Biology subjects

Di Bucchianico, S.

Publications and source records attributed to Di Bucchianico, S..

5 recordsLinked to original sources

bioRxiv2026

Multi-Modal Toxicological Evaluation of NiO nanoparticles and ionic nickel in a Human Lung-Cardiac Co-Culture System

Nickel is a widespread environmental and occupational contaminant associated with respiratory and cardiovascular toxicity, yet the mechanisms linking pulmonary exposure to adverse cardiac effects remain poorly understood. This study aimed to establish and evaluate a human in vitro lung-heart co-culture model for investigating cardiovascular responses following pulmonary exposure. Human alveolar epithelial A549 cells were exposed at the air-liquid interface to different concentrations of NiO nanoparticles or NiCl2 for 4- and 24-hours. Following cloud exposure, A549 cells were co-cultured with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Cytotoxicity, metabolic activity, cytokine release, DNA damage, epigenetic alterations, and cardiac electrophysiological function were assessed. Nickel translocation across the epithelial barrier was quantified to facilitate interpretation of downstream cardiomyocyte effects. Exposure to both nickel forms induced cytotoxicity and resulted in measurable nickel translocation into the basolateral compartment. NiCl2 exhibited a time-dependent increase in basolateral nickel concentrations, whereas NiO translocation remained relatively stable over time. Cytokine profiling revealed selective induction of IL-8 and IL-18, with no significant changes in IL-1{beta}, IL-6, IL-10, or TNF-. Genotoxicity analyses demonstrated cell type-specific responses, characterized by delayed DNA strand breaks in A549 cells and early but transient DNA damage in hiPSC-CMs. Oxidative DNA damage was particularly pronounced in hiPSC-CMs following NiCl2 exposure. Global DNA methylation was reduced in hiPSC-CMs without corresponding changes in DNA methyltransferase activity. Electrophysiological assessment showed transient increases in conduction velocity, while beating frequency and field potential duration remained largely unaffected. Overall, the lung-heart co-culture model successfully captured both pulmonary and cardiac responses to nickel exposure and provided evidence for direct and indirect mechanisms of cardiotoxicity. Nickel translocation across the epithelial barrier, together with inflammatory and oxidative stress-related signalling, may contribute to downstream cardiac effects. These findings highlight the utility of this human-relevant platform for investigating systemic cardiovascular consequences of inhaled toxicants.

pharmacology and toxicology↗

bioRxiv2026

Railway Catenary Sparking as a Source of Toxic Copper Ultrafine Particles: Evidence from Realistic In Vitro Inhalation Exposure

Railway catenary sparking generates airborne ultrafine particles (UFPs) that may pose health risks due to their metallic composition and ability to penetrate deep into the alveolar region of the lungs. Copper, widely used in wires and pantographs, is a major component of these emissions, making copper-rich particles common in railway environments such as subways. However, exposure levels and health impacts remain poorly characterized, and localized hotspots may represent an underrecognized risk in densely populated areas. This study investigated the toxicity of copper UFPs under realistic dosimetry and deposition conditions. Copper UFPs were generated using a spark discharge generator and applied to two in vitro lung models: a 3D co-culture of Calu-3 epithelial cells, THP-1-derived macrophages, and EA.hy926 endothelial cells, and a monoculture of A549 alveolar epithelial cells. Cells were exposed at the air-liquid interface (ALI) using an automated platform to mimic inhalation exposure and UFPs deposition. Copper deposition ranged from 6.5 to 41 ng/cm2, within occupationally relevant levels. A549 cells showed cytotoxic responses consistent with previous studies, whereas the 3D co-culture model revealed broader adverse effects, including inflammation, impaired epithelial barrier integrity, oxidative stress, and early DNA damage. Inflammatory activation also differed between models: A549 cells mainly exhibited transcriptional responses, while the 3D model showed significant secretion of IL-6 and IL-8, associated with interferon signaling. These findings highlight the potential health risks of copper UFPs from railway systems and emphasize the need for improved characterization of UFP exposure in environmental and occupational railway settings.

pharmacology and toxicology↗

bioRxiv2026

Extracellular Vesicle-Enriched Secretome from Mesenchymal Stromal Cells Protects Against Chemically, Particulate-, and Ischemia-Induced Innate-Immunity Induced Inflammation

