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Inflammation is a protective response of the body to various injuries, which is strictly regulated by a variety of factors, including immune cells and soluble mediators. However, dysfunction of this defensive mechanism often results in inflammation‑driven diseases, such as deep vein thrombosis (DVT). The complex relationship between inflammatory cell activity and DVT has not been fully elucidated. The present study aimed to investigate the role of interleukin‑6 (IL6) signaling transduction in DVT. To this aim, the expression levels of transmembrane isoforms of the IL6 receptor (IL6R) and the glycoprotein 130 responsible for the IL6 cis‑signaling were evaluated in the peripheral blood mononuclear cells of patients with DVT and of healthy controls. The results indicated that leukocytes from patients with DVT exhibited overexpression of both IL6R and gp130 membrane isoforms and that these were strongly associated with the occurrence of DVT. Overall, the present findings indicated that IL6 cis‑signaling may have a direct involvement in the leukocyte activation in DVT and may serve as a predictive biomarker of DVT development.

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.

Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.

IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome Atlas (TCGA) datasets to explore the role of IL6, IL6R, IL6ST, and IL6R transmembrane isoform expression and their epigenetic regulation in different cancer types. IL6 was significantly modulated in 70% of tumor types, revealing either up- or down-regulation in an approximately equal number of tumors. Furthermore, IL6R and IL6ST were downregulated in more than 10 tumors. Interestingly, the correlation analysis demonstrated that only the IL6R expression was negatively affected by the DNA methylation within the promoter region in most tumors. Meanwhile, only the IL6ST expression was extensively modulated by miRNAs including miR-182-5p, which also directly targeted all three genes. In addition, IL6 upregulated miR-181a-3p, mirR-214-3p, miR-18a-5p, and miR-938, which in turn inhibited the expression of IL6 receptors. Finally, the patients’ survival rate was significantly affected by analyzed targets in some tumors. Our results suggest the relevance of epigenetic regulation of IL6 signaling and pave the way for further studies to validate these findings and to assess the prognostic and therapeutic predictive value of these epigenetic markers on the clinical outcome and survival of cancer patients.

Aim: Despite the serious side effects, analgesics acting on opioid receptors are still considered the best way to get antinociception. Matrix metalloproteinases, a large family of zinc-dependent proteases implicated in many pathological conditions, such as diabetes and osteoarthritis, are also involved in inflammation and pain. Methodology & results: Looking for evidence of possible interactions of opioid pathways and inflammation mediators, molecular modeling studies of a series of recently developed μ-opioid receptor benzomorphanic agonists together with biological data on pain and inflammation molecular targets, allowed us to hypothesize a possible correlation between μ-opioid receptor system and MMP-9. Conclusion: A new compound, (-)-MML1017, emerged as a possible dual-acting agent able to interact selectively and potently with the two molecular targets.

Particular features in the pulp of blood oranges are marked levels of anthocyanin, a class of polyphenolic compounds well known to exert numerous health-promoting actions on human wellbeing including anti-obesity effects. In this study, we investigated

Complementary and alternative medicines represent an interesting field of research on which worldwide academics are focusing many efforts. In particular, the possibility to exploit pharmaceutical technology strategies, such as the nanoencapsulation, for the delivery of essential oils is emerging as a promising strategy not only in Italy but also all over the world. The aim of this work was the development of nanostructured lipid carriers (NLC) for the delivery of essential oils (Lavandula, Mentha, and Rosmarinus) by intranasal administration, an interesting topic in which Italian contributions have recently increased. Essential oil-loaded NLC, projected as a possible add-on strategy in the treatment of neurodegenerative diseases, were characterized in comparison to control formulations prepared with Tegosoft CT and Neem oil. Homogeneous (polydispersity index, PDI &lt, 0.2) nanoparticles with a small size (&lt, 200 nm) and good stability were obtained. Morphological and physical-chemical studies showed the formation of different structures depending on the nature of the liquid oil component. In particular, NLC prepared with Lavandula or Rosmarinus showed the formation of a more ordered structure with higher cytocompatibility on two cell lines, murine and human fibroblasts. Taken together, our preliminary results show that optimized positively charged NLC containing Lavandula or Rosmarinus can be proposed as a potential add-on strategy in the treatment of neurodegenerative diseases through intranasal administration, due to the well-known beneficial effects of essential oils and the mucoadhesive properties of NLC.

