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Showing papers by "University of Palermo published in 2015"


Journal ArticleDOI
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

3,690 citations


Journal ArticleDOI
TL;DR: Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels and there was evidence of a reduction in the rate of cardiovascular events.
Abstract: BackgroundAlirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. MethodsWe conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. ResultsAt week 24, the difference between the alirocumab and placebo ...

1,832 citations


Journal ArticleDOI
TL;DR: In this critical review, some of the most promising electrochemical tools for the treatment of wastewater contaminated by organic pollutants are discussed in detail and the critical assessment of the reactors that can be used to put these technologies into practice is devoted.
Abstract: Traditional physicochemical and biological techniques, as well as advanced oxidation processes (AOPs), are often inadequate, ineffective, or expensive for industrial water reclamation. Within this context, the electrochemical technologies have found a niche where they can become dominant in the near future, especially for the abatement of biorefractory substances. In this critical review, some of the most promising electrochemical tools for the treatment of wastewater contaminated by organic pollutants are discussed in detail with the following goals: (1) to present the fundamental aspects of the selected processes; (2) to discuss the effect of both the main operating parameters and the reactor design on their performance; (3) to critically evaluate their advantages and disadvantages; and (4) to forecast the prospect of their utilization on an applicable scale by identifying the key points to be further investigated. The review is focused on the direct electrochemical oxidation, the indirect electrochemical oxidation mediated by electrogenerated active chlorine, and the coupling between anodic and cathodic processes. The last part of the review is devoted to the critical assessment of the reactors that can be used to put these technologies into practice.

1,197 citations


Journal ArticleDOI
TL;DR: In this article, the results of research on the use of basalt fiber as reinforcement of different matrices as polymer (both thermoplastic and thermoset), metal and concrete has been presented.
Abstract: In recent years, both industrial and academic world are focussing their attention toward the development of sustainable composites, reinforced with natural fibres. In particular, among the natural fibres (i.e. animal, vegetable or mineral) that can be used as reinforcement, the basalt ones represent the most interesting for their properties. The aim of this review is to illustrate the results of research on this topical subject. In the introduction, mechanical, thermal and chemical properties of basalt fibre have been reviewed. Moreover, its main manufacturing technologies have been described. Then, the effect of using this mineral fibre as reinforcement of different matrices as polymer (both thermoplastic and thermoset), metal and concrete has been presented. Furthermore, an overview on the application of this fibre in biodegradable matrix composites and in hybrid composites has been provided. Finally, the studies on the industrial applications of basalt fibre reinforced composites have been reviewed.

795 citations


Journal ArticleDOI
TL;DR: This consensus paper aims to improve awareness of the need for early detection and management of FH children by recommending cascade screening of families using a combined phenotypic and genotypic strategy.
Abstract: Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is 10 years, or ideally 50% reduction from baseline if 8–10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.

581 citations


Journal ArticleDOI
TL;DR: It is shown that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes and decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.

574 citations


Journal ArticleDOI
TL;DR: Modern methods based on nucleic acid and protein analysis are described, which represent unprecedented tools to render agriculture more sustainable and safe, avoiding expensive use of pesticides in crop protection.
Abstract: Plant diseases are responsible for major economic losses in the agricultural industry worldwide. Monitoring plant health and detecting pathogen early are essential to reduce disease spread and facilitate effective management practices. DNA-based and serological methods now provide essential tools for accurate plant disease diagnosis, in addition to the traditional visual scouting for symptoms. Although DNA-based and serological methods have revolutionized plant disease detection, they are not very reliable at asymptomatic stage, especially in case of pathogen with systemic diffusion. They need at least 1–2 days for sample harvest, processing, and analysis. Here, we describe modern methods based on nucleic acid and protein analysis. Then, we review innovative approaches currently under development. Our main findings are the following: (1) novel sensors based on the analysis of host responses, e.g., differential mobility spectrometer and lateral flow devices, deliver instantaneous results and can effectively detect early infections directly in the field; (2) biosensors based on phage display and biophotonics can also detect instantaneously infections although they can be integrated with other systems; and (3) remote sensing techniques coupled with spectroscopy-based methods allow high spatialization of results, these techniques may be very useful as a rapid preliminary identification of primary infections. We explain how these tools will help plant disease management and complement serological and DNA-based methods. While serological and PCR-based methods are the most available and effective to confirm disease diagnosis, volatile and biophotonic sensors provide instantaneous results and may be used to identify infections at asymptomatic stages. Remote sensing technologies will be extremely helpful to greatly spatialize diagnostic results. These innovative techniques represent unprecedented tools to render agriculture more sustainable and safe, avoiding expensive use of pesticides in crop protection.

