28 results on '"MARTA NOVO"'
Search Results
2. Transcriptome analysis of aphids exposed to glandular trichomes in tomato reveals stress and starvation related responses
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Rosario Planelló, Lola Llorente, Óscar Herrero, Marta Novo, Lidia Blanco-Sánchez, Juan Antonio Díaz-Pendón, Rafael Fernández-Muñoz, Victoria Ferrero, and Eduardo de la Peña
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Medicine ,Science - Abstract
Abstract Understanding the responses of insect herbivores to plant chemical defences is pivotal for the management of crops and pests. However, the mechanisms of interaction are not entirely understood. In this study, we compared the whole transcriptome gene expression of the aphid Macrosiphum euphorbiae grown on two different varieties of tomato that differ in their inducible chemical defences. We used two isogenic lines of tomato with a shared genetic background that only differ in the presence of type IV glandular trichomes and their associated acylsucrose excretions. This works also reports a de novo transcriptome of the aphid M. euphorbiae. Subsequently, we identified a unique and distinct gene expression profile for the first time corresponding to aphid´s exposure to type IV glandular trichomes and acylsugars. The analysis of the aphid transcriptome shows that tomato glandular trichomes and their associated secretions are highly efficient in triggering stress-related responses in the aphid, and demonstrating that their role in plant defence goes beyond the physical impediment of herbivore activity. Some of the differentially expressed genes were associated with carbohydrate, lipid and xenobiotic metabolisms, immune system, oxidative stress response and hormone biosynthesis pathways. Also, the observed responses are compatible with a starvation syndrome. The transcriptome analysis puts forward a wide range of genes involved in the synthesis and regulation of detoxification enzymes that reveal important underlying mechanisms in the interaction of the aphid with its host plant and provides a valuable genomic resource for future study of biological processes at the molecular level using this aphid.
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- 2022
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3. Applying sunscreens on earthworms: Molecular response of Eisenia fetida after direct contact with an organic UV filter
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Dolores Trigo, Ana-Belén Muñiz-González, Marta Novo, S. Casquero, and J.L. Martínez Guitarte
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Receptors, Steroid ,Eisenia fetida ,Environmental Engineering ,010504 meteorology & atmospheric sciences ,UV filter ,Endocrine System ,Endocrine Disruptors ,010501 environmental sciences ,medicine.disease_cause ,01 natural sciences ,Superoxide dismutase ,chemistry.chemical_compound ,Gene expression ,medicine ,Animals ,Environmental Chemistry ,Oligochaeta ,Waste Management and Disposal ,0105 earth and related environmental sciences ,biology ,Superoxide Dismutase ,biology.organism_classification ,Pollution ,Endocrine disruptor ,chemistry ,Biochemistry ,biology.protein ,Xenobiotic ,Ecdysone receptor ,Sunscreening Agents ,Genotoxicity - Abstract
The use of organic Ultraviolet (UV) filters has increased in the last years, either in sunscreens, other cosmetics, or even food packaging. These filters may end up in soil and water since the Wastewater Treatment Plants may not successfully remove them. Among them, benzophenones are known to act as endocrine disruptors. However, most of the studies are directed towards vertebrates and aquatic invertebrates, while there is a lack of information on the molecular mechanisms affected by these compounds on soil dwelling invertebrates. Here, we study the impact of direct acute (48 h) contact of 4-hydroxybenzophenone (4-OHBP) at two sublethal concentrations (0.02 and 0.2 mg/mL) on gene expression of the earthworm Eisenia fetida. Investigated genes were involved in endocrine pathways, stress response, detoxification mechanisms, genotoxicity, energy metabolism and epigenetics. Three of them were identified for the first time in earthworms. Our results suggest that exposure to 4-OHBP affected endocrine pathways, causing an increase in the Ecdysone receptor gene (EcR) expression. Moreover, the UV filter induced changes in the CuZn superoxide dismutase gene (CuZn SOD), indicating an effect in the stress response. Finally, significant changes were detected for glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) expression, indicating that energy metabolism is influenced by the 4-OHBP and highlighting the risks of using GAPDH as an internal reference for Real Time PCR.
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- 2019
4. Oleuropein, a component of extra virgin olive oil, lowers postprandial glycaemia in healthy subjects
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Valentina Castellani, Romano Silvestri, Cristina Nocella, Simona Bartimoccia, Vittoria Cammisotto, Marta Novo, Francesco Violi, Lorenzo Loffredo, and Roberto Carnevale
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0301 basic medicine ,Pharmacology ,medicine.medical_specialty ,Meal ,030109 nutrition & dietetics ,Isoprostane ,business.industry ,Insulin ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Placebo ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Postprandial ,Endocrinology ,chemistry ,Oleuropein ,Internal medicine ,Medicine ,Hydroxytyrosol ,Pharmacology (medical) ,business ,Oxidative stress - Abstract
AIMS Extra virgin olive oil lowers postprandial glycaemia. We investigated if oleuropein, a component of extra virgin olive oil, exerts a similar effect on postprandial glycaemia and the underlying mechanism. METHODS Twenty healthy subjects were randomly allocated in a cross-over design to 20 mg oleuropein or placebo immediately before lunch. Postprandial glycaemia along with blood insulin, dipeptidyl-peptidase-4 (DPP-4) and glucagon-like peptide-1 and oxidative stress, which included soluble NADPH oxidase-derived peptide activity (sNox2-dp), 8-iso-prostaglandin-2α and platelet p47phox phosphorylation, were analysed before and 2 h after meal. RESULTS After 2 h, subjects who assumed oleuropein had significantly lower blood glucose, DPP-4 activity and higher insulin and glucagon-like peptide-1 compared to placebo. Furthermore, sNox2-dp, 8-iso-PGF2α and platelet p47phox phosphorylation were significantly lower in oleuropein- compared to placebo-treated subjects. DPP-4 significantly correlated with sNox2-dp [Spearman's rho (Rs) = 0.615; P
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- 2018
5. Endocrine disruptors in soil: Effects of bisphenol A on gene expression of the earthworm Eisenia fetida
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I. Verdú, José-Luis Martínez-Guitarte, Marta Novo, and Dolores Trigo
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0301 basic medicine ,Eisenia fetida ,Health, Toxicology and Mutagenesis ,Gene Expression ,Physiology ,Endocrine Disruptors ,010501 environmental sciences ,Biology ,Ecotoxicology ,medicine.disease_cause ,01 natural sciences ,Soil ,03 medical and health sciences ,chemistry.chemical_compound ,Phenols ,Detoxification ,Gene expression ,medicine ,Animals ,Soil Pollutants ,Metallothionein ,Endocrine system ,Epigenetics ,Benzhydryl Compounds ,Oligochaeta ,0105 earth and related environmental sciences ,Public Health, Environmental and Occupational Health ,General Medicine ,biology.organism_classification ,Pollution ,030104 developmental biology ,chemistry ,Xenobiotic ,Biomarkers ,Genotoxicity - Abstract
Xenobiotics such as bisphenol A (BPA), are present in biosolids, which are applied as organic fertilizers in agricultural fields. Their effects on soil life have been poorly assessed, and this is particularly important in the case of earthworms, which represent the main animal biomass in this medium. In the present work we study the impacts of BPA on gene expression of Eisenia fetida, a widely used ecotoxicological model. Chronic soil tests and acute contact tests were performed, and gene expression was analyzed in total tissue and in masculine reproductive organs of the earthworms. The genes studied in this research played a role in endocrine pathways, detoxification mechanisms, stress response, epigenetics, and genotoxicity. Most of the genes were identified for the first time, providing potentially useful biomarkers for future assessments. For chronic exposures, no changes were detected in whole-body tissue; however, masculine reproductive organs showed changes in the expression of genes related to endocrine function (EcR, MAPR, AdipoR), epigenetic mechanisms (DNMTs), genotoxicity (PARP1), and stress responses (HSC70 4). For acute exposures, the expression of one epigenetic-related gene was altered for both whole-body tissues and male reproductive organs (Piwi2). Further changes were detected for whole-body tissues involved in detoxification (Metallothionein), stress (HSC70 4), and genotoxicity (PARP1) mechanisms. Acute exposure effects were also tested in whole-body tissues of juveniles, showing changes in the expression of Metallothionein and Piwi2. The molecular changes found in the analyzed earthworms indicate that exposure to BPA may have negative implications in their populations. Particularly interesting are the alterations related to epigenetic mechanisms, which suggest that future generations may be impacted. This study is the first to evaluate the molecular effects of BPA on soil organisms, and further assays will be necessary to better characterize the true environmental repercussions. Capsule: Levels of gene expression in total-body tissues and masculine reproductive organs were analyzed in earthworms after exposure to bisphenol A and we observed associated changes in detoxification, endocrine, epigenetic, genotoxic and stress pathways.
