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San Fedele Superiore, Italy

Verze P.,University of Naples Federico II | Cai T.,Santa Chiara Regional Hospital | Lorenzetti S.,Istituto Superiore di Sanit
Nature Reviews Urology | Year: 2016

Ejaculation is a synchronized cascade of events that has the ultimate goal of activating sperm and enabling them to reach an egg for fertilization. The seminal plasma contains a complex mixture of fluids that is secreted from the testes, epididymis and male accessory glands. The prostate gland has a pivotal role in this process, as prostatic fluid enriched in Zn 2+, citrate and kallikreins is crucial for the molecular synchronization of the functional cascade triggered by ejaculatory stimuli. The prostate is the target of a number of common diseases that can affect male fertility at different ages. In both young and aged men, prostatic diseases or an unhealthy prostate can affect spermatozoa functioning and, therefore, male fertility. Consideration of prostate physiology emphasizes a number of points: the central role of Zn 2+ and citrate in the regulation of prostate epithelium homeostasis and in ejaculation; the influence of bacteria-related prostatic inflammation on male fertility; and the potential role of prostatic inflammation in promoting the development of prostatic hyperplastic growth and carcinogenesis. © 2016 Macmillan Publishers Limited. Source

Giorgi C.,Istituto Superiore di Sanit | Franconi R.,ENEA | Rybicki E.P.,University of Cape Town
Expert Review of Vaccines | Year: 2010

Human papillomaviruses are the etiological agents of cervical cancer, one of the two most prevalent cancers in women in developing countries. Currently available prophylactic vaccines are based on the L1 major capsid protein, which forms virus-like particles when expressed in yeast and insect cell lines. Despite their recognized efficacy, there are significant shortcomings: the vaccines are expensive, include only two oncogenic virus types, are delivered via intramuscular injection and require a cold chain. Plant expression systems may provide ways of overcoming some of these problems, in particular the expense. In this article, we report recent promising advances in the production of prophylactic and therapeutic vaccines against human papillomavirus by expression of the relevant antigens in plants, and discuss future prospects for the use of such vaccines. © 2010 Expert Reviews Ltd. Source

Lassmann H.,Medical University of Vienna | Niedobitek G.,Sana Klinikum Lichtenberg Unfallkrankenhaus | Aloisi F.,Istituto Superiore di Sanit | Middeldorp J.M.,VU University Amsterdam
Brain | Year: 2011

Recent epidemiological and immunological studies provide evidence for an association between Epstein-Barr virus infection and multiple sclerosis, suggesting a role of Epstein-Barr virus infection in disease induction and pathogenesis. A key question in this context is whether Epstein-Barr virus-infected B lymphocytes are present within the central nervous system and the lesions of patients with multiple sclerosis. Previous studies on this topic provided highly controversial results, showing Epstein-Barr virus reactivity in B cells in the vast majority of multiple sclerosis cases and lesions, or only exceptional Epstein-Barr virus-positive B cells in rare cases. In an attempt to explain the reasons for these divergent results, a workshop was organized under the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which is presented here. This report summarizes the current knowledge of Epstein-Barr virus biology and shows that Epstein-Barr virus infection is highly complex. There are still major controversies, how to unequivocally identify Epstein-Barr virus infection in pathological tissues, particularly in situations other than Epstein-Barr virus-driven lymphomas or acute Epstein-Barr virus infections. It further highlights that unequivocal proof of Epstein-Barr virus infection in multiple sclerosis lesions is still lacking, due to issues related to the sensitivity and specificity of the detection methods. © 2011 The Author. Source

Morini L.,University of Pavia | Falcon M.,University of Murcia | Pichini S.,Istituto Superiore di Sanit | Garcia-Algar O.,Institute Municipal dInvestigacio Mdica Hospital Del Mar | And 3 more authors.
Analytical Biochemistry | Year: 2011

The aim of this study was to develop a method for the determination of ethyl-glucuronide (EtG) and ethyl-sulfate (EtS), two direct ethanol metabolites, in early placental and fetal human tissues, as potential biomarkers of transplacental ethanol transfer from the mother to the fetus. Placental and fetal tissue samples were obtained from women undergoing voluntary termination of pregnancy at 12 weeks of gestation. Samples were deproteinized and directly injected into a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) system. Limits of detection of 13.0 and 23.0 pmol/g and lower limits of quantification of 22.0 and 40.0 pmol/g were reached for EtG and EtS, respectively. Inter- and intraday imprecision and accuracy were always lower than 15%. The method was applied to 70 samples (35 placentas and 35 fetal tissues). Of 35 samples, 4 samples collected from 4 women tested positive for EtG and EtS, always showing higher concentrations for EtG. The placenta/fetal tissue ratio for EtG was 2.9 ± 0.9, whereas EtS showed a ratio of 1.7 ± 0.7. Preliminary results suggest that these metabolites are present in both tissues. Further studies should now corroborate the hypothesis, not yet confirmed, that transplacental transfer of ethanol takes place not only for the parent compound but also for EtG and EtS. © 2011 Elsevier Inc. All rights reserved. Source

Lombardo Y.,University of Palermo | Scopelliti A.,University of Palermo | Cammareri P.,Cellular and Molecular Oncology | Todaro M.,University of Palermo | And 7 more authors.
Gastroenterology | Year: 2011

Background & Aims: The limited clinical response observed in many patients with colorectal cancer may be related to the presence of chemoresistant colorectal cancer stem cells (CRC-SCs). Bone morphogenetic protein 4 (BMP4) promotes the differentiation of normal colonic stem cells. We investigated whether BMP4 might be used to induce differentiation of CRC-SCs and for therapeutic purposes. Methods: CRC-SCs were isolated from 25 tumor samples based on expression of CD133 or using a selection culture medium. BMP4 expression and activity on CRC-SCs were evaluated in vitro; progeny of the stem cells were evaluated by immunofluorescence, immunoblot, and flow cytometry analyses. The potential therapeutic effect of BMP4 was assessed in immunocompromised mice after injection of CRC-SCs that responded to chemotherapy (n = 4) or that did not (n = 2). Results: CRC-SCs did not express BMP4 whereas differentiated cells did. Recombinant BMP4 promoted differentiation and apoptosis of CRC-SCs in 12 of 15 independent experiments; this effect did not depend on Small Mothers against decapentaplegic (Smad)4 expression level or microsatellite stability. BMP4 activated the canonical and noncanonical BMP signaling pathways, including phosphoInositide 3-kinase (PI3K) and PKB (protein kinase B)/AKT. Mutations in PI3K or loss of Phosphatase and Tensin homolog (PTEN) in Smad4-defective tumors made CRC-SCs unresponsive to BMP4. Administration of BMP4 to immunocompromised mice with tumors that arose from CRC-SCs increased the antitumor effects of 5-fluorouracil and oxaliplatin. Conclusions: BMP4 promotes terminal differentiation, apoptosis, and chemosensitization of CRC-SCs in tumors that do not have simultaneous mutations in Smad4 and constitutive activation of PI3K. BMP4 might be developed as a therapeutic agent against cancer stem cells in advanced colorectal tumors. © 2011 AGA Institute. Source

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