Castanea sativa is particularly exploited in the Mediterranean basin, for fruit and wood production. Several authors studied the possible effects of C. sativa compounds as interesting ingredients f...

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.

Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.

The emerging trend in new vaccine development is to identify protective antigens and develop peptide-based vaccines able to offer a better immunogenicity/risk ratio. Nanogel (nGEL) can be designed to optimally present the delivered antigen to the immune system in controlled release formulations promoting their targeting to specific immune populations. Final properties of nGEL (size, surface charge) may be determining factors in designing the induced immune response. Taking into account these considerations, the aim of the study is the design of nGEL based on Dextran Sulfate (DS) and ϵ-Poly-lysine (ePL) of tunable size and surface charge by Response Surface Methodology (RSM) approach for nasal administration. nGEL systems were obtained by a mild and environmental-friendly physical cross-linking method. Based on the desirability function, the optimized formulation showed similar observed and predicted responses (errors

The genus Teucrium (Lamiaceae) includes 300 species widespread all around the world, which are perennial herbs or shrubs commonly, named germanders. In Italy, Teucrium flavum L., Teucrium fruticans L., and Teucrium siculum Rafin are mostly present in Liguria, Sicily, and Sardegna. Teucrium species are characterized by mono and sesquiterpene hydrocarbons, flavonoids, fatty acid esters, and essential oils. Many species of this genus show antioxidant, antimicrobial, and antifungal activities, rendering them useful as natural preservative ingredients. In view of the interesting biological properties reported for Teucrium spp., in this study we determined the total phenol and flavonoid content of inflorescence extracts of T. flavum L., T. fruticans L., and T. siculum Rafin. In addition, we investigated the in vitro antioxidant and antibacterial activities of inflorescence extracts against pathogenic bacteria. Obtained results demonstrated that extracts had in vitro antioxidant activity and showed antim...

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr&reg, ) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and &gamma, H2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr&reg, exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin &alpha, 5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr&reg, suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr&reg, as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.

[Image: see text] We report the development of molecular hybrids in which a nitrate group serving as nitric oxide (NO) donor is covalently joined to σ receptor ligands to give candidates for double-targeted cancer therapy. The compounds have been evaluated in radioligand binding assay at both σ receptors and selected compounds tested for NO release. Compounds 9, 15, 18, 19, and 21 were subjected to MTT test. Compound 15 produced a significant reduction of MCF-7 and Caco-2 cellular viability with comparable IC(50) as doxorubicin, being also not toxic for fibroblast HFF-1 cells. Compound 15 has shown a σ(1) receptor antagonist/σ(2) receptor agonist profile. Two derivatives of compound 15 lacking the nitrate group did not induce a reduction of MCF-7 cellular viability, suggesting a potential synergistic effect between the σ receptors and the NO-mediated events. Overall, the combination of NO donor and σ receptors ligands provided compounds with beneficial effects for the treatment of cancer.

