Aurelio Minuti

RESEARCH, TEACHING, or OTHER INTERESTS

Biochemistry, Genetics and Molecular Biology, Cell Biology, Endocrinology, Cancer Research

Scopus Publications

Bioactivated Glucoraphanin Improves Cell Survival, Upregulating Phospho-AKT, and Modulates Genes Involved in DNA Repair in an In Vitro Alzheimer’s Disease Model: A Network-Transcriptomic Analysis
Aurelio Minuti, Emanuela Mazzon, Renato Iori, Luigi Chiricosta, and Osvaldo Artimagnella
MDPI AG
Background/Objectives: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, for which a definitive cure is still missing. Recently, natural compounds have been investigated for their possible neuroprotective role, including the bioactivated product of glucoraphanin (GRA), the sulforaphane (SFN), which is highly rich in cruciferous vegetables. It is known that SFN alleviates neuronal dysfunction, apoptosis, and oxidative stress in the brain. In the light of this evidence, the aim of this study was to investigate the molecular effects of SFN pre-treatment in differentiated SH-SY5Y neurons exposed to β-amyloid (Aβ). Methods: To this end, we first evaluated first cell viability via the Thiazolyl Blue Tetrazolium Bromide (MTT) assay, and then we analyzed the transcriptomic profiles by next-generation sequencing (NGS). Finally, we used a network analysis in order to understand which biological processes are affected, validating them by Western blot assay. Results: SFN pre-treatment counteracted Aβ-induced loss of cell viability. The network-transcriptomic analysis revealed that SFN upregulates genes associated with DNA repair, such as ABRAXAS1, BRCA1, BRCA2, CDKN1A, FANCA, FANCD2, FANCE, NBN, and XPC. Finally, SFN also increased the phosphorylation of AKT, which is associated with DNA repair and cell survival. Conclusions: These data suggest that SFN is a natural compound that could be suitable in the prevention of AD, thanks to its neuroprotective role in increasing cell survival, potentially restoring DNA damage induced by Aβ exposure.


Bioactivated Glucoraphanin Modulates Genes Involved in Necroptosis on Motor-Neuron-like Nsc-34: A Transcriptomic Study
Aurelio Minuti, Alessandra Trainito, Agnese Gugliandolo, Ivan Anchesi, Luigi Chiricosta, Renato Iori, Emanuela Mazzon, and Marco Calabrò
MDPI AG
Research on bioactive compounds has grown recently due to their health benefits and limited adverse effects, particularly in reducing the risk of chronic diseases, including neurodegenerative conditions. According to these observations, this study investigates the activity of sulforaphane (RS-GRA) on an in vitro model of differentiated NSC-34 cells. We performed a transcriptomic analysis at various time points (24 h, 48 h, and 72 h) and RS-GRA concentrations (1 µM, 5 µM, and 10 µM) to identify molecular pathways influenced by this compound and the effects of dosage and prolonged exposure. We found 39 differentially expressed genes consistently up- or downregulated across all conditions. Notably, Nfe2l2, Slc1a5, Slc7a11, Slc6a9, Slc6a5, Sod1, and Sod2 genes were consistently upregulated, while Ripk1, Glul, Ripk3, and Mlkl genes were downregulated. Pathway perturbation analysis showed that the overall dysregulation of these genes results in a significant increase in redox pathway activity (adjusted p-value 1.11 × 10−3) and a significant inhibition of the necroptosis pathway (adjusted p-value 4.64 × 10−3). These findings suggest RS-GRA’s potential as an adjuvant in neurodegenerative disease treatment, as both increased redox activity and necroptosis inhibition may be beneficial in this context. Furthermore, our data suggest two possible administration strategies, namely an acute approach with higher dosages and a chronic approach with lower dosages.


