IRIS UNIME
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Quantitative Analysis of Point Clouds for the Description of Complex Dynamical Systems: New Formulation of Differential Entropy and Analytical Strategies in Football Matches
No full textSwitching to brodalumab after failure of IL ‐ 17A inhibitors in psoriatic patients: A real‐life multicentre study
No full textOrthonormal Right-Handed Killing Frames on the Two-Sphere and Solutions to Maxwell’s Equations - via de Broglie Waves - in tempered complex 3-field space: a Schwartz linear isomorphism model
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PCB 153 Modulates Genes Involved in Proteasome and Neurodegeneration-Related Pathways in Differentiated SH-SY5Y Cells: A Transcriptomic Study
No full text: Polychlorinated biphenyls (PCBs) are persistent environmental contaminants associated with neurotoxicity and increased risk of neurodegenerative diseases. PCB 153, a highly abundant non-coplanar congener, bioaccumulates in human tissues and impairs homeostasis. This study investigated the transcriptomic effects of PCB 153 (2,2',4,4',5,5'-Hexachlorobiphenyl) in retinoic acid (RA)-differentiated SH-SY5Y neuronal cells to identify early, sub-cytotoxic molecular alterations. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after 24 h exposure to increasing PCB 153 concentrations. RNA-Seq was performed on cells treated with 5 μM PCB 153, the highest non-cytotoxic dose. Sequencing reads were quality-filtered, aligned to the human genome, and analyzed with DESeq2. Functional enrichment was conducted using Gene Ontologies and KEGG pathways. Western blot analyses were performed to assess protein level changes in selected targets. RNA-Seq identified 1882 significantly altered genes (q-value < 0.05). Gene Ontology analysis revealed strong enrichment of proteasome-related terms, with most proteasomal subunits displaying coordinated upregulation. KEGG analysis further showed significant enrichment of Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), and other neurodegenerative disease pathways. These findings indicate that PCB 153 triggers a pronounced proteostatic response in neuron-like cells, suggesting early disruption of protein homeostasis that may contribute to mechanisms associated with neurodegeneration
Depigmenting action and bioimaging of luminescent BODIPY-based piperazinyl phenol derivatives
No full textMelanin biosynthesis is a complex enzymatic process regulated by tyrosinase (TYR, EC 1.14.18.1) that initiates the process catalyzing the conversion of L-tyrosine to L-DOPA and L-DOPA to dopaquinone. The two transformations occur on the same active site of the enzyme composed of six histidine residues that coordinate two copper ions. TYR has been recognized as one of the most popular therapeutic targets for controlling melanin synthesis. Herein we report the synthesis of BODIPY-based piperazinyl phenol derivatives, that were designed to develop luminescent probes for the detection of TYR activity; additionally, these molecules might contemporarily act as TYR inhibitors through the piperazinyl phenolic fragment. Molecular docking studies pointed out the ability of the new compounds to bind the active site of Agaricus bisporus mushroom tyrosinase (AbTYR). Mitochondrial cytotoxic assay revealed that all the synthesized compounds were not cytotoxic up to 50 μM concentration. Their inhibitory effects were tested against monophenolase and diphenolase activities of AbTYR; as results two of the three new compounds provided to be more active than the starting reagent 4-(piperazin-1-yl)phenol for monophenolase activity. The most active inhibitor (IC50 value of 17.10 μM) was investigated through fluorescence spectroscopy and results corroborate the binding with AbTYR. Moreover, zebrafish embryos were used as a model organism for depigmentation studies and the introduction of fluorescent BODIPY moiety on the pharmacophoric fragment deeply improved its biocompatibility when compared to parent compounds and reflected its biodistribution
Targeting redox homeostasis and cell survival signaling with a flavonoid-rich extract of bergamot juice in in vitro and in vivo colorectal cancer models