BACKGROUND: Berries are worldwide recognized as “superfoods” due to the high content of bioactive compounds and the health benefits deriving from their consumption. OBJECTIVE: The present study was planned to assess and to compare the chemical profile and the in vitro antioxidant, hypoglycaemic, and anti-inflammatory activities of Vaccinium corymbosum L. berries and leaves extracts obtained by different extraction procedures. Ethanol was chosen as solvent because it is a GRAS (Generally Recognized As Safe) and widely used for the extraction of polar compounds. METHODS: Different extraction techniques such asmaceration, ultrasound-assisted extraction, Soxhlet extractor and decoction, have been applied by using food grade ethanol/water as solvent mixture, selected as environmentally friendly solvents. Extracts obtained from fruits and leaves were chemically investigated by liquid chromatography-electrospray ionization quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) and for their potential in vitro antioxidant, hypoglycaemic, and anti-inflammatory effects. RESULTS: Some iridoids were detected for the first time in V. corymbosum. Dried leaves extracted by decoction and ethanol with Soxhlet apparatus showed the highest 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals scavenging activity with IC50 value of 0.77μg/mL, which is 2.2-time lower than that positive control ascorbic acid. A promising inhibition of the production of nitrate/nitrite, critical mediators of inflammation, was found. The decoction of berries showed the highest activity in counteracting nitric oxide (NO.) production. Furthermore, two leaves extracts (decoction of dried leaves and hydroalcoholic maceration of fresh leaves) were particularly active as α-amylase inhibitors with IC50 values of 16.16 and 20.55 μg/mL, respectively. CONCLUSIONS: This work could provide valuable basis for future research on V. corymbosum to improve recovery of specific active compounds such as flavonoids and iridoids

Curcumin is a polyphenol compound extracted from the rhizome of Curcuma longa Linn (family Zingiberaceae) commonly used as a spice to color and flavor food. Several preclinical studies have suggested beneficial roles for curcumin as an adjuvant therapy in free radical-based diseases, mainly neurodegenerative disorders. Indeed, curcumin belongs to the family of hormetins and the enhancement of the cell stress response, mainly the heme oxygenase-1 system, is actually considered the common denominator for this dual response. However, evidence-based medicine has clearly demonstrated the lack of any therapeutic effect of curcumin to contrast the onset or progression of neurodegeneration and related diseases. Finally, the curcumin safety profile imposes a careful analysis of the risk/benefit balance prior to proposing chronic supplementation with curcumin.

Nowadays, agro-food by-products represent a potential low-cost source of biologically active ingredients which have been paid significant attention as nutraceuticals, medicine, food and cosmetics. In a previous study we evaluated the total sugars, metals and polyphenols of olive mill wastewater (OMWW) from a Cerasuola olive cultivar. In the present work we selectively recovered a sugar and mineral enriched fraction (SMEF) from Cerasuola OMWW by a green adsorption/desorption process. The SMEF was mainly found to be composed of monosaccharides and potassium by HPLC-ELSD and ICP-MS. The in vitro cytotoxicity on human fibroblasts, at different concentrations of the fraction, was investigated by MTT and comet assays. In addition, intracellular reactive oxygen species (ROS) production, apoptosis and cell morphological changes were examined. The physical stability of a formulation containing the SMEF (1% w/w) and its in vivo skin effects were also assessed.Our results highlighted that the SMEF showed a toxic effect at higher concentrations (i.e. cell viability reduction, DNA fragmentation and morphological alterations) well correlated with high ROS levels. Conversely, at low concentrations (0.5% and 1% w/w), no significant changes were observed. For the first time, through stability studies and in vivo tests, we also demonstrated that the SMEF formulation is stable and safe for topical application, since skin hydration improvement without negative effects was observed after 7 days of its use. Therefore, the SMEF has great potential to be used for cosmeceutical applications.

Cancers of the digestive tract, in particular colorectal cancer (CRC), are among those most responsive to dietary modification. Research has shown that approximately 75% of all sporadic cases of CRC are directly influenced by diet. Many natural compounds have been investigated for their potential usefulness as cancer chemopreventive agents as they have been thought to suppress carcinogenesis mainly during the initiation phase due to their radical scavenger activity. Since there is an increasing interest in the in vivo protective effects of natural compounds contained in plants against oxidative damage involved in several human diseases such as cancer, the aim of the present research was to test the effects of a Celtis aetnensis (Tornab.) Strobl twig extract on a human colon carcinoma cell line (Caco2). In order to elucidate the mechanisms of action of this extract, LDH release, GSH content, ROS levels, caspase-3 and γ-GCS expression were also evaluated. The results revealed that the Celtis aetnensis extract reduced the cell viability of the Caco2 cells inducing apoptosis at the lowest concentration and necrosis at higher dosages. In addition, this extract caused an increase in the levels of ROS, a decrease in RSH levels and in the expression of HO-1. The expression of γ-GCS was not modified in the Celtis aetnensis-treated Caco-2 cells. These results suggest an interference of this extract on the oxidant/antioxidant cell balance with consequent cell damage. The present study supports the growing body of data suggesting the bioactivities of Celtis aetnensis (Tornab.) Strobl and its potential impact on cancer therapy and on human health.

