73 results on '"Marica Cariello"'
Search Results
2. Intestinal Pgc1α ablation protects from liver steatosis and fibrosis
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Elena Piccinin, Maria Arconzo, Maria Laura Matrella, Marica Cariello, Arnaud Polizzi, Yannick Lippi, Justine Bertrand-Michel, Hervé Guillou, Nicolas Loiseau, Gaetano Villani, and Antonio Moschetta
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Metabolic dysfunction-associated steatotic liver disease ,Metabolic dysfunction-associated steatohepatitis ,Gut–liver axis ,Cholesterol ,Peroxisome proliferator-activated receptor-gamma coactivator 1α ,NAFLD ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: The gut–liver axis modulates the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of conditions characterised by hepatic steatosis and a progressive increase of inflammation and fibrosis, culminating in metabolic dysfunction-associated steatohepatitis. Peroxisome proliferator-activated receptor-gamma coactivator 1α (Pgc1α) is a transcriptional co-regulator of mitochondrial activity and lipid metabolism. Here, the intestinal-specific role of Pgc1α was analysed in liver steatosis and fibrosis. Methods: We used a mouse model in which Pgc1α was selectively deleted from the intestinal epithelium. We fed these mice and their wild-type littermates a Western diet to recapitulate the major features of liver steatosis (after 2 months of diet) and metabolic dysfunction-associated steatohepatitis (after 4 months of diet). The chow diet was administered as a control diet. Results: In humans and mice, low expression of intestinal Pgc1α is inversely associated with liver steatosis, inflammation, and fibrosis. Intestinal disruption of Pgc1α impairs the transcription of a wide number of genes, including the cholesterol transporter Niemann–Pick C1-like 1 (Npc1l1), thus limiting the uptake of cholesterol from the gut. This results in a lower cholesterol accretion in the liver and a decreased production of new fatty acids, which protect the liver from lipotoxic lipid species accumulation, inflammation, and related fibrotic processes. Conclusions: In humans and mice, intestinal Pgc1α induction during Western diet may be another culprit driving hepatic steatosis and fibrosis. Here, we show that enterocyte-specific Pgc1α ablation protects the liver from steatosis and fibrosis by reducing intestinal cholesterol absorption, with subsequent decrease of cholesterol and de novo fatty acid accumulation in the liver. Impact and implications: Liver diseases result from several insults, including signals from the gut. Although the incidence of liver diseases is continuously increasing worldwide, effective drug therapy is still lacking. Here, we showed that the modulation of an intestinal coactivator regulates the liver response to a Western diet, by limiting the uptake of dietary cholesterol. This results in a lower accumulation of hepatic lipids together with decreased inflammation and fibrosis, thus limiting the progression of liver steatosis and fibrosis towards severe end-stage diseases.
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- 2023
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3. Low Adherence to Mediterranean Diet Characterizes Metabolic Patients with Gastrointestinal Cancer
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Carlo De Matteis, Lucilla Crudele, Raffaella Maria Gadaleta, Ersilia Di Buduo, Fabio Novielli, Stefano Petruzzelli, Marica Cariello, and Antonio Moschetta
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gastrointestinal cancer ,Mediterranean diet ,Chrono Med Diet Score ,nutrition ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Background. Gastrointestinal (GI) cancers are one of the most relevant causes of death globally, frequently associated with poor dietary patterns. The Mediterranean Diet (MedDiet) contributes to cancer prevention. To assess adherence to MedDiet, our research group validated a new score, the Chrono Med Diet Score (CMDS), that captures increased visceral adiposity. Methods. We enrolled 401 subjects who underwent an evaluation for metabolic diseases and specific screening procedures according to current guidelines and were asked to answer CMDS. A total of 71 new cancer cases were recorded, including 40 GI and 31 non-gastrointestinal (NON-GI) cancers. Results. We found that CMDS was reduced in subjects who were diagnosed with cancers. Patients who reported a CMDS score of 12 or less had an over three times increased risk of being diagnosed with GI cancers and presented increased waist circumference and triglycerides and reduced HDL cholesterol compared to adherent subjects. Conclusions. Low CMDS values capture the risk for cancer diagnosis, especially for GI cancers. Thus, CMDS, along with waist circumference, can be considered as a bona fide marker for increased risk of cancer, requiring anticipated screening procedures for the detection of premalignant and early stage GI cancers in patients with low adherence to MedDiet.
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- 2024
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4. Reduction in gut‐derived MUFAs via intestinal stearoyl‐CoA desaturase 1 deletion drives susceptibility to NAFLD and hepatocarcinoma
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Simon Ducheix, Elena Piccinin, Claudia Peres, Oihane Garcia‐Irigoyen, Justine Bertrand‐Michel, Allan Fouache, Marica Cariello, Jean‐Marc Lobaccaro, Hervé Guillou, Carlo Sabbà, James M. Ntambi, and Antonio Moschetta
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Nonalcoholic fatty liver disease (NAFLD) is defined by a set of hepatic conditions ranging from steatosis to steatohepatitis (NASH), characterized by inflammation and fibrosis, eventually predisposing to hepatocellular carcinoma (HCC). Together with fatty acids (FAs) originated from adipose lipolysis and hepatic lipogenesis, intestinal‐derived FAs are major contributors of steatosis. However, the role of mono‐unsaturated FAs (MUFAs) in NAFLD development is still debated. We previously established the intestinal capacity to produce MUFAs, but its consequences in hepatic functions are still unknown. Here, we aimed to determine the role of the intestinal MUFA‐synthetizing enzyme stearoyl‐CoA desaturase 1 (SCD1) in NAFLD. We used intestinal‐specific Scd1‐KO (iScd1−/−) mice and studied hepatic dysfunction in different models of steatosis, NASH, and HCC. Intestinal‐specific Scd1 deletion decreased hepatic MUFA proportion. Compared with controls, iScd1−/− mice displayed increased hepatic triglyceride accumulation and derangement in cholesterol homeostasis when fed a MUFA‐deprived diet. Then, on Western diet feeding, iScd1−/− mice triggered inflammation and fibrosis compared with their wild‐type littermates. Finally, intestinal‐Scd1 deletion predisposed mice to liver cancer. Conclusions: Collectively, these results highlight the major importance of intestinal MUFA metabolism in maintaining hepatic functions and show that gut‐derived MUFAs are protective from NASH and HCC.
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- 2022
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5. Total serum FGF-21 levels positively relate to visceral adiposity differently from its functional intact form
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Lucilla Crudele, Oihane Garcia-Irigoyen, Marica Cariello, Marilidia Piglionica, Natasha Scialpi, Marilina Florio, Giuseppina Piazzolla, Patrizia Suppressa, Carlo Sabbà, Raffaella Maria Gadaleta, and Antonio Moschetta
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visceral obesity ,HDL cholesterol ,intact FGF21 ,waist circumference ,vitamin D ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
ObjectiveIncreased Fibroblast Growth Factor-21 (FGF-21) circulating levels have been described in obesity. In this observational study, we analysed a group of subjects with metabolic disorders to unravel the putative link between visceral adiposity and FGF-21 serum levels.MethodsTotal and intact serum FGF-21 concentration was measured with an ELISA assay respectively in 51 and 46 subjects, comparing FGF-21 levels in dysmetabolic conditions. We also tested Spearman’s correlations between FGF-21 serum levels and biochemical and clinical metabolic parameters.ResultsFGF-21 was not significantly increased in high-risk conditions such as visceral obesity, Metabolic Syndrome, diabetes, smoking, and atherosclerosis. Waist Circumference (WC), but not BMI, positively correlated with total FGF-21 levels (r=0.31, p
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- 2023
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6. Platelets from patients with visceral obesity promote colon cancer growth
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Marica Cariello, Elena Piccinin, Emanuela Pasculli, Maria Arconzo, Roberta Zerlotin, Simona D’Amore, Francesca Mastropasqua, Claudia Peres, Giusi Graziano, Gaetano Villani, Graziano Pesole, and Antonio Moschetta
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Biology (General) ,QH301-705.5 - Abstract
Platelets from patients with visceral obesity, which highly express miR-19a, can strongly promote colon cancer growth in a xenograft colon cancer model, with miR-19a administration by AAV injection increasing tumor growth.
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- 2022
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7. AST to Platelet Ratio Index (APRI) is an easy-to-use predictor score for cardiovascular risk in metabolic subjects
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Carlo De Matteis, Marica Cariello, Giusi Graziano, Stefano Battaglia, Patrizia Suppressa, Giuseppina Piazzolla, Carlo Sabbà, and Antonio Moschetta
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Medicine ,Science - Abstract
Abstract Visceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.
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- 2021
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8. Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS)
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Carlo De Matteis, Lucilla Crudele, Stefano Battaglia, Tiziana Loconte, Arianna Rotondo, Roberta Ferrulli, Raffaella Maria Gadaleta, Giuseppina Piazzolla, Patrizia Suppressa, Carlo Sabbà, Marica Cariello, and Antonio Moschetta
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nutrition ,Mediterranean diet ,biomarkers ,score ,cardiovascular risk ,visceral adiposity ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Adherence to the Mediterranean diet (MedDiet) leads to reduction of mortality from all causes, especially in subjects with cardiovascular disease, obesity, and diabetes. Numerous scores have been proposed to evaluate the adherence to MedDiet, mainly focused on eating habits. In this study, we verified whether existing validated MedDiet scores, namely, MEDI-LITE and the Mediterranean Diet Score (MDS), could be associated with visceral adiposity. Failing to find a significant association with adiposity, we proposed the validation of a new, easy-to-use adherence questionnaire, the Chrono Med-Diet score (CMDS). CMDS contains eleven food categories, including chronobiology of dietary habits and physical activity. Compared to the MEDI-LITE score and MDS, low values of CMDS are linked to increased waist circumference (WC) and dysmetabolic conditions. CMDS was also inversely correlated with cardiovascular risk (CVR), as well as Fatty Liver Index (FLI). In conclusion, the CMDS is a novel questionnaire to study the adherence to the MedDiet that, focusing on type and timing of carbohydrates intake, has the peculiar capability of capturing subjects with abdominal obesity, thus being an easy-to-use instrument of personalized medicine.
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- 2023
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9. Transcriptional Regulation of Metabolic Pathways via Lipid-Sensing Nuclear Receptors PPARs, FXR, and LXR in NASHSummary
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Marica Cariello, Elena Piccinin, and Antonio Moschetta
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Nonalcoholic Steatohepatitis (NASH) ,Nuclear Receptors ,Peroxisome Proliferator Activated Receptors (PPARs) ,Farnesoid X Receptor (FXR) ,Liver X Receptor (LXR) ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Nonalcoholic fatty liver disease comprises a wide spectrum of liver injuries from simple steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is defined when liver steatosis is associated with inflammation, hepatocyte damage, and fibrosis. A genetic predisposition and environmental insults (ie, dietary habits, obesity) are putatively responsible for NASH progression. Here, we present the impact of the lipid-sensing nuclear receptors in the pathogenesis and treatment of NASH. In detail, we discuss the pros and cons of the putative transcriptional action of the fatty acid sensors (peroxisome proliferator-activated receptors), the bile acid sensor (farnesoid X receptor), and the oxysterol sensor (liver X receptors) in the pathogenesis and bona fide treatment of NASH.
