Fabio Cibella’s research while affiliated with Institute of Biomedical Technologies, Italian National Research Council and other places

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may impact postnatal growth trajectories, increasing the risk of various diseases later in life. This issue is of particular concern in industrially contaminated areas, where environmental matrices contain mixtures of pollutants. This study aimed to evaluate the associations between cord serum concentrations of organochlorine pollutants (hexachlorobenzene-HCB and polychlorinated biphenyls-PCBs) and essential elements (EEs), and weight growth trajectories during the first year of life. We analyzed data from 237 infants enrolled in the Neonatal Environment and Health Outcomes (NEHO) cohort. Using the Group-Based Multivariate Trajectory modeling approach, we identified three distinct growth trajectories from birth to 12 months, classified as “Higher,” “Normal,” and “Lower.” Multinomial regression models were then applied to the whole sample and stratified by sex to assess the associations between individual exposures and the identified child growth trajectories. HCB exposure was associated with an increased risk of reduced growth during the first year of life in both the overall sample and among males [higher vs normal: ORMale=0.33 (95%CI Male:0.12;0.87); lower vs normal: ORMale=2.17 (95% CI Male:0.94;5.00)]. Conversely, PCB-180 exposure was linked to higher growth only in females [higher vs normal: ORFemale= 24.10 (95% CI Female:1.33;438.24)]. Elevated levels of selenium in cord serum were negatively associated with excessive growth [higher vs normal:OROverall=0.50 (95% CI Overall: 0.26;0.97)]. These findings suggest sex-specific effects on the growth profile during the first year of life, with different chemical exposures contributing to different outcomes.

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body’s defense systems going beyond the well-established associations with defense systems and delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health.

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body's defence systems going beyond the well-established associations with defence system delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health.

Extracellular vesicles (EVs), comprising exosomes and microvesicles, are small membranous structures secreted by nearly all cell types. They have emerged as crucial mediators in intercellular communication, playing pivotal roles in diverse physiological and pathological processes, notably within the realm of immunity. These roles go beyond mere cellular interactions, as extracellular vesicles stand as versatile and dynamic components of immune regulation, impacting both innate and adaptive immunity. Their multifaceted involvement includes immune cell activation, antigen presentation, and immunomodulation, emphasising their significance in maintaining immune homeostasis and contributing to the pathogenesis of immune-related disorders. Extracellular vesicles participate in immunomodulation by delivering a wide array of bioactive molecules, including proteins, lipids, and nucleic acids, thereby influencing gene expression in target cells. This manuscript presents a comprehensive review that encompasses in vitro and in vivo studies aimed at elucidating the mechanisms through which EVs modulate human immunity. Understanding the intricate interplay between extracellular vesicles and immunity is imperative for unveiling novel therapeutic targets and diagnostic tools applicable to various immunological disorders, including autoimmune diseases, infectious diseases, and cancer. Furthermore, recognising the potential of EVs as versatile drug delivery vehicles holds significant promise for the future of immunotherapies.

Protecting the health of pregnant women from environmental stressors is crucial for reducing theburden of non-communicable diseases. In industrially contaminated sites, this action is particularlychallenging due to the heterogeneous pollutant mixtures in environmental matrices. The aim of thisstudy was to evaluate distribution patterns of mercury, hexachlorobenzene and polychlorobiphenylsin the serum of 161 pregnant women recruited in the framework of the Neonatal Environmentand Health Outcomes (NEHO) cohort and living both inside and outside the National PriorityContaminated Site (NPCS) of Priolo. Food macro-categories were determined, and serum levels ofcontaminants were used to perform k-means cluster analysis and identify the role of food in pollutanttransfer from the environment. Two groups of mothers with high and low measured pollutant levelswere distinguished. Concentrations in mothers in the high-exposure cluster were at least twofold forall the evaluated pollutants (p < 0.0001) and included mothers living inside and outside NPCS, witha predominance of individuals from the NPCS (p = 0.045). Fish consumption was higher in the high-exposure cluster (p = 0.019). These findings suggest a link between contamination of environmentalmatrices such as sediment with maternal exposure, through the intake of local food. Suchconsideration appears poorly investigated in the context of contaminated sites.

