In vitro exposure to PM2.5 of olfactory Ensheathing cells and SH-SY5Y cells and possible association with neurodegenerative processes.

PM2.5 exposure represents a risk factor for the public health. PM2.5 is able to cross the blood-alveolar and blood-brain barriers and reach the brain through three routes: nasal olfactory pathway, nose-brain pathway, blood-brain barrier pathway. We evaluated the effect of PM2.5 to induce cytotoxicity and reduced viability on in vitro cultures of OECs (Olfactory Ensheathing Cells) and SH-SY5Y cells. PM2.5 samples were collected in the metropolitan area of Catania, and the gravimetric determination of PM2.5, characterization of 10 trace elements and 16 polycyclic aromatic hydrocarbons (PAHs) were carried out for each sample. PM2.5 extracts were exposed to cultures of OECs and SH-SY5Y cells for 24-48-72 h, and the cell viability assay (MTT) was evaluated. Assessment of mitochondrial and cytoskeleton damage, and the assessment of apoptotic process were performed in the samples that showed lower cell viability. We have found an annual average value of PM2.5 = 16.9 µg/m3 and a maximum value of PM2.5 = 27.6 µg/m3 during the winter season. PM2.5 samples collected during the winter season also showed higher concentrations of PAHs and trace elements. The MTT assay showed a reduction in cell viability for both OECs (44%, 62%, 64%) and SH-SY5Y cells (16%, 17%, 28%) after 24-48-72 h of PM2.5 exposure. Furthermore, samples with lower cell viability showed a decrease in mitochondrial membrane potential, increased cytotoxicity, and also impaired cellular integrity and induction of the apoptotic process after increased expression of vimentin and caspase-3 activity, respectively. These events are involved in neurodegenerative processes and could be triggered not only by the concentration and time of exposure to PM2.5, but also by the presence of trace elements and PAHs on the PM2.5 substrate. The identification of more sensitive cell lines could be the key to understanding how exposure to PM2.5 can contribute to the onset of neurodegenerative processes.

Internalization of Pegylated Er:Y2O3 Nanoparticles inside HCT-116 Cancer Cells: Implications for Imaging and Drug Delivery.

Lanthanide-doped nanoparticles, featuring sharp emission peaks with narrow bandwidth, exhibit high downconversion luminescence intensity, making them highly valuable in the fields of bioimaging and drug delivery. High-crystallinity Y2O3 nanoparticles (NPs) doped with Er3+ ions were functionalized by using a pegylation procedure to confer water solubility and biocompatibility. The NPs were thoroughly characterized using transmission electron microscopy (TEM), inductively coupled plasma mass spectrometry (ICP-MS), and photoluminescence measurements. The pegylated nanoparticles were studied both from a toxicological perspective and to demonstrate their internalization within HCT-116 cancer cells. Cell viability tests allowed for the identification of the "optimal" concentration, which yields a detectable fluorescence signal without being toxic to the cells. The internalization process was investigated using a combined approach involving confocal microscopy and ICP-MS. The obtained data clearly indicate the efficient internalization of NPs into the cells with emission intensity showing a strong correlation with the concentrations of nanoparticles delivered to the cells. Overall, this research contributes significantly to the fields of nanotechnology and biomedical research, with noteworthy implications for imaging and drug delivery applications.

DNA Damage and Apoptosis as In-Vitro Effect Biomarkers of Titanium Dioxide Nanoparticles (TiO2-NPs) and the Food Additive E171 Toxicity in Colon Cancer Cells: HCT-116 and Caco-2.