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- 2018
6. Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis
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Lorenzo Loffredo, Simona Battaglia, Francesco Violi, Gaetano Pannitteri, M. Del Ben, Marta Novo, Francesco Baratta, Cristina Nocella, P. Ludovica, Roberto Carnevale, Fabrizio Ceci, and Francesco Angelico
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Male ,Time Factors ,Brachial Artery ,Endocrinology, Diabetes and Metabolism ,Rome ,Medicine (miscellaneous) ,030204 cardiovascular system & hematology ,Dinoprost ,medicine.disease_cause ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Chocolate ,Endothelial dysfunction ,education.field_of_study ,Cross-Over Studies ,Nutrition and Dietetics ,Fatty liver ,food and beverages ,Middle Aged ,Vasodilation ,Treatment Outcome ,Biochemistry ,NADPH Oxidase 2 ,cardiovascular system ,Female ,030211 gastroenterology & hepatology ,Cardiology and Cardiovascular Medicine ,Adult ,medicine.medical_specialty ,Population ,Dark chocolate ,Nitric Oxide ,03 medical and health sciences ,food ,Internal medicine ,medicine ,Humans ,education ,business.industry ,medicine.disease ,food.food ,Oxidative Stress ,Milk Chocolate ,Cross-Sectional Studies ,Endocrinology ,cocoa ,endothelial function ,nicotinamide adenine dinucleotide phosphate oxidase ,non-alcoholic steatohepatitis ,oxidative stress ,polyphenols ,medicine (miscellaneous) ,endocrinology, diabetes and metabolism ,nutrition and dietetics ,cardiology and cardiovascular medicine ,Endothelium, Vascular ,Steatosis ,Steatohepatitis ,business ,Biomarkers ,Oxidative stress - Abstract
Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH.In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa85%) versus low content (milk chocolate, cocoa35%) of polyphenols on FMD and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p 0.001 and from 15.9 ± 3.6 to 20.6 ± 4.9 μM, p 0.001, respectively) in subjects given dark but not in those given milk chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p 0.001) and NOx (Rs: 0.557; p 0.001).Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients.
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- 2018
7. Low-grade endotoxemia, gut permeability and platelet activation in patients with impaired fasting glucose
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Simona Bartimoccia, Marta Novo, Francesco Baratta, Cristina Nocella, M. Del Ben, Roberto Carnevale, Vittoria Cammisotto, Daniele Pastori, Francesco Angelico, Sebastiano Sciarretta, Giovanni Targher, and Francesco Violi
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Blood Glucose ,Lipopolysaccharides ,Male ,0301 basic medicine ,endocrine system diseases ,P-selectin ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Oxidized low density lipoprotein ,0302 clinical medicine ,impaired blood glucose ,Nutrition and Dietetics ,Zonulin ,Fasting ,Middle Aged ,Lipopolysaccharide ,Platelet activation ,Lipoproteins, LDL ,Female ,Cardiology and Cardiovascular Medicine ,Cholera Toxin ,medicine.medical_specialty ,liposaccarides ,platelet activation ,Permeability ,03 medical and health sciences ,Internal medicine ,Diabetes mellitus ,Glucose Intolerance ,medicine ,Humans ,Protein Precursors ,Aged ,Chi-Square Distribution ,Haptoglobins ,business.industry ,Case-control study ,nutritional and metabolic diseases ,medicine.disease ,Impaired fasting glucose ,Endotoxemia ,Gastrointestinal Tract ,Oxidative Stress ,Cross-Sectional Studies ,030104 developmental biology ,Endocrinology ,Case-Control Studies ,Multivariate Analysis ,Linear Models ,business ,Body mass index ,Biomarkers ,Oxidative stress - Abstract
Impaired fasting glucose (IFG) is associated with an increased risk of cardiovascular disease but the underlying mechanisms are still unclear. Aim of the study was to investigate the interplay between platelet activation, lipopolysaccharides (LPS) and markers of oxidative stress in patients with IFG and control subjects.We performed a cross-sectional study including 35 patients with IFG and 35 control subjects who were well comparable for age, sex, body mass index and smoking history. Serum levels of LPS, zonulin (a marker of gut permeability), oxidized LDL and plasma levels of soluble P-selectin, were measured. Patients with IFG had significantly higher levels of sP-selectin, LPS, zonulin and oxLDL compared to control subjects. The IFG status (beta coefficient: 0.518, p 0.001), higher LPS (beta coefficient: 0.352, p = 0.001) and female sex (beta coefficient: 0.179, p = 0.042) were independently associated with higher sP-selectin; in addition, oxLDL was positively associated with sP-selectin (r = 0.530, p 0.001) and LPS (r = 0.529, p = 0.001). In IFG patients, we found a significant association between LPS and zonulin (r = 0.521, p = 0.001); this association was confirmed at multivariable analysis (beta coefficient: 0.512, p = 0.007).Our study provides evidence that patients with IFG have increased platelet activation, and suggests LPS as a potential trigger for in vivo platelet activation in this patient population.
