Simonetta Palleschi

The widespread presence of micro- and nanoplastics (MNPs) in the environment represents an emerging risk for human and environment health. New Approach Methodologies (NAMs) offer valuable tools to improve the mechanistic understanding of nanoscale processes and support hazard identification without animal testing. This study investigated the biological effects of exposure to 0–100 µg/mL 100 and 20 nm polystyrene (PS-NPs) and 100 nm polycaprolactone nanoplastics (PCL-NPs) using advanced in vitro intestinal models and the 3R-compliant in vivo Caenorhabditis elegans model. In vitro endpoints included cytotoxicity, oxidative stress, DNA damage, cellular internalization, and barrier integrity, while in vivo analyses focused on oxidative stress and locomotor behavior across multiple exposed generations. PS-NPs induced significant DNA damage in vitro, particularly at ≥50 µg/mL after 24–48 h exposure, and were rapidly internalized by cells, with 20 nm particles also detected in the nucleus. In contrast, 100 nm PCL-NPs elicited weaker biological responses. In vivo, PS-NPs caused an increase in oxidative stress response and locomotor behavior across exposed generations, whereas PCL-NPs produced milder effects, consistent with in vitro findings. These results support the potential of integrated NAMs for assessing human health risks associated with MNP exposure within a One Health framework.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a key contributor to the development of heart failure with preserved ejection fraction in individuals with obesity. This study aimed to investigate whether MASLD and diastolic dysfunction are independently associated with abdominal obesity through shared metabolic and oxidative mechanisms. We conducted a cross-sectional study in a tertiary university hospital including patients aged ≥ 50 years with obesity and MASLD. Clinical, anthropometric, biochemical, and oxidative stress parameters were collected, and hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (FibroScan^®). Patients were stratified according to the presence or absence of echocardiographic diastolic dysfunction. A total of 73 patients was included in the analysis and 27.4% had diastolic dysfunction. Patients with diastolic dysfunction were older and had higher body weight, body mass index (BMI) and waist circumference. Markers of hepatic steatosis, including fatty liver index (FLI) and controlled attenuation parameter (CAP), were higher in patients with diastolic dysfunction, whereas fibrosis measures were not. CAP was independently associated with diastolic dysfunction after adjustment for age and sex, but this association was lost after further adjustment for waist circumference, suggesting a mediating role of central adiposity. Plasma glutathione was inversely associated with FLI, but oxidative stress markers were not associated with diastolic dysfunction or steatosis severity. In conclusion, in patients ≥ 50 years with MASLD and obesity, diastolic dysfunction was common and closely related to abdominal obesity, highlighting MASLD as a multisystem condition with early cardiac involvement.

Background: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects with MASLD, obesity and/or T2D, aged ≥ 50 years. Methods: Anthropometric and clinical parameters, non-invasive indices for steatosis and fibrosis and FibroScan^® data were collected. Results: Among 213 patients (65.7% women, median age 63.0 years and mean Body Mass Index (BMI 34.9 kg/m²), men had higher body weight and waist circumference (WC), whereas women showed higher BMI and waist-to-height ratio (WHtR), and were more likely to exceed WC sex-specific and WHtR risk cut-offs. While transaminases values were higher in men, sex-specific cut-offs revealed that women more frequently exceeded these thresholds. No sex-differences were found for Fatty Liver Index (FLI), Fibrosis-4 (FIB-4) or FibroScan^®, although higher rate of mild fibrosis in women. The diagnostic accuracy of FLI for detecting steatosis was significantly higher in men and unsatisfactory in women (Area Under the ROC Curve, AUC 0.863 vs. 0.655). Conclusions: While MASLD is more common in men, these results suggest that postmenopausal women with visceral obesity showed similar or worse liver and cardiometabolic profiles than men, despite appearing healthier based on standard clinical parameters. Notably, common markers like transaminases and the FLI were less accurate in detecting steatosis in women, underscoring the need for sex-specific diagnostic criteria and greater clinical attention to older women, particularly those with central obesity, to ensure early identification and management of MASLD.

