EVALUATION OF THE QUALITY OF REHABILITATION TREATMENT IN NEURODEVELOPMENTAL DISORDER

Complex disability is very difficult to manage. It usually subtends very serious clinical pictures, because it affect several body systems, or because it is associated with intellectual disability and behavioral disorders. Often affected patients are unable to communicate their basic needs. All these factors combine to make the management of these patients very complex, and those who care for them realize how important it is to find a way to detect their state and to identify their potential capabilities. Developing appropriate rehabilitation programs for these patients requires additional effort and an assessment capacity that is as objective as possible. Few scales cited in the literature are capable of evaluating these aspects in patients with complex disabilities, among them the Barthel Index (Mahoney & Barthel 1965) and the Vineland Adaptive Behavior scale II (Sparrow et al. 2005). The majority of these scales often tend to depict the data regarding the disease to a degree of severity that precludes adequate individual rehabilitation program development. There is a dire need for a more appropriate instrument, an observational grid that is capable of identifying the potential of this patient population and evaluate the effectiveness of rehabilitation interventions provided. The aim of the study is to evaluate the efficacy of rehabilitation interventions in a group of patients with IQ <32 (determined by the Vineland II scale) using an evaluation tool created ad hoc called D-Rubrics, designed with the intent to identify “microdifferences” between baseline (T0) and post-rehabilitation (T1). The goal is part of a more long term-term objective which involves developing an effective assessment tool for patients with complex disabilities. Such an assessment tool should be practical, easy to administer and useful in both clinical and research settings

Lipid Biomarkers in Liquid Biopsies: Novel Opportunities for Cancer Diagnosis

Altered cellular metabolism is a well-established hallmark of cancer. Although most studies have focused on the metabolism of glucose and glutamine, the upregulation of lipid metabolism is also frequent in cells undergoing oncogenic transformation. In fact, cancer cells need to meet the enhanced demand of plasma membrane synthesis and energy production to support their proliferation. Moreover, lipids are precursors of signaling molecules, termed lipid mediators, which play a role in shaping the tumor microenvironment. Recent methodological advances in lipid analysis have prompted studies aimed at investigating the whole lipid content of a sample (lipidome) to unravel the complexity of lipid changes in cancer patient biofluids. This review focuses on the application of mass spectrometry-based lipidomics for the discovery of cancer biomarkers. Here, we have summarized the main lipid alteration in cancer patients&rsquo; biofluids and uncovered their potential use for the early detection of the disease and treatment selection. We also discuss the advantages of using biofluid-derived extracellular vesicles as a platform for lipid biomarker discovery. These vesicles have a molecular signature that is a fingerprint of their originating cells. Hence, the analysis of their molecular cargo has emerged as a promising strategy for the identification of sensitive and specific biomarkers compared to the analysis of the unprocessed biofluid

Extracellular Vesicles as Conveyors of Membrane-Derived Bioactive Lipids in Immune System

Over the last 20 years, extracellular vesicles (EVs) have been established as an additional way to transmit signals outside the cell. They are membrane-surrounded structures of nanometric size that can either originate from the membrane invagination of multivesicular bodies of the late endosomal compartment (exosomes) or bud from the plasma membrane (microvesicles). They contain proteins, lipids, and nucleic acids&mdash;namely miRNA, but also mRNA and lncRNA&mdash;which are derived from the parental cell, and have been retrieved in every fluid of the body. As carriers of antigens, either alone or in association with major histocompatibility complex (MHC) class II and class I molecules, their immunomodulatory properties have been extensively investigated. Moreover, recent studies have shown that EVs may carry and deliver membrane-derived bioactive lipids that play an important function in the immune system and related pathologies, such as prostaglandins, leukotrienes, specialized pro-resolving mediators, and lysophospholipids. EVs protect bioactive lipids from degradation and play a role in the transcellular synthesis of prostaglandins and leukotrienes. Here, we summarized the role of EVs in the regulation of immune response, specifically focusing our attention on the emerging role of EVs as carriers of bioactive lipids, which is important for immune system function

Lipid Biomarkers in Liquid Biopsies: Novel Opportunities for Cancer Diagnosis

Altered cellular metabolism is a well-established hallmark of cancer. Although most studies have focused on the metabolism of glucose and glutamine, the upregulation of lipid metabolism is also frequent in cells undergoing oncogenic transformation. In fact, cancer cells need to meet the enhanced demand of plasma membrane synthesis and energy production to support their proliferation. Moreover, lipids are precursors of signaling molecules, termed lipid mediators, which play a role in shaping the tumor microenvironment. Recent methodological advances in lipid analysis have prompted studies aimed at investigating the whole lipid content of a sample (lipidome) to unravel the complexity of lipid changes in cancer patient biofluids. This review focuses on the application of mass spectrometry-based lipidomics for the discovery of cancer biomarkers. Here, we have summarized the main lipid alteration in cancer patients’ biofluids and uncovered their potential use for the early detection of the disease and treatment selection. We also discuss the advantages of using biofluid-derived extracellular vesicles as a platform for lipid biomarker discovery. These vesicles have a molecular signature that is a fingerprint of their originating cells. Hence, the analysis of their molecular cargo has emerged as a promising strategy for the identification of sensitive and specific biomarkers compared to the analysis of the unprocessed biofluid

