Gian Carlo Tenore

Diabetes-associated corneal dysfunction involves oxidative stress, epithelial injury and disrupted nerve–epithelial communication, contributing to delayed wound healing and reduced corneal sensitivity. Local formulations combining antioxidant activity with support for ocular surface hydration and epithelial integrity may help preserve corneal homeostasis under metabolic stress. This study evaluated whether a Pycnogenol-based ophthalmic formulation (POF), containing polyphenol-rich pine bark extract, sodium hyaluronate, lipids and vitamins, supports corneal homeostasis in streptozotocin (STZ)-treated pre-hatching chicken embryos. Chemical profiling by mass spectrometry and biocompatibility testing were followed by corneal biochemical, histological, gene-expression and nerve-labelling analyses. Circulating glucose and insulin were measured to contextualize corneal responses. POF was well tolerated under the tested conditions. STZ induced hyperglycaemia, reduced circulating insulin, increased corneal oxidative/metabolic biomarkers and disrupted epithelial organization. Following 3 h of POF exposure, corneal stress biomarkers decreased and epithelial organization improved, without significant changes in circulating glucose or insulin. These effects were accompanied by modulation of inflammatory, matrix-remodelling and vascular endothelial growth factor-related gene expression. Neurotrophic gene expression and the fluorescently labelled nerve-associated area also increased. Overall, these findings support the protective potential of the complete formulation in corneal tissue under diabetes-associated oxidative/metabolic stress.

Hypertension remains a major global health challenge, and pharmacological therapy is often constrained by tolerability issues. Adjunctive approaches targeting the nitric oxide synthase and soluble guanylate cyclase–cyclic guanosine monophosphate (sGC–cGMP) pathway may offer additional benefits. This study investigated the efficacy and safety of a nutraceutical formulation combining grape pomace extract (Taurisolo^®) and L-arginine in patients with grade 1 and grade 2 hypertension. The formulation was designed to enhance nitric oxide (NO) bioavailability and support sGC–cGMP signaling. Taurisolo^®, a polyphenol-rich extract, is known for its antioxidant and endothelial-protective properties, while L-arginine serves as the physiological substrate for endothelial NO synthase. Clinical outcomes included blood pressure changes, renal function parameters, and health-related quality of life assessed through the SF-12 questionnaire. Supplementation with Taurisolo^® plus L-arginine resulted in significant and sustained reductions in systolic and diastolic blood pressure, with renal function remaining stable throughout the study. Participants also reported meaningful improvements in perceived health, emotional well-being, vitality, and social functioning. The intervention was well tolerated, with no major adverse effects. These findings support the potential of Taurisolo^® combined with L-arginine as a safe and effective adjunctive strategy to conventional antihypertensive therapy, warranting further mechanistic investigation.

Background/Objectives: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite increasingly recognized as a pro-atherogenic factor and a biomarker of cardiometabolic risk. Dietary patterns and adiposity are key modulators of circulating TMAO levels; however, evidence on the impact of very-low-energy ketogenic therapy (VLEKT) on TMAO metabolism, particularly in women with obesity, remains limited. This study aimed to investigate the effects of VLEKT on circulating TMAO concentrations, with specific focus on treatment duration and body composition (BC) changes. Methods: This study included 43 adult women with obesity eligible for VLEKT based on meal replacements. Anthropometric measurements and BC were assessed using standardized protocols and bioelectrical impedance analysis at baseline and post-intervention. Serum TMAO concentrations were quantified by validated HPLC–ESI–MS/MS. Results: After VLEKT, participants exhibited significant reductions in body weight, BMI, waist girth, fat mass (FM), and circulating TMAO levels. Greater reductions in TMAO were observed in women with longer ketogenic exposure and more pronounced FM loss. Changes in TMAO levels correlated negatively with VLEKT duration and positively with FM variations. In multivariate models, treatment duration and FM reduction emerged as independent predictors of TMAO decrease. A Receiver Operating Characteristic (ROC) analysis identified a FM reduction ≥14.25% as the optimal threshold associated with clinically relevant TMAO lowering. Conclusions: VLEKT reduces circulating TMAO levels in women with obesity. This effect appears to be primarily driven by the duration of ketogenic exposure and the magnitude of FM loss, rather than total weight reduction alone, highlighting the relevance of BC-targeted interventions in modulating gut microbiota-derived cardiometabolic risk markers.