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- 2021
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10. Enterocyte superoxide dismutase 2 deletion drives obesity
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Oihane Garcia-Irigoyen, Fabiola Bovenga, Marilidia Piglionica, Elena Piccinin, Marica Cariello, Maria Arconzo, Claudia Peres, Paola Antonia Corsetto, Angela Maria Rizzo, Marta Ballanti, Rossella Menghini, Geltrude Mingrone, Philippe Lefebvre, Bart Staels, Takuji Shirasawa, Carlo Sabbà, Gaetano Villani, Massimo Federici, and Antonio Moschetta
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Obesity medicine ,Lipid ,Molecular physiology ,Science - Abstract
Summary: Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid-deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal Sod2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal Sod2 levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.
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- 2022
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11. Bile Salt Hydrolase-Competent Probiotics in the Management of IBD: Unlocking the 'Bile Acid Code'
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Raffaella Maria Gadaleta, Marica Cariello, Lucilla Crudele, and Antonio Moschetta
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bile acids ,BSH-competent bacteria ,gut microbiota ,intestinal inflammation ,probiotics ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Bile acid (BA) species and the gut microbiota (GM) contribute to intestinal mucosa homeostasis. BAs shape the GM and, conversely, intestinal bacteria with bile salt hydrolase (BSH) activity modulate the BA pool composition. The mutual interaction between BAs and intestinal microorganisms also influences mucosal barrier integrity, which is important for inflammatory bowel disease (IBD) pathogenesis, prevention and therapy. High levels of secondary BAs are detrimental for the intestinal barrier and increase the intestinal inflammatory response and dysbiosis. Additionally, a lack of BSH-active bacteria plays a role in intestinal inflammation and BA dysmetabolism. Thus, BSH-competent bacteria in probiotic formulations are being actively studied in IBD. At the same time, studies exploring the modulation of the master regulator of BA homeostasis, the Farnesoid X Receptor (FXR), in intestinal inflammation and how this impacts the GM are gaining significant momentum. Overall, the choice of probiotic supplementation should be a peculiar issue of personalized medicine, considering not only the disease but also the specific BA and metabolic signatures of a given patient.
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- 2022
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12. Intestinal FXR Activation via Transgenic Chimera or Chemical Agonism Prevents Colitis-Associated and Genetically-Induced Colon Cancer
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Marica Cariello, Roberta Zerlotin, Emanuela Pasculli, Elena Piccinin, Claudia Peres, Emanuele Porru, Aldo Roda, Raffaella Maria Gadaleta, and Antonio Moschetta
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Farnesoid X Receptor (FXR) ,colitis ,colon cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The Farnesoid X Receptor (FXR) is the master regulator of Bile Acids (BA) homeostasis orchestrating their synthesis, transport and metabolism. Disruption of BA regulation has been linked to gut-liver axis diseases such as colorectal cancer (CRC). In this study, firstly we examined the role of constitutive activation of intestinal FXR in CRC; then we pre-clinically investigated the therapeutic potential of a diet enriched with a synthetic FXR agonist in two models of CRC (chemically-induced and genetic models). We demonstrated that mice with intestinal constitutive FXR activation are protected from AOM/DSS-induced CRC with a significant reduction of tumor number compared to controls. Furthermore, we evaluated the role of chemical FXR agonism in a DSS model of colitis in wild type (WT) and FXRnull mice. WT mice administered with the FXR activating diet showed less morphological alterations and decreased inflammatory infiltrates compared to controls. The FXR activating diet also protected WT mice from AOM/DSS-induced CRC by reducing tumors’ number and size. Finally, we proved that the FXR activating diet prevented spontaneous CRC in APCMin/+ mice via an FXR-dependent modulation of BA homeostasis. Our results demonstrate that intestinal FXR activation prevented both inflammation- and genetically-driven colorectal tumorigenesis by modulating BA pool size and composition. This could open new avenues for the therapeutic management of intestinal inflammation and tumorigenesis.
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- 2022
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13. let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects.
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Annalisa Contursi, Maria Arconzo, Marica Cariello, Marilidia Piglionica, Simona D'Amore, Michele Vacca, Giusi Graziano, Raffaella Maria Gadaleta, Rosa Valanzano, Renato Mariani-Costantini, Gaetano Villani, Antonio Moschetta, and Elena Piccinin
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Medicine ,Science - Abstract
The crypt-villus axis represents the essential unit of the small intestine, which integrity and functions are fundamental to assure tissue and whole-body homeostasis. Disruption of pathways regulating the fine balance between proliferation and differentiation results in diseases development. Nowadays, it is well established that microRNAs (miRNAs) play a crucial role in the homeostasis maintenance and perturbation of their levels may promote tumor development. Here, by using microarray technology, we analysed the miRNAs differentially expressed between the crypt and the villus in mice ileum. The emerged miRNAs were further validated by Real Time qPCR in mouse model (ApcMin/+), human cell lines and human tissue samples (FAP) of colorectal cancer (CRC). Our results indicated that miRNAs more expressed in the villi compartment are negatively regulated in tumor specimens, thus suggesting a close association between these microRNAs and the differentiation process. Particularly, from our analysis let-7e appeared to be a promising target for possible future therapies and a valuable marker for tumor staging, being upregulated in differentiated cells and downregulated in early-stage colonic adenoma samples.
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- 2021
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14. Monocyte-to-HDL Ratio (MHR) Predicts Vitamin D Deficiency in Healthy and Metabolic Women: A Cross-Sectional Study in 1048 Subjects
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Carlo De Matteis, Lucilla Crudele, Marica Cariello, Stefano Battaglia, Giuseppina Piazzolla, Patrizia Suppressa, Carlo Sabbà, Elena Piccinin, and Antonio Moschetta
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vitamin D ,MHR index ,metabolic syndrome ,gender difference ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Vitamin D deficiency is often linked with Metabolic Syndrome, both being more frequent with ageing and associated with an increase inflammatory state. Recently, monocytes-to-high density lipoprotein (HDL) ratio (MHR) has emerged as a powerful index to predict systemic inflammation. In this cross-sectional study, we investigated the association between circulating vitamin D level (25-OH vitamin D) and inflammatory status in a population of 1048 adult individuals. Our study reveals an inverse association between 25-OH vitamin D levels and MHR in the overall population. When the population is stratified by gender, waist circumference, and body mass index (BMI), we observed that while in men this relation is strongly significative only in condition of central obesity, in women a lifelong negative correlation exists between circulating 25-OH vitamin D and MHR and it is independent of the metabolic status. These observations underscore the relevance of circulating biomarkers such as MHR in the prediction of systemic inflammatory conditions sustained by vitamin D deficiency also in healthy and young women.
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- 2022
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15. Corrigendum to ‘Fibroblast growth factor 19 modulates intestinal microbiota and inflammation in presence of farnesoid x receptor’
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Raffaella Maria Gadaleta, Oihane Garcia-Irigoyen, Marica Cariello, Natasha Scialpi, Claudia Peres, Stefania Vetrano, Gionatha Fiorino, Silvio Danese, Brian Ko, Jian Luo, Emanuele Porru, Aldo Roda, Carlo Sabbá, and Antonio Moschetta
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Medicine ,Medicine (General) ,R5-920 - Published
- 2020
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16. Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor
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Raffaella Maria Gadaleta, Oihane Garcia-Irigoyen, Marica Cariello, Natasha Scialpi, Claudia Peres, Stefania Vetrano, Gionatha Fiorino, Silvio Danese, Brian Ko, Jian Luo, Emanuele Porru, Aldo Roda, Carlo Sabbà, and Antonio Moschetta
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Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Disruption of bile acid (BA) homeostasis plays a key role in intestinal inflammation. The gut-liver axis is the main site for the regulation of BA synthesis and BA pool size via the combined action of the nuclear Farnesoid X Receptor (FXR) and the enterokine Fibroblast Growth Factor 19 (FGF19). Increasing evidence have linked derangement of BA metabolism with dysbiosis and mucosal inflammation. Thus, here we aimed to investigate the potential action of an FGF19 analogue on intestinal microbiota and inflammation. Methods: A novel engineered non-tumorigenic variant of the FGF19 protein, M52-WO 2016/0168219 was generated. WT and FXRnull mice were injected with AAV-FGF19-M52 or the control AAV-GFP and subjected to Sodium Dextran Sulphate-induced colitis. Findings: FGF19-M52 reduced BA synthesis and pool size, modulated its composition and protected mice from intestinal inflammation. These events were coupled with preservation of the intestinal epithelial barrier integrity, inhibition of inflammatory immune response and modulation of microbiota composition. Interestingly, FGF19-M52-driven systemic and local anti-inflammatory activity was completely abolished in Farnesoid X Receptor (FXR)null mice, thus underscoring the need of FXR to guarantee enterocytes’ fitness and complement FGF19 anti-inflammatory activity. To provide a translational perspective, we also show that circulating FGF19 levels are reduced in patients with Crohn's disease. Interpretation: Reactivation of the FXR-FGF19 axis in a murine model of intestinal inflammation could bona fide provide positive changes in BA metabolism with consequent reduction of intestinal inflammation and modulation of microbiota. These results point to the therapeutic potential of FGF19 in the treatment of intestinal inflammation with concomitant derangement of BA homeostasis. Funding: A. Moschetta is funded by MIUR-PRIN 2017
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- 2020
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17. Gender, BMI and fasting hyperglycaemia influence Monocyte to-HDL ratio (MHR) index in metabolic subjects.
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Stefano Battaglia, Natasha Scialpi, Elsa Berardi, Gianfranco Antonica, Patrizia Suppressa, Francesco Arcangelo Diella, Francesca Colapietro, Roberta Ruggieri, Giuseppe Guglielmini, Alessia Noia, Giusi Graziano, Carlo Sabbà, and Marica Cariello
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Medicine ,Science - Abstract
Metabolic Syndrome (MS) is characterized by a low-grade inflammatory state causing an alteration of non-invasive indexes derived from blood count, namely monocyte-to-HDL ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). We analyse a population of 771 subjects (394 controls and 377 MS patients) to evaluate the best predictive index of MS. The diagnosis of MS was made according to the 2006 criteria of the International Diabetes Federation (IDF). We performed ROC curve analyses to evaluate the best predictor index of MS. MHR cut-off value was used to classify the population in two different groups and to create the outcome variable of the Recursive Partitioning and Amalgamation (RECPAM) analysis. This method is a tree-structured approach that defines "risk profiles" for each group of dichotomous variables. We showed that MHR index is significantly linked to body mass index (BMI), waist circumference, creatinine, C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR). ROC curve defined an MHR cut-off value of 6.4, which was able to identify two patient groups with significant differences in waist circumference, blood pressure, creatinine, estimated glomerular filtration rate and fasting plasma glucose. RECPAM analysis demonstrated that gender, BMI categorization and hyperglycaemia were the most important risk determinants of increased MHR index that can be considered bona fide a useful and easily obtainable tool to suggest the presence of peculiar metabolic features that predict MS.