The classical light interactions of nanosilicon, which is a dielectric material, are exceedingly weak for radius r ≪ λ (wavelength), scaling as r6. It exhibits geometrical anisotropy-based depolarization, which is the basis for the very weak response in isotropic structures (nanosphere). Recently, surface enhanced Raman scattering (SERS) in DNA decorated with ultrasmall Si nanoparticles has been demonstrated, affording an effective alternative to plasmon–metal particles. In this paper, we execute fundamental quantum atomistic computation of 1 nm hydrogenated Si particles, with different surface reconstruction and termination, including Si–H, H–Si–Si–H (dimer molecules), or oxygenated dimer bridges (H–Si–O–Si–H). We obtain the mechanical vibrational modes of the particles. Our results show that by changing the surface configuration one can control the symmetry and normal vibration modes, and enhance the polarizability, polarity, and light interactions (scattering, absorption, and depolarization/memory). The low frequency polarizability (Raman scattering) shifts spatially from the interior to the surface, while the infrared polarity remains on the surface, but its bandwidth narrows spectrally. The results support previous infrared absorption and light scattering and depolarization measurements, as well recent SERS, which enable Si nanoparticles to be an effective alternative to plasmonic metal particles. Molecular surface reconstruction in terms of Si dimers and bridges were suggested as the source of the novel nonlinear and anisotropic luminescence and photonic properties of Si nanoparticles. Such control affords potential for optimizing the design and operation of a wide range of opto-electronic advanced scattering and luminescence devices.

Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.

Surface enhanced Raman scattering (SERS), in which sample molecules are placed in the proximity of conducting nanostructures, subjects the molecules to intense electron oscillation (plasmon) field. The intense field, however, may cause heavy distortion and thermal damage to the molecule as well as non-separable and heavy convolution with the metal electronic structure. We utilized 3-nm red luminescent Si nanoparticles decorating the DNA molecules (drawn electrostatically) to enhance Raman scattering in solution at 532 nm. We demonstrated that the nanoparticles enhance the spectral resolution and intensity of vibrations of DNA by two orders of magnitude and reveal vibrations that are otherwise weak or forbidden. Theoretically, we conducted calculations of Mie scattering and three-dimensional finite-difference time-domain scattering and obtained the wavelength dependence of the near-field distribution from single or dimer Si particles. The simulations show moderate intensity enhancement (25–40-fold) and exciton resonances. Moreover, it shows that the near field is highly confined, extending only to 3–5 Å from the Si particle (atomic scale) compared to several nanometers for metal nanoparticles. The observed SERS-type characteristics are understood in terms of polarization-based light scattering, which is possible by the use of Si of highly reduced size for which the polarizability and exciton processes are strong. However, multilayers contribute to metal SERS, and monolayers/single molecules dominate the Si case. Weaker but highly confined, ultra-short range polarization-based scattering provides an alternative to plasmon and Mie scattering, while providing practical, straightforward interpretation of vibration printing of bio-medical species without compromising the molecular structure.

Hemodiafiltration with on-line endogenous reinfusion (HFR) is an extracorporeal dialytic method that combines diffusion, convection and adsorption. HFR-Supra (HFR-S) is a second-generation system with increased convective permeability and adsorption capability. Previous studies suggested that HFR reduces oxidative stress compared to standard haemodialysis. The principal aim of the present study was to compare antioxidant vitamins behavior and oxidative status of hemodialysis patients treated with HFR and HFR-S. The study was designed as a multicenter, randomized, crossover trial. Forty-one patients were recruited from 19 dialysis centers and after a 4-month washout stabilization period in on-line hemodiafiltration (ol-HDF), each patient was randomized to a sequence of treatments (HFR-S followed by HFR or viceversa) with each treatment applied over 6 months. Plasma levels of Advanced Oxidation Protein Products, Total Antioxidant Status, vitamins C, A and E and their ligands (Retinol Binding Protein and total lipids) were measured at baseline and at the end of each treatment period. Results show that the higher convective permeability of HFR-S with respect to HFR did not produce additional beneficial effects on the patients’ oxidative status, a slight decrease of both Vitamin A and Retinol Binding Protein being the only difference registered in the long-term. However, as compared to ol-HDF, both the re-infusive techniques allowed to reduce the intradialytic loss of Vitamin C and, in the long-term, improve the patients’ oxidative status and increase Retinol Binding Protein plasma values. No significant differences were found between the Vitamin C concentration of pre- and post cartridge UF neither in HFR-S nor in HFR showing that the sorbent resin does not adsorb Vitamin C. HFR-S and HFR are almost equivalent in term of impact on antioxidant vitamins and oxidative status of hemodialysis patients. Nonetheless, as compared to ol-HDF, both treatments produced a sensible sparing of Vitamin C and may represent a new approach for reducing oxidative stress and related complications in dialysis patients. Long-term effects of re-infusive treatments on patients’ cardiovascular morbidity and mortality need to be evaluated. ClinicalTrials.gov Identifier NCT01492491 , retrospectively registered in 10 December 2011.