Extracellular Vesicles as New Players in Cellular Senescence

Cell senescence is associated with the secretion of many factors, the so-called “senescence-associated secretory phenotype”, which may alter tissue microenvironment, stimulating the organism to clean up senescent cells and replace them with newly divided ones. Therefore, although no longer dividing, these cells are still metabolically active and influence the surrounding tissue. Much attention has been recently focused not only on soluble factors released by senescent cells, but also on extracellular vesicles as conveyors of senescence signals outside the cell. Here, we give an overview of the role of extracellular vesicles in biological processes and signaling pathways related to senescence and aging

Insight into the Role of Extracellular Vesicles in Lysosomal Storage Disorders

Extracellular vesicles (EVs) have received increasing attention over the last two decades. Initially, they were considered as just a garbage disposal tool; however, it has progressively become clear that their protein, nucleic acid (namely miRNA and mRNA), and lipid contents have signaling functions. Besides, it has been established that cells release different types of vesicular structures for which characterization is still in its infancy. Many stress conditions, such as hypoxia, senescence, and oncogene activation have been associated with the release of higher levels of EVs. Further, evidence has shown that autophagic&ndash;lysosomal pathway abnormalities also affect EV release. In fact, in neurodegenerative diseases characterized by the accumulation of toxic proteins, although it has not become clear to what extent the intracellular storage of undigested materials itself has beneficial/adverse effects, these proteins have also been shown to be released extracellularly via EVs. Lysosomal storage disorders (LSDs) are characterized by accumulation of undigested substrates within the endosomal&ndash;lysosomal system, due either to genetic mutations in lysosomal proteins or to treatment with pharmacological agents. Here, we review studies investigating the role of lysosomal and autophagic dysfunction on the release of EVs, with a focus on studies exploring the release of EVs in LSD models of both genetic and pharmacological origin. A better knowledge of EV-releasing pathways activated in lysosomal stress conditions will provide information on the role of EVs in both alleviating intracellular storage of undigested materials and spreading the pathology to the neighboring tissue

Protein and Lipid Content of Milk Extracellular Vesicles: A Comparative Overview

The characterization of the protein and lipid cargo of milk extracellular vesicles from different mammal species is crucial for understanding their biogenesis and biological functions, as well as for a comprehensive description of the nutritional aspects of animal milk for human diet. In fact, milk EVs have been reported to possess relevant biological effects, but the molecules/biochemical pathways underlying these effects have been poorly investigated. The biochemical characterization is an important initial step for the potential therapeutic and diagnostic use of natural or modified milk EVs. The number of studies analysing the protein and lipid composition of milk EVs is limited compared to that investigating the nucleic acid cargo. Here, we revised the literature regarding the protein and lipid content of milk EVs. Until now, most investigations have shown that the biochemical cargo of EVs is different with respect to that of other milk fractions. In addition, even if these studies derived mostly from bovine and human milk EVs, comparison between milk EVs from different animal species and milk EVs biochemical composition changes due to different factors including lactation stages and health status is also beginning to be reported

Protein and Lipid Content of Milk Extracellular Vesicles: A Comparative Overview

The characterization of the protein and lipid cargo of milk extracellular vesicles from different mammal species is crucial for understanding their biogenesis and biological functions, as well as for a comprehensive description of the nutritional aspects of animal milk for human diet. In fact, milk EVs have been reported to possess relevant biological effects, but the molecules/biochemical pathways underlying these effects have been poorly investigated. The biochemical characterization is an important initial step for the potential therapeutic and diagnostic use of natural or modified milk EVs. The number of studies analysing the protein and lipid composition of milk EVs is limited compared to that investigating the nucleic acid cargo. Here, we revised the literature regarding the protein and lipid content of milk EVs. Until now, most investigations have shown that the biochemical cargo of EVs is different with respect to that of other milk fractions. In addition, even if these studies derived mostly from bovine and human milk EVs, comparison between milk EVs from different animal species and milk EVs biochemical composition changes due to different factors including lactation stages and health status is also beginning to be reported

Oncogenic H-Ras Expression Induces Fatty Acid Profile Changes in Human Fibroblasts and Extracellular Vesicles

Extracellular vesicles (EVs) are lipid bilayer surrounded particles that are considered an additional way to transmit signals outside the cell. Lipids have not only a structural role in the organization of EVs membrane bilayer, but they also represent a source of lipid mediators that may act on target cells. Senescent cells are characterized by a permanent arrest of cell proliferation, but they are still metabolically active and influence nearby tissue secreting specific signaling mediators, including those carried by EVs. Notably, cellular senescence is associated with increased EVs release. Here, we used gas chromatography coupled to mass spectrometry to investigate the total fatty acid content of EVs released by fibroblasts undergoing H-RasV12-induced senescence and their parental cells. We find that H-RasV12 fibroblasts show increased level of monounsaturated and decreased level of saturated fatty acids, as compared to control cells. These changes are associated with transcriptional up-regulation of specific fatty acid-metabolizing enzymes. The EVs released by both controls and senescent fibroblasts show a higher level of saturated and polyunsaturated species, as compared to parental cells. Considering that fibroblasts undergoing H-RasV12-induced senescence release a higher number of EVs, these findings indicate that senescent cells release via EVs a higher amount of fatty acids, and in particular of polyunsaturated and saturated fatty acids, as compared to control cells