglio 3rd, 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, [...]

  • All disease begins in the (leaky) gut

All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases

Febbraio 6th, 2020|

Abstract Improved hygiene leading to reduced exposure to microorganisms has been implicated as one possible cause for the recent “epidemic” of chronic inflammatory diseases (CIDs) in industrialized countries. That is the essence of the hygiene hypothesis that argues that rising incidence of CIDs may be, at least in part, the result of lifestyle and environmental changes that have made us too “clean” for our own good, so causing changes in our microbiota. Apart from genetic makeup and exposure to environmental triggers, inappropriate increase in intestinal permeability (which may be influenced by the composition of the gut microbiota), a “hyper-belligerent” immune [...]

  • Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL/STAT5 Pathway

Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL/STAT5 Pathway

Febbraio 6th, 2020|

Abstract Some species of clover are reported to have beneficial effects in human diseases. However, little is known about the activity of the forage plant Trifolium repens, or white clover, which has been recently found to exert a hepatoprotective action. Scientific interest is increasingly focused on identifying new drugs, especially natural products and their derivatives, to treat human diseases including cancer. We analyzed the anticancer effects of T. repens in several cancer cell lines. The phytochemical components of T. repens were first extracted in a methanol solution and then separated into four fractions by ultra-high-performance liquid chromatography. The effects of the total extract and each [...]

  • Indole-3-lactic acid a metabolite of tryptophan

Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine

Gennaio 16th, 2020|

Abstract Background Necrotizing enterocolitis (NEC), a necrotic inflammation of the intestine, represents a major health problem in the very premature infant. Although prevention is difficult, the combination of ingestion of maternal-expressed breastmilk in conjunction with a probiotic provides the best protection. In this study, we establish a mechanism for breastmilk/probiotic protection. Methods Ultra-high-performance liquid chromatography-tandem mass spectrometry of Bifidobacterium longum subsp. infantis (B. infantis) secretions was used to identify an anti-inflammatory molecule. Indole-3-lactic acid (ILA) was then tested in an established human immature small intestinal cell line, necrotizing colitis enterocytes, and other immature human enteroids for anti-inflammatory effects and to establish developmental function. ILA [...]

  • children’s cancer drug

Shortage of vital children’s cancer drug stirs fear and outrage

Ottobre 18th, 2019|

A critical shortage of a chemotherapy used to treat most childhood cancers has galvanized oncologists and parents of sick children. The U.S. medical community has become increasingly accustomed to dealing with chronic shortages of mainstay drugs, but vincristine is irreplaceable—and a big reason for the 85% cure rate in pediatric cancer. The shortage has driven worried parents to launch social media campaigns and petition drives, while the Children's Oncology Group, the world's leading pediatric cancer research collaboration, on Wednesday issued a "call to action" to guarantee pediatric cancer drug supplies. "There is no substitute for vincristine," said Peter C. Adamson, chair of the oncology group and a [...]