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- 2020
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18. Metabolic syndrome and idiopathic sudden sensori-neural hearing loss.
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Massimo Rinaldi, Giada Cavallaro, Marica Cariello, Natasha Scialpi, and Nicola Quaranta
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Medicine ,Science - Abstract
The purpose of this study was to evaluate the association between the presence of Metabolic Syndrome (MetS) and idiopathic sudden sensorineural hearing loss (ISSHL) and the impact of MetS on recovery of patients with ISSHL. 39 Patients with ISSHL and 44 controls were enrolled in this study. Demographic, clinical characteristics and hearing recovery were evaluated. MetS was defined according to the diagnostic criteria of International Diabetes Federation (IDF) consensus definition. Patients affected by ISSHL presented a body mass index (BMI), waist circumference, waist hip ratio (WHR), fasting glucose and blood pressure significantly higher compared to controls. Considering patients with central obesity, 5 controls and 15 ISSHL patients met the criteria of MetS. According to Siegel criteria, a complete or partial recovery was observed in 60% of patients with MetS and in 91,66% of patients without MetS. MetS was associated with ISSHL and this association negatively influenced the hearing recovery of these patients.
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- 2020
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19. Adhesion of Platelets to Colon Cancer Cells Is Necessary to Promote Tumor Development in Xenograft, Genetic and Inflammation Models
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Marica Cariello, Elena Piccinin, Roberta Zerlotin, Marilidia Piglionica, Claudia Peres, Chiara Divella, Anna Signorile, Gaetano Villani, Giuseppe Ingravallo, Carlo Sabbà, and Antonio Moschetta
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colon cancer ,platelets ,P-selectin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Platelets represent the linkage between tissue damage and inflammatory response with a putative role in tumorigenesis. Given the importance of the microenvironment in colon cancer development, we elucidated the eventual role of platelets-cancer cells crosstalk in in vivo colon cancer models. To evaluate the involvement of platelets in intestinal tumorigenesis, we first analyzed if the ablation of β-integrin P-selectin that drives platelets-cell adhesion, would contribute to platelets-colon cancer cell interaction and drive cancer progression. In a xenograft tumor model, we observed that when tumors are inoculated with platelets, the ablation of P-selectin significantly reduced tumor growth compared to control platelets. Furthermore, in genetic models, as well as in chronic colitis-associated colorectal carcinogenesis, P-selectin ablated mice displayed a significant reduction in tumor number and size compared to control mice. Taken together, our data highlights the importance of platelets in the tumor microenvironment for intestinal tumorigenesis. These results support the hypothesis that a strategy aimed to inhibit platelets adhesion to tumor cells are able to block tumor growth and could represent a novel therapeutic approach to colon cancer treatment.
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- 2021
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20. Extra-Virgin Olive Oil from Apulian Cultivars and Intestinal Inflammation
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Marica Cariello, Annalisa Contursi, Raffaella Maria Gadaleta, Elena Piccinin, Stefania De Santis, Marilidia Piglionica, Ada Fiorenza Spaziante, Carlo Sabbà, Gaetano Villani, and Antonio Moschetta
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olive oil ,inflammatory bowel disease ,intestinal inflammation ,animal experimentation ,mouse model ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Inflammatory bowel disease (IBD) is a multifactorial intestinal disorder characterized by chronic intestinal inflammation. The etiology of IBD is still unclear, although genetic, environmental and host factors have been associated to the disease. Extra-virgin olive oil (EVO) is a central component of the Mediterranean diet and it decreases chronic inflammation by interfering with arachidonic acid and NF-κB signaling pathways. Specifically, the different components of EVO are able to confer advantages in terms of health in their site of action. For instance, oleic acid displays a protective effect in liver dysfunction and gut inflammation, whereas phenolic compounds protect colon cells against oxidative damage and improve the symptoms of chronic inflammation in IBD. Given the biological properties of EVO, we investigated whether its administration is able to confer protection in a mouse model of dextrane sodium sulfate (DSS)-induced colitis. Four EVO cultivars from the Apulian Region of Italy, namely Ogliarola (Cima di Bitonto), Coratina, Peranzana and Cima di Mola, respectively, were used. Administration of EVO resulted in reduced body weight loss in our colitis model. Furthermore, mice treated with Ogliarola, Coratina and Cima di Mola EVO displayed a reduction of rectal bleeding and IL-1β, TGFβ, IL-6 gene expression levels. Furthermore, Ogliarola, Coratina and Peranzana EVO administration ameliorated intestinal permeability and histopathological features of inflammation. Our data further validate the well-known positive effects of EVO supplementation in promoting human health and suggest the bona fide contribution of EVO in preventing onset and reducing progression of intestinal inflammation.
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- 2020
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21. Identification of peculiar gene expression profile in peripheral blood mononuclear cells (PBMC) of celiac patients on gluten free diet.
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Moris Sangineto, Giusi Graziano, Simona D'Amore, Roberto Salvia, Giuseppe Palasciano, Carlo Sabbà, Michele Vacca, and Marica Cariello
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Medicine ,Science - Abstract
Celiac disease (CD) is a systemic disorder characterized by an immune-mediated reaction to gluten and a wide spectrum of clinical manifestations. Currently, the main treatment of CD is represented by adherence to a gluten-free diet (GFD) which determines the resolution of symptoms, and the normalization of the serology and of the duodenal villous atrophy. In the present study, we aimed to identify changes in gene expression in peripheral blood mononuclear cells (PBMCs) of celiac patients on GFD for at least 2 years, in order to identify novel disease biomarkers and candidate targets for putative therapeutic approaches. Microarray analysis was performed on PBMCs from 17 celiac patients on long-term GFD and 20 healthy controls. We identified 517 annotated genes that were significantly modulated between celiac patients and controls. Significant biological pathways were functionally clustered using the Core Function of Ingenuity System Pathway Analysis (IPA). Intriguingly, despite being on a GFD, celiac patients exhibited a peculiar PBMC profile characterized by an aberrant expression of genes involved in the regulation of immunity, inflammatory response, metabolism, and cell proliferation. Random forest algorithm was then used to validate the prediction ability of core genes as classifiers of the "celiac status". In conclusion, our study identified a characteristic PBMCs signature profile in clinically asymptomatic celiac patient.
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- 2018
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22. Extra Virgin Olive Oil: Lesson from Nutrigenomics
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Stefania De Santis, Marica Cariello, Elena Piccinin, Carlo Sabbà, and Antonio Moschetta
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extra virgin olive oil ,polyphenol content ,fatty acids ,nutrigenomics ,human health ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Extra virgin olive oil (EVOO) consumption has a beneficial effect on human health, especially for prevention of cardiovascular disease and metabolic disorders. Here we underscore the peculiar importance of specific cultivars used for EVOO production since biodiversity among cultivars in terms of fatty acids and polyphenols content could differently impact on the metabolic homeostasis. In this respect, the nutrigenomic approach could be very useful to fully dissect the pathways modulated by different EVOO cultivars in terms of mRNA and microRNA transcriptome. The identification of genes and miRNAs modulated by specific EVOO cultivars could also help to discover novel nutritional biomarkers for prevention and/or prognosis of human disease. Thus, the nutrigenomic approach depicts a novel scenario to investigate if a specific EVOO cultivar could have a positive effect on human health by preventing the onset of cardiovascular disease and/or chronic inflammatory disorders also leading to cancer.
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- 2019
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23. Role of Oleic Acid in the Gut-Liver Axis: From Diet to the Regulation of Its Synthesis via Stearoyl-CoA Desaturase 1 (SCD1)
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Elena Piccinin, Marica Cariello, Stefania De Santis, Simon Ducheix, Carlo Sabbà, James M. Ntambi, and Antonio Moschetta
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olive oil ,oleic acid ,MUFA ,stearoyl-CoA desaturase ,liver ,gut ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The consumption of an olive oil rich diet has been associated with the diminished incidence of cardiovascular disease and cancer. Several studies have attributed these beneficial effects to oleic acid (C18 n-9), the predominant fatty acid principal component of olive oil. Oleic acid is not an essential fatty acid since it can be endogenously synthesized in humans. Stearoyl-CoA desaturase 1 (SCD1) is the enzyme responsible for oleic acid production and, more generally, for the synthesis of monounsaturated fatty acids (MUFA). The saturated to monounsaturated fatty acid ratio affects the regulation of cell growth and differentiation, and alteration in this ratio has been implicated in a variety of diseases, such as liver dysfunction and intestinal inflammation. In this review, we discuss our current understanding of the impact of gene-nutrient interactions in liver and gut diseases, by taking advantage of the role of SCD1 and its product oleic acid in the modulation of different hepatic and intestinal metabolic pathways.
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- 2019
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24. Clustering nuclear receptors in liver regeneration identifies candidate modulators of hepatocyte proliferation and hepatocarcinoma.
- Author
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Michele Vacca, Simona D'Amore, Giusi Graziano, Andria D'Orazio, Marica Cariello, Vittoria Massafra, Lorena Salvatore, Nicola Martelli, Stefania Murzilli, Giuseppe Lo Sasso, Renato Mariani-Costantini, and Antonio Moschetta
- Subjects
Medicine ,Science - Abstract
Liver regeneration (LR) is a valuable model for studying mechanisms modulating hepatocyte proliferation. Nuclear receptors (NRs) are key players in the control of cellular functions, being ideal modulators of hepatic proliferation and carcinogenesis.We used a previously validated RT-qPCR platform to profile modifications in the expression of all 49 members of the NR superfamily in mouse liver during LR. Twenty-nine NR transcripts were significantly modified in their expression during LR, including fatty acid (peroxisome proliferator-activated receptors, PPARs) and oxysterol (liver X receptors, Lxrs) sensors, circadian masters RevErbα and RevErbβ, glucocorticoid receptor (Gr) and constitutive androxane receptor (Car). In order to detect the NRs that better characterize proliferative status vs. proliferating liver, we used the novel Random Forest (RF) analysis to selected a trio of down-regulated NRs (thyroid receptor alpha, Trα; farsenoid X receptor beta, Fxrβ; Pparδ) as best discriminators of the proliferating status. To validate our approach, we further studied PPARδ role in modulating hepatic proliferation. We first confirmed the suppression of PPARδ both in LR and human hepatocellular carcinoma at protein level, and then demonstrated that PPARδ agonist GW501516 reduces the proliferative potential of hepatoma cells.Our data suggest that NR transcriptome is modulated in proliferating liver and is a source of biomarkers and bona fide pharmacological targets for the management of liver disease affecting hepatocyte proliferation.
