👤 Elisabetta Ferretti

The diagnosis of Alzheimer's disease (AD) traditionally relies on cerebrospinal fluid and plasma levels of amyloid beta and phosphorylated tau. Although informative, these biomarkers represent a narrow, hypothesis-driven approach to intercept the disease. Data-driven analysis was applied on demographic data, apolipoprotein E ( Statistical analyses revealed differences among groups in many cholesterol-related analytes. These findings support the hypothesis that systemic alterations also occur during the preclinical stages of dementia, which can be detected by ML models on blood biomarkers. Machine learning on blood tests detects preclinical cognitive decline.Glycolysis metabolites are predictive for distinguishing stable MCI and AD from HC.Amino acids, lipoproteins, and fatty acids are the most predictive features.Inflammatory and metabolic biomarkers represent a biosignature of cognitive health. Show less

Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy. In this study, we analyzed the biological and molecular effects of pemigatinib on different cancer cell models (lung, bladder, and gastric), which are currently objective of clinical trial investigations. NCI-H1581 lung, KATO III gastric and RT-112 bladder cancer cell lines were evaluated for FGFR expression by qRT-PCR and Western blot. Cell lines were treated with Pem and then characterized for cell proliferation, apoptosis, production of intracellular reactive oxygen species (ROS), and induction of senescence. The expression of microRNAs with tumor suppressor functions was analyzed by qRT-PCR, while modulation of the proteins coded by their target genes was evaluated by Western blot and mRNA. Descriptive statistics was used to analyze the various data and student's t test to compare the analysis of two groups. Pemigatinib exposure triggered distinct signaling pathways and reduced the proliferative ability of all cancer cells, inducing G1 phase cell cycle arrest and strong intracellular stress resulting in ROS production, senescence and apoptosis. Pemigatinib treatment also caused the upregulation of microRNAs (miR-133b, miR-139, miR-186, miR-195) with tumor suppressor functions, along with the downregulation of validated protein targets with oncogenic roles (c-Myc, c-MET, CDK6, EGFR). These results contribute to clarifying the biological effects and molecular mechanisms mediated by the anti-FGFR TKI pemigatinib in distinct tumor settings and support its exploitation for combined therapies. Show less

Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging. Many treatments, including enzyme replacement therapy (for CLN1 and CLN2 diseases), stem-cell therapy (for CLN1, CLN2, and CLN8 diseases), gene therapy vector (for CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN10, and CLN11 diseases), and pharmacological drugs (for CLN1, CLN2, CLN3, and CLN6 diseases) have been evaluated for safety and efficacy in pre-clinical and clinical studies. Currently, cerliponase alpha for CLN2 disease is the only approved therapy for NCL. Lacking is any study of potential treatments for CLN4, CLN9, CLN12, CLN13 or CLN14 diseases. This review provides an overview of genetics for each CLN disease, and we discuss the current understanding from pre-clinical and clinical study of potential therapeutics. Various therapeutic interventions have been studied in many experimental animal models. Combination of treatments may be useful to slow or even halt disease progression; however, few therapies are unlikely to even partially reverse the disease and a complete reversal is currently improbable. Early diagnosis to allow initiation of therapy, when indicated, during asymptomatic stages is more important than ever. Show less

Recent studies have demonstrated that Apo AIV exerts a protective effect against atherosclerosis. Moreover, Qin et al. (Am. J. Physiol. 274 (1998) H1836) have demonstrated that Apo AIV, isolated from rat plasma, exerts an inhibitory effect against Cu(2+)-induced lipid peroxidation of intestinal lymph and LDL. The aim of the study was to investigate whether human Apo AIV exerts a protective effect against Cu(2+)-induced lipid peroxidation. Our results demonstrated that human Apo AIV exerted an inhibitory effect against Cu(2+) and AAPH induced lipid peroxidation of VLDL, as shown by the lower increase in the levels of TBARS and conjugated dienes in lipoproteins preincubated with Apo AIV. In addition, the tryptophan (Trp) and probe 2-(dimethylamino)-6-lauroylnaphthalene (Laurdan) fluorescence studies demonstrated that the modifications of spectral properties in both lipoproteins preincubated with Apo AIV were lower with respect to ox-lipoproteins, suggesting that Apo AIV prevents the modification of physico-chemical properties due to peroxidation. Show less