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- 2017
8. Relationship of PCSK9 and Urinary Thromboxane Excretion to Cardiovascular Events in Patients With Atrial Fibrillation
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Daniele Pastori, Cristina Nocella, Alessio Farcomeni, Simona Bartimoccia, Maria Santulli, Fortunata Vasaturo, Roberto Carnevale, Danilo Menichelli, Francesco Violi, Pasquale Pignatelli, Mirella Saliola, Marco Antonio Casciaro, Domenico Ferro, Tommasa Vicario, Fabiana Albanese, Francesco Cribari, Alberto Paladino, Francesco Del Sole, Marta Novo, Vittoria Cammisotto, Paola Andreozzi, Tiziana Di Stefano, Patrizia Iannucci, and Elio Sabbatini
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Male ,medicine.medical_specialty ,animal structures ,Thromboxane ,Urinary system ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Atrial Fibrillation ,medicine ,risk factors ,Humans ,Prospective Studies ,030212 general & internal medicine ,Myocardial infarction ,Stroke ,Aged ,business.industry ,cholesterol ,myocardial infarction ,platelets ,stroke ,Cardiovascular Diseases ,Female ,Incidence ,Proprotein Convertase 9 ,Thromboxane B2 ,Cardiology and Cardiovascular Medicine ,PCSK9 ,fungi ,Atrial fibrillation ,medicine.disease ,Proprotein convertase ,Cardiology ,Kexin ,Settore SECS-S/01 - Statistica ,business - Abstract
Background: Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No...
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- 2017
9. Is There an Interplay Between Adherence to Mediterranean Diet, Antioxidant Status, and Vascular Disease in Atrial Fibrillation Patients?
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Daniele Pastori, Francesco Violi, Danilo Menichelli, Pasquale Pignatelli, Roberto Carnevale, Marta Novo, Isabella Leo, Cristina Nocella, and Simona Bartimoccia
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Male ,medicine.medical_specialty ,GPX3 ,Mediterranean diet ,atrial fibrillation ,cardiovascular events ,gluthatione peroxidase ,mediterranean diet ,physiology ,biochemistry ,molecular biology ,clinical biochemistry ,cell biology ,Physiology ,Clinical Biochemistry ,030204 cardiovascular system & hematology ,Diet, Mediterranean ,Biochemistry ,Gastroenterology ,Superoxide dismutase ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Vascular Diseases ,030212 general & internal medicine ,Prospective cohort study ,Molecular Biology ,Aged ,General Environmental Science ,Aged, 80 and over ,Glutathione Peroxidase ,biology ,Superoxide Dismutase ,Proportional hazards model ,Vascular disease ,business.industry ,Incidence ,Incidence (epidemiology) ,Atrial fibrillation ,Cell Biology ,medicine.disease ,Surgery ,Treatment Outcome ,biology.protein ,Patient Compliance ,Regression Analysis ,General Earth and Planetary Sciences ,Female ,business - Abstract
Mediterranean Diet (Med-Diet) is associated with reduced incidence of vascular events (VEs) in atrial fibrillation (AF), but the mechanism accounting for its beneficial effect is only partially known. We hypothesized that Med-Diet may reduce VEs by improving antioxidant status, as assessed by glutathione peroxidase 3 (GPx3) and superoxide dismutase (SOD). We performed a prospective cohort study investigating the relationship between adherence to Med-Diet, serum baseline GPx3 and SOD activities, and the occurrence of VEs in 690 AF patients. GPx3 activity was directly associated with Med-Diet score (B = 0.192, p 0.001) and inversely with age (B = -0.124, p = 0.001), after adjustment for potential confounders; Med-Diet weakly affected SOD levels. During a mean follow-up of 46.1 ± 28.2 months, 89 VEs were recorded; patients with VEs had lower GPx3 levels compared with those without VEs (p = 0.002); and no differences regarding SOD activity were found. Multivariable Cox regression analysis showed that age (Hazard ratio [HR]:1.065, p 0.001), logGPx3 (above median, HR: 0.629, p 0.05), and Med-Diet score (HR: 0.547, p 0.05) predicted VEs. Med-Diet favorably modulates antioxidant activity of GPx3 in AF, resulting in reduced VEs rate. We hypothesize that the modulation of GPx3 levels by Med-Diet could represent an additional nutritional strategy to prevent VEs in AF patients. Antioxid. Redox Signal. 25, 751-755.
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- 2016
10. The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study
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Valeria Raparelli, Marco Proietti, Giulio Francesco Romiti, Andrea Lenzi, Stefania Basili, The EVA Collaborative Group, Claudio Tiberti, Federica Panimolle, Andrea Isidori, Elisa Giannetta, Mary Anna Venneri, Laura Napoleone, Marta Novo, Silvia Quattrino, Simona Ceccarelli, Eleni Anastasiadou, Francesca Megiorni, Cinzia Marchese, Enrico Mangieri, Gaetano Tanzilli, Nicola Viceconte, Francesco Barillà, Carlo Gaudio, Vincenzo Paravati, Guglielmo Tellan, Evaristo Ettorre, Adriana Servello, Fabio Miraldi, Andrea Moretti, Alessandra Tanzilli, Piergiovanni Mazzonna, Suleyman Al Kindy, Riccardo Iorio, Martina Di Iorio, Gennaro Petriello, Laura Gioffrè, Eleonora Indolfi, Gaetano Pero, Nino Cocco, Loredana Iannetta, Sara Giannuzzi, Emilio Centaro, Sonia Cristina Sergi, Filippo Toriello, Eleonora Ruscio, Tommaso Todisco, Nicolò Sperduti, Giuseppe Santangelo, Giacomo Visioli, Marco Vano, Marco Borgi, Ludovica Maria Antonini, Silvia Robuffo, Claudia Tucci, Agostino Rossoni, Valeria Spugnardi, Annarita Vernile, Mariateresa Santoliquido, Verdiana Santori, Giulia Tosti, Fabrizio Recchia, Francesco Morricone, Roberto Scacciavillani, Alice Lipari, Andrea Zito, Floriana Testa, Giulia Ricci, Ilaria Vellucci, Marianna Vincenti, Silvia Pietropaolo, Camilla Scala, Nicolò Rubini, Marta Tomassi, Daria Amoroso, Lucia Stefanini, Simona Bartimoccia, Giovanni Talerico, Pasquale Pignatelli, Roberto Cangemi, Salvatore Minisola, Sergio Morelli, Antonio Fraioli, Silvia Nocchi, Mario Fontana, Sebastiano Filetti, Massimo Fiorilli, Danilo Toni, Anne Falcou, Louise Pilote, Tabeth Tsitsi Jiri, Muhammad Ahmer Wali, Amanpreet Kaur, Malik Elharram, Anna Rita Vestri, Patrizia Ferroni, Clara Crescioli, Cristina Antinozzi, Francesca Serena Pignataro, Tiziana Bellini, Alessandro Trentini, Roberto Carnevale, Cristina Nocella, Carlo Catalano, Iacopo Carbone, Nicola Galea, Giuliano Bertazzoni, Marianna Suppa, Antonello Rosa, Gioacchino Galardo, Maria Alessandroni, Lorena Cipollone, Alessandro Coppola, Mariangela Palladino, Giulio Illuminati, Fabrizio Consorti, Paola Mariani, Fabrizio Neri, Paolo Salis, Antonio Segatori, Laurent Tellini, and Gianluca Costabile
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0301 basic medicine ,Diabetes, Employment status, Gender, Ischemic heart disease, Medication adherence, Personality traits, Sex ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,030209 endocrinology & metabolism ,Disease ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,NO ,Settore MED/11 ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,gender ,sex ,Personality ,Medicine ,Social determinants of health ,Gender role ,Big Five personality traits ,Prospective cohort study ,Original Research ,media_common ,lcsh:RC648-665 ,diabetes ,business.industry ,Vascular disease ,medicine.disease ,employment status ,ischemic heart disease ,medication adherence ,personality traits ,030104 developmental biology ,business - Abstract
Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated. Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD. Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence. Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99). Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner.
