<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Marcuzzi, Annalisa</style></author><author><style face="normal" font="default" size="100%">Piscianz, Elisa</style></author><author><style face="normal" font="default" size="100%">Tommasini, Alberto</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The Complex Interplay between Lipids, Immune System and Interleukins in Cardio-Metabolic Diseases.</style></title><secondary-title><style face="normal" font="default" size="100%">Int J Mol Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Int J Mol Sci</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Anti-Inflammatory Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Cardiovascular Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypolipidemic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Immune System</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation</style></keyword><keyword><style  face="normal" font="default" size="100%">Interleukins</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipid Metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipids</style></keyword><keyword><style  face="normal" font="default" size="100%">Metabolic Diseases</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Dec 14</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">19</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response-and interleukins-had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/30558209?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Bossi, Fleur</style></author><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">Giudici, Fabiola</style></author><author><style face="normal" font="default" size="100%">Bramante, Alessandra</style></author><author><style face="normal" font="default" size="100%">Furlanis, Giulia</style></author><author><style face="normal" font="default" size="100%">Stenner, Elisabetta</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Carretta, Renzo</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Association between thyroid hormones and TRAIL.</style></title><secondary-title><style face="normal" font="default" size="100%">Clin Biochem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Clin. Biochem.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hyperthyroidism</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypothyroidism</style></keyword><keyword><style  face="normal" font="default" size="100%">Leukocytes, Mononuclear</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Thyroxine</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword><keyword><style  face="normal" font="default" size="100%">Triiodothyronine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Nov</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">50</style></volume><pages><style face="normal" font="default" size="100%">972-976</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;INTRODUCTION: &lt;/b&gt;Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression. This study aimed at evaluating whether overt thyroid disorders affected circulating TRAIL levels.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;TRAIL circulating levels were measured in euthyroid, hyperthyroid, and hypothyroid patients before and after thyroid function normalization. Univariate and multivariate analyses were performed to evaluate the correlation between thyroid hormones and TRAIL. Then, the stimulatory effect of both triiodothyronine (T3) and thyroxine (T4) on TRAIL was evaluated in vitro on peripheral blood mononuclear cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Circulating levels of TRAIL significantly increased in hyperthyroid and decreased in hypothyroid patients as compared to controls. Once thyroid function was restored, TRAIL levels normalized. There was an independent association between TRAIL and both fT3 and fT4. Consistent with these findings, T3 and T4 stimulated TRAIL release in vitro.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;Here we show that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. Given the overlap between the metabolic effects of thyroid hormones and TRAIL, this work sheds light on the possibility that TRAIL might be one of the molecules mediating thyroid hormones peripheral effects.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">16-17</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28551332?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">Bossi, Fleur</style></author><author><style face="normal" font="default" size="100%">Candido, Riccardo</style></author><author><style face="normal" font="default" size="100%">Stenner, Elisabetta</style></author><author><style face="normal" font="default" size="100%">Carretta, Renzo</style></author><author><style face="normal" font="default" size="100%">Barbone, Fabio</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Circulating osteoprotegerin is associated with chronic kidney disease in hypertensive patients.</style></title><secondary-title><style face="normal" font="default" size="100%">BMC Nephrol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">BMC Nephrol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Biomarkers</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Follow-Up Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypertension</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteoprotegerin</style></keyword><keyword><style  face="normal" font="default" size="100%">Random Allocation</style></keyword><keyword><style  face="normal" font="default" size="100%">Renal Insufficiency, Chronic</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 Jul 06</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">18</style></volume><pages><style face="normal" font="default" size="100%">219</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Osteoprotegerin (OPG) is a glycoprotein that plays an important regulatory role in the skeletal, vascular, and immune system. It has been shown that OPG predicts chronic kidney disease (CKD) in diabetic patients. We hypothesized that OPG could be a risk marker of CKD development also in non-diabetic hypertensive patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;A case-control study was carried out to measure circulating OPG levels in 42 hypertensive patients with CKD and in 141 hypertensive patients without CKD. A potential relationship between OPG and the presence of CKD was investigated and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of OPG that best explained the presence of CKD. Secondly, to evaluate whether OPG increase could affect the kidney, 18 C57BL/6J mice were randomized to be treated with saline or recombinant OPG every 3 weeks for 12 weeks.