Mesenchymal stromal cells (MSCs) are multipotent cells with well-established regenerative and immunomodulatory properties, making them promising candidates for the treatment of inflammatory diseases. However, the therapeutic effects of MSCs are largely mediated by their secretome, particularly extracellular vesicles (EVs), which deliver bioactive molecules capable of modulating inflammatory responses. We generated an extracellular vesicle-enriched secretome (EVES) from MSCs under scalable, Good Manufacturing Practice (GMP)-compliant conditions and assessed its therapeutic efficacy in diverse disease models, including lung inflammation and kidney injury induced by distinct innate immune stimuli. EVES was isolated from the secretome of umbilical cord blood-derived MSCs cultured in a chemically defined medium. In vitro, EVES significantly and dose-dependently attenuated cytokine release from airway epithelial cells and macrophages stimulated with inflammatory agents such as lipopolysaccharide or reactive particles. In murine models of lung inflammation, EVES reduced neutrophil infiltration and suppressed multiple cytokines and chemokines in a dose-dependent manner. In models of kidney injury, EVES enhanced tubular epithelial cell proliferation, improved renal histology, and markedly reduced tubular necrosis following ischemia-reperfusion injury. Collectively, these findings demonstrate that MSC-derived EVES exhibits robust and broad-spectrum therapeutic activity across multiple disease contexts driven by innate immune activation, supporting its potential as a scalable, cell-free therapeutic platform.

cell biology↗

bioRxiv2026

Anti-oxidant and anti-inflammatory Effects of Aerosolised microalgal-derived extracellular vesicles in Bronchial Epithelial-Macrophage Co-cultures at the Air-Liquid Interface

AbstractInflammation and oxidative stress are key drivers in the pathogenesis of chronic lung diseases, including asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease. Extracellular vesicles derived from the marine microalga Tetraselmis chuii, referred to as nanoalgosomes, have recently gained attention as natural nanocarriers that possess inherent antioxidant and anti-inflammatory properties. In this study, we investigated the biocompatibility and protective effects of aerosolized nanoalgosomes in a bronchial epithelial-macrophage co-culture model at the air-liquid interface. Co-cultures of CALU-3 epithelial cells and differentiated THP-1 macrophages were primed with aerosolised nanoalgosomes and subsequently exposed to either oxidative stress (tert-butyl hydroperoxide) or an inflammatory stimulus (lipopolysaccharide; LPS). Epithelial barrier integrity and cytotoxicity were evaluated using transepithelial electrical resistance and lactate dehydrogenase release assays, respectively, while intracellular reactive oxygen species levels and cytokine secretion were measured to assess antioxidant and immunomodulatory responses. Nanoalgosomes were non-cytotoxic, preserved epithelial barrier integrity, and significantly reduced oxidative stress. In addition, nanoalgosomes priming attenuated LPS-induced secretion of pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-8, IL-18, TNF-) as well as the anti-inflammatory cytokine IL-10, suggesting a balanced immunomodulatory response. Overall, aerosolized nanoalgosomes maintained epithelial homeostasis and mitigated both oxidative and inflammatory stress, underscoring their potential as a safe, sustainable, and effective therapeutic strategy for chronic inflammatory lung diseases. Given their natural origin, excellent biocompatibility, and suitability for aerosol delivery, nanoalgosomes represent a promising class of inhalable biotherapeutics.

pharmacology and toxicology↗

bioRxiv2024

In vitro genotoxic and mutagenic potentials of combustion particles from marine fuels with different sulfur contents

Ship emissions cause serious environmental impacts and adverse effects toward human health. Therefore, the International Maritime Organization (IMO) restricted the fuel sulfur content (FSC) of marine fuels: FSC must be <0.5% m/m or <0.1% m/m in sulfur emission control areas, covering a range of fuels from distillate diesel-like fuels to low-sulfur heavy fuel oils (HFOs). As a result, ship emissions, e.g., sulfur oxides and particulate matter (PM) have been reduced. However, how FSC correlates with the toxicological potential of ship emissions is still uncertain. The objective of this study was to understand how the physical and chemical properties of particulate emissions from a marine engine operating on five marine fuels with different FSCs influence their toxicological outcome. For this scope, cytotoxic, genotoxic, mutagenic, and pro-inflammatory potentials of collected particles were evaluated in lung cell model systems. The involvement of intracellular reactive oxygen species and xenobiotic metabolism was also explored. While PM from different fuels combustion resulted in up to approximately 20% of reduction of cytotoxicity at the highest concentration, other toxicological outcomes, including clonogenic and genotoxic potentials, showed a stronger trend with the polycyclic aromatic hydrocarbon contents in PM compared with FSC. This trend was supported by evidence of a significant increase in gene mutation frequency and alterations in cellular mechanisms induced by an aromatic-rich HFO with an intermediate FSC. In conclusion, apart from reducing FSC in marine fuels, additional particle abatement systems should be considered to reduce the adverse effects of particulate emissions from shipping operations on human health.

pharmacology and toxicology↗