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- 2019
11. Digoxin and Platelet Activation in Patients With Atrial Fibrillation: In Vivo and In Vitro Study
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Daniele Pastori, Maria Santulli, Fortunata Vasaturo, Simona Bartimoccia, Marta Novo, Roberto Carnevale, Francesco Violi, Silvia Piconese, Pasquale Pignatelli, Cristina Nocella, and Vittoria Cammisotto
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Platelets ,Blood Platelets ,Male ,Digoxin ,medicine.medical_specialty ,Cardiotonic Agents ,Thromboxane ,Blotting, Western ,In Vitro Techniques ,030204 cardiovascular system & hematology ,Thromboxane A2 ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Internal medicine ,Clinical Studies ,medicine ,Humans ,In vitro study ,Arrhythmia and Electrophysiology ,Platelet aggregation ,In patient ,Prospective Studies ,030212 general & internal medicine ,Platelet activation ,Phosphorylation ,Original Research ,Aged ,business.industry ,Group IV Phospholipases A2 ,Atrial fibrillation ,Ion Channels/Membrane Transport ,Flow Cytometry ,Platelet Activation ,medicine.disease ,Cardiology and Cardiovascular Medicine ,Increased risk ,Case-Control Studies ,Cardiology ,Female ,business ,Biomarkers ,medicine.drug - Abstract
Background Digoxin use was shown to be associated with an increased risk of cardiovascular events in atrial fibrillation ( AF ). We hypothesized that digoxin may affect cardiovascular risk by increasing platelet activation. Methods and Results Post hoc analysis of a prospective study of anticoagulated patients with AF . Patients were divided into 2 groups balanced for age, sex, and cardiovascular risk factors: digoxin users (n=132) and nonusers (n=388). Urinary excretion of 11‐dehydro‐thromboxane B 2 (TxB 2 ), a marker of platelet activation, and serum digoxin concentration ( SDC ) were measured. In vitro experiments were performed on platelets from healthy subjects and AF patients, which were incubated with scalar doses of digoxin (0.6–2.4 ng/mL) with or without prestimulation with a sub‐threshold of collagen. Median 11‐dehydro‐TxB 2 was 105.0 ( interquartile range, 60.0–190.0) ng/mg creatinine, and median SDC was 0.65 ( interquartile range, 0.40–1.00) ng/mL. Urinary 11‐dehydro‐TxB 2 and SDC were correlated ( r s =0.350, P SDC showed higher 11‐dehydro‐TxB 2 compared with non–digoxin users ( P =0.019). In vitro study showed an increased basal platelet activation in patients with AF compared with healthy subjects . Digoxin (2.4 ng/mL) induced calcium mobilization, PAC ‐1 (procaspase‐activating compound 1) and platelet aggregation in AF patients but not in healthy subjects . After pretreatment with a sub‐threshold of collagen, digoxin dose‐dependent induced calcium mobilization, arachidonic acid release, TxB 2 biosynthesis, PAC ‐1 and soluble platelet selectin expression, and platelet aggregation, which were inhibited by antibody against digoxin. Conclusions We found a significant in vivo correlation between SDC and platelet activation. Supratherapeutic SDC increased in vitro platelet aggregation via calcium‐related phospholipase A 2 phosphorylation. Our findings may have clinical implications for AF patients treated with digoxin.
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- 2018
12. Remnant Lipoprotein Cholesterol and Cardiovascular and Cerebrovascular Events in Patients with Non-Alcoholic Fatty Liver Disease
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Francesco Angelico, Daniele Pastori, Maria Del Ben, Marta Novo, Francesco Violi, Nicholas Cocomello, and Francesco Baratta
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medicine.medical_specialty ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Gastroenterology ,Article ,03 medical and health sciences ,Liver disease ,chemistry.chemical_compound ,cardiovascular events ,0302 clinical medicine ,cholesterol remnants ,Interquartile range ,Internal medicine ,NAFLD ,Medicine ,Risk factor ,business.industry ,Cholesterol ,lcsh:R ,Hazard ratio ,Fatty liver ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,digestive system diseases ,chemistry ,lipids (amino acids, peptides, and proteins) ,030211 gastroenterology & hepatology ,Metabolic syndrome ,business ,Lipoprotein - Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by an atherogenic dyslipidaemia and an increased cardiovascular risk. Remnant lipoprotein cholesterol (RLP-C) is emerging as a novel cardiovascular risk factor, but its predictive value in patients with NAFLD is unknown. We investigated factors affecting RLP-C levels, and the association with major adverse cardiovascular and cerebrovascular events (MACCE) in NAFLD. A prospective observational cohort study was carried out including 798 unselected patients with cardio-metabolic diseases screened by ultrasound for the presence of NAFLD. Fasting RLP-C (mg/dL) was calculated as total cholesterol—(HDL (high-density lipoprotein) + LDL (low-density-lipoprotein)). Primary endpoint of the follow-up study was a combined endpoint of MACCE. Patients with NAFLD (79.2%) had higher median fasting RLP-C in comparison to those without (27.0 vs. 20.0 mg/ dL, respectively p <, 0.001). Metabolic syndrome, NAFLD, age above median, and female sex were independently associated to fasting RLP-C above the median. In patients with NAFLD, values of RLP-C were associated with liver disease severity, as shown by the increasing value of RLP-C across tertiles of aspartate aminotransferase (AST) (p = 0.002) and gamma-glutamyl transpeptidase (GGT) (p <, 0.001). Furthermore, levels of RLP-C and Hamaguchi score, were significantly correlated (r = 0.193, p <, 0.001). During a median follow-up of 32 months (interquartile range: 14.2–51.7, 1700 person-years), 41 MACCE (2.41%/year) were registered in 596 NAFLD patients. The rate of events was higher in NAFLD patients with RLP-C above the median compared to those below (log-rank test p = 0.040). Age (hazard ratio (HR) 1.039, 95% confidence interval (CI), 1.005–1.074, p = 0.024), previous cardiovascular events (HR 2.210, 95% CI, 1.052–4.643, p = 0.036), female sex (HR 0.454, 95% CI, 0.208–0.989, p = 0.047) and RLP-C above the median (HR 2.202, 95% CI, 1.132–4.285, p = 0.020) were associated with MACCE. In conclusion, we found that NAFLD was independently associated with higher circulating RLP-C, and that high RLP-C levels were predictive of MACCE in patients with NAFLD.