- Published
- 2014
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25. Correlation between serum tryptase, mast cells positive to tryptase and microvascular density in colo-rectal cancer patients: possible biological-clinical significance.
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Michele Ammendola, Rosario Sacco, Giuseppe Sammarco, Giuseppe Donato, Severino Montemurro, Eustachio Ruggieri, Rosa Patruno, Ilaria Marech, Marica Cariello, Angelo Vacca, Cosmo Damiano Gadaleta, and Girolamo Ranieri
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Tryptase is a serin protease stored and released from mast cells (MCs) that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC) patients before (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT) and microvascular density (MVD) in primary tumour tissue. METHODS: A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system) were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated by image analysis methods. RESULTS: The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT and MVD (r = 0.73; p = 0.001) was found. CONCLUSION: Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.
- Published
- 2014
- Full Text
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26. AST to Platelet Ratio Index (APRI) is an easy-to-use predictor score for cardiovascular risk in metabolic subjects
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Antonio Moschetta, Giuseppina Piazzolla, Stefano Battaglia, Giusi Graziano, Carlo De Matteis, Carlo Sabbà, Patrizia Suppressa, and Marica Cariello
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,Science ,Liver fibrosis ,Population ,Disease ,030204 cardiovascular system & hematology ,Gastroenterology ,Article ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Predictive Value of Tests ,Fibrosis ,Internal medicine ,medicine ,Humans ,Platelet ,Aspartate Aminotransferases ,Obesity ,education ,Aged ,Metabolic Syndrome ,education.field_of_study ,Multidisciplinary ,Platelet Count ,business.industry ,Fatty liver ,Age Factors ,Cardiometabolic Risk Factors ,Middle Aged ,medicine.disease ,030104 developmental biology ,Premenopause ,Cardiovascular Diseases ,Research Design ,Medicine ,Female ,Viral hepatitis ,business ,Biomarkers ,Visceral Obesity ,Non-alcoholic fatty liver disease - Abstract
Visceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.
- Published
- 2021
27. Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis
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Lucilla Crudele, Carlo De Matteis, Elena Piccinin, Raffaella Maria Gadaleta, Marica Cariello, Ersilia Di Buduo, Giuseppina Piazzolla, Patrizia Suppressa, Elsa Berardi, Carlo Sabbà, and Antonio Moschetta
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Hepatology ,Gastroenterology ,Internal Medicine ,Immunology and Allergy - Abstract
Dysmetabolic conditions could drive liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), increasing susceptibility to hepatocellular carcinoma (HCC). We therefore aimed to identify novel predictive biomarkers of HCC in patients with and without liver fibrosis.A total of 1,234 patients with putative metabolic conditions and NAFLD were consecutively assessed in our outpatient clinic. Clinical and biochemical data were recorded, and then liver ultrasonography was performed annually for 5 years to detect HCC onset. For the analysis, the population was first divided according to HCC diagnosis; then a further subdivision of those who did not develop HCC was performed based on the presence or absence of liver fibrosis at time 0.Sixteen HCC cases were recorded in 5 years. None of our patients had been diagnosed with cirrhosis before HCC was detected. Compared to patients who did not develop HCC, those who did had higher liver transaminases and fibrosis scores at time 0 (This study identifies HDL-c as aVisceral adiposity and its associated conditions, such as chronic inflammation and insulin resistance, may play a pivotal role in hepatocellular carcinoma development in patients with non-alcoholic fatty liver disease. We provide new insights on the underlying mechanisms of its pathogenesis, shedding light on the involvement of low levels of "good" HDL-cholesterol. We recommend integrating dietary regimens and advice on healthy lifestyles into the clinical management of non-alcoholic fatty liver disease, with the goal of reducing the incidence of hepatocellular carcinoma.
- Published
- 2022
28. The gut-liver axis in cholangiopathies: focus on bile acid based pharmacological treatment
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Marica Cariello, Raffaella M. Gadaleta, and Antonio Moschetta
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Bile Acids and Salts ,Cholestasis ,Liver ,Liver Cirrhosis, Biliary ,Cholangitis, Sclerosing ,Gastroenterology ,Bile ,Humans ,Liver Transplantation - Abstract
This review analyses the main features of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and provides an overview of the currently available (bile acid) bile acid related treatments.In PBC, biliary injury is the consequence of a dysregulated intrahepatic and systemic immune response. Given the close association between PSC and inflammatory bowel disease (IBD), the microbiota represents an important factor in the development of PSC. Bile acid based pharmacological treatments could represent promising therapeutic strategies in the management of cholangiopathies.Cholangiopathies include a spectrum of diseases resulting in cholestasis, an impairment of bile flow in the biliary tree, leading to biliary obstruction and damage as well as liver inflammation and fibrosis. PSC and PBC are highly heterogeneous cholangiopathies and progressive disorders with defined pathophysiological mechanisms. Curative treatments have not been established, and although their prevalence is low, they are a frequent indication for liver transplantation in the advanced stages of cholangiopathies. These diseases still present with unmet therapeutic strategies, also taking into account that on average 30-40% of patients undergoing liver transplantation will have recurrence of the original illness.
- Published
- 2022
29. Adhesion of Platelets to Colon Cancer Cells Is Necessary to Promote Tumor Development in Xenograft, Genetic and Inflammation Models
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Gaetano Villani, Marilidia Piglionica, Roberta Zerlotin, Elena Piccinin, Marica Cariello, Chiara Divella, Claudia Peres, Carlo Sabbà, Anna Signorile, Antonio Moschetta, and Giuseppe Ingravallo
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Cancer Research ,Tumor microenvironment ,P-selectin ,business.industry ,Colorectal cancer ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Inflammation ,medicine.disease_cause ,medicine.disease ,Article ,Oncology ,colon cancer ,Genetic model ,Cancer cell ,platelets ,Cancer research ,Medicine ,medicine.symptom ,business ,Carcinogenesis ,RC254-282 - Abstract
Simple Summary Platelets are small, anucleate, metabolically active cells and they represent an important linkage between tissue damage and inflammatory response. Several studies focused on the central role of platelets in inflammation and tumor development through their direct interaction with other cell types. Mice lacking the vascular adhesion molecules P-selectin exhibited a reduction in tumor metastases. We demonstrated that P-selectin-ablated platelets reduced tumor growth in a xenograft adenocarcinoma model. Furthermore, the lack of P-selectin decreased colon cancer progression in genetic mouse models and in chemically-induced colitis colorectal carcinogenesis. Our results suggest that platelets-cancer cells crosstalk via P-selectin is fundamental for tumor development. Abstract Platelets represent the linkage between tissue damage and inflammatory response with a putative role in tumorigenesis. Given the importance of the microenvironment in colon cancer development, we elucidated the eventual role of platelets-cancer cells crosstalk in in vivo colon cancer models. To evaluate the involvement of platelets in intestinal tumorigenesis, we first analyzed if the ablation of β-integrin P-selectin that drives platelets-cell adhesion, would contribute to platelets-colon cancer cell interaction and drive cancer progression. In a xenograft tumor model, we observed that when tumors are inoculated with platelets, the ablation of P-selectin significantly reduced tumor growth compared to control platelets. Furthermore, in genetic models, as well as in chronic colitis-associated colorectal carcinogenesis, P-selectin ablated mice displayed a significant reduction in tumor number and size compared to control mice. Taken together, our data highlights the importance of platelets in the tumor microenvironment for intestinal tumorigenesis. These results support the hypothesis that a strategy aimed to inhibit platelets adhesion to tumor cells are able to block tumor growth and could represent a novel therapeutic approach to colon cancer treatment.
- Published
- 2021
30. Suppression of Hepatic Bile Acid Synthesis by a non-tumorigenic FGF19 analogue Protects Mice from Fibrosis and Hepatocarcinogenesis
- Author
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Natasha Scialpi, Antonio Moschetta, Raffaella Maria Gadaleta, Brian Ko, Claudia Peres, Emanuele Porru, Marica Cariello, Aldo Roda, Carlo Sabbà, and Jian Luo
- Subjects
Liver Cirrhosis ,0301 basic medicine ,Carcinoma, Hepatocellular ,medicine.drug_class ,lcsh:Medicine ,Cholesterol 7 alpha-hydroxylase ,Fibroblast growth factor ,Article ,Bile Acids and Salts ,Mice ,03 medical and health sciences ,Gastrointestinal Agents ,Fibrosis ,medicine ,Animals ,lcsh:Science ,Mice, Knockout ,Biological Products ,Multidisciplinary ,Bile acid ,Chemistry ,lcsh:R ,FGF19 ,medicine.disease ,Fibroblast Growth Factors ,Disease Models, Animal ,Treatment Outcome ,030104 developmental biology ,Cancer research ,Mutant Proteins ,Farnesoid X receptor ,lcsh:Q ,Hepatic fibrosis ,Homeostasis - Abstract
Critical regulation of bile acid (BA) pool size and composition occurs via an intensive molecular crosstalk between the liver and gut, orchestrated by the combined actions of the nuclear Farnesoid X receptor (FXR) and the enterokine fibroblast growth factor 19 (FGF19) with the final aim of reducing hepatic BA synthesis in a negative feedback fashion. Disruption of BA homeostasis with increased hepatic BA toxic levels leads to higher incidence of hepatocellular carcinoma (HCC). While native FGF19 has anti-cholestatic and anti-fibrotic activity in the liver, it retains peculiar pro-tumorigenic actions. Thus, novel analogues have been generated to avoid tumorigenic capacity and maintain BA metabolic action. Here, using BA related Abcb4−/− and Fxr−/− mouse models of spontaneous hepatic fibrosis and HCC, we explored the role of a novel engineered variant of FGF19 protein, called FGF19-M52, which fully retains BA regulatory activity but is devoid of the pro-tumoral activity. Expression of the BA synthesis rate-limiting enzyme Cyp7a1 is reduced in FGF19-M52-treated mice compared to the GFP-treated control group with consequent reduction of BA pool and hepatic concentration. Treatment with the non-tumorigenic FGF19-M52 strongly protects Abcb4−/− and Fxr−/− mice from spontaneous hepatic fibrosis, cellular proliferation and HCC formation in terms of tumor number and size, with significant reduction of biochemical parameters of liver damage and reduced expression of several genes driving the proliferative and inflammatory hepatic scenario. Our data bona fide suggest the therapeutic potential of targeting the FXR-FGF19 axis to reduce hepatic BA synthesis in the control of BA-associated risk of fibrosis and hepatocarcinoma development.
