Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells

Epidemiological data indicate that the daily consumption of extra‑virgin olive oil (EVOO), a common dietary habit of the Mediterranean area, lowers the incidence of certain types of cancer, in particular bladder neoplasm. The aim of the present study was to evaluate the antiproliferative activity of polyphenols extracted from EVOO on bladder cancer (BCa), and to clarify the biological mechanisms that trigger cell death. Furthermore, we also evaluated the ability of low doses of extra‑virgin olive oil extract (EVOOE) to modulate the in vitro activity of paclitaxel or mitomycin, two antineoplastic drugs used in the management of different types of cancer. Our results showed that EVOOE significantly inhibited the proliferation and clonogenic ability of T24 and 5637 BCa cells in a dose‑dependent manner. Furthermore, cell cycle analysis after EVOOE treatment showed a marked growth arrest prior to mitosis in the G2/M phase for both cell lines, with the subsequent induction of apoptosis only in the T24 cells. Notably, simultaneous treatment of mitomycin C and EVOOE reduced the drug cytotoxicity due to inhibition of ROS production. Conversely, the co‑treatment of T24 cells with paclitaxel and the polyphenol extract strongly increased the apoptotic cell death at each tested concentration compared to paclitaxel alone. Our results support the epidemiological evidence indicating that olive oil consumption exerts health benefits and may represent a starting point for the development of new anticancer strategies

Pediatric liver diseases: current challenges and future perspectives

Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases

Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol (InRapa) that maximizes brain delivery and reduce systemic side effects. Methods: Ts65Dn mice were administered with InRapa for 12 weeks, starting at 6 months of age demonstrating, at the end of the treatment by radial arms maze and novel object recognition testing, rescued cognition. Results: The analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation. In addition, a reduction of oxidative stress markers was also observed. Discussion: These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals

Film deposition, X-ray diffraction and optical absorption of novel (R-NH3)2ZnCl4 hybrid perovskites

Organic-inorganic (CnH2n+1NH3)2MX4 hybrid perovskites (where M is a divalent metal and X a halide) are presently attracting much attention, due to their unique electronic properties and excellent film processability [1]. These self-assembling structures contain 2D semiconductor layers ((MX6)=) alternately stacked with organic ammonium layers. Excitons resulting from the low dimensionality of the semiconductor sheets have binding energy of several tenths eV, and are expected to have interesting potentialities for optoelectronic and electronic applications [2]. In this communication we report on the preparation and the basic X-ray and optical characterization of the novel (CnH2n+1NH3)2ZnCl4 (1<n<6) compounds, deposited as thin films by spin-coating alcoholic solutions of stoichiometric precursors on glass and quartz substrates. X-ray diffraction data prove that the as-prepared films are single phase, well crystallized and with a dominant in-plane grain orientation. The distance between the inorganic sheets, as measured through the "d" parameters, linearly increases with the amine chain length ("n" value) (Fig.1a), thus suggesting that the organic chains are ordered perpendicularly to the film surface. The diffraction pattern refinement is presently in progress, in order to assign the appropriate space group and to determine the in-plane lattice parameters. Room temperature optical absorption spectra exhibit a maximum at about 240 nm, which is almost independent on "n" (Fig.1b). Such finding is consistent with the results we obtained in the homologous series of Cu-based hybrids [3] and suggests that also in the Zn-compounds the optical absorption phenomena are related to the inorganic cluster of the structure. References. [1] D.B.Mitzi, K.Chondroudis, C.R. Kagan, IBM J.Res.Dev. 45, 29-45, 2001; [2] M.Era, S.Morimoto, T.Tsutsui, S.Saito, Appl.Phys.Lett 65, 676-678, 1994; [3] F.Chiarella, A.Zappettini, T.Besagni, F.Licci, A.Cassinese, M.Barra, R.Vaglio, C.Aruta, Cryst.Res.Technol. 40, 1028-1032, 2005

Bipolar disorder and antithyroid antibodies: review and case series

Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms

Síndrome Oculoglandular de Parinaud: presentación de un caso

Presentamos el caso de una adolescente de 14 años que consultó por adenopatías en región preauricular izquierda. En el interrogatorio dirigido surgió el contacto con gatos, registrándose el antecedente de una conjuntivitis homolateral, por lo cual se planteó el Síndrome de Parinaud por enfermedad por arañazo de gato entre los diagnósticos diferenciales.We report the case of a 14-year-old patient with adenopathies in the preauricular region. During the interview, the patient stated having had contact with cats, and a history of conjunctivitis comes up. These led to the diagnosis of Parinaud syndrome caused by cat scratch disease

Erythrocyte's aging in microgravity highlights how environmental stimuli shape metabolism and morphology