- Published
- 2018
13. Corrigendum to 'Glucocorticoids impair platelet thromboxane biosynthesis in community-acquired pneumonia' [Pharmacol. Res. 131 (2018) 66-74]
- Author
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Lucia Stefanini, Roberto Cangemi, Francesco Violi, Chiara Zerbinati, Marta Novo, Camilla Calvieri, Valentina Castellani, Cristina Nocella, Roberto Carnevale, Alessandra D'Amico, and Vittoria Cammisotto
- Subjects
Pharmacology ,chemistry.chemical_compound ,Community-acquired pneumonia ,Biosynthesis ,chemistry ,business.industry ,Thromboxane ,Medicine ,Platelet ,business ,medicine.disease - Published
- 2018
14. Abstract 529: Digoxin and Platelet Activation in Atrial fibrillation Patients
- Author
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Francesco Violi, Pasquale Pignatelli, Daniele Pastori, Simona Bartimoccia, Marta Novo, Cristina Nocella, and Roberto Carnevale
- Subjects
medicine.medical_specialty ,Digoxin ,business.industry ,Atrial fibrillation ,medicine.disease ,Increased risk ,Thromboxanes ,Internal medicine ,medicine ,Cardiology ,Platelet activation ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background: digoxin use was shown to be associated with an increased risk of cardiovascular events In atrial fibrillation (AF) . We hypothesized that digoxin may affect cardiovascular risk by increasing platelet activation. Methods: This is a post-hoc analysis from an observational prospective study of AF patients treated with vitamin K antagonists. Patients were divided into two groups balanced for age, sex and cardiovascular risk factors: digoxin users (n=132) and non-users (n=388). Urinary excretion of 11-dehydro-thromboxane B 2 (TxB 2 ), a marker of platelet activation and serum digoxin concentration (SDC) were measured. In vitro experiments were performed on platelets from healthy subjects treated with scalar doses of digoxin (0.6 - 2.4 ng/ml). Results: Mean age of digoxin users was 75.2±7.2 years and 47.7% were women. Median overall 11-dehydro-TxB 2 was 105.0 (IQR 60.0-190.0) ng/mg creatinine, and median SDC was 0.65 (IQR 0.40-1.00) ng/ml. Urinary 11-dehydro-TxB 2 and SDC were significantly correlated (rS=0.350, p2 compared to non-digoxin users (p=0.019). In vitro study showed that digoxin at concentration ≥1.2 ng/ml induced calcium mobilization, arachidonic acid (AA) release, TxB 2 biosynthesis and platelet aggregation, that were inhibited by the calcium chelator Ethylenediaminetetraacetic acid (EDTA) or by the specific phospholipase A 2 (PLA 2 ) inhibitor Arachidonyl trifluoromethyl ketone (ACOOCF3). Conclusion: We found a significant in vivo correlation between SDC and platelet activation. In vitro study showed that supra-therapeutic digoxin concentrations increased platelet aggregation via calcium-related PLA 2 phosphorylation. This finding provides new insights into the association between digoxin use and cardiovascular complications in AF patients.
- Published
- 2018
15. Incidence of bleeding in patients with atrial fibrillation and advanced liver fibrosis on treatment with vitamin K or non-vitamin K antagonist oral anticoagulants
- Author
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Joseph Tassone Eliezer, Elisa Grifoni, Daniele Pastori, Rossella Marcucci, Alessio Farcomeni, Elio Sabbatini, Pasquale Pignatelli, Patrizia Iannucci, Tiziana Di Stefano, Marco Antonio Casciaro, Cristina Nocella, Francesco Violi, Simona Bartimoccia, Marta Novo, Mirella Saliola, Rony Gingis, Alberto Paladino, Francesco Perticone, Danilo Menichelli, Francesco Del Sole, Angela Sciacqua, Luigi Anastasio, Vittoria Cammisotto, Gregory Y.H. Lip, Roberto Carnevale, and Francesco Cribari
- Subjects
Oral ,Male ,Liver Cirrhosis ,medicine.medical_specialty ,Vitamin K ,medicine.drug_class ,Liver fibrosis ,Administration, Oral ,Hemorrhage ,030204 cardiovascular system & hematology ,Vitamin k ,Gastroenterology ,Risk Assessment ,03 medical and health sciences ,Outcome Assessment (Health Care) ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,In patient ,NOAC ,Atrial fibrillation ,Bleeding ,Vitamin K antagonists ,Aged ,Female ,Incidence ,Middle Aged ,Proportional Hazards Models ,Stroke ,Anticoagulants ,Atrial Fibrillation ,business.industry ,Incidence (epidemiology) ,Antagonist ,Vitamin K antagonist ,medicine.disease ,Anticoagulant therapy ,Administration ,030211 gastroenterology & hepatology ,Cardiology and Cardiovascular Medicine ,business ,Settore SECS-S/01 - Statistica - Abstract
To investigate the incidence of bleeding events in atrial fibrillation (AF) patients treated with vitamin K (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) screened for the presence of liver fibrosis (LF).Previous studies provided conflicting results on bleeding risk in AF patients with liver disease on VKAs, and no data on NOACs in this setting are available.Post-hoc analysis of a prospective, observational multicentre study including 2330 AF outpatients treated with VKAs (n = 1297) or NOACs (n = 1033). Liver damage was quantified by the FIB-4 score (3.25), a validated marker of LF. The primary endpoint was the incidence of any bleeding, according to ISTH classification.A high FIB-4 was present in 129 (5.5%) patients: 77 (5.9%) on VKA and 52 (5.0%) on NOACs (p = 0.344). During follow-up, 357 (15.3%) patients experienced a bleeding: 261 (80 major and 180 minor) with VKAs (7.2%/year), and 96 (40 major and 56 minor) with NOACs (6.4%/year). In VKA-treated patients, but not in those on NOACs, FIB-43.25 was associated with higher major bleeding (14.3% vs. 5.6%, log-rank test p 0.001). Multivariable Cox regression model showed that FIB-4 was associated with major bleeding only in VKA-treated patients (HR: 3.075, 95% CI 1.626-5.818, p = 0.001). On multivariable analysis, FIB-4 was not significantly associated with CVEs neither in VKA or NOAC-treated patients.We found a significant association between LF and major bleedings in AF patients treated with VKA, which was not evident in patients on NOACs.