Background: Oedema is a multifactorial condition arising from the interplay between increased microvascular permeability, impaired lymphatic clearance, and sustained inflammation. Conventional treatments often fail, highlighting alternative therapies. This study explores a novel nutraceutical formulation (NF) based on the combination of different natural extracts, i.e., Melilotus officinalis L., Olea europaea L., Morinda citrifolia L., Quercus robur L., and bromelain, aimed at reducing inflammation, a key contributor to oedema pathophysiology. In vitro assays further demonstrated that NF exhibits a marked antioxidant capacity and effectively inhibits key enzymes of the arachidonic acid cascade, supporting its ability to counteract oxidative stress and inflammatory signalling involved in oedema pathophysiology. Methods: The antioxidant and anti-inflammatory properties of NF were assessed in vitro using radical scavenging assays and enzyme inhibition tests targeting key components of the arachidonic acid cascade. The immunomodulatory effects of NF were investigated in RAW264.7 macrophages by flow cytometry and RT-qPCR to evaluate macrophage polarisation and cytokine expression. The anti-oedematous and vascular effects were further examined in vivo using acetic acid–induced inflammation and carrageenan-induced paw oedema models in thirty male Sprague–Dawley rats (Charles River, Calco, Italy). Results: The study demonstrated that NF significantly modulates macrophage polarisation, reducing the proportion of pro-inflammatory M1 macrophages (F4/80⁺CD11b⁺) by 3.23 times compared to control (p < 0.01). A quantitative PCR analysis further confirmed a decrease in pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) by 51.3% (95% CI 48.0–58.7, p < 0.001), 64.1% (95% CI 57.0–71.2, p < 0.001), and 53.7% (95% CI 51.7–55.7, p < 0.001), respectively compared to the control, while anti-inflammatory markers (Arg-1, CD206) increased significantly, suggesting a shift towards an M2 anti-inflammatory state. The NF ability to contrast the pathological alteration characteristic of this disease was further tested in the rat oedema model of thirty male Sprague-Dawley rats. The NF treatment reduced LTB4 and plasma protein levels compared to the control group. In addition, NF could decrease the paw thickness in the rat-based carrageenan-induced oedema model (Charles River, Calco, Italy; n = 30) by 22.5% compared to the control (95% CI 11.0–34.0, p < 0.05). Conclusions: These results suggest that NF may provide a multi-target approach to support the management of some physiopathological changes in complex oedema-related conditions by both modulating inflammation and restoring vascular functionality.

Background: Humans are constantly exposed to environmental microplastic (MP) particles, which can be absorbed through the gut and exert adverse health effects. This study aimed to investigate the harmful effects of environmental polyethylene MPs (PE, 2.6 μm) on differentiated Caco‐2 (D‐Caco‐2) intestinal epithelial cells and to assess the protective potential of Limoncella apple polyphenol extract (LAPE). Methods: D‐Caco‐2 cells were exposed to PE, LAPE, or their combination. Cell viability and lipid peroxidation were evaluated using MTT and TBARS assays, respectively. The organization of F‐actin and alkaline phosphatase proteins was evaluated by immunofluorescence, whereas occludin and NF‐κB were evaluated by Western blot analysis. Results: PE reduced D‐Caco‐2 viability and impaired cell differentiation by increasing lipid peroxidation. In addition, PE destructured F‐actin organization and altered the expression of occludin, a tight‐junction protein. Conclusions: Our findings show that PE increases oxidative stress, triggering epithelial–mesenchymal transition and dedifferentiation in Caco‐2 cells. Interestingly, LAPE, owing to its antioxidant and anti‐inflammatory properties, counteracted the harmful effects of PE, suggesting its potential as a nutraceutical strategy to prevent MP‐induced damage in the gastrointestinal (GI) tract.