No full textBackground/Objectives: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Evidence suggests that a polyphenol-rich diet may lower the risk of CRC. The aim of this study was to demonstrate the potential antitumor effects of a flavonoid-rich extract of bergamot juice (BJe) in both in vitro and in vivo CRC models, assessing the underlying mechanisms. Methods: CRC cells, among which HCT-116, have been employed to assess the fine mechanism of action of BJe, whereas a mouse model of azoxymethane (AOM)-induced CRC was exploited to appreciate the anti-cancer effects of BJe. Results: BJe inhibited the growth of several CRC cells, especially HCT-116. In this cell line, BJe induced apoptosis and blocked the cell cycle in the G1 phase, as well as modulated the gene expression of apoptosis- and cell cycle-related factors. Moreover, BJe prompted reactive oxygen species production and impaired mitochondrial membrane potential. In the nucleus of these cancerous cells, BJe induced DNA damage as confirmed by the raised levels of 8-oxo-2 '-deoxyguanosine and phosphorylation of histone H2A.X. In mice with AOM-induced CRC, BJe was able to lower the number of aberrant crypt foci. Moreover, BJe reduced the percentage of mice bearing both polyps and tumors, as well as their number. Conclusions: Our study supports the role of BJe against CRC, providing knowledge on the underlying mechanism of action
Circulating miRNAs as biomarkers of skeletal fragility in pituitary disorders
No full textBackground. Endocrine disorders such as acromegaly, Cushing’s syndrome, and growth hormone deficiency (GHD) are associated with skeletal fragility that is not fully captured by bone mineral density (BMD) assessment. Circulating microRNAs (miRNAs), key regulators of bone metabolism, may serve as novel biomarkers of bone quality.
Methods. This study investigated circulating serum miRNA profiles in patients with acromegaly (n=20), Cushing’s syndrome (n=14), and GHD (n=10) compared with unaffected controls (n=20). A panel of 14 bone-related miRNAs was analyzed through quantitative PCR.
Results. Distinct, disease-specific expression patterns were observed: in acromegaly, seven miRNAs (miR-100-5p, miR-148a-3p, miR-194- 5p, miR-21-5p, miR-23a-3p, miR-29b-3p, and miR-422a ) were significantly upregulated; in Cushing’s syndrome, only miR-550a-3p was upregulated; in GHD, five miRNAs (miR-125b-5p, miR-133a- 3p, miR-145-5p, miR-30e-5p, miR-335-5p) were downregulated.
Across all endocrine conditions, osteoporotic patients displayed a consistent downregulation of 13 circulating miRNAs, suggesting a shared molecular fingerprint of secondary osteoporosis. Diagnostic performance analyses revealed that multi-miRNA signatures provided higher accuracy than individual markers, with AUC values
>0.9 for acromegaly and GHD, and a 13-miRNA osteoporosis
signature reaching an AUC of 1.0. These findings support the role of circulating miRNAs as integrative biomarkers of skeletal fragility in endocrine disorders.
Conclusion. Circulating miRNA profiles mirror the molecular
mechanisms underlying endocrine-related osteoporosis and may complement conventional imaging for early diagnosis, risk stratification, and monitoring. Their integration into clinical practice could enable a transition toward dynamic, molecularly informed assessment of bone health
Chemical and Radiometric Profiling of Indoor Particulate Matter in a Cultural Heritage Site: The Case of Saronno’s Sanctuary
No full textEnsuring good air quality in indoor environments of historical and artistic significance is essential not only for protecting valuable artworks but also for safeguarding human health. While many studies in this field tend to focus on the preservation of cultural heritage, fewer have addressed the impact on visitors and worshippers. Yet, places such as museums, galleries, churches, and other religious sites attract large numbers of people, making indoor air quality a key factor for their well-being. This study focused on evaluating air quality within the Santuario della Beata Vergine dei Miracoli in Saronno, Italy, a religious site that welcomes large numbers of visitors and worshippers each year. A detailed analysis of particulate matter was conducted, including chemical characterization by ICP-MS for metals, ion chromatography for water-soluble ions, and thermal–optical analysis for the carbonaceous fraction, as well as assessments of size distribution and radiometric properties. The results indicated overall good air quality conditions: concentrations of heavy metals were below levels of concern (<35 ng m−3), and gross alpha, beta, and 137Cs activity concentrations remained below the minimum detectable thresholds. Hence, no significant health risks were identified