Cannabinerol Prevents Endoplasmic Reticulum and Mitochondria Dysfunctions in an In Vitro Model of Alzheimer’s Disease: A Network-Based Transcriptomic Analysis
Luigi Chiricosta, Aurelio Minuti, Agnese Gugliandolo, Stefano Salamone, Federica Pollastro, Emanuela Mazzon, and Osvaldo Artimagnella
MDPI AG
Neurodegenerative disorders are affecting millions of people worldwide, impacting the healthcare system of our society. Among them, Alzheimer’s disease (AD) is the most common form of dementia, characterized by severe cognitive impairments. Neuropathological hallmarks of AD are β-amyloid (Aβ) plaques and neurofibrillary tangles, as well as endoplasmic reticulum and mitochondria dysfunctions, which finally lead to apoptosis and neuronal loss. Since, to date, there is no definitive cure, new therapeutic and prevention strategies are of crucial importance. In this scenario, cannabinoids are deeply investigated as promising neuroprotective compounds for AD. In this study, we evaluated the potential neuroprotective role of cannabinerol (CBNR) in an in vitro cellular model of AD via next-generation sequencing. We observed that CBNR pretreatment counteracts the Aβ-induced loss of cell viability of differentiated SH-SY5Y cells. Moreover, a network-based transcriptomic analysis revealed that CBNR restores normal mitochondrial and endoplasmic reticulum functions in the AD model. Specifically, the most important genes regulated by CBNR are related mainly to oxidative phosphorylation (COX6B1, OXA1L, MT-CO2, MT-CO3), protein folding (HSPA5) and degradation (CUL3, FBXW7, UBE2D1), and glucose (G6PC3) and lipid (HSD17B7, ERG28, SCD) metabolism. Therefore, these results suggest that CBNR could be a new neuroprotective agent helpful in the prevention of AD dysfunctions.


Polychlorinated Biphenyls (PCBS)-induced oxidative stress and inflammation in human thyrocytes: involvement of AhR and NRF-2/HO-1 pathway
Rosaria M. Ruggeri, Aurelio Minuti, Fiorenza Gianì, Roberta Masto, Davide Romano, Federica Aliquò, Alfredo Campennì, Salvatore Campo, Salvatore Cannavò, and Angela D’Ascola
Springer Science and Business Media LLC



Antimicrobial Susceptibility of Staphylococcus aureus Strains and Effect of Phloretin on Biofilm Formation
Giuseppina Mandalari, Aurelio Minuti, Erminia La Camera, Davide Barreca, Orazio Romeo, and Antonia Nostro
Springer Science and Business Media LLC



Endocan Knockdown Down-Regulates the Expression of Angiogenesis-Associated Genes in Il-1ß Activated Chondrocytes
Michele Scuruchi, Federica Aliquò, Angela Avenoso, Giuseppe Mandraffino, Giovanna Vermiglio, Aurelio Minuti, Salvatore Campo, Giuseppe Maurizio Campo, and Angela D’Ascola
MDPI AG
Endocan is a small soluble proteoglycan (PG) known to be involved in inflammation and angiogenesis. Increased endocan expression was found in the synovia of arthritic patients and chondrocytes stimulated with IL-1ß. Considering these findings, we aimed to investigate the effects of endocan knockdown on the modulation of pro-angiogenic molecules expression in a model of IL-1ß-induced inflammation in human articular chondrocytes. Endocan, VEGF-A, MMP-9, MMP-13, and VEGFR-2 expression was measured in both normal and endocan knockdown chondrocytes stimulated with IL-1ß. VEGFR-2 and NF-kB activation were also measured. Results have shown that endocan, VEGF-A, VEGFR-2, MMP-9, and MMP-13 were significantly up-regulated during IL-1ß-induced inflammation; interestingly, the expression of such pro-angiogenic molecules and NF-kB activation were significantly reduced by endocan knockdown. These data support the hypothesis that endocan released by activated chondrocytes may be involved in the mechanisms that stimulate cell migration and invasion, as well as angiogenesis, in the pannus of arthritic joints.


Endocan Promotes Pro-Tumorigenic Signaling in Lung Cancer Cells: Modulation of Cell Proliferation, Migration and lncRNAs H19 and HULC Expression
Federica Aliquò, Aurelio Minuti, Angela Avenoso, Giuseppe Mandraffino, Giuseppe Maurizio Campo, Salvatore Campo, Angela D‘Ascola, and Michele Scuruchi
MDPI AG
Endocan is a circulating proteoglycan secreted by several cell lines and identified as a potential biomarker of inflammation and angiogenesis. Endocan-increased expression has been found in a broad spectrum of human tumors, including lung cancer, and is associated with a poor prognosis. To elucidate the possible mechanism, this study aimed to investigate the role of endocan in non-small-cell lung carcinoma (NSCLC) using an in vitro model of cultured cells. Endocan expression was knocked down by using a specific small interfering RNA. The effects of endocan knockdown have been evaluated on VEGF-A, VEGFR-2, HIF-1α, the long non-coding RNAs H19 and HULC expression, and AKT and ERK 1/2 degree of activation. Cell migration and proliferation have been studied as well. VEGF-A, VEGFR-2, HIF-1α, and the long non-coding RNAs H19 and HULC expression were significantly affected by endocan knockdown. These effects correlated with a reduction of cell migration and proliferation and of AKT and ERK 1/2 activation. Our findings suggest that endocan promotes a more aggressive cancer cell phenotype in NSCLC.