This study investigated the DNA damage and apoptosis in colon cancer cells HCT-116 and Caco-2 induced by engineered titanium dioxide nanoparticles (TiO2-NPs) (60 nm) and titanium dioxide food additive E171. MTT assays showed that both chemical forms significantly reduced cancer cell viability in a dose-dependent manner. In particular the food additive E171 induced a pronounced inhibitory effect on the growth of HCT-116 and Caco-2 cell lines (E171 IC50: 3.45 mg/L for HTC-116 and 1.88 mg/L Caco-2; TiO2-NPs 60 nm IC50: 41.1 mg/L for HTC-116 and 14.3 mg/L for Caco-2). A low level of genotoxicity was observed in Caco-2 cells, especially when treated with TiO2 60 nm. Western blot analysis showed that HCT116 and Caco-2 treated cells did not overexpress apoptotic markers such as cleaved Caspase 3 and cleaved Parp. Moreover, further analysis by quantitative real-time PCR (qRT-PCR) showed that TiO2-NPs and E171 did not promote the expression of Bax or downregulation of Bcl-2, nor did they increase the Bax/Bcl-2 ratio. The assay data provide clear evidence that TiO2 can cause DNA damage but does not induce apoptosis or decrease long-term cell proliferation. In addition, the results show that E171 has a slightly higher level of cytotoxicity and genotoxicity. This suggests that exposure to E171 may be hazardous to health and that further research on biological effects is needed to promote safer practices in the use of this compound.

In vitro cytoxicity profile of e-cigarette liquid samples on primary human bronchial epithelial cells.

Cigarette smoke is associated to severe chronic diseases. The most harmful components of cigarette smoke derive from the combustion process, which are significantly reduced in the electronic cigarette aerosol, thus providing a valid option in harm reduction strategies. To develop safer products, it is therefore necessary to screen electronic cigarette liquids (e-liquids) to meet high safety standards defined by government regulations. The aim of the present study was to evaluate the presence of metal- and plastic-derived contaminants in four different commercial e-liquids with high concentration of nicotine and their cytotoxic effect in normal human bronchial epithelial cells by a number of in vitro assays, in comparison with the 1R6F reference cigarette, using an air-liquid interface (ALI) exposure system. Moreover, we evaluated the effect of aerosol exposure on oxidative stress by measuring the production of reactive oxygen species and mitochondrial potential. Our results showed no contaminants in all e-liquids and a significantly reduced cytotoxic effect of e-liquid aerosol compared to cigarette smoke as well as a maintained mitochondria integrity. Moreover, no production of reactive oxygen species was detected with e-cigarette aerosol. In conclusion, these results support the reduced toxicity potential of e-cigs compared to tobacco cigarettes in an in vitro model resembling real life smoke exposure.

Benefits of Physical Activity during and after Thyroid Cancer Treatment on Fatigue and Quality of Life: A Systematic Review.

BACKGROUND: Several epidemiological studies have provided evidence of the usefulness of physical activity for cancer prevention, increased survival and quality of life (QoL), but no comprehensive review is available on the effects on thyroid cancer. The present systematic review provides an overview of the effects of physical activity on fatigue, QoL and health-related quality of life (HRQoL) in patients with thyroid cancer diagnosis both during and after treatment, with a focus on sex. METHODS: A literature search was conducted in the PubMed and Scopus databases. We included studies investigating the impact of physical activity during and after thyroid cancer treatment, including fatigue, QoL and/or HRQoL among the outcomes. Review articles, conference papers, short communications and articles written in a language other than English articles were excluded. Study selection followed the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA). Two reviewers independently selected the studies and assessed their eligibility. The same two reviewers independently screened studies, extracted data and assessed the risk of bias. Outcomes of interest were fatigue, QoL and HRQoL. The Newcastle-Ottawa Scale was used to assess the quality of the selected studies. We compared the outcomes between groups of patients with subclinical hyperthyroidism undergoing a physical activity program and a sedentary group, evaluating the possible presence of sex differences. RESULTS AND DISCUSSION: We found five studies eligible for inclusion in our review; only two were prospective studies including an exercise training program. One study was a quasi-experimental study with a non-equivalent control group. Three out of five studies comprised low-quality evidence with a high risk of bias. CONCLUSION: The level of confidence in the available evidence is very low. A close association between physical activity and fatigue, QoL and HRQoL in patients with thyroid cancer diagnosis with a focus on sex can neither be supported nor refuted. Future studies are needed to understand which training programs are optimal, both in terms of beneficial effects and to avoid potential adverse responses, in addition to focusing on gender differences. The protocol of this systematic review was registered with PROSPERO: CRD42022322519.