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Circulating OPG levels were significantly higher in hypertensive patients with CKD, and there was a significant inverse association between OPG and renal function, that was independent from other variables. ROC analysis showed that OPG levels had a high statistically predictive value on CKD in hypertensive patients, which was greater than that of hypertension. The OPG best cut-off value associated with CKD was 1109.19 ng/L. In the experimental study, OPG delivery significantly increased the gene expression of pro-inflammatory and pro-fibrotic mediators, as well as the glomerular nitrosylation of proteins.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;This study shows that OPG is associated with CKD in hypertensive patients, where it might have a higher predictive value than that of hypertension for CKD development. Secondly, we found that OPG delivery significantly increased the expression of molecular pathways involved in kidney damage. Further longitudinal studies are needed not only to evaluate whether OPG predicts CKD development but also to clarify whether OPG should be considered a risk factor for CKD.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/28683789?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bossi, Fleur</style></author><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">TRAIL modulates the immune system and protects against the development of diabetes.</style></title><secondary-title><style face="normal" font="default" size="100%">J Immunol Res</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Immunol Res</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immune System</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, TNF-Related Apoptosis-Inducing Ligand</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">2015</style></volume><pages><style face="normal" font="default" size="100%">680749</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;TRAIL or tumor necrosis factor (TNF) related apoptosis-inducing ligand is a member of the TNF superfamily of proteins, whose best characterized function is the induction of apoptosis in tumor, infected, or transformed cells through activation of specific receptors. In nontransformed cells, however, the actions of TRAIL are less well characterized. Recent studies suggest that TRAIL may be implicated in the development and progression of diabetes. Here we review TRAIL biological actions, its effects on the immune system, and how and to what extent it has been shown to protect against diabetes.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/25759846?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author><author><style face="normal" font="default" size="100%">Thomas, Merlin</style></author><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">Tikellis, Christos</style></author><author><style face="normal" font="default" size="100%">Candido, Riccardo</style></author><author><style face="normal" font="default" size="100%">Catena, Cristiana</style></author><author><style face="normal" font="default" size="100%">Mulatero, Paolo</style></author><author><style face="normal" font="default" size="100%">Barbone, Fabio</style></author><author><style face="normal" font="default" size="100%">Radillo, Oriano</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Osteoprotegerin increases in metabolic syndrome and promotes adipose tissue proinflammatory changes.</style></title><secondary-title><style face="normal" font="default" size="100%">Mol Cell Endocrinol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mol. Cell. Endocrinol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adipose Tissue</style></keyword><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Blood Glucose</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Mass Index</style></keyword><keyword><style  face="normal" font="default" size="100%">C-Reactive Protein</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Cholesterol, HDL</style></keyword><keyword><style  face="normal" font="default" size="100%">Cholesterol, LDL</style></keyword><keyword><style  face="normal" font="default" size="100%">Diet, High-Fat</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation</style></keyword><keyword><style  face="normal" font="default" size="100%">Insulin</style></keyword><keyword><style  face="normal" font="default" size="100%">Insulin Resistance</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Metabolic Syndrome X</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Obesity</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteoprotegerin</style></keyword><keyword><style  face="normal" font="default" size="100%">Triglycerides</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Aug 25</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">394</style></volume><pages><style face="normal" font="default" size="100%">13-20</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Inflammation is believed to link obesity to insulin resistance, as in the setting of metabolic syndrome (MetS). Osteoprotegerin (OPG) is a soluble protein that seems to exert proatherogenic and prodiabetogenic effects. This study aims at determining OPG levels in MetS and whether OPG might contribute to MetS development and progression.