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931.
Martin Tauschmann Barbara Prietl Gerlies Treiber Gregor Gorkiewicz Patrizia Kump Christoph H?genauer Thomas R. Pieber 《PloS one》2013,8(11)
The gastrointestinal immune system is involved in the development of several autoimmune-mediated diseases, including inflammatory bowel disease, multiple sclerosis, and type 1 diabetes mellitus. Alterations in T-cell populations, especially regulatory T cells (Tregs), are often evident in patients suffering from these diseases. To be able to detect changes in T-cell populations in diseased tissue, it is crucial to investigate T-cell populations in healthy individuals, and to characterize their variation among different regions of the gastrointestinal (GI) tract. While limited data exist, quantitative data on biopsies systematically drawn from various regions of the GI tract are lacking, particularly in healthy young humans. In this report, we present the first systematic assessment of how T cells—including Tregs—are distributed in the gastrointestinal mucosa throughout the GI tract of healthy young humans by means of multi-parameter FACS analysis. Gastroduodenoscopy and colonoscopy were performed on 16 healthy volunteers aged between 18 and 32. Biopsies were drawn from seven GI regions, and were used to determine the frequencies of CD8+-, CD4+- and Tregs in the gastrointestinal mucosa by means of multi-parameter FACS analysis. Our data show that there is significant variation in the baseline T-cell landscape along the healthy human gastrointestinal tract, and that mucosal T-cell analyses from a single region should not be taken as representative of the entire gastrointestinal tract. We show that certain T-cell subsets in the gastrointestinal mucosa vary significantly among regions; most notably, that Tregs are enriched in the appendiceal orifice region and the ascending colon, and that CD8pos T cells are enriched in the gastric mucosa. 相似文献
932.
Patrizia Gena Maria Mastrodonato Piero Portincasa Elena Fanelli Donatella Mentino Amaia Rodríguez Raúl A. Marinelli Catherine Brenner Gema Frühbeck Maria Svelto Giuseppe Calamita 《PloS one》2013,8(10)
One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma. 相似文献
933.
Kevin B. Myant Patrizia Cammareri Ewan J. McGhee Rachel A. Ridgway David J. Huels Julia B. Cordero Sarah Schwitalla Gabriela Kalna Erinn-Lee Ogg Dimitris Athineos Paul Timpson Marcos Vidal Graeme I. Murray Florian R. Greten Kurt I. Anderson Owen J. Sansom 《Cell Stem Cell》2013,12(6):761-773
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934.
Alessandra De Robertis Federica Mennillo Marco Rossi Silvia Valensin Patrizia Tunici Elisa Mori Nicola Caradonna Maurizio Varrone Massimiliano Salerno 《PloS one》2014,9(5)
Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas. 相似文献
935.
Orla M. Doyle Eric Westman Andre F. Marquand Patrizia Mecocci Bruno Vellas Magda Tsolaki Iwona K?oszewska Hilkka Soininen Simon Lovestone Steve C. R. Williams Andrew Simmons 《PloS one》2014,9(8)
We propose a novel approach to predicting disease progression in Alzheimer’s disease (AD) – multivariate ordinal regression – which inherently models the ordered nature of brain atrophy spanning normal aging (CTL) to mild cognitive impairment (MCI) to AD. Ordinal regression provides probabilistic class predictions as well as a continuous index of disease progression – the ORCHID (Ordinal Regression Characteristic Index of Dementia) score. We applied ordinal regression to 1023 baseline structural MRI scans from two studies: the US-based Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the European based AddNeuroMed program. Here, the acquired AddNeuroMed dataset was used as a completely independent test set for the ordinal regression model trained on the ADNI cohort providing an optimal assessment of model generalizability. Distinguishing CTL-like (CTL and stable MCI) from AD-like (MCI converters and AD) resulted in balanced accuracies of 82% (cross-validation) for ADNI and 79% (independent test set) for AddNeuroMed. For prediction of conversion from MCI to AD, balanced accuracies of 70% (AUC of 0.75) and 75% (AUC of 0.81) were achieved. The ORCHID score was computed for all subjects. We showed that this measure significantly correlated with MMSE at 12 months (ρ = –0.64, ADNI and ρ = –0.59, AddNeuroMed). Additionally, the ORCHID score can help fractionate subjects with unstable diagnoses (e.g. reverters and healthy controls who later progressed to MCI), moderately late converters (12–24 months) and late converters (24–36 months). A comparison with results in the literature and direct comparison with a binary classifier suggests that the performance of this framework is highly competitive. 相似文献
936.
Guya Diletta Marconi Susi Zara Marianna De Colli Valentina Di Valerio Monica Rapino Patrizia Zaramella Arben Dedja Veronica Macchi Raffaele De Caro Andrea Porzionato 《PloS one》2014,9(8)
Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized. 相似文献
937.