Dietary habits and thyroid cancer risk: A hospital-based case-control study in Sicily (South Italy).

Several studies have investigated the role of diet as a risk and/or protective factor against thyroid cancer, both considering individual foods, groups of foods and dietary patterns, but the results are not consistent. The aim of the study was to investigate the relationship between dietary habits and thyroid cancer. Cases and controls were recruited at the University Hospital "G. Rodolico" of Catania. The dietary habits were defined through the "Lifestyle Assessment Questionnaire". The frequency of consumption of each food item was reported on a 4-level scale (never, one time a week, 2-3 times a week, every day of the week). We computed the odds ratios (ORs) of thyroid cancer and the corresponding 95% confidence intervals (CIs) according to the median of control group daily intake of each food group, using multiple logistic regression models adjusted for major confounding factors. Starchy foods (OR = 1.39, 95% CI 0.83-2.32), sweets (OR = 1.39, 95% CI 0.81-2.40) and products rich in salt and fat showed a positive association with thyroid cancer risk. Conversely, an inverse association with disease risk was found for vegetables (cruciferous OR = 0.30, 95% CI 0.10-0.92, non cruciferous OR = 0.57 (0.20-1.57) milk and dairy products (OR = 0.68, 95% CI 0.40-1.13) and seafood (OR = 0.68, 95% CI 0.34-1.22). An increased risk was observed for consumption of iodized salts (OR 2.06, 95% CI 1.21-3.51), tea (OR = 1.42, 95% CI 0.84-2.41) and coca-cola (OR = 3.08, 95% CI 1.53-6.20). Finally, our results confirm the protective effect of a daily water intake of 1-2 L, but unfortunately this quantity is usually consumed by about a quarter of the sample. Dietary habits appear to modify the risk of thyroid carcinoma. A diet with a limited consumption of starchy foods, products rich in salt, fat and sugar and a higher consumption of, cruciferous/non-cruciferous vegetables, milk and dairy products and seafood could be protective towards thyroid cancer. Moreover, the water intake should be increased and the actual need to consume iodized salt should be verified for each subject/area. These results warrant further investigations and, if confirmed, they might have important public health implications for the reduction of thyroid cancer through the improvement of dietary habits.

Fish-Based Baby Food Concern-From Species Authentication to Exposure Risk Assessment.

In this work, two different but complementary approaches were used to evaluate the reliability of fish-based baby foods as a source of safe nourishment for babies. More specifically, barcoding analysis based on the Cytochrome Oxidase I sequences was used for fish species authentication and an analysis of metal/metalloid levels was performed to estimate the exposure risk assessment derived from consumption of selected fish-based baby food in infants and toddlers. COI DNA barcoding revealed that in three samples the species detected did not match the common name of the species shown on the label. In particular, G. chalcogrammus and M. australis were found in place of M. merluccius and O. mykiss was found in place of S. salar. The analysis of exposure risk assessment indicated a low risk for developing chronic systemic and carcinogenic effects in infants and toddler, under an exposure scenario based on daily consumption of a single box of fish-based baby food. However, it is important to highlight that in order to provide a comprehensive risk assessment it would be important to supplement the levels of exposure resulting from the total diet. Overall, our results suggest that more attention should be paid by authorities to ensure the safety of food for infants and toddlers.

Physical Activity and Thyroid Cancer Risk: A Case-Control Study in Catania (South Italy).