Psoriasis is a chronic inflammatory skin disease whose pathogenesis involves not only cutaneous inflammation but also intestinal dysbiosis and oxidative stress (OxS). Monoclonal antibodies targeting interleukin (IL)-17 and IL-23 have demonstrated significant immunomodulatory effects; however, their impact on systemic parameters requires further investigation. We conducted a study on 33 patients with plaque psoriasis treated with anti-IL-17 or anti-IL-23 monoclonal antibodies. Dermatological parameters (Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI)), biomarkers of intestinal dysbiosis (trimethylamine-N-oxide (TMAO)) and OxS (reactive oxygen metabolites (d-ROMs) and oxidized LDL (oxLDL)) were evaluated. Anthropometric, metabolic, and adipose-derived hormonal parameters (adipokines) were also monitored. After 16 weeks of therapy, significant improvements were observed in PASI and DLQI scores (p < 0.001). TMAO levels were significantly reduced (p = 0.02), as were d-ROMs and oxLDL (p < 0.001). No significant changes were found in weight, body mass index, lipid profile, or adipokine levels (visfatin, leptin and adiponectin). Our data indicate that monoclonal antibody therapy not only improves psoriasis severity but also exerts beneficial effects on systemic biomarkers of dysbiosis and OxS, independent of metabolic or hormonal changes. These findings suggest a systemic mechanism of action, supporting a multifactorial therapeutic effect with potential implications for the prevention of cardiovascular risk.

Background: Abscisic acid (ABA), a phytohormone widely distributed in nature, has recently emerged as an endogenous regulator of glucose homeostasis in humans. Specifically, scientific studies have demonstrated that exogenous ABA supplementation improves glycemic control and reduces insulin requirements, with significant advantages in prediabetic subjects. Beyond its metabolic role, growing evidence suggests that ABA is also involved in immune responses, including those associated with pulmonary diseases. Despite these promising results, the evaluation of plasma ABA levels remains largely unexplored in clinical practice. Methods: This study aimed to evaluate whether plasma ABA concentrations differ among healthy individuals, patients with type 2 diabetes, and smokers, in order to clarify the role of ABA as a potential biomarker of both metabolic imbalance and smoking-related inflammatory stress. Results: Our findings show that ABA levels were significantly higher in healthy subjects (10.9 ± 3.8 ng/mL) compared to diabetic patients (6.8 ± 4.2 ng/mL, p < 0.01 vs. healthy subjects), with the lowest levels observed in smokers (3.5 ± 2.5 ng/mL, p < 0.0001 vs. healthy subjects and p < 0.0001 vs. diabetic patients). Moreover, a significant correlation was observed between ABA plasma concentration and number of cigarettes smoked (R² = −0.6776, p = 0.0001). Conclusions: Overall, these results highlight the relevance of measuring ABA plasma levels in both metabolic and inflammatory conditions, confirming its role as a biomarker for identifying individuals who can benefit from exogenous supplementation.

Buffalo mozzarella cheese whey (CW) and ricotta cheese exhausted whey (RCEW) are valuable by-products of the Mozzarella di Bufala Campana PDO production chain. This study characterized their microbial communities using an integrated culture-dependent and -independent approach. Metabarcoding analysis revealed that the dominance of lactic acid bacteria (LAB), including Streptococcus thermophilus, Lactobacillus delbrueckii, and Lactobacillus helveticus, alongside diverse heat-resistant yeasts such as Cyberlindnera jadinii. Culture-based isolation identified subdominant lactic acid bacteria strains, not detected by sequencing, belonging to Leuconostoc mesenteroides, Enterococcus faecalis, and Enterococcus durans. These strains were further assessed for their probiotic potential. E. faecalis CW1 and E. durans RCEW2 showed tolerance to acidic pH, bile salts, and lysozyme, as well as a strong biofilm-forming capacity and antimicrobial activity against Bacillus cereus and Staphylococcus aureus. Moreover, bile salt resistance suggests potential functionality in cholesterol metabolism. These findings support the potential use of CW and RCEW as reservoirs of novel, autochthonous probiotic strains and underscore the value of regional dairy by-products in food biotechnology and gut health applications.