- Published
- 2018
31. Abdominal obesity negatively influences key metrics of reverse cholesterol transport
- Author
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Antonio Moschetta, Alice Ossoli, Laura Calabresi, Marica Cariello, Emanuela Pasculli, Alessia Noia, Carlo Sabbà, Patrizia Suppressa, Jennifer Härdfeldt, Giuseppina Piazzolla, E Berardi, Sara Simonelli, Marilidia Piglionica, and Natasha Scalpi
- Subjects
education.field_of_study ,medicine.medical_specialty ,Waist ,Cholesterol ,business.industry ,Reverse cholesterol transport ,Population ,Cell Biology ,medicine.disease ,chemistry.chemical_compound ,High-density lipoprotein ,Endocrinology ,chemistry ,Glycation ,Internal medicine ,Obesity, Abdominal ,medicine ,medicine.symptom ,Metabolic syndrome ,education ,business ,Molecular Biology ,Abdominal obesity - Abstract
Cardiometabolic risk factors increase the risk of atherosclerotic cardiovascular disease (ASCVD), but whether these metabolic anomalies affect the anti-atherogenic function of reverse cholesterol transport (RCT) is not yet clearly known. The present study aimed to delineate if the function and maturation of high density lipoprotein (HDL) particles cross-sectionally associate with surrogate markers of ASCVD in a population comprising of different degree of cardiometabolic risk. We enrolled 131 subjects and characterized cardiometabolic risk based on the IDF criteria's for metabolic syndrome (MS). In this population, cholesterol efflux capacity (CEC), Lecithin-cholesterol acyltransferase (LCAT) and ApoA-1 glycation was associated with waist circumference, abdominal visceral fat (VFA) and abdominal subcutaneous fat. In multivariate analyses, VFA was identified as a critical contributor for low CEC and LCAT. When stratified into groups based on the presence of cardiometabolic risk factors, we found a prominent reduction in CEC and LCAT as a function of the progressive increase of cardiometabolic risk from 0-2, 0-3 to 0-4/5, whereas an increase in Pre-β-HDL and ApoA-1 glycation was observed between the lowest and highest risk groups. These findings confirm the connection between MS and its predisposing conditions to an impairment of atheroprotective efflux-promoting function of HDLs. Furthermore, we have identified the bona fide pathogenically contribution of abdominal obesity to profound alterations of key metrics of RCT.
- Published
- 2021
32. let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects
- Author
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Antonio Moschetta, Marilidia Piglionica, Maria Arconzo, Gaetano Villani, Annalisa Contursi, Marica Cariello, Giusi Graziano, Rosa Valanzano, Elena Piccinin, Michele Vacca, Raffaella Maria Gadaleta, Renato Mariani-Costantini, and Simona D'Amore
- Subjects
Male ,0301 basic medicine ,Colorectal cancer ,Cellular differentiation ,Biochemistry ,Mice ,0302 clinical medicine ,Gastrointestinal Cancers ,Medicine and Health Sciences ,Cyclin D1 ,Multidisciplinary ,Cell Differentiation ,Animal Models ,Adenomas ,Nucleic acids ,medicine.anatomical_structure ,Oncology ,Experimental Organism Systems ,Adenomatous Polyposis Coli ,030220 oncology & carcinogenesis ,Medicine ,Anatomy ,Colorectal Neoplasms ,Research Article ,Adenoma ,Colon ,Transgene ,Science ,Adenomatous Polyposis Coli Protein ,Crypt ,Down-Regulation ,Mouse Models ,Mice, Transgenic ,Gastroenterology and Hepatology ,Biology ,Research and Analysis Methods ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,Model Organisms ,Downregulation and upregulation ,Cell Line, Tumor ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Non-coding RNA ,Colorectal Cancer ,Natural antisense transcripts ,Biology and life sciences ,Cancers and Neoplasms ,medicine.disease ,Small intestine ,Gene regulation ,Gastrointestinal Tract ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,Animal Studies ,Gene chip analysis ,Cancer research ,RNA ,Gene expression ,Digestive System ,Developmental Biology - Abstract
The crypt-villus axis represents the essential unit of the small intestine, which integrity and functions are fundamental to assure tissue and whole-body homeostasis. Disruption of pathways regulating the fine balance between proliferation and differentiation results in diseases development. Nowadays, it is well established that microRNAs (miRNAs) play a crucial role in the homeostasis maintenance and perturbation of their levels may promote tumor development. Here, by using microarray technology, we analysed the miRNAs differentially expressed between the crypt and the villus in mice ileum. The emerged miRNAs were further validated by Real Time qPCR in mouse model (ApcMin/+), human cell lines and human tissue samples (FAP) of colorectal cancer (CRC). Our results indicated that miRNAs more expressed in the villi compartment are negatively regulated in tumor specimens, thus suggesting a close association between these microRNAs and the differentiation process. Particularly, from our analysis let-7e appeared to be a promising target for possible future therapies and a valuable marker for tumor staging, being upregulated in differentiated cells and downregulated in early-stage colonic adenoma samples.
- Published
- 2021
33. Corrigendum to ‘Fibroblast growth factor 19 modulates intestinal microbiota and inflammation in presence of farnesoid x receptor’
- Author
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Claudia Peres, Gionatha Fiorino, Carlo Sabbà, Jian Luo, Stefania Vetrano, Brian Ko, Marica Cariello, Aldo Roda, Emanuele Porru, Oihane Garcia-Irigoyen, Raffaella Maria Gadaleta, Natasha Scialpi, Silvio Danese, and Antonio Moschetta
- Subjects
lcsh:R5-920 ,business.industry ,lcsh:R ,lcsh:Medicine ,Inflammation ,General Medicine ,Fibroblast growth factor ,General Biochemistry, Genetics and Molecular Biology ,medicine ,Cancer research ,Farnesoid X receptor ,medicine.symptom ,business ,lcsh:Medicine (General) - Published
- 2020
34. Contributors
- Author
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Itziar Abete, Xabier Agirre, Jennie Ahlgren, Gorka Alkorta-Aranburu, Rocío Aller, Cristina Andres-Lacueva, Daniel Antonio de Luis, Darwin Babino, Shimrit Bar-El Dadon, Maria Luisa Bonet, Laura Bordoni, Patrick Borel, Annet M. Bosch, Steven Brown, Dolores Busso, Nadia Calabriso, Antonio Capurso, Cristiano Capurso, Marica Cariello, Maria Annunziata Carluccio, Patricia Casas-Agustench, Carol L. Cheatham, Adela Chirita-Emandi, Geetha Chittoor, Myung-Sook Choi, Sang-Woon Choi, Paul Cordero, Fernando J. Corrales, Víctor Cortés, Nicholas C.P. Cross, Ana B. Crujeiras, Rui Curi, Raffaele De Caterina, David de Lorenzo, Charles Desmarchelier, Olivia Dong, Ramón Estruch, Teresa Ezponda, Michael Fenech, Lynnette R. Ferguson, Karina Fischer, Luigi Fontana, Simonetta Friso, Rosita Gabbianelli, Marat Garaulet, Oihane Garcia-Irigoyen, Angel Gil, Purificación Gómez-Abellán, Ulf Görman, William S. Harris, Alain de J. Hernandez-Vazquez, Paul Hugenholtz, Lara K. Hyde, Clara Ibáñez, Olatz Izaola, Peter J.H. Jones, Richard Kirwan, Martin Kohlmeier, Natalia I. Krupenko, Eun-Young Kwon, Dudley W. Lamming, Rosa M. Lamuela-Raventos, Dominique Langin, Simon Langley-Evans, Cátia Lira do Amaral, Jesus Lopez-Minguez, Rosalinda Madonna, Maria L. Mansego, Clarisse Marotz, J. Alfredo Martinez, Marika Massaro, Susan McRitchie, Bayan Mesmar, Fermín I. Milagro, María J. Moreno-Aliaga, Isabel Moreno-Indias, Antonio Moschetta, Santiago Navas-Carretero, Mihai Niculescu, Karin Nordström, Francisco J. Novo, Jude A. Oben, Leticia Odriozola, Jose M. Ordovas, Andreu Palou, Virginia R. Parslow, Wimal Pathmasiri, José Luis Pérez-Castrillón, Louis Pérusse, Elena Piccinin, Julio Plaza-Diaz, Felipe Prósper, Lu Qi, Jessica C. Ralston, Ana Ramírez de Molina, George Rasti, Ram Reifen, Giulia Renda, José A. Riancho, José Antonio Riancho del Moral, Fernando Rivadeneira, Helen M. Roche, Marta Ruiz-Mambrilla, Francisco Javier Ruiz-Ojeda, Francisca Salas-Pérez, Rodrigo San-Cristobal, Nicolás Santander, José L. Santos, Jörg Saupe, Egeria Scoditti, Charles N. Serhan, Nicolas G. Simonet, Artemis P. Simopoulos, Nanette Steinle, Susan C.J. Sumner, Francisco J. Tinahones, Alejandro Vaquero, Itzel Vazquez-Vidal, Antonio Velazquez-Arellano, Nathalie Viguerie, Manlio Vinciguerra, Francesco Visioli, José L. Vizmanos, Johannes von Lintig, Venkata Saroja Voruganti, Ronald J.A. Wanders, Tiange Wang, Tim Wiltshire, Deyang Yu, Amir Zarrinpar, Steven H. Zeisel, and Maria Angeles Zulet
- Published
- 2020
35. Metabolic syndrome and idiopathic sudden sensori-neural hearing loss
- Author
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Natasha Scialpi, Nicola Quaranta, Giada Cavallaro, Massimo Rinaldi, and Marica Cariello
- Subjects
Male ,Physiology ,Otology ,Blood Pressure ,Deafness ,Cardiovascular Medicine ,Weight Gain ,Biochemistry ,Vascular Medicine ,Body Mass Index ,Medical Conditions ,0302 clinical medicine ,Waist–hip ratio ,Medicine and Health Sciences ,Medicine ,030223 otorhinolaryngology ,Hearing Disorders ,Metabolic Syndrome ,Multidisciplinary ,Organic Compounds ,Monosaccharides ,Middle Aged ,Lipids ,Chemistry ,Cholesterol ,Physiological Parameters ,Cardiovascular Diseases ,Physical Sciences ,Female ,medicine.symptom ,Research Article ,medicine.medical_specialty ,Waist ,Hearing Loss, Sensorineural ,Science ,Cardiology ,Carbohydrates ,03 medical and health sciences ,Internal medicine ,Neural hearing loss ,Humans ,Obesity ,business.industry ,Body Weight ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Recovery of Function ,Hearing Loss, Sudden ,Cardiovascular Disease Risk ,medicine.disease ,Glucose ,Blood pressure ,Otorhinolaryngology ,Metabolic syndrome ,business ,Body mass index ,Weight gain ,030217 neurology & neurosurgery - Abstract
The purpose of this study was to evaluate the association between the presence of Metabolic Syndrome (MetS) and idiopathic sudden sensorineural hearing loss (ISSHL) and the impact of MetS on recovery of patients with ISSHL. 39 Patients with ISSHL and 44 controls were enrolled in this study. Demographic, clinical characteristics and hearing recovery were evaluated. MetS was defined according to the diagnostic criteria of International Diabetes Federation (IDF) consensus definition. Patients affected by ISSHL presented a body mass index (BMI), waist circumference, waist hip ratio (WHR), fasting glucose and blood pressure significantly higher compared to controls. Considering patients with central obesity, 5 controls and 15 ISSHL patients met the criteria of MetS. According to Siegel criteria, a complete or partial recovery was observed in 60% of patients with MetS and in 91,66% of patients without MetS. MetS was associated with ISSHL and this association negatively influenced the hearing recovery of these patients.