BACKGROUND: The health benefits of physical activity are well established, but the association between physical activity and thyroid cancer remains poorly understood. The aim of the study was to investigate the relationship between physical activity and thyroid cancer in order to determine type, frequency, and duration of exercise needed to maximize prevention. METHOD: Cases, diagnosed from January 2009 to July 2018, and controls were enrolled at the University Hospital "Policlinico-Vittorio Emanuele" of Catania (South Italy). Logistic regression models were used to estimate the crude and adjusted odds ratios (ORs) and their 95% confidence intervals. RESULTS: A total of 106 cases (91.2% papillary type) and 217 controls were enrolled. Physical activity was rare in Catania (32.8%) and was not correlated to risk of total thyroid cancer (OR: 0.997; 95% CI: 0.515-1.929). Conversely, walking every day for at least 60 minutes reduced the risk of thyroid cancer (OR: 0.357; 95% CI: 0.157-0.673). CONCLUSIONS: Our study showed that daily walking duration was associated with lower risk of thyroid cancer using a case-control study. Unfortunately, the frequency of physical activity often declines with age, particularly among the elderly, thus more research on physical activity adherence is needed to determine which approaches are most effective in promoting sustained physical activity participation.

α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload.

Iron toxicity is associated with organ injury and has been reported in various clinical conditions, such as hemochromatosis, thalassemia major, and myelodysplastic syndromes. Therefore, iron chelation therapy represents a pivotal therapy for these patients during their lifetime. The aim of the present study was to assess the iron chelating properties of α-lipoic acid (ALA) and how such an effect impacts on iron overload mediated toxicity. Human mesenchymal stem cells (HS-5) and animals (zebrafish, n = 10 for each group) were treated for 24 h with ferric ammonium citrate (FAC, 120 µg/mL) in the presence or absence of ALA (20 µg/mL). Oxidative stress was evaluated by reduced glutathione content, reactive oxygen species formation, mitochondrial dysfunction, and gene expression of heme oxygenase-1b and mitochondrial superoxide dismutase; organ injury, iron accumulation, and autophagy were measured by microscopical, cytofluorimetric analyses, and inductively coupled plasma‒optical mission Spectrometer (ICP-OES). Our results showed that FAC results in a significant increase of tissue iron accumulation, oxidative stress, and autophagy and such detrimental effects were reversed by ALA treatment. In conclusion, ALA possesses excellent iron chelating properties that may be exploited in a clinical setting for organ preservation, as well as exhibiting a good safety profile and low cost for the national health system.

Systematic review of arsenic in fresh seafood from the Mediterranean Sea and European Atlantic coasts: A health risk assessment.

Arsenic in the environment pose major threats to human health, and especially the inorganic form can result in adverse health effects. This review analyse papers from 2004 to 2017 on As in fresh fish and molluscs caught in the Mediterranean sea and the European coast of the Atlantic ocean allowing the identification of the marine area with a greater As bioavailability and in particular the identification of the European populations more exposed to In-As by consuming fresh seafood. Results were separated on the base of the fishing site and the concentrations were reworked to assess the average daily intake to In-As as well as Target Hazard Quotient and Cancer Risk. Overall, the greater availability in Tot-As concentration in the pelagic compartment found in the Mediterranean Sea is not present along the European coasts of Atlantic Ocean. Furthermore, only in the Mediterranean Sea, results highlighted significant differences between Tot-As concentrations in seafood subgroups. In both areas, In-As concentrations showed the following trend: molluscs > pelagic > demersal with significant differences between subgroups. The European populations more exposed to In-As from fish and molluscs are the French, Spanish, Italian and Greek, with particular regards to children of 3-6 years old, which should minimize the consumption of molluscs to avoid carcinogenic and non-carcinogenic risks.

In vivo exposure of the marine sponge Chondrilla nucula Schmidt, 1862 to cadmium (Cd), copper (Cu) and lead (Pb) and its potential use for bioremediation purposes.