Betula etnensis Raf. (Birch Etna) belonging to the Betulaceae family grows on the eastern slope of Etna. Many bioactive compounds present in Betula species are considered promising anticancer agents. In this study, we evaluated the effects of B. etnensis Raf. bark methanolic extract on a human colon cancer cell line (CaCo2). In order to elucidate the mechanisms of action of the extract, cellular redox status, cell cycle, and heme oxygenase-1 (HO-1) expression in ferroptosis induction were evaluated. Cell viability and proliferation were tested by tetrazolium (MTT) assayand cell cycle analysis, while cell death was evaluated by annexin V test and lactic dehydrogenase (LDH) release. Cellular redox status was assessed by measuring thiol groups (RSH) content, reactive oxygen species (ROS) production, lipid hydroperoxide (LOOH) levels and (&gamma, glutamylcysteine synthetase) &gamma, GCS and HO-1 expressions. The extract significantly reduced cell viability of CaCo2, inducing necrotic cell death in a concentration-depending manner. In addition, an increase in ROS levels and a decrease of RSH content without modulation in &gamma, GCS expression were detected, with an augmentation in LOOH levels and drastic increase in HO-1 expression. These results suggest that the B. etnensis Raf. extract promotes an oxidative cellular microenvironment resulting in CaCo2 cell death by ferroptosis mediated by HO-1 hyper-expression.

Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high-risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high-grade vs. low-grade) and status (deceased vs. alive); differential analyses of miRNA expression among these groups were performed. A total of 20 deregulated miRNAs for each group were identified. In total 7 miRNAs were common between the groups. The majority of common miRNAs belonged to the miR-506-514 cluster, known to be involved in UM development. The prognostic value of the 20 selected miRNAs related to tumor stage was assessed. The deregulation of 12 miRNAs (6 upregulated and 6 downregulated) was associated with a worse prognosis of patients with UM. Subsequently, miRCancerdb and microRNA Data Integration Portal bioinformatics tools were used to identify a set of genes associated with the 20 miRNAs and to establish their interaction levels. By this approach, 53 different negatively and positively associated genes were identified. Finally, DIANA-mirPath prediction pathway and Gene Ontology enrichment analyses were performed on the lists of genes previously generated to establish their functional involvement in biological processes and molecular pathways. All the miRNAs and genes were involved in molecular pathways usually altered in cancer, including the mitogen-activated protein kinase (MAPK) pathway. Overall, the findings of the presents study demonstrated that the miRNAs of the miR-506-514 cluster, hsa-miR-592 and hsa-miR-199a-5p were the most deregulated miRNAs in patients with high-grade disease compared to those with low-grade disease and were strictly related to the overall survival (OS) of the patients. However, further in vitro and translational approaches are required to validate these preliminary findings.

Resveratrol, a polyphenol present in grapes and other edible plants, possesses several important pharmacological activities, including anticancer activity. Nevertheless, its therapeutic use is still limited because of some unfavourable physicochemical and pharmacokinetic properties, mainly, poor cellular uptake and too rapid metabolism resulting in elimination from the body. To meet these drawbacks, some resveratrol conjugates would be useful, which would possess improved stability, uptake and bioavailability than the lead compound, and the ability to release it once it is internalized into the cell. In this paper we report a synthetic strategy which allowed us to obtain new amphiphilic resveratrol derivatives starting from different selectively protected resveratrol phosphoramidites or even from the resveratrol triphosphoramidite. Specifically, resveratrol was conjugated through phosphate bridge(s) to different lipophilic groups related to membrane lipids, such as cholesteryl or diacylglycero moieties. All the new lipoconjugates were tested towards human neuroblastoma SH-SY5Y cells and proved to be significantly more active than resveratrol, with a concentration-dependent activity.