- Published
- 2018
16. Blood hydrogen peroxide break-down activity in healthy subjects and in patients at risk of cardiovascular events
- Author
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Francesco Violi, Lucia Stefanini, Alessandra D'Amico, Pasquale Pignatelli, Stefania Basili, Daniele Pastori, Cristina Nocella, Marta Novo, Vittoria Cammisotto, Roberto Carnevale, and Simona Bartimoccia
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Myocardial Infarction ,Assay ,030204 cardiovascular system & hematology ,Age and sex ,Risk Assessment ,Brain Ischemia ,Cardiovascular events ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,In patient ,Prospective Studies ,Myocardial infarction ,Aged ,Aged, 80 and over ,business.industry ,Healthy subjects ,Antioxidant ,Atrial fibrillation ,Hydrogen peroxide ,Cardiology and Cardiovascular Medicine ,Reproducibility of Results ,Middle Aged ,Prognosis ,medicine.disease ,Stroke ,030104 developmental biology ,Ischemic Attack, Transient ,Cohort ,Ischemic stroke ,Disease Progression ,Cardiology ,Female ,Spectrophotometry, Ultraviolet ,business ,Biomarkers - Abstract
Antioxidant status has been shown to be associated with cardiovascular events (CVEs). The aim of the study was to develop an assay measuring serum hydrogen peroxide (HWe developed the HBA assay in 121 HS and validated it in 842 AF patients. The occurrence of CVEs was registered and correlated with HBA in AF during a median follow-up of 30.6 months (3226 patient-years). A combined endpoint of CVEs included fatal/non-fatal ischemic stroke and myocardial infarction, cardiovascular death and transient ischemic attack.In HS, median HBA was 61.2% [IQR: 52.9-69.4]. AF patients disclosed lower HBA than 30 HS balanced for age and sex (48.6% [IQR: 24.7-65.1] vs. 59.4% [IQR: 49.2-66.2], p0.001). During a mean follow-up of 30.6 months (3226 patient-years), 168 CVEs occurred (5.2%/year). A multivariable Cox's proportional hazards regression analysis showed that age group 3 (71-80 years, HR:5.419, p = 0.020), age group 4 (80 years, HR:9.783, p = 0.002), diabetes (HR:1.464, p = 0.049), previous cardiac events (HR:1.887, p = 0.001) and HBA (below median, HR:2.313, p0.001) predicted CVEs.We developed an easy assay to measure serum HBA, which was associated with CVEs in AF patients. This assay may represent an additional useful tool for cardiovascular risk stratification and should be validated in other high-risk populations.
- Published
- 2018
17. Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet
- Author
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Francesco Violi, Danilo Menichelli, Maria Santulli, Marta Novo, Cristina Nocella, Daniele Pastori, Pasquale Pignatelli, Roberto Carnevale, and Vittoria Cammisotto
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Time Factors ,Vitamin K ,Mediterranean diet ,Rome ,Myocardial Ischemia ,Kaplan-Meier Estimate ,Coronary Artery Disease ,Arrhythmias ,030204 cardiovascular system & hematology ,Diet, Mediterranean ,0302 clinical medicine ,Risk Factors ,Cardiovascular Disease ,Atrial Fibrillation ,Arrhythmia and Electrophysiology ,Prospective Studies ,Prospective cohort study ,Original Research ,Aged, 80 and over ,lipopolysaccharide ,Hazard ratio ,Atrial fibrillation ,Intestines ,Treatment Outcome ,Cohort ,lipids (amino acids, peptides, and proteins) ,Female ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,cardiovascular events ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Platelet activation ,Risk factor ,Aged ,Bacteria ,business.industry ,Anticoagulants ,atrial fibrillation ,thromboxane ,Protective Factors ,Platelet Activation ,medicine.disease ,Gastrointestinal Microbiome ,Cerebrovascular Disorders ,030104 developmental biology ,Endocrinology ,Patient Compliance ,Cerebrovascular Disease/Stroke ,business ,Biomarkers ,Mace - Abstract
Background Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut‐derived lipopolysaccharide ( LPS ) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events ( MACE ) in atrial fibrillation ( AF ) and (2) its relationship with adherence to a Mediterranean diet (Med‐diet). Methods and Results This was a prospective single‐center study including 912 AF patients treated with vitamin K antagonists (3716 patient‐years). The primary end point was a composite of MACE . Baseline serum LPS , adherence to Med‐diet (n=704), and urinary excretion of 11‐dehydro‐thromboxane B 2 (TxB 2 , n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS , respectively (log‐rank test P =0.004). Log‐ LPS (hazard ratio 1.194, P =0.009), age (hazard ratio 1.083, P P =0.004) and cardiac events (hazard ratio 1.822, P MACE . In the whole cohort, AF (versus sinus rhythm) (β 0.087, P =0.014) and low‐density lipoprotein cholesterol (β 0.069, P =0.049) were associated with circulating LPS . Furthermore, Med‐diet score (β −0.137, P LPS , with fruits (β −0.083, P =0.030) and legumes (β −0.120, P =0.002) negatively associated with log‐ LPS levels. Log‐ LPS and log‐TxB 2 were highly correlated (r=0.598, P LPS (β 0.574, P P 2 . Conclusions In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med‐diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.
