Davide Barreca

Neurodegenerative diseases represent a significant clinical challenge. Understanding the pathogenic mechanisms is essential for developing more effective therapies, and mitochondria appear to play a key role in these processes. Since current treatments are limited to symptom management, natural strategies capable of preserving mitochondrial function could represent a promising preventive and therapeutic approach in neurodegeneration. This study aims at investigating the molecular mechanisms underlying the neuroprotective potential of an anthocyanin-rich extract from Callistemon citrinus flower (Cce) in differentiated SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA). Exposure of cells to 6-OHDA inhibited cell viability and caused cell death, events hindered by the pre-treatment with Cce. Furthermore, it restored normal cell cycle distribution, as well as hampered 6-OHDA-induced apoptosis. Given the pro-oxidant effect of 6-OHDA, we observed that Cce reduced reactive oxygen species in stressed SH-SY5Y cells, along with recovering their antioxidant protection system. Focusing on mitochondria, Cce was able to protect their membranes from 6-OHDA, as suggested by the restoration of mitochondrial membrane potential. This led to a reduction in release of cytochrome c and the consequent activation of caspases 9 and 3, characteristic of the intrinsic apoptotic pathway, supporting our initial findings. Our results indicate that Cce prevents SH-SY5Y cell death induced by 6-OHDA via the preservation of mitochondrial integrity mainly through to its antioxidant properties, encouraging further studies to support its exploitation in the management of neurodegeneration.

Anthocyanins are plant polyphenols widely regarded as antioxidants, yet they can exert concentration-dependent effects and act as pro-oxidants in specific contexts. Although their protective role in stressed testicular cells is established, their impact on Leydig cell steroidogenesis under non-pathological conditions remains poorly understood. Here, we investigated how an anthocyanin-enriched fraction from Callistemon citrinus (0–1.00 μg/mL) affects androgen synthesis in murine TM3 Leydig cells. Cell viability, intracellular ROS, antioxidant capacity, mitochondrial function, androstenedione production, steroidogenic gene expression, and the exometabolome by ¹H-NMR were assessed. The fraction exhibited biphasic, dose-dependent effects. At 0.01 μg/mL, it induced a mitohormetic response, upregulating mitochondrial complexes III and V. Conversely, higher concentrations (0.10–1.00 μg/mL) reduced metabolic activity, increased intracellular ROS, and significantly suppressed androstenedione synthesis independently of Star. These concentrations also induced dose-dependent repression of Cyp17a1, concomitant with upregulation of Nr0b2, encoding the transcriptional repressor Small Heterodimer Partner (SHP). Overall, the data support a redox-dependent mechanism whereby elevated ROS promotes Nr0b2 expression, leading to Cyp17a1 suppression and impaired androstenedione production. These findings challenge the view of anthocyanins as uniformly beneficial for male fertility and identify Callistemon citrinus as a sustainable source of bioactive anthocyanins capable of modulating redox–endocrine homeostasis in a dose-dependent manner under basal conditions.

Supramolecular nanoparticles offer an efficient strategy to enhance the solubility, stability, and bioavailability of poorly water-soluble therapeutic molecules. In this study, water-dispersible SNPs were successfully prepared from dicarboxyl-bis-pillar[5]arene (H) and cetyltrimethylammonium bromide (CTAB) using a microemulsion method. Dynamic light scattering revealed that the resulting CTAB/H nanoparticles possessed a size distribution centered around 40 nm, a positive surface charge (+15 mV), and exhibited high colloidal stability over three months. ¹H NMR, 2D TOCSY, 2D NOESY, diffusion ordered NMR spectroscopy, and UV-Vis investigations confirmed the inclusion of the CTAB alkyl chain within the pillar[5]arene cavity, supporting the formation of stable supramolecular assemblies capable of efficiently encapsulating the poorly water-soluble flavonol quercetin (Q). The CTAB/H system displayed low cytotoxicity (up to 50 µg/mL) and pronounced antioxidant activity, as evidenced by DPPH, ABTS, and FRAP assays. Quercetin-loaded nanoparticles (CTAB/H/Q) enhanced cellular uptake and exhibited a marked cytoprotective effect against H₂O₂-induced oxidative stress in NIH-3T3 fibroblasts.

Metabolic syndrome (MetS) represents a global health challenge mainly driven by chronic low-grade inflammation and persistent oxidative stress (OS). Current therapeutic and nutritional strategies often fail to resolve these interconnected core pathologies due to the multifactorial nature of MetS. Anthocyanins (ACNs), a class of potent dietary flavonoids, offer significant promise due to their established pleiotropic effects, including robust antioxidant activity through modulation of the Nrf2/ARE pathway, anti-inflammatory effects via NF-κB suppression, and overall support for glucose and lipid homeostasis. However, the therapeutic efficacy of ACNs is characterized by interindividual variability, which is intrinsically linked to their low systemic bioavailability. This heterogeneity in the response is due to the complex interplay between genetic polymorphisms affecting absorption, distribution, metabolism, and excretion (ADME), as well as the specific biotransformation capacity of the gut microbiome. This review proposes that achieving the full clinical potential of ACNs requires moving beyond conventional nutritional advice. We propose that precision nutrition, which integrates multi-omics data (e.g., genomics, metagenomics, and metabolomics), can determine the individual phenotype, predict functional metabolic response, and tailor safer and effective ACN-rich interventions. This integrated, multifactorial approach is essential for optimizing the antioxidant and metabolic benefits of ACNs for the prevention and management of MetS and its associated pathologies.