553 citations


Journal ArticleDOI
TL;DR: There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age and their potential to be safe and effective in extending human healthspan.
Abstract: The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

458 citations


Journal ArticleDOI
TL;DR: The most important clinical issues confronting physicians and their patients with PCOS are highlighted to highlight, including the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging.

418 citations


Journal ArticleDOI
TL;DR: Experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of non-Celiac Gluten Sensitivity are reported, to help the clinician to reach a firm and positive diagnosis of NCGS.
Abstract: Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

414 citations


Journal ArticleDOI
TL;DR: In this paper, kenaf fibers were pre-treated in a NaOH solution (6% in weight) at room temperature for two different periods (48 and 144) to clean their surface removing each impurity whereas 144h of immersion time had detrimental effect on the fibers surface and, consequently, on their mechanical properties.
Abstract: In this work, kenaf fibers were pre-treated in a NaOH solution (6% in weight) at room temperature for two different periods (48 and 144 h). The chemical treatment of kenaf fibers for 48 h allowed to clean their surface removing each impurity whereas 144 h of immersion time had detrimental effect on the fibers surface and, consequently, on their mechanical properties. Untreated and NaOH treated kenaf fibers (i.e. for 48 h) were also used as reinforcing agent of epoxy resin composites. The effect of the stacking sequence (i.e. using unidirectional long fibers or randomly oriented short fibers) and the chemical treatment on the static mechanical properties was evaluated showing that the composites exhibit higher moduli in comparison to the neat resin. As regards the strength properties, only the composites reinforced with unidirectional layers show higher strength than the neat resin. Moreover, the alkali treatment increased the mechanical properties of the composites, due to the improvement of fiber–matrix compatibility. The dynamic mechanical analysis showed that the storage and the loss moduli are mainly influenced by the alkali treatment above the glass transition temperature. Moreover, the alkali treatment led to a notable reduction of tan δ peaks in addition to significant shifts of tan δ peaks to higher temperatures whereas the stacking sequence did not influence the trends of storage modulus, loss modulus and damping of the composites.

Journal ArticleDOI
TL;DR: It was found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo.
Abstract: BackgroundCrohn’s disease–related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. MethodsIn a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn’s disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn’s Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. ResultsThe proportions of patients who reached the prim...

Journal ArticleDOI
TL;DR: In this article, the authors discuss how changes in water level and salinity related to climate change and water abstraction affect the ecosystem structure, function, biodiversity and ecological state of lakes and reservoirs.
Abstract: According to the Intergovernmental Panel on Climate Change report released in September 2014, unprecedented changes in temperature and precipitation patterns have been recorded globally in recent decades and further change is predicted to occur in the near future, mainly as the result of human activity. In particular, projections show that the Mediterranean climate zone will be markedly affected with significant implications for lake water levels and salinity. This may be exacerbated by increased demands for irrigation water. Based on long-term data from seven lakes and reservoirs covering a geographical gradient of 52° of latitudes and a literature review, we discuss how changes in water level and salinity related to climate change and water abstraction affect the ecosystem structure, function, biodiversity and ecological state of lakes and reservoirs. We discuss mitigation measures to counteract the negative effects on ecological status that are likely to result from changes in climate and water abstraction practices. Finally, we highlight research required to improve knowledge of the impacts of anthropogenically induced changes on lake water level and consequent changes in salinity.

Journal ArticleDOI
TL;DR: A new exosome-mediated mechanism by which CSC-like CD90+ cells could influence their tumor microenvironment by promoting angiogenic phenotype and cell-to-cell adhesion is indicated.
Abstract: Background CD90+ liver cancer cells have been described as cancer stem-cell-like (CSC), displaying aggressive and metastatic phenotype. Using two different in vitro models, already described as CD90+ liver cancer stem cells, our aim was to study their interaction with endothelial cells mediated by the release of exosomes.