- Published
- 2020
36. Nutrients and Genes in the Liver
- Author
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Elena Piccinin, Marica Cariello, Antonio Moschetta, and Oihane Garcia-Irigoyen
- Subjects
Biochemistry ,Nuclear receptor ,Chemistry ,Lipogenesis ,Metabolism ,Liver X receptor ,Energy source ,Carbohydrate-responsive element-binding protein ,Fish oil ,Sterol - Abstract
Dietary fats are an important energy source, which form an essential part of membranes and function as precursors of important molecules, such as hormones. Changes in the dietary fatty acids composition can deeply influence health and susceptibility to diseases. For example, current dietary guidelines discourage consumption of saturated fatty acids and encourage consumption of unsaturated fatty acids such as n-3 fatty acids that are contained in fish oil. N-3 fatty acids intake is associated with decreased plasma triglyceride concentrations and cardiac arrhythmias prevention. Dietary fatty acids, like other nutrients, are able to influence biological processes by altering DNA transcription through nuclear receptors. Specifically, the liver X receptor (LXR) exerts a main function in liver fatty acids metabolism via sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate response element-binding protein (ChREBP). Alterations on this nuclear receptor may alter normal metabolism and contribute to the pathogenesis of various diseases.
- Published
- 2020
37. Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor
- Author
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Stefania Vetrano, Raffaella Maria Gadaleta, Claudia Peres, Gionatha Fiorino, Antonio Moschetta, Brian Ko, Marica Cariello, Oihane Garcia-Irigoyen, Carlo Sabbà, Silvio Danese, Emanuele Porru, Natasha Scialpi, Aldo Roda, Jian Luo, Gadaleta, Raffaella Maria, Garcia-Irigoyen, Oihane, Cariello, Marica, Scialpi, Natasha, Peres, Claudia, Vetrano, Stefania, Fiorino, Gionatha, Danese, Silvio, Ko, Brian, Luo, Jian, Porru, Emanuele, Roda, Aldo, Sabbà, Carlo, and Moschetta, Antonio
- Subjects
0301 basic medicine ,Male ,Cytoplasmic and Nuclear ,Anti-Inflammatory Agents ,lcsh:Medicine ,Receptors, Cytoplasmic and Nuclear ,Intestinal inflammation ,Ulcerative ,Inbred C57BL ,Fibroblast growth factor ,Mice ,0302 clinical medicine ,Crohn Disease ,Nuclear receptors ,Receptors ,lcsh:R5-920 ,DSS-colitis ,Bile acid ,Chemistry ,General Medicine ,Colitis ,Recombinant Proteins ,Cell biology ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,lcsh:Medicine (General) ,Corrigendum ,medicine.drug_class ,Inflammation ,General Biochemistry, Genetics and Molecular Biology ,Bile Acids and Salts ,03 medical and health sciences ,medicine ,Animals ,Humans ,lcsh:R ,FGF19 ,medicine.disease ,Bile acids ,Gastrointestinal Microbiome ,Fibroblast Growth Factors ,Mice, Inbred C57BL ,030104 developmental biology ,Nuclear receptor ,Enterokine ,Farnesoid X receptor ,Colitis, Ulcerative ,Peptides ,Dysbiosis - Abstract
Background: Disruption of bile acid (BA) homeostasis plays a key role in intestinal inflammation. The gut-liver axis is the main site for the regulation of BA synthesis and BA pool size via the combined action of the nuclear Farnesoid X Receptor (FXR) and the enterokine Fibroblast Growth Factor 19 (FGF19). Increasing evidence have linked derangement of BA metabolism with dysbiosis and mucosal inflammation. Thus, here we aimed to investigate the potential action of an FGF19 analogue on intestinal microbiota and inflammation. Methods: A novel engineered non-tumorigenic variant of the FGF19 protein, M52-WO 2016/0168219 was generated. WT and FXRnull mice were injected with AAV-FGF19-M52 or the control AAV-GFP and subjected to Sodium Dextran Sulphate-induced colitis. Findings: FGF19-M52 reduced BA synthesis and pool size, modulated its composition and protected mice from intestinal inflammation. These events were coupled with preservation of the intestinal epithelial barrier integrity, inhibition of inflammatory immune response and modulation of microbiota composition. Interestingly, FGF19-M52-driven systemic and local anti-inflammatory activity was completely abolished in Farnesoid X Receptor (FXR)null mice, thus underscoring the need of FXR to guarantee enterocytes’ fitness and complement FGF19 anti-inflammatory activity. To provide a translational perspective, we also show that circulating FGF19 levels are reduced in patients with Crohn's disease. Interpretation: Reactivation of the FXR-FGF19 axis in a murine model of intestinal inflammation could bona fide provide positive changes in BA metabolism with consequent reduction of intestinal inflammation and modulation of microbiota. These results point to the therapeutic potential of FGF19 in the treatment of intestinal inflammation with concomitant derangement of BA homeostasis. Funding: A. Moschetta is funded by MIUR-PRIN 2017
- Published
- 2019
38. Nuclear receptor FXR, bile acids and liver damage: Introducing the progressive familial intrahepatic cholestasis with FXR mutations
- Author
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Elena Piccinin, Antonio Moschetta, Marica Cariello, Oihane Garcia-Irigoyen, and Carlo Sabbà
- Subjects
0301 basic medicine ,Cholagogues and Choleretics ,medicine.medical_specialty ,Receptors, Cytoplasmic and Nuclear ,Mice, Transgenic ,Cholestasis, Intrahepatic ,Retinoid X receptor ,Biology ,Bile Acids and Salts ,Mice ,03 medical and health sciences ,Cholestasis ,Internal medicine ,medicine ,Animals ,Humans ,Intestinal Mucosa ,ABCB11 ,Molecular Biology ,Clinical Trials as Topic ,Progressive familial intrahepatic cholestasis ,Epithelial Cells ,FGF19 ,ABCB4 ,medicine.disease ,G protein-coupled bile acid receptor ,Fibroblast Growth Factors ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Liver ,Mutation ,Molecular Medicine ,Farnesoid X receptor ,Signal Transduction - Abstract
The nuclear receptor farnesoid X receptor (FXR) is the master regulator of bile acids (BAs) homeostasis since it transcriptionally drives modulation of BA synthesis, influx, efflux, and detoxification along the enterohepatic axis. Due to its crucial role, FXR alterations are involved in the progression of a plethora of BAs associated inflammatory disorders in the liver and in the gut. The involvement of the FXR pathway in cholestasis development and management has been elucidated so far with a direct role of FXR activating therapy in this condition. However, the recent identification of a new type of genetic progressive familial intrahepatic cholestasis (PFIC) linked to FXR mutations has strengthen also the bona fide beneficial effects of target therapies that by-pass FXR activation, directly promoting the action of its target, namely the enterokine FGF19, in the repression of hepatic BAs synthesis with reduction of total BA levels in the liver and serum, accomplishing one of the major goals in cholestasis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.
- Published
- 2018
39. Intracoronary monocyte expression pattern and HDL subfractions after non-ST elevation myocardial infarction
- Author
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Antonio Moschetta, Pasquale Caldarola, Lucilla Crudele, Jennifer Härdfeldt, Giusi Graziano, Alice Ossoli, Marilidia Piglionica, Roberta Zerlotin, Maria Arconzo, Michele Vacca, Roberto Salvia, Carlo Sabbà, Laura Calabresi, Stefano Battaglia, David Rutigliano, and Marica Cariello
- Subjects
Male ,0301 basic medicine ,Apolipoprotein E ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Monocytes ,Coronary artery disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Non-ST Elevated Myocardial Infarction ,Liver X receptor ,Molecular Biology ,biology ,business.industry ,Cholesterol ,Unstable angina ,Cholesterol, HDL ,Reverse cholesterol transport ,Middle Aged ,medicine.disease ,Coronary Vessels ,Lipids ,Cross-Sectional Studies ,030104 developmental biology ,chemistry ,ABCA1 ,Cardiology ,biology.protein ,Molecular Medicine ,Female ,lipids (amino acids, peptides, and proteins) ,business - Abstract
Aims Coronary artery disease (CAD) is described as a range of clinical conditions including myocardial infarction (MI) and unstable angina. Lipid and apolipoprotein profiles together with the study of cholesterol deposit and efflux serve to identify novel pre and post infarct scenarios for the treatment of these patients. In (non-ST elevation myocardial infarction) NSTEMI patients, we analysed both systemic and intracoronary serum ability to accept cholesterol as well as cholesterol efflux capacity (CEC) of monocytes in terms of expression of genes involved in the reverse cholesterol transport (RCT). Methods and results While HDL-C quantity was similar between systemic and coronary arterial blood, in 21 NSTEMI patients we observed a significant reduction of the preβ-HDL fraction and the levels of Apolipoproteins AI, AII, B and E in coronary versus systemic serum. These data are complemented with the observed reduction of CEC. On the contrary, compared to systemic arterial monocytes, in coronary microenvironment of NSTEMI patients after myocardial infarction, the monocytes exhibited a higher mRNA expression of nuclear receptor LXRα and its targets ABCA1 and APOE, which drive cholesterol efflux capacity. Conclusion In this cross-sectional study we observe that in the immediate post infarction period, there is a spontaneous bona fide ligand-induced activation of the LXR driven cholesterol efflux capacity of intracoronary monocytes to overcome the reduced serum ability to accept cholesterol and to inhibit the post-infarction pro-inflammatory local microenvironment.