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODOLOGY/PRINCIPAL FINDINGS: &lt;/b&gt;Circulating OPG was measured in 46 patients with MetS and 63 controls, and was found significantly elevated in those with MetS. In addition, circulating and tissue OPG was significantly increased in high-fat diet (HFD) fed C57BL6 mice, which is one of the animal models for the study of MetS. To evaluate the consequences of OPG elevation, we delivered this protein to C57BL6 mice, finding that it promoted systemic and adipose tissue proinflammatory changes in association with metabolic abnormalities.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS/SIGNIFICANCE: &lt;/b&gt;These data suggest that OPG may trigger adipose tissue proinflammatory changes in MetS/HFD-induced obesity.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1-2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24998520?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Tikellis, Christos</style></author><author><style face="normal" font="default" size="100%">Candido, Riccardo</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Cooper, Mark E</style></author><author><style face="normal" font="default" size="100%">Thomas, Merlin C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation.</style></title><secondary-title><style face="normal" font="default" size="100%">Clin Sci (Lond)</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Clin. Sci.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adiposity</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Calorimetry</style></keyword><keyword><style  face="normal" font="default" size="100%">Cytokines</style></keyword><keyword><style  face="normal" font="default" size="100%">Dietary Fats</style></keyword><keyword><style  face="normal" font="default" size="100%">Energy Intake</style></keyword><keyword><style  face="normal" font="default" size="100%">Glucose Tolerance Test</style></keyword><keyword><style  face="normal" font="default" size="100%">Hyperglycemia</style></keyword><keyword><style  face="normal" font="default" size="100%">Hyperinsulinism</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation Mediators</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidation-Reduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Palmitic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Real-Time Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Nov</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">123</style></volume><pages><style face="normal" font="default" size="100%">547-55</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] has recently been shown to ameliorate the natural history of DM (diabetes mellitus). It has not been determined yet whether systemic TRAIL delivery would prevent the metabolic abnormalities due to an HFD [HF (high-fat) diet]. For this purpose, 27 male C57bl6 mice aged 8 weeks were randomly fed on a standard diet, HFD or HFD+TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection. Body composition was evaluated; indirect calorimetry studies, GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed. Pro-inflammatory cytokines, together with adipose tissue gene expression and apoptosis, were measured. TRAIL treatment reduced significantly the increased adiposity associated with an HFD. Moreover, it reduced significantly hyperglycaemia and hyperinsulinaemia during a GTT and it improved significantly the peripheral response to insulin. TRAIL reversed the changes in substrate utilization induced by the HFD and ameliorated skeletal muscle non-esterified fatty acids oxidation rate. This was associated with a significant reduction of pro-inflammatory cytokines together with a modulation of adipose tissue gene expression and apoptosis. These findings shed light on the possible anti-adipogenic and anti-inflammatory effects of TRAIL and open new therapeutic possibilities against obesity, systemic inflammation and T2DM (Type 2 DM).&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22616837?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Milani, Daniela</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">TRAIL as biomarker and potential therapeutic tool for cardiovascular diseases.</style></title><secondary-title><style face="normal" font="default" size="100%">Curr Drug Targets</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Curr Drug Targets</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Biological Markers</style></keyword><keyword><style  face="normal" font="default" size="100%">Cardiovascular Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Prognosis</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Aug</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">13</style></volume><pages><style face="normal" font="default" size="100%">1215-21</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;This review focuses on TNF-related apoptosis-inducing ligand (TRAIL), also called Apo2 ligand, a protein belonging to the TNF superfamily. TRAIL can be found either in its transmembrane or circulating form, and its mostly studied peripheral effect is the induction of cellular apoptosis. Here, we discuss the evidences supporting the use of TRAIL as biomarker of cardiovascular diseases as well as the evidences showing the potential beneficial therapeutic effects of TRAIL on cardiovascular diseases and diabetes.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22676911?