The aim of the present study was to investigate, in the Statens Seruminstitut Rabbit Cornea (SIRC) cell line, the presence of epithelial and fibroblastic markers, comparing their levels with those of the human Retinal Pigmented Epithelial (ARPE-19) cell line, and the Human Keratocyte (HK) cell line, respectively. SIRC cells, often described as of epithelial origin, are used as a corneal epithelial barrier model to study the permeability of ophthalmic drugs. However, they show a morphology that is more consistent with a fibroblastic cell phenotype, similar to corneal keratocytes. Our comparative analyses of cell type specific markers demonstrated that SIRC do not express cytokeratins 19 and 16 (typical of ARPE-19) and cytokeratin 9 (typical of HK); they do express cytokeratins 3 and 18 common to all three cell lines, and cytokeratin 12 typical of ARPE-19. Tight junction proteins were absent in HK, and lower in SIRC than in ARPE-19. All cell lines expressed the markers lumican and vimentin, with SIRC expressing intermediate levels between HK and ARPE-19; alpha-SMA was highly expressed in all lines. These markers, considered typical of fibroblasts, can be, however, expressed by epithelial cells during wound healing. These results might suggest that long-term in vitro cultivation of cell lines leads to a derangement of their specific phenotype, most likely due to genetic and epigenetic factors. This could be the reason why SIRC cells came to exhibit a hybrid nature between epithelial and fibroblastic cells.

The evaluation of DNA damage in aquatic organisms represents one of the most widely used biomarkers in the assessment and monitoring of marine pollution. Our previous research highlighted the presence of DNA damage in hepatic nuclei and blood cells of Coris julis specimens collected from Augusta harbor (Syracuse, Italy), a site highly polluted. In this work, we investigated on the ability of different natural compounds with antioxidant and immunostimulating properties, such as resveratrol (50 μM, 100 μM), amygdalin (100 μM, 200 μM), and Urtica dioica roots extract (50 and/or 100 μg/ml), in reducing DNA damage of C. julis. Blood cells were analyzed by atypical cellular comet assay. The results confirmed that Augusta specimens are the most damaged and showed that resveratrol, followed by amygdalin and U. dioica roots extract, drastically reduced DNA damage. This finding evidences the effectiveness of three natural compounds for DNA protection suggesting the possible use of feed enriched with antioxidant compounds in aquaculture practices for organisms damaged by natural and anthropic insults.

Astrocytes are actively involved in brain development, in mature CNS regulation, and in brain plasticity. They play a critical role in response to cerebral injuries and toxicants through a reaction known as “reactive gliosis,” which is characterized by specific structural and functional features. A large amount of literature highlights the central role of astrocytes in mediating methylmercury (MeHg) neurotoxicity. In fact, mercury is the major neurotoxic pollutant that continues to arouse interest in research because of the severe risk it poses to human health. In this article, we focus on the action of MeHg on human astrocyte (HA) reactivity. We clearly demonstrate that MeHg induces a state of cellular suffering by promoting delayed and atypical astrocyte reactivity mediated by impairment of the proliferative and trophic component of the astrocyte together with an inflammatory state. This condition is generated by negative modulation of the major proteins of the filamentous network, which is manifested by the destabilization of astrocytic cytoarchitecture. Our data confirms the toxic effects of MeHg on HA reactivity and allows us to hypothesize that the establishment of this state of suffering and the delayed onset of a typical astrocytic reactivity compromise the main protective function of HA. © 2013 Wiley Periodicals, Inc.