Oxidative stress (OS), defined by an imbalance between reactive oxygen species (ROS) production and antioxidant defences, plays a bivalent and paradoxical role in the male reproductive system. At physiological levels, ROS are indispensable for sperm capacitation, hyperactivation and acrosome reaction, which are crucial for fertilization. However, excessive ROS – stemming from both endogenous sources (e.g. mitochondrial metabolism, enzyme‐mediated reactions, seminal leukocytes) and exogenous factors (e.g. environmental pollutants and lifestyle behaviours) – can trigger detrimental OS reactions, including lipid peroxidation, DNA damage and impaired sperm function, contributing to male infertility. This dualistic nature of OS complicates defining the distinction between its physiological and pathological concentrations of ROS. This review comprehensively examines the complex interplay between ROS and OS in male reproduction, delineating how lifestyle factors can contribute to this imbalance and what mechanisms are implicated. Furthermore, we discuss current and emerging non‐pharmacological strategies aimed at mitigating pathological OS, including antioxidant supplementation (e.g. resveratrol, vitamins C and E, coenzyme Q10), dietary interventions such as adherence to the Mediterranean diet and lifestyle modifications like regular moderate exercise and stress management techniques. By elucidating these multifaceted aspects, our analysis provides critical insights into maintaining redox homeostasis and advancing clinical interventions for improved male reproductive health. image

The necessity to produce new biodegradable polymeric materials, to overcome the economic model, based on the linear economy, and to apply the circular economy model is a global problem. As a result, components unutilized derived from industrial processes are becoming increasingly valuable and useful to create new materials. This work focuses on the production of bioplastics based on poly (vinyl) alcohol (PVA) that have been modified with flavonoid fraction, liquid fraction obtained after digestion with cellulase and pectinase, and the solid material remaining after enzyme treatment, obtained from Citrus bergamia by-product (the so-called “pastazzo”). This last one is an almost completely unutilized product, although it is a potential rich source of biological active compounds. Enzymatic and non-enzymatic green extraction protocol have been employed to separate the different fractions and to make it more suitable to functionalize the PVA, suppling new properties to the bioplastics in a dose-dependent manner. Morpho-functional analysis was conducted by SEM, XRD, colorimetry, UV–visible and ATR-FTIR spectroscopy. Regarding optical properties, the obtained results show that transparency of the film in terms of light transmittance (T%) for PVA alone is very high, but when functionalized it had a reduced T%. From the data obtained, the functionalized films acquire antioxidant activity, as well as good mechanical properties, making them good candidates for biodegradable packaging for preserving the shelf life of different fruits and vegetables as confirmed by the food fresh-keeping test performed on apple samples.

Bacterial nanocellulose (BNC) has gained considerable interest over the last decade due to its unique properties and versatile applications. However, the low yield and the high production cost significantly limit its industrial scalability. The proposed study explores the isolation of new BNC producers from date palm sap and the use of date waste extract as a sustainable carbon source to improve BNC productivity. Results revealed three potential BNC producers identified as Komagataeibacter sp. IS20, Komagataeibacter sp. IS21, and Komagataeibacter sp. IS22 with production yield of 1.7 g/L, 0.8 g/L and 1.8 g/L, respectively, in Hestrin-Schramm (HS) medium. The biopolymer characterization indicated the presence of type I cellulose, a high thermal stability, and a highly dense network made of cellulose nanofibrils for all BNC samples. The isolate IS22, showing the highest productivity, was selected for an optimization procedure using a full factorial design with date waste extract as a carbon source. The BNC yield increased to 6.59 g/L using 4% date waste extract and 2% ethanol after 10 days of incubation compared to the standard media (1.8 g/L). Two probiotic strains, including Bacillus subtilis (BS), and Lactobacillus plantarum (LP) were successfully encapsulated into BNC matrix through a co-culture approach. The BNC-LP and BNC-BS composites showed antibacterial activity against Pseudomonas aeruginosa. BNC–probiotic composites have emerged as a promising strategy for the effective delivery of viable probiotics in a wide range of applications. Overall, this study supports the use of date waste extract as a sustainable carbon source to enhance BNC productivity and reduce the environmental footprint using a high-yielding producer (IS22). Furthermore, the produced BNC demonstrated promising potential as an efficient carrier matrix for probiotic delivery.

Candidiasis arises from the proliferation of Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against C. albicans, C. glabrata, and C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (6), with fungistatic and fungicidal effects against C. glabrata and C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound 6 affected the cell membrane integrity in C. albicans strain 16. Finally, carboxamide 6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release.