- Published
- 2017
18. Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil
- Author
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Maria Del Ben, Daniele Pastori, Francesco Violi, Roberto Carnevale, Francesco Angelico, Alessio Farcomeni, Marta Novo, Vittoria Cammisotto, Cristina Nocella, and Simona Bartimoccia
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,medicine.medical_specialty ,Lipopolysaccharide ,Extra-virgin olive oil ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,Inflammation ,Oxidative phosphorylation ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Glucose Intolerance ,medicine ,Humans ,Intestinal Mucosa ,Receptor ,Olive Oil ,lipopolysaccharide ,oxidative stress ,medicine (miscellaneous) ,nutrition and dietetics ,Oxidase test ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Cross-Over Studies ,Fasting ,Middle Aged ,Impaired fasting glucose ,medicine.disease ,Postprandial Period ,Oxidative Stress ,Endocrinology ,chemistry ,Polyphenol ,NADPH Oxidase 2 ,lipids (amino acids, peptides, and proteins) ,Female ,medicine.symptom ,Settore SECS-S/01 - Statistica ,Oxidative stress - Abstract
Post-prandial phase is characterized by enhanced oxidative stress but the underlying mechanism is unclear. We investigated if gut-derived lipopolysaccharide (LPS) is implicated in this phenomenon and the effect of extra virgin olive oil (EVOO) in patients with impaired fasting glucose (IFG). This is a randomized cross-over interventional study including 30 IFG patients, to receive a lunch with or without 10 g of EVOO. Serum LPS, Apo-B48, markers of oxidative stress such as oxidized LDL (oxLDL) and soluble Nox2-derived peptide (sNox2-dp), a marker of nicotinamide-adenine-dinucleotide-phosphate oxidase isoform Nox2 activation, and plasma polyphenols were determined before, 60 and 120 min after lunch. In patients not given EVOO oxidative stress as assessed by sNox2-dp and oxLDL significantly increased at 60 and 120 min concomitantly with an increase of LPS and Apo-B48. In these patients, changes of LPS were correlated with Apo-B48 (Rs = 0.542, p = 0.002) and oxLDL (Rs = 0.463, p = 0.010). At 120 min, LPS (β − 15.73, p
- Published
- 2017
19. P2641Circulating lipopolysaccharides and risk of major adverse cardiovascular events in atrial fibrillation: association with mediterranean diet adherence
- Author
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Maria Santulli, Daniele Pastori, Roberto Carnevale, Francesco Violi, Francesco Baratta, Vittoria Cammisotto, Danilo Menichelli, Marta Novo, Cristina Nocella, and Pasquale Pignatelli
- Subjects
Cardiovascular event ,medicine.medical_specialty ,Mediterranean diet ,business.industry ,Internal medicine ,Cardiology ,Medicine ,Atrial fibrillation ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease - Published
- 2017
20. Extra Virgin Olive Oil and Cardiovascular Diseases: Benefits for Human Health
- Author
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Roberto Carnevale, Lucia Stefanini, Francesco Violi, Alessandra D'Amico, Valentina Castellani, Luca Fianchini, Vittoria Cammisotto, Cristina Nocella, and Marta Novo
- Subjects
0301 basic medicine ,Risk ,medicine.medical_specialty ,Antioxidant ,anti-atherosclerotic nutrient ,cardiovascular disease ,endothelial dysfunction ,extra virgin olive oil ,nutraceutical ,Mediterranean diet ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Vasodilator Agents ,Physiology ,Context (language use) ,Diet, Mediterranean ,Antioxidants ,Immunomodulation ,03 medical and health sciences ,chemistry.chemical_compound ,Nutraceutical ,Functional Food ,Epidemiology ,medicine ,Food Quality ,Immunology and Allergy ,Animals ,Humans ,Myocardial infarction ,Stroke ,Olive Oil ,030109 nutrition & dietetics ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,medicine.disease ,Oleic acid ,chemistry ,Cardiovascular Diseases ,Dietary Supplements ,business - Abstract
Background and Objective: The cardioprotective properties of Mediterranean Diet were demonstrated for the first time from the Seven Country Study. In the last few decades, numerous epidemiological studies, as well as intervention trial, confirmed this observation, pointing out the close relationship between the Mediterranean diet and cardiovascular diseases. In this context, extra virgin olive oil (EVOO), the most representative component of this diet, seems to be relevant in lowering the incidence of cardiovascular events, including myocardial infarction and stroke. From a chemical point of view, 98-99% of the total weight of EVOO is represented by fatty acids, especially monounsaturated fatty acids such as oleic acid. Tocopherols, polyphenols and other minor constituents represent the remaining 1-2%. All these components may potentially contribute to ”health maintenance” with their beneficial effects by EVOOO. Methods: Studies that examined the effect of EVOO supplementation in healthy subjects and in individuals at cardiovascular risk were included. Conclusion: The studies analyzed demonstrated the role of EVOO as anti-inflammatory, antioxidant and vasodilatory nutrient that may contribute to lower the atherosclerotic burden.
- Published
- 2017
21. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis
- Author
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Oliviero Riggio, Francesco Violi, Antonio Sili Scavalli, Anna Severino, Valeria Raparelli, Stefania Basili, Chiara Pasquale, Roberto Carnevale, Simona Bartimoccia, Vittoria Cammisotto, Elena De Falco, Clara Crescioli, Marta Novo, and Cristina Nocella
- Subjects
DNA, Bacterial ,Lipopolysaccharides ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,endotoxin ,Cirrhosis ,LPS ,Lipopolysaccharide ,Von Willebrand factor ,cirrhosis ,factor VIII ,hypercoagulability ,hepatology ,medicine.disease_cause ,Umbilical vein ,NO ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Escherichia coli ,Human Umbilical Vein Endothelial Cells ,Humans ,Thrombophilia ,Secretion ,Receptor ,biology ,Weibel-Palade Bodies ,business.industry ,Middle Aged ,medicine.disease ,Thrombosis ,Gastrointestinal Microbiome ,Endotoxins ,Endocrinology ,Cross-Sectional Studies ,chemistry ,Italy ,030220 oncology & carcinogenesis ,biology.protein ,030211 gastroenterology & hepatology ,Female ,business - Abstract
Patients with cirrhosis display enhanced blood levels of factor VIII, which may result in harmful activation of the clotting system; however, the underlying mechanism is unknown.We performed a cross-sectional study in patients with cirrhosis (n=61) and matched controls (n=61) comparing blood levels of factor VIII, von Willebrand factor (vWf), lipopolysaccharide (LPS) and positivity for Escherichia coli DNA. Furthermore, we performed an in vitro study to investigate if LPS, in a concentration range similar to that found in the peripheral circulation of cirrhotic patients, was able to elicit factor VIII secretion from human umbilical vein endothelial cells (HUVEC).Patients with cirrhosis displayed higher serum levels of LPS (55.8 [42.2-79.9] vs. 23.0 [7.0-34.0]pg/ml, p0.001), factor VIII (172.0 [130.0-278.0] vs. 39.0 [26.0-47.0]U/dl, p0.0001), vWf (265.0 [185.0-366.0] vs. 57.0 [48.0-65.0]U/dl, p0.001) and positivity for Escherichia coli DNA (88% vs. 3%, p0.001, n=34) compared to controls. Serum LPS correlated significantly with factor VIII (r=0.80, p0.001) and vWf (r=0.63, p0.001). Only LPS (beta-coefficient=0.70, p0.0001) independently predicted factor VIII levels. The in vitro study showed that LPS provoked factor VIII and vWf release from HUVEC via formation and secretion of Weibel-Palade bodies, a phenomenon blunted by pre-treating HUVEC with an inhibitor of Toll-like receptor 4.The study provides the first evidence that LPS derived from gut microbiota increases the systemic levels of factor VIII via stimulating its release by endothelial cells. Lay summary: Cirrhosis is associated with thrombosis in portal and systemic circulation. Enhanced levels of factor VIII have been suggested to play a role but the underlying mechanism is still unclear. Here we show that patients with cirrhosis display a concomitant increase of factor VIII and lipopolysaccharide (LPS) from Escherichia coli and suggest that LPS contributes to the release of factor VIII from endothelial cells.