Aims: The lung epithelial cells form a physical barrier to the external environment acting as the first line of defence against potentially harmful environmental stimuli. These cells interact with several other cellular components, of which macrophages are some of the most relevant. We analysed the effects of the PBDE-47 on the microRNA cargo of THP-1 macrophage like derived small Extracellular Vesicles (sEVs) and the effects on A549 lung epithelial cells. Main methods: sEVs from M(LPS) THP-1 macrophage-like cells after PBDE-47 treatment (sEVsPBDE+LPS) were characterized by nanoparticle tracking analysis and their microRNA cargo studied by qPCR. Confocal microscopy was applied to study sEVs cellular uptake by A549 cells. The expression of tight junctions (TJs), adhesion molecules, inflammation markers and mucus production in A549 cultured in air liquid interface (ALI) conditions were studied by Real Time PCR and confocal microscopy. Key findings: sEVsPBDE+LPS microRNA cargo analysis showed that the PBDE-47 modulated the expression of the miR-15a-5p, miR29a-3p, miR-143-3p and miR-122-5p. Furthermore, ALI cultured A549 cells incubated with sEVsPBDE+LPS showed that zonula occludens-1 (p ≤ 0.04), claudin (p ≤ 0.02), E-cadherin (p ≤ 0.006) and Vimentin (p ≤ 0.0008) mRNAs were increased in A549 cells after sEVsPBDE+LPS treatment. Indeed, Interleukin (IL)-8 (p ≤ 0.008) and mucin (MUC5AC and MUC5B) (p ≤ 0.03 and p ≤ 0.0001) mRNA expression were up- and down-regulated, respectively. Significance: PBDE-47 treated macrophages secrete sEVs with altered microRNA cargo that affect the mRNA expression of TJs, adhesion molecules, cytokines and EMT markers damaging the normal function of the lung epithelium, potentially contributing to the development of lung diseases.

2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) is one of the most widespread environmental brominated flame-retardant congeners which has also been detected in animal and human tissues. Several studies have reported the effects of PBDEs on different health issues, including neurobehavioral and developmental disorders, reproductive health, and alterations of thyroid function. Much less is known about its immunotoxicity. The aim of our study was to investigate the effects that treatment of THP-1 macrophage-like cells with PBDE-47 could have on the content of small extracellular vesicles’ (sEVs) microRNA (miRNA) cargo and their downstream effects on bystander macrophages. To achieve this, we purified sEVs from PBDE-47 treated M(LPS) THP-1 macrophage-like cells (sEVsPBDE+LPS) by means of ultra-centrifugation and characterized their miRNA cargo by microarray analysis detecting the modulation of 18 miRNAs. Furthermore, resting THP-1 derived M(0) macrophage-like cells were cultured with sEVsPBDE+LPS, showing that the treatment reshaped the miRNA profiles of 12 intracellular miRNAs. This dataset was studied in silico, identifying the biological pathways affected by these target genes. This analysis identified 12 pathways all involved in the maturation and polarization of macrophages. Therefore, to evaluate whether sEVsPBDE+LPS can have some immunomodulatory activity, naïve M(0) THP-1 macrophage-like cells cultured with purified sEVsPBDE+LPS were studied for IL-6, TNF-α and TGF-β mRNAs expression and immune stained with the HLA-DR, CD80, CCR7, CD38 and CD209 antigens and analyzed by flow cytometry. This analysis showed that the PBDE-47 treatment does not induce the expression of specific M1 and M2 cytokine markers of differentiation and may have impaired the ability to make immunological synapses and present antigens, down-regulating the expression of HLA-DR and CD209 antigens. Overall, our study supports the model that perturbation of miRNA cargo by PBDE-47 treatment contributes to the rewiring of cellular regulatory pathways capable of inducing perturbation of differentiation markers on naïve resting M(0) THP-1 macrophage-like cells.

Citation: Cuttitta, G.; Ferraro, M.; Cibella, F.; Alfano, P.; Bucchieri, S.; Patti, A.M.; Muratori, R.; Pace, E.; Bruno, A. Relationship among Body Composition, Adipocytokines, and Irisin on Exercise Capacity and Quality of Life in COPD: A Pilot Study. Biomolecules 2023, 13, 48. Abstract: Adipose tissue is an endocrine organ that interferes with the severity of chronic obstructive pulmonary disease (COPD). Although inflammatory markers, body composition, and nutritional status have a significant impact on pulmonary function, the real contribution of adipocytokines and myokines in COPD is still controversial. We aimed to evaluate the role played by the body composition , leptin, adiponectin, haptoglobin, and irisin on the functional exercise capacity, respiratory function, and quality of life (QoL) in COPD. In 25 COPD (20% GOLD-1; 60% GOLD-2; 20% GOLD-3) patients and 26 matched control subjects, we find that leptin, total adiponectin and haptoglobin are significantly increased whereas the 6 min walk test (6MWT) and physical functioning scores are significantly decreased in COPD versus controls. A significant positive relationship is found between leptin and fat mass and between 6MWT and the good health indicators of nutritional status. A significant inverse relationship is found between 6MWT and leptin and fat mass, FEV 1 and haptoglobin, and irisin and haptoglobin. Phase angle and leptin level are significant predictors for functional exercise capacity assessed with 6MWT. Taken altogether, the results of this pilot study further support the role played by body composition and adipocytokines on exercise capacity respiratory function and QoL in COPD.