Journal ArticleDOI
TL;DR: It is demonstrated that co-composting considerably promoted biochars’ positive effects, largely by nitrate (nutrient) capture and delivery, and hypothesize that surface ageing plus non-conventional ion-water bonding in micro- and nano-pores promoted nitrate capture in biochar particles.
Abstract: Soil amendment with pyrogenic carbon (biochar) is discussed as strategy to improve soil fertility to enable economic plus environmental benefits. In temperate soils, however, the use of pure biochar mostly has moderately-negative to -positive yield effects. Here we demonstrate that co-composting considerably promoted biochars' positive effects, largely by nitrate (nutrient) capture and delivery. In a full-factorial growth study with Chenopodium quinoa, biomass yield increased up to 305% in a sandy-poor soil amended with 2% (w/w) co-composted biochar (BC(comp)). Conversely, addition of 2% (w/w) untreated biochar (BC(pure)) decreased the biomass to 60% of the control. Growth-promoting (BC(comp)) as well as growth-reducing (BC(pure)) effects were more pronounced at lower nutrient-supply levels. Electro-ultra filtration and sequential biochar-particle washing revealed that co-composted biochar was nutrient-enriched, particularly with the anions nitrate and phosphate. The captured nitrate in BC(comp) was (1) only partly detectable with standard methods, (2) largely protected against leaching, (3) partly plant-available, and (4) did not stimulate N2O emissions. We hypothesize that surface ageing plus non-conventional ion-water bonding in micro- and nano-pores promoted nitrate capture in biochar particles. Amending (N-rich) bio-waste with biochar may enhance its agronomic value and reduce nutrient losses from bio-wastes and agricultural soils.

Journal ArticleDOI
TL;DR: Biology and physiology of EPCs are described, their clinical relevance as both new predictive, diagnostic, and prognostic CVD biomarkers and therapeutic agents are outlined, and a very crucial aspect of E PCs “characterization and definition” is underline, which seems to be the real cause of large heterogeneity existing in literature data on this topic.
Abstract: Advanced knowledge in the field of stem cell biology and their ability to provide a cue for counteracting several diseases are leading numerous researchers to focus their attention on "regenerative medicine" as possible solutions for cardiovascular diseases (CVDs). However, the lack of consistent evidence in this arena has hampered the clinical application. The same condition affects the research on endothelial progenitor cells (EPCs), creating more confusion than comprehension. In this review, this aspect is discussed with particular emphasis. In particular, we describe biology and physiology of EPCs, outline their clinical relevance as both new predictive, diagnostic, and prognostic CVD biomarkers and therapeutic agents, discuss advantages, disadvantages, and conflicting data about their use as possible solutions for vascular impairment and clinical applications, and finally underline a very crucial aspect of EPCs "characterization and definition," which seems to be the real cause of large heterogeneity existing in literature data on this topic.

Journal ArticleDOI
TL;DR: In this article, the authors show evidence for a discrete microbial signature in the terminal ileum of patients with ankylosing spondylitis compared with healthy control subjects.
Abstract: Objective Ankylosing spondylitis (AS) is a common, highly heritable immune-mediated arthropathy that occurs in genetically susceptible individuals exposed to an unknown but likely ubiquitous environmental trigger There is a close relationship between the gut and spondyloarthritis, as exemplified in patients with reactive arthritis, in whom a typically self-limiting arthropathy follows either a gastrointestinal or urogenital infection Microbial involvement in AS has been suggested; however, no definitive link has been established The aim of this study was to determine whether the gut in patients with AS carries a distinct microbial signature compared with that in the gut of healthy control subjects Methods Microbial profiles for terminal ileum biopsy specimens obtained from patients with recent-onset tumor necrosis factor antagonist-naive AS and from healthy control subjects were generated using culture-independent 16S ribosomal RNA gene sequencing and analysis techniques Results Our results showed that the terminal ileum microbial communities in patients with AS differ significantly (P < 0001) from those in healthy control subjects, driven by a higher abundance of 5 families of bacteria (Lachnospiraceae [P = 0001], Ruminococcaceae [P = 0012], Rikenellaceae [P = 0004], Porphyromonadaceae [P = 0001], and Bacteroidaceae [P = 0001]) and a decrease in the abundance of 2 families of bacteria (Veillonellaceae [P = 001] and Prevotellaceae [P = 0004]) Conclusion We show evidence for a discrete microbial signature in the terminal ileum of patients with AS compared with healthy control subjects The microbial composition was demonstrated to correlate with disease status, and greater differences were observed between disease groups than within disease groups These results are consistent with the hypothesis that genes associated with AS act, at least in part, through effects on the gut microbiome