- Published
- 2017
22. Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production
- Author
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Daniele Pastori, Roberto Cangemi, Camilla Calvieri, Marta Novo, Francesco Violi, Cristina Nocella, Pasquale Pignatelli, Roberto Carnevale, and Simona Bartimoccia
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,Time Factors ,Lipopolysaccharide ,Platelet Aggregation ,Thromboxane ,030204 cardiovascular system & hematology ,Dinoprost ,p38 Mitogen-Activated Protein Kinases ,chemistry.chemical_compound ,0302 clinical medicine ,Platelet ,Phosphorylation ,Receptor ,Hematology ,Middle Aged ,Receptor antagonist ,Community-Acquired Infections ,NADPH Oxidase 2 ,lipids (amino acids, peptides, and proteins) ,Female ,LPS ,community-acquired pneumonia ,oxidative stress ,platelet activation ,Adult ,Blood Platelets ,medicine.medical_specialty ,medicine.drug_class ,03 medical and health sciences ,Thromboxane A2 ,Internal medicine ,medicine ,Pneumonia, Bacterial ,Humans ,Platelet activation ,Calcium Signaling ,Aged ,Dose-Response Relationship, Drug ,Group IV Phospholipases A2 ,NADPH Oxidases ,Hydrogen Peroxide ,Enzyme Activation ,Toll-Like Receptor 4 ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,Eicosanoid ,Case-Control Studies ,Proto-Oncogene Proteins c-akt ,Ex vivo - Abstract
SummaryThe effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15–100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP patients serum endotoxins were significantly higher compared to 10 controls (145 [115–187] vs 18 [6–21] pg/ml; pSupplementary Material to this article is available online at www.thrombosis-online.com
- Published
- 2016
23. Enhanced urinary excretion of thromboxane B2 in non-alcoholic fatty liver disease. Implication for antiplatelet treatment
- Author
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Roberto Carnevale, Marta Novo, Giancarlo Labbadia, Daniele Pastori, M. Delben, Francesco Baratta, Francesco Violi, and Francesco Angelico
- Subjects
medicine.medical_specialty ,business.industry ,Fatty liver ,Non alcoholic ,Disease ,medicine.disease ,Thromboxane B2 ,chemistry.chemical_compound ,Endocrinology ,Urinary excretion ,chemistry ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2018
24. Assessment of blood hydrogen peroxide break-down activity (HBA) in healthy subjects and in patients with atrial fibrillation: relation to cardiovascular events
- Author
-
Vittoria Cammisotto, Daniele Pastori, Francesco Violi, Roberto Carnevale, Cristina Nocella, Pasquale Pignatelli, and Marta Novo
- Subjects
medicine.medical_specialty ,010405 organic chemistry ,business.industry ,Healthy subjects ,Atrial fibrillation ,010402 general chemistry ,medicine.disease ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Cardiology ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Hydrogen peroxide - Published
- 2018
25. Increased gut permeability is associated with oxidative stress in patients with NAFLD
- Author
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Maria Del Ben, Francesco Violi, Roberto Carnevale, Francesco Baratta, Francesco Angelico, Marta Novo, Giancarlo Labbadia, and Daniele Pastori
- Subjects
medicine.medical_specialty ,Endocrinology ,Hepatology ,business.industry ,Internal medicine ,Gut permeability ,medicine ,In patient ,business ,medicine.disease_cause ,Oxidative stress - Published
- 2018
26. HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity
- Author
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Francesco Violi, Daniele Pastori, Ivano Mezzaroma, Pasquale Pignatelli, Roberto Carnevale, Francesco Di Campli, Marta Novo, Alessandra Fantauzzi, Antonella Esposito, and Simona Bartimoccia
- Subjects
Adult ,Blood Platelets ,Male ,Microbiology (medical) ,Cart ,medicine.medical_specialty ,HIV-1 ,Isoprostanes ,NOX ,Platelet activation ,CD40 Ligand ,HIV Infections ,Chromosomal translocation ,Dinoprost ,medicine.disease_cause ,In vivo ,Internal medicine ,Humans ,Medicine ,Platelet ,chemistry.chemical_classification ,Reactive oxygen species ,Membrane Glycoproteins ,business.industry ,NADPH Oxidases ,virus diseases ,Middle Aged ,Ligand (biochemistry) ,Oxidative Stress ,Infectious Diseases ,Endocrinology ,chemistry ,NADPH Oxidase 2 ,Immunology ,Female ,business ,Biomarkers ,hormones, hormone substitutes, and hormone antagonists ,Oxidative stress - Abstract
HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress.We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α).sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels.HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress.
- Published
- 2015
27. Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only
- Author
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Lucile Grimbert, Maria-Nieves Sanz, Mélanie Gressette, Catherine Rucker-Martin, Marta Novotova, Audrey Solgadi, Ahmed Karoui, Susana Gomez, Kaveen Bedouet, Eric Jacquet, Christophe Lemaire, Vladimir Veksler, Mathias Mericskay, Renée Ventura-Clapier, Jérôme Piquereau, and Anne Garnier
- Subjects
Heart ,AMP-activated protein kinase ,Fibrosis ,Cardiolipins ,Energy metabolism ,Medicine ,Physiology ,QP1-981 - Abstract
Highlights AMPK is a metabolic sensor of cellular energy which regulates energy homeostasis. We generated a cardiac-specific inducible deletion of Ampkα2 and demonstrated that this deletion induces mild cardiac dysfunction in male only. Cardiac dysfunction observed in males was associated with cardiac fibrosis and cardiac cardiolipin remodeling that are not seen in females. Although no significant cardiac function alteration was noticed in ovariectomized female Ampkα2ciKO mice, these latter exhibited cardiac fibrosis and mild cardiolipins remodeling. Our results show a higher dependence on AMPK signaling fibrosis and cardiolipin biosynthesis/maturation in males, either due to the absence of female hormones protection or/and to the action of male hormones. This may contribute to the known difference in cardiovascular risk and outcome between sexes.
- Published
- 2021
- Full Text
- View/download PDF
28. SARS-CoV-2 Exploits Non-Canonical Autophagic Processes to Replicate, Mature, and Egress the Infected Vero E6 Cells
- Author
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Juraj Koči, Marta Novotová, Monika Sláviková, Boris Klempa, and Ivan Zahradník
- Subjects
SARS-CoV-2 ,autophagy ,mitophagy ,virus maturation ,virus egress ,gene regulation ,Medicine - Abstract
The coronavirus transforms the cytoplasm of susceptible cells to support virus replication. It also activates autophagy-like processes, the role of which is not well understood. Here, we studied SARS-CoV-2-infected Vero E6 cells using transmission electron microscopy and autophagy PCR array. After 6–24 h post-infection (hpi), the cytoplasm of infected cells only contained double-membrane vesicles, phagophores, and phagosomes engulfing virus particles and cytoplasmic debris, including damaged mitochondria. The phagosomes interacted with the viral nucleoprotein complex, virus particles, mitochondria, and lipid droplets. The phagosomes transformed into egress vacuoles, which broke through the plasmalemma and discharged the virus particles. The Vero E6 cells exhibited pronounced virus replication at 6 hpi, which stabilized at 18–24 hpi at a high level. The autophagy PCR array tests revealed a significant upregulation of 10 and downregulation of 8 autophagic gene markers out of 84. Altogether, these results underline the importance of autophagy-like processes for SARS-CoV-2 maturation and egress, and point to deviations from a canonical autophagy response.
- Published
- 2022
- Full Text
- View/download PDF
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