Bifidobacterium longum W11 is a commercialized probiotic that has an exopolysaccharide (EPS) layer covering its surface which could play a role in the beneficial properties attributed to the strain; thus, we have carried out chemical and biological analyses of this polymer. The eps cluster putatively involved in the polymer synthesis presented a unique structural organization not previously reported in bifidobacteria. B. longum W11 produced a complex polysaccharide blend with the main component composed of glucose and galactose. An exhaustive structural analysis identified two different repeating units: one linear [→6)-β-Galf-(1→3)-α-Galp-(1→] and one, more abundant, with the same backbone in which the β-Galf is 5-substituted by a β-Glcp unit. The antioxidant capability and the lack of toxicity of the whole EPS W11 mixture, as well as some functional characteristics of the producing strain, such as the in vitro resistance to gastrointestinal conditions and the adhesion of colonocytes, were also determined., The authors acknowledge to the Spanish Ministry of Economy, Industry and Competitiveness (MINEICO) and FEDER funds for the financial support through the project AGL2015-64901-R. The authors also thank the Italian Ministry of Education, University and Research for the fellowship PON 01_01802 and the University of Catania for a grant application (FIR2014).

A multibiomarkers approach was used in order to estimate and monitor marine pollution. Coris julis (Linneaus, 1758) was chosen as a sentinel organism, and the specimens were collected from three well-known sites along the Ionic coast of Sicily: the protected marine area (P.M.A) “Cyclop’s Islands” of Acitrezza (CT), used as a control site, Riposto (CT), and the industrial site of Augusta (SR). Abiotic levels of contaminants were also detected. High levels of biotic and abiotic accumulation were found at the industrial site in which the presence of genotoxic and oxidative damage were also evidenced, measured by Micronuclei, Alkaline and Fpg-modified Comet assays. The protein expression analysis showed metallothioneins (MTs) as good tissue-specific markers of metal accumulation. Their levels were significantly higher in muscle than in liver tissue for all the sampling sites, with a positive correlation among tissue levels and the degree of pollution at the sites. Conversely, heat shock proteins 70 (HSP70) expression was higher in Augusta and Riposto than in the control site, but no significant difference was found between the examined tissues among all sites.

New roles have been discovered for the adipose mass/tissue of obese subjects linked to the production of different cytokines, leptin and oxidative stress, all together playing a crucial role in developing obesity, insulin resistance, metabolic syndrome, and the pathogenesis of various diseases. Inflammatory status and plasma oxidative stress have been reported as also characterizing a new metabolic condition known as normal-weight obese (NWO) syndrome observed in women with normal index but fat mass (FM) >30%. The aim of the present study was to investigate in NWO women, compared with preobese-obese (OB) and control normal weight (NW) subjects, the occurrence of DNA damage, particularly oxidative DNA damage, by using different Comet assay versions. Our goal was to find out some possible new early hallmarks of obesity. We observed above all increase in DNA damage both in OB and NWO women, compared with NW subjects, underlining DNA to be involved in oxidative stress related to metabolic abnormalities occurring in obesity. In addition, the use of either pH >13 versus pH 12.1 alkaline Comet assay versions or pH 12.1 in presence of Fpg enzyme versus pH 12.1 alone, allow us to draw attention to two possible new early differentiated hallmarks: first, alkali labile sites higher in OB compared to NWO; second, 8-oxo-dG level slightly higher in NWO than in OB women. These preliminary results encourage planning broad cohort studies in order to verify and validate these hypothesized predictive/prognostic new hallmarks.

The blenny Parablennius sanguinolentus was selected as a useful bioindicator of environmental pollution. Chemical parameters in water and sediments from three different sampling sites along the Sicilian Ionian coast were determined and metal concentrations in fish muscle were measured. DNA fragmentation and oxidation in erythrocytes and hepatocytes was determined by the Comet assay and HSP70 expression levels were evaluated in the liver. The results show an increased level of chromium in sediments and high polycyclic aromatic hydrocarbon (PAH) concentrations in water at one site. The bioaccumulation of metals in muscle tissue shows high concentrations of lead in some samples. A high percentage of DNA damage in blood and liver cells, as well as high hepatic levels of HSP70, were found in all the sites. The results demonstrate the usefulness of an integrated chemical and biological approach for the determination of environmental stress.