Journal ArticleDOI
TL;DR: If new interferon-free, well-tolerated anti-HCV treatment regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.

Journal ArticleDOI
TL;DR: This document, produced by the collaboration of the American Association of Clinical Endocrinologists and the Androgen Excess Society, aims to highlight the most important clinical issues confronting physicians and their patients with PCOS.

Journal ArticleDOI
TL;DR: Statin use was associated with protection towards the full spectrum of liver damage in individuals at risk of non-alcoholic steatohepatitis, however, the I148M PNPLA3 risk variant limited this beneficial effect.

Journal ArticleDOI
TL;DR: Experimental results show that the solution outperforms four relevant works based on RGB-D image fusion, hierarchical Maximum Entropy Markov Model, Markov Random Fields, and Eigenjoints, respectively, and the ability to recognize the activities in real time show promise for applied use.
Abstract: In this paper, we present a method for recognizing human activities using information sensed by an RGB-D camera, namely the Microsoft Kinect. Our approach is based on the estimation of some relevant joints of the human body by means of the Kinect; three different machine learning techniques, i.e., K-means clustering, support vector machines, and hidden Markov models, are combined to detect the postures involved while performing an activity, to classify them, and to model each activity as a spatiotemporal evolution of known postures. Experiments were performed on Kinect Activity Recognition Dataset, a new dataset, and on CAD-60, a public dataset. Experimental results show that our solution outperforms four relevant works based on RGB-D image fusion , hierarchical Maximum Entropy Markov Model , Markov Random Fields , and Eigenjoints , respectively. The performance we achieved, i.e., precision/recall of 77.3% and 76.7%, and the ability to recognize the activities in real time show promise for applied use.

Journal ArticleDOI
TL;DR: The aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.
Abstract: Statins are one of the most commonly prescribed drugs in clinical practice They are usually well tolerated and effectively prevent cardiovascular events Most adverse effects associated with statin therapy are muscle-related The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance' Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented

Journal ArticleDOI
05 Feb 2015-Oncogene
TL;DR: This study designs TAZ as a novel biomarker and a possible therapeutic target for BC and finds that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs).
Abstract: Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.

Journal ArticleDOI
TL;DR: The aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.
Abstract: Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin-associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10 – 15% of patients.In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was ...