The study aimed to test the cadmium (Cd), copper (Cu) and lead (Pb) bioaccumulation capacity of the marine sponge Chondrilla nucula and to measure the expression of metallothioneins (MTs) by a western blotting assay to explore metal tolerance and its potential use as a bioremediator in contaminated coastal areas. C. nucula was sampled in a protected marine area in order to perform experiments on organisms living in a healthy environment. Under laboratory conditions, the sponges were exposed to increasing concentrations of Cd, Cu and Pb in tanks filled with artificial seawater set up for the experiments. For each metal, three waterborne concentrations (mgL-1) of Cd (0.02-0.04-0.08), Cu (0.1-0.2-0.4) and Pb (0.2-0.4-0.8) were considered separately. SPSS 20.0 was used for statistical analysis. Significant differences in bioaccumulation across levels of each metal were highlighted. Moreover, the amount accumulated in sponges increased proportionately with increasing levels of exposure for each metal as well as MT expression after Cd and Pb exposure. The results demonstrate the efficiency of C. nucula in accumulating high levels of Cu, but a low tolerance to progressively higher concentrations for Cd and Pb. The study suggests the suitability of the use of this species in bioremediation plans for moderately contaminated environments. However, the biological response in the field should be verified by the use of transplanted organisms from a control site to a polluted site.

Implication of dietary phthalates in breast cancer. A systematic review.

Phthalates are endocrine-disrupting for their ability to change the normal function of human endocrine system. Their action on the reproductive system, both on male and female, is the most one investigated by international scientific community. The aim of this systematic review was to gather the available information regarding the role of phthalates on breast carcinogenesis focusing our research in their intake through the diet. Research was performed according the PRISMA methodology and 25 scientific articles published between 2000 and 2018 were selected. The main source of exposure to phthalates is diet, mainly through the consumption of food and beverages wrapped in different plastic packaging. Several in vitro studies suggest that certain phthalates may be associated to breast cancer since they can bind and activate the estrogen receptors. However, results of epidemiological studies are debated, yet. It's necessary to plan the future studies more carefully to have more representative data on phthalate exposure by replacing urinary matrix with piliferous one, by including as confounding factors not only the other risk factors but also prevention one as diet and miRNA expression and, finally, by direct the study considering not only the estrogenic activity of phthalates and so including also the ER negative tumors.

PAHs in seafood from the Mediterranean Sea: An exposure risk assessment.

Seafood represent an important food source for human, and seafood quality is associated with marine environment quality. PAHs are one of the main organic environmental contaminants and they can be introduced into the body through different way (ingestion, inhalation, dermal absorption). We present data on bioaccumulation of the sixteen PAHs, defined priority by the U.S.- EPA, in Sardina pilchardus, Solea solea and Donax trunculus, three species caught in the Catania Gulf and highly consumed by the local population. The risk to develop chronic systemic and carcinogenic effects due to the consumption of these target species was evaluated through the EDI, THQ and CR. EDI derived from D. trunculus ingestion falls within the range calculated by the EFSA. The THQ is less than 1, and the CR calculated for the Benzo(a)Pyrene is at the limit of the ARL (1✕10-5). EDI derived from S. pilchardus and S. solea ingestion are below the range calculated by the EFSA. The THQ is less than 1, and the CR is below the acceptable risk level. The contamination level found in local seafood determines a low risk to develop chronic systemic effects, but the cancer risk could be of health concern especially for high-frequency molluscs consumers.

Lead exposure and plasma mRNA expression in ERBB2 gene.