Production of Chlorella vulgaris as a source of essential fatty acids in a tubular photobioreactor continuously fed with air enriched with CO2 at different concentrations
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Erika Y. Ortiz Montoya Alessandro A. Casazza Bahar Aliakbarian Patrizia Perego Attilio Converti João C. Monteiro de Carvalho 《Biotechnology progress》2014,30(4):916-922
To reduce CO2 emissions and simultaneously produce biomass rich in essential fatty acids, Chlorella vulgaris CCAP 211 was continuously grown in a tubular photobioreactor using air alone or air enriched with CO2 as the sole carbon source. While on one hand, nitrogen‐limited conditions strongly affected biomass growth, conversely, they almost doubled its lipid fraction. Under these conditions using air enriched with 0, 2, 4, 8, and 16% (v/v) CO2, the maximum biomass concentration was 1.4, 5.8, 6.6, 6.8, and 6.4 gDB L?1 on a dry basis, the CO2 consumption rate 62, 380, 391, 433, and 430 L?1 day?1, and the lipid productivity 3.7, 23.7, 24.8, 29.5, and 24.4 mg L?1 day?1, respectively. C. vulgaris was able to grow effectively using CO2‐enriched air, but its chlorophyll a (3.0–3.5 g 100gDB?1), chlorophyll b (2.6–3.0 g 100gDB?1), and lipid contents (10.7–12.0 g 100gDB?1) were not significantly influenced by the presence of CO2 in the air. Most of the fatty acids in C. vulgaris biomass were of the saturated series, mainly myristic, palmitic, and stearic acids, but a portion of no less than 45% consisted of unsaturated fatty acids, and about 80% of these were high added‐value essential fatty acids belonging to the ω3 and ω6 series. These results highlight that C. vulgaris biomass could be of great importance for human health when used as food additive or for functional food production. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:916–922, 2014 相似文献
938.
Silvana Galderisi Alessandro Rossi Paola Rocca Alessandro Bertolino Armida Mucci Paola Bucci Paola Rucci Dino Gibertoni Eugenio Aguglia Mario Amore Antonello Bellomo Massimo Biondi Roberto Brugnoli Liliana Dell'Osso Diana De Ronchi Gabriella Di Emidio Massimo Di Giannantonio Andrea Fagiolini Carlo Marchesi Palmiero Monteleone Lucio Oldani Federica Pinna Rita Roncone Emilio Sacchetti Paolo Santonastaso Alberto Siracusano Antonio Vita Patrizia Zeppegno Mario Maj Italian Network For Research on Psychoses 《World psychiatry》2014,13(3):275-287
In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia. 相似文献
939.
Clara Natoli Davide Brocco Isabella Sperduti Antonio Nuzzo Nicola Tinari Michele De Tursi Antonino Grassadonia Lorenzo Mazzilli Stefano Iacobelli Teresa Gamucci Patrizia Vici the “FOLLOW-UP” Study Group 《PloS one》2014,9(4)
Purpose
Breast cancer follow-up procedures after primary treatment are still a controversial issue. Aim of this study was to investigate, through a web-based survey, surveillance methodologies selected by Italian oncologists in everyday clinical practice.Methods
Referents of Italian medical oncology units were invited to participate to the study via e-mail through the SurveyMonkey website. Participants were asked how, in their institution, exams of disease staging and follow-up are planned in asymptomatic women and if surveillance continues beyond the 5th year.Results
Between February and May 2013, 125 out of 233 (53.6%) invited referents of Italian medical oncology units agreed to participate in the survey. Ninety-seven (77.6%) referents state that modalities of breast cancer follow-up are planned according to the risk of disease progression at diagnosis and only 12 (9.6%) oncology units apply the minimal follow-up procedures according to international guidelines. Minimal follow-up is never applied in high risk asymptomatic women. Ninety-eight (78.4%) oncology units continue follow-up in all patients beyond 5 years.Conclusions
Our survey shows that 90.4% of participating Italian oncology units declare they do not apply the minimal breast cancer follow-up procedures after primary treatment in asymptomatic women, as suggested by national and international guidelines. Interestingly, about 80.0% of interviewed referents performs the so called “tailored follow-up”, high intensity for high risk, low intensity for low risk patients. There is an urgent need of randomized clinical trials able to determine the effectiveness of risk-based follow-up modalities, their ideal frequency and persistence in time. 相似文献940.
Stefano Mattioli Andrea Farioli Patrizia Legittimo Lucia Miligi Alessandra Benvenuti Alessandra Ranucci Alberto Salvan Roberto Rondelli Corrado Magnani 《PloS one》2014,9(11)