Journal ArticleDOI
Heather J. Cordell1, Younghun Han2, George F. Mells3, Yafang Li2  +474 moreInstitutions (155)
TL;DR: This work discovers and validate six previously unknown risk loci for PBC and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Abstract: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Journal ArticleDOI
TL;DR: Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer.
Abstract: Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Journal ArticleDOI
TL;DR: This study identifies for the first time a fraction of vesicles from lemon juice obtained as a result of different ultracentrifugation, and shows that isolated nanovesicles inhibit cancer cell proliferation in different tumor cell lines, by activating a TRAIL-mediated apoptotic cell death.
Abstract: // Stefania Raimondo 1 , Flores Naselli 1 , Simona Fontana 1 , Francesca Monteleone 1 , Alessia Lo Dico 1 , Laura Saieva 1 , Giovanni Zito 2 , Anna Flugy 1 , Mauro Manno 3 , Maria Antonietta Di Bella 1 , Giacomo De Leo 1 , Riccardo Alessandro 1 1 Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli Studi di Palermo, sezione di Biologia e Genetica, Palermo, Italy 2 Laboratorio di Ingegneria Tissutale – Piattaforme Innovative per l’Ingegneria Tissutale (PON01–00829), Istituto Ortopedico Rizzoli, Palermo, Italy 3 Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy Correspondence to: Riccardo Alessandro, e-mail: riccardo.alessandro@unipa.it Keywords: cancer, exosome-like nanovesicles, Citrus limon L., TRAIL-mediated cell death Received: April 03, 2015 Accepted: May 08, 2015 Published: May 18, 2015 ABSTRACT Nanosized vesicles are considered key players in cell to cell communication, thus influencing physiological and pathological processes, including cancer. Nanovesicles have also been found in edible-plants and have shown therapeutic activity in inflammatory bowel diseases; however information on their role in affecting cancer progression is missing. Our study identify for the first time a fraction of vesicles from lemon juice ( Citrus limon L.), obtained as a result of different ultracentrifugation, with density ranging from 1,15 to 1,19 g/ml and specific proteomic profile. By using an in vitro approach, we show that isolated nanovesicles inhibit cancer cell proliferation in different tumor cell lines, by activating a TRAIL-mediated apoptotic cell death. Furthermore, we demonstrate that lemon nanovesicles suppress CML tumor growth in vivo by specifically reaching tumor site and by activating TRAIL-mediated apoptotic cell processes. Overall, this study suggests the possible use of plant-edible nanovesicles as a feasible approach in cancer treatment.

Journal ArticleDOI
TL;DR: Consumption of poultry meat, as part of a vegetable-rich diet, is associated with a risk reduction of developing overweight and obesity, cardiovascular diseases, and type 2 diabetes mellitus and is considered moderately protective or neutral on cancer risk.
Abstract: The relationship between the consumption of meat and health is multifaceted, and it needs to be analyzed in detail, with specific attention to the relevant differences that characterize the effects of the different meat types, as yet considered by only a limited literature. A variable but moderate energy content, highly digestible proteins (with low levels of collagen) of good nutritional quality, unsaturated lipids (mainly found in the skin and easily removed), B-group vitamins (mainly thiamin, vitamin B6, and pantothenic acid), and minerals (like iron, zinc, and copper) make poultry meat a valuable food. Epidemiological studies performed across the world, in highly diverse populations with different food preferences and nutritional habits, provide solid information on the association between poultry consumption, within a balanced diet, and good health. Consumption of poultry meat, as part of a vegetable-rich diet, is associated with a risk reduction of developing overweight and obesity, cardiovascular diseases, and type 2 diabetes mellitus. Also, white meat (and poultry in particular) is considered moderately protective or neutral on cancer risk. The relevance of poultry meat for humans also has been recognized by the UN Food and Agricultural Organization (FAO), who considers this widely available, relatively inexpensive food to be particularly useful in developing countries, where it can help to meet shortfalls in essential nutrients. Moreover, poultry meat consumption also contributes to the overall quality of the diet in specific ages and conditions (prior to conception, during pregnancy up to the end of breastfeeding, during growth, and in the geriatric age) and is suitable for those who have an increased need for calorie and protein compared to the general population.

Journal ArticleDOI
TL;DR: Gut-derived IL-17+ and IL-22+ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.
Abstract: Background The aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS). Methods ILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed. Results ILC3 characterised as Lyn − RORc − Tbet + NKp44 + cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R + cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1. Conclusions Gut-derived IL-17 + and IL-22 + ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.

Journal ArticleDOI
TL;DR: It is reported how IR could stimulate inflammatory factors to affect cell fate via multiple pathways, describing their roles on gene expression regulation, fibrosis and invasive processes.
Abstract: Ionizing radiation (IR) activates both pro-and anti-proliferative signal pathways producing an imbalance in cell fate decision. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular radiation-dependent response. Radiation therapy can modulate anti-tumour immune responses, modifying tumour and its microenvironment. In this review, we report how IR could stimulate inflammatory factors to affect cell fate via multiple pathways, describing their roles on gene expression regulation, fibrosis and invasive processes. Understanding the complex relationship between IR, inflammation and immune responses in cancer, opens up new avenues for radiation research and therapy in order to optimize and personalize radiation therapy treatment for each patient.