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Candido, Riccardo</style></author><author><style face="normal" font="default" size="100%">Zacchigna, Serena</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">TRAIL shows potential cardioprotective activity.</style></title><secondary-title><style face="normal" font="default" size="100%">Invest New Drugs</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Invest New Drugs</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apolipoproteins E</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cardiotonic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Experimental</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Type 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetic Cardiomyopathies</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Knockout</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Jun</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">30</style></volume><pages><style face="normal" font="default" size="100%">1257-60</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated that TRAIL (administrated as either recombinant soluble TRAIL or as AAV-TRAIL expression viral vector) reduced the development of cardiomyopathy in the ApoE(-/-) diabetic mouse model. These data suggest, for the first time, that therapeutically administration of TRAIL might have a cardioprotective effect.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21197620?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Candido, Riccardo</style></author><author><style face="normal" font="default" size="100%">Sabato, Nicoletta</style></author><author><style face="normal" font="default" size="100%">Carretta, Renzo</style></author><author><style face="normal" font="default" size="100%">Corallini, Federica</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets.</style></title><secondary-title><style face="normal" font="default" size="100%">Mol Cell Endocrinol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mol. Cell. Endocrinol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Blood Glucose</style></keyword><keyword><style  face="normal" font="default" size="100%">Blood Pressure</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Weight</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Lineage</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Movement</style></keyword><keyword><style  face="normal" font="default" size="100%">Chemokine CCL2</style></keyword><keyword><style  face="normal" font="default" size="100%">Connective Tissue Growth Factor</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Insulin</style></keyword><keyword><style  face="normal" font="default" size="100%">Islets of Langerhans</style></keyword><keyword><style  face="normal" font="default" size="100%">Macrophages</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Monocytes</style></keyword><keyword><style  face="normal" font="default" size="100%">Organ Size</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteoprotegerin</style></keyword><keyword><style  face="normal" font="default" size="100%">Peptidyl-Dipeptidase A</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, Angiotensin, Type 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Systole</style></keyword><keyword><style  face="normal" font="default" size="100%">Transforming Growth Factor beta</style></keyword><keyword><style  face="normal" font="default" size="100%">Vascular Cell Adhesion Molecule-1</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Jan 1</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">331</style></volume><pages><style face="normal" font="default" size="100%">136-42</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Although serum osteoprotegerin (OPG) is significantly increased in diabetic subjects, its potential role in beta cell dysfunction has not been investigated. This study aimed to assess the effect of full-length OPG administered in vivo in mice on pancreatic islet structure and function and its interaction with the renin-angiotensin system (RAS). OPG-treated mice showed increased islet monocyte/macrophage infiltration, fibrosis and apoptosis with reduction of islet function. The remodeling of islet architecture was associated with increased pancreatic expression of components of the RAS, growth factor genes (transforming growth factor β and connective tissue growth factor) and inflammatory molecules (monocyte chemotactic protein-1 and vascular adhesion molecule type 1). Prevention of these changes with improvement of insulin secretion was observed in ramipril treated animals. Our data suggest that OPG might play an important role in promoting beta cell dysfunction and that the upregulation of the local RAS represents one possible mechanism responsible for the OPG-induced beta cell dysfunction.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/20832449?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">Pickering, Raelene J</style></author><author><style face="normal" font="default" size="100%">Tsorotes, Despina</style></author><author><style face="normal" font="default" size="100%">Wang, Bo</style></author><author><style face="normal" font="default" size="100%">Bernardi, Stella</style></author><author><style face="normal" font="default" size="100%">Kantharidis, Phillip</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author><author><style face="normal" font="default" size="100%">Thomas, Merlin C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Osteoprotegerin promotes vascular fibrosis via a TGF-β1 autocrine loop.