- Published
- 2021
40. Lipid metabolism in colon cancer: Role of Liver X Receptor (LXR) and Stearoyl-CoA Desaturase 1 (SCD1)
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Antonio Moschetta, Marica Cariello, and Elena Piccinin
- Subjects
0301 basic medicine ,Clinical Biochemistry ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,Humans ,Liver X receptor ,Molecular Biology ,Liver X Receptors ,Chemistry ,Fatty Acids ,Cancer ,Lipid metabolism ,General Medicine ,Lipid Metabolism ,medicine.disease ,030104 developmental biology ,Nuclear receptor ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Lipogenesis ,Cancer cell ,Cancer research ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Stearoyl-CoA desaturase-1 ,Stearoyl-CoA Desaturase - Abstract
Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. Although several genetic alterations have been associated with CRC onset and progression, nowadays the reprogramming of cellular metabolism has been recognized as a fundamental step of the carcinogenic process. Intestinal tumor cells frequently display an aberrant activation of lipid metabolism. Indeed, to satisfy the growing needs of a continuous proliferation, cancer cells can either increase the uptake of exogenous lipids or upregulate the endogenous lipogenesis and cholesterol synthesis. Therefore, strategies aimed at limiting lipid accumulation are now under development in order to counteract malignancies. Two major players of lipids metabolism have been so far identified for their contribution to CRC development: the nuclear receptor Liver X Receptor (LXRs) and the enzyme Stearoyl-CoA Desaturase 1 (SCD1). Whereas LXR is mainly recognized for its role as a cholesterol sensor, finally promoting the loss of cellular cholesterol and whole-body homeostasis, SCD1 acts as the major regulator of new fatty acids, finely tuning the monounsaturated fatty acids (MUFA) to saturated fatty acids (SFA) ratio. Intriguingly, SCD1 is directly regulated by LXRs. Despite LXRs agonists have elicited great interest as a promising therapeutic target for cancer, LXR's ability to induce SCD1 and new fatty acids synthesis represent a major obstacle in the development of new effective treatments. Thus, further investigations are required to fully dissect the concomitant modulation of both players, to develop specific therapies aimed at blocking intestinal cancer cells proliferation, eventually counteracting CRC progression.
- Published
- 2021
41. Long-term Administration of Nuclear Bile Acid Receptor FXR Agonist Prevents Spontaneous Hepatocarcinogenesis in Abcb4−/− Mice
- Author
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Aldo Roda, Roberta Zerlotin, Claudia Peres, Marica Cariello, Emanuele Porru, Antonio Moschetta, Carlo Sabbà, Cariello, Marica, Peres, Claudia, Zerlotin, Roberta, Porru, Emanuele, Sabbà, Carlo, Roda, Aldo, and Moschetta, Antonio
- Subjects
0301 basic medicine ,Agonist ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Carcinoma, Hepatocellular ,medicine.drug_class ,Transgene ,Receptors, Cytoplasmic and Nuclear ,lcsh:Medicine ,Biology ,Article ,Bile Acids and Salts ,03 medical and health sciences ,Mice ,Gastrointestinal Agents ,Fibrosis ,Internal medicine ,medicine ,Animals ,Receptor ,lcsh:Science ,Multidisciplinary ,Bile acid ,Liver Neoplasms ,lcsh:R ,medicine.disease ,G protein-coupled bile acid receptor ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Nuclear receptor ,Liver ,Farnesoid X receptor ,lcsh:Q - Abstract
Altered bile acid (BA) signaling is associated with hepatotoxicity. The farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates BA homeostasis. Mice with FXR ablation present hepatocarcinoma (HCC) due to high toxic BA levels. Mice with Abcb4 ablation accumulate toxic BA within the bile ducts and present HCC. We have previously shown that intestinal specific activation of FXR by transgenic VP16-FXR chimera is able to reduce BA pool size and prevent HCC. Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulphate) to Fxr−/− and Abcb4−/− mice. HCC number and size were significantly reduced by INT-767 administration. In contrast, no changes in HCC tumor number and size were observed in Fxr−/− mice fed with or without INT-767. Notably, INT-767 preserved the hepatic parenchyma, improved hepatic function and down-regulated pro-inflammatory cytokines. Moreover, in Abcb4−/− mice INT-767 prevented fibrosis by reducing collagen expression and deposition. Thus, long term activation of FXR is able to reduce BA pool, reprogram BA metabolism and prevent HCC. These data provide the impetus to address the bona fide therapeutic potential of FXR activation in disease with BA-associated development of HCC.
- Published
- 2017
42. Role of Oleic Acid in the Gut-Liver Axis: From Diet to the Regulation of Its Synthesis via Stearoyl-CoA Desaturase 1 (SCD1)
- Author
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Antonio Moschetta, Simon Ducheix, Carlo Sabbà, Elena Piccinin, Marica Cariello, Stefania De Santis, and James M. Ntambi
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0301 basic medicine ,lcsh:TX341-641 ,Review ,liver ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Essential fatty acid ,Humans ,MUFA ,stearoyl-CoA desaturase ,chemistry.chemical_classification ,Nutrition and Dietetics ,Cell growth ,Fatty acid ,olive oil ,Diet ,Gastrointestinal Tract ,Metabolic pathway ,Stearoyl-CoA Desaturase ,Oleic acid ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,oleic acid ,030220 oncology & carcinogenesis ,gut ,lipids (amino acids, peptides, and proteins) ,Stearoyl-CoA desaturase-1 ,lcsh:Nutrition. Foods and food supply ,Food Science - Abstract
The consumption of an olive oil rich diet has been associated with the diminished incidence of cardiovascular disease and cancer. Several studies have attributed these beneficial effects to oleic acid (C18 n-9), the predominant fatty acid principal component of olive oil. Oleic acid is not an essential fatty acid since it can be endogenously synthesized in humans. Stearoyl-CoA desaturase 1 (SCD1) is the enzyme responsible for oleic acid production and, more generally, for the synthesis of monounsaturated fatty acids (MUFA). The saturated to monounsaturated fatty acid ratio affects the regulation of cell growth and differentiation, and alteration in this ratio has been implicated in a variety of diseases, such as liver dysfunction and intestinal inflammation. In this review, we discuss our current understanding of the impact of gene-nutrient interactions in liver and gut diseases, by taking advantage of the role of SCD1 and its product oleic acid in the modulation of different hepatic and intestinal metabolic pathways.
- Published
- 2019
43. Extra Virgin Olive Oil: Lesson from Nutrigenomics
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Antonio Moschetta, Carlo Sabbà, Elena Piccinin, Stefania De Santis, and Marica Cariello
- Subjects
0301 basic medicine ,Metabolic homeostasis ,polyphenol content ,lcsh:TX341-641 ,Disease ,Review ,Biology ,human health ,fatty acids ,extra virgin olive oil ,Transcriptome ,03 medical and health sciences ,Human health ,Human disease ,nutrigenomics ,Humans ,Olive Oil ,Nutritional biomarkers ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Polyphenols ,food and beverages ,Biotechnology ,030104 developmental biology ,Nutrigenomics ,Dietary Supplements ,business ,lcsh:Nutrition. Foods and food supply ,Food Science ,Olive oil - Abstract
Extra virgin olive oil (EVOO) consumption has a beneficial effect on human health, especially for prevention of cardiovascular disease and metabolic disorders. Here we underscore the peculiar importance of specific cultivars used for EVOO production since biodiversity among cultivars in terms of fatty acids and polyphenols content could differently impact on the metabolic homeostasis. In this respect, the nutrigenomic approach could be very useful to fully dissect the pathways modulated by different EVOO cultivars in terms of mRNA and microRNA transcriptome. The identification of genes and miRNAs modulated by specific EVOO cultivars could also help to discover novel nutritional biomarkers for prevention and/or prognosis of human disease. Thus, the nutrigenomic approach depicts a novel scenario to investigate if a specific EVOO cultivar could have a positive effect on human health by preventing the onset of cardiovascular disease and/or chronic inflammatory disorders also leading to cancer.
- Published
- 2019
44. The Enterokine Fibroblast Growth Factor 15/19 in Bile Acid Metabolism
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Marilidia Piglionica, Raffaella Maria Gadaleta, Antonio Moschetta, and Marica Cariello
- Subjects
0301 basic medicine ,FGF21 ,Bile acid ,Glycogen ,medicine.drug_class ,FGF19 ,Cholesterol 7 alpha-hydroxylase ,Fibroblast growth factor ,Cell biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,medicine ,Glucose homeostasis ,Farnesoid X receptor - Abstract
The endocrine fibroblast growth factors (FGFs), FGF19, FGF21, and FGF23, play a key role in whole-body homeostasis. In particular, FGF19 is a postprandial hormone regulating glucose homeostasis, glycogen and protein synthesis, and primary bile acid (BA) metabolism. In the ileum, BA-dependent farnesoid X receptor (FXR) activation induces the production of FGF19, which reaches the liver through the portal system where it represses the expression of CYP7A1, the rate-limiting enzyme of hepatic de novo BAs synthesis. Dysregulation of BA levels associated with alteration in FGF19 level has been depicted in different pathological conditions of the gut-liver axis. Furthermore, FGF19 exploits strong anti-cholestatic and anti-fibrotic activities in the liver. However, native FGF19 seems to retain peculiar hepatic pro-tumorigenic actions. Recently engineered FGF19 analogues have been recently synthetized, with fully retained BA regulatory activity but without intrinsic pro-tumoral action, thus opening bona fide novel pharmacological strategy for the treatment of gut-liver axis diseases.
- Published
- 2019
45. Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis
- Author
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Marica Cariello, Simona D'Amore, Antonio Tamburro, Antonio Moschetta, Andria D'Orazio, Francesco Dimitri Petridis, Marco Di Eusanio, Roberto Di Bartolomeo, Carlo Sabbà, David Rutigliano, Fabio Pellegrini, Gianluca Folesani, Giuseppe Palasciano, Michele Vacca, Giusi Graziano, Lorena Salvatore, Vacca, Michele, DI EUSANIO, Marco, Cariello, Marica, Graziano, Giusi, D'Amore, Simona, Petridis, FRANCESCO DIMITRI, D'Orazio, Andria, Salvatore, Lorena, Tamburro, Antonio, Folesani, Gianluca, Rutigliano, David, Pellegrini, Fabio, Sabbà, Carlo, Palasciano, Giuseppe, DI BARTOLOMEO, Roberto, and Moschetta, Antonio
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Chemokine ,Physiology ,Adipose tissue ,Inflammation ,030204 cardiovascular system & hematology ,Biology ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Epicardial adipose tissue ,microRNA ,medicine ,Humans ,Genetic Predisposition to Disease ,CCL13 ,Coronary atherosclerosis ,miRNA ,Aged ,Aged, 80 and over ,Regulation of gene expression ,Genome, Human ,MicroRNA ,Lipid metabolism ,Middle Aged ,Atherosclerosis ,Lipid Metabolism ,Metabolic syndrome ,MicroRNAs ,030104 developmental biology ,Adipose Tissue ,Gene Expression Regulation ,Nuclear receptor ,Atherosclerosi ,biology.protein ,Gene expression ,Chemokines ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Human ,Genome-Wide Association Study - Abstract
Background Epicardial adipose tissue (EAT) is an atypical fat depot surrounding the heart with a putative role in the development of atherosclerosis. Methods and results We profiled genes and miRNAs in perivascular EAT and subcutaneous adipose tissue (SAT) of metabolically healthy patients without coronary artery disease (CAD) vs. metabolic patients with CAD. Compared with SAT, a specific tuning of miRNAs and genes points to EAT as a tissue characterized by a metabolically active and pro-inflammatory profile. Then, we depicted both miRNA and gene signatures of EAT in CAD, featuring a down-regulation of genes involved in lipid metabolism, mitochondrial function, nuclear receptor transcriptional activity, and an up-regulation of those involved in antigen presentation, chemokine signalling, and inflammation. Finally, we identified miR-103-3p as candidate modulator of CCL13 in EAT, and a potential biomarker role for the chemokine CCL13 in CAD. Conclusion EAT in CAD is characterized by changes in the regulation of metabolism and inflammation with miR-103-3p/CCL13 pair as novel putative actors in EAT function and CAD.