The determination of the function of cells in zero-gravity conditions is a subject of interest in many different research fields. Due to their metabolic unicity, the characterization of the behaviour of erythrocytes maintained in prolonged microgravity conditions is of particular importance. Here, we used a 3D-clinostat to assess the microgravity-induced modifications of the structure and function of these cells, by investigating how they translate these peculiar mechanical stimuli into modifications, with potential clinical interest, of the biochemical pathways and the aging processes. We compared the erythrocyte's structural parameters and selected metabolic indicators that are characteristic of the aging in microgravity and standard static incubation conditions. The results suggest that, at first, human erythrocytes react to external stimuli by adapting their metabolic patterns and the rate of consumption of the cell resources. On longer timeframes, the cells translate even small differences in the environment mechanical solicitations into structural and morphologic features, leading to distinctive morphological patterns of agin

A multilevel data integration resource for breast cancer study

BACKGROUND: Breast cancer is one of the most common cancer types. Due to the complexity of this disease, it is important to face its study with an integrated and multilevel approach, from genes, transcripts and proteins to molecular networks, cell populations and tissues. According to the systems biology perspective, the biological functions arise from complex networks: in this context, concepts like molecular pathways, protein-protein interactions (PPIs), mathematical models and ontologies play an important role for dissecting such complexity. RESULTS: In this work we present the Genes-to-Systems Breast Cancer (G2SBC) Database, a resource which integrates data about genes, transcripts and proteins reported in literature as altered in breast cancer cells. Beside the data integration, we provide an ontology based query system and analysis tools related to intracellular pathways, PPIs, protein structure and systems modelling, in order to facilitate the study of breast cancer using a multilevel perspective. The resource is available at the URL http://www.itb.cnr.it/breastcancer. CONCLUSIONS: The G2SBC Database represents a systems biology oriented data integration approach devoted to breast cancer. By means of the analysis capabilities provided by the web interface, it is possible to overcome the limits of reductionist resources, enabling predictions that can lead to new experiments

Enhanced aldehydes detection by ZnO nano-tetrapod based gas sensors

Metal oxides are very important materials in gas-sensing and the possibility to obtain them as crystalline nanostructures represents an essential chance to improve sensors sensitivity an lifetime. Zinc oxide (ZnO) is a versatile material that is today widely studied because of the large number of possible application fields. The availability of this material in a large number of nanostructures makes it very interesting for the realization of gas sensors. In this field ZnO nano-tetrapods can find a suitable and reliable application, since they can be obtained by vapour phase growth, starting from metallic Zn, with very large yield and low production costs. In the present work authors report the excellent results obtained in: (i) developing an optimized growth process for the production of ZnO tetrapods, (ii) realizing a gas sensing device based on these nanostructures and (iii) the very promising results obtained in the detection of some volatile organic compounds (VOC). In particular a very high response and a remarkable sub-ppm detection limit is demonstrated for aldehydes. Furthermore, the reaction mechanisms, which take place on the surface of ZnO tetrapods, are discussed as a function of temperature and it is shown that the response curves measured at different temperatures can provide a powerful tool for adding selectivity to aldehydes detection towards particular interfering compounds (e.g. alcohols)

A new approach for the synthesis of ZnO nanoparticles sensitized with metal chalcogenides

The present communication is a response to renewed interest in nanostructure based "coupled compounds", like ZnO-MeX (where Me = Cd, Pb,... and X = S, Se) which can find extensive use in the fabrication of a number of solid state devices, such as photoconductive, solar cells, electroluminescent cells, photocatalysts. Various oxide semiconductors, like TiO2 and ZnO, are known to have appropriate properties for these applications, although there are some drawbacks associated with their use: (i) charge carrier recombination occurs within a few nanoseconds, (ii) band edge absorption threshold does not allow the utilization of visible light. One of the main approaches to overcome these particular limitations involves the contact of the semiconductor particle with another semiconductor, called "sensitizer". For example, this is the case of nanostructured ZnO particles combined with metal chalcogenides. Infact it is known that in these coupled systems the absorption threshold is extended to the visible region and the photogenerated electrons are quickly transferred from sulphide/selenide layer into to the lower lying conduction band of ZnO, thus limiting recombination effects. In order to produce this type of material we have combined ZnO nanoparticles, in the specific "tetrapod" morphology, with nanoparticles of metal chalcogenides. The main innovative aspects of the preparation procedure are the following: &#61485; the use of appropriate organic solvents to keep both ZnO and the formed metal chalcogenides completely suspended and dispersed in the liquid; &#61485; an in situ direct formation of metal chalcogenides keeping pH value in the range 6-8 (no use of ammonia salt or complexing agents); &#61485; the limited use of chemical reagents, i.e. only metal and sulphur/selenium precursors are involved; &#61485; the possibility to deposit the "coupled compounds" in form of thin films directly from the liquid suspension onto the substrates (silicon, alumina, glass, TCO layers, etc.). This paper reports details on the preparation procedure, results of morphological and structural investigations (XRD, SEM), compositional analysis (EDS microanalysis) and optical-electrical measurements (I-V, impedance spectroscopy, etc.), which point out the great potentiality of the proposed method for the synthesis of different "sensitized nano-compounds"