</style></title><secondary-title><style face="normal" font="default" size="100%">Atherosclerosis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Atherosclerosis</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apolipoproteins E</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Proliferation</style></keyword><keyword><style  face="normal" font="default" size="100%">Collagen</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibronectins</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibrosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Transgenic</style></keyword><keyword><style  face="normal" font="default" size="100%">Muscle, Smooth, Vascular</style></keyword><keyword><style  face="normal" font="default" size="100%">Myocytes, Smooth Muscle</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteoprotegerin</style></keyword><keyword><style  face="normal" font="default" size="100%">Platelet-Derived Growth Factor</style></keyword><keyword><style  face="normal" font="default" size="100%">Transforming Growth Factor beta1</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">218</style></volume><pages><style face="normal" font="default" size="100%">61-8</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;This study was designed to evaluate the potential role of osteoprotegerin (OPG) in arterial fibrosis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Aortic samples were analyzed after in vivo treatment of ApoE(-/-) mice with recombinant human OPG. Mouse vascular smooth muscle cells (VSMC) were exposed in vitro to recombinant OPG and analyzed for markers of inflammation and fibrosis, such as fibronectin, collagen I, III, IV and transforming growth factor-β1 (TGF-β1). Conversely, the potential modulation of endogenous OPG expression and release by VSMC was analyzed in response to different pro-atherosclerotic cytokines, TGF-β1, platelet derived growth factor (PDGF) and angiogensin II (Ang II).&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;In vivo treatment with human OPG induced signs of fibrosis and up-regulated the arterial expression of TGF-β1. Consistently, in vitro treatment of VSMC with human OPG induced the expression of fibronectin, collagen type I, III, IV, metalloprotein-2 (MMP-2) and MMP-9, as well as of TGF-β1. On the other hand, exposure to recombinant TGF-β1 promoted the expression/release of endogenous OPG and mediated the increase of OPG release induced by PDGF and Ang II in VSMC.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Taken together, these data support a pathogenic role for OPG in the development and progression of atherosclerotic lesions and suggest the existence of a vicious circle between TGF-β1 and OPG.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21679949?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Zauli, Giorgio</style></author><author><style face="normal" font="default" size="100%">Toffoli, Barbara</style></author><author><style face="normal" font="default" size="100%">di Iasio, Maria Grazia</style></author><author><style face="normal" font="default" size="100%">Celeghini, Claudio</style></author><author><style face="normal" font="default" size="100%">Fabris, Bruno</style></author><author><style face="normal" font="default" size="100%">Secchiero, Paola</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Treatment with recombinant tumor necrosis factor-related apoptosis-inducing ligand alleviates the severity of streptozotocin-induced diabetes.</style></title><secondary-title><style face="normal" font="default" size="100%">Diabetes</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Diabetes</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Experimental</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Islets of Langerhans</style></keyword><keyword><style  face="normal" font="default" size="100%">Leukocytes, Mononuclear</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Recombinant Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Suppressor of Cytokine Signaling Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">TNF-Related Apoptosis-Inducing Ligand</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2010 May</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">59</style></volume><pages><style face="normal" font="default" size="100%">1261-5</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;OBJECTIVE: &lt;/b&gt;To evaluate the potential therapeutic effect of recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) treatment in a model of type 1 diabetes.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESEARCH DESIGN AND METHODS: &lt;/b&gt;Recombinant TRAIL was added in vitro to primary human and mouse peripheral blood mononuclear cells (PBMCs) and isolated human islets to evaluate the expression of the immunoregulatory gene SOCS1. Diabetes was induced by five consecutive daily injections of low-concentration (50 mg/kg) streptozotocin (STZ) in C57 black mice (n = 24). A group of these mice (n = 12) was co-injected with recombinant TRAIL (20 microg/day) for 5 days, and the diabetic status (glycemia and body weight) was followed over time. After 6 weeks, circulating levels of insulin, TNF-alpha, and osteoprotegerin (OPG) were measured, and animals were killed to perform the histological analysis of the pancreas.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;The in vitro exposure of both PBMCs and human islets to recombinant TRAIL significantly upregulated the expression of SOCS1. With respect to STZ-treated animals, mice co-injected with STZ+TRAIL were characterized by 1) lower levels of hyperglycemia, 2) higher levels of body weight and insulinemia, 3) a partial preservation of pancreatic islets with normal morphology, and 4) a lower expression of both systemic (TNF-alpha and OPG) and pancreatic (vascular cell adhesion molecule [VCAM]-1) inflammatory markers.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Overall, these data demonstrate that the administration of recombinant TRAIL ameliorates the severity of STZ-induced type 1 diabetes, and this effect was accompanied by the upregulation of SOCS1 expression.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/20185810?dopt=Abstract</style></custom1></record></records></xml>