- Published
- 2015
46. Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse cholesterol transport in circulating CD14+ cells of patients with metabolic syndrome
- Author
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Antonio Moschetta, Natasha Scialpi, Massimiliano Copetti, Marilidia Piglionica, Giuseppe Di Tullio, Giusi Graziano, Michele Vacca, Marica Cariello, Giuseppe Palasciano, Simona D'Amore, Jennifer Härdfeldt, Carlo Sabbà, Vacca, Michele [0000-0002-1973-224X], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Physiology ,Lipopolysaccharide Receptors ,Down-Regulation ,Inflammation ,03 medical and health sciences ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,microRNA ,medicine ,ABCA1 Gene ,Humans ,3' Untranslated Regions ,Cells, Cultured ,Metabolic Syndrome ,Binding Sites ,biology ,Chemistry ,Cholesterol ,Three prime untranslated region ,Reverse cholesterol transport ,Cholesterol, HDL ,nutritional and metabolic diseases ,Biological Transport ,Middle Aged ,medicine.disease ,MicroRNAs ,030104 developmental biology ,Endocrinology ,ABCA1 ,Case-Control Studies ,biology.protein ,Leukocytes, Mononuclear ,lipids (amino acids, peptides, and proteins) ,Female ,medicine.symptom ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,Transcriptome ,ATP Binding Cassette Transporter 1 - Abstract
Aims Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors associated with atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling inflammatory, immune and metabolic responses. In order to further elucidate the link between inflammation and the HDL cholesterol pathway in MS, we focussed on the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player in cholesterol efflux (CE). Methods and results ABCA1 mRNA levels are suppressed in CD14+ cells of MS patients and are negatively correlated to body mass index (BMI), insulin-resistance (HOMA-IR) and cardiovascular risk, and positively to HDL cholesterol and CE. miRNA target in silico prediction identified a putative modulatory role of ABCA1 for the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) target miR-9-5p, whose expression pattern was up-regulated in CD14+ cells of MS patients, positively correlated to BMI, HOMA-IR, and triglycerides, and negatively to ABCA1 mRNA levels, HDL cholesterol and CE. Ectopic gain and loss of miR-9-5p function in macrophages modulated ABCA1 mRNA and protein levels, ABCA1 miRNA 3’-untranslated region target sequence reporter assay, and CE into HDL, thus confirming ABCA1 as a target of miR-9-5p. Conclusions We identified the NF-κB target miR-9-5p as a negative regulator of ABCA1 adding a novel target pathway in the relationship between inflammation and HDL-driven reverse cholesterol transport for prevention or treatment of atherosclerosis in MS.
- Published
- 2018
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47. The gut-liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19
- Author
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Marilidia Piglionica, Antonio Moschetta, and Marica Cariello
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,medicine.drug_class ,Receptors, Cytoplasmic and Nuclear ,Antineoplastic Agents ,Cholesterol 7 alpha-hydroxylase ,Bile Acids and Salts ,03 medical and health sciences ,Liver disease ,Cholestasis ,Drug Discovery ,medicine ,Animals ,Bile ,Humans ,Molecular Targeted Therapy ,Receptor ,Cholesterol 7-alpha-Hydroxylase ,Pharmacology ,Bile acid ,Chemistry ,Liver Neoplasms ,FGF19 ,medicine.disease ,Fibroblast Growth Factors ,Gastrointestinal Tract ,030104 developmental biology ,Cell Transformation, Neoplastic ,Nuclear receptor ,Liver ,Drug Design ,Cancer research ,Farnesoid X receptor ,Signal Transduction - Abstract
Elevated bile acid (BA) concentrations in the liver is associated with severe disease, including cholestasis and hepatocellular carcinoma. The nuclear Farnesoid X Receptor (FXR) is the master regulator of BAs homeostasis. In the ileum, BA-dependent FXR activation induces the production of the fibroblast growth factor FGF19, a hormone that reaches the liver through the portal system where it represses the expression of CYP7A1, the rate limiting enzyme in the process of hepatic BAs synthesis. This gut-liver FXR-FGF19 dual action is the paradigm of physiological BA regulation and it is currently targeted in the clinical practice for liver disease such as primary cholangitis. At a variance of FXR activation, native FGF19 has strong anti-cholestatic and anti-fibrotic activity in the liver but it retains peculiar pro-tumorigenic actions. Thus, novel analogues have been generated to avoid tumorigenic capacity while maintaining BA metabolic action. Here we present a novel and intriguing view on the putative possibility to target the FXR-FGF19 duo in order to offer a bona fide promising therapeutic approach to bile acid promoted hepatocarcinoma.
- Published
- 2018
48. Tissue-specific actions of FXR in metabolism and cancer
- Author
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Carlo Sabbà, Marica Cariello, Antonio Moschetta, and Raffaella Maria Gadaleta
- Subjects
Receptors, Cytoplasmic and Nuclear ,Lipid metabolism ,Cell Biology ,Metabolism ,Biology ,Pathogenesis ,Structure-Activity Relationship ,Glucose ,Liver ,Biochemistry ,Transcription (biology) ,Neoplasms ,Animals ,Homeostasis ,Humans ,Farnesoid X receptor ,Intestinal Mucosa ,Molecular Biology ,Transcription factor ,Hormone - Abstract
The nuclear Farnesoid X Receptor (FXR) is a transcription factor critically involved in metabolic homeostasis in the gut-liver axis. FXR activity is mediated by hormonal and dietary signals and driven by bile acids (BAs), which are the natural FXR ligands. Given the great physiological importance in BA homeostasis, as well as in the regulation of glucose and lipid metabolism, FXR plays a pivotal role in the pathogenesis of a wide range of disease of the liver, biliary tract and intestine, including hepatic and colorectal cancer. In the last years several studies have shown the relative FXR tissue-specific importance, highlighting synergism and additive effects in the liver and intestine. Gain- and loss-of-FXR-function mouse models have been generated in order to identify the biological processes and the molecular FXR targets. Taking advantage of the knowledge on the structure-activity relationship of BAs for FXR, semi-synthetic and synthetic molecules have been generated to obtain more selective and powerful FXR activators than BAs. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics.
- Published
- 2015
49. LXRs, SHP, and FXR in Prostate Cancer: Enemies or
- Author
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Marica, Cariello, Simon, Ducheix, Salwan, Maqdasy, Silvère, Baron, Antonio, Moschetta, and Jean-Marc A, Lobaccaro
- Subjects
Male ,FXR ,Receptors, Androgen ,SHP ,lipid metabolism ,Animals ,Humans ,Prostatic Neoplasms ,Receptors, Cytoplasmic and Nuclear ,Original Article ,LXR ,prostate cancer ,Liver X Receptors - Abstract
Androgens and androgen receptor (AR, NR3C4) clearly play a crucial role in prostate cancer progression. Besides, the link between metabolic disorders and the risk of developing a prostate cancer has been emerging these last years. Interestingly, “lipid” nuclear receptors such as LXRα/NR1H3 and LXRβ/NR1H2 (as well as FXRα/NR1H4 and SHP/NR0B2) have been described to decrease the lipid metabolism, while AR increases it. Moreover, these former orphan nuclear receptors can regulate androgen levels and modulate AR activity. Thus, it is not surprising to find such receptors involved in the physiology of prostate. This review is focused on the roles of liver X receptors (LXRs), farnesoid X receptor (FXR), and small heterodimeric partner (SHP) in prostate physiology and their capabilities to interfere with the androgen-regulated pathways by modulating the levels of active androgen within the prostate. By the use of prostate cancer cell lines, mice deficient for these nuclear receptors and human tissue libraries, several authors have pointed out the putative possibility to pharmacologically target these receptors. These data open a new field of research for the development of new drugs that could overcome the castration resistance in prostate cancer, a usual phenomenon in patients.
- Published
- 2017
50. Endothelial-to-mesenchymal transition and renal fibrosis in ischaemia/reperfusion injury are mediated by complement anaphylatoxins and Akt pathway
- Author
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Alessandra Stasi, Edwin V Amersfoort, Antonia Loverre, Michele Battaglia, Simona Simone, Francesco Staffieri, Loreto Gesualdo, Antonio Crovace, Giuseppe Lucarelli, Beatrijs Oortwijn, Chiara Divella, Giuseppe Grandaliano, Margherita Gigante, Giuseppe Castellano, Marica Cariello, Vincenzo Montinaro, Pasquale Ditonno, and Claudia Curci
- Subjects
Anaphylatoxins ,Pathology ,medicine.medical_specialty ,Endothelium ,Swine ,Kidney ,Peritubular capillaries ,Fibrosis ,medicine ,Renal fibrosis ,Settore MED/14 - NEFROLOGIA ,Animals ,Humans ,complement ,Anaphylatoxin ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,Transplantation ,business.industry ,Akt/PKB signaling pathway ,Endothelial Cells ,ischaemia/reperfusion ,Fibroblasts ,medicine.disease ,endothelial-to-mesenchymal transition ,Disease Models, Animal ,medicine.anatomical_structure ,Nephrology ,Reperfusion Injury ,Cancer research ,Female ,Kidney Diseases ,business ,Proto-Oncogene Proteins c-akt ,Reperfusion injury ,Signal Transduction - Abstract
Background Increasing evidence demonstrates a phenotypic plasticity of endothelial cells (ECs). Endothelial-to-mesenchymal transition (EndMT) contributes to the development of tissue fibrosis. However, the pathogenic factors and signalling pathways regulating this process in ischaemia/reperfusion (I/R) injury are still poorly understood. Methods We investigated the possible role of complement in the induction of this endothelial dysfunction in a swine model of renal I/R injury by using recombinant C1 inhibitor in vivo. Results Here, we showed that I/R injury reduced the density of renal peritubular capillaries and induced tissue fibrosis with generation of CD31(+)/α-SMA(+) and CD31(+)/FPS-1(+) cells indicating EndMT. When we inhibited complement, the process of EndMT became rare, with preserved density of peritubular capillaries and significant reduction in renal fibrosis. When we activated ECs by anaphylatoxins in vitro, C3a and C5a led to altered endothelial phenotype with increased expression of fibroblast markers and decrease expression of specific endothelial markers. The activation of Akt pathway was pivotal for the C3a and C5a-induced EndMT in vitro. In accordance, inhibition of complement in vivo led to the abrogation of Akt signalling, with hampered EndMT and tissue fibrosis. Conclusions Our data demonstrate a critical role for complement in the acute induction of EndMT via the Akt pathway. Therapeutic inhibition of these systems may be essential to prevent vascular damage and tissue fibrosis in transplanted kidney.
- Published
- 2014
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