Epidemiologic data for carcinogenicity in those exposed to lead (Pb) suggests relations with cancers although the totality of the evidence is inconsistent. Alterations in the expression of ERBB receptors have been studied during the development and malignant transformation of different kinds of human tumors where they induce proliferation, angiogenesis and metastasis generation. Relevant clinical data demonstrate the role of ERBB2 receptors in the development and malignancy of human cancers. Therefore, the objective of the present investigation is to give more information on the link between plasma mRNA expression in ERBB2 gene and lead blood levels in a healthy population. Blood samples, socio­demographic, exposure and health data were obtained from 48 healthy men. Real­time polymerase chain reaction assays were performed to detect ERBB2 gene transcripts, ΔΔCt method was used to quantify gene expression. Pb blood level was assayed using high­resolution sector field inductively coupled mass spectrometry and is expressed in µg/dl. Plasma mRNA expression in ERBB2 gene was 6.44±3.07 ΔΔCt; Pb blood levels was 16.07±6.74 µg/dl. Regression analysis revealed a significant association (r2=0.5345; p<0.0001) between Pb levels and mRNA expression in ERBB2. So far, it has still not been established if the expression of ERBB2 receptors is influenced by Pb exposure. On the base of the above reported data, we believe an in vitro study might be useful, to understand the molecular mechanisms implicated.

Polycyclic aromatic hydrocarbons in Haliotis tuberculata (Linnaeus, 1758) (Mollusca, Gastropoda): Considerations on food safety and source investigation.

Polycyclic aromatic hydrocarbons were analyzed in wild specimens of Haliotis tuberculata from three sites of the Sothern Ionian Sea. The species Ht is commonly found at these sites and has significant commercial value. Main results revealed mean values of benzo(a)pyrene higher than the threshold set by Regulation No. 835/2011/EU in all sampling sites and the sum of selected PAHs, expressed as ΣPAH4 by EC Regulation, were below the limit set by the same Regulation in ME and VSG. We found generally higher concentrations than literature finding, especially for low molecular weight PAHs, and results of diagnostic ratios highlighted both pyrolytic and petrogenic sources. The potential human health risks due consumption of Ht by local inhabitants have been assessed by exposure daily intake (EDI), target hazard quotient (THQ) and lifetime cancer risk (CR). EDI values were below the intake range reviewed by EFSA for each class of contaminant. BaP daily intake was below the value of 10 ng/Kg/day, suggested by JFCFA, and CRBaP was slightly higher than the acceptable risk level (ARL) of 1×10(-5). Conversely, target hazard quotient (THQ) resulted always below 1, thus the risk to develop chronic systemic effects due naphthalene, acenaphthene, fluorene, anthracene, fluoranthene and pyrene was low.

Heavy metals concentrations in fish and shellfish from eastern Mediterranean Sea: consumption advisories.

The present study evaluate concentrations of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), nickel (Ni), vanadium (V) and zinc (Zn) in fish and shellfish from the Gulf of Catania. Heavy metal analysis was carried on with an ICP-MS, and consumption rates advisory for minimizing chronic systemic and non cancer endpoints in child and adults have been estimated. Among metals investigated, only Cd and Pb have a limit set by European Community for human consumption, and the thresholds were not been exceeded in analyzed species. The As, toxic in its inorganic form, have not a regulatory limit yet, but the Environmental Protection Agency and the World Health Organization provide a reference dose, a cancer slope factor and a tolerable intake, applicable in the risk factors assessment. Arsenic target hazard quotient (THQ) values, suggest that human should minimizing meals/week of analyzed species to avoid deleterious effect during lifetime, furthermore, with As cancer risk assessment, for most of the fish, the risk for cancer is greater than the acceptable lifetime risk of 10(-5). Our results give important finding about the consumption limits on certain metals, especially for As, all for minimizing potential health risks in population.

Heavy metals concentrations in fish from Sicily (Mediterranean Sea) and evaluation of possible health risks to consumers.

Cadmium, lead, mercury and chromium concentrations in fish muscle tissue taken from various Sicilian areas were detected. Fish caught in Siracusa, nearby a petrochemical industrial area, were more contaminated by cadmium, lead and chromium (respectively 0.366, 0.32, 0.72 µg/g) than those from the other sites. In the Sicily Channel, we found the highest bioaccumulation of mercury (0.31 µg/g). Although some metals concentrations exceed the limits set by the European regulation, the estimated weekly intake was below the Provisional Tolerable Weekly Intake established by the European Food and Safety Authority, and the Target Hazard Quotient values